Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Homemade oral supplement: a proposal for the nutritional recovery of children and adolescents with cancer

Objective The aim of this study was to evaluate the impact of homemade oral supplements on the nutritional recovery of patients with mild or severe malnutrition or at nutritional risk. Methods Eight recipes of homemade oral supplements containing 30% to 35% of the total energy expenditure were proposed. The patients with severe malnutrition (group B) received the oral supplement for 2 weeks and the others for 4 weeks (group A). Oral supplementation with homemade supplements was compared with oral supplementation with store-bought supplements, investigated earlier with a protocol with the same design. Results Homemade oral supplements contain much lower amounts of certain micronutrients but are five times cheaper than store-bought supplements. In group A, 88% of the patients taking homemade oral supplements and 84% of the patients taking store-bought supplements responded positively to supplementation. In group B, 22% of the patients taking homemade oral supplements and 25% of the patients taking store-bought supplements recovered. The difference was not significant. The impact of store-bought supplementation on the triceps skinfold thicknesses and arm circumferences of the patients in group A was greater than that obtained with homemade supplements. In group B, the effect on triceps skinfold thickness was not significant (p=0.16). Patients taking homemade or store-bought oral supplements presented similar protein and energy intakes and improvements in nutritional status. Only the body composition of patients in group A taking store-bought oral supplements was better. Conclusion The results obtained by this study suggest that the therapeutic use of homemade oral supplements is an alternative capable of promoting the nutritional recovery of cancer patients, especially those who cannot afford store-bought supplements.Objetivo Avaliar o impacto do suplemento oral artesanal na recuperação do estado nutricional de pacientes com desnutrição leve, grave e com risco nutricional. Métodos Propuseram-se oito receitas de suplementos visando ofertar entre 30,0% e 35,0% do gasto energético total. Os pacientes com desnutrição grave (grupo B) receberam o suplemento oral por duas semanas, e os demais pacientes (grupo A), por quatro semanas. Para a comparação dos resultados obtidos com o emprego do suplemento oral artesanal, foram utilizados dados referentes a um protocolo anterior, com o mesmo desenho, entretanto, com a utilização de suplemento oral industrializado. Resultados O suplemento oral artesanal fica muito aquém no que diz respeito a alguns micronutrientes, entretanto é cinco vezes mais barato do que a preparação com o suplemento oral industrializado. Os pacientes do grupo A com suplemento oral artesanal apresentaram 88,0% de resposta positiva na semana de avaliação, enquanto os com suplemento oral industrializado tiveram 84,0%. No grupo B, foram recuperados 22,0% dos pacientes com suplemento oral artesanal e 25,0% do grupo com suplemento oral industrializado, não apresentando, portanto, diferença significante. Comparando o impacto do industrializado com o do artesanal na prega cutânea tricipital e circunferência do braço, verificou-se que o suplemento oral industrializado no grupo A apresentou melhores resultados que o suplemento oral artesanal, e no grupo B, esse efeito observado na prega cutânea não foi significante (p=0,16). Os consumos de energia e de proteína, assim como a evolução nutricional, foram semelhantes entre suplemento oral industrializado e suplemento oral artesanal. Apenas a composição corpórea no grupo A com suplemento oral industrializado apresentou melhores resultados. Conclusão Os resultados apresentados neste estudo sugerem que o emprego da terapia com suplemento artesanal seja uma opção capaz de auxiliar na recuperação nutricional de pacientes oncológicos e uma opção para populações financeiramente desfavorecidas.Hospital Samaritano de São PauloInstituto Adriana GarófoloUniversidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Instituto de Oncologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUNIFESP, Depto. de Pediatria Instituto de Oncologia PediátricaUNIFESP, Depto. de PediatriaSciEL

Varieties of living things: Life at the intersection of lineage and metabolism

publication-status: Publishedtypes: Articl

Postpartum psychiatric disorders

Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential

Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences

Data availability: The 1000 Genomes phase I integrated callset used in this study is publicly available at [The 1000 Genomes Project. http://www.1000genomes.org/]. For a list of samples used in this study, refer to Table S1 in Additional file 1. Additional files: Additional file 1: This file contains supplementary Tables ST1 to ST4 (https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2014-15-6-r88/MediaObjects/13059_2014_3364_MOESM1_ESM.xlsx). Additional file 2: This file contains supplementary Figures F1 to F16 (https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2014-15-6-r88/MediaObjects/13059_2014_3364_MOESM2_ESM.pdf). Additional file 3: Full list of participants and institutions in the 1000 Genomes Project (https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2014-15-6-r88/MediaObjects/13059_2014_3364_MOESM3_ESM.pdf).Copyright © 2014 Colonna et al. Background: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. Results: We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. Conclusions: We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.The Wellcome Trust (098051), an Italian National Research Council (CNR) short-term mobility fellowship from the 2013 program to VC, and an EMBO Short Term Fellowship ASTF 324–2010 to VC