BACKGROUND: This study highlights an unusual and previously unreported adverse event (AE) following the minimally invasive treatment of pancreatic walled-off necrosis (WON). The standard treatment for WON currently involves primary drainage via an ultrasound-guided endoscopic, typically transgastric, approach. This method is associated with lower mortality and morbidity rates compared to traditional surgery. However, emerging AEs from these procedures may necessitate the involvement of a multidisciplinary team. Our case highlights the potential for gastrovesical fistula development as a rare AE following endoscopic drainage. Treatment for our patient prioritized individualized and non-surgical strategy, although surgical revision was also considered. CASE DESCRIPTION: A 42-year-old male presented with a large symptomatic pancreatic WON refractory to conservative management, necessitating transgastric drainage. Despite the gradual evacuation of the WON contents, treatment was complicated by stent-related issues, including inadvertent bladder penetration. Rather than surgical correction, a collaborative approach among urology, gastroenterology, and surgery teams was employed, focusing on conservative treatment strategies. This approach successfully resolved the fistula, leading to the patient's full recovery. CONCLUSIONS: Given the increasing use of endoscopic transluminal drainage in (peri)pancreatic collections, it is crucial to be aware of all potential AEs. To our knowledge, this is the first documented case of gastrovesical fistula following drainage of WON. Early recognition and a multidisciplinary approach are vital to manage this event.
- Publication type
- Journal Article MeSH
- Case Reports MeSH
About 15% of colorectal cancer (CRC) patients have first-degree relatives affected by the same malignancy. However, for most families the cause of familial aggregation of CRC is unknown. To identify novel high-to-moderate-penetrance germline variants underlying CRC susceptibility, we performed whole exome sequencing (WES) on four CRC cases and two unaffected members of a Polish family without any mutation in known CRC predisposition genes. After WES, we used our in-house developed Familial Cancer Variant Prioritization Pipeline and identified two novel variants in the solute carrier family 15 member 4 (SLC15A4) gene. The heterozygous missense variant, p. Y444C, was predicted to affect the phylogenetically conserved PTR2/POT domain and to have a deleterious effect on the function of the encoded peptide/histidine transporter. The other variant was located in the upstream region of the same gene (GRCh37.p13, 12_129308531_C_T; 43 bp upstream of transcription start site, ENST00000266771.5) and it was annotated to affect the promoter region of SLC15A4 as well as binding sites of 17 different transcription factors. Our findings of two distinct variants in the same gene may indicate a synergistic up-regulation of SLC15A4 as the underlying genetic cause and implicate this gene for the first time in genetic inheritance of familial CRC.
- MeSH
- Genetic Predisposition to Disease MeSH
- Colorectal Neoplasms * genetics pathology MeSH
- Humans MeSH
- Membrane Transport Proteins genetics MeSH
- Nerve Tissue Proteins genetics MeSH
- Pedigree MeSH
- Exome Sequencing MeSH
- Germ Cells pathology MeSH
- Germ-Line Mutation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
To date, the effects of specific modification types and sites on protein lifetime have not been systematically illustrated. Here, we describe a proteomic method, DeltaSILAC, to quantitatively assess the impact of site-specific phosphorylation on the turnover of thousands of proteins in live cells. Based on the accurate and reproducible mass spectrometry-based method, a pulse labeling approach using stable isotope-labeled amino acids in cells (pSILAC), phosphoproteomics, and a unique peptide-level matching strategy, our DeltaSILAC profiling revealed a global, unexpected delaying effect of many phosphosites on protein turnover. We further found that phosphorylated sites accelerating protein turnover are functionally selected for cell fitness, enriched in Cyclin-dependent kinase substrates, and evolutionarily conserved, whereas the glutamic acids surrounding phosphosites significantly delay protein turnover. Our method represents a generalizable approach and provides a rich resource for prioritizing the effects of phosphorylation sites on protein lifetime in the context of cell signaling and disease biology.
- MeSH
- Cell Cycle physiology MeSH
- Cyclin-Dependent Kinases genetics metabolism MeSH
- Phosphoproteins chemistry metabolism MeSH
- Phosphorylation MeSH
- Glutamates metabolism MeSH
- Mass Spectrometry methods MeSH
- Isotope Labeling methods MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Peptides metabolism MeSH
- Peroxiredoxin VI chemistry metabolism MeSH
- Proteolysis * MeSH
- Proteome genetics metabolism MeSH
- Proteomics methods MeSH
- Amino Acid Sequence MeSH
- RNA Splicing Factors chemistry metabolism MeSH
- Signal Transduction genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Achievement of equity in health requires development of a health system in which everyone has a fair opportunity to attain their full health potential. The current, large country-level variation in the reported incidence and prevalence of treated end-stage kidney disease indicates the existence of system-level inequities. Equitable implementation of kidney replacement therapy (KRT) programs must address issues of availability, affordability, and acceptability. The major structural factors that impact equity in KRT in different countries are the organization of health systems, overall health care spending, funding and delivery models, and nature of KRT prioritization (transplantation, hemodialysis or peritoneal dialysis, and conservative care). Implementation of KRT programs has the potential to exacerbate inequity unless equity is deliberately addressed. In this review, we summarize discussions on equitable provision of KRT in low- and middle-income countries and suggest areas for future research.
- Publication type
- Journal Article MeSH
- Review MeSH
Genetic variation occurring within conserved functional protein domains warrants special attention when examining DNA variation in the context of disease causation. Here we introduce a resource, freely available at www.prot2hg.com, that addresses the question of whether a particular variant falls onto an annotated protein domain and directly translates chromosomal coordinates onto protein residues. The tool can perform a multiple-site query in a simple way, and the whole dataset is available for download as well as incorporated into our own accessible pipeline. To create this resource, National Center for Biotechnology Information protein data were retrieved using the Entrez Programming Utilities. After processing all human protein domains, residue positions were reverse translated and mapped to the reference genome hg19 and stored in a MySQL database. In total, 760 487 protein domains from 42 371 protein models were mapped to hg19 coordinates and made publicly available for search or download (www.prot2hg.com). In addition, this annotation was implemented into the genomics research platform GENESIS in order to query nearly 8000 exomes and genomes of families with rare Mendelian disorders (tgp-foundation.org). When applied to patient genetic data, we found that rare (<1%) variants in the Genome Aggregation Database were significantly more annotated onto a protein domain in comparison to common (>1%) variants. Similarly, variants described as pathogenic or likely pathogenic in ClinVar were more likely to be annotated onto a domain. In addition, we tested a dataset consisting of 60 causal variants in a cohort of patients with epileptic encephalopathy and found that 71% of them (43 variants) were propagated onto protein domains. In summary, we developed a resource that annotates variants in the coding part of the genome onto conserved protein domains in order to increase variant prioritization efficiency.Database URL: www.prot2hg.com.
- MeSH
- Molecular Sequence Annotation methods MeSH
- Data Mining methods MeSH
- Databases, Genetic * MeSH
- Data Curation methods MeSH
- Genetic Variation * MeSH
- Genome, Human genetics MeSH
- Genomics methods MeSH
- Internet MeSH
- Humans MeSH
- Protein Domains genetics MeSH
- Proteins chemistry genetics metabolism MeSH
- Computational Biology methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
With rising demand for biomass, cropland expansion and intensification represent the main strategies to boost agricultural production, but are also major drivers of biodiversity decline. We investigate the consequences of attaining equal global production gains by 2030, either by cropland expansion or intensification, and analyse their impacts on agricultural markets and biodiversity. We find that both scenarios lead to lower crop prices across the world, even in regions where production decreases. Cropland expansion mostly affects biodiversity hotspots in Central and South America, while cropland intensification threatens biodiversity especially in Sub-Saharan Africa, India and China. Our results suggest that production gains will occur at the costs of biodiversity predominantly in developing tropical regions, while Europe and North America benefit from lower world market prices without putting their own biodiversity at risk. By identifying hotspots of potential future conflicts, we demonstrate where conservation prioritization is needed to balance agricultural production with conservation goals.
Linking diversity to biological processes is central for developing informed and effective conservation decisions. Unfortunately, observable patterns provide only a proportion of the information necessary for fully understanding the mechanisms and processes acting on a particular population or community. We suggest conservation managers use the often overlooked information relative to species absences and pay particular attention to dark diversity (i.e., a set of species that are absent from a site but that could disperse to and establish there, in other words, the absent portion of a habitat-specific species pool). Together with existing ecological metrics, concepts, and conservation tools, dark diversity can be used to complement and further develop conservation prioritization and management decisions through an understanding of biodiversity relativized by its potential (i.e., its species pool). Furthermore, through a detailed understanding of the population, community, and functional dark diversity, the restoration potential of degraded habitats can be more rigorously assessed and so to the likelihood of successful species invasions. We suggest the application of the dark diversity concept is currently an underappreciated source of information that is valuable for conservation applications ranging from macroscale conservation prioritization to more locally scaled restoration ecology and the management of invasive species.
- MeSH
- Biodiversity * MeSH
- Ecology MeSH
- Ecosystem MeSH
- Conservation of Natural Resources * MeSH
- Introduced Species MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The crayfish plague agent, Aphanomyces astaci, has spread throughout Europe, causing a significant decline in native European crayfish. The introduction and dissemination of this pathogen is attributed to the spread of invasive North American crayfish, which can act as carriers for A. astaci. As native European crayfish often succumb to infection with A. astaci, determining the prevalence of this pathogen in non-native crayfish is vital to prioritize native crayfish populations for managed translocation. In the current study, 23 populations of invasive signal crayfish (Pacifastacus leniusculus) from the UK were tested for A. astaci presence using quantitative PCR. Altogether, 13 out of 23 (56·5%) populations were found to be infected, and pathogen prevalence within infected sites varied from 3 to 80%. Microsatellite pathogen genotyping revealed that at least one UK signal crayfish population was infected with the A. astaci genotype group B, known to include virulent strains. Based on recent crayfish distribution records and the average rate of signal crayfish population dispersal, we identified one native white-clawed crayfish (Austropotamobius pallipes) population predicted to come into contact with infected signal crayfish within 5 years. This population should be considered as a priority for translocation.
- MeSH
- Aphanomyces isolation & purification MeSH
- Host-Parasite Interactions MeSH
- Prevalence MeSH
- Astacoidea parasitology MeSH
- Conservation of Natural Resources * MeSH
- Introduced Species MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- United Kingdom MeSH
Prioritizing brownfields for redevelopment in real estate portfolios can contribute to more sustainable regeneration and land management. Owners of large real estate and brownfield portfolios are challenged to allocate their limited resources to the development of the most critical or promising sites, in terms of time and cost efficiency. Authorities worried about the negative impacts of brownfields - in particular in the case of potential contamination - on the environment and society also need to prioritize their resources to those brownfields that most urgently deserve attention and intervention. Yet, numerous factors have to be considered for prioritizing actions, in particular when adhering to sustainability principles. Several multiple-criteria decision analysis (MCDA) approaches and tools have been suggested in order to support these actors in managing their brownfield portfolios. Based on lessons learned from the literature on success factors, sustainability assessment and MCDA approaches, researchers from a recent EU project have developed the web-based Timbre Brownfield Prioritization Tool (TBPT). It facilitates assessment and prioritization of a portfolio of sites on the basis of the probability of successful and sustainable regeneration or according to individually specified objectives. This paper introduces the challenges of brownfield portfolio management in general and reports about the application of the TBPT in five cases: practical test-uses by two large institutional land owners from Germany, a local and a regional administrative body from the Czech Republic, and an expert from a national environmental authority from Romania. Based on literature requirements for sustainability assessment tools and on the end-users' feedbacks from the practical tests, we discuss the TBPT's strengths and weaknesses in order to inform and give recommendations for future development of prioritization tools.
- MeSH
- Humans MeSH
- Decision Support Techniques MeSH
- Environmental Restoration and Remediation methods MeSH
- Conservation of Natural Resources methods MeSH
- Environmental Pollution MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Germany MeSH
- Romania MeSH
Agricultural land abandonment is recognized as a major environmental threat in Europe, being particularly pronounced in south-eastern Europe, where knowledge on its effects is limited. Taking the Balkan Peninsula as a case study, we investigated agricultural abandonment impact on passerine communities at regional level. We set up a standard methodology for site selection (70 sites) and data collection, along a well-defined forest-encroachment gradient that reflects land abandonment in four countries: Albania, Bulgaria, Croatia and Greece. Regardless the different socio-economic and political histories in the Balkans that led to diverse land abandonment patterns in space and time, rural abandonment had a consistent negative effect on bird communities, while regional-level analysis revealed patterns that were hidden at local level. The general trends were an increase of forest-dwelling bird species at the expense of farmland birds, the decline of overall bird species richness, as well as the decline of Species of European Conservation Concern (SPECs) richness and abundance. Many farmland bird species declined with land abandonment, whereas few forest species benefited from the process. In conclusion, our results support CAP towards hampering rural land abandonment and preserving semi-open rural mosaics in remote upland areas, using a suite of management measures carefully tailored to local needs. The maintenance of traditional rural landscapes should be prioritized in the Balkans, through the timely identification of HNV farmland that is most prone to abandonment. We also suggest that coordinated transnational research is needed, for a better assessment of conservation options in remote rural landscapes at European scale, including the enhancement of wild grazers' populations as an alternative in areas where traditional land management is rather unlikely to be re-established.
- MeSH
- Biodiversity MeSH
- Forests MeSH
- Birds * MeSH
- Conservation of Natural Resources MeSH
- Agriculture * MeSH
- Environment * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Albania MeSH
- Bulgaria MeSH
- Croatia MeSH
- Europe MeSH
- Greece MeSH
- Europe, Eastern MeSH
