Refining empiric subgroups of pediatric sepsis using machine-learning techniques on observational data.

Sepsis contributes to 1 of every 5 deaths globally with 3 million per year occurring in children. To improve clinical outcomes in pediatric sepsis, it is critical to avoid "one-size-fits-all" approaches and to employ a precision medicine approach. To advance a precision medicine approach to pediatric sepsis treatments, this review provides a summary of two phenotyping strategies, empiric and machine-learning-based phenotyping based on multifaceted data underlying the complex pediatric sepsis pathobiology. Although empiric and machine-learning-based phenotypes help clinicians accelerate the diagnosis and treatments, neither empiric nor machine-learning-based phenotypes fully encapsulate all aspects of pediatric sepsis heterogeneity. To facilitate accurate delineations of pediatric sepsis phenotypes for precision medicine approach, methodological steps and challenges are further highlighted.

Early triggers of moderately high-fat diet-induced kidney damage.

Most of the obesity murine models inducing renal injury use calorie-enriched foods, where fat represents 60% of the total caloric supply, however, this strategy doubles the standard proportion of fat ingestion in obese patients. Therefore, it is crucial to study the impact of a high-fat intake on kidney physiology that resembles common obesity in humans to understand the trigger mechanisms of the long-term consequences of overweight and obesity. In this study, we analyzed whether chronic feeding with a moderately high fat diet (MHFD) representing 45% of total calories, may induce kidney function and structural injury compared to C57BL/6 mice fed a control diet. After 14 weeks, MHFD induced significant mice obesity. At the functional level, obese mice showed signs of kidney injury characterized by increased albuminuria/creatinine ratio and higher excretion of urinary biomarkers of kidney damage. While, at the structural level, glomerular hypertrophy was observed. Although, we did not detect renal fibrosis, the obese mice exhibited a significant elevation of Tgfb1 mRNA levels. Kidney damage caused by the exposure to MHFD was associated with greater oxidative stress, renal inflammation, higher endoplasmic reticulum (ER)-stress, and disruption of mitochondrial dynamics. In summary, our data demonstrate that obesity induced by a milder fat content diet is enough to establish renal injury, where oxidative stress, inflammation, ER-stress, and mitochondrial damage take relevance, pointing out the importance of opportune interventions to avoid the long-term consequences associated with obesity and metabolic syndrome.

An integrative view of serpins in health and disease: the contribution of SerpinA3.

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular diseases, and kidney disorders are intensively studied to find effective therapeutic targets. Given the serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin has been associated with diverse pathophysiological events. In particular, we focus here on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.