Childhood predictors of adolescent behaviour: The prospective association of familial factors with meeting physical activity guidelines

Little is known about the longitudinal association of familial socio-demographic factors, behaviours, attitudes, or home environment with meeting physical activity guidelines. Our objective was to a) describe 4-year change in the prevalence of meeting guidelines, and characteristics of participants across categories of physical activity maintenance, and b) identify familial factors in childhood that are longitudinally associated with meeting guidelines in adolescence. Data on 17 parent- and child-reported family variables and objectively measured physical activity (ActiGraph GT1M) were available from 406 children (10.3 ± 0.3 years, 53.5% female) participating in the SPEEDY study. Average duration of week- and weekend day moderate-to-vigorous physical activity (MVPA, ≥ 2000 cpm) at baseline and follow-up (14.3 ± 0.3 years) were calculated to determine whether participants met 60 min MVPA/day guidelines at each assessment. Descriptives were calculated across four MVPA change categories. Multi-level logistic regression examined the association of baseline familial factors with meeting guidelines at follow-up, adjusting for sex, baseline physical activity, family socio-economic position, and school clustering. At follow-up, 51.5% and 36.1% of adolescents met guidelines on weekdays and weekend days, respectively (baseline: 68.0%, 67.2%). Girls were less likely than boys to remain sufficiently active, particularly on weekdays. Family social support was positively associated with adolescents meeting guidelines at weekends (OR 1.2; 95% CI 1.0-1.4). The presence of play equipment at home was negatively associated with meeting guidelines on weekdays (OR 0.5; 95% CI 0.3-0.8). Interventions that foster parent's facilitation of physical activity may help to encourage the upkeep of healthy behaviours during the transition from childhood to adolescence.The SPEEDY study is funded by the National Prevention Research Initiative (G0501294) (http://www.npri.org.uk), consisting of the following Funding Partners: British Heart Foundation; Cancer Research UK; Department of Health; Diabetes UK; Economic and Social Research Council; Medical Research Council; Health and Social Care Research and Development Office for the Northern Ireland; Chief Scientist Office, Scottish Government Health Directorates; Welsh Assembly Government and World Cancer Research Fund. The work was also undertaken under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which is funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust. Kirsten Corder reports receiving the following grants: Lead Applicant - A cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of the GoActive programme to increase physical activity among 13–14 year-old adolescents. Project: 13/90/18 National Institute for Health Research Public Health Research Programme Sept 2015 – Feb 2019. Co-Applicant - Opportunities within the school environment to shift the distribution of activity intensity in adolescents. Department of Health Policy Research Programme. Dec 2013 – Nov 2016. Kirsten Corder is a Director of Ridgepoint Consulting Limited, an operational improvement consultancy

Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation

In 1997, the first consensus guidelines for haematopoietic SCT (HSCT) in autoimmune diseases (ADs) were published, while an international coordinated clinical programme was launched. These guidelines provided broad principles for the field over the following decade and were accompanied by comprehensive data collection in the European Group for Blood and Marrow Transplantation (EBMT) AD Registry. Subsequently, retrospective analyses and prospective phase I/II studies generated evidence to support the feasibility, safety and efficacy of HSCT in several types of severe, treatment-resistant ADs, which became the basis for larger-scale phase II and III studies. In parallel, there has also been an era of immense progress in biological therapy in ADs. The aim of this document is to provide revised and updated guidelines for both the current application and future development of HSCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments. Patient safety considerations are central to guidance on patient selection and HSCT procedural aspects within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and EBMT accredited centres. A need for prospective interventional and non-interventional studies, where feasible, along with systematic data reporting, in accordance with EBMT policies and procedures, is emphasized

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Radiolog

A role for m6A RNA methylation in heart failure development?

Vascular Surger

Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity

Background: The presence of "anti-DNA antibodies in abnormal titres" is a well established criterion for SLE classification, but there is no agreement on the performance of this test. Objective: To study the correlation between clinical findings and five different solid and solution phase anti-DNA antibody assays. Methods: 158 consecutively collected ANA positive sera were studied in a double blind fashion. Anti-DNA antibodies were determined by different solid phase assays (ssDNA-, dsDNA- specific ELISA, EliA anti-dsDNA assay, Crithidia luciliae assay), and by an experimental solution phase anti-DNA assay using biotinylated pUC18 plasmid, human, calf thymus, and E coli DNA. Antibody affinity was determined by surface plasmon resonance. Clinical data were obtained independently of the laboratory analyses and later related to the anti-dsDNA findings. Results: Anti-dsDNA antibodies were most frequently detected by ELISA, but were not specific for SLE as they were present in up to 30% of other disease groups. Those detected by the Crithidia luciliae assay were predictive for SLE, while antibodies binding in solution phase ELISA using the pUC18 correlated strongly with the Crithidia luciliae assay. Surface plasmon resonance analysis showed that antibody binding to pUC18 was not due to higher relative affinity for dsDNA in general, but apparently to specificity for that plasmid DNA. Serum samples from three patients with lupus nephritis were positive in both pUC18 solution phase and Crithidia luciliae assays. Conclusions: Assay principle selection is decisive for the detection of clinically significant anti-DNA antibodies. Revision of the anti-DNA antibody criterion in the SLE classification may be needed

Inhibition Of Microrna-494 Halts Atherosclerotic Plaque Progression And Stabilizes Advanced Atherosclerotic Lesions

Inhibition of miR-494 reduces early carotid artery atherosclerosis. However, patients   generally   present   with   advanced atherosclerosis. Therefore, we investigated the effect of miR-494 inhibition on advanced atherosclerotic plaques.LDLr-/-  mice  were  placed  on  a  Western  Type  Diet  (WTD). After  four  weeks,  semi-constrictive  collars  were  placed  around  both carotid  arteries  to  induce  local  plaque formation.  After  10  weeks  of WTD,  a  subset  of  mice  (n   10)  was  sacrificed  as  baseline.  Remaining mice  were  placed  on  normal  chow  and  3rd Generation  Antisense  Oli-gonucleotides   (3GAs)   against   miR-494   (3GA-494;   n¼10)   or   negative control  (3GA-ctrl;  n¼10)  were  administered  (i.v.,  1  mg/mouse)  imme- diately  and  at  two  and  four  weeks  after  diet  switch.  After  5  weeks,  all mice  were  sacrificed.3GA-ctrl  mice   showed   increased   carotid   artery   plaque   size compared to baseline, even though plasma cholesterol levels were reduced upon diet-replacement (before: 863±115 mg/dL vs. after: 214±13 mg/dL). 3GA-494 treatment resulted in a further cholesterol reduction (3GA-494: 154±6   mg/dL,   Pdecreased compared to control and 3GA-494 mice had similar plaque sizes to baseline mice (baseline: 30±8*103 mm2, 3GA-ctrl: 56±16*103 mm2 vs. 3GA-494: 23±9*103 mm2, Pplaque size remained similar between groups, however, increased intra-plaque collagen (3GA- ctrl:  37±3%  vs.  3GA-494:  55±3%,  P3GA-494: 12±1%, P¼0.1) was reduced aftermiR-494 inhibition.Our results show that treatment with 3GA-494 halts plaque progression  in the carotid artery and increases plaque stability in aortic root plaques. Furthermore, 3GA-494 treatment reduces plasma cholesterolels.Biopharmaceutic

Accelerated treatment with rtPA for pulmonary embolism induced circulatory arrest

Patients with circulatory arrest due to pulmonary embolism (PE) should be treated with fibrinolytics. Current guidelines do not specify which regimen to apply, and it has been suggested that the regimen of 100 mg rtPA/2 h should be used, because this is recommended for hemodynamic instable PE in the ESC/ERS Guideline. This two hour regimen, however, is incompatible with key principles of cardiopulmonary resuscitation (CPR), such as employment of interventions that allow fast evaluation of effectiveness, and limitation of the total duration of CPR to avoid poor neurological outcomes. Additionally, the low flow-state during CPR has important consequences for the pharmacokinetic properties of rtPA. Arguably, the volume of distribution is lower, the metabolism reduced and the half life time longer. Therefore, these changes largely discard the rationale to use high dosages of rtPA over a prolonged period of time. More importantly, these changes highlight that the guideline recommendations, based on studies in patients without circulatory arrest, cannot be easily translated to the situation of circulatory arrest. An accelerated regimen of rtPA (0.6 mg/kg/15 min., max 50 mg) is mentioned by the 2019 ESC/ERS Guideline. However, empirical support or a rationale is not provided. Due to the rarity of the situation and ethical difficulties associated with randomizing unconscious patients, a randomized head-to-head comparison between the two regimens is unlikely to ever be performed. With this comprehensive overview of the pharmacokinetics of rtPA and current literature, a strong rationale is provided that the accelerated protocol is the regimen of choice for patients with PE-induced circulatory arrest