Weather extremes associated with increased Ross River virus and Barmah Forest virus notifications in NSW: learnings for public health response.

OBJECTIVE: To examine the sequence of environmental and entomological events prior to a substantial increase in Ross River virus (RRV) and Barmah Forest virus (BFV) notifications with a view to informing future public health response. METHODS: Rainfall, tidal, mosquito and human arboviral notification data were analysed to determine the temporality of events. RESULTS: Following two extremely dry years, there was a substantial increase in the abundance of mosquitoes along coastal New South Wales (NSW) two weeks after a significant rainfall event and high tides in February 2020. Subsequently, RRV and BFV notifications in north east NSW began to increase eight and nine weeks respectively after the high rainfall, with RRV notifications peaking 12 weeks after the high rainfall. CONCLUSIONS: Mosquito bite avoidance messaging should be instigated within two weeks of high summer rainfall, especially after an extended dry period. IMPLICATIONS FOR PUBLIC HEALTH: Intense summertime rain events, which are expected to increase in frequency in south-east Australia with climate change, can lead to significant increases in arboviral disease. These events need to be recognised by public health practitioners to facilitate timely public health response. This has taken on added importance since the emergence of Japanese encephalitis virus in southeastern Australia in 2022.

A Comparison of the Health Effects of Ambient Particulate Matter Air Pollution from Five Emission Sources.

This article briefly reviews evidence of health effects associated with exposure to particulate matter (PM) air pollution from five common outdoor emission sources: traffic, coal-fired power stations, diesel exhaust, domestic wood combustion heaters, and crustal dust. The principal purpose of this review is to compare the evidence of health effects associated with these different sources with a view to answering the question: Is exposure to PM from some emission sources associated with worse health outcomes than exposure to PM from other sources? Answering this question will help inform development of air pollution regulations and environmental policy that maximises health benefits. Understanding the health effects of exposure to components of PM and source-specific PM are active fields of investigation. However, the different methods that have been used in epidemiological studies, along with the differences in populations, emission sources, and ambient air pollution mixtures between studies, make the comparison of results between studies problematic. While there is some evidence that PM from traffic and coal-fired power station emissions may elicit greater health effects compared to PM from other sources, overall the evidence to date does not indicate a clear ‘hierarchy’ of harmfulness for PM from different emission sources. Further investigations of the health effects of source-specific PM with more advanced approaches to exposure modeling, measurement, and statistics, are required before changing the current public health protection approach of minimising exposure to total PM mass.

Childhood interstitial lung disease: A systematic review.

OBJECTIVES: Childhood interstitial lung disease (chILD) is a group of rare chronic and complex disorders of variable pathology. There has been no systematic review of published chILD research. This study aimed to describe chILD classification systems, epidemiology, morbidity, treatments, outcomes, and the impact of chILD on families and the burden on health services. METHODS: A systematic literature search for original studies on chILD was undertaken in the major biomedical databases to the end of December 2013. Epidemiological studies, case series and studies describing classification systems were included. Single case studies were excluded. RESULTS: The search yielded 37 publications that met study criteria. Four different chILD classification systems have been proposed in the past decade. The incidence of chILD has been estimated at 0.13-16.2 cases/100,000 children/year. One to five new cases presented to individual hospitals each year. In developed countries, the median mortality was 13% (6-19%). Morbidity and outcomes were highly variable and not systematically reported. Corticosteroids and hydroxychloroquine were the most common treatments. The impact of chILD on families and the burden on health services has not been studied. CONCLUSIONS: The heterogeneity of the chILD group of disorders, different determinations of what constitutes a chILD disorder and, a paucity of large epidemiological studies precludes consolidation of results across studies. Consensus on chILD classification is needed to support diagnosis and allow direct comparisons of research evidence. Active disease surveillance and international patient registries are required to advance understanding and management of chILD.

Bone marrow-derived HL mitigates bone marrow-derived CETP-mediated decreases in HDL in mice globally deficient in HL and the LDLr.

The objective of this study was to determine the combined effects of HL and cholesteryl ester transfer protein (CETP), derived exclusively from bone marrow (BM), on plasma lipids and atherosclerosis in high-fat-fed, atherosclerosis-prone mice. We transferred BM expressing these proteins into male and female double-knockout HL-deficient, LDL receptor-deficient mice (HL(-/-)LDLr(-/-)). Four BM chimeras were generated, where BM-derived cells expressed 1) HL but not CETP, 2) CETP and HL, 3) CETP but not HL, or 4) neither CETP nor HL. After high-fat feeding, plasma HDL-cholesterol (HDL-C) was decreased in mice with BM expressing CETP but not HL (17 ± 4 and 19 ± 3 mg/dl, female and male mice, respectively) compared with mice with BM expressing neither CETP nor HL (87 ± 3 and 95 ± 4 mg/dl, female and male mice, respectively, P < 0.001 for both sexes). In female mice, the presence of BM-derived HL mitigated this CETP-mediated decrease in HDL-C. BM-derived CETP decreased the cholesterol component of HDL particles and increased plasma cholesterol. BM-derived HL mitigated these effects of CETP. Atherosclerosis was not significantly different between BM chimeras. These results suggest that BM-derived HL mitigates the HDL-lowering, HDL-modulating, and cholesterol-raising effects of BM-derived CETP and warrant further studies to characterize the functional properties of these protein interactions.

Childhood interstitial lung disease due to surfactant protein C deficiency: frequent use and costs of hospital services for a single case in Australia.

BACKGROUND: Rare chronic diseases of childhood are often complex and associated with multiple health issues. Such conditions present significant demands on health services, but the degree of these demands is seldom reported. This study details the utilisation of hospital services and associated costs in a single case of surfactant protein C deficiency, an example of childhood interstitial lung disease. METHODS: Hospital records and case notes for a single patient were reviewed. Costs associated with inpatient services were extracted from a paediatric hospital database. Actual costs were compared to cost estimates based on both disease/procedure-related cost averages for inpatient hospital episodes and a recently implemented Australian hospital funding algorithm (activity-based funding). RESULTS: To age 8 years and 10 months the child was a hospital inpatient for 443 days over 32 admissions. A total of 298 days were spent in paediatric intensive care. Investigations included 58 chest x-rays, 9 bronchoscopies, 10 lung function tests and 11 sleep studies. Comprehensive disease management failed to prevent respiratory decline and a lung transplant was required. Costs of inpatient care at three tertiary hospitals totalled $966,531 (Australian dollars). Disease- and procedure-related cost averages underestimated costs of paediatric inpatient services for this patient by 68%. An activity-based funding algorithm that is currently being adopted in Australia estimated the cost of hospital health service provision with more accuracy. CONCLUSIONS: Health service usage and inpatient costs for this case of rare chronic childhood respiratory disease were substantial. This case study demonstrates that disease- and procedure-related cost averages are insufficient to estimate costs associated with rare chronic diseases that require complex management. This indicates that the health service use for similar episodes of hospital care is greater for children with rare diseases than other children. The impacts of rare chronic childhood diseases should be considered when planning resources for paediatric health services.

Leukocyte-derived hepatic lipase increases HDL and decreases en face aortic atherosclerosis in LDLr-/- mice expressing CETP.

In addition to hepatic expression, cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are expressed by human macrophages. The combined actions of these proteins have profound effects on HDL structure and function. It is not known how these HDL changes influence atherosclerosis. To elucidate the role of leukocyte-derived HL on atherosclerosis in a background of CETP expression, we studied low density lipoprotein receptor-deficient mice expressing human CETP (CETPtgLDLr -/-) with a leukocyte-derived HL deficiency (HL -/- BM). HL(-/-) bone marrow (BM), CETPtgLDLr(-/-) mice were generated via bone marrow transplantation. Wild-type bone marrow was transplanted into CETPtgLDLr(-/-) mice to generate HL +/+ BM, CETPtgLDLr(-/-) controls. The chimeras were fed a high-fat, high-cholesterol diet for 14 weeks to promote atherosclerosis. In female HL(-/-) BM, CETPtgLDLr(-/-) mice plasma HDL-cholesterol concentration during high-fat feeding was decreased 27% when compared with HL +/+ BM, CETPtgLDLr(-/-) mice (P < 0.05), and this was associated with a 96% increase in en face aortic atherosclerosis (P < 0.05). In male CETPtgLDLr(-/-) mice, leukocyte-derived HL deficiency was associated with a 16% decrease in plasma HDL-cholesterol concentration and a 25% increase in aortic atherosclerosis. Thus, leukocyte-derived HL in CETPtgLDLr(-/-) mice has an atheroprotective role that may involve increased HDL levels.

High-density lipoproteins: an emerging target in the prevention of cardiovascular disease.

High-density lipoproteins (HDLs) have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target HDL and its ability to protect against the development of atherosclerotic plaque. This paper will review how the promotion of the functional properties of HDL inhibits the formation of atherosclerotic plaque and stabilises lesions in patients with established disease.

Formation of high density lipoproteins containing both apolipoprotein A-I and A-II in the rabbit.

Human plasma HDLs are classified on the basis of apolipoprotein composition into those that contain apolipoprotein A-I (apoA-I) without apoA-II [(A-I)HDL] and those containing apoA-I and apoA-II [(A-I/A-II)HDL]. ApoA-I enters the plasma as a component of discoidal particles, which are remodeled into spherical (A-I)HDL by LCAT. ApoA-II is secreted into the plasma either in the lipid-free form or as a component of discoidal high density lipoproteins containing apoA-II without apoA-I [(A-II)HDL]. As discoidal (A-II)HDL are poor substrates for LCAT, they are not converted into spherical (A-II)HDL. This study investigates the fate of apoA-II when it enters the plasma. Lipid-free apoA-II and apoA-II-containing discoidal reconstituted HDL [(A-II)rHDL] were injected intravenously into New Zealand White rabbits, a species that is deficient in apoA-II. In both cases, the apoA-II was rapidly and quantitatively incorporated into spherical (A-I)HDL to form spherical (A-I/A-II)HDL. These particles were comparable in size and composition to the (A-I/A-II)HDL in human plasma. Injection of lipid-free apoA-II and discoidal (A-II)rHDL was also accompanied by triglyceride enrichment of the endogenous (A-I)HDL and VLDL as well as the newly formed (A-I/A-II)HDL. We conclude that, irrespective of the form in which apoA-II enters the plasma, it is rapidly incorporated into spherical HDLs that also contain apoA-I to form (A-I/A-II)HDL.

What is so special about apolipoprotein AI in reverse cholesterol transport?

An initial step in reverse cholesterol transport is the movement of unesterified cholesterol from peripheral cells to high-density lipoproteins (HDLs). This transfer usually occurs in extracellular spaces, such as the subendothelial space of a vessel wall, and is promoted by the interaction of lipid-free or lipid-poor apolipoprotein (apo)AI with ATP binding cassette A1 cellular transporters on macrophages (MPhi). Because HDL does not interact with MPhi ATP binding cassette A1 and apoAI is not synthesized by macrophages, this apoAI must be generated from spherical HDL. In this brief review, we propose that spherical apoAI is derived from HDL by remodeling events that are accomplished by proteins secreted by cholesteryl ester-loaded foam cells, including the lipid transfer proteins, phospholipid transfer protein, and cholesteryl ester transfer protein, and the triglyceride hydrolases hepatic lipase and lipoprotein lipase.

Apolipoprotein E enhances hepatic lipase-mediated hydrolysis of reconstituted high-density lipoprotein phospholipid and triacylglycerol in an isoform-dependent manner.

This study compares the kinetics of hepatic lipase (HL)-mediated phospholipid and triacylglycerol hydrolysis in spherical, reconstituted high-density lipoproteins (rHDL) that contain either apolipoprotein E2 (apoE2), apoE3, apoE4, or apoA-I as the sole apolipoprotein. HL-mediated phospholipid hydrolysis was assessed by incubating various concentrations of rHDL that contained only cholesteryl esters (CE) in their core, (E2/CE)rHDL, (E3/CE)rHDL, (E4/CE)rHDL, and (A-I/CE)rHDL, with a constant amount of HL. The rate of phospholipid hydrolysis was determined as the formation of nonesterified fatty acid mass. HL-mediated triacylglycerol hydrolysis was assessed in rHDL containing CE, unlabeled triacylglycerol, and [(3)H]triacylglycerol in their core, (E2/TG)rHDL, (E3/TG)rHDL, (E4/TG)rHDL, and (A-I/TG)rHDL. Triacylglycerol hydrolysis was determined as the ratio of (3)H-labeled hydrolysis products to (3)H-labeled unhydrolyzed triacylglycerol. The rates of phospholipid hydrolysis in the (E2/CE)rHDL, (E3/CE)rHDL, and (E4/CE)rHDL were significantly greater than that in the (A-I/CE)rHDL. The rates of triacylglycerol hydrolysis were also greater in the (E2/TG)rHDL, (E3/TG)rHDL, and (E4/TG)rHDL compared to the (A-I/TG)rHDL, although to a lesser degree than observed with phospholipid hydrolysis. Furthermore, the rates of both phospholipid and triacylglycerol hydrolyses were greater in the (E2)rHDL than in either the (E3)rHDL or the (E4)rHDL. These results show that apoE increases the rate of HL-mediated phospholipid and triacylglycerol hydrolysis in rHDL and that this influence is isoform dependent.