Management of donor-specific antibodies in lung transplantation

The formation of antibodies against donor human leukocyte antigens poses a challenging problem both for donor selection as well as postoperative graft function in lung transplantation. These donor-specific antibodies limit the pool of potential donor organs and are associated with episodes of antibody-mediated rejection, chronic lung allograft dysfunction, and increased mortality. Optimal management strategies for clearance of DSAs are poorly defined and vary greatly by institution; most of the data supporting any particular strategy is limited to small-scale retrospective cohort studies. A typical approach to antibody depletion may involve the use of high-dose steroids, plasma exchange, intravenous immunoglobulin, and possibly other immunomodulators or small-molecule therapies. This review seeks to define the current understanding of the significance of DSAs in lung transplantation and outline the literature supporting strategies for their management

Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia-Induced Lung Injury.

AIMS: Studies have linked severe hyperoxia, or prolonged exposure to very high oxygen levels, with worse clinical outcomes. This study investigated the role of epidermal growth factor receptor (EGFR) in hyperoxia-induced lung injury at very high oxygen levels (\u3e95%). RESULTS: Effects of severe hyperoxia (100% oxygen) were studied in mice with genetically inhibited EGFR and wild-type littermates. Despite the established role of EGFR in lung repair, EGFR inhibition led to improved survival and reduced acute lung injury, which prompted an investigation into this protective mechanism. Endothelial EGFR genetic knockout did not confer protection. EGFR inhibition led to decreased levels of cleaved caspase-3 and poly (ADP-ribosyl) polymerase (PARP) and decreased terminal dUTP nick end labeling- (TUNEL-) positive staining in alveolar epithelial cells and reduced ERK activation, which suggested reduced apoptosis CONCLUSION: In conditions of severe hyperoxia (\u3e95% for \u3e24 h), EGFR inhibition led to improved survival, decreased lung injury, and reduced cell death. These findings further elucidate the complex role of EGFR in acute lung injury

Development of a mobile application for detection of adolescent mental health problems and feasibility assessment with primary health care workers

INTRODUCTION : There has been a sharp increase in the use of digital health interventions in global health, particularly mobile health applications, in recent years. The extreme shortage of health care providers trained in mental health screening and intervention in low- and middle-income countries raises questions about the applicability of mobile applications to deliver these services due to their accessibility and availability. This exploratory paper describes the development and feasibility assessment of a mobile screening application for the detection of mental disorders among adolescents in Zambia and South Africa. METHODS : Eighty-two health care workers (HCW) working in primary care evaluated the acceptability and practicality of the mobile screening application after receiving brief training. The evaluation included questions from the Mobile Application Rating Scale (MARS) as well as open-ended questions. RESULTS : The acceptability of the screening app was high and study participants were positive about using the app in routine care. Problems with internet connectivity, and time and staff constraints were perceived as the main barriers to regular use. CONCLUSION : HCW in primary care were able and willing to use a mobile screening app for the detection of mental health problems among treatment-seeking adolescents. Implementation in clinical practice needs to be further evaluated.Erasmus + Capacity Building.https://www.tandfonline.com/loi/imhn20hj2023Psychiatr

Rabbit haemorrhagic disease: virus persistence and adaptation in Australia

In Australia, the rabbit haemorrhagic disease virus (RHDV) has been used since 1996 to reduce numbers of introduced European rabbits (Oryctolagus cuniculus) which have a devastating impact on the native Australian environment. RHDV causes regular, short disease outbreaks, but little is known about how the virus persists and survives between epidemics. We examined the initial spread of RHDV to show that even upon its initial spread, the virus circulated continuously on a regional scale rather than persisting at a local population level and that Australian rabbit populations are highly interconnected by virus-carrying flying vectors. Sequencing data obtained from a single rabbit population showed that the viruses that caused an epidemic each year seldom bore close genetic resemblance to those present in previous years. Together, these data suggest that RHDV survives in the Australian environment through its ability to spread amongst rabbit subpopulations. This is consistent with modelling results that indicated that in a large interconnected rabbit meta-population, RHDV should maintain high virulence, cause short, strong disease outbreaks but show low persistence in any given subpopulation. This new epidemiological framework is important for understanding virus–host co-evolution and future disease management options of pest species to secure Australia's remaining natural biodiversity

PLINK output

Output files generated by PLINK association test for 78 samples in two groups (36 dead, 42 survivors). Details about the analysis are at https://github.org/hdetering/orycun

Data from: Resistance to RHD virus in wild Australian rabbits: comparison of susceptible and resistant individuals using a genomewide approach

Deciphering the genes involved in disease resistance is essential if we are to understand host–pathogen coevolutionary processes. The rabbit haemorrhagic disease virus (RHDV) was imported into Australia in 1995 as a biocontrol agent to manage one of the most successful and devastating invasive species, the European rabbit (Oryctolagus cuniculus). During the first outbreaks of the disease, RHDV caused mortality rates of up to 97%. Recently, however, increased genetic resistance to RHDV has been reported. Here, we have aimed to identify genomic differences between rabbits that survived a natural infection with RHDV and those that died in the field using a genomewide next-generation sequencing (NGS) approach. We detected 72 SNPs corresponding to 133 genes associated with survival of a RHD infection. Most of the identified genes have known functions in virus infections and replication, immune responses or apoptosis, or have previously been found to be regulated during RHD. Some of the genes identified in experimental studies, however, did not seem to play a role under natural selection regimes, highlighting the importance of field studies to complement the genomic background of wildlife diseases. Our study provides a set of candidate markers as a tool for the future scanning of wild rabbits for their resistance to RHDV. This is important both for wild rabbit populations in southern Europe where RHD is regarded as a serious problem decimating the prey of endangered predator species and for assessing the success of currently planned RHDV variant biocontrol releases in Australia

High adaptive variability and virus-driven selection on major histocompatibility complex (MHC) genes in invasive wild rabbits in Australia

The rabbit haemorrhagic disease virus (RHDV) was imported into Australia in 1995 as a biocontrol agent to manage one of the most successful and devastating invasive species, the European rabbit (Oryctolagus cuniculus cuniculus). During the first disease outbreaks, RHDV caused mortality rates of up to 97% and reduced Australian rabbit numbers to very low levels. However, recently increased genetic resistance to RHDV and strong population growth has been reported. Major histocompatibility complex (MHC) class I immune genes are important for immune responses against viruses, and a high MHC variability is thought to be crucial in adaptive processes under pathogen-driven selection. We asked whether strong population bottlenecks and presumed genetic drift would have led to low MHC variability in wild Australian rabbits, and if the retained MHC variability was enough to explain the increased resistance against RHD. Despite the past bottlenecks we found a relatively high number of MHC class I sequences distributed over 2–4 loci. We identified positive selection on putative antigen-binding sites of the MHC. We detected evidence for RHDV-driven selection as one MHC supertype was negatively associated with RHD survival, fitting expectations of frequency-dependent selection. Gene duplication and pathogen-driven selection are possible (and likely) mechanisms that maintained the adaptive potential of MHC genes in Australian rabbits. Our findings not only contribute to a better understanding of the evolution of invasive species, they are also important in the light of planned future rabbit biocontrol in Australia.This study was funded by the Priority Programme of the German Science Foundation (DFG) ‘Host-parasite co-evolution—rapid reciprocal adaptation and its genetic basis’ (SPP 1399, PI: So 428/7-1).Peer reviewe

STACKS output

Output of the STACKS ref_map.pl pipeline run for mapped reads of 78 samples (reads archived at ENA, accession PRJEB20958). Details about the analysis can be found at https://github.com/hdetering/orycun