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Interaction Between the Matrix Protein and the Polymerase Complex of Respiratory Syncytial Virus
No full textThe global burden of respiratory syncytial virus (RSV) and severe associated disease is prodigious. RSV-specific vaccines have been launched recently but there is no antiviral medicine commercially available. RSV polymerase (L) protein is one of the promising antiviral targets, along with fusion and nucleocapsid proteins. During medicinal chemistry campaigns, two potent L-protein inhibitors (PC786 and PC751) were identified. Both compounds inhibited the RSV A/B-induced cytopathic effect in HEp-2 cells equally, but PC786 was more potent than PC751 in bronchial epithelial cells. Repeated treatment with escalating concentrations on RSV A2-infected HEp-2 cells revealed both inhibitors led to a Y1631H mutation in the L protein, but only PC786 induced a mutation in the M protein (V153A). By L protein fragment and M protein binding analysis, we showed that the M protein interacts with the 1392–1735 amino acid region of the L protein, where PC786 potentially binds. In addition, PC786 treatment or PC786-induced mutant RSV was found to increase M-protein nuclear localisation later in infection, concomitant with delayed fusion protein localisation at the budding viral filaments. As M protein is known to play a key role in virus assembly and budding late in infection, our data suggests that disrupting the interaction between the M and L proteins could provide a novel target for antiviral development.</p
Functional Foods and Nutraceuticals for the Management of Cardiovascular Disease Risk in Postmenopausal Women
No full textCardiovascular disease (CVD) is a leading cause of death in women and risk of development is greatly increased following menopause. Menopause occurs over several years and is associated with hormonal changes, including a reduction in estradiol and an increase in follicle-stimulating hormone. This hormonal shift may result in an increased risk of developing abdominal adiposity, insulin resistance, dyslipidemia, vascular dysfunction, hypertension, type 2 diabetes mellitus (T2DM), metabolic dysfunction-associated fatty liver disease (MAFLD), and metabolic syndrome (MetS). Furthermore, with the onset of menopause, there is an increase in oxidative stress that is associated with impaired vascular function, inflammation, and thrombosis, further increasing the risk of CVD development. Despite the harmful consequences of the menopause transition being well known, women in premenopausal, perimenopausal, and postmenopausal stages are unlikely to be enrolled in research studies. Therefore, investigations on the prevention and treatment of cardiovascular and metabolic disease in middle-aged women are still relatively limited. Whilst lifestyle interventions are associated with reduced CVD risk in this population sample, the evidence still remains inconclusive. Therefore, it is important to explore the effectiveness of early intervention and potential therapeutic approaches to maintain cellular redox balance, preserve endothelium, and reduce inflammation. Glycine, N-acetylcysteine, and L-theanine are amino acids with potential antioxidant and anti-inflammatory activity and are identified as therapeutic interventions in the management of age-related and metabolic diseases. The benefits of the intake of these amino acids for improving factors associated with cardiovascular health are discussed in this review. Future studies using these amino acids are warranted to investigate their effect on maintaining the vascular health and cardiovascular outcomes of postmenopausal women.</p
Reducing exposure to residential wood smoke in Australia: health equity, environmental justice, and implementation challenges and opportunities
No full textBACKGROUND AND AIM[|]Wood heater smoke, a major modifiable source of air pollution in Australian cities and towns, reduces community health and wellbeing. In addition to impacts on local air quality, their carbon dioxide, methane and black carbon emissions contribute to climate change. When operated in the home environment, even modern wood heater emissions are much higher than manufacturers’ claims, implying that current Australian wood heater standards are insufficient to protect public health. The affordability and suitability of wood heaters, compared to cleaner domestic heating options, such as reverse cycle air conditioning, is questionable in residential areas.[¤]METHOD[|]The effect of particulate air pollution (PM2.5) from wood heaters on mortality in the Australian Capital Territory (ACT) was estimated using health impact assessment methods. We also analysed the policy context and options for reducing wood heater smoke exposure, and their effectiveness, distributional effects, health co-benefits, potential trade-offs, implementation challenges and opportunities.[¤]RESULTS[|]The annual impact of wood heater pollution on mortality in the ACT was estimated to be 11-63 attributable deaths, equivalent to 57–333 million (AUD) each year. The ACT was the first regional government in Australia to announce in 2023 that it will phase out wood heaters (by 2045). However, government programs to reduce the number of wood heaters, e.g. offering rebates for decommissioning, have not been effective due to social, behavioural and financial reasons, and industry opposition.[¤]CONCLUSIONS[|]Current interventions aiming to reduce the numbers of wood heaters in the ACT and other Australian regions have proved largely ineffective, raising questions about their design, implementation, health equity and environmental justice implications. More comprehensive policies involving registration of existing wood heaters, awareness raising of their health and environmental impacts, stronger financial incentives for decommissioning, and mandatory removal of units before a property is sold, may help reduce the health burden of wood heater pollution in Australia.[¤
Validation of the PECUNIA reference unit costs templates in Spain:a useful tool for multi-national economic evaluations of health technologies
Get PDFBackground: The PECUNIA Project was funded by the H2020 programme in which 10 partners from six countries participated. The aim was to develop standardized, harmonized and validated methods and tools to calculate costs in different sectors (such as health and social care, education among others), with the purpose of facilitating comparability of economic evaluations of health technologies across European countries. In this paper we report the first validation of the developed reference unit cost templates in Spain. Methods: The evaluation of the PECUNIA Reference Unit Cost (RUC) Templates involved usability, transferability and feasibility assessment. Applicability tests were performed to estimate the cost of a selection of 15 resource items by means of the RUC templates in Spain and in four Spanish regions. External validation involved comparison with existing unit costs. Results: It was possible to estimate the cost of five services (dental care and general practitioner in the Canary Islands, general practitioner in Spain [tariffs], health-related day care centre and education services provided in a special education school in the Basque Country), car vandalism as an example of potential health-related consequences, and informal care in Spain. The templates were feasible although data completeness depended on the type of data needed to estimate the costs. The templates are transferable across countries although comparability depends on the services available in each jurisdiction. Conclusions: The PECUNIA RUC Templates are free and feasible tools to estimate comparable reference unit costs across countries. Although more validation exercises are needed, they seem useful tools to perform robust multi-national economic evaluations and increase the transferability of cost-effectiveness studies of health technologies in Europe. However, they cannot compensate for the lack of data across jurisdictions.</p
Nurse experiences of partnership nursing when caring for children with long-term conditions and their families:A qualitative systematic review
No full textAimTo explore the experiences of partnership nursing among nurses when caring for children and young people with long-term conditions, and their families.BackgroundPartnership nursing is promoted as a positive model of care among paediatric nurses, where shared roles and decision-making, parental participation, mutual trust and respect, communication and negotiation are valued to create positive care experiences and enhance patient outcomes. Little is known about how nurses use partnership with both the patient and the parents in this triad to deliver partnership nursing.DesignA qualitative systematic review followed Joanna Briggs Institute meta-aggregation approach and has been reported according to PRISMA guidelines.MethodsA comprehensive systematic search was conducted in seven electronic databases. Studies were assessed according to a pre-determined inclusion criteria. Qualitative findings with illustrative participant quotes were extracted from included studies and grouped into categories to inform overall synthesised findings. Methodological quality assessment was conducted.FindingsA total of 5837 publications were screened, and 41 qualitative studies were included. Three overarching synthesised findings were identified: (1) Using education to promote feelings of safety and support, (2) Partnering to develop a strong therapeutic relationship and (3) Optimising communication underpinned by shared decision-making principles to deliver individualised care.ConclusionNurses demonstrated successful partnership in their practice, but focused on developing dyadic nurse–parent and dyadic nurse–child partnerships. Future practice development that creates a three-way triadic partnership may aid therapeutic relationships and shared decision-making.Implications for clinical practiceClinicians can reflect on how dyadic partnerships (focusing on the child or the parent) may exclude opportunities for coherent care. Further exploration in practice, policy and research as to how nurses determine child competency and child and parent level of engagement in triadic partnership may improve the potential of meaningful shared decision-making
Access to senior secondary science and mathematics:Examining the evidence for stratification in an Australian school system
No full textThis research investigates access to senior school science and mathematics subjects offered in the final year of secondary schooling. Using data from the most populous Australian state of New South Wales, we examine whether stratification occurs in access to science and mathematics curricula. We find that the opportunity to study these subjects differs by key school characteristics, including location, socioeconomic composition and school sector. We find that while some science subjects and entry level mathematics are offered in most schools, substantial inequalities exist in access to the most advanced level of mathematics and chemistry. School location, socioeconomic composition, enrolment size and the availability of teachers predict the probability of whether a school offers the least and most advanced science and mathematics subjects. The findings highlight that stratification in curricula offerings occurs systemically and may intensify educational inequalities.<br/
Humor, Ridicule, and the Far Right:Mainstreaming Exclusion Through Online Animation
No full textThis paper critically examines the use of online humor and ridicule to promote and normalize far-right exclusionary discourses. Through a critical qualitative study of the Please Explain miniseries, a series of thirty-four short web cartoons produced by Australian far-right populist party, Pauline Hanson’s One Nation, we explore the strategic use of humor in the communicative arsenal of the contemporary far-right. Drawing on critical discourse analysis and thematic analysis, we examine how humor is used to soften articulations of exclusionary and supremacist ideas, including racism, misogyny, and queerphobia. Our findings suggest that the frivolity and irony of the online animated genre works to stretch the boundaries of the sayable, potentially making the content more palatable to non-far-right audiences. We argue that the strategic use of exclusionary humor forms part of a wider project of far-right discursive mainstreaming that simultaneously (re)legitimizes everyday expressions of exclusion
Combining Heat and Altitude Training to Enhance Temperate, Sea-Level Performance
No full textBACKGROUND: Repeated exposure to heat (ie, plasma volume expansion) or altitude (ie, increase in total hemoglobin mass), in conjunction with exercise, induces hematological adaptations that enhance endurance performance in each respective environment. Recently, combining heat and altitude training has become increasingly common for athletes preparing to compete in temperate, sea-level conditions.PURPOSE: To review the physiological adaptations to training interventions combining thermal and hypoxic stimuli and summarize the implications for temperate, sea-level performance. Current Evidence: To date, research on combining heat and hypoxia has employed 2 main approaches: simultaneously combining the stressors during training or concurrently training in the heat and sleeping at altitude, sometimes with additional training in hypoxia. When environmental stimuli are combined in a training session, improvements in aerobic fitness and time-trial performance in temperate, sea-level conditions are generally similar in magnitude to those observed with heat, or altitude, training alone. Similarly, training in the heat and sleeping at altitude does not appear to provide any additional hematological or nonhematological benefits for temperate; sea-level performance relative to training in hot, hypoxic, or control conditions.CONCLUSIONS: Current research regarding combined heat and altitude interventions does not seem to indicate that it enhances temperate, sea-level performance to a greater extent than "traditional" (heat or hypoxia alone) training approaches. A major challenge in implementing combined-stressor approaches lies in the uncertainty surrounding the prescription of dosing regimens (ie, exercise and environmental stress). The potential benefits of conducting heat and altitude exposure sequentially (ie, one after the other) warrants further investigation.</p
Response to COVID-19 vaccination in patients on cancer therapy:Analysis in a SARS-CoV-2-naïve population
No full textBackground: Cancer patients have increased morbidity and mortality from COVID-19, but may respond poorly to vaccination. The Evaluation of COVID-19 Vaccination Efficacy and Rare Events in Solid Tumors (EVEREST) study, comparing seropositivity between cancer patients and healthy controls in a low SARS-CoV-2 community-transmission setting, allows determination of vaccine response with minimal interference from infection. Methods: Solid tumor patients from The Canberra Hospital, Canberra, Australia, and healthy controls who received COVID-19 vaccination between March 2021 and January 2022 were included. Blood samples were collected at baseline, pre-second vaccine dose and at 1, 3 (primary endpoint), and 6 months post-second dose. SARS-CoV-2 anti-spike-RBD (S-RBD) and anti-nucleocapsid IgG antibodies were measured. Results: Ninety-six solid tumor patients and 20 healthy controls were enrolled, with median age 62 years, and 60% were female. Participants received either AZD1222 (65%) or BNT162b2 (35%) COVID-19 vaccines. Seropositivity 3 months post vaccination was 87% (76/87) in patients and 100% (20/20) in controls (p =.12). Seropositivity was observed in 84% of patients on chemotherapy, 80% on immunotherapy, and 96% on targeted therapy (differences not satistically significant). Seropositivity in cancer patients increased from 40% (6/15) after first dose, to 95% (35/37) 1 month after second dose, then dropped to 87% (76/87) 3 months after second dose. Conclusion: Most patients and all controls became seropositive after two vaccine doses. Antibody concentrations and seropositivity showed a decrease between 1 and 3 months post vaccination, highlighting need for booster vaccinations. SARS-CoV-2 infection amplifies S-RBD antibody responses; however, cannot be adequately identified using nucleocapsid serology. This underlines the value of our COVID-naïve population in studying vaccine immunogenicity.</p
A Systematic Review on the Studies of Thermal Comfort in Urban Residential Buildings in China
Get PDFThere have been fruitful publications on thermal comfort of urban residential buildings in China. However, there is a lack of reviews on this topic to perform a comprehensive analysis and find opportunities to meet occupants’ thermal comfort needs while improving building energy efficiencies. This paper addresses this issue by presenting a systematic review on the advancements in research on thermal comfort in urban residential buildings in China. Firstly, two common thermal comfort research approaches, i.e., field studies and laboratory studies, are discussed. Secondly, eleven main thermal comfort evaluation indicators are summarized. Finally, this paper analyzes the thermal comfort survey data from different researchers, discusses the impacts of adaptive behaviors on human thermal comfort, and provides recommendations for future research on urban residential thermal comfort. It was found that people have higher and higher requirements for their indoor thermal environment as time goes by, especially in the winter; the thermoneutral temperature is higher in warmer climate regions in the summer but lower in the winter than in colder climate regions; the thermoneutral temperature tends to increase with the indoor air temperature due to an adaptation to the indoor thermal environment. The outcomes of this paper provide valuable information on thermal comfort behaviors of urban residents in different climate zones in China, which can serve as a resource for the academic community conducting future research on thermal comfort and assist policymakers in enhancing building energy efficiencies without compromising the occupants’ comfort