Saffold Virus, a Human Theiler's-Like Cardiovirus, Is Ubiquitous and Causes Infection Early in Life

The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease

A global experiment on motivating social distancing during the COVID-19 pandemic

Significance Communicating in ways that motivate engagement in social distancing remains a critical global public health priority during the COVID-19 pandemic. This study tested motivational qualities of messages about social distancing (those that promoted choice and agency vs. those that were forceful and shaming) in 25,718 people in 89 countries. The autonomy-supportive message decreased feelings of defying social distancing recommendations relative to the controlling message, and the controlling message increased controlled motivation, a less effective form of motivation, relative to no message. Message type did not impact intentions to socially distance, but people’s existing motivations were related to intentions. Findings were generalizable across a geographically diverse sample and may inform public health communication strategies in this and future global health emergencies. Abstract Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A synthesis of the tetracyclic carboskeleton of isaindigotidione

An efficient synthesis of the unique indolizino[7,6-c]quinoline carboskeleton of isaindigotidione has been achieved. This strategy employed L-proline and isatin as the main building blocks in the construction of the framework. Four transformations occurred in a one-pot operation to furnish the tetracyclic nucleus. © 2004 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Retro-commissioning for buildings : problems and the way forward for a policy research study

World Building Congress 2022, 26-30 June 2022, Melbourne, Australia202212 bcvcVersion of RecordPublishe

Invasive pneumococcal disease burden in Hong Kong children

In a retrospective, population-based study, we estimated the age-specific incidence of invasive pneumococcal disease in Hong Kong between 1995 and 2004. The incidence rates per 100,000 were 18.3 (95% confidence interval [CI], 13.9-23.3) for children aged ≤2 years, 15.6 (95% CI, 12.8-18.6) for children aged ≤5 years and 1 (95% CI, 0.52-1.7) for children aged 6-14 years. The findings indicate a significant disease burden. © 2006 Lippincott Williams & Wilkins.link_to_subscribed_fulltex

Phacoemulsification Versus Combined Phacotrabeculectomy in Medically Controlled Chronic Angle Closure Glaucoma with Cataract

Objective: To compare phacoemulsification alone versus combined phacotrabeculectomy in medically controlled chronic angle closure glaucoma (CACG) with coexisting cataract. Design: Randomized clinical trial. Participants: Seventy-two medically controlled CACG eyes with coexisting cataract. Intervention: Recruited patients were randomized into group 1 (phacoemulsification alone) or group 2 (combined phacotrabeculectomy with adjunctive mitomycin C). Postoperatively, patients were reviewed every 3 months for 2 years. Main Outcome Measures: Intraocular pressure (IOP) and requirement for topical glaucoma drugs. Results: Thirty-five CACG eyes were randomized into group 1, and 37 CACG eyes were randomized into group 2. There were no statistically significant differences (P>0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 1 month (P = 0.001) and 3 months (P = 0.008). Combined phacotrabeculectomy with adjunctive mitomycin C resulted in 0.80 less topical glaucoma drugs (P<0.001) in the 24-month postoperative period compared with phacoemulsification alone. The differences in IOP control were, however, not associated with differences in glaucomatous progression. Combined surgery was associated with more postoperative (P<0.001) complications compared with phacoemulsification alone. Conclusions: Combined phacotrabeculectomy with adjunctive mitomycin C may be marginally more effective than phacoemulsification alone in controlling IOP in medically controlled CACG eyes with coexisting cataract. Combined surgery may be associated with more complications and additional surgery in the postoperative period. Further study is needed to determine whether the marginally better IOP control of combined surgery justifies the potential additional risks of complications and further surgery. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. © 2008 American Academy of Ophthalmology.link_to_subscribed_fulltex

Theiler’s murine encephalomyelitis virus infection induces a redistribution of heat shock proteins 70 and 90 in BHK-21 cells, and is inhibited by novobiocin and geldanamycin

Theiler’s murine encephalomyelitis virus (TMEV) is a positive-sense RNA virus belonging to the Cardiovirus genus in the family Picornaviridae. In addition to other host cellular factors and pathways, picornaviruses utilise heat shock proteins (Hsps) to facilitate their propagation in cells. This study investigated the localisation of Hsps 70 and 90 in TMEV-infected BHK-21 cells by indirect immunofluorescence and confocal microscopy. The effect of Hsp90 inhibitors novobiocin (Nov) and geldanamycin (GA) on the development of cytopathic effect (CPE) induced by infection was also examined. Hsp90 staining was uniformly distributed in the cytoplasm of uninfected cells but was found concentrated in the perinuclear region during late infection where it overlapped with the signal for non-structural protein 2C within the viral replication complex. Hsp70 redistributed into the vicinity of the viral replication complex during late infection, but its distribution did not overlap with that of 2C. Inhibition of Hsp90 by GA and Nov had a negative effect on virus growth over a 48-h period as indicated by no observable CPE in treated compared to untreated cells. 2C was detected by Western analysis of GA-treated infected cell lysates at doses between 0.01 and 0.125 μM, suggesting that processing of viral precursors was not affected in the presence of this drug. In contrast, 2C was absent in cell lysates of Nov-treated cells at doses above 10 μM, although CPE was evident 48 hpi. This is the first study describing the dynamic behaviour of Hsps 70 and 90 in TMEV-infected cells and to identify Hsp90 as an important host factor in the life cycle of this virus