An Unexpectedly Broad Thermal and Salinity-Tolerant Estuarine Methanogen Community

Moderately thermophilic (Tmax, ~55 °C) methanogens are identified after extended enrichments from temperate, tropical and low-temperature environments. However, thermophilic methanogens with higher growth temperatures (Topt ≥ 60 °C) are only reported from high-temperature environments. A microcosm-based approach was used to measure the rate of methane production and methanogen community structure over a range of temperatures and salinities in sediment from a temperate estuary. We report short-term incubations (<48 h) revealing methanogens with optimal activity reaching 70 °C in a temperate estuary sediment (in situ temperature 4–5 °C). While 30 °C enrichments amended with acetate, H2 or methanol selected for corresponding mesophilic trophic groups, at 60 °C, only hydrogenotrophs (genus Methanothermobacter) were observed. Since these methanogens are not known to be active under in situ temperatures, we conclude constant dispersal from high temperature habitats. The likely provenance of the thermophilic methanogens was studied by enrichments covering a range of temperatures and salinities. These enrichments indicated that the estuarine sediment hosted methanogens encompassing the global activity envelope of most cultured species. We suggest that estuaries are fascinating sink and source environments for microbial function study

Assessing the content validity of the revised Health of the Nation Outcome Scales 65+: the HoNOS Older Adults

Aims and method: Recently, the Health of the Nation Outcome Scales (HoNOS) 65+ was revised. Twenty-five experts from Australia and New Zealand completed an anonymous web-based survey about the content validity of the revised measure, the HoNOS Older Adults (HoNOS OA). Results: All 12 HoNOS OA scales were rated by most (≥75%) experts as ‘important’ or ‘very important’ for determining overall clinical severity among older adults. Ratings of sensitivity to change, comprehensibility and comprehensiveness were more variable, but mostly positive. Experts’ comments provided possible explanations. For example, some experts suggested that additional older adult-specific examples be included in the glossary (e.g., for scales measuring depressed mood, problems with relationships, and problems with activities of daily living). Clinical implications: Experts agreed that the HoNOS OA measures important constructs. Training may be needed to orient experienced raters to the rationale for some revisions. Further psychometric testing of the HoNOS OA is recommended

Assessing the content validity of the revised Health of the Nation Outcome Scales (HoNOS 2018)

The Health of the Nation Outcome Scales (HoNOS) comprises 12 scales that cover the kinds of problems that may be experienced by working-age adults in contact with specialised mental health services. Drawing on 20 years’ experience in clinical practice, a collaborative, international review of the HoNOS was undertaken and a revised measure (known as the HoNOS 2018) was published. In this study, 32 experts from Australia, England and New Zealand completed an anonymous web-based survey to assess the relevance, comprehensiveness and comprehensibility (aspects of content validity) of the HoNOS 2018. The experts rated 11 of the 12 HoNOS 2018 scales as ‘important’ or ‘very important’ for determining the overall clinical severity (item-level content validity index or I-CVI ≥ 0.75). Evaluations of the scales’ ability to capture change, comprehensiveness and comprehensibility were more variable, but generally positive. Experts’ comments provided further insights into this variability; for example, they noted that some scales combine multiple phenomena, which can result in ambiguity in item wording and assessment challenges. Results from this study suggest that the revisions have not altered the importance of the scales. Given the measure’s breadth of content, training remains important for ensuring rating fidelity. Inter-rater reliability and utility testing are indicated

Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia.

Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCCmec) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens

Assessing the content validity of the revised Health of the Nation Outcome Scales 65+: the HoNOS Older Adults

Aims and method: Recently, the Health of the Nation Outcome Scales (HoNOS) 65+ was revised. Twenty-five experts from Australia and New Zealand completed an anonymous web-based survey about the content validity of the revised measure, the HoNOS Older Adults (HoNOS OA). Results: All 12 HoNOS OA scales were rated by most (≥75%) experts as ‘important’ or ‘very important’ for determining overall clinical severity among older adults. Ratings of sensitivity to change, comprehensibility and comprehensiveness were more variable, but mostly positive. Experts’ comments provided possible explanations. For example, some experts suggested that additional older adult-specific examples be included in the glossary (e.g., for scales measuring depressed mood, problems with relationships, and problems with activities of daily living). Clinical implications: Experts agreed that the HoNOS OA measures important constructs. Training may be needed to orient experienced raters to the rationale for some revisions. Further psychometric testing of the HoNOS OA is recommended

Identification of source and sink populations for the emergence and global spread of the East-Asia clone of Community-Associated MRSA

Background: Our understanding of the factors influencing the emergence, dissemination and global distribution of epidemic clones of bacteria is limited. ST59 is a major epidemic clone of community-associated MRSA in East Asia, responsible for extensive morbidity and mortality, but has a much lower prevalence in other parts of the world. The geographic origin of ST59 and its international routes of dissemination are unclear and disputed in the literature. Results: To investigate the origin and spread of the ST59 clone, we obtained whole genome sequences of isolates from four continents, sampled over more than a decade, and carried out a time-scaled phylogeographic analysis. We discover that two distinct ST59 clades emerged concurrently, in East Asia and the USA, but underwent clonal expansion at different times. The East Asia clade was strongly enriched for gene determinants associated with antibiotic resistance, consistent with regional differences in antibiotic usage. Both clones spread independently to Australia and Europe, and we found evidence of the persistence of multi-drug resistance following export from East Asia. Direct transfer of strains between Taiwan and the USA was not observed in either direction, consistent with geographic niche exclusion. Conclusions: Our results resolve a longstanding controversy regarding the origin of the ST59 clone, revealing the major global source and sink populations and routes for the spread of multi-drug resistant clones. Additionally, our findings indicate that diversification of the accessory genome of epidemic clones partly reflects region-specific patterns of antibiotic usage, which may influence bacterial fitness after transmission to different geographic locations

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent.

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere

Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer

Reovirus type 3 Dearing (T3D) has demonstrated oncolytic activity in vitro, in in vivo murine models and in early clinical trials. However the true potential of oncolytic viruses may only be realized fully in combination with other modalities such as chemotherapy, targeted therapy and radiotherapy. In this study, we examine the oncolytic activity of reovirus T3D and chemotherapeutic agents against human prostate cancer cell lines, with particular focus on the highly metastatic cell line PC3 and the chemotherapeutic agent docetaxel. Docetaxel is the standard of care for metastatic prostate cancer and acts by disrupting the normal process of microtubule assembly and disassembly. Reoviruses have been shown to associate with microtubules and may require this association for efficient viral replication