Distal protection devices during percutaneous coronary and carotid interventions

Distal embolization of particulate matter complicates percutaneous coronary and peripheral interventions more often than had been recognized until recently. A number of distal protection devices are under development. The PercuSurge GuardWire™ is a balloon occlusion thrombectomy device approved by the United States Food and Drug Administration for saphenous vein graft intervention. A number of filter devices utilize an expandable filter mounted on the angioplasty guidewire to facilitate entrapment of particles and safe removal. The Parodi Anti-Emboli System™ is an example of a catheter occlusion device that establishes protection by reversing blood flow in the target vessel

A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans

We thank Sara Wassell for assistance during study days, Michelle Venables and Les Bluck for study design, as well as Sumantra Ray for expert technical support in the human study. The research was supported by grants MR/P011705/1, MC_UP_A090_1006 and MR/P01836X/1 from the UK Medical Research Council. JLG is supported by the Imperial Biomedical Research Centre, NIHR.Peer reviewe

Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans

BACKGROUND: Myo-inositol (MI) is incorporated into numerous biomolecules, including phosphoinositides and inositol phosphates. Disturbance of inositol availability or metabolism is associated with various disorders, including neurological conditions and cancers, while supplemental MI has therapeutic potential in conditions such as depression, polycystic ovary syndrome and congenital anomalies. Inositol status may be influenced by diet, synthesis, transport, utilisation and catabolism. OBJECTIVES: We aimed to investigate potential genetic regulation of circulating MI status and to evaluate correlation of MI concentration with other metabolites. METHODS: Gas chromatography mass spectrometry was used to determine plasma MI concentration of more than 2,000 healthy, young adults (aged 18-28 years) from the Trinity Student Study. Genotyping data was used to test association of plasma MI with SNPs in candidate genes, encoding inositol transporters and synthesising enzymes, and test for genome-wide association. We evaluated potential correlation of plasma MI with D-chiro inositol, glucose and other metabolites by Spearman's rank correlation. RESULTS: Mean plasma MI showed a small but significant difference between males and females (28.5 and 26.9 µM, respectively). Candidate gene analysis revealed several nominally significant associations with plasma MI, most notably for SLC5A11, encoding a sodium-coupled inositol transporter, also known as SMIT2 (sodium-dependent myo-inositol transporter 2). However, these did not survive correction for multiple testing. Subsequent testing for genome-wide association with plasma MI did not identify associations of genome-wide significance (p < 5 × 10-8). However, 8 SNPs exceeded the threshold for suggestive significant association with plasma MI concentration (p < 1 × 10-5), 3 of which were located within or close to genes: MTDH, LAPTM4B and ZP2. We found significant positive correlation of plasma MI concentration with concentration of D-chiro-inositol and several other biochemicals including glucose, methionine, betaine, sarcosine and tryptophan. CONCLUSION: Our findings suggest potential for modulation of plasma MI in young adults by variation in SLC5A11 which is worthy of further investigation

The initial U.S. experience with the Tempo active fixation temporary pacing lead in structural heart interventions

ObjectivesThis multicenter retrospective study of the initial U.S. experience evaluated the safety and efficacy of temporary cardiac pacing with the Tempo® Temporary Pacing Lead.BackgroundDespite increasing use of temporary cardiac pacing with the rapid growth of structural heart procedures, temporary pacing leads have not significantly improved. The Tempo lead is a new temporary pacing lead with a soft tip intended to minimize the risk of perforation and a novel active fixation mechanism designed to enhance lead stability.MethodsData from 269 consecutive structural heart procedures were collected. Outcomes included device safety (absence of clinically significant cardiac perforation, new pericardial effusion, or sustained ventricular arrhythmia) and efficacy (clinically acceptable pacing thresholds with successful pace capture throughout the index procedure). Postprocedure practices and sustained lead performance were also analyzed.ResultsThe Tempo lead was successfully positioned in the right ventricle and achieved pacing in 264 of 269 patients (98.1%). Two patients (0.8%) experienced loss of pace capture. Procedural mean pace capture threshold (PCT) was 0.7 ± 0.8 mA. There were no clinically significant perforations, pericardial effusions, or sustained device‐related arrhythmias. The Tempo lead was left in place postprocedure in 189 patients (71.6%) for mean duration of 43.3 ± 0.7 hr (range 2.5–221.3 hr) with final PCT of 0.84 ± 1.04 mA (n = 80). Of these patients, 84.1% mobilized out of bed with no lead dislodgment.ConclusionThe Tempo lead is safe and effective for temporary cardiac pacing for structural heart procedures, provides stable peri and postprocedural pacing and allows mobilization of patients who require temporary pacing leads.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154941/1/ccd28476.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154941/2/ccd28476_am.pd

Open letter from UK based academic scientists to the secretaries of state for digital, culture, media and sport and for health and social care regarding the need for independent funding for the prevention and treatment of gambling harms

First paragraph: Dear secretaries of state, As leading academic scientists studying gambling behaviours and its harms, we are writing to express our concern about the continuing support shown for the voluntary system of funding treatment, prevention and research in Great Britain. We feel compelled to write to you following the Betting and Gaming Council’s (BGC) recent announcement (17 June 2020) that five of its operators will now allocate the long awaited increase in funding for prevention and treatment, first promised on 2 August 2019, to GambleAware rather than the charity Action Against Gambling Harms. Irrespective of which organisation funds are given to, the BGC’s announcement exemplifies the longstanding weakness of a funding system that allows the gambling industry to regulate the availability and distribution of vital funds to address gambling harms across our communities. As we outline below, the continuance of this arrangement produces several negative effects that undermine the collective effort to reduce harms from gambling. It is also our belief that funds for research into gambling harms and their reduction should primarily be distributed through recognised independent organisations, such as UK Research and Innovation. We hereby urge you, as the secretaries of state with responsibilities for addressing gambling harms, to implement a statutory levy to fund effective prevention and treatment of gambling harms that is free both from industry influence and the perception of industry influence...... [Read more in the article]Additional co-authors: Carolyn Downs, Simon Dymond, Emanuele Fino, Elizabeth Goyder, Cindy Gray, Mark Griffiths, Peter Grindrod, Lee Hogan, Alice Hoon, Richard James, Bev John, Jill Manthorpe, Jim McCambridge, David McDaid, Martin McKee, Sally McManus, Antony Moss, Caroline Norrie, David J Nutt, Jim Orford, Rob Pryce, Gerda Reith, Amanda Roberts, Emmett Roberts, Gareth Roderique-Davies, Jim Rogers, Robert D Rogers, Stephen Sharman, John Strang, Richard Tunney, John Turner, Robert West, David Zendl

Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells

RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and is frequently mutated in acute leukemia, therapy-related leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1 are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state, but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well defined. Here we show that Runx1 deficiency decreases both apoptosis and proliferation, but only minimally impacts the frequency of long term repopulating HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We attempt to resolve these discrepancies by showing that Runx1 deficiency alters the expression of several key HSC markers, and that the number of functional LT-HSCs varies depending on the criteria used to score them. Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access