The organ shortage is widely acknowledged as the most critical factor hindering the full realization of success for solid organ transplantation. Innovation in the areas of donor management and organ ...preservation offers the most realistic hope to improve both the quality and size of the current organ supply. Although the basic science dissecting the complex processes of brain death and ischemia/reperfusion injury is replete with exciting discoveries, the clinical science investigating donor management and organ preservation is sparse in contrast. This review will survey the current landscape of trials to mitigate organ injury through interventions administered to donors in vivo or organs ex vivo. Consideration will then be given to the scientific, logistical and ethical obstacles that impede the transformation of laboratory breakthroughs into innovative treatments that simultaneously improve organ quality and supply.
Substantial scientific, ethical, and logistical obstacles obstruct innovation and progress in donor intervention and organ preservation—two critically important investigative areas that offer the potential of improving transplant outcomes and increasing organ supply.
We aimed to determine whether frailty, a validated geriatric construct of increased vulnerability to physiologic stressors, predicts mortality in liver transplant candidates. Consecutive adult ...outpatients listed for liver transplant with laboratory Model for End‐Stage Liver Disease (MELD) ≥ 12 at a single center (97% recruitment rate) underwent four frailty assessments: Fried Frailty, Short Physical Performance Battery (SPPB), Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales. Competing risks models associated frailty with waitlist mortality (death/delisting for being too sick for liver transplant). Two hundred ninety‐four listed liver transplant patients with MELD ≥ 12, median age 60 years and MELD 15 were followed for 12 months. By Fried Frailty score ≥3, 17% were frail; 11/51 (22%) of the frail versus 25/243 (10%) of the not frail died/were delisted (p = 0.03). Each 1‐unit increase in the Fried Frailty score was associated with a 45% (95% confidence interval, 4–202) increased risk of waitlist mortality adjusted for MELD. Similarly, the adjusted risk of waitlist mortality associated with each 1‐unit decrease (i.e. increasing frailty) in the Short Physical Performance Battery (hazard ratio 1.19, 95% confidence interval 1.07–1.32). Frailty is prevalent in liver transplant candidates. It strongly predicts waitlist mortality, even after adjustment for liver disease severity demonstrating the applicability and importance of the frailty construct in this population.
In this study, the researchers report that frailty, a validated geriatric construct of increased vulnerability to physiologic stressors, is highly prevalent in patients with cirrhosis awaiting liver transplantation and strongly predicts waitlist mortality, demonstrating the applicability and importance of the frailty construct in this population.
The remarkable reduction of delayed graft function rates after kidney transplantation achieved simply by cooling deceased donor organs to 34–35°C evidences the yet untapped potential to improve not ...only organ quality but also quantity through innovative and well‐designed donor intervention research. See the related article from Rodrigue et al on page 278.
•Ensemble learning is utilized to predict the remaining fatigue life.•Multiple machine learning methods are aggregated to improve the performance.•The present algorithm is vry effective and stable.
...An effective approach is proposed to predict the remaining fatigue life (RFL) of structures with stochastic parameters. The extended finite element method (XFEM) was firstly used to produce a large amount of datasets associated with structural responses and RFL. Then, a RFL prediction model was developed using the ensemble learning algorithm, which employed multiple machine-learning algorithms to learn useful degradation patterns of the structures from the XFEM datasets. Several numerical examples were investigated to evaluate the performance of proposed RFL prediction approach. The analysis results demonstrate that the ensemble learning is able to effectively predict the RFL of the structures with stochastic parameters.
Paclitaxel (Taxol®) is one of the best antineoplastic drugs found from nature in the past decades. Like many other anticancer drugs, there are difficulties in its clinical administration due to its ...poor solubility. Therefore an adjuvant called Cremophor EL has to be employed, but this has been found to cause serious side-effects. However, nanoparticles of biodegradable polymers can provide an ideal solution to the adjuvant problem and realise a controlled and targeted delivery of the drug with better efficacy and fewer side-effects. The present research proposes a novel formulation for fabrication of nanoparticles of biodegradable polymers containing d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) to replace the current method of clinical administration and, with further modification, to provide an innovative solution for oral chemotherapy. In the modified solvent extraction/evaporation technique employed in this research, the emulsifier/stabiliser/additive and the matrix material can play a key role in determining the morphological, physicochemical and pharmaceutical properties of the produced nanoparticles. We found that vitamin E TPGS could be a novel surfactant as well as a matrix material when blended with other biodegradable polymers. The nanoparticles composed of various formulations and manufactured under various conditions were characterised by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. The drug encapsulation efficiency (EE) and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was concluded that vitamin E TPGS has great advantages for the manufacture of polymeric nanoparticles for controlled release of paclitaxel and other anti-cancer drugs. Nanoparticles of nanometer size with narrow distribution can be obtained. A drug encapsulation efficiency as high as 100% can be achieved and the release kinetics can be controlled.
We aimed to evaluate the accuracy and interchangeability of stroke volume and cardiac output measured by electrical velocimetry and transthoracic echocardiography during cesarean delivery.We enrolled ...20 parturients in this prospective observational study. We recorded the stroke volume and cardiac output using both methods and compared the values at seven specific time points. We analyzed the data using linear regression analysis for Pearson's correlation coefficients and Bland-Altman analysis to determine percentage errors. We conducted a trending ability analysis based on the four-quadrant plot with the concordance rate and correlation coefficient.We recorded 124 paired datasets during cesarean delivery. The correlation coefficients of the measured cardiac output and stroke volume between the two methods were 0.397 (P < .001) and 0.357 (P < .001). The 95% limits of agreement were -1.0 to 8.1 L min for cardiac output and -10.4 to 90.4 ml for stroke volume. Moreover, the corresponding percentage errors were 62% and 60%. The concordance correlation coefficients were 0.447 (95% CI: 0.313-0.564) for stroke volume and 0.562 (95% CI: 0.442-0.662) for cardiac output. Both methods showed a moderate trending ability for stroke volume (concordance rate: 82% (95% CI: 72-90%)) and cardiac output (concordance rate: 85% (95% CI: 78-93%)).Our findings indicated that electrical velocimetry monitoring has limited accuracy, precision, and interchangeability with transthoracic echocardiography; however, it had a moderate trending ability for stroke volume and cardiac output measurements during cesarean delivery.
The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody‐mediated liver allograft rejection at the 11th (Paris, France, June 5–10, 2011), ...12th (Comandatuba, Brazil, August 19–23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5–10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody‐mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.
The Banff Working Group comprehensively updates guidelines for liver allograft pathology on the basis of pertinent literature, data review, and discussion over the last 5 years. See the editorial from O'Grady on page 2773.
Aim
To investigate whether static magnetic fields (SMFs) have a positive effect on the migration and dentinogenesis of dental pulp stem cells (DPSCs) to promote reparative dentine formation.
...Methodology
In vitro scratch assays and a traumatic pulp exposure model were performed to evaluate the effect of 0.4‐Tesla (T) SMF on DPSC migration. The cytoskeletons of the DPSCs were identified by fluorescence immunostaining and compared with those of a sham‐exposed group. Dentinogenic evaluation was performed by analysing the expressions of DMP‐1 and DSPP marker genes using a quantitative real‐time polymerase chain reaction (qRT‐PCR) process. Furthermore, the formation of calcified deposits was examined by staining the dentinogenic DPSCs with Alizarin Red S dye. Finally, the role played by the p38 MAPK signalling pathway in the migration and dentinogenesis of DPSCs under 0.4‐T SMF was investigated by incorporating p38 inhibitor (SB203580) into the in vitro DPSC experiments. The Student's t‐test and the Kruskal–Wallis test followed by Dunn's post hoc test with a significance level of P < 0.05 were used for statistical analysis.
Results
The scratch assay results revealed that the application of 0.4‐T SMF enhanced DPSCs migration towards the scratch wound (P < 0.05). The cytoskeletons of the SMF‐treated DPSCs were found to be aligned perpendicular to the scratch wound. After 20 days of culture, the SMF‐treated group had a greater number of out‐grown cells than the sham‐exposed group (nonmagnetized control). For the SMF‐treated group, the DMP‐1 (P < 0.05) and DSPP genes (P < 0.05), analysed by qRT‐PCR, exhibited a higher expression. The distribution of calcified nodules was also found to be denser in the SMF‐treated group when stained with Alizarin Red S dye (P < 0.05). Given the incorporation of p38 inhibitor SB203580 into the DPSCs, cell migration and dentinogenesis were suppressed. No difference was found between the SMF‐treated and sham‐exposed cells (P > 0.05).
Conclusion
0.4‐T SMF enhanced DPSC migration and dentinogenesis through the activation of the p38 MAPK‐related pathway.
Abstract The solar type J radio burst is a variant of type III bursts, which are a probe for understanding solar energetic electrons and local electron density. This study investigates a type J burst ...event on 2017 September 9. We have combined the data from the extreme-ultraviolet (EUV) imaging and the EUV Imaging Spectrometer (EIS) to analyze the event. Within 4 minutes several type J bursts with similar morphology occur. Two of them, with clear fundamental and second harmonic bands, are studied in detail. We find a delay of 2 ± 0.5 s between their different harmonic bands. During type J bursts, only one coronal loop brightens significantly at its northern footpoint, in correlation with the continuous injection of erupting jets into the loop. The EUV intensity of the brightening footpoint is correlated with the radio flux at 245 and 410 MHz, with correlation coefficients of 0.2 and 0.4, respectively. These observations suggest that the type J bursts should originate from this coronal loop. By analyzing the electron number density distribution along the coronal loop diagnosed from the EIS data and the time evolution of the plasma frequency calculated from the type J burst, we determine that the velocities of the energetic electrons exciting the two type Js are 0.10 ± 0.02 c and 0.12 ± 0.02 c . Our results confirm previous studies on type J bursts.