Flavivirus maturation leads to the formation of an occupied lipid pocket in the surface glycoproteins.

Flaviviruses such as Dengue (DENV) or Zika virus (ZIKV) assemble into an immature form within the endoplasmatic reticulum (ER), and are then processed by furin protease in the trans-Golgi. To better grasp maturation, we carry out cryo-EM reconstructions of immature Spondweni virus (SPOV), a human flavivirus of the same serogroup as ZIKV. By employing asymmetric localised reconstruction we push the resolution to 3.8 Å, enabling us to refine an atomic model which includes the crucial furin protease recognition site and a conserved Histidine pH-sensor. For direct comparison, we also solve structures of the mature forms of SPONV and DENV to 2.6 Å and 3.1 Å, respectively. We identify an ordered lipid that is present in only the mature forms of ZIKV, SPOV, and DENV and can bind as a consequence of rearranging amphipathic stem-helices of E during maturation. We propose a structural role for the pocket and suggest it stabilizes mature E.

Left ventricular systolic dysfunction and atrial fibrillation in older people in the community--a need for screening?

BACKGROUND: Heart failure and stroke are major causes of morbidity and mortality in older people. Angiotensin converting enzyme inhibitors improve symptoms and survival in left ventricular systolic dysfunction. Anticoagulants are effective in stroke prevention in atrial fibrillation with aspirin being a less effective alternative. OBJECTIVES: To determine the prevalence of left ventricular systolic dysfunction, health services utilisation and prescribing of diuretics and angiotensin converting enzyme inhibitors in left ventricular systolic dysfunction, and the prevalence of atrial fibrillation and anti-platelet/thrombotic therapy in atrial fibrillation in older people in the community. METHODS: 500 subjects were drawn by two-stage random sampling from 5,002 subjects aged 70 years and over living at home. Subjects were screened for atrial fibrillation and left ventricular systolic dysfunction using electrocardiography and echocardiography. RESULTS: The population prevalence amongst older people of left ventricular systolic dysfunction was 9.8% and of atrial fibrillation 7.8%. More than two-thirds of those with left ventricular systolic dysfunction were not on angiotensin converting enzyme inhibitors. Of those in atrial fibrillation, 35% were taking aspirin, 24% were taking warfarin and 41% were on neither aspirin nor warfarin. Nearly 90% of older people in the community have had contact with their general practitioner over the past year, and over half of those with left ventricular systolic dysfunction have had contact with hospital-based services over the past 2 years. CONCLUSIONS: Left ventricular systolic dysfunction is under-treated in older people in the community. Despite the high level of contact with hospital and community-based services, the majority of those with systolic left ventricular dysfunction are not on angiotensin converting enzyme inhibitors and a significant proportion of those in atrial fibrillation are not on any treatment for stroke prevention.

European reference values for Doppler indices of left ventricular diastolic filling.

The European Study Group on diastolic heart failure requires objective evidence of abnormal left ventricular diastolic function to establish the diagnosis of diastolic heart failure, which is common in older people. Reference values for Doppler indices of transmitral flow, used to assess left ventricular diastolic function, have not been reported for people 70 years and over in Europe. The aim of this study was to establish reference values for these Doppler indices of transmitral flow in older people. A random sample of 355 subjects aged 70 and over, living in the community underwent clinical assessment and echocardiography. Asymptomatic subjects with no cardiovascular disease and cardiovascular risk factors were identified. Measurements of five commonly used Doppler indices of transmitral flow from these subjects were obtained and reference range expressed as mean+/-2 standard deviations and as percentiles. We have therefore generated reference Doppler values of transmitral flow for people aged over 70 in a British population.

Inhaler technique in older people in the community.

BACKGROUND: Good inhaler technique and medication concordance is important for symptom and disease control in chronic airways disease. OBJECTIVES: Establish the prevalence of inhaler use; the main inhaler devices used by older people at home; their ability to use the inhalers they have been prescribed; and the relationship between perceived ease of use and actual performance. DESIGN: Cross-sectional population based study. SUBJECTS: Subjects aged 70 years and over living at home. METHODS: 500 subjects were randomly selected from 5002 subjects aged 70 years and over living at home. Inhalers used over the previous 24 hours were identified by a nurse on home visit. Those with cognitive impairment were excluded. Inhaler system was assessed and graded by a doctor as acceptable (perfect or minor errors) or unacceptable (major errors), using previously published criteria. Perceived ease of use of the device was rated as easy, moderate or difficult. RESULTS: 423 subjects participated in the study. The population prevalence of inhaler use was 15.8% (12.0, 19.7). Of the 91 inhaler devices used, 39 (42.8%) were metered dose inhalers, 34 (37.4%) were metered dose inhalers with large volume spacers, and 18 (19.8%) were breath-actuated devices. Thirty-two subjects (82.1%) using metered dose inhalers had an acceptable technique compared with 33 (97.1%) of those using metered dose inhalers with large volume spacers and 13 (72.2%) of those using breath-actuated devices (P < 0.05). Up to three quarters of inhalers were considered easy to use but 12% of subjects who rated their inhaler device as being easy to use made major errors. CONCLUSION: Metered dose inhaler was the most frequently prescribed inhaler and was used correctly by most subjects especially in combination with large volume spacers. Major errors were more common with breath-actuated devices. Inhaler technique should be checked as patients' perception of their inhaler skills correlates poorly with actual performance.

Diastolic heart failure in older people.

OBJECTIVES: To determine the prevalence of diastolic heart failure in older people in the community, identify associated risk factors and measure its impact on function and quality of life. DESIGN: Cross-sectional population-based study. METHODS: A two-stage random sample of 500 subjects was drawn from 5,002 subjects aged 70 years and over living at home. Diastolic heart failure was diagnosed by a panel of three physicians, based on clinical assessment and echocardiographic indicators of diastolic dysfunction. MAIN OUTCOME MEASURES: Prevalence of diastolic heart failure and its effect on function and quality of life as measured by Nottingham Extended Activities of Daily Living, Hospital Anxiety and Depression and SF-36 questionnaires. RESULTS: The prevalence of diastolic heart failure was 5.54% (95% CI = 3.71, 7.87) and was higher in women (8.32%) than in men (1.25%), P = 0.008. On multivariate analysis of variance, diastolic heart failure was associated with female gender and history of ischaemic heart disease. Subjects with diastolic heart failure had significantly poorer functional status and physical health than those without heart failure. CONCLUSIONS: Diastolic heart failure is relatively common in older people and is associated with adverse affects in older people's lives.