756-1 Non Surgical Septum Reduction: A New Treatment for Hypertrophic Obstructive Cardiomyopathy (HOCM)

In patients with HOCM and marked intraventricular gradients resistant to conventional drug treatment with beta blockers and/or Verapamil surgical resection of the muscular septal bulge has been advocated. We have investigated a new catheter treatment in 5 patients with HOCM and significant LV ouflow tract gradients. All patients were in class 3 NYHA with angina and shortness of breath. Intraventricular gradients were measured with transeptally introduced Brockenbrough catheters in the LV inflow tract and arterial catheters in the aortic root. All patients were studied at rest, during the Valsalva manoeuvre, after nitrates and after Isoproterenol infusion. The measurements were repeated during balloon occlusion of the first major septal branch of the left anterior descending coronary artery. — In all patients the resting intraventricular gradient was reduced to less than 20mm/Hg and provocative testing (nitrates and post extrasystolic potentation) failed to create typical increments. The longest inflation time was 30 minutes. Three patients had Verapamil 0.5mg injected through the angioplasty balloon which resulted in a longer lasting gradient/reduction after deflation of the balloon.–After informed consent, 2 patient had 3–5ml of desiccated alcohol infused through the inflated balloon catheter in order to devitalise the offending myocardium. This resulted in a CK elevation up to 2,500 units and permanent abolition of the intraventricular gradient accompanied by marked clinical improvement.From these preliminary observations we conclude that non surgical septum ablation maybe a promising new technique for the treatment of HOCM. Further studies are warranted

Larval Transport Modeling of Deep-Sea Invertebrates Can Aid the Search for Undiscovered Populations

Background: Many deep-sea benthic animals occur in patchy distributions separated by thousands of kilometres, yet because deep-sea habitats are remote, little is known about their larval dispersal. Our novel method simulates dispersal by combining data from the Argo array of autonomous oceanographic probes, deep-sea ecological surveys, and comparative invertebrate physiology. The predicted particle tracks allow quantitative, testable predictions about the dispersal of benthic invertebrate larvae in the south-west Pacific. Principal Findings: In a test case presented here, using non-feeding, non-swimming (lecithotrophic trochophore) larvae of polyplacophoran molluscs (chitons), we show that the likely dispersal pathways in a single generation are significantly shorter than the distances between the three known population centres in our study region. The large-scale density of chiton populations throughout our study region is potentially much greater than present survey data suggest, with intermediate 'stepping stone' populations yet to be discovered. Conclusions/Significance: We present a new method that is broadly applicable to studies of the dispersal of deep-sea organisms. This test case demonstrates the power and potential applications of our new method, in generating quantitative, testable hypotheses at multiple levels to solve the mismatch between observed and expected distributions: probabilistic predictions of locations of intermediate populations, potential alternative dispersal mechanisms, and expected population genetic structure. The global Argo data have never previously been used to address benthic biology, and our method can be applied to any non-swimming larvae of the deep-sea, giving information upon dispersal corridors and population densities in habitats that remain intrinsically difficult to assess.Irish Research Council for Science, Engineering and TechnologyScience Foundation Irelan

The effect of age on outcomes of coronary artery bypass surgery compared with balloon angioplasty or bare-metal stent implantation among patients with multivessel coronary disease. A collaborative analysis of individual patient data from 10 randomized trials.

OBJECTIVES: This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain. METHODS: Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year. RESULTS: Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages

Moving conferences online: lessons learned from an international virtual meeting

We consider the opportunities and challenges associated with organizing a conference online, using a case study of a medium-sized (approx. 400 participants) international conference held virtually in August 2020. In addition, we present quantifiable evidence of the participants' experience using the results from an online post-conference questionnaire. Although the virtual meeting was not able to replicate the in-person experience in some aspects (e.g. less engagement between participants) the overwhelming majority of respondents found the meeting an enjoyable experience and would join similar events again. Notably, there was a strong desire for future in-person meetings to have at least some online component. Online attendance by lower-income researchers was higher compared with a past, similar-themed in-person meeting held in a high-income nation, but comparable to one held in an upper-middle-income nation. This indicates that online conferences are not a panacea for diversity and inclusivity, and that holding in-person meetings in developing economies can be at least as effective. Given that it is now relatively easy to stream contents of meetings online using low-cost methods, there are clear benefits in making all presented content accessible online, as well as organizing online networking events for those unable to attend in person

Divergent Roles of Salmonella Pathogenicity Island 2 and Metabolic Traits during Interaction of S. enterica Serovar Typhimurium with Host Cells

The molecular mechanisms of virulence of the gastrointestinal pathogen Salmonella enterica are commonly studied using cell culture models of infection. In this work, we performed a direct comparison of the interaction of S. enterica serovar Typhimurium (S. Typhimurium) with the non-polarized epithelial cell line HeLa, the polarized cell lines CaCo2, T84 and MDCK, and macrophage-like RAW264.7 cells. The ability of S. Typhimurium wild-type and previously characterized auxotrophic mutant strains to enter host cells, survive and proliferate within mammalian cells and deploy the Salmonella Pathogenicity Island 2-encoded type III secretion system (SPI2-T3SS) was quantified. We found that the entry of S. Typhimurium into polarized cells was much more efficient than entry into non-polarized cells or phagocytic uptake. While SPI2-T3SS dependent intracellular proliferation was observed in HeLa and RAW cells, the intracellular replication in polarized cells was highly restricted and not affected by defective SPI2-T3SS. The contribution of aromatic amino acid metabolism and purine biosynthesis to intracellular proliferation was distinct in the various cell lines investigated. These observations indicate that the virulence phenotypes of S. Typhimurium are significantly affected by the cell culture model applied

A blueprint for an inclusive, global deep-sea Ocean Decade field programme

The ocean plays a crucial role in the functioning of the Earth System and in the provision of vital goods and services. The United Nations (UN) declared 2021–2030 as the UN Decade of Ocean Science for Sustainable Development. The Roadmap for the Ocean Decade aims to achieve six critical societal outcomes (SOs) by 2030, through the pursuit of four objectives (Os). It specifically recognizes the scarcity of biological data for deep-sea biomes, and challenges the global scientific community to conduct research to advance understanding of deep-sea ecosystems to inform sustainable management. In this paper, we map four key scientific questions identified by the academic community to the Ocean Decade SOs: (i) What is the diversity of life in the deep ocean? (ii) How are populations and habitats connected? (iii) What is the role of living organisms in ecosystem function and service provision? and (iv) How do species, communities, and ecosystems respond to disturbance? We then consider the design of a global-scale program to address these questions by reviewing key drivers of ecological pattern and process. We recommend using the following criteria to stratify a global survey design: biogeographic region, depth, horizontal distance, substrate type, high and low climate hazard, fished/unfished, near/far from sources of pollution, licensed/protected from industry activities. We consider both spatial and temporal surveys, and emphasize new biological data collection that prioritizes southern and polar latitudes, deeper (&gt; 2000 m) depths, and midwater environments. We provide guidance on observational, experimental, and monitoring needs for different benthic and pelagic ecosystems. We then review recent efforts to standardize biological data and specimen collection and archiving, making “sampling design to knowledge application” recommendations in the context of a new global program. We also review and comment on needs, and recommend actions, to develop capacity in deep-sea research; and the role of inclusivity - from accessing indigenous and local knowledge to the sharing of technologies - as part of such a global program. We discuss the concept of a new global deep-sea biological research program ‘Challenger 150,’ highlighting what it could deliver for the Ocean Decade and UN Sustainable Development Goal 14