Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors

Trost E, Al-Dilaimi A, Papavasiliou P, et al. Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors. BMC Genomics. 2011;12(1): 383.ABSTRACT: Corynebacterium ulcerans has been detected as a commensal in domestic and wild animals that may serve as reservoirs for zoonotic infections. During the last decade, the frequency and severity of human infections associated with C. ulcerans appear to be increasing in various countries. As the knowledge of genes contributing to the virulence of this bacterium was very limited, the complete genome sequences of two C. ulcerans strains detected in the metropolitan area of Rio de Janeiro were determined and characterized by comparative genomics: C. ulcerans 809 was initially isolated from an elderly woman with fatal pulmonary infection and C. ulcerans BR-AD22 was recovered from a nasal sample of an asymptomatic dog. The circular chromosome of C. ulcerans 809 has a total size of 2,502,095 bp and encodes 2,182 predicted proteins, whereas the genome of C. ulcerans BR-AD22 is 104,279 bp larger and comprises 2,338 protein-coding regions. The minor difference in size of the two genomes is mainly caused by additional prophage-like elements in the C. ulcerans BR-AD22 chromosome. Both genomes show a highly similar order of orthologous coding regions; and both strains share a common set of 2,076 genes, demonstrating their very close relationship. A screening for prominent virulence factors revealed the presence of phospholipase D (Pld), neuraminidase H (NanH), endoglycosidase E (EndoE), and subunits of adhesive pili of the SpaDEF type that are encoded in both C. ulcerans genomes. The rbp gene coding for a putative ribosome-binding protein with striking structural similarity to Shiga-like toxins was additionally detected in the genome of the human isolate C. ulcerans 809. The molecular data deduced from the complete genome sequences provides considerable knowledge of virulence factors in C. ulcerans that is increasingly recognized as an emerging pathogen. This bacterium is apparently equipped with a broad and varying set of virulence factors, including a novel type of a ribosome-binding protein. Whether the respective protein contributes to the severity of human infections (and a fatal outcome) remains to be elucidated by genetic experiments with defined bacterial mutants and host model systems

Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition

Pathogenic variants in ATP-dependent chromatin remodeling proteins are a recurrent cause of neurodevelopmental disorders (NDDs). The NURF complex consists of BPTF and either the SNF2H ( SMARCA5) or SNF2L ( SMARCA1) ISWI-chromatin remodeling enzyme. Pathogenic variants in BPTF and SMARCA5 were previously implicated in NDDs. Here, we describe 40 individuals from 30 families with de novo or maternally inherited pathogenic variants in SMARCA1. This novel NDD was associated with mild to severe ID/DD, delayed or regressive speech development, and some recurrent facial dysmorphisms. Individuals carrying SMARCA1 loss-of-function variants exhibited a mild genome-wide DNA methylation profile and a high penetrance of macrocephaly. Genetic dissection of the NURF complex using Smarca1, Smarca5, and Bptfsingle and double mouse knockouts revealed the importance of NURF composition and dosage for proper forebrain development. Finally, we propose that genetic alterations affecting different NURF components result in a NDD with a broad clinical spectrum

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Victor

“Victor”, an interactive/immersive performance inspired by the book “Frankenstein or The Modern Prometheus” by Mary Shelley. The protagonist of the book Victor Frankenstein creates and animates a new creature through chemical materials and old/dismembered body parts that belong to people who are no longer alive. In the play “Victor”, the viewer had the opportunity to experience but also to execute the story. The participants enter Victor’s workspace and pass through various interactive stations that give life to the creature. The choices which are made along the journey, in uence the nal performance

Dark tourism acceptance and peacebuilding in troubled destinations

Dark tourism represents an established area of research and has a world-leading academic center for dark tourism scholarship, research and teaching. Extended body of research proved that troubled destinations need to acknowledge their pasts. This acknowledgement is absolutely necessary for the construction of identity but also peacebuilding; while moving forward without talking about the past increases trauma within a destination. However, a debate still exists on how dark tourism places and spaces are interpreted. Reflecting on the timeline of historical past events, the Greek Cypriot and Turkish Cypriot authorities have different representations of collective memories. This chapter discusses and debates how tourism can support peacebuilding activities through the acknowledgement of all dark sites within the island of Cyprus and include them in specialized tours, where the tourists personally can acknowledge the island’s dark and turbulent past. Acknowledgement rather than dismissiveness can pave the path towards peacebuilding

Cancer patients with large defects. Reconstructional options: a case study

Referimo-nos ao caso de um paciente masculino de setenta e cinco anos de idade, com um carcinoma espinocelular (SCC), que se originou na parte exterior da orelha direita há quatro anos. Sofreu uma remoção cirúrgica da parte lesionada combinada com dissecção modificada do pescoço e reconstrução com o uso de retalho peitoral maior. Além disso, teve radioterapia com 6000 rads na região temporal direita. Há dois meses o paciente mostrou urna recorrência expansiva no que diz respeito ao músculo temporal e ao osso, o osso litóide, os músculos masseter e os músculos pterigóideos, a parte direita da mandíbula, a glândula da parótida com o nervo facial, e o bulbo superior da veia jugular interna. Sofreu uma remoção cirúrgica da lesão afetada até as extremidades saudáveis e reconstrução estética e funcional com a utilização combinada de uma prótese de metal fixa do côndilo e da mandíbula direita e o uso de músculo-cutâneo trapezious flap. Apresentamos o relato de um caso sobre as opções de reconstrução que nós temos em nossos dias para proporcionar qualidade de vida a doentes que sofrem de cancro.We report a case of a seventy-five years old male patient with a squamous cell carcinoma (SCC) originated from the right external ear four years ago. He was undergone surgical removal of the lesion with a combination of modified neck dissection and reconstruction with the use of pectoralis major flap. Furthermore, he had radiotherapy with 6000 rads of the right temporal region. Two months ago the patient showed an extended recurrence concerning the temporal muscle and bone, the lithoid bone, the maseter and the pterygoids muscles, the right part of the mandible, the parotid gland with the facial nerve, and the superior bulb of the internal jugular vein. He had a surgical removal of the lesion in extended healthy margins and functional and esthetic reconstruction of the defect with a combination of metal fixed prosthesis of the condyle and the right mandible and the use of myocutaneous trapezious flap. This is a case report of the reconstruction options we have nowadays to provide quality of life in cancer patients

Novel and Gene Mutations With Diverse Phenotypic Features and the Question on the Existence of a Broader Spectrum of Dravet Syndrome

In the light of modern molecular technologies, the understanding of the complexity of the numerous genotype–phenotype correlations regarding Dravet syndrome is mandatory. Motivated by 2 patients, whose whole-exome sequencing revealed novel mutations that exemplify the phenotypic and genetic heterogeneities associated with typical and atypical Dravet syndrome presentations, the authors discuss the existence of a broader spectrum of Dravet syndrome. The first patient is a 4-year-old boy with fairly typical Dravet syndrome and a novel sodium channel α1 subunit gene mutation of high-predicted combined pathogenicity likelihood. The second patient is a 15-year-old boy with some atypical features of Dravet syndrome, harboring a novel mutation of the γ-aminobutyric acid receptor α1 subunit gene, whose role in this syndrome pathogenesis has recently been highlighted. A brief review of the literature reveals that none of the current diagnostic criteria is thoroughly predictive of the disease, and phenotypic discrepancies are common among patients carrying atypical Dravet syndrome mutations. The authors conclude that the discussion of a Dravet syndrome spectrum is relevant