The vitamin D receptor (VDR) is critical in regulating intestinal homeostasis and emerging evidence demonstrates that VDR deficiency is a critical factor in inflammatory bowel disease pathology. ...However, no clinical data exist regarding the intestinal expression of VDR in patients after allogeneic haematopoietic stem cell transplantation (HSCT). Analyzing intestinal biopsies from 90 patients undergoing HSCT with mortality follow-up, we demonstrated that patients with severe acute gastrointestinal graft versus host disease (GI-GvHD) showed significant downregulation of VDR gene expression compared to mild or no acute GI-GvHD patients (p = 0.007). Reduced VDR expression was already detectable at acute GI-GvHD onset compared to GvHD-free patients (p = 0.01). These results were confirmed by immunohistochemistry (IHC) where patients with severe acute GI-GvHD showed fewer VDR+ cells (p = 0.03) and a reduced VDR staining score (p = 0.02) as compared to mild or no acute GI-GvHD patients. Accordingly, low VDR gene expression was associated with a higher cumulative incidence of treatment-related mortality (TRM) (p = 1.6x10-6) but not with relapse-related mortality (RRM). A multivariate Cox regression analysis identified low VDR as an independent risk factor for TRM (p = 0.001, hazard ratio 4.14, 95% CI 1.78-9.63). Furthermore, VDR gene expression significantly correlated with anti-microbial peptides (AMPs) gene expression (DEFA5: r = 0.637, p = 7x10-5, DEFA6: r 0 0.546, p = 0.001). In conclusion, our findings suggest an essential role of the VDR in the pathogenesis of gut GvHD and the prognosis of patients undergoing HSCT.
Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation ...(allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR43) and at the onset of GvHD (p 0.000 for GPR109A, p=0.006 for GPR43) and correlated strongly with FOXP3 and NLRP3 expression. The use of broad-spectrum antibiotics (Abx) drastically suppressed GPR expression as well as FOXP3 expression in patients' gut biopsies (p=0.000 for GPRs, FOXP3 mRNA and FOXP3+ cellular infiltrates). Logistic regression analysis revealed treatment with Abx as an independent factor associated with GPR and FOXP3 loss. The upregulation of GPRs was evident only in the absence of Abx (p=0.001 for GPR109A, p=0.014 for GPR43) at GvHD onset. Thus, GPR expression seems to be upregulated in the presence of commensal bacteria and associates with infiltration of FOXP3+ T regs, suggesting a protective, regenerative immunomodulatory response. However, Abx, which has been shown to induce dysbiosis, interferes with this protective response.
•Through engineering principles, the TubeSpin® bioreactor 600 was characterized.•High gas transfer, rapid mixing, and low specific power consumption were observed.•Routine animal cell cultivation, ...medium scale 100–500mL was demonstrated.•High cell densities were achieved with all orbitally shaken bioreactors tested.
Orbitally shaken bioreactors (OSRs) support the efficient cultivation of mammalian cells in suspension at various scales of operation. Here we introduce a disposable culture vessel with a ventilated cap having a nominal volume of 600mL (TubeSpin® bioreactor 600) for medium-scale cell cultivation. It has a conical bottom designed to fit into a standard swinging bucket rotor to facilitate cell/liquid separation by centrifugation. At shaking frequencies suitable for mammalian cell cultivation (140–220rpm), the volumetric mass transfer coefficient (kLa) ranged from 15 to 40h−1, the mixing time was less than 20s, and the specific power consumption ranged from 0.03 to 0.5kW/m3. To define the working conditions for the TubeSpin® bioreactor 600, we measured cell growth and environmental culture conditions such as pH and dissolved O2 and CO2 concentrations over a range of shaking frequencies and working volumes using a stable CHO-derived cell line expressing a human IgG antibody. The optimal cultivation conditions were observed at working volumes of 300–500mL and shaking frequencies of 180–220rpm. In 300-mL batch cultures of the same cell line in a TubeSpin® bioreactor 600, 1-L cylindrical glass bottle, and 1-L Erlenmeyer shake flask, the maximum cell densities and recombinant antibody yields were similar. This study demonstrated the suitability of the TubeSpin® bioreactor 600 for cell culture applications with suspension-adapted CHO cells at culture volumes up to 500mL.
Aim: Although several patients with kidney disease have simultaneous dysfunction of the parasympathetic and sympathetic nervous systems, orthostatic hypotension during a hemodialysis (HD) procedure ...impacts not only the form of treatment but overall comfort of life for patients with HD. Despite a number of methods that are not invasive and have already been used to assess autonomous functioning, a system for monitoring malfunction throughout filtration of blood therapy which has yet to be discovered. Methods: Regarding the purpose of monitoring the autonomous function of stable 40 regular HD patients and 35 healthy controls, we examined the clinical application of the laser-Doppler blood flow meter (LDF). By detecting the periflux blood flow decreasing velocity (PDV) while combined with the Valsalva manoeuvre, the LDF device which was used for an autonomous test. We also looked at the relationship between PDV and traditional atherosclerosis testing. Results: The baseline PDV (5.30 ± 2.93), comparative to subjects who were in excellent condition (9.65 ± 7.10), was substantially decreased in the HD populace. Furthermore, we discovered a substantial connection between PDV and established parameters like heart rate fluctuation and ankle-brachial blood pressure indexing. Conclusion: Regarding assessing autonomous functioning in hemodialysis patients, evaluation of PDV by LDF is just as effective as the standard approach. The benefit from regular and recurring assessments of autonomous dysfunction is made possible by the device's ease.
Background
In the last two decades, Nepal has experienced an increase in both forest fire frequency and area, but very little is known about its spatiotemporal dimension. A limited number of studies ...have researched the extent, timing, causative parameters, and vulnerability factors regarding forest fire in Nepal. Our study analyzed forest fire trends and patterns in Nepal for the last two decades and analyzed forest fire-vulnerability risk based on historical incidents across the country.
Results
We analyzed the spatial and temporal patterns of forest fires and the extent of burned area using the Mann-Kendall trend test and two machine-learning approaches maximum entropy (MaxEnt), and deep neural network (DNN). More than 78% of the forest fire burned area was recorded between March and May. The total burned area has increased over the years since 2001 by 0.6% annually. The forest fire-vulnerability risk obtained from both approaches was categorized into four classes—very high, high, low, and very low.
Conclusions
Although burned area obtained from both models was comparable, the DNN slightly outperformed the MaxEnt model. DNN uses a complex structure of algorithms modeled on the human brain that enables the processing of the complex relationship between input and output dataset, making DNN-based models recommended over MaxEnt. These findings can be very useful for initiating and implementing the most suitable forest management intervention.
Recently, cylindrical lithium-ion battery cells have been widely used in electric vehicles due to efficient automated production and cheap kilowatt-hour capacity. For optimal operation of a cell, the ...internal temperature of the cell should be maintained within the range of 15–35 °C by employing suitable cooling mechanism. This study comprehensively compares multiple air-cooling configurations specifically designed for lithium-ion battery three-series and three-parallel (3S3P) modules using. The methodology involves an experimental phase to measure the parameters of Bernardi's equation, essential for calculating heat generation with consideration of both Joule's heat and entropic heat. Subsequently, a numerical simulation using Ansys Fluent examines battery heat generation within the 3S3P modules, employing diverse air-cooling configurations. Each configuration undergoes simulation with the aid of design of experiments and parametric analysis, allowing the observation of cooling behavior across various input parameters. To ensure reliability of simulation, the cooling of the unit cell module is simulated under similar conditions. The comparison between these simulated results and experimental values is conducted to validate the accuracy of the overall analysis methodology. The heat measurements indicated a unit cell heat output of 0.9028 W at an average rate of 0.85C. Among the investigated air-cooling configurations, the SIDO (Single Input Double Output) arrangement stood out as the most effective in maintaining a consistently lower average cell temperature, as determined through the application of the response curve method. This study emphasizes the importance of air-cooling design for improving the performance and safety of lithium-ion battery modules used in electric vehicles.
•Heat measurement of cell is done to compare lithium-ion battery air-cooling designs effectively.•Response curve method optimized data for battery cooling system parameter enhancement.•SIDO air cooling maintains lower cell temperature compared to other configurations.
Abstract Background Takotsubo cardiomyopathy is a syndrome of transient cardiac dysfunction that is frequently associated with sudden emotional or physical stress. Epinephrine use has been implicated ...in precipitating takotsubo cardiomyopathy in multiple case reports and case series. We sought to systematically review the current English literature on this association. Methods We searched relevant articles on takotsubo cardiomyopathy associated with epinephrine administration and extracted data on demographic characteristics, clinical features, investigations and clinical outcomes. Results We identified total of 41 cases from 36 articles. The mean age of presentation was (47.07 ± 15.73 years) with strong female preponderance (83%, P = 0.0001). The most common symptom at presentation was chest pain (82%). Mean peak troponin I level was (7.12 ± 11.22 ng/ml). The most common EKG abnormality was ST elevation, seen in 40% of patients. The most common finding on echocardiography was apical hypokinesis, seen in 48.78% cases. Patients younger than 45 were less likely to have apical cardiomyopathy ( n = 5/20, 25%) compared to patients with age > 45 ( n = 14/21, 66%, p value 0.001, OR 0.17). The most common route of administration of epinephrine was intravenous (65.85%). All patients except one survived with complete recovery of systolic function reported in most cases within an average of 14.7 days. Conclusion Exposure to epinephrine in clinical practice can trigger takotsubo cardiomyopathy, which is rapidly reversible with good prognosis in most cases. This review further supports the notion that both exogenous and endogenous catecholamines are associated with the pathogenesis of Takotsubo cardiomyopathy.
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