COVID-19 and changes in activity and treatment of ST elevation MI from a UK cardiac centre.

Background: The international healthcare response to COVID-19 has been driven by epidemiological data related to case numbers and case fatality rate. Second order effects have been less well studied. This study aimed to characterise the changes in emergency activity of a high-volume cardiac catheterisation centre and to cautiously model any excess indirect morbidity and mortality. Method: Retrospective cohort study of patients admitted with acute coronary syndrome fulfilling criteria for the heart attack centre (HAC) pathway at St. Bartholomew's hospital, UK. Electronic data were collected for the study period March 16th - May 16th 2020 inclusive and stored on a dedicated research server. Standard governance procedures were observed in line with the British Cardiovascular Intervention Society audit. Results: There was a 28% fall in the number of primary percutaneous coronary interventions (PCIs) for ST elevation myocardial infarction (STEMI) during the study period (111 vs. 154) and 36% fewer activations of the HAC pathway (312 vs. 485), compared to the same time period averaged across three preceding years. In the context of 'missing STEMIs', the excess harm attributable to COVID-19 could result in an absolute increase of 1.3% in mortality, 1.9% in nonfatal MI and 4.5% in recurrent ischemia. Conclusions: The emergency activity of a high-volume PCI centre was significantly reduced for STEMI during the peak of the first wave of COVID-19. Our data can be used as an exemplar to help future modelling within cardiovascular workstreams to refine aggregate estimates of the impact of COVID-19 and inform targeted policy action

Variational perturbation theory for electrolyte solutions

In most approaches to the statistical mechanics, the focus is on the particles in the system, where the partition function is given as an integral over their positions and orientations. In this chapter, we consider a field theoretic perspective, where the focus is on the interaction fields generated by the particles in the system, rather than the particles themselves. This approach has some advantages in that it can account for the large scale fluctuations in the system with natural approximation schemes. The two that are considered in this work are the mean-field approximation and variational perturbation theory. For electrolyte solutions, this leads naturally to the Poisson-Boltzmann theory and its improved modifications

The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high energy phosphate metabolism

Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF-pathway manipulation is of therapeutic interest, however global, systemic upregulation of HIF may have as yet unknown effects on multiple processes. We utilized a mouse model of Chuvash polycythemia (CP), a rare genetic disorder which modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart. An integrated in and ex vivo approach was employed. In comparison to wild-type controls, CP mice had evidence (using in vivo MRI) of pulmonary hypertension, right ventricular hypertrophy, and increased left ventricular ejection fraction. Glycolytic flux (measured using 3H glucose) in the isolated, contracting, perfused CP heart was 1.8-fold higher. Net lactate efflux was 1.5-fold higher. Furthermore, in vivo 13C magnetic resonance spectroscopy (MRS) of hyperpolarized 13C1 pyruvate revealed a 2-fold increase in real-time flux through lactate dehydrogenase in the CP hearts, and a 1.6-fold increase through pyruvate dehydrogenase. 31P MRS of perfused CP hearts under increased workload (isoproterenol infusion) demonstrated increased depletion of phosphocreatine relative to ATP. Intriguingly, no changes in cardiac gene expression were detected. In summary, a modest systemic dysregulation of the HIF pathway resulted in clear alterations in cardiac metabolism and energetics. However, in contrast to studies generating high HIF levels within the heart, the CP mice showed neither the predicted changes in gene expression nor any degree of LV impairment. We conclude that the effects of manipulating HIF on the heart are dose-dependent. New and noteworthy This is the first integrative metabolic and functional study of the effects of modest HIF manipulation within the heart. Of particular note, the combination (and correlation) of perfused heart metabolic flux measurements with the new technique of real-time in vivo MR spectroscopy using hyperpolarized pyruvate is a novel development

Intentions to use contraceptives in Pakistan: implications for behavior change campaigns

<p>Abstract</p> <p>Background</p> <p>Since 1990-91, traditional method use has increased at a faster rate in Pakistan than modern method use. The importance of hormonal methods or the IUD has diminished and that of traditional methods has increased in the method mix. There is a need to identify factors motivating and deterring the adoption of specific family planning methods among married men and women in Pakistan.</p> <p>Methods</p> <p>In addition to social and demographic characteristics of respondents, a representative household survey collected information on psychological correlates of family planning behavior from 1,788 non-pregnant wives and 1,805 husbands with not-pregnant wives. Males and females were from separate households. Principal components analysis was conducted to identify the underlying constructs that were important for each gender. Multinomial logistic regression analysis was conducted to determine the correlates of male and female intentions to use contraceptive methods.</p> <p>Results</p> <p>Amongst women, the perception that her in-laws support family planning use was the strongest determinant of her intentions to use contraceptive methods. A woman's belief in the importance of spacing children and her perception that a choice of methods and facilities with competent staff were available were also powerful drivers of her intentions to use contraceptive methods. The strongest obstacle to a woman's forming an intention to use contraceptive methods was her belief that family planning decisions were made by the husband and fertility was determined by God's will. Fears that family planning would harm a woman's womb lowered a woman's intentions to use methods requiring procedures, such as the IUD and female sterilization.</p> <p>The perception that a responsible, caring, husband uses family planning to improve the standard of living of his family and to protect his wife's health was the most important determinant of a man's intention to use condoms. A husband's lack of self-efficacy in being able to discuss family planning with his wife was the strongest driver of the intention to use withdrawal. A man's fear that contraceptives would make a woman sterile and harm her womb lowered his intention to use modern contraceptive methods.</p> <p>Conclusions</p> <p>These findings highlight the importance of having secondary target audiences such as mothers-in-law and husbands in family planning behavior change campaigns implemented in Pakistan. Campaigns that stress the importance of child spacing are likely to have an impact. Client perceptions of the quality of care are important determinants of intentions to use contraceptive methods in Pakistan. Client concerns that the IUD and sterilization procedures might harm a woman's womb and cause sterility should be addressed. The findings suggest that there is a need to assess the actual quality of service delivery in Pakistan.</p

The Union of Hearts Depicted: Gladstone, Home Rule and United Ireland

First paragraph: William Ewart Gladstone detested political cartoons. They embodied caricature, the exaggeration of a particular feature into a deformity to excite ridicule or hatred. Cartoons, Gladstone once pointed out, had not existed in ancient Greece. There the ideal of human beauty was so deeply cherished that its distortion was not tolerated. Yet cartoons did the statesman powerful service during his long career. Their very frequency consolidated his image as a popular politician, bringing out qualities such as courage and tenacity that he was happy to have publicised. Nowhere, however, did they advance his cause more than in Ireland after the introduction of Home Rule. The nationalist journal United Ireland, as the illustrations in this paper will show, gave currency to striking depictions of Gladstone; and they vividly portrayed the union of hearts between England and Ireland that he preached so persistently in the late 1880s. The purpose of this article is to examine a sample of the cartoons, but first they need to be placed in their context

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. 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.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

&lt;b&gt;Background&lt;/b&gt;: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. &lt;b&gt;Methods/design&lt;/b&gt;: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken