Bmc Med
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Excess body weight is a major risk factor for cardiometabolic diseases. The complex molecular mechanisms of body weight change-induced metabolic perturbations are not fully understood. Specifically, in-depth molecular characterization of long-term body weight change in the general population is lacking. Here, we pursued a multi-omic approach to comprehensively study metabolic consequences of body weight change during a seven-year follow-up in a large prospective study. ⋯ Long-term weight change in the general population globally associates with serum metabolite concentrations. An integrated metabolomics and transcriptomics approach improved the understanding of molecular mechanisms underlying the association of weight gain with changes in lipid and amino acid metabolism, insulin sensitivity, mitochondrial function as well as blood cell development and function.
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Alcohol consumption patterns change across life and this is not fully captured in cross-sectional series data. Analysis of longitudinal data, with repeat alcohol measures, is necessary to reveal changes within the same individuals as they age. Such data are scarce and few studies are able to capture multiple decades of the life course. Therefore, we examined alcohol consumption trajectories, reporting both average weekly volume and frequency, using data from cohorts with repeated measures that cover different and overlapping periods of life. ⋯ This is the first attempt to synthesise longitudinal data on alcohol consumption from several overlapping cohorts to represent the entire life course and illustrates the importance of recognising that this behaviour is dynamic. The aetiological findings from epidemiological studies using just one exposure measure of alcohol, as is typically done, should be treated with caution. Having a better understanding of how drinking changes with age may help design intervention strategies.
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The tumor microenvironment (TME) is being increasingly recognized as a key factor in multiple stages of disease progression, particularly local resistance, immune-escaping, and distant metastasis, thereby substantially impacting the future development of frontline interventions in clinical oncology. An appropriate understanding of the TME promotes evaluation and selection of candidate agents to control malignancies at both the primary sites as well as the metastatic settings. ⋯ As benign cells in TME niches actively modulate response of cancer cells to a broad range of standard chemotherapies and targeted agents, cancer-oriented therapeutics should be combined with TME-targeting treatments to achieve optimal clinical outcomes. Overall, a body of updated information is delivered to summarize recently emerging and rapidly progressing aspects of TME studies, and to provide a significant guideline for prospective development of personalized medicine, with the long term aim of providing a cure for cancer patients.
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Over 90% of the world's severe and fatal Plasmodium falciparum malaria is estimated to affect young children in sub-Sahara Africa, where it remains a common cause of hospital admission and inpatient mortality. Few children will ever be managed on high dependency or intensive care units and, therefore, rely on simple supportive treatments and parenteral anti-malarials. ⋯ Human trials of supportive therapies carried out on the basis of pathophysiology studies, have so far made little progress on reducing mortality; despite appearing to reduce morbidity endpoints, more often than not they have led to an excess of adverse outcomes. This review highlights the spectrum of complications in African children with severe malaria, the therapeutic challenges of managing these in resource-poor settings and examines in-depth the results from clinical trials with a view to identifying the treatment priorities and a future research agenda.
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Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. ⋯ We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.