Determinants of Low Bone Turnover in Type 2 Diabetes-the Role of PTH.

Determinants of low bone turnover in type 2 diabetes (T2DM) are poorly understood. To investigate the relationship between markers of bone turnover, glycaemic control, disease duration and calciotropic hormones in T2DM we assessed baseline biochemical data from the DiabOS Study, a prospective multicenter observational cohort study. In a cross-sectional study-design data from 110 postmenopausal women and men aged 50-75 years diagnosed with T2DM for at least 3 years and 92 non-diabetic controls were evaluated. Biochemical markers of bone formation (N-terminal propeptide of type I procollagen [PINP]), bone-specific alkaline phosphatase [BAP]) and resorption (C-terminal cross-linking telopeptide of type I collagen [CTX]), measures of calcium homeostasis (intact parathormone [iPTH], 25-Hydroxyvitamin D, calcium, magnesium) and glycaemic control were assessed. After adjustment for age, gender and body mass index (BMI), patients with T2DM had lower serum levels of PINP (p < 0.001), CTX (p < 0.001), iPTH (p = 0.03) and magnesium (p < 0.001) compared to controls. Serum calcium, creatinine, 25-Hydroxyvitamin D and sclerostin did not differ between both groups. In multivariate linear regression analyses only serum iPTH remained an independent determinant of bone turnover markers in T2DM (PINP: p = 0.02; CTX: p < 0.001 and BAP: p < 0.01), whereas glycated haemoglobin (HbA1c), disease duration, age and BMI were not associated with bone turnover. In conclusion low bone turnover in T2DM is associated with low iPTH. The underlying mechanism remains to be elucidated.

VascuFit: vascular effects of non-linear periodized exercise training in sedentary adults with elevated cardiovascular risk - protocol for a randomized controlled trial.

BACKGROUND: Early vascular aging (EVA) is increasingly prevalent in the general population. Exercise is important for primary cardiovascular prevention, but often insufficient due to ineffective training methods and a lack of biomarkers suitable to monitor its vascular effects. VascuFit will assess the effectiveness of non-linear periodized aerobic exercise (NLPE) in a non-athletic sedentary population to improve both established and promising biomarkers of EVA. METHODS: Forty-three sedentary adults, aged 40-60 years, with elevated cardiovascular risk will either engage in 8 weeks of ergometer-based NLPE (n = 28) or receive standard exercise recommendations (n = 15). The primary outcome will be the change of brachial-arterial flow-mediated dilation (baFMD) after versus before the intervention. Secondary outcomes will be the change in static vessel analysis (SVA; clinical biomarker of microvascular endothelial function), endomiRs (microRNAs regulating key molecular pathways of endothelial cell homeostasis) and circulating cellular markers of endothelial function (mature endothelial cells, endothelial progenitor cells). Tertiary outcomes will be the change in sphingolipidome, maximum oxygen capacity, and traditional cardiovascular risk factors (blood pressure, triglycerides, cholesterol, fasting glucose, high-sensitivity C-reactive protein). DISCUSSION: We expect an improvement of baFMD of at least 2.6% and significant pre-post intervention differences of SVA and endomiRs as well as of the tertiary outcomes in the intervention group. VascuFit may demonstrate the effectiveness of NLPE to improve endothelial function, thus vascular health, in the general sedentary population. Furthermore, this project might demonstrate the potential of selected molecular and cellular biomarkers to monitor endothelial adaptations to aerobic exercise. TRIAL REGISTRATION: The trial was registered on www. CLINICALTRIALS: gov (NCT05235958) in February 11th 2022.

Bone Microarchitecture and Strength in Long-Standing Type 1 Diabetes.

Type 1 diabetes (T1DM) is associated with an increased fracture risk, specifically at nonvertebral sites. The influence of glycemic control and microvascular disease on skeletal health in long-standing T1DM remains largely unknown. We aimed to assess areal (aBMD) and volumetric bone mineral density (vBMD), bone microarchitecture, bone turnover, and estimated bone strength in patients with long-standing T1DM, defined as disease duration ≥25 years. We recruited 59 patients with T1DM (disease duration 37.7 ± 9.0 years; age 59.9 ± 9.9 years.; body mass index [BMI] 25.5 ± 3.7 kg/m2 ; 5-year median glycated hemoglobin [HbA1c] 7.1% [IQR 6.82-7.40]) and 77 nondiabetic controls. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT) at the ultradistal radius and tibia, and biochemical markers of bone turnover were assessed. Group comparisons were performed after adjustment for age, gender, and BMI. Patients with T1DM had lower aBMD at the hip (p < 0.001), distal radius (p = 0.01), lumbar spine (p = 0.04), and femoral neck (p = 0.05) as compared to controls. Cross-linked C-telopeptide (CTX), a marker of bone resorption, was significantly lower in T1DM (p = 0.005). At the distal radius there were no significant differences in vBMD and bone microarchitecture between both groups. In contrast, patients with T1DM had lower cortical thickness (estimate [95% confidence interval]: -0.14 [-0.24, -0.05], p < 0.01) and lower cortical vBMD (-28.66 [-54.38, -2.93], p = 0.03) at the ultradistal tibia. Bone strength and bone stiffness at the tibia, determined by homogenized finite element modeling, were significantly reduced in T1DM compared to controls. Both the altered cortical microarchitecture and decreased bone strength and stiffness were dependent on the presence of diabetic peripheral neuropathy. In addition to a reduced aBMD and decreased bone resorption, long-standing, well-controlled T1DM is associated with a cortical bone deficit at the ultradistal tibia with reduced bone strength and stiffness. Diabetic neuropathy was found to be a determinant of cortical bone structure and bone strength at the tibia, potentially contributing to the increased nonvertebral fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Food antigen-specific IgE in dogs with suspected food hypersensitivity.

OBJECTIVE: Knowledge of cross-reactions in food-sensitive dogs will influence the choice of elimination diets and the long-term management of those patients. The objective of this study was to evaluate food allergen-specific IgE tests of suspected allergic dogs for concurrent positive reactions as possible evidence for cross reactions between allergens. MATERIAL AND METHODS: Results of serum IgE tests from 760 suspected allergic dogs submitted to 2 laboratories were evaluated statistically. After the tested allergens were grouped by their phylogenetic relationship, odds ratios as well as a sensitivity analysis of the odds ratios were performed to evaluate if concurrent positive IgE results to 2 allergens occurred more often than expected. RESULTS: Within related allergen pairs 27% (laboratory 1) and 72% (laboratory 2) of the pairs could be considered as associated. For the unrelated allergen pairs only 6.8% and 10.6% of the analyzed pairs were considered associated respectively. Strong correlations were shown in the group of ruminant allergens, especially beef and lamb, and grain allergens. High rates of concurrent reactions were also detected in the poultry group, especially between chicken and duck, as well as between pork and ruminant allergens, and soy and grain allergens. CONCLUSION: As our results showed not only correlations within related but also between non-related allergens, the possible relevance of carbohydrate moieties as well as panallergens for canine hypersensitivities warrants further study. Further investigations are necessary to distinguish co-sensitization from cross-reactions and determine the clinical relevance of food-specific IgE reactivity. CLINICAL RELEVANCE: Due to possible cross reactivity related allergens, especially beef and lamb as well as grain allergens, should not be used for an elimination diet to avoid false results.

Oxygen uptake during mini trampoline exercise in normal-weight, endurance-trained adults and in overweight-obese, inactive adults: A proof-of-concept study.

OBJECTIVES: To examine cardiorespiratory exertion during mini trampoline exercises of different intensities in both endurance-trained athletes and overweight-obese adults. METHODS: Physically healthy participants (Group A: normal-weight, endurance-trained athletes; Group B: inactive, overweight-obese adults) participated in two measurement appointments and three training sessions in between appointments, in which participants familiarized themselves with the use of the mini trampoline and the execution of the exercises. The primary outcome was the ⩒O2peak for each of the six mini trampoline exercises relative to the ⩒O2peak as established during an all-out exercise test on a bike ergometer during the first measurement appointment. Secondary outcomes were average ⩒O2 as well as maximum and average heart rate. RESULTS: The six mini trampoline exercises generated ⩒O2peak values between 42% and 81% in the endurance-trained athletes and between 58% and 87% in the overweight-obese participants, both in relation to the bike ergometer ⩒O2peak. Average ⩒O2 values ranged from 35% to 69% (endurance-trained athletes) and from 48% to 71% (overweight-obese participants), depending on exercise. Average heart rate likewise lay in a range that can be categorized as moderate-to-vigorous aerobic exercise for both groups. A moderate-to-strong correlation (0.658 to 0.875, depending on exercise) between bike ergometer ⩒O2peak and mini trampoline ⩒O2peak was found for all six exercises. CONCLUSIONS: Mini trampoline exercise has the potential to produce training intensities that concur with established exercise guidelines. The exercise intensity is self-adjusting and allows for an effective and safe workout for different users with a wide range of fitness levels.

Does obesity attenuate the beneficial cardiovascular effects of cardiorespiratory fitness?

BACKGROUND AND AIMS: Higher cardiorespiratory fitness is associated with lower pulse wave velocity and arterial stiffness in normal weight individuals, and this has not been examined in obese individuals. It is unclear whether an altered body composition acts as a modifier of the association between cardiorespiratory fitness and arterial stiffness. We examined the association between peak oxygen uptake and brachial-ankle pulse wave velocity and analysed whether body composition attenuates this association in obese middle-aged individuals. METHODS: Bio-impedance analysis-derived body composition assessment in 212 healthy and sedentary either overweight or obese individuals was followed by measurement of brachial-ankle pulse wave velocity and spiroergometric peak oxygen uptake. Multivariate analysis was performed to analyse the association between peak oxygen uptake and brachial-ankle pulse wave velocity and to assess the moderating effect of several body composition-related interaction terms (BMI, total body mass, body fat mass, waist circumference, waist-to-height ratio) on this association. RESULTS: Peak oxygen uptake was inversely associated with brachial-ankle pulse wave velocity (ß = -0.059, 95% CI = -0.099; -0.018, p = 0.005). Testing for the impact of different body composition-related interaction terms on this association showed no significance, 95% CI lateralized towards positivity. CONCLUSIONS: This study shows an inverse association between cardiorespiratory fitness and arterial stiffness in middle-aged obese individuals. We also found a tendency towards an attenuating impact of an obese body composition on this association. Physical fitness seems to be a stronger modulator of cardiovascular risk than body composition but the success of training efforts may be compromised by obesity.

Injury potential of thrown sharp kitchen and household utensils.

We examined the possibility of inflicting serious injuries with sharp objects in an experimental setting by throwing four sharp objects from different distances and with different throwing techniques. Using an overarm-handle (OA/H), overarm-blade (OA/B), underarm-handle (UA/H), underarm-blade (UA/B) and thrust (T/H) throwing technique, 10 adults (sex ratio 1:1) threw a chef's knife, a skinning knife, a paring knife and office scissors from 4 m and 2 m distance at synthetic abdomen models made of 10% gelatin covered with synthetic skin. The amount of hits and penetrations of the target and their penetration depth were noted, as was the rotation of the blade tip towards the target along its flight trajectory. The chef's knife injury/hit ratio was 0.167/4 m and 0.160/2 m; the skinning knife recorded an injury/hit ratio of 0.087/4 m and 0.153/2 m; the paring knife of 0.087/4 m and 0.113/2 m; and the scissors 0.087/4 m and 0.067/2 m. Mean penetration depths were as follows: the chef's knife: 4 m, 4.42 cm, 2 m, 3.41 cm; the skinning knife: 4 m, 4.19 cm, 2 m, 4.11 cm; the paring knife: 4 m, 1.62 cm, 2 m, 1.55 cm; and the scissors: 4 m, 2.08 cm, 2 m, 0.95 cm. Handle-throw penetration-depths were: 4 m: 3.77 cm and 2 m: 2.86 cm; blade-throw depths were: 4 m: 3.14 cm and 2 m: 2.69 cm. Overarm-throw penetration-depths were: 4 m: 3.62 cm and 2 m: 3.25 cm; and underarm-throw penetration-depths were 4 m: 3.30 cm and 2 m: 2.30 cm. No thrust-throws with the paring knife and scissors could pierce the target. The tips pointed toward the target at angles of 60°-120°, earlier in handle-throws than blade-throws, especially with the paring knife and the scissors. When thrown, especially with a handle-held technique, heavier objects pierced more often and more deeply. Thrust-throws at short distances are unlikely to pierce a human.

The Obesity Factor: How Cardiorespiratory Fitness is Estimated More Accurately in People with Obesity.

OBJECTIVE: Cardiopulmonary exercise testing is clinically used to estimate cardiorespiratory fitness (CRF). The relation to total body mass (TBM) leads to an underestimation of CRF in people with obesity and to inappropriate prognostic and therapeutic decisions. This study aimed to determine body composition-derived bias in the estimation of CRF in people with obesity. METHODS: Two hundred eleven participants (58.8% women; mean BMI 35.7 kg/m2 [± 6.94; 20.7-58.6]) were clinically examined, and body composition (InBody720; InBody Co., Ltd., Seoul, South Korea) and spiroergometrical peak oxygen consumption (VO2 peak) were assessed. The impacts of TBM, lean body mass (LBM), and skeletal muscle mass (SMM) on CRF estimates were analyzed by the application of respective weight models. Linear regression and plotting of residuals against BMI were performed on the whole study population and two subgroups (BMI < 30 kg/m2 and BMI ≥ 30 kg/m2 ). RESULTS: For every weight model, Δmean VO2 peak (expected - measured) was positive. LBM and SMM had a considerable impact on VO2 peak demand (P = 0.001; ΔR2 = 2.3%; adjusted R2 = 56% and P = 0.001; ΔR2 = 2.7%; adjusted R2 = 56%), whereas TBM did not. Confounding of body composition on VO2 peak did not differ in LBM and SMM. CONCLUSIONS: TBM-adjusted overestimation of relative VO2 demand is much higher in people with obesity than in those without. LBM or SMM adjustment may be superior alternatives, although small residual body composition-derived bias remains.

Teaching bioprocess engineering to undergraduates: Multidisciplinary hands-on training in a one-week practical course.

Bioprocess engineering is a highly interdisciplinary field of study which is strongly benefited by practical courses where students can actively experience the interconnection between biology, engineering, and physical sciences. This work describes a lab course developed for 2nd year undergraduate students of bioprocess engineering and related disciplines, where students are challenged with a real-life bioprocess-engineering application, the production of recombinant protein in a fed-batch process. The lab course was designed to introduce students to the subject of operating and supervising an experiment in a bioreactor, along with the analysis of collected data and a final critical evaluation of the experiment. To provide visual feedback of the experimental outcome, the organism used during class was Escherichia coli which carried a plasmid to recombinantly produce enhanced green fluorescent protein (eGFP) upon induction. This can easily be visualized in both the bioreactor and samples by using ultraviolet light. The lab course is performed with bioreactors of the simplest design, and is therefore highly flexible, robust and easy to reproduce. As part of this work the implementation and framework, the results, the evaluation and assessment of student learning combined with opinion surveys are presented, which provides a basis for instructors intending to implement a similar lab course at their respective institution.

Whole-body MRI-based fat quantification: a comparison to air displacement plethysmography.

PURPOSE: To demonstrate the feasibility of an algorithm for MRI whole-body quantification of internal and subcutaneous fat and quantitative comparison of total adipose tissue to air displacement plethysmography (ADP). MATERIALS AND METHODS: For comparison with ADP, whole-body MR data of 11 volunteers were obtained using a continuously moving table Dixon sequence. Resulting fat images were corrected for B1 related intensity inhomogeneities before fat segmentation. RESULTS: The performed MR measurements of the whole body provided a direct comparison to ADP measurements. The segmentation of subcutaneous and internal fat in the abdomen worked reliably with an accuracy of 98%. Depending on the underlying model for fat quantification, the resultant MR fat masses represent an upper and a lower limit for the true fat masses. In comparison to ADP, the results were in good agreement with ρ ≥ 0.97, P < 0.0001. CONCLUSION: Whole-body fat quantities derived noninvasively by using a continuously moving table Dixon acquisition were directly compared with ADP. The accuracy of the method and the high reproducibility of results indicate its potential for clinical applications.

Peripheral vessel scout imaging based on continuously moving table acquisition of projection data.

A fast and spatially seamless peripheral vessel scout is desirable for subsequent planning of magnetic resonance (MR) angiography. We implemented a continuously moving table sequence providing projection data with time-of-flight contrast of the entire lower extremities in less than 2 minutes. Variation of arterial signal during the cardiac cycle and autocorrelation were exploited to enhance vessel-to-background contrast. Subjective image analysis revealed excellent vessel depiction, indicating that the proposed scout allows for seamless expedited visualization of major arterial structures.

Identification of an aliphatic epoxide and the corresponding dihydrodiol as novel congeners of zearalenone in cultures of Fusarium graminearum.

The mycotoxin zearalenone (ZEN) is produced by various Fusarium fungi and frequently found as a contaminant in food and feed. There are reports in the literature that several closely related analogues of ZEN are also formed in cultures of Fusarium species. We have therefore analyzed the organic extract from a 40 day culture of Fusarium graminearum by LC-DAD-MS and detected 15 compounds, which could be congeners of ZEN because of their ultraviolet, mass spectroscopy, and tandem mass spectroscopy spectra. In addition to confirming the previously reported α- and ß-stereoisomers of 5-hydroxy-ZEN and 10-hydroxy-ZEN, we identified seven ZEN congeners for the first time. One of the major novel congeners was shown by nuclear magnetic resonance spectroscopy and chemical synthesis to have the structure of an aliphatic ZEN epoxide, whereas two minor products proved to be the corresponding dihydrodiols. In addition, three stereoisomers of a cyclization product of the dihydrodiols, carrying a spiro-acetal group, were identified as fungal products for the first time. The latter may be artifacts, because the ZEN epoxide and dihydrodiol are unstable under acidic conditions and rearrange easily to the spiro-acetal compounds.