Inadequate Choline Intake in Pregnant Women in Germany

Choline is an essential nutrient that is involved in various developmental processes during pregnancy. While the general adequate choline intake (AI) for adults has been set at 400 mg/day by the European Food Safety Authority (EFSA), an AI of 480 mg/day has been derived for pregnant women. To date, the choline intake of pregnant women in Germany has not been investigated yet. Therefore, in this survey, the total choline intake from dietary and supplementary sources in pregnant women was estimated using an online questionnaire. A total of 516 pregnant women participated in the survey, of which 283 met the inclusion criteria (13 to 41 weeks of gestational age, 19–45 years). 224 (79%) of the participants followed an omnivorous diet, 59 (21%) were vegetarian or vegan. Median choline intake was 260.4 (±141.4) mg/day, and only 19 women (7%) achieved the adequate choline intake. The median choline intake of omnivores was significantly higher than that of vegetarians/vegans (269.5 ± 141.5 mg/day vs. 205.2 ± 101.2 mg/day; p < 0.0001). 5% (13/283) of pregnant women took choline-containing dietary supplements. In these women, dietary supplements provided 19% of the total choline intake. Due to the importance of choline for the developmental processes during pregnancy, the study results prove the urgent need for an improved choline supply for pregnant women

Computed tomographic angiography in the evaluation of brain death

According to Polish criteria two neurophysiological methods are used to demonstrate the cessation of brain function: electroencephalography (EEG) and brain stem auditory evoked potentials. Among the techniques measuring cerebral blood flow, conventional angiography of the four cerebral arterial axes is the reference standard for imaging brain death. Thus, it is an invasive examination which needs an experienced neuroradiologist and the availability of an angiography suite. The use of a computed tomographic (CT) scan to diagnose BD was proposed as early as 1978. This exam developed widely these last years thanks to a new generation of multirow CT which allows visualization of opacified cerebral vessels. The aim of the present study was to determine the accuracy of CT-a for the confirmation of BD. We examined four patients with suspicion of BD according to clinical criteria defined by law. CT scan was performed without and with injection of contrast material, followed by cerebral angiography. In our material CT-angiography showed opacification of A2-ACA in two patients (patient 1 and 2). In all our patients the results of CT-angiography fulfill the criteria proposed by the French Society of Neuroradiology in 2007 - absence of perfusion of M4 middle cerebral artery segments (M4-MCA) and deep cerebral veins. In conventional angiography one patient (patient 2) showed, at the level of the anterior and middle cerebral artery, a phenomenon already described as "stasis filling". CT angiography seemes to be a promising radiological exam in the diagnosis of BD. When confirmatory examinations are required among brain-dead patients for whom the clinical diagnosis remains essential, it may be an interesting alternative to conventional cerebral angiography, which is more invasive and constraining, and to EEG when it is unavailable or inadequate

High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study

(1) Background: Spermidine is a biogenic polyamine that plays a crucial role in mammalian metabolism. As spermidine levels decline with age, spermidine supplementation is suggested to prevent or delay age-related diseases. However, valid pharmacokinetic data regarding spermidine remains lacking. Therefore, for the first time, the present study investigated the pharmacokinetics of oral spermidine supplementation. (2) Methods: This study was designed as a randomized, placebo-controlled, triple-blinded, two-armed crossover trial with two 5-day intervention phases separated by a washout phase of 9 days. In 12 healthy volunteers, 15 mg/d of spermidine was administered orally, and blood and saliva samples were taken. Spermidine, spermine, and putrescine were quantified by liquid chromatography–mass spectrometry (LC–MS/MS). The plasma metabolome was investigated using nuclear magnetic resonance (NMR) metabolomics. (3) Results: Compared with a placebo, spermidine supplementation significantly increased spermine levels in the plasma, but it did not affect spermidine or putrescine levels. No effect on salivary polyamine concentrations was observed. (4) Conclusions: This study’s results suggest that dietary spermidine is presystemically converted into spermine, which then enters systemic circulation. Presumably, the in vitro and clinical effects of spermidine are at least in part attributable to its metabolite, spermine. It is rather unlikely that spermidine supplements with doses <15 mg/d exert any short-term effects

Monitoring C5AR2 expression using a floxed tdtomato-C5AR2 knock-in mouse

The biological significance of C5a receptor [(C5aR)2/C5L2], a seven-transmembrane receptor binding C5a and C5adesArg, remains ill-defined. Specific ligation of C5aR2 inhibits C5a-induced ERK1/2 activation, strengthening the view that C5aR2 regulates C5aR1- mediated effector functions. Although C5aR2 and C5aR1 are often coexpressed, a detailed picture of C5aR2 expression in murine cells and tissues is still lacking. To close this gap, we generated a floxed tandem dye (td)Tomato-C5aR2 knock-in mouse that we used to track C5aR2 expression in tissue-residing and circulating immune cells. We found the strongest C5aR2 expression in the brain, bone marrow, and airways. All myeloid-derived cells expressed C5aR2, although with different intensities. C5aR2 expression in blood and tissue neutrophils was strong and homogeneous. Specific ligation of C5aR2 in neutrophils from tdTomato-C5aR2 mice blocked C5a-driven ERK1/2 phosphorylation, demonstrating functionality of C5aR2 in the reporter mice. In contrast to neutrophils, we found tissue-specific differences in C5aR2 expression in eosinophils, macrophages, and dendritic cell subsets. Naive and activated T cells stained negative for C5aR2, whereas B cells from different tissues homogeneously expressed C5aR2. Also, NK cell subsets in blood and spleen strongly expressed C5aR2. Activation of C5aR2 in NK cells suppressed IL-12/IL-18-induced IFN-g production. Intratracheal IL-33 challenge resulted in decreased C5aR2 expression in pulmonary eosinophils and monocytederived dendritic cells. In summary, we provide a detailed map of murine C5aR2 immune cell expression in different tissues under steady-state conditions and upon pulmonary inflammation. The C5aR2 knock-in mouse will help to reliably track and conditionally delete C5aR2 expression in experimental models of inflammation

Table_2_A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects – A real-life post-marketing study.docx

IntroductionImpaired glucose homeostasis is a significant risk factor for cardiometabolic diseases, whereas the efficacy of available standard therapies is limited, mainly because of poor adherence. This post-marketing study assessed the glucose-lowering potential of a synbiotic-based formulation.MethodsOne hundred ninety-two participants were enrolled in a digital nutrition program with continuous glucose monitoring (CGM) and received a study product comprising Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine. Participants underwent a first sensor phase without supplementation, followed by a 14-day supplementation phase without sensor, and completed by a second sensor phase while continuing supplementation. Fasting glucose levels were determined before and after supplementation by CGM. In addition, the postprandial glycemic response to an oral glucose challenge, body weight, HbA1c concentrations, and BMI was analyzed. Subgroup analyses of subjects with elevated glucose and HbA1c levels vs. normoglycemic subjects were performed.ResultsSupplementation with the study product resulted in significant improvements in glucose parameters (delta values: fasting glucose –2,13% ± 8.86; iAUC0–120 –4.91% ± 78.87; HbA1c: –1.20% ± 4.72) accompanied by a significant weight reduction (−1.07 kg ± 2.30) in the study population. Subgroup analyses revealed that the improvements were mainly attributed to a prediabetic subgroup with elevated fasting glucose and HbA1c values before supplementation (delta values: fasting glucose −6.10% 4± 7.89; iAUC0–120 –6.28% ± 115.85; HbA1c −3.31% ± 4.36; weight: −1.47 kg ± 2.82).ConclusionThis study indicates that the synbiotic composition is an effective and convenient approach to counteract hyperglycemia. Further placebo-controlled studies are warranted to test its efficacy in the treatment of cardiometabolic diseases.</p

Table_4_A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects – A real-life post-marketing study.docx

IntroductionImpaired glucose homeostasis is a significant risk factor for cardiometabolic diseases, whereas the efficacy of available standard therapies is limited, mainly because of poor adherence. This post-marketing study assessed the glucose-lowering potential of a synbiotic-based formulation.MethodsOne hundred ninety-two participants were enrolled in a digital nutrition program with continuous glucose monitoring (CGM) and received a study product comprising Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine. Participants underwent a first sensor phase without supplementation, followed by a 14-day supplementation phase without sensor, and completed by a second sensor phase while continuing supplementation. Fasting glucose levels were determined before and after supplementation by CGM. In addition, the postprandial glycemic response to an oral glucose challenge, body weight, HbA1c concentrations, and BMI was analyzed. Subgroup analyses of subjects with elevated glucose and HbA1c levels vs. normoglycemic subjects were performed.ResultsSupplementation with the study product resulted in significant improvements in glucose parameters (delta values: fasting glucose –2,13% ± 8.86; iAUC0–120 –4.91% ± 78.87; HbA1c: –1.20% ± 4.72) accompanied by a significant weight reduction (−1.07 kg ± 2.30) in the study population. Subgroup analyses revealed that the improvements were mainly attributed to a prediabetic subgroup with elevated fasting glucose and HbA1c values before supplementation (delta values: fasting glucose −6.10% 4± 7.89; iAUC0–120 –6.28% ± 115.85; HbA1c −3.31% ± 4.36; weight: −1.47 kg ± 2.82).ConclusionThis study indicates that the synbiotic composition is an effective and convenient approach to counteract hyperglycemia. Further placebo-controlled studies are warranted to test its efficacy in the treatment of cardiometabolic diseases.</p

Table_1_A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects – A real-life post-marketing study.docx

IntroductionImpaired glucose homeostasis is a significant risk factor for cardiometabolic diseases, whereas the efficacy of available standard therapies is limited, mainly because of poor adherence. This post-marketing study assessed the glucose-lowering potential of a synbiotic-based formulation.MethodsOne hundred ninety-two participants were enrolled in a digital nutrition program with continuous glucose monitoring (CGM) and received a study product comprising Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine. Participants underwent a first sensor phase without supplementation, followed by a 14-day supplementation phase without sensor, and completed by a second sensor phase while continuing supplementation. Fasting glucose levels were determined before and after supplementation by CGM. In addition, the postprandial glycemic response to an oral glucose challenge, body weight, HbA1c concentrations, and BMI was analyzed. Subgroup analyses of subjects with elevated glucose and HbA1c levels vs. normoglycemic subjects were performed.ResultsSupplementation with the study product resulted in significant improvements in glucose parameters (delta values: fasting glucose –2,13% ± 8.86; iAUC0–120 –4.91% ± 78.87; HbA1c: –1.20% ± 4.72) accompanied by a significant weight reduction (−1.07 kg ± 2.30) in the study population. Subgroup analyses revealed that the improvements were mainly attributed to a prediabetic subgroup with elevated fasting glucose and HbA1c values before supplementation (delta values: fasting glucose −6.10% 4± 7.89; iAUC0–120 –6.28% ± 115.85; HbA1c −3.31% ± 4.36; weight: −1.47 kg ± 2.82).ConclusionThis study indicates that the synbiotic composition is an effective and convenient approach to counteract hyperglycemia. Further placebo-controlled studies are warranted to test its efficacy in the treatment of cardiometabolic diseases.</p

Table_3_A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects – A real-life post-marketing study.docx

IntroductionImpaired glucose homeostasis is a significant risk factor for cardiometabolic diseases, whereas the efficacy of available standard therapies is limited, mainly because of poor adherence. This post-marketing study assessed the glucose-lowering potential of a synbiotic-based formulation.MethodsOne hundred ninety-two participants were enrolled in a digital nutrition program with continuous glucose monitoring (CGM) and received a study product comprising Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine. Participants underwent a first sensor phase without supplementation, followed by a 14-day supplementation phase without sensor, and completed by a second sensor phase while continuing supplementation. Fasting glucose levels were determined before and after supplementation by CGM. In addition, the postprandial glycemic response to an oral glucose challenge, body weight, HbA1c concentrations, and BMI was analyzed. Subgroup analyses of subjects with elevated glucose and HbA1c levels vs. normoglycemic subjects were performed.ResultsSupplementation with the study product resulted in significant improvements in glucose parameters (delta values: fasting glucose –2,13% ± 8.86; iAUC0–120 –4.91% ± 78.87; HbA1c: –1.20% ± 4.72) accompanied by a significant weight reduction (−1.07 kg ± 2.30) in the study population. Subgroup analyses revealed that the improvements were mainly attributed to a prediabetic subgroup with elevated fasting glucose and HbA1c values before supplementation (delta values: fasting glucose −6.10% 4± 7.89; iAUC0–120 –6.28% ± 115.85; HbA1c −3.31% ± 4.36; weight: −1.47 kg ± 2.82).ConclusionThis study indicates that the synbiotic composition is an effective and convenient approach to counteract hyperglycemia. Further placebo-controlled studies are warranted to test its efficacy in the treatment of cardiometabolic diseases.</p