Betatrophin is downregulated in pregnant women with a history of RYGB operation and a high risk of postprandial hypoglycaemia

Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. So far, no data exist about the role of betatrophin in pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation with a high risk of postprandial hypoglycaemia. In this prospective clinical study, an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed between the 24th and 28th week of pregnancy and 3-6 months post-partum in a cohort of obese and normal-weight pregnant women, as well as in women with a history of RYGB operation. In the cohort of pregnant women with RYGB and exaggerated risk of postprandial hypoglycaemic events, basal and dynamic betatrophin levels during the OGTT were lower than in the obese or normal-weight pregnant women (basal levels: 13.66 ± 5.88 vs. 19.03 ± 4.15 vs. 15.68 ± 6.48, p = 0.016; OGTT 60': 13.33 ± 5.40 vs. 17.37 ± 3.16 vs. 15.84 ± 4.99, p = 0.030). During the OGTT, basal and dynamic betatrophin levels at 60' were positively associated with glucose levels at 60 min (r = 0.55, p = 0.01 and r = 0.45, p = 0.039). This positive association was followed by significant hypoglycaemic events in the RYGB group. It was only in the RYGB group that betatrophin was negatively related to the disposition index (rho = -0.53, p = 0.014). After pregnancy there was a decrease in basal and stimulated betatrophin levels during the OGTT in all three patient groups. In comparison to normal-weight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort

Diagnosis of osteoporosis in statin-treated patients is dose-dependent

Objective Whether HMG-CoA-reductase inhibition, the main mechanism of statins, plays a role in the pathogenesis of osteoporosis, is not entirely known so far. Consequently, this study was set out to investigate the relationship of different kinds and dosages of statins with osteoporosis, hypothesising that the inhibition of the synthesis of cholesterol could influence sex-hormones and therefore the diagnosis of osteoporosis. Methods Medical claims data of all Austrians from 2006 to 2007 was used to identify all patients treated with statins to compute their daily defined dose averages of six different types of statins. We applied multiple logistic regression to analyse the dose-dependent risks of being diagnosed with osteoporosis for each statin individually. Results In the general study population, statin treatment was associated with an overrepresentation of diagnosed osteoporosis compared with controls (OR: 3.62, 95% CI 3.55 to 3.69, p<0.01). There was a highly non-trivial dependence of statin dosage with the ORs of osteoporosis. Osteoporosis was underrepresented in low-dose statin treatment (0–10 mg per day), including lovastatin (OR: 0.39, CI 0.18 to 0.84, p<0.05), pravastatin (OR: 0.68, 95% CI 0.52 to 0.89, p<0.01), simvastatin (OR: 0.70, 95% CI 0.56 to 0.86, p<0.01) and rosuvastatin (OR: 0.69, 95% CI 0.55 to 0.87, p<0.01). However, the exceeding of the 40 mg threshold for simvastatin (OR: 1.64, 95% CI 1.31 to 2.07, p<0.01), and the exceeding of a 20 mg threshold for atorvastatin (OR: 1.78, 95% CI 1.41 to 2.23, p<0.01) and for rosuvastatin (OR: 2.04, 95% CI 1.31 to 3.18, p<0.01) was related to an overrepresentation of osteoporosis. Conclusion Our results show that the diagnosis of osteoporosis in statin-treated patients is dose-dependent. Thus, osteoporosis is underrepresented in low-dose and overrepresented in high-dose statin treatment, demonstrating the importance of future studies’ taking dose-dependency into account when investigating the relationship between statins and osteoporosis

Major Depressive Disorder (MDD) and Antidepressant Medication Are Overrepresented in High-Dose Statin Treatment

Objective: To examine the dose-dependent relationship of different types of statins with the occurrence of major depressive disorder (MDD) and prescription of antidepressant medication. Methods: This cross-sectional study used medical claims data for the general Austrian population (n = 7,481,168) to identify all statin-treated patients. We analyzed all patients with MDD undergoing statin treatment and calculated the average defined daily dose for six different types of statins. In a sub-analysis conducted independently of inpatient care, we investigated all patients on antidepressant medication (statin-treated patients: n = 98,913; non-statin-treated patients: n = 789,683). Multivariate logistic regression analyses were conducted to calculate the risk of diagnosed MDD and prescription of antidepressant medication in patients treated with different types of statins and dosages compared to non-statin-treated patients. Results: In this study, there was an overrepresentation of MDD in statin-treated patients when compared to non-statin-treated patients (OR: 1.22, 95% CI: 1.20–1.25). However, there was a dose dependent relationship between statins and diagnosis of MDD. Compared to controls, the ORs of MDD were lower for low-dose statin-treated patients (simvastatin>0– 0– 0– 40– 60–80 mg:OR: 5.27, 95% CI: 4.21–6.60; atorvastatin>40– 60– 20– < =40 mg:OR: 2.09, 95% CI: 1.31–3.34). The results were confirmed in a sex-specific analysis and in a cohort of patients taking antidepressants, prescribed independently of inpatient care. Conclusions: This study shows that it is important to carefully re-investigate the relationship between statins and MDD. High-dose statin treatment was related to an overrepresentation, low-dose statin treatment to an underrepresentation of MDD

Increase in testosterone levels is related to a lower risk of conversion of prediabetes to manifest diabetes in prediabetic males

Background: Testosterone plays an important role in the regulation of glucose metabolism. While earlier studies have shown that it has a protective effect in males, unfavorable effects of testosterone on glucose metabolism have been reported in females; however, whether there is a sex-specific relationship between testosterone and glucose metabolism in patients with prediabetes has not been investigated in detail hitherto. Methods: This cross-sectional analysis investigated 423 males and 287 females with diagnosed prediabetes. Detailed assessment of their metabolic profiles was performed, including a 2‑h oral glucose tolerance test (OGTT), HbA1c levels, calculation of insulin resistance with homeostatic model assessment for insulin resistance (HOMA-IR), assessment of lipid metabolism, anthropometric parameters and the fatty liver index (FLI). By using Spearman's correlation test, we investigated the sex-specific relationship between testosterone and metabolism in the prediabetic individuals. Results: In the present study, prediabetic females (mean age 58.6 years, confidence interval [CI: 57.6 y; 59.5 y]) were characterized by lower fasting plasma glucose levels (104.2 mg/dl [CI: 103.0 mg/dl; 105.4 mg/dl] vs. 106.9 mg/dl [CI: 106.0 mg/dl; 107.8 mg/dl]) and a lower FLI (49.5 [CI: 45.7; 53.2] vs. 58.8 [CI: 55.8; 61.8]), but presented with a higher risk of developing manifest type 2 diabetes in the next 10 years (FINDRISK score: 17.6 [CI: 17.1; 18.1] vs. 16.1 [CI: 15.7; 16.5]) when compared to prediabetic males (mean age: 58.04 years [CI: 57.0 y; 59.1 y]). Testosterone was negatively related to insulin resistance (HOMA-IR: Spearman's ρ: -0.33, p < 0.01), 2‑h stimulated glucose levels during the OGTT (ρ = -0.18, p < 0.01), HbA1c levels (ρ = -0.13, p < 0.05), FLI and BMI in prediabetic males; however, no relationship between testosterone and metabolic parameters could be found in prediabetic females. Conclusion: The increase of testosterone levels in males was related to a more favorable glucose metabolism, including lower HbA1c, lower stimulated glucose levels and higher insulin sensitivity; however, in prediabetic females, testosterone was not related to glucose metabolism

Supplementary Material for: Immunoglobulin Class Profiles of ABO Antibodies in Saliva and Serum of Healthy Individuals

Introduction: The coronavirus disease (COVID-19) pandemic gave rise to studies investigating the association of ABO blood group with COVID-19 susceptibility. It is hypothesized that ABO antibodies might play a role in neutralizing SARS-CoV-2. However, ABO antibodies were exclusively analyzed in blood samples. Investigation of ABO antibodies in saliva, an easy-to-obtain surrogate for respiratory secretions, may provide novel insights into mucosal immunity crucial in early defense against respiratory pathogens. Methods: In this study, saliva and serum samples from healthy individuals with known blood groups were investigated using a flow cytometric method for separate anti-A/anti-B IgA, IgM, and IgG class antibody detection. Saliva samples were additionally tested using hemagglutination-based neutral and indirect anti-human globulin test gel cards. This method comparison was complemented by dilution experiments with a high-titer anti-A/anti-B WHO standard. Results: In saliva, IgA was the most abundant ABO antibody class, followed by IgM; IgG was detected only in low levels in all non-AB blood types. In serum, IgM was the predominant ABO antibody class in all non-AB blood types, followed by IgA and IgG, the latter mainly detected in group O individuals. Saliva and serum samples of group O individuals yielded the highest variability of ABO-specific antibody levels. Regardless of sample material and blood type, major interindividual differences in ABO antibody reactivities were recorded. Antibody levels correlated moderately between these two body fluids. There were no significant sex and age-group differences in ABO antibody levels in both serum and saliva. WHO standard dilution experiments yielded technique-specific limits of detection, illustrating the inherent differences of immunofluorescence versus agglutination. Conclusion: For the first time, salivary ABO antibodies were investigated by separate detection of the three most relevant antibody classes IgA, IgM, and IgG in a healthy cohort. This study opens new perspectives regarding mucosal ABO antibody class profiles and their potential influence on respiratory infections

Similar effect of intermittent theta burst and sham stimulation on corticospinal excitability: a 5-day repeated sessions study

Despite accumulating evidence of inter- and intra-individual variability in response to theta burst stimulation, it is widely believed that in therapeutic applications, repeated sessions can have a "build-up" effect that increases the response over and above that seen in a single session. However, strong evidence for this is lacking. Therefore, we examined whether daily administration of intermittent theta burst stimulation (iTBS) over the primary motor cortex induces cumulative changes in transcranial magnetic stimulation measures of cortical excitability, above the changes induced by sham stimulation. Over 5 consecutive days, 20 healthy participants received either active iTBS or sham stimulation. Each day, baseline measures of cortical excitability were assessed before and up to 30 min after the intervention. There was no significant difference in the rate of response between iTBS and sham stimulation on any of the 5 days. There was no iTBS specific cumulative increase of corticospinal excitability. The likelihood that an individual would remain a responder from day-to-day was low in both groups, implying high within-subject variability of both active and sham iTBS after-effects. In contrast, we found a high within-subject repeatability of resting and active motor threshold, and baseline motor evoked potential amplitude. In summary, sham stimulation has similar effect to active iTBS on corticospinal excitability, even when applied repeatedly for 5 days. Our results might be relevant to research and clinical applications of theta burst stimulation protocols. This article is protected by copyright

Programmable systems for intelligence in automobiles (PRYSTINE): Final results after Year 3

Autonomous driving is disrupting the automotive industry as we know it today. For this, fail-operational behavior is essential in the sense, plan, and act stages of the automation chain in order to handle safety-critical situations on its own, which currently is not reached with state-of-the-art approaches. The European ECSEL research project PRYSTINE realizes Fail-operational Urban Surround perceptION (FUSION) based on robust Radar and LiDAR sensor fusion and control functions in order to enable safe automated driving in urban and rural environments. This paper showcases some of the key exploitable results (e.g., novel Radar sensors, innovative embedded control and E/E architectures, pioneering sensor fusion approaches, AI-controlled vehicle demonstrators) achieved until its final year 3

Programmable Systems for Intelligence in Automobiles (PRYSTINE): Final results after Year 3

Autonomous driving is disrupting the automotive industry as we know it today. For this, fail-operational behavior is essential in the sense, plan, and act stages of the automation chain in order to handle safety-critical situations on its own, which currently is not reached with state-of-the-art approaches.The European ECSEL research project PRYSTINE realizes Fail-operational Urban Surround perceptION (FUSION) based on robust Radar and LiDAR sensor fusion and control functions in order to enable safe automated driving in urban and rural environments. This paper showcases some of the key exploitable results (e.g., novel Radar sensors, innovative embedded control and E/E architectures, pioneering sensor fusion approaches, AI-controlled vehicle demonstrators) achieved until its final year 3