The relationship between oxidised LDL, endothelial progenitor cells and coronary endothelial function in patients with CHD

Objective The balance between coronary endothelial dysfunction and repair is influenced by many protective and deleterious factors circulating in the blood. We studied the relationship between oxidised low-density lipoprotein (oxLDL), circulating endothelial progenitor cells (EPCs) and coronary endothelial function in patients with stable coronary heart disease (CHD). Methods 33 patients with stable CHD were studied. Plasma oxLDL was measured using ELISA, coronary endothelial function was assessed using intracoronary acetylcholine infusion and EPCs were quantified using flow cytometry for CD34+/KDR+ cells. Results Plasma oxLDL correlated positively with the number of EPCs in the blood (r=0.46, p=0.02). There was a positive correlation between the number of circulating EPCs and coronary endothelial function (r=0.42, p=0.04). There was no significant correlation between oxLDL and coronary endothelial function. Conclusions Plasma levels of oxLDL are associated with increased circulating EPCs in the blood of patients with CHD, which may reflect a host-repair response to endothelial injury. Patients with stable CHD had a high prevalence of coronary endothelial dysfunction, which was associated with lower numbers of circulating EPCs, suggesting a mechanistic link between endothelial dysfunction and the pathogenesis of atherosclerosis

Removing Orbital Debris with Lasers

Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.Comment: 37 pages, 15 figures, in preparation for submission to Advances in Space Researc

eQTL Catalogue 2023: New datasets, X chromosome QTLs, and improved detection and visualisation of transcript-level QTLs

The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs). We are continuously updating the resource to further increase its utility for interpreting genetic associations with complex traits. Over the past two years, we have increased the number of uniformly processed studies from 21 to 31 and added X chromosome QTLs for 19 compatible studies. We have also implemented Leafcutter to directly identify splice-junction usage QTLs in all RNA sequencing datasets. Finally, to improve the interpretability of transcript-level QTLs, we have developed static QTL coverage plots that visualise the association between the genotype and average RNA sequencing read coverage in the region for all 1.7 million fine mapped associations. To illustrate the utility of these updates to the eQTL Catalogue, we performed colocalisation analysis between vitamin D levels in the UK Biobank and all molecular QTLs in the eQTL Catalogue. Although most GWAS loci colocalised both with eQTLs and transcript-level QTLs, we found that visual inspection could sometimes be used to distinguish primary splicing QTLs from those that appear to be secondary consequences of large-effect gene expression QTLs. While these visually confirmed primary splicing QTLs explain just 6/53 of the colocalising signals, they are significantly less pleiotropic than eQTLs and identify a prioritised causal gene in 4/6 cases

1962: Abilene Christian College Bible Lectures - Full Text

THE RESTORATION PRINCIPLE” Being the Abilene Christian College Annual Bible Lectures 1962 Price: $3.95 Published by ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE ACC Station Abilene, Texa

Heritability and mechanisms of n-3 long chain polyunsaturated fatty acid deposition in the flesh of Atlantic salmon

N-3 long chain polyunsaturated fatty acids (n-3LC-PUFA) are essential components of vertebrate membrane lipids and are crucially deficient in modern Western diets. The main human dietary source for n-3LC-PUFA is fish and seafood, particularly oily fish and over 50% of global fish production is currently supplied by aquaculture. However, increasing pressure to include vegetable oils, which are devoid of n-3LC-PUFA, in aquaculture feeds reduces the content of these crucial nutrients in farmed fish flesh. The aim of this study was to measure the heritability and infer mechanisms determining flesh n-3LC-PUFA content in Atlantic salmon. This was achieved by analysing flesh lipid parameters in 48 families of Atlantic salmon, and by measuring differences in hepatic mRNA expression in families with high and low flesh n-3LC-PUFA. The results show that flesh n-3LC-PUFA level is a highly heritable trait (h2 = 0.77±0.14) and indicate the involvement of increased lipid transport, most likely in the form of very low density lipoprotein (VLDL) from liver. This increase in lipid transport may be associated with increased activity of a transcription factor, hepatic nuclear factor 4α (HNF4α), possibly as a result of family differences in transforming growth factor β1 (Tgfβ1) signalling. This study paves the way for identification of quantitative trait loci and gene interaction networks that are associated with levels of n-3LC-PUFA in fish flesh. Such markers can be used to assist the sustainable production of Atlantic salmon and provide optimal levels of critical nutrients for human consumers

Positive and negative effects of antipsychotic medication: an international online survey of 832 recipients

Background: Antipsychotic medication is currently the treatment of choice for psychosis, but few studies directly survey the first hand experience of recipients. Objectives: To ascertain the experiences and opinions of users of an international sample of antipsychotic drugs regarding positive and negative effects. Method: An online direct-to-consumer questionnaire was completed by 832 users of antipsychotics, from 30 countries – predominantly USA, UK and Australia. This is the largest such sample to date. Results: Over half (56%) thought the drugs reduced the problems they were prescribed for, but 27% thought they made them worse. Slightly less people found the drugs generally ‘Helpful’ (41%) than found them ‘Unhelpful’ (43%). While 35% reported that their ‘quality of life’ was ‘improved’, 54% reported that it was made ‘worse’. The average number of adverse effects reported was 11, with an average of five at the ‘severe’ level. Fourteen effects were reported by 57% or more participants, most commonly: ‘Drowsiness, feeling tired, sedation’ (92%), ‘Loss of motivation’ (86%), ‘Slowed thoughts’ (86%), and ‘Emotional numbing’ (85%). Suicidality was reported to be a side effect by 58%. Older people reported particularly poor outcomes and high levels of adverse effects. Duration of treatment was unrelated to positive outcomes but significantly related to negative outcomes. Most respondents (70%) had tried to stop taking the drugs. The most common reasons people wanted to stop were the side effects (64%) and worries about long-term physical health (52%). Most (70%) did not recall being told anything at all about side effects. Conclusions Clinical implications are discussed, with a particular focus on the principles of informed consent, and involving patients in decision making about their own lives

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks