Summary
Introduction
The most widely used protocol for the induction of experimental allergic airway inflammation in mice involves sensitization by intraperitoneal (i.p.) injections of the antigen ...ovalbumin (OVA) used in conjunction with the adjuvant aluminium hydroxide (alum). Although adjuvants are frequently used, there are questions regarding the necessity of alum for murine asthma studies due to the non‐physiological nature of this chemical.
Objective
The objective of this study was to compare experimental asthma phenotypes between adjuvant and adjuvant‐free protocols of murine allergic airway inflammation in an attempt to develop a standardized alternative to adjuvant use.
Method
An adjuvant‐free OVA model of experimental asthma was investigated in BALB/c mice using i.p. or subcutaneous (s.c.) sensitization routes. For the s.c. sensitization, β‐galactosidase (β‐gal) was also tested as an antigen. In addition, OVA adjuvant and adjuvant‐free sensitization protocols were compared in BALB/c and C57BL/6 mice. Open‐field testing was performed to assess the effect of alum on mouse behaviour.
Results
Comparison of adjuvant vs. adjuvant‐free and i.p. vs. s.c. protocols revealed that both adjuvant use and route of antigen application significantly influenced OVA‐specific antibody production. Comparison of adjuvant and adjuvant‐free protocols in this study clearly demonstrated the non‐requirement of alum for the induction of acute allergic airway inflammation, as both protocols induce a similar disease phenotype. BALB/c mice were significantly more susceptible than C57BL/6 mice to sensitization. Using the improved s.c. adjuvant‐free protocol, it was demonstrated that alternative antigens such as β‐gal can also be utilized. Behavioural studies indicated severe distress in mice treated with alum.
Conclusion
The OVA s.c. adjuvant‐free protocol used in this study generates a phenotype comparable to the benchmark adjuvant protocol widely used in the literature. The adjuvant‐free alternative avoids the added complication of non‐physiological adjuvants that may interfere with asthma treatment or prevention strategies.
Dyskalemic paralyses are characterised by single or periodic episodes with muscle weakness that affect mostly the proximal skeletal muscles. Symptoms may last for a few hours or persist for several ...days, spontaneous recovery is common. Familial cases can be distinguished from secondary, non-familial forms which are based on other diseases, for example, of the thyroid gland, kidneys or gastrointestinal tract. Familial cases are mostly inherited in an autosomal-dominant pattern and belong to the channelopathies. Both groups are characterised by changed potassium levels in the blood during an episode. A detailed and accurate medical history (plus family history, use of medication and eating habits) often easily leads to the diagnosis. Provoking tests or instrumental and histological investigations can help to solve difficult cases. Treatment focuses on relieving acute symptoms and attacks can be managed by correcting the blood potassium to a normal level. Changing eating and/or exercise habits and also permanent medical treatment helps to prevent further attacks.
There is a paucity of data on nodular regenerative hyperplasia after liver transplant. We aim to define the clinical disease trajectory and identify predictors of outcome for this rare diagnosis
This ...is a retrospective review of postulated risk factors and outcome in patients with nodular regenerative hyperplasia. Patients were classified as having a late presentation if nodular regenerative hyperplasia was diagnosed > 48 months from transplant, and symptomatic if portal hypertensive symptoms were present. Forty-nine of 3,711 (1.3%) adult recipients developed nodular regenerative hyperplasia, and mortality was 32.7% with an average follow up of 84.6 months. The MELD-Na 6 months after diagnosis did not change significantly. Patients with symptomatic portal hypertension at the time of diagnosis had a significantly higher risk of mortality (51.8%) compared to patients with liver test abnormalities alone (10.5%). 44.9% of patients had no previously postulated risk factor. Anastomotic vascular complications do not appear to be the etiology in most patients. The results suggest the vast majority of patients presenting with liver test abnormalities alone have stable disease and excellent long term survival, in contrast to the 56.3% mortality seen in patients that present more than 48 months after LT with symptomatic portal hypertension at diagnosis.
Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted ...renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6.4 %), 16 (3.9 %) increased, and 10 (2.4 %) decreased. Based on cPRA adjudication, cPRA differences generally resulted from a small number of specificities with subtle fluctuations around the borderline of the participating centers’ cutoff for unacceptable antigen listing. All five COVID recovered patients with an increased cPRA were female (p = 0.02). In summary, exposure to this virus or vaccine does not increase HLA antibody specificities and their MFI in approximately 99 % of cases and 97 % of sensitized patients. These results have implications for virtual crossmatching at the time of organ offer after SARS-CoV-2 infection or vaccination, and these events of unclear clinical significance should not influence vaccination programs.
Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large ...datasets might not predict outcomes locally.
Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (
= 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (
= 5,792) to previously published DCD scoring systems.
The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635
. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not.
DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.
The question of how far the larvae of marine organisms disperse is fundamental to an understanding of their population dynamics, the management of exploited species and the conservation of marine ...biodiversity. It is generally assumed that larvae disperse away from their natal population so that local populations operate as 'open' systems, driven by recruitment of larvae from other sub-populations. However, this assumption has never been critically tested. Here we show for the first time that juveniles from a coral reef fish population can return to their natal reef. We marked otoliths (ear bones) of over 10 million developing embryos of the damselfish, Pomacentrus amboinensis, at Lizard Island (Great Barrier Reef). Subsequently, from an examination of 5,000 juveniles settling at the same location, we found 15 marked individuals. On the basis of an estimate of the proportion of embryos marked (0.5-2%), as many as 15-60% of juveniles may be returning to their natal population (self-recruitment). We challenge the assumption that long-distance dispersal is the norm for reef fish populations.
Monitoring of the PD level of a 10kV, 6.4MVA generator in a Danish Power Plant over a couple of years has caused increasing concern about the generator's VPI insulation condition. This paper presents ...an analysis of the PD activity in the generator with an advanced PD monitoring system. The measurements were performed as on-line measurements during normal operation as well as during the start up and shut down sequences. Winding temperature and the generator load were recorded simultaneously with the PD measurements. A correlation has been established between the temporal development of PD intensity and factors like winding temperature and load level. Analyses were performed on the PD development with respect to pulse magnitude and frequency, including advanced pulse shape analyses, in order to determine PD-origin and characteristics. A comparable high PD level was recorded which, combined with experiences from early types of generators with global VPI insulation, led to the decision that the generator should be refurbished. The results described and analyzed in this paper are based on the service period with the original insulation until refurbishment.
This paper deals with transient conditions in the collection grid of offshore wind farms under different faults. A model of a standard wind farm was established in two versions, with a floating and a ...grounded collection grid respectively. Line to ground faults and three-phase to ground faults were applied at critical points at worst-case phase angle and the results compared. The simulations show that it is better with a grounded collection grid, since lack of a ground reference will prevent the system from recovering after a line to ground fault.
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