Changes in plasma fatty acid composition are associated with improvements in obesity and related metabolic disorders: A therapeutic approach to overweight adolescents

Background & aims: In recent years, obesity has reached alarming levels among children and adolescents. The study of plasma fatty acid (FA) composition, as a reflection of diet, and its associations with other parameters, that are closely linked to obesity and the cardiometabolic profile, may be useful for setting nutritional goals for obesity treatment and prevention. This study explored the relationship between plasma FA levels and body fat and cardiometabolic risk markers, in overweight adolescents. Methods: A multidisciplinary weight loss program was followed by 127 overweight and obese adolescents aged 12-17 years old. Plasma FA composition, anthropometric indicators of adiposity and biochemical parameters were analyzed at baseline, two months (the end of the intensive intervention phase) and six months (the end of the extensive phase). Results: While saturated fatty acid (SFA) and n-6 polyunsaturated fatty acid (PUFA) levels decreased significantly during the intervention, monounsaturated fatty acid (MUFA) and n-3 PUFA showed the opposite trend. The decrease in SFA C14:0 was associated with a reduction in total and LDL cholesterol, apolipoprotein B and insulin. The increase in MUFAs, especially C18:1n-9, was related to a reduction in weight, fat mass, fat mass index and glucose. Regarding PUFAs, changes in the n-3 series were not associated with any of the parameters studied, whereas the reduction in n-6 PUFA5 was directly related to weight, fat mass, total and HDL cholesterol, apolipoprotein Al, glucose and insulin, and inversely associated with diastolic blood pressure. The adolescents with greater weight loss presented significant changes in MUFAs, n-6 PUFA5 and C14:0. Conclusions: Modifications in plasma FA composition were associated with adiposity reduction and cardiometabolic profile improvement in an anti-obesity program aimed at adolescents. The changes observed in FA composition were related to the success of the treatment, since the individuals most affected by these variations were those who presented the greatest weight loss

Elevated catalase expression in a fungal pathogen is a double-edged sword of iron

We thank our colleagues in the Aberdeen Fungal Group, Lloyd Peck (British Antarctic Survey) and John Helmann (Cornell University) for insightful discussions. We thank Christophe d’Enfert and Melanie Legrand (Institut Pasteur) for help with the design of barcodes and provision of the CIp10-PTET-GTw overexpression vector and CEC2908 strain. We are grateful to the following Core Facilities at the University of Aberdeen for their excellent technical assistance, advice and support: the Medical Research Facility; the Centre for Genome Enabled Biology and Medicine; the Iain Fraser Cytometry Centre; the Microscopy and Histology Facility; Aberdeen Proteomics; and the qPCR Facility.Peer reviewedPublisher PD

A Computational Approach to Understand In Vitro Alveolar Morphogenesis

Primary human alveolar type II (AT II) epithelial cells maintained in Matrigel cultures form alveolar-like cysts (ALCs) using a cytogenesis mechanism that is different from that of other studied epithelial cell types: neither proliferation nor death is involved. During ALC formation, AT II cells engage simultaneously in fundamentally different, but not fully characterized activities. Mechanisms enabling these activities and the roles they play during different process stages are virtually unknown. Identifying, characterizing, and understanding the activities and mechanisms are essential to achieving deeper insight into this fundamental feature of morphogenesis. That deeper insight is needed to answer important questions. When and how does an AT cell choose to switch from one activity to another? Why does it choose one action rather than another? We report obtaining plausible answers using a rigorous, multi-attribute modeling and simulation approach that leveraged earlier efforts by using new, agent and object-oriented capabilities. We discovered a set of cell-level operating principles that enabled in silico cells to self-organize and generate systemic cystogenesis phenomena that are quantitatively indistinguishable from those observed in vitro. Success required that the cell components be quasi-autonomous. As simulation time advances, each in silico cell autonomously updates its environment information to reclassify its condition. It then uses the axiomatic operating principles to execute just one action for each possible condition. The quasi-autonomous actions of individual in silico cells were sufficient for developing stable cyst-like structures. The results strengthen in silico to in vitro mappings at three levels: mechanisms, behaviors, and operating principles, thereby achieving a degree of validation and enabling answering the questions posed. We suggest that the in silico operating principles presented may have a biological counterpart and that a semiquantitative mapping exists between in silico causal events and in vitro causal events

Multiple Cellular Responses to Serotonin Contribute to Epithelial Homeostasis

Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover) enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis) form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A), we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis) to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers)

Cyclic AMP signalling pathways in the regulation of uterine relaxation

Studying the mechanism(s) of uterine relaxation is important and will be helpful in the prevention of obstetric difficulties such as preterm labour, which remains a major cause of perinatal mortality and morbidity. Multiple signalling pathways regulate the balance between maintaining relative uterine quiescence during gestation, and the transition to the contractile state at the onset of parturition. Elevation of intracellular cyclic AMP promotes myometrial relaxation, and thus quiescence, via effects on multiple intracellular targets including calcium channels, potassium channels and myosin light chain kinase. A complete understanding of cAMP regulatory pathways (synthesis and hydrolysis) would assist in the development of better tocolytics to delay or inhibit preterm labour. Here we review the enzymes involved in cAMP homoeostasis (adenylyl cyclases and phosphodiesterases) and possible myometrial substrates for the cAMP dependent protein kinase. We must emphasise the need to identify novel pharmacological targets in human pregnant myometrium to achieve safe and selective uterine relaxation when this is indicated in preterm labour or other obstetric complications

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true