Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring

Increasing maternal obesity is a challenge that has an impact on all aspects of female reproduction. Lean and obese pregnant women gain similar fat mass, but lean women store fat in the lower-body compartment and obese women in central compartments. In the non-pregnant, central storage of fat is associated with adipocyte hypertrophy and represents a failure to adequately store excess fatty acids, resulting in metabolic dysregulation and ectopic fat accumulation (lipotoxicity). Obese pregnancy is associated with exaggerated metabolic adaptation, endothelial dysfunction and increased risk of adverse pregnancy outcome. We hypothesize that the preferential storage of fat in central rather than ‘safer’ lower-body depots in obese pregnancy leads to lipotoxicity. The combination of excess fatty acids and oxidative stress leads to the production of oxidized lipids, which can be cytotoxic and influence gene expression by acting as ligands for nuclear receptors. Lipid excess and oxidative stress provoke endothelial dysfunction. Oxidized lipids can inhibit trophoblast invasion and influence placental development, lipid metabolism and transport and can also affect fetal developmental pathways. As lipotoxicity has the capability of influencing both maternal endothelial function and placental function, it may link maternal obesity and placentally related adverse pregnancy outcomes such as miscarriage and pre-eclampsia. The combination of excess/altered lipid nutrient supply, suboptimal in utero metabolic environment and alterations in placental gene expression, inflammation and metabolism may also induce obesity in the offspring

Flexible Organic Crystals for Light Delivery in Biological Tissues

PDF Tools Share Optically transmissive materials are indispensable for the transmission of light or light-encoded signals in telecommunications and optobiomedical techniques. Here, we propose that slender crystals of small organic molecules can be used as optically transparent, flexible, lightweight, and emissive media to deliver photons into or through biological tissues as an alternative to silica- or polymer-based light waveguides. We demonstrate that organic crystals remain transmissive in various porcine tissues, and their efficiency in light transduction depends on the intrinsic optical properties of the crystal, optical path, geometry of excitation, and the type of tissue. Moreover, elastically or plastically deformable organic crystals remain mechanically compliant and can be bent after they have been embedded in the tissue, opening prospects for designing a new class of biocompatible light waveguiding elements based on crystalline organic materials. In vivo implantation and toxicity assays capitalize on mechanical flexibility and biocompatibility in animal models. Within a broader context, the high transparency, anisotropy, and biocompatibility of some organic crystals turn this emerging class of materials into a prospective platform for delivering photons for specific interaction with target cells in tissues for applications such as photodynamic therapy and optogenetics

Endoplasmic reticulum stress-induced hepatocellular death pathways mediate liver injury and fibrosis via Stimulator of Interferon Genes.

Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT, IRF3-, TRAM-, TRIF-, and STING-deficient mice. We report that acute CCl4 administration to WT mice resulted in early ER stress, activation of IRF3 and Type-I IFNs, followed by hepatocyte apoptosis and liver injury, accompanied by liver fibrosis upon repeated administration of CCl4. Deficiency of IRF3 or STING prevented hepatocyte death and fibrosis both in acute or chronic CCl4. In contrast, mice deficient in Type-I IFN receptors or in TLR4-signaling adaptors, TRAM or TRIF, upstream of IRF3, were not protected from hepatocyte death and/or fibrosis suggesting that the pro-apoptotic role of IRF3 is independent of TLR signaling in fibrosis. Hepatocyte death is required for liver fibrosis with causal involvement of STING and IRF3. Thus, our results identify that IRF3, by its association with STING in the presence of ER stress, couples hepatocyte apoptosis with liver fibrosis, and indicate that innate immune signaling modulates outcomes of liver fibrosis via modulation of hepatocyte death in the liver

Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations

BACKGROUND: Chronic alcohol consumption is associated with neuroinflammation, neuronal damage, and behavioral alterations including addiction. Alcohol-induced neuroinflammation is characterized by increased expression of proinflammatory cytokines (including TNFalpha, IL-1beta, and CCL2) and microglial activation. We hypothesized chronic alcohol consumption results in peripheral immune cell infiltration to the CNS. Since chemotaxis through the CCL2-CCR2 signaling axis is critical for macrophage recruitment peripherally and centrally, we further hypothesized that blockade of CCL2 signaling using the dual CCR2/5 inhibitor cenicriviroc (CVC) would prevent alcohol-induced CNS infiltration of peripheral macrophages and alter the neuroinflammatory state in the brain after chronic alcohol consumption. METHODS: C57BL/6J female mice were fed an isocaloric or 5% (v/v) ethanol Lieber DeCarli diet for 6 weeks. Some mice received daily injections of CVC. Microglia and infiltrating macrophages were characterized and quantified by flow cytometry and visualized using CX3CR1(eGFP/+) CCR2(RFP/+) reporter mice. The effect of ethanol and CVC treatment on the expression of inflammatory genes was evaluated in various regions of the brain, using a Nanostring nCounter inflammation panel. Microglia activation was analyzed by immunofluorescence. CVC-treated and untreated mice were presented with the two-bottle choice test. RESULTS: Chronic alcohol consumption induced microglia activation and peripheral macrophage infiltration in the CNS, particularly in the hippocampus. Treatment with CVC abrogated ethanol-induced recruitment of peripheral macrophages and partially reversed microglia activation. Furthermore, the expression of proinflammatory markers was upregulated by chronic alcohol consumption in various regions of the brain, including the cortex, hippocampus, and cerebellum. Inhibition of CCR2/5 decreased alcohol-mediated expression of inflammatory markers. Finally, microglia function was impaired by chronic alcohol consumption and restored by CVC treatment. CVC treatment did not change the ethanol consumption or preference of mice in the two-bottle choice test. CONCLUSIONS: Together, our data establish that chronic alcohol consumption promotes the recruitment of peripheral macrophages into the CNS and microglia alterations through the CCR2/5 axis. Therefore, further exploration of the CCR2/5 axis as a modulator of neuroinflammation may offer a potential therapeutic approach for the treatment of alcohol-associated neuroinflammation

Relationship Between Excessive Gestational Weight Gain and Neonatal Adiposity in Women With Mild Gestational Diabetes Mellitus:

To evaluate the relationships between excessive gestational weight gain, neonatal adiposity, and adverse obstetric outcomes in women with mild gestational diabetes mellitus (GDM)

Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes

Use of Carpenter-Coustan compared to National Diabetes Data Group (NDDG) criteria increases the number of women diagnosed with GDM by 30-50%, but whether treatment of this milder GDM reduces adverse outcomes is unknown. We explored the effects of the diagnostic criteria used on the benefits of GDM treatment

UEMS Training Requirements for Angiology and Vascular Medicine: European Standards of Postgraduate Medical Specialist Training (ETR Document)

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Participation in boys and girls clubs: motivation and stage environment fit

This article presents the results of semi-structured in-depth interviews conducted with 54 youth attending six elementary school-based and middle school-based Boys and Girls Clubs in two low-income communities. The first goal of this study was to examine why youth choose to participate in these clubs. The most commonly reported motives include fun activities, opportunities to be with friends, parent has to work, and getting help with homework. The second goal was to examine youths' perceptions of staff, peers, activities, and the extent to which clubs are organized in a way to support the need for relatedness, competence, and autonomy. Variations in youths' perceptions of the quality of relationships with staff and peers, level of interest and challenge, and opportunities for decision making, by developmental level (elementary versus middle school) are discussed. Implications of our findings for sustaining youths' interest and continued involvement in out-of-school youth development programs are highlighted. © 2010 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69176/1/20369_ftp.pd

Is There a Threshold Oral Glucose Tolerance Test Value for Predicting Adverse Pregnancy Outcome?

To determine whether there is a threshold 3-hour OGTT value associated with accelerated risk of adverse pregnancy outcomes

The Obstetric and Neonatal Implications of a Low Value on the 50-g Glucose Screening Test

To assess the relationship between a low 50-g 1-hour glucose loading test (GLT) and maternal and neonatal outcomes in women without diabetes