Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR) compared with normal newborns (AGA). This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth.</p> <p>Methods</p> <p>Whole villous tissue was collected at birth from FGR (N = 20) and AGA neonates (N = 28). Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks), and principal component analysis and connectivity map.</p> <p>Results</p> <p>The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates.</p> <p>Conclusion</p> <p>These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.</p

Sotagliflozin in patients with diabetes and chronic kidney disease

BACKGROUND: The efficacy and safety of sodium-glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney disease with or without albuminuria have not been well studied. METHODS: We conducted a multicenter, double-blind trial in which patients with type 2 diabetes mellitus (glycated hemoglobin level, ≥7%), chronic kidney disease (estimated glomerular filtration rate, 25 to 60 ml per minute per 1.73 m 2 of body-surface area), and risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or placebo. The primary end point was changed during the trial to the composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. The trial ended early owing to loss of funding. RESULTS: Of 19,188 patients screened, 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292 assigned to the placebo group, and followed for a median of 16 months. The rate of primary end-point events was 5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.63 to 0.88; P<0.001). The rate of deaths from cardiovascular causes per 100 patient-years was 2.2 with sotagliflozin and 2.4 with placebo (hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.35). For the original coprimary end point of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, the hazard ratio was 0.84 (95% CI, 0.72 to 0.99); for the original coprimary end point of the first occurrence of death from cardiovascular causes or hospitalization for heart failure, the hazard ratio was 0.77 (95% CI, 0.66 to 0.91). Diarrhea, genital mycotic infections, volume depletion, and diabetic ketoacidosis were more common with sotagliflozin than with placebo. CONCLUSIONS: In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure than placebo but was associated with adverse events. (Funded by Sanofi and Lexicon Pharmaceuticals; SCORED ClinicalTrials.gov number, NCT03315143.)

Adherence to guidelines in CHF therapy in Germany - a subgroup analysis of the Mahler survey

Background and objective: The MAHLER survey examined the impact of the European guidelines for the treatment of chronic heart failure (CHF). Especially, the trial addressed the question whether adherence to treatment guidelines leads to a reduction in the rate of CHF and cardiovascular (CV) hospitalization. The present sub-study presents the Germany specific data of the MAHLER study and compares the results with the results in other European countries. Patients and method: The global adherence index (GAI) shows the proportion of correctly prescribed heart failure medications per patient. Class adherence indicators for angiotensin-converting enzyme (AC) inhibitors, beta-blockers, spironolactone, diuretics and cardiac glycosides and general adherence indicators (GAI3 adherence to first three classes of heart failure medications, GAI5 adherence to five classes) were constructed. In the German sub-study, 251 patients were included, who were seen by 21 cardiologists in private practice (mean age 68.6 +/- 10.4 years; 173 man, 78 woman; 158 NYHA II; 91 NYHA III, 2 NYHA IV). Results: Mean adherence to CHF therapy guidelines was 63% for GAI3, 62% for GAI5. Compared to the other MAHLER-study countries, Germany was on place two and three concerning GAI3 and GAI5, respectively. Strong adherence to treatment guidelines in Germany led to a reductionof CHF and CV hospitalization rate by 40% (p <0.033). Thus, the German data confirm the results of the international study indicating that a good GAI3 performance is an independent predictor of time to hospitalization. Hithero, the relative risk for hospitalization was higher for CHF patients in Germany than for patients in all other European countries. Conclusions: In Germany like in other European countries, guideline adherence for CHF therapy leads to a reduction in hospitalization rate

A Comprehensive Study of Particle Size Distributions with the Use of PostInjection Strategies in DI Diesel Engines

[EN] Control strategies such as variations in injection pressure and timing have been used by researchers to reduce in-cylinder exhaust emissions and meet legislation standards. Postinjection has been studied for several years and is now well known as an efficient strategy for reducing soot emission. Diesel gaseous and particle mass emissions have been progressively reduced over the last twenty years as a consequence of increasingly restrictive emission legislation and the application of aftertreatment devices. The main objective of this work is to better understand the effect of postinjection on particle size distribution in diesel exhaust. The approach uses a modern, well-instrumented research engine test cell equipped with a flexible high pressure fuel injection system. The results of this work provide guidelines for developing strategies to reduce particle size distribution in diesel engines. A major improvement in particle size distribution was found in the accumulation mode by using a close postinjection of a small quantity of fuel. For reduction in nucleation mode, a relationship was found with close postinjections of large quantities of fuel. Copyright © American Association for Aerosol Research.We would like to thank the R&D&D&I Linguistic Assistance Office, Universidad Politecnica de Valencia, Spain, for granting financial support for the linguistic revision of this paper.Desantes, J.; Bermúdez, V.; García Martínez, A.; Linares Rodríguez, WG. (2011). A Comprehensive Study of Particle Size Distributions with the Use of PostInjection Strategies in DI Diesel Engines. Aerosol Science and Technology. 45(10):1161-1175. doi:10.1080/02786826.2011.582898S11611175451