Delayed control of herpes simplex virus infection and impaired CD4(+) T-cell migration to the skin in mouse models of DOCK8 deficiency.

DOCK8 deficiency in humans and mice leads to multiple defects in immune cell numbers and function. Patients with this immunodeficiency have a high morbidity and mortality, and are distinguished by chronic cutaneous viral infections, including those caused by herpes simplex virus (HSV). The underlying mechanism of the specific susceptibility to these chronic cutaneous viral infections is currently unknown, largely because the effect of DOCK8 deficiency has not been studied in suitable models. A better understanding of these mechanisms is required to underpin the development of more specific therapies. Here we show that DOCK8-deficient mice have poor control of primary cutaneous herpes simplex lesions and this is associated with increased virus loads. Furthermore, DOCK8-deficient mice showed a lack of CD4(+) T-cell infiltration into HSV-infected skin.

Relative risks of childhood developmental vulnerabilities in three Australian communities with exposure to per- and polyfluoroalkyl substances: data linkage study.

Background: Aqueous film forming foams (AFFF) containing per- and polyfluoroalkyl substances (PFAS) caused local environmental contamination in three Australian residential areas: Katherine in the Northern Territory (NT), Oakey in Queensland (Qld) and Williamtown in New South Wales (NSW). We examined whether children who lived in these areas had higher risks of developmental vulnerabilities than children who lived in comparison areas without known contamination. Methods: All children identified in the Medicare Enrolment File-a consumer directory for Australia's universal healthcare insurance scheme-who ever lived in exposure areas, and a sample of children who ever lived in selected comparison areas, were linked to the Australian Early Development Census (AEDC). The AEDC data were available from four cycles: 2009, 2012, 2015 and 2018. For each exposure area, we estimated relative risks (RRs) of developmental vulnerability on each of five AEDC domains and a summary measure, adjusting for sociodemographic characteristics and other potential confounders. Findings: We included 2,429 children from the NT, 2,592 from Qld and 510 from NSW. We observed lower risk of developmental vulnerability in the Communication skills and general knowledge domain in Katherine (RR = 0.74, 95% confidence interval (CI) 0.57 to 0.97), and higher risks of developmental vulnerability in the same domain (RR = 1.49, 95% CI 1.18 to 1.87) and in the Physical health and wellbeing domain in Oakey (RR = 1.31, 95% CI 1.06 to 1.61). Risks of developmental vulnerabilities on other domains were not different from those in the relevant comparison areas or were uncertain due to small numbers of events. Conclusion: There was inadequate evidence for increased risks of developmental vulnerabilities in children who ever lived in three PFAS-affected areas in Australia.

Factors related to under-treatment of secondary cardiovascular risk, including primary healthcare: Australian National Health Survey linked data analysis.

OBJECTIVE: To inform national evidence gaps on cardiovascular disease (CVD) preventive medication use and factors relating to under-treatment - including primary healthcare engagement - among CVD survivors in Australia. METHODS: Data from 884 participants with self-reported CVD from the 2014-15 National Health Survey were linked to primary care and pharmaceutical dispensing data for 2016 through the Multi-Agency Data Integration Project. Logistic regression quantified the relation of combined blood pressure- and lipid-lowering medication use to participant characteristics. RESULTS: Overall, 94.8% had visited a general practitioner (GP) and 40.0% were on both blood pressure- and lipid-lowering medications. Medication use was least likely in: women versus men (OR=0.49[95%CI:0.37-0.65]), younger participants (e.g. 45-64y versus 65-85y: OR=0.58[0.42-0.79])and current versus never-smokers (OR=0.73[0.44-1.20]). Treatment was more likely in those with ≥9 versus ≤4 conditions (OR=2.15[1.39-3.31]), with ≥11 versus 0-2 GP visits/year (OR=2.62[1.53-4.48]) and with individual CVD risk factors (e.g. high blood pressure OR=3.13 [2.34-4.19]) versus without); the latter even accounting for GP service-use frequency. CONCLUSIONS: Younger people, smokers, those with infrequent GP visits or without CVD risk factors were the least likely to be on medication. IMPLICATIONS FOR PUBLIC HEALTH: Substantial under-treatment, even among those using GP services, indicates opportunities to prevent further CVD events in primary care.