There has been an exponential rise in research into the microbiota of the human gastrointestinal tract, particularly of the genomic content (the microbiome). The vast number of micro-organisms residing in our gut has an integral role in essential processes, including growth and development. Probiotics, live micro-organisms with putative benefits on health have become ubiquitous as treatments for many conditions, despite often limited robust clinical trial data. However, the resurgence of faecal microbial transplantation as an effective treatment modality provides further promise that manipulation of our microbiome can have clinical benefits. This review will present the recent evidence for the role of the microbiome in development and growth, and focus on the evidence for its manipulation in paediatric diseases. We will show that while there is promising data in specific diseases, there remain many unanswered questions. Only through a deeper understanding of our complex internal ecosystem will we be able to move to the next stage of targeted microbial therapy.Aim of the study The diagnosis of heart failure in the emergency department (ED) is challenging. The aim of this study was to evaluate systolic time intervals (STIs) using phonoelectrocardiography for the diagnosis of heart failure (HF) in ED patients with undifferentiated dyspnea. Methods A total of 855 patients with dyspnea and suspected HF were prospectively enrolled. They underwent echocardiographic measurements of left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP) testing and computerized phonoelectrocardiography to assess STIs including electromechanical activation time (EMAT), left ventricular ejection time (LVET) and EMAT/LVET ratio. Diagnosis accuracy of STIs was calculated including sensitivity, specificity, likelihood ratio and receiver operating characteristic (ROC) curve. Results Patients with HF (n=530) had significantly higher EMAT and lower LVET compared to non HF patients. ROC curve c-statistic was 0.74, 0.72, and 0.78 respectively for EMAT, LVET, and EMAT/LVET. Sensitivity and specificity of EMAT/LVET at acut-off=40% were 72% and 88%respectively.EMAT/LVET had the highest correlation with LVEF(r=0.48). In patients with intermediate BNP (n=107), positive likelihood ratio increased from 1.8with BNP alone to 3.6 with BNP combined to EMAT/LVET. Patients without HF had STIs values not significantly different from those with preserved LVEF (≥45%). Conclusions Given their immediate availability, phonoelectrocardiography STIs’ parameters and particularly EMAT/LVET ratio could have an important role in the diagnosis approach of HF in patients with undifferentiated dyspnea in the ED.Antenatal glucocorticoid therapy reduces mortality in the preterm infant, but evidence suggests off-target adverse effects on the developing cardiovascular system. Whether deleterious effects are direct on the offspring or secondary to alterations in uteroplacental physiology is unclear. Here, we isolated direct effects of glucocorticoids using the chicken embryo, a model system in which the effects on the developing heart and circulation of therapy can be investigated, independent of effects on the mother and/or the placenta. Fertilized chicken eggs were incubated and divided randomly into control (C) or dexamethasone (Dex) treatment at day 14 out of the 21-day incubation period. RNA Synthesis inhibitor Combining functional experiments at the isolated organ, cellular and molecular levels, embryos were then studied close to term. Chicken embryos exposed to dexamethasone were growth restricted and showed systolic and diastolic dysfunction, with an increase in cardiomyocyte volume but decreased cardiomyocyte nuclear density in the left ventricle. Underlying mechanisms included a premature switch from tissue accretion to differentiation, increased oxidative stress, and activated signaling of cellular senescence. These findings, therefore, demonstrate that dexamethasone treatment can have direct detrimental off-target effects on the cardiovascular system in the developing embryo, which are independent of effects on the mother and/or placenta.Hepatocellular carcinoma (HCC) is an aggressive malignancy which is often associated with a complex tumor microenvironment due to etiology-induced cellular inflammation. γδ T-cells are known to detect and react to chronic inflammation, which is linked to cancer development, progression and metastasis. Our recent genomic study revealed an increased infiltration of several immune cell types including γδ T-cells in tumor microenvironments of a Thai HCC subtype associated with a good prognosis. Here, we quantified the amount of γδ T-cells using a γδ T-cell-specific gene signature in 247 Chinese HCC patients. We also validated the γδ T-cell signature in American HCC patients. Additionally, such an association was only found in tumor transcriptomic data but not in adjacent non-tumor transcriptomic data, suggesting a selective enrichment of γδ T-cells in the tumor microenvironment. Moreover, the γδ T-cell signature was positively correlated with the expression of natural killer cell receptor genes such as NKG2D, and cytolytic T-cell genes granzymes (GRNXX) and perforin (PRF1), suggesting a stronger T-cell mediated cytotoxic activity. Furthermore, we found that the γδ T cell-specific gene expression is positively correlated with the expression of CCL4/CCL5 and CCR1/CCR5, the receptors for γδ T-cells. We validated these results using immunohistochemical analysis of formalin-fixed, paraffin-embedded tumor biopsies from 182 HCC patients. Moreover, we found evidence of CCL4/CCL5-mediated recruitment of γδ T cells both in vitro and in a murine orthotopic Hepa1-6 HCC model. We propose that CCL4/CCL5 may interact with their receptor CCR1/CCR5, which may facilitate the recruitment of γδ T-cells from peripheral blood or peritumor regions to the tumor regions. Consequently, an increasing infiltration of γδ T-cells in tumors may enhance anti-tumor immunity and improve patients’ prognosis.The interface between the mammalian host and its environment is formed by barrier tissues, for example, of the skin, and the respiratory and the intestinal tracts. On the one hand, barrier tissues are colonized by site-adapted microbial communities, and on the other hand, they contain specific myeloid cell networks comprising macrophages, dendritic cells, and granulocytes. These immune cells are tightly regulated in function and cell number, indicating important roles in maintaining tissue homeostasis and immune balance in the presence of commensal microorganisms. The regulation of myeloid cell density and activation involves cell-autonomous ‘single-loop circuits’ including autocrine mechanisms. However, an array of microenvironmental factors originating from nonimmune cells and the microbiota, as well as the microanatomical structure, impose additional layers of regulation onto resident myeloid cells. This review discusses models integrating these factors into cell-specific programs to instruct differentiation and proliferation best suited for the maintenance and renewal of immune homeostasis in the tissue-specific environment.