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Superior mesenteric artery during intestinal loop formation and its positional changes from the extracoelom to the abdominal cavity
No full textIntroduction: Features of the superior mesenteric artery (SMA) and its intestinal branches during the embryonic and early fetal periods have not been fully described. We aimed to comprehensively elucidate the characteristics of intestinal branch artery formation in the SMA. Methods: Serial tissue sections of seven early fetal specimens belonging to the Blechschmidt Collection were digitalized and used for segmentation and reconstruction of the intestinal loop, SMA trunk, intestinal branch arteries, and mesentery for further analysis. Results: The intestinal branch arteries fed the intestinal tract from the oral side to the anal side, according to the order of their origin from the root to the periphery of the SMA trunk. SMA and intestinal branches were not as strongly conserved in their morphology as indicated in previous research but varied between specimens. Most intestinal branch arteries exhibited frequent branching with small intervals at the periphery, whereas the proximal branch exhibited few branches. Only a few peripheral branches made contact with the neighboring intestinal branch arteries. The fetal intestinal branch artery architecture differed greatly from that of adults. There were considerable inter- and intra-specimen variations in the intestinal tract length per feeding intestinal branch artery. The SMA branching arteries did not always supply each tertiary loop individually, and not every loop is connected to one artery. Conclusion: This study elucidates the characteristics of forming the SMA intestinal branch arteries. Specifically, the findings suggest that the SMA is similar to other arteries in that its branches show a level of variability in feeding tissues
Atrial dysfunction: a contrast-free marker for HFpEF in obese diabetics—insights from comprehensive CMR and serum biomarker analyses
No full textAbstract Background The diagnostic criteria for HFpEF remain inconsistently defined, further confounded by comorbidities such as obesity and type 2 diabetes mellitus (T2DM), which are thought to contribute to its pathogenesis via chronic pro-inflammatory mechanisms. This study aimed to evaluate the relationship between advanced cardiac magnetic resonance (CMR) imaging and pro-fibrotic and inflammatory serum biomarkers, assessing their potential to discriminate HFpEF from associated comorbid conditions. Methods This was an exploratory analysis of a prospective cohort study of 35 obese/overweight participants (mean age 64 ± 8 years, 23% females), including 16 with T2DM, 13 with HFpEF (NYHA II–III) and T2DM, and 6 healthy controls. All subjects underwent comprehensive contrast-enhanced CMR at a 3 T scanner (Philips Ingenia, The Netherlands), including assessment of left ventricular and left atrial (LA) volumetry and function, myocardial perfusion reserve (MPR), and diffuse fibrosis imaging (ECV). Obtained serum biomarkers were Pentraxin-3, Galectin-3 and Interleukin-1 Receptor-Like 1 (IL1RL1). Statistical analyses included one-way ANOVA, Tukey test, Pearson’s correlation, regression and receiver operating characteristic analyses, and intra-class correlation. Results In multivariable regression, impaired measures of LA structure and function emerged as the only independent discriminators of HFpEF, with LA maximum volume showing an OR of 1.13 (95% CI 1.05–1.28), reservoir strain of 0.71 (95% CI 0.44–0.89), conduit strain of 0.57 (95% CI 0.32–0.82) and booster strain of 0.70 (95% CI 0.48–0.89) per unit increase. No differences in MPR nor ECV were observed between the groups. While serum biomarkers Galectin-3 and Pentraxin-3 were significantly higher in HFpEF vs. obese controls (16.1 ng/ml ± 3.8 ng/ml vs. 10.6 ng/ml ± 3.7 ng/ml, p = 0.011, and 0.84 ng/ml ± 0.67 ng/ml vs. 0.21 ng/ml ± 0.05 ng/ml, p = 0.031, respectively), these biomarkers remained within normal limits and showed only moderate correlations with CMR metrics. Highest inter-study reproducibility was seen in MPR (ICC: 0.94), LA Reservoir Strain (ICC: 0.84) and serum biomarkers (ICC: 0.087–0.93). Conclusion CMR markers of diffuse fibrosis and microvascular dysfunction may not differentiate HFpEF from obese or diabetic controls. However, left atrial function assessment may evolve to be a reproducible and practical CMR marker, effectively distinguishing HFpEF independent of fibrotic remodeling
Decoding the impact of exercise and αCGRP signaling on murine post-traumatic osteoarthritis progression
No full textAbstract Background Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage breakdown, subchondral bone remodeling, and inflammation. Mechanical stress, such as exercise, can influence OA progression, acting as either a therapeutic intervention or a risk factor depending on intensity. The sensory neuropeptide αCGRP plays a role in modulating cartilage, bone, and inflammatory responses, making it a potential mediator of exercise effects on OA. This study investigated the impact of αCGRP deficiency and exercise intensity on OA progression in a post-traumatic murine model. Methods OA was induced in male αCGRP knockout (KO) and wild type (C57Bl/6J) mice via destabilization of the medial meniscus (DMM). Mice underwent moderate or intense treadmill exercise for up to 6 weeks (8 weeks post-surgery). Histological analyses were performed to assess cartilage degradation. Subchondral and metaphyseal bone morphology as well as cartilage stiffness were evaluated by nanoCT and atomic force microscopy (AFM), respectively. Serum inflammatory markers were analyzed using multiplex immunoassays. Results Serum levels of proinflammatory markers were elevated in αCGRP-deficient mice, particularly after intense exercise, independent of OA progression. DMM surgery induced significant cartilage degradation. Gross cartilage morphology was not influenced by exercise intensity or αCGRP deficiency, but αCGRP deficiency prevented articular cartilage extracellular matrix stiffening after DMM and intense exercise. Subchondral bone sclerosis was induced by αCGRP deficiency and DMM but mitigated by intense exercise. In metaphyseal bone, intense exercise induced trabecular loss in αCGRP-deficient mice. Conclusions This study highlights αCGRP as an intrinsic regulator of joint and bone responses to mechanical loading during OA. While cartilage degradation after DMM and treadmill exercise was unaffected by lack of αCGRP, its deficiency altered ECM stiffness, bone remodeling, and inflammatory responses. These findings position αCGRP as a critical regulator of joint homeostasis, particularly for bone health during running exercise and OA progression
Success rates of simulated multi-pulse defibrillation protocols are sensitive to application timing with individual, protocol-specific optimal timings
No full textVentricular fibrillation is a lethal condition where the heartbeat becomes too disorganised to maintain proper circulation. It is treated with defibrillation, which applies an electric shock in an attempt to reset the heart rhythm. As the high energy of this shock risks long-term harm to the patient, means of reducing it without compromising treatment efficacy are of great interest. One approach to maintaining efficacy is to improve the success rate of such low-energy shocks (i.e., pulses) through the proper timing of their application as defibrillation protocols, which consist of one or more pulses with predetermined inter-pulse periods. In practice, however, the effects of application timing remain to be tested for any of the multi-pulse protocols proposed in literature. We use (de)fibrillation simulations to show that such timing matters: The success rate of single-pulse protocols can vary by as much as 80 percentage points depending on timing, and using more shocks in succession only lessens this sensitivity up to a point. We also present evidence that feedback-based defibrillation on a shock-by-shock basis may be the only practical means of using timing to increase treatment efficacy, as we also generally find any optimal application timings to be specific to each combination of protocol and fibrillation episode
Carers’ Perspective on Voluntary Stopping of Eating and Drinking: A Systematic Mixed-Methods Review of Motives and Attitudes
No full textBackground/Objectives: Voluntary stopping of eating and drinking (VSED) is a way to hasten death or end life prematurely. VSED is controversial, and research is essential to inform this debate. The aim was to systematically synthesize empirical data on the attitudes, motives, and experiences related to VSED from the perspective of caregivers. Methods: This systematic mixed-methods review (PROSPERO CRD42022283743) included qualitative and quantitative research. The MEDLINE, CINAHL, PsycINFO, Google Scholar, and BELIT databases were searched for English and German articles published between 1 January 2013 and 12 November 2021. Studies examining experiences, attitudes, and knowledge regarding VSED were eligible. We analyzed the data inductively after quantitative data transformation. Quality and confidence were assessed using the Mixed Methods Appraisal Tool (MMAT) and GRADE-CERQual approach, respectively. Results: We identified 22 articles, including 16 studies. The participants were healthcare professionals and relatives, but not those who chose VSED. The motives for VSED are based on high symptom burdens and are closely related to self-determination. Most perceive VSED as a natural death and accept the patient’s decision. However, this acceptance also depends on other factors, such as patient characteristics. Most healthcare professionals would accompany patients during VSED, sometimes leading to advocacy. Relatives often play an active role in VSED and may experience distressing grief if they struggle with their support or the dying situation. The confidence in the review findings ranged from moderate to very low. Our findings on the challenging and positive experiences related to VSED and the resulting needs have been published elsewhere. Conclusions: VSED is a complex phenomenon affecting patients, nursing staff, physicians, and relatives. We provide an empirical basis for VSED to support research, debate, and practice
Cerebral Near-Infrared Spectroscopy and Electrical Cardiometry During Endotracheal Suction in Ventilated Infants Following Surgery: A Feasibility Study
No full textBackground: Near-Infrared Spectroscopy (NIRS) and Electrical Cardiometry (EC) are promising non-invasive techniques for monitoring tissue oxygenation and hemodynamics, particularly in surgically ill infants who struggle to maintain cerebral oxygenation and systemic perfusion. There is limited data regarding the combined use of these techniques during respiratory procedures such as endotracheal suction in intubated infants. Methods: The effects of 38 endotracheal suction maneuvers on cerebral oxygenation and cardiovascular hemodynamics were investigated in seven intubated infants following non-cardiac surgery. Parameters such as cerebral oxygenation and EC-derived metrics including heart rate, stroke volume, and cardiac output were assessed. Results: Gestational and postnatal age were 31 weeks and 16 days. During endotracheal suction, the heart rate decreased but returned to baseline afterward. After the procedure, the cerebral oxygenation, stroke volume, and cardiac output increased. Conclusions: Cerebral and systemic hemodynamics were altered during endotracheal suction maneuvers in ventilated infants. Combining NIRS and EC for monitoring cardiovascular and cerebrovascular physiology may enable more individualized therapy, helping to minimize cerebral injury in this vulnerable population
Longest Common Subsequence with Gap Constraints
No full textAbstract We consider the longest common subsequence problem in the context of subsequences with gap constraints. In particular, following Day et al. (2022), we consider the setting when the distance (i. e., the gap) between two consecutive symbols of the subsequence has to be between a lower and an upper bound (which may depend on the position of those symbols in the subsequence or on the symbols bordering the gap) as well as the case where the entire subsequence is found in a bounded range (defined by a single upper bound), considered by Kosche et al. (2022). In all these cases, we present efficient algorithms for determining the length of the longest common constrained subsequence between two given strings, and discuss lower bounds for the respective problems
Correction: Multi-modal dataset creation for federated learning with DICOM-structured reports
No full textIs a Malleable Active Site Loop the Key to High Substrate Promiscuity? Hybrid, Biocatalytic Route to Structurally Diverse Taxoid Side Chains with Remarkable Dual Stereocontrol
No full textAbstract These studies reveal the first structure of Clostridium acetobutylicum alcohol dehydrogenase (CaADH), a protein exhibiting remarkable substrate promiscuity and stereochemical fidelity. The CaADH enzyme is utilized here for synthesizing 20 potential aryl isoserine side chains for the Taxotere family of tubulin‐binding chemotherapeutics. The approach involves dynamic reductive kinetic resolution (DYRKR) upon the corresponding α‐chloro‐β‐keto esters, showing high D‐ syn stereoselectivity, including those leading to the clinically relevant milataxel (Ar = 2‐furyl) and simotaxel (Ar = 2‐thienyl) side chains. Furthermore, various cross‐coupling chemistries performed on the p ‐bromophenyl isoserine side chain significantly enhance the structural diversity of the taxoid side chain library obtained (16 additional taxoid side chains). The CaADH structure is notable: (i) the nicotinamide cofactor is bound in an anti‐ conformation, with the amide carbonyl occupying the ketone binding pocket, and (ii) a flexible loop near the active site likely contributes to the remarkable substrate promiscuity observed in CaADH. We present our perspective on the dynamic nature of the CaADH active site through molecular dynamics simulation, proposing a halogen bonding model as a potential mechanism for the remarkable selectivity for an ( S )‐configured C─Cl bond, in addition to the D‐facial selectivity, demonstrated across 20 diverse substrates by this remarkable short‐chain dehydrogenase enzyme.National Science Foundation https://doi.org/10.13039/100000001National Institutes of Health https://doi.org/10.13039/10000000
