Management and outcome of patients with established coronary artery disease: the Euro Heart Survey on coronary revascularization

Aims The purpose of the Euro Heart Survey Programme of the European Society of Cardiology is to evaluate to which extent clinical practice endorses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe. The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD). Methods and results Between November 2001 and March 2002, 7769 consecutive patients undergoing invasive evaluation at 130 hospitals (31 countries) were screened for the presence of one or more coronary stenosis >50% in diameter. Patient demographics and comorbidity, clinical presentation, invasive parameters, treatment options, and procedural techniques were prospectively entered in an electronic database (550 variables+29 per diseased coronary segment). Major adverse cardiac events (MACE) were evaluated at 30 days and 1 year. Out of 5619 patients with angiographically proven coronary stenosis (72% of screened population), 53% presented with stable angina while ST elevation myocardial infarction (STEMI) was the indication for coronary angiography in 16% and non-ST segment elevation myocardial infarction or unstable angina in 30%. Only medical therapy was continued in 21%, whereas mechanical revascularization was performed in the remainder [percutaneous coronary intervention (PCI) in 58% and coronary artery bypass grafting (CABG) in 21%]. Patients referred for PCI were younger, were more active, had a lower risk profile, and had less comorbid conditions. CABG was performed mostly in patients with left main lesions (21%), two- (25%), or three-vessel disease (67%) with 4.1 diseased segments, on average. Single-vessel PCI was performed in 82% of patients with either single- (45%), two- (33%), or three-vessel disease (21%). Stents were used in 75% of attempted lesions, with a large variation between sites. Direct PCI for STEMI was performed in 410 cases, representing 7% of the entire workload in the participating catheterization laboratories. Time delay was within 90 min in 76% of direct PCI cases. In keeping with the recommendations of practice guidelines, the survey identified under-use of adjunctive medication (GP IIb/IIIa receptor blockers, statins, and angiotensin-converting enzyme-inhibitors). Mortality rates at 30 days and 1 year were low in all subgroups. MACE primarily consisted of repeat PCI (12%). Conclusion The current Euro Heart Survey on coronary revascularization was performed in the era of bare metal stenting and provides a global European picture of the invasive approach to patients with CAD. These data will serve as a benchmark for the future evaluation of the impact of drug-eluting stents on the practice of interventional cardiology and bypass surger

Fermiology and superconductivity studies on the non-tetrachalcogenafulvalene structured organic superconductor beta-(BDA-TTP)_2SbF_6

The quantum oscillatory effect and superconductivity in a non-tetrachalcogenafulvalene (TCF) structure based organic superconductor beta-(BDA-TTP)_2SbF_6 are studied. Here the Shubnikov-de Haas effect (SdH) and angular dependent magnetoresistance oscillations (AMRO) are observed. The oscillation frequency associated with a cylindrical Fermi surface is found to be about 4050 tesla, which is also verified by the tunnel diode oscillator (TDO) measurement. The upper critical field Hc2 measurement in a tilted magnetic field and the TDO measurement in the mixed state reveal a highly anisotropic superconducting nature in this material. We compared physical properties of beta-(BDA-TTP)_2SbF_6 with typical TCF structure based quasi two-dimensional organic conductors. A notable feature of beta-(BDA-TTP)_2SbF_6 superconductor is a large value of effective cyclotron mass m_c^*=12.4+/1.1 m_e, which is the largest yet found in an organic superconductor. A possible origin of the enhanced effective mass and its relation to the superconductivity are briefly discussed.Comment: 8 pages, 10 figure

Non-human TRIM5 variants enhance recognition of HIV-1-infected cells by CD8+ T cells

Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type-1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two non-human TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the non-immunosuppressive analog of cyclosporin A, SmBz-CsA, we found a significant reduction in CD107a/MIP1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for non-human TRIM5 variants in cellular immunity. We hypothesise that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE: New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The non-human TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T-cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection

Understanding oversize/overweight industry freight flow and safety in Kansas using the Kansas Truck Routing and Intelligent Permitting System (K-TRIPS)

Master of ScienceDepartment of Civil EngineeringEric J. FitzsimmonsOversize and overweight (OSOW) trucks are an integral part of traffic movement throughout the state of Kansas and the United States as a whole, along with the freight they haul. The unique dimensions (length, width, height, and weight) of these loads makes the movement of them more challenging, and less safe for all on the road. With key east-west and north-south interstate access, Kansas is many times a required pass through point for these OSOW trucks. The Kansas Department of Transportation (KDOT) developed an automated permitting system called the Kansas Truck Routing and Intelligent Permitting System (K-TRIPS) to award permits for all large trucks in the state, including OSOW trucks. Using four years of data from K-TRIPS (2014-2017), the research team developed a series of heat maps using ArcGIS to help visualize the routes OSOW trucks were using to travel through the state of Kansas. It was found that around 87 percent of the approximately 72,000 annual OSOW trips in Kansas were taken by five industries (general construction equipment, general freight, agriculture equipment/implements, wind energy, and oil and gas equipment), and that the majority of fluctuation in the consistency of routes travelled came from two industries (wind energy and oil and gas equipment). The four years of K-TRIPS data, along with three years of crash data (2014-2016, provided by KDOT), were used to develop a logistic regression to determine factors that increased the odds of a fatal/injury (F/I) crash occurring among OSOW crashes. This was warranted due to the fact that the mass action areas aligned with the routes with the highest travel density, along with the discovery of two separate locations in the state with multiple crashes with the same sequence of events. It was found that three separate first harmful event (FHE) categories (Other non-collision, Motor vehicle in-transport, and Fixed object) were significant and all increased the odds of an F/I crash occurring, if they were the FHE. The odds of an F/I crash were higher for an asphalt road than a concrete road. Lastly, the later into the day it was, the lower the odds are to be in an F/I crash. The research team found a unique and important connection between yearly heat maps of OSOW truck routing and OSOW crashes. The mass action areas were found to have similar locations the highest-travelled routes during the three years of the dataset. These findings were similar to previous research that indicated through statistical analyses that when the percentage of trucks increased on a roadway, the amount of predicted crashes increased. This finding could be a primer for the state of Kansas to upgrade safety measures on known truck corridors that experience a high number of OSOW trucks. The ability to reduce fatal or serious injury crashes involving OSOW would have a positive net benefit for the state of Kansas, however considerable investment will be needed by the state to address all OSOW crash concerns

Economic potential of flexible balloon biogas digester among smallholder farmers: A case study from Uganda

This work was supported by the UK DFID grant on ‘The New and Emerging Technologies Research Competition (NET-RC) initiative (Grant No. DFID NET-RC A06502). We gratefully acknowledge the financial support from DFID. We also extend our thanks to the households participated in the survey. The views expressed in this paper are those of the authors and do not necessarily reflect those of DFID or the affiliated organizations. Our final thanks go to the two anonymousreviewers for their invaluable and critical comments that have remarkably improved the paper.Peer reviewedPostprin

Are smallholder farmers willing to pay for a flexible balloon biogas digester? Evidence from a case study in Uganda

This work was supported by the UK DFID grant on ‘The New and Emerging Technologies Research Competition (NET-RC) initiative (Grant No. DFID NET-RC A06502). We gratefully acknowledge the financial support from DFID. We also extend our thanks to the households participated in the survey. The views expressed in this paper are those of the authors and do not necessarily reflect those of DFID or the affiliated organizations.Peer reviewedPostprin

Superior antigen-specific CD4+ T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

BACKGROUND: The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses. METHODS: This observer-blind study, conducted in the United States (US) and Spain during the 2008-2009 influenza season, evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine (TIV) in >/=65 year-old adults.Medically-stable adults aged >/=65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV (TIV/AS03) or TIV. Healthy adults aged 18-40 years received only TIV. Blood samples were collected on Day 0, Day 21, Day 42 and Day 180. Influenza-specific CD4+ T cells, defined by the induction of the immune markers CD40L, IL-2, IFN-gamma, or TNF-alpha, were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells. RESULTS: A total of 192 adults were vaccinated: sixty nine and seventy three >/=65 year olds received TIV/AS03 and TIV, respectively; and fifty 18 - 40 year olds received TIV. In the >/=65 year-old group on Day 21, the frequency of CD4+ T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV (p /=65 year-old recipients of TIV/AS03 than in the 18 - 40 year old recipients of TIV on Days 21 (p = 0.006) and 42 (p = 0.011). CONCLUSION: This positive effect of AS03 Adjuvant System on the CD4+ T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population. TRIAL REGISTRATION: (Clinicaltrials.gov.). NCT00765076

Effects and Implications of Wearing a Face Mask on Cardiopulmonary Performance During Exercise

The coronavirus disease 2019 (COVID-19) pandemic has prompted the use of a face mask (FM) to minimize the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. The use of an FM being an accepted precautionary measure to reduce viral transmission, there is a need for examining the physiological effects of wearing an FM, specifically during exercise. PURPOSE: To assess the impact of wearing a surgical FM on cardiopulmonary parameters and exercise performance. METHODS: Nine males and 9 females (age = 21.6 ± 2.5 yrs; BMI = 24.4 ± 3.1 kg/m2) participated in 2 laboratory visits where they completed a graded maximal exercise test using a modified Bruce Protocol. Participants were randomized to which laboratory visit they would complete first, with face mask (WFM) or without face mask (WOFM), which were performed at least 48 hours apart. Expired gases, blood pressure, heart rate, blood O2 saturation including perfusion index, and the Borg Rating of Perceived Exertion (RPE) were measured and compared between the WFM and WOFM trials at 6 different intensities (rest, 40%, 55%, 70%, 80%, and 100% VO2max), using a two-way repeated measures ANOVA. RESULTS: There was a significant difference in VO2 (p = 0.001 and n2 = 0.73) between the WFM (38.5 ± 6.8 mL/kg/min) and WOFM (44.3 ± 7.4 mL/kg/min) trials only at the 100% VO2max intensity, where significantly lower values were also found during the WFM trial for respiratory rate (40.0 ± 6.8 vs 47.8 ± 8.9 bpm, p = 0.001, n2 = 0.62), respiratory exchange ratio (1.07 ± 0.08 vs 1.14 ± 0.64, p = 0.001, n2 = 0.52), and the partial pressure of expired oxygen (125.7 ± 3.5 vs 129.4 ± 3.1 mmHg, p = 0.0001, n2 = 0.54). In contrast, the partial pressure of expired carbon dioxide (32.8 ± 3.1 vs 30.8 ± 3.3 mmHg, p = 0.01, n2 = 0.33) was significantly higher during the WFM trial only at 100% VO2max intensity. No other parameters significantly differed at any of the intensities. CONCLUSION: Oxygen consumption was lower with face masks only as participants advanced from 80% to maximal effort. Notably, participants had a slower respiratory rate and exhaled a higher concentration of carbon dioxide with face masks. This result suggests that expired carbon dioxide accumulated under the face masks and participants subsequently rebreathed this expired carbon dioxide. There is no evidence that suggests exercise below 80% of VO2max while wearing face masks will cause any concerning changes in cardiopulmonary parameters. However, it is recommended that future studies examine how different types of face masks may affect cardiopulmonary function during exercise in a variety of subject populations

Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3

Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping) that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to search for drugs that might correct these changes.Funding: This study has been supported: (i) by MICINN (SAF2009-11847 and SAF2015-68580-C2-1-R), CIBERNED (CB06/05/0089) and “Fundación Eugenio Rodríguez Pascual”, to JFR; (ii) by the Research and Education Component of the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin, to CJH; and (iii) by Fundação para a Ciência e Tecnologia through the project POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014) and co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), to PM. Carmen Rodríguez-Cueto was a predoctoral fellow supported by FPI Program-Ministry of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio