Search

Supplemental Digital Content is available in the text.

Retrospective study to examine the outcomes of acute kidney injury requiring dialysis (AKI-D) patients that received outpatient hemodialysis as part of continued AKI-D care and explore factors associated with recovery of kidney function and discontinuation of dialysis.

The association between altered gut microbiota, intestinal permeability, inflammation and cardiometabolic diseases is becoming increasingly clear but remains poorly understood1,2. Indoleamine 2,3-dioxygenase is an enzyme induced in many types of immune cells, including macrophages in response to inflammatory stimuli, and catalyzes the degradation of tryptophan along the kynurenine pathway. Indoleamine 2,3-dioxygenase activity is better known for its suppression of effector T cell immunity and its activation of regulatory T cells3,4. However, high indoleamine 2,3-dioxygenase activity predicts worse cardiovascular outcome5–9and may promote atherosclerosis and vascular inflammation6, suggesting a more complex role in chronic inflammatory settings. Indoleamine 2,3-dioxygenase activity is also increased in obesity10–13, yet its role in metabolic disease is still unexplored. Here, we show that obesity is associated with an increase of intestinal indoleamine 2,3-dioxygenase activity, which shifts tryptophan metabolism from indole derivative and interleukin-22 production toward kynurenine production. Indoleamine 2,3-dioxygenase deletion or inhibition improves insulin sensitivity, preserves the gut mucosal barrier, decreases endotoxemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. These beneficial effects are due to rewiring of tryptophan metabolism toward a microbiota-dependent production of interleukin-22 and are abrogated after treatment with a neutralizing anti-interleukin-22 antibody. In summary, we identify an unexpected function of indoleamine 2,3-dioxygenase in the fine tuning of intestinal tryptophan metabolism with major consequences on microbiota-dependent control of metabolic disease, which suggests indoleamine 2,3-dioxygenase as a potential therapeutic target.

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5bproximal promoter and represses its expression. Silencing of Cox5bdecreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5bsilencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5Bgene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion.

This paper aims at designing optimal gear shift strategies for conventional passenger vehicles equipped with discrete ratio transmissions. In order to study quantitatively an optimal trade-off between the fuel economy and the driveability, the vehicle driveability is addressed in a fuel-optimal gear shift algorithm based on dynamic programming by three methods: method 1, weighted inverse of power reserve; method 2, constant power reserve; method 3, variable power reserve. Furthermore, another method based on stochastic dynamic programming is proposed to derive an optimal gear shift strategy over a number of driving cycles in an average sense, hence taking into account the vehicle driveability. In contrast with the dynamic-programming-based strategy, the obtained gear shift strategy based on stochastic dynamic programming is real time implementable. A comparative analysis of all proposed gear shift methods is given in terms of the improvements in the fuel economy and the driveability. The variable-power-reserve method achieves the highest fuel economy without sacrificing the driveability.

Sickle cell disease causes several kidney manifestations. They include defects in urine concentration, impaired handling of potassium and hydrogen ion, albuminuria, acute kidney injury, and chronic kidney disease to name a few. Glomerular hyperfiltration, tubular hyperfunctioning, endothelial damage from repeated sickling and vaso-occlusive episodes, and iron-induced proinflammatory changes in the glomerular mesangium and tubulointerstitium are some of the mechanisms of kidney damage. Albuminuria is one of the most and common clinical features of kidney disease and progresses with age. Kidney disease in patients with sickle cell is associated with increased mortality. Annual screening for proteinuria starting at age 10 years and limiting the use of nonsteroidal anti-inflammatory agents and the use of angiotensin-converting enzyme inhibitors may help in early detection and delaying the progression of kidney disease. Adequate hydration, angiotensin-converting enzyme inhibitors, and adequate control of sickle cell are the main stay of treatment for albuminuria. The hemoglobin goal for patients with sickle cell nephropathy is lesser (10 g/dL) than that for patients with chronic kidney disease due to other causes given that a higher hemoglobin level increases viscosity and the risk of precipitating vaso-occlusive episodes. A multidisciplinary approach is recommended for managing patients with sickle cell and kidney diseases.

Navarrete x Kajiyama Dance Theater creates interdisciplinary performance works using movement, theater, art installation, and site-specific environments. Our work has been influenced by ritual, cultural studies, and the political and environmental concerns of the world in which we live.