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Lower muscular strength is associated with greater liver fat content and higher serum liver enzymes—“The Sedentary's Liver” The Study of Health in Pomerania
Get PDFWe investigated the associations of low handgrip strength (HGS, i.e., a marker of muscular fitness) with liver fat content (LFC) and serum liver enzymes in a population‐based setting. We used data from 2700 participants (51.7% women), aged 21–90 years, from two independent cohorts of the population‐based Study of Health in Pomerania (SHIP‐START‐2 and SHIP‐TREND‐0). Cross‐sectional, multivariable adjusted regression models were performed to examine the associations of HGS with LFC, measured by magnetic resonance imaging and serum liver enzymes. We found significant inverse associations of HGS with both LFC and serum liver enzymes. Specifically, a 10‐kg lower HGS was associated with a 0.59% (95% confidence interval [CI]: 0.24–0.94; p = 0.001) higher LFC, a 0.051 µkatal/L (95% CI: 0.005–0.097; p = 0.031) higher gamma‐glutamyltransferase (GGT) concentration and a 0.010 µkatal/L (95% CI: 0.001–0.020; p = 0.023) higher aspartate aminotransferase (AST) concentration. The adjusted odds‐ratio for prevalent hepatic steatosis (defined by a MRI‐PDFF ≥5.1%) per 10‐kg lower HGS was 1.21 (95% CI: 1.04–1.40; p = 0.014). When considering only obese individuals, those with low HGS had a 1.58% (95% CI: 0.18–2.98; p = 0.027) higher mean LFC and higher chance of prevalent hepatic steatosis (adjusted OR 1.74, 95% CI: 1.15–2.62; p = 0.009) compared to individuals with high HGS. We found similar associations in individuals with overweight, but not in those with normal weight. Lower HGS was strongly associated with both higher LFC and higher serum GGT and AST concentrations. Future studies might clarify whether these findings reflect adverse effects of a sedentary lifestyle or aging on the liver
Performance control during longitudinal activation fMRI studies
Get PDFThe documentation of performance during functional imaging represents a standard procedure employed to control for compliance, sensorimotor, and cognitive demands. In the case of motor tasks, preciseness, force, and frequency have a significant impact on the magnitude of functional activation. Questionnaires are used in psychological investigations to control for cognitive demand, while psychophysiological documentation is employed to record bodily responses. For longitudinal intervention studies, it is of utmost importance to implement meticulous pre- and post-performance controls and balance to accurately assess changes over time. Any changes in compliance may introduce additional uncontrolled variables, which can hinder the interpretation of functional magnetic resonance imaging (fMRI)-related changes. This narrative review presents strategies for controlling and balancing performance in functional imaging approaches to document neuroplasticity in rehabilitative studies. These strategies include not only motor-related aspects, such as precision, velocity, and force, but also timing aspects, such as the start and stop of movement periods. In addition, it discusses strategies for the modulation and control of movement aspects with visual feedback, as well as for the control of physiological changes during experimental modulation. Although these measures require additional care, which is often more demanding than the neuroimaging part of the study, they are crucial for a relevant interpretation and publication of fMRI studies
The composition of the stent microbiome is associated with morbidity and adverse events during endoscopic drainage therapy of pancreatic necroses and pseudocysts
Get PDFBackground
Development of pancreatic necroses or pseudocysts are typical complications of pancreatitis and may require endoscopic drainage therapy using metal or plastic stents. Microbial infection of these lesions poses a major challenge. So far, the composition and significance of the microbial colonization on drainage stents are largely unknown although it may impact outcomes during endoscopic drainage therapy.
Methods
A total of 26 stents used for drainage of pancreatic lesions were retrieved and the stent microbiome was determined by 16S rRNA gene sequencing. Additional analysis included comparison of the stent microbiome to the intracavitary necrosis microbiome as well as scanning electron microscopy (SEM) and micro-computed tomography (μCT) imaging of selected metal or plastic stents.
Results
The stent microbiome comprises a large proportion of opportunistic enteric pathogens such as Enterococcus (14.4%) or Escherichia (6.1%) as well as oral bacteria like Streptococcus (13.1%). Increased levels of opportunistic enteric pathogens were associated with a prolonged hospital stay ( r = 0.77, p = 3e−06) and the occurrence of adverse events during drainage therapy ( p = 0.011). Higher levels of oral bacteria were associated ( r = −0.62, p = 8e-04) with shorter durations of inpatient treatment. SEM and μCT investigations revealed complex biofilm networks on the stent surface.
Conclusion
The composition of the stent microbiome is associated with prolonged hospital stays and adverse events during endoscopic drainage therapy, highlighting the need for effective infection control to improve patient outcomes. In addition to systemic antibiotic therapy, antimicrobial stent coatings could be a conceivable option to influence the stent microbiome and possibly enhance control of the necrotic microflora
Investigation of Gastric Water Emptying in Older Adults assessed by Salivary Caffeine Kinetics and a Novel Tablet Formulation
Get PDFNowadays, life expectancy is consistently rising, and the population of older people is growing exponentially worldwide. Even though older people are the main end users of drug products, yet they are significantly underrepresented in clinical trials focused on new drug entities. Currently, clinical trials predominantly involve younger adults, overlooking the physiological changes relevant to oral drug absorption in older individuals. This exclusion is concerning given the incidence of changes in the physiology of the aging gastrointestinal tract that may impact gastric emptying and motility and therefore oral drug absorption. In particular, gastric emptying of water is an important parameter for oral biopharmaceutics since clinical bioavailability and bioequivalence studies typically include the ingestion of oral formulations with a glass of water under fasted and fed state conditions.
Even though plentiful of studies have investigated gastric water emptying in younger volunteers, this is not the case in older people. Data from gastric emptying studies in older people is limited and contradictory, whereas the occurrence of the Magenstrasse in the fed state in older individuals has been up to date not investigated. A patient-centred approach to drug development is crucial, ensuring that medications are appropriately tested and optimized for the physiological needs of older patients, particularly under varying prandial conditions. To close these knowledge gaps, in this work the gastric emptying rate of water was assessed using the indirect method of salivary caffeine kinetics. This non-invasive method was further advanced by the development of a novel formulation containing the salivary marker caffeine to increase its suitability for use in older people, and therefore patient acceptability and compliance with the study procedure.
Summarized, the results of this thesis can be outlined as follows:
First, an extensive literature review was conducted to gather all relevant information regarding previous clinical studies investigating age-dependent changes in the physiological characteristics of the gastrointestinal tract relevant to oral drug absorption. Results from gastric emptying studies in older individuals are controversial, mainly because of different methods, study designs, and measurement parameters used.
Second, a novel rapid-disintegrating and dissolving tablet formulation containing caffeine was developed to advance the salivary caffeine method to be applied in the study including older individuals. According to this method, gastric water emptying is indirectly assessed by evaluating the pharmacokinetic profile of salivary caffeine concentrations. The new tablet formulation was successfully validated against the previous formulation (i.e. the ice capsule) in healthy young adults in a clinical study under fasted and fed state conditions.
Third, the impact of advanced age in gastric water emptying was investigated with the aforementioned method. Healthy older and healthy younger volunteers were recruited in a clinical study in fasted (after overnight fasting) and fed state (after the intake of a low-fat breakfast). Differences between gastric emptying of the two population groups was evaluated indirectly by evaluating the AUC ratios (%) of salivary caffeine concentrations in specific time segments. No significant difference could be proven (p > 0.05), which indicates that gastric water emptying remains unchanged in relation to healthy aging.
These results provide a better understanding in oral drug absorption in older individuals and facilitate the drug development of oral drug products specified to the needs of the aging population. However, taking into consideration the high proportion of older people affected by multimorbidity, polypharmacy and frailty, we could surely say that these outcomes are not representative of the whole cohort of older individuals. As the aging population is very heterogeneous, a useful approach would be to investigate the impact of these factors by creating subgroups of this population and studying specific parameters separately (e.g. older individuals with multimorbidity versus healthy older individuals). Given these factors, future studies are needed to better understand how they may affect gastric emptying rates and motility. This will lead to a better understanding of the underlying mechanism of any changes observed in oral drug absorption and disposition in older adults, and therefore improve oral drug development
Quantifying ecosystem services of rewetted peatlands − the MoorFutures methodologies
Get PDFIn 2011, MoorFutures® were introduced as the first standard for generating credits from peatland rewetting. We developed methodologies to quantify ecosystem services before and after rewetting with a focus on greenhouse gas emissions, water quality, evaporative cooling and mire-typical biodiversity. Both standard and premium approaches to assess these services were developed, and tested in the rewetted polder Kieve (NE-Germany). The standard approaches are default tier 1 estimation procedures, which require little time and few, mainly vegetation data. Based on the Greenhouse gas Emission Site Type (GEST) approach, emissions decreased from 1,306 t CO2e in the baseline scenario to 532 t CO2e in the project scenario, whereas 5 years after rewetting they were assessed to be 543 t CO2e per year. Nitrate release assessed via Nitrogen Emission Site Types (NEST) was estimated to decrease from 1,088 kg N (baseline) to 359 kg N (project), and appeared to be 309 kg N per year 5 years after rewetting. The heat flux − determined with Evapotranspiration Energy Site Types (EEST) – decreased from 6,691 kW (baseline) to 1,926 kW (project), and was 2,250 kW per year 5 years after rewetting. Mire-specific biodiversity was estimated to increase from very low (baseline) to high (project), but was only low 5 years after rewetting. The premium approaches allow quantifying a particular ecosystem service with higher accuracy by measuring or modelling. The approaches presented here have been elaborated for North-Germany but can be adapted for other regions. We encourage scientists to use our research as a model for assessing peatland ecosystem services including biodiversity in other geographical regions. Using vegetation mapping and indicator values derived from meta-analyses is a cost-efficient and robust approach to inform payment for ecosystem services schemes and to support conservation planning at regional to global scales
Increase in ascorbate content in leaves of Hordeum vulgare after spraying with cold atmospheric plasma-treated water in combination with waterlogging and re-aeration
Get PDFFlood events are likely to increase in the near future and are one of the events most threatening to agricultural production. Barley is the fourth most important crop and the cereal most sensitive to excessive moisture stress. Improving the stress tolerance of crops to a variety of stress factors caused by a more volatile climate is an important task for the coming years. The aim of this study was to investigate the efficacy of cold atmospheric plasma-treated water (PTW) as a foliar spray to stimulate the antioxidant system of Hordeum vulgare and thereby improve plant stress tolerance. For this purpose, we analysed the components of the ascorbate-glutathione cycle in barley leaves and roots without stress and under waterlogging conditions. PTW increased the content of total and reduced ascorbate in leaves as well as the content of reduced ascorbate in roots four weeks after treatment. This was observed both, under stress free conditions and after waterlogging and re-aeration. In leaves, enzyme activities also increased after re-aeration, and in roots, total and reduced glutathione levels increased after waterlogging compared to the control. The accumulation of low molecular weight antioxidants may increase tolerance to a variety of stress factors through more efficient scavenging of ROS. Overall, treatment of plants with PTW may trigger an adaptive response that leads to mitigation of the negative effects of stress, and thus, could be used as a priming agent for protection against subsequent more severe stress factors that occur in the plants' natural environment
Plant roots but not hydrology control microbiome composition and methane flux in temperate fen mesocosms
Get PDFThe rewetting of formerly drained peatlands can help to counteract climate change through the reduction of CO2 emissions. However, this can lead to resuming CH4 emissions due to changes in the microbiome, favoring CH4-producing archaea. How plants, hydrology and microbiomes interact as ultimate determinants of CH4 dynamics is still poorly understood. Using a mesocosm approach, we studied peat microbiomes, below-ground root biomass and CH4 fluxes with three different water level regimes (stable high, stable low and fluctuating) and four different plant communities (bare peat, Carex rostrata, Juncus inflexus and their mixture) over the course of one growing season. A significant difference in microbiome composition was found between mesocosms with and without plants, while the difference between plant species identity or water regimes was rather weak. A significant difference was also found between the upper and lower peat, with the difference increasing as plants grew. By the end of the growing season, the methanogen relative abundance was higher in the sub-soil layer, as well as in the bare peat and C. rostrata pots, as compared to J. inflexus or mixture pots. This was inversely linked to the larger root area of J. inflexus. The root area also negatively correlated with CH4 fluxes which positively correlated with the relative abundance of methanogens. Despite the absence or low abundance of methanotrophs in many samples, the integration of methanotroph abundance improved the quality of the correlation with CH4 fluxes, and methanogens and methanotrophs together determined CH4 fluxes in a structural equation model. However, water regime showed no significant impact on plant roots and methanogens, and consequently, on CH4 fluxes. This study showed that plant roots determined the microbiome composition and, in particular, the relative abundance of methanogens and methanotrophs, which, in interaction, drove the CH4 fluxes
Challenging Diagnosis of Late Abdominal Pregnancy: A Case Study of Misdiagnosis and Fetal Death in the Third Trimester
Get PDFBACKGROUND: Abdominal pregnancy is a rare form of extrauterine pregnancy that usually results in a poor outcome; it is associated with serious fetal and maternal morbidity. The diagnosis of advanced abdominal pregnancy is sometimes challenging and should be identified early, at a routine antenatal examination. There are still no evidence-based management strategies for late abdominal pregnancy. This report presents a case of a patient with an abdominal pregnancy and a non-viable fetus.
CASE REPORT: A 34-year-old woman presented as an emergency 2 months after the diagnosis of intrauterine fetal death at 33 weeks of gestation. During subsequent surgery, the pregnancy was found to be an undiagnosed abdominal pregnancy. The patient had been admitted due to abdominal pain and increasingly deteriorating general condition. On admission, clinical examination and abdominal ultrasound were carried out and the diagnosis of fetal death was confirmed. The diagnosis of extrauterine pregnancy, however, was initially missed, and a decision to induce labor was made. After unsuccessful induction of labor and deterioration of the patient’s general condition, a laparotomy was performed, and the diagnosis of abdominal pregnancy was confirmed. A severely macerated fetus and placenta were delivered. Relative to others with this condition, the patient had a very good postoperative outcome with prolonged healing of the surgical incision. Informed consent for publication was obtained from the patient.
CONCLUSIONS: The diagnosis of late abdominal pregnancy can be missed despite clinical and sonographic examination. This diagnosis should be considered and excluded in similar suspected clinical findings. Proper operative planning in a tertiary center with a well-experienced team is crucial
Automated intracranial vessel segmentation of 4D flow MRI data in patients with atherosclerotic stenosis using a convolutional neural network
Get PDFIntroduction
Intracranial 4D flow MRI enables quantitative assessment of hemodynamics in patients with intracranial atherosclerotic disease (ICAD). However, quantitative assessments are still challenging due to the time-consuming vessel segmentation, especially in the presence of stenoses, which can often result in user variability. To improve the reproducibility and robustness as well as to accelerate data analysis, we developed an accurate, fully automated segmentation for stenosed intracranial vessels using deep learning.
Methods
154 dual-VENC 4D flow MRI scans (68 ICAD patients with stenosis, 86 healthy controls) were retrospectively selected. Manual segmentations were used as ground truth for training. For automated segmentation, deep learning was performed using a 3D U-Net. 20 randomly selected cases (10 controls, 10 patients) were separated and solely used for testing. Cross-sectional areas and flow parameters were determined in the Circle of Willis (CoW) and the sinuses. Furthermore, the flow conservation error was calculated. For statistical comparisons, Dice scores (DS), Hausdorff distance (HD), average symmetrical surface distance (ASSD), Bland-Altman analyses, and interclass correlations were computed using the manual segmentations from two independent observers as reference. Finally, three stenosis cases were analyzed in more detail by comparing the 4D flow-based segmentations with segmentations from black blood vessel wall imaging (VWI).
Results
Training of the network took approximately 10 h and the average automated segmentation time was 2.2 ± 1.0 s. No significant differences in segmentation performance relative to two independent observers were observed. For the controls, mean DS was 0.85 ± 0.03 for the CoW and 0.86 ± 0.06 for the sinuses. Mean HD was 7.2 ± 1.5 mm (CoW) and 6.6 ± 3.7 mm (sinuses). Mean ASSD was 0.15 ± 0.04 mm (CoW) and 0.22 ± 0.17 mm (sinuses). For the patients, the mean DS was 0.85 ± 0.04 (CoW) and 0.82 ± 0.07 (sinuses), the HD was 8.4 ± 3.1 mm (CoW) and 5.7 ± 1.9 mm (sinuses) and the mean ASSD was 0.22 ± 0.10 mm (CoW) and 0.22 ± 0.11 mm (sinuses). Small bias and limits of agreement were observed in both cohorts for the flow parameters. The assessment of the cross-sectional lumen areas in stenosed vessels revealed very good agreement (ICC: 0.93) with the VWI segmentation but a consistent overestimation (bias ± LOA: 28.1 ± 13.9%).
Discussion
Deep learning was successfully applied for fully automated segmentation of stenosed intracranial vasculatures using 4D flow MRI data. The statistical analysis of segmentation and flow metrics demonstrated very good agreement between the CNN and manual segmentation and good performance in stenosed vessels. To further improve the performance and generalization, more ICAD segmentations as well as other intracranial vascular pathologies will be considered in the future
Pregnancy-related factors induce immune tolerance through regulation of sCD83 release
Get PDFA well-balanced maternal immune system is crucial to maintain fetal tolerance in case of infections during pregnancy. Immune adaptations include an increased secretion of soluble mediators to protect the semi-allogeneic fetus from excessive pro-inflammatory response. B lymphocytes acquire a higher capacity to express CD83 and secrete soluble CD83 (sCD83) upon exposure to bacteria-derived components such as LPS. CD83 possesses immune modulatory functions and shows a promising therapeutic potential against inflammatory conditions. The administration of sCD83 to pregnant mice reduces LPS-induced abortion rates. The increased CD83 expression by endometrial B cells as compared to peripheral blood B cells suggests its modulatory role in the fetal tolerance, especially in the context of infection. We postulate that in pregnancy, CD83 expression and release is controlled by pregnancy-related hormones. The intra- and extracellular expression of CD83 in leukocytes from peripheral blood or decidua basalis and parietalis at term were analyzed by flow cytometry. After treatment with pregnancy-related hormones and LPS, ELISA and qPCR were performed to study sCD83 release and CD83 gene expression, respectively. Cleavage prediction analysis was used to find potential proteases targeting CD83. Expression of selected proteases was analyzed by ELISA. Higher levels of CD83 were found in CD11c+ dendritic cells, CD3+ T cells and CD19+ B cells from decidua basalis and decidua parietalis after LPS-stimulation in vitro. An increase of intracellular expression of CD83 was also detected in CD19+ B cells from both compartments. Stimulated B cells displayed significantly higher percentages of CD83+ cells than dendritic cells and T cells from decidua basalis and peripheral blood. Treatment of B lymphocytes with pregnancy-related molecules (E2, P4, TGF-β1 and hCG) enhanced the LPS-mediated increase of CD83 expression, while dexamethasone led to a reduction. Similarly, the release of sCD83 was increased under TGF-β1 treatment but decreased upon dexamethasone stimulation. Finally, we found that the hormonal regulation of CD83 expression is likely a result from a balance between gene transcription from CD83 and the modulation of the metalloproteinase MMP-7. Thus, data supports and complements our previous murine studies on hormonal regulation of CD83 expression, reinforcing its immunomodulatory relevance in anti-bacterial responses during pregnancy