Fibroblast Growth Factor 23 and Adverse Clinical Outcomes in Type 2 Diabetes:a Bitter-Sweet Symphony

Purpose of Review: Fibroblast growth factor 23 (FGF23) is a key phosphate-regulating hormone that has been associated with adverse outcomes in patients with chronic kidney disease (CKD). Emerging data suggest that FGF23 plays a specific role in type 2 diabetes, partly independent of kidney function. We aimed to summarize current literature on the associations between FGF23 and outcomes in patients with type 2 diabetes with or without CKD. Recent Findings: Several cohort studies have shown strong associations between plasma FGF23 and cardiovascular outcomes in diabetic CKD. Moreover, recent data suggest that FGF23 are elevated and may also be a risk factor for cardiovascular disease and mortality in type 2 diabetes patients without CKD, although the magnitude of the association is smaller than in CKD patients. Summary: Diabetes-related factors may influence plasma FGF23 levels, and a higher FGF23 levels seem to contribute to a higher cardiovascular and mortality risk in patients with type 2 diabetes. Although this risk may be relevant in diabetic individuals with preserved kidney function, it is strongly accentuated in diabetic nephropathy. Future studies should clarify if FGF23 is merely a disease severity marker or a contributor to adverse outcomes in type 2 diabetes and establish if antidiabetic medication can modify FGF23 levels

Regionalisation of asset values for risk analyses

International audienceIn risk analysis there is a spatial mismatch of hazard data that are commonly modelled on an explicit raster level and exposure data that are often only available for aggregated units, e.g. communities. Dasymetric mapping techniques that use ancillary information to disaggregate data within a spatial unit help to bridge this gap. This paper presents dasymetric maps showing the population density and a unit value of residential assets for whole Germany. A dasymetric mapping approach, which uses land cover data (CORINE Land Cover) as ancillary variable, was adapted and applied to regionalize aggregated census data that are provided for all communities in Germany. The results were validated by two approaches. First, it was ascertained whether population data disaggregated at the community level can be used to estimate population in postcodes. Secondly, disaggregated population and asset data were used for a loss evaluation of two flood events that occurred in 1999 and 2002, respectively. It must be concluded that the algorithm tends to underestimate the population in urban areas and to overestimate population in other land cover classes. Nevertheless, flood loss evaluations demonstrate that the approach is capable of providing realistic estimates of the number of exposed people and assets. Thus, the maps are sufficient for applications in large-scale risk assessments such as the estimation of population and assets exposed to natural and man-made hazards

Dietary Patterns Based on Estimated Glomerular Filtration Rate and Kidney Function Decline in the General Population:The Lifelines Cohort Study

No specific dietary patterns have been established that are linked with loss of kidney function. We aimed to identify an estimated glomerular filtration rate-based dietary pattern (eGFR-DP) and to evaluate its association with eGFR decline and chronic kidney disease (CKD) incidence in the general population. We included 78,335 participants from the Lifelines cohort in the Northern Netherlands. All participants had an eGFR >60 mL/min/1.73 m2 at baseline and completed a second visit five years later. The eGFR-DP was constructed at baseline using a 110-item food frequency questionnaire by reduced rank regression, stratified by sex. Logistic regression was performed to evaluated the association between the eGFR-DP score and either a ≥20% eGFR decline or incident CKD. Among women, eGFR-DP were characterized by high consumption of egg, cheese, and legumes and low consumption of sweets, white meat, and commercially prepared dishes. In men, eGFR-DP were characterized by high consumption of cheese, bread, milk, fruits, vegetables, and beer and low consumption of white and red meat. A higher eGFR-DP score was associated with a lower risk of a ≥20% eGFR decline (OR 4th vs. 1st quartile, women: 0.79 [95% CI: 0.73-0.87]; men: 0.67 [0.59-0.76]). The association between the eGFR-DP score and CKD incidence was lost upon adjustment for baseline eGFR. Our results provide support for dietary interventions to prevent kidney function decline in the general population

Estimation of the regional stock of residential buildings as a basis for a comparative risk assessment in Germany

International audienceOne important prerequisite for a comparable quantitative risk assessment for different types of hazards (e.g., earthquakes, windstorms and floods) is the use of a common database about and financial appraisal of the assets at risk. For damage assessments it is necessary to represent the values at risk on a regional disaggregated scale and to intersect them with hazard scenarios. This paper presents a methodology and results of a financial appraisal of residential buildings for all communities in Germany. The calculated values are defined as replacement values for the reference year 2000. The resulting average replacement costs for residential buildings per inhabitant amount to EUR 46 600, with considerable differences between communities. The inventory can be used for the calculations of direct losses from various natural disasters within the project "Risk Map Germany''

Mortality in kittens is associated with a shift in ileum mucosa-associated enteroccoci from E. hirae to biofilm-forming E. faecalis and adherent E. coli

Approximately ~15% of foster kittens die before 8-wks of age with most of these kittens demonstrating clinical signs or post-mortem evidence of enteritis. While a specific cause of enteritis is not determined in most cases; these kittens are often empirically administered probiotics that contain enterococci. The enterococci are members of the commensal intestinal microbiota but can also function as opportunistic pathogens. Given the complicated role of enterococci in health and disease, it would be valuable to better understand what constitutes a “healthy” enterococcal community in these kittens and how this microbiota is impacted by severe illness. In this study, we characterize the ileum mucosa-associated enterococcal community of 50 apparently healthy and 50 terminally ill foster kittens. In healthy kittens, E. hirae was the most common species of ileum mucosa-associated enterococci and was often observed to adhere extensively to the small intestinal epithelium. These E. hirae isolates generally lacked virulence traits. In contrast, non-E. hirae enterococci, notably E. faecalis, were more commonly isolated from the ileum mucosa of kittens with terminal illness. Isolates of E. faecalis had numerous virulence traits and multiple antimicrobial resistance. Moreover, attachment of E. coli to the intestinal epithelium was significantly associated with terminal illness and was not observed in any kitten with adherent E. hirae. These findings identify a significant difference in species of enterococci cultured from the ileum mucosa of kittens with terminal illness compared to healthy kittens. In contrast to prior case studies that associate enteroadherent E. hirae with diarrhea in young animals, these controlled studies identified E. hirae as more often isolated from healthy kittens and adherence of E. hirae as more common and extensive in healthy compared to sick kittens

The dehydration of N-acetylglucosamine (GlcNAc) to enantiopure dihydroxyethyl acetamidofuran (Di-HAF)

The first multi-gram synthesis of enantiopure dihydroxyethyl acetamidofuran (Di-HAF) is reported. Under optimized conditions, GlcNAc dehydrates in pyridine in the presence of phenylboronic acid and triflic acid to afford Di-HAF in 73% yield and 99.3% ee in just 30 minutes. This protocol opens the door for further research on this bio-renewable building block which is now available as a chiral pool synthon. A plausible mechanism of its formation and of the subsequent dehydration of Di-HAF into well-known 3-acetamido-5-acetylfuran (3A5AF) is proposed.</p

Observational and Genetic Evidence for Bidirectional Effects Between Red Blood Cell Traits and Diastolic Blood Pressure

Background: Previous studies have found associations of red blood cell traits (hemoglobin and red blood cell count, RBC) with blood pressure; whether these associations are causal is unknown.Methods: We performed cross-sectional analyses in the Lifelines Cohort Study (n=167,785). Additionally, we performed bidirectional two sample Mendelian randomization (MR) analyses to explore the causal effect of the two traits on systolic (SBP) and diastolic blood pressure (DBP), using genetic instrumental variables regarding hemoglobin and RBC identified in UK Biobank (n=350,475) and International Consortium of Blood Pressure studies for SBP and DBP (n= 757,601).Results: In cross-sectional analyses we observed positive associations with hypertension and blood pressure for both hemoglobin (OR=1.18, 95% CI: 1.16 to 1.20 for hypertension; B=0.11, 95% CI: 0.11 to 0.12 for SBP; B=0.11, 95% CI: 0.10 to 0.11 for DBP, all per SD) and RBC (OR=1.14, 95% CI: 1.12 to 1.16 for hypertension; B=0.11, 95% CI: 0.10 to 0.12 for SBP; B=0.08, 95% CI: 0.08 to 0.09 for DBP, all per SD). MR analyses suggested that higher hemoglobin and RBC cause higher DBP (inverse variance weighted [IVW] B=0.11, 95% CI: 0.07 to 0.16 for hemoglobin; B=0.07, 95% CI: 0.04 to 0.10 for RBC, all per SD). Reverse MR analyses (all per SD) suggested causal effects of DBP on both hemoglobin (B=0.06, 95% CI: 0.03 to 0.09) and RBC (B=0.08, 95% CI: 0.04 to 0.11). No significant effects on SBP were found.Conclusions: Our results suggest bidirectional causal relationships of hemoglobin and RBC with DBP, but not with SBP