Exercise and physical performance in older adults with sarcopenic obesity: a systematic review

Sarcopenic obesity is characterized by low muscle mass and high body fat; prevalence increases with age, particularly after age 65 years. For this systematic literature review we searched scientific databases for studies on exercise interventions for improving physical performance in adults with sarcopenic obesity; also, we identified potential gaps in clinical practice guidelines that need to be addressed

Optimization of organotypic cultures of mouse spleen for staining and functional assays

By preserving cell viability and three-dimensional localization, organotypic culture stands out among the newest frontiers of cell culture. It has been successfully employed for the study of diseases among which neoplasias, where tumoral cells take advantage of the surrounding stroma to promote their own proliferation and survival. Organotypic culture acquires major importance in the context of the immune system, whose cells cross-talk in a complex and dynamic fashion to elicit productive responses. However, organotypic culture has been as yet poorly developed for and applied to primary and secondary lymphoid organs. Here we describe in detail the development of a protocol suitable for the efficient cutting of mouse spleen, which overcomes technical difficulties related to the peculiar organ texture, and for optimized organotypic culture of spleen slices. Moreover, we used microscopy, immunofluorescence, flow cytometry and qRT-PCR to demonstrate that the majority of cells residing in spleen slices remain alive and maintain their original location in the organ architecture for several days after cutting. The development of this protocol represents a significant technical improvement in the study of the lymphoid microenvironment in both physiological and pathological conditions involving the immune system

Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice

Non-specific mental retardation (NSMR) is a common human disorder characterized by mental handicap as the only clinical symptom. Among the recently identified MR genes is GDI1, which encodes αGdi, one of the proteins controlling the activity of the small GTPases of the Rab family in vesicle fusion and intracellular trafficking. We report the cognitive and behavioral characterization of mice carrying a deletion of Gdi1. The Gdi1-deficient mice are fertile and anatomically normal. They appear normal also in many tasks to assess spatial and episodic memory and emotional behavior. Gdi1-deficient mice are impaired in tasks requiring formation of short-term temporal associations, suggesting a defect in short-term memory. In addition, they show lowered aggression and altered social behavior. In mice, as in humans, lack of Gdi1 spares most central nervous system functions and preferentially impairs only a few forebrain functions required to form temporal associations. The general similarity to human mental retardation is striking, and suggests that the Gdi1 mutants may provide insights into the human defect and into the molecular mechanisms important for development of cognitive function

A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.

Mutations in the diastrophic dysplasia sulfate transporter (DTDST or SLC26A2) cause a family of recessively inherited chondrodysplasias including, in order of decreasing severity, achondrogenesis 1B, atelosteogenesis 2, diastrophic dysplasia (DTD) and recessive multiple epiphyseal dysplasia. The gene encodes a widely distributed sulfate/chloride antiporter of the cell membrane whose function is crucial for the uptake of inorganic sulfate, which is needed for proteoglycan sulfation. To provide new insights in the pathogenetic mechanisms leading to skeletal and connective tissue dysplasia and to obtain an in vivo model for therapeutic approaches to DTD, we generated a Dtdst knock-in mouse with a partial loss of function of the sulfate transporter. In addition, the intronic neomycine cassette in the mutant allele contributed to the hypomorphic phenotype by inducing abnormal splicing. Homozygous mutant mice were characterized by growth retardation, skeletal dysplasia and joint contractures, thereby recapitulating essential aspects of the DTD phenotype in man. The skeletal phenotype included reduced toluidine blue staining of cartilage, chondrocytes of irregular size, delay in the formation of the secondary ossification center and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts. In spite of the generalized nature of the sulfate uptake defect, significant proteoglycan undersulfation was detected only in cartilage. Chondrocyte proliferation and apoptosis studies suggested that reduced proliferation and/or lack of terminal chondrocyte differentiation might contribute to reduced bone growth. The similarity with human DTD makes this mouse strain a useful model to explore pathogenetic and therapeutic aspects of DTDST-related disorders

Parametric POMDPs for planning in continuous state spaces

This thesis is concerned with planning and acting under uncertainty in partially-observable continuous domains. In particular, it focusses on the problem of mobile robot navigation given a known map. The dominant paradigm for robot localisation is to use Bayesian estimation to maintain a probability distribution over possible robot poses. In contrast, control algorithms often base their decisions on the assumption that a single state, such as the mode of this distribution, is correct. In scenarios involving significant uncertainty, this can lead to serious control errors. It is generally agreed that the reliability of navigation in uncertain environments would be greatly improved by the ability to consider the entire distribution when acting, rather than the single most likely state. The framework adopted in this thesis for modelling navigation problems mathematically is the Partially Observable Markov Decision Process (POMDP). An exact solution to a POMDP problem provides the optimal balance between reward-seeking behaviour and information-seeking behaviour, in the presence of sensor and actuation noise. Unfortunately, previous exact and approximate solution methods have had difficulty scaling to real applications. The contribution of this thesis is the formulation of an approach to planning in the space of continuous parameterised approximations to probability distributions. Theoretical and practical results are presented which show that, when compared with similar methods from the literature, this approach is capable of scaling to larger and more realistic problems. In order to apply the solution algorithm to real-world problems, a number of novel improvements are proposed. Specifically, Monte Carlo methods are employed to estimate distributions over future parameterised beliefs, improving planning accuracy without a loss of efficiency. Conditional independence assumptions are exploited to simplify the problem, reducing computational requirements. Scalability is further increased by focussing computation on likely beliefs, using metric indexing structures for efficient function approximation. Local online planning is incorporated to assist global offline planning, allowing the precision of the latter to be decreased without adversely affecting solution quality. Finally, the algorithm is implemented and demonstrated during real-time control of a mobile robot in a challenging navigation task. We argue that this task is substantially more challenging and realistic than previous problems to which POMDP solution methods have been applied. Results show that POMDP planning, which considers the evolution of the entire probability distribution over robot poses, produces significantly more robust behaviour when compared with a heuristic planner which considers only the most likely states and outcomes

Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials

Development and testing of a model for risk and protective factors for eating disorders and higher weight among emerging adults: A study protocol

© 2019 Research has demonstrated that eating disorders (ED) and higher weight have lifetime co-occurrence suggesting that they may be best considered within a common etiological model. Although we know that body dissatisfaction is likely to be a risk factor for both outcomes, other proposed risk and protective factors for each condition have not been adequately explored. The current paper tests a conceptual model that is based on a review of the existing literature from both areas of scholarship. It considers biological, sociocultural, psychological, and behavioral factors that may contribute to both outcomes. The model will be tested in a longitudinal design with an initial sample of 600 emerging adults (aged 18–30) per country in nine different countries (total sample = 5400 participants). Questionnaires will be completed online on two occasions, 12 months apart. The first full phase of the study commenced in July 2018, the same time Body Image was approached to publish this protocol paper (the final revised paper was submitted in September 2019), and data collection will be finalized in December 2019. Multi-group path analysis will identify the biopsychosocial predictors – both cross-sectionally and longitudinally – of both ED and higher weight, and how these vary across countries and gender

Level of agreement between objectively determined body composition and perceived body image in 6- To 8-year-old South African children- To Body Composition-Isotope Technique study

To assess the level of agreement between body size self-perception and actual body size determined by body mass index (BMI) z-score and body fatness measured by the deuterium dilution method (DDM) in South African children aged 6-8 years. A cross-sectional sample of 202 children (83 boys and 119 girls) aged 6-8 years from the Body Composition-Isotope Technique study (BC-IT) was taken. Subjective measures of body image (silhouettes) were compared with the objective measures of BMI z-score and body fatness measured by the DDM. The World Health Organization BMI z-scores were used to classify the children as underweight, normal, overweight, or obese. DDM-measured fatness was classified based on the McCarthy centile curves set at 2nd, 85th and 95th in conjunction with fatness cut-off points of 25% in boys and 30% in girls. Data were analyzed using SPSS v26. Of 202 children, 32.2%, 55.1%, 8.8%, and 2.4% perceived their body size as underweight, normal, overweight, and obese, respectively. Based on BMI z-score, 18.8%, 72.8%, 6.9%, and 1.5% were classified as underweight, normal, overweight, and obese, respectively. Body fatness measurement showed that 2.5%, 48.0%, 21.8%, and 29.7% were underweight, normal weight, overweight, and obese, respectively