Increased burden of cardiovascular disease in people with liver disease: unequal geographical variations, risk factors and excess years of life lost

BACKGROUND: People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes. METHODS: We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD). RESULTS: The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50–59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages. CONCLUSIONS: We developed a public online app (https://lailab.shinyapps.io/cvd_in_liver_disease/) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment

Imaging the real shape of nanoclusters in scanning force microscopy

A quantitative comparison between experiment and theory is given for the constant height mode imaging of metal nanoclusters in dynamic scanning force microscopy. We explain the fundamental mechanisms in the contrast formation with the help of the system Pd/MgO(001). The comparison shows that the shape and size of nanoclusters are precisely imaged due to the sharpness of the tip’s last nanometer. This quantitative comparison proves our previously proposed model for the contrast formation.Peer reviewe

TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD

© 2016 Thorburn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Exposure to non-pathogenic Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88). The involvement of TLR2, TLR4 and MyD88 in the pathogenesis of AAD and asthma is incompletely understood, and has not been studied in S. pneumoniae-mediated suppression of AAD. We investigated the role of TLR2, TLR4 and MyD88 in the development of AAD and S. pneumoniae-mediated suppression of AAD. Methods and Findings OVA-induced AAD and killed S. pneumoniae-mediated suppression of AAD were assessed in wild-type, TLR2-/- , TLR4-/- , TLR2/4-/- and MyD88-/- BALB/c mice. During OVA-induced AAD, TLR2, TLR4 and MyD88 were variously involved in promoting eosinophil accumulation in bronchoalveolar lavage fluid and blood, and T-helper type (Th)2 cytokine release from mediastinal lymph node T cells and splenocytes. However, all were required for the induction of airways hyperresponsiveness (AHR). In S. pneumoniae-mediated suppression of AAD, TLR2, TLR4 and MyD88 were variously involved in the suppression of eosinophilic and splenocyte Th2 responses but all were required for the reduction in AHR. Conclusions These results highlight important but complex roles for TLR2, TLR4 and MyD88 in promoting the development of OVA-induced AAD, but conversely in the S. pneumoniae-mediated suppression of AAD, with consistent and major contributions in both the induction and suppression of AHR. Thus, TLR signaling is likely required for both the development of asthma and the suppression of asthma by S. pneumoniae, and potentially other immunoregulatory therapies

The mitochondrial genome of Parascaris univalens - implications for a “forgotten” parasite

© Jabbar et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The file attached is the Published/publisher’s pdf version of the article

Numerical Modeling of the Internal Temperature in the Mammary Gland

The microwave thermometry method for the diagnosis of breast cancer is based on an analysis of the internal temperature distribution.This paper is devoted to the construction of a mathematical model for increasing the accuracy of measuring the internal temperature of mammary glands, which are regarded as a complex combination of several components, such as fat tissue, muscle tissue, milk lobules, skin, blood flows, tumor tissue. Each of these biocomponents is determined by its own set of physical parameters. Our numerical model is designed to calculate the spatial distributions of the electric microwave field and the temperature inside the biological tissue. We compare the numerical simulations results to the real medical measurements of the internal temperature.Comment: 8 pages, 4 figure

Pledging to harm:A linguistic appraisal analysis of judgment comparing realized and non-realized violent fantasies

Intent is a psychological quality that threat assessors view as a required step on a threatener’s pathway to action. Recognizing the presence of intent in threatening language is therefore crucial to determining whether a threat is credible. Nevertheless, a ‘lack of empirical guidance’ (p. 326) is available concerning how violent intent is expressed linguistically. Using the subsystem of judgment in Appraisal analysis, this study compares realized with non-realized ‘pledges to harm’, revealing occasionally counterintuitive patterns of stancetaking by both author types – for example, that the non-realized texts are both prosodically more violent and more threatening, while the realized pledges are more ethically nuanced – which may begin to shed light on which attitudinal markers reliably correlate with an author’s intention to do future harm

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Maternal Particulate Matter Exposure Impairs Lung Health and Is Associated with Mitochondrial Damage.

Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM2.5 (PM2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM2.5 exerted transgenerational impairment on lung health

A National Survey of Musculoskeletal Impairment in Rwanda: Prevalence, Causes and Service Implications

BACKGROUND: Accurate information on the prevalence and causes of musculoskeletal impairment (MSI) is lacking in low income countries. We present a new survey methodology that is based on sound epidemiological principles and is linked to the World Health Organisation's International Classification of Functioning. METHODS: Clusters were selected with probability proportionate to size. Households were selected within clusters through compact segment sampling. 105 clusters of 80 people (all ages) were included. All participants were screened for MSI by a physiotherapist and medical assistant. Possible cases plus a random sample of 10% of non-MSI cases were examined further to ascertain diagnosis, aetiology, quality of life, and treatment needs. FINDINGS: 6757 of 8368 enumerated individuals (80.8%) were screened. There were 352 cases, giving an overall prevalence for MSI of 5.2%. (95% CI 4.5-5.9) The prevalence of MSI increased with age and was similar in men and women. Extrapolating these estimates, there are approximately 488,000 MSI diagnoses in Rwanda. Only 8.2% of MSI cases were severe, while the majority were moderate (43.7%) or mild (46.3%). Diagnostic categories comprised 11.5% congenital, 31.3% trauma, 3.8% infection, 9.0% neurological, and 44.4% non-traumatic non infective acquired. The most common individual diagnoses were joint disease (13.3%), angular limb deformity (9.7%) and fracture mal- and non-union (7.2%). 96% of all cases required further treatment. INTERPRETATION: This survey demonstrates a large burden of MSI in Rwanda, which is mostly untreated. The survey methodology will be useful in other low income countries, to assist with planning services and monitoring trends

Staphylococcus aureus infection dynamics

Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used "survival" model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed