High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta

Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. © 2013 the American Physiological Society.This study was supported by a grant from the Carlos III Health Institute (CP08/00106), the Spanish Ministry of Science and Innovation (SAF2009-11282), and the FP7-PEOPLE-2009-RG (PIRG06-GA-2009-25369) to G. Perdomo; a grant from the Consejería de Salud, Junta de Andalucía (N°0269/05.2005) to J. L. Bartha; and grant from the Carlos III Health Institute (PI11/00676) to F. Bugatto.Peer Reviewe

Changes in the Serotype Distribution of Streptococcus Pneumoniae Causing Otitis Media After PCV13 Introduction in Spain

One of the beneficial effects of pneumococcal conjugate vaccines (PCVs) has been a decrease in the incidence of non-invasive infections, such as otitis media (OM) caused by vaccine serotypes. In this study, we analyzed the epidemiology of pneumococcal OM before and after PCV13 introduction in 2010. Between 2008 and 2016, the middle ear exudates from 2653 children under 14 years of age with OM were studied in two Spanish provinces (Gipuzkoa and Barcelona), and S. pneumoniae was isolated in 235 (8.9%) of cases. The 204 available isolates were serotyped and distributed in three 3-year periods: one before and two after PCV13 introduction (early and late post-PCV13). A significant decrease in the rate of OM caused by S. pneumoniae was observed mainly due to a decrease in infections caused by all PCV13 serotypes, although exceptions were observed including the persistence of serotype 3 in Gipuzkoa and a weak re-emergence of serotype 19F in both regions. The rate and diversity of non-PCV13 serotypes increased in both regions and an emerging clone causing OM was detected in each region: serotype 23B ST2372 in Gipuzkoa and serotype 11A ST838/ST6521 in Barcelona. The introduction of PCV13 has been followed by a change in the epidemiology of pneumococcal OM, with a decrease in the rate of vaccine serotypes accompanied by an increase in the diversity of non-vaccine serotype and the clonal spreading of different single clones in each region.JMM was funded in part by the Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES-26). CMA was funded in part by the Centro de Investigacion Biomedica en Red de de Epidemiologia y Salud Publica (CIBERESP-57). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was funded in part by the Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES-26) and de Epidemiologia y Salud Publica (CIBERESP-57)

High-resolution mapping of forest carbon stocks in the Colombian Amazon

High-resolution mapping of tropical forest carbon stocks can assist forest management and improve implementation of large-scale carbon retention and enhancement programs. Previous high-resolution approaches have relied on field plot and/or light detection and ranging (LiDAR) samples of aboveground carbon density, which are typically upscaled to larger geographic areas using stratification maps. Such efforts often rely on detailed vegetation maps to stratify the region for sampling, but existing tropical forest maps are often too coarse and field plots too sparse for high-resolution carbon assessments. We developed a top-down approach for high-resolution carbon mapping in a 16.5 million ha region (> 40%) of the Colombian Amazon – a remote landscape seldom documented. We report on three advances for large-scale carbon mapping: (i) employing a universal approach to airborne LiDAR-calibration with limited field data; (ii) quantifying environmental controls over carbon densities; and (iii) developing stratification- and regression-based approaches for scaling up to regions outside of LiDAR coverage. We found that carbon stocks are predicted by a combination of satellite-derived elevation, fractional canopy cover and terrain ruggedness, allowing upscaling of the LiDAR samples to the full 16.5 million ha region. LiDAR-derived carbon maps have 14% uncertainty at 1 ha resolution, and the regional map based on stratification has 28% uncertainty in any given hectare. High-resolution approaches with quantifiable pixel-scale uncertainties will provide the most confidence for monitoring changes in tropical forest carbon stocks. Improved confidence will allow resource managers and decision makers to more rapidly and effectively implement actions that better conserve and utilize forests in tropical regions

High levels of anti-tuberculin (IgG) antibodies correlate with the blocking of T-cell proliferation in individuals with high exposure to Mycobacterium tuberculosis

OBJECTIVES: To determine the effect of anti-tuberculin antibodies in the T-cell proliferation in response to tuberculin and Candida antigens in individuals with different levels of tuberculosis (TB) risk. METHODS: Sixteen high-risk TB individuals, 30 with an intermediate TB risk (group A), and 45 with a low TB risk (group B), as well as 49 control individuals, were studied. Tuberculin skin test (TST) results were analyzed and serum levels of antibodies (IgG and IgM) against purified protein derivative (PPD) were measured by ELISA. Tuberculin and Candida antigens were used to stimulate T-cell proliferation in the presence of human AB serum or autologous serum. RESULTS: High levels of anti-tuberculin IgG antibodies were found to be significantly associated with the blocking of T-cell proliferation responses in cultures stimulated with tuberculin but not with Candida antigens in the presence of autologous serum. This phenomenon was particularly frequent in high-risk individuals with high levels of anti-tuberculin IgG antibodies in the autologous serum when compared to the other risk groups, which exhibited lower levels of anti-tuberculin antibodies. CONCLUSIONS: Although cellular immunity plays a central role in the protection against TB, humoral immunity is critical in the control of Mycobacterium tuberculosis infection in high-risk individuals with latent TB infection

Second-trimester Ultrasound and Neuropathologic Findings in Congenital Zika Virus Infection.

Zika virus is a mosquito-borne virus that causes congenital Zika syndrome, characterized by microcephaly and other fetal brain anomalies. This case report presents a case of Zika virus-related fetal brain anomalies including pathologic evidence of cerebral neuronal apoptosis and macrophage infiltrates and intracerebral calcification, ventriculomegaly and corpus callosum dysgenesis detected by ultrasound at 18 weeks of pregnancy

The Cytokine Profile in Acute Chikungunya Infection is Predictive of Chronic Arthritis 20 Months Post Infection

The cytokine profile during acute chikungunya infection that predicts future chronic arthritis has not yet been investigated. We conducted a nested case-control study comparing serum cytokine concentrations during acute chikungunya infection in cases (n = 121) that reported the presence of chronic joint pain versus age- and gender-matched controls (n = 121) who reported recovery at 20 months post infection. We observed that a robust cytokine response during acute infection was correlated with a decreased incidence of chronic joint pain and that low TNFα, IL-13, IL-2, and IL-4 during acute infection was predictive of chronic joint pain. These data suggest that a robust cytokine response is necessary for viral clearance and cytokines that are related to immune tolerance during acute infection may be protective for chronic arthritis pathogenesis