Search

Introduction: Due to a lack of robust population denominators, Australia is unable to accurately monitor changes in the HIV epidemic for some populations. The ratio of HIV transmission relative to the number of people with HIV (an incidence prevalence ratio, or IPR) can measure such changes. The IPR is measured against an IPR benchmark derived from post‐HIV acquisition life expectancy, to indicate whether an HIV epidemic is shrinking or growing. Using IPRs and Australia‐specific IPR benchmarks, this study aims to describe the Australian HIV epidemic among three groups: men with HIV attributed to male‐to‐male sex, women with HIV and people with HIV attributed to injection drug use. Methods: Using mathematical modelling derived from HIV notifications, cohort and administrative data, IPRs were generated for each of the three groups. These IPRs were compared with IPR benchmarks derived from post‐HIV acquisition mortality estimates using abridged life tables for men, women and people who inject drugs. The IPR benchmark for men was applied to people with HIV attributed to male‐to‐male sex. Trends in the IPR over time were described for each reported population from 2015 to 2022. Results: Overall, the IPR fell by 80%, from 0.040 (range: 0.034−0.045) in 2015 to 0.008 (range: 0.003−0.013) in 2022 and fell below the benchmark (0.022) in 2020. Among people with HIV attributed to male‐to‐male sex, the IPR fell by 85%, from 0.041 (range: 0.034−0.047) in 2015 to 0.006 (range: 0.003−0.024) in 2022 and fell below the benchmark (0.022) in 2020. Among women with HIV, the IPR fell by 56%, from 0.032 (range: 0.026−0.039) in 2015 to 0.014 (range: 0.003−0.029) in 2022 and fell below the benchmark (0.022) in 2019. Among people with HIV attributed to injection drug use, the IPR fell by 61%, from 0.036 (range: 0.022−0.047) in 2015 to 0.014 (range: 0.002−0.057) in 2022 and fell below the benchmark (0.028) in 2019. Conclusions: Australian IPRs in all populations examined have dropped below the level required to sustain the HIV epidemic at current levels. By applying this method in other contexts, the changing scale of HIV epidemics may be better described for populations lacking robust population denominators. [ABSTRACT FROM AUTHOR]

Introduction: Decentralized molecular testing for infectious disease diagnosis at the point-of-care (POC) is critical to address inequities in access to timely, informed health care. The COVID-19 pandemic accelerated the demand, development and adoption of POC tests for infectious diseases globally. This has provided opportunities to maximize the individual benefits and public health impact of POC testing, particularly in remote and resource-limited primary care settings. Despite this, there remains a lack of harmonized, regulatory compliance and quality management frameworks for the delivery of molecular POC testing networks outside the laboratory setting. Areas Covered: This Perspective describes real-world lessons and experiences of delivering a fit-for-purpose, quality framework for one of the world's largest decentralized molecular POC testing programs for infectious disease across rural and remote Australian communities. Here we detail unique, key considerations to ensure the quality of POC testing in primary health settings with global application. Expert Opinion: There is an ethical and public health imperative to provide sustained access to decentralized POC testing for infectious disease in primary care. Genuine partnerships across stakeholders and disciplines are essential to deliver well governed, fit-for-purpose quality management POC testing frameworks and increase equitable access to timely, high-quality person-centered care. [ABSTRACT FROM AUTHOR]

Meeting the resource demand for an increasing human population has led to the emergence of the aquaculture industry as the fastest growing sector for food production worldwide. Modern finfish aquaculture has raised environmental concerns and, to address this, Integrated Multi-Trophic Aquaculture (IMTA) has gained popularity as a means to minimise environmental impacts. This is done by culturing extractive species alongside fed species to utilise excess nutrients and enhance their own growth. The current study, based within the Atlantic Area of Europe, identified suitable habitats for the three species Sparus aurata, Mytilus galloprovincialis and Ulva rigida, for use in a new IMTA system. Models were created using MaxEnt software and input into GIS software (ArcMap 10.8.1) for analysis. For all species, the AUC results in the model were >0.9, with values of 0.931 (S. aurata), 0.928 (M. galloprovincialis) and 0.939 (U. rigida), demonstrating significant predictive power. Jackknife testing of the model for each species identified the mean sea surface temperature (°C) and Chlorophyll A (mg m–3) concentration as the two most important variables. The model showed that areas of >50% suitability could be found throughout the study area, although the most suitable sites were in coastal areas in more southern latitudes. To identify the feasibility of establishing an IMTA system in different areas, the shipping density, MPA status and the locations of harbours were added to the maps for further consideration. Using this study, and the species-specific information identified by the model, the aquaculture industry will be better equipped to identify potential IMTA sites and integrate these systems into the EU market for sustainable production.

BackgroundWorld Health Organization (WHO) recommendations for starting and stopping mass antibiotic distributions are based on a clinical sign of trachoma, which is indirectly related to actual infection with the causative agent, Chlamydia trachomatis.MethodsThis study aimed to understand the effect of SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) interventions on ocular chlamydia in Amhara, Ethiopia, by describing the infection prevalence in a population-based sample of children aged 1-5 years. Trachoma surveys were conducted in all districts of Amhara, from 2011 to 2015 following approximately 5 years of SAFE. Ocular swabs were collected from randomly selected children to estimate the zonal prevalence of chlamydial infection. The Abbott RealTime polymerase chain reaction assay was used to detect C. trachomatis DNA.ResultsA total of 15632 samples were collected across 10 zones of Amhara. The prevalence of chlamydial infection in children aged 1-5 years was 5.7% (95% confidence interval, 4.2%-7.3%; zonal range, 1.0%-18.5%). Chlamydial infection and trachomatous inflammation-intense (TI) among children aged 1-9 years were highly correlated at the zonal level (Spearman correlation [r] = 0.93; P < .001), while chlamydial infection and trachomatous inflammation-follicular were moderately correlated (r = 0.57; P = .084).ConclusionsAfter 5 years of SAFE, there is appreciable chlamydial infection in children aged 1-5 years, indicating that transmission has not been interrupted and that interventions should continue. The sign TI was highly correlated with chlamydial infection and can be used as a proxy indicator of infection.

BackgroundHormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC.MethodsKC;Hsl+/+ and KC;Hsl-/- mice were fed standard rodent chow for 20 weeks. At sacrifice, the incidence of PDAC was determined and inflammation in the mesenteric adipose tissue and pancreas was assessed histologically and by immunofluorescence. To determine statistical significance, ANOVA and two-tailed Student's t-tests were performed. To compare PDAC incidence, a two-sided Fisher's exact test was used.ResultsCompared to KC;Hsl+/+ mice, KC;Hsl-/- mice gained similar weight and displayed adipose tissue and pancreatic inflammation. In addition, KC;Hsl-/- mice had reduced levels of plasma insulin and leptin. Importantly, the increased adipose tissue and pancreatic inflammation was associated with a significant increase in PDAC incidence in KC;Hsl-/- mice.ConclusionsHSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model.

INTRODUCTION UNAIDS has set the ambitious target to eliminate the global transmission of HIV by 2030 [1] and Australia is aiming for “virtual elimination” by the end of 2022 [2]. [...], : Introduction: Australia has set the goal for the virtual elimination of HIV transmission by the end of 2022, yet accurate information is lacking on the level of HIV transmission occurring among residents. We developed a method for estimating the timing of HIV acquisition among migrants, relative to their arrival in Australia. We then applied this method to surveillance data from the Australian National HIV Registry with the aim of ascertaining the level of HIV transmission among migrants to Australia occurring before and after migration, and to inform appropriate local public health interventions. Methods: We developed an algorithm incorporating CD4[sup.+] T‐cell decline back‐projection and enhanced variables (clinical presentation, past HIV testing history and clinician estimate of the place of HIV acquisition) and compared it to a standard algorithm which uses CD4[sup.+] T‐cell back‐projection only. We applied both algorithms to all new HIV diagnoses among migrants to estimate whether HIV infection occurred before or after arrival in Australia. Results: Between 1 January 2016 and 31 December 2020, 1909 migrants were newly diagnosed with HIV in Australia, 85% were men, and the median age was 33 years. Using the enhanced algorithm, 932 (49%) were estimated to have acquired HIV after arrival in Australia, 629 (33%) before arrival (from overseas), 250 (13%) close to arrival and 98 (5%) were unable to be classified. Using the standard algorithm, 622 (33%) were estimated to have acquired HIV in Australia, 472 (25%) before arrival, 321 (17%) close to arrival and 494 (26%) were unable to be classified. Conclusions: Using our algorithm, close to half of migrants diagnosed with HIV were estimated to have acquired HIV after arrival in Australia, highlighting the need for tailored culturally appropriate testing and prevention programmes to limit HIV transmission and achieve elimination targets. Our method reduced the proportion of HIV cases unable to be classified and can be adopted in other countries with similar HIV surveillance protocols, to inform epidemiology and elimination efforts.

Author(s): Matthew B. Osman [sup.1] , Jessica E. Tierney [sup.1] , Jiang Zhu [sup.2] , Robert Tardif [sup.3] , Gregory J. Hakim [sup.3] , Jonathan King [sup.1] , Christopher J. [...], Climate changes across the past 24,000 years provide key insights into Earth system responses to external forcing. Climate model simulations.sup.1,2 and proxy data.sup.3-8 have independently allowed for study of this crucial interval; however, they have at times yielded disparate conclusions. Here, we leverage both types of information using paleoclimate data assimilation.sup.9,10 to produce the first proxy-constrained, full-field reanalysis of surface temperature change spanning the Last Glacial Maximum to present at 200-year resolution. We demonstrate that temperature variability across the past 24 thousand years was linked to two primary climatic mechanisms: radiative forcing from ice sheets and greenhouse gases; and a superposition of changes in the ocean overturning circulation and seasonal insolation. In contrast with previous proxy-based reconstructions.sup.6,7 our results show that global mean temperature has slightly but steadily warmed, by ~0.5 °C, since the early Holocene (around 9 thousand years ago). When compared with recent temperature changes.sup.11, our reanalysis indicates that both the rate and magnitude of modern warming are unusual relative to the changes of the past 24 thousand years. Paleoclimate datasets are integrated with a climate model to reconstruct global surface temperature since the Last Glacial Maximum, showing sustained warming until the mid-Holocene.

The human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many human diseases, such as amyloid diseases, cancer, and neuropathies, making TRiC a potential therapeutic target. A detailed structural understanding of its ATP-dependent folding mechanism and substrate recognition is therefore of great importance. Of particular health-related interest is the mutation Histidine 147 to Arginine (H147R) in human TRiC subunit 5 (CCT5), which has been associated with hereditary sensory neuropathy. In this paper, we describe the crystal structures of CCT5 and the CCT5-H147R mutant, which provide important structural information for this vital protein-folding machine in humans. This first X-ray crystallographic study of a single human CCT subunit in the context of a hexadecameric complex can be expanded in the future to the other 7 subunits that form the TRiC complex.

Electron cryomicroscopy (cryo-EM) has been used to determine the atomic coordinates (models) from density maps of biological assemblies. These models can be assessed by their overall fit to the experimental data and stereochemical information. However, these models do not annotate the actual density values of the atoms nor their positional uncertainty. Here, we introduce a computational procedure to derive an atomic model from a cryo-EM map with annotated metadata. The accuracy of such a model is validated by a faithful replication of the experimental cryo-EM map computed using the coordinates and associated metadata. The functional interpretation of any structural features in the model and its utilization for future studies can be made in the context of its measure of uncertainty. We applied this protocol to the 3.3-Å map of the mature P22 bacteriophage capsid, a large and complex macromolecular assembly. With this protocol, we identify and annotate previously undescribed molecular interactions between capsid subunits that are crucial to maintain stability in the absence of cementing proteins or cross-linking, as occur in other bacteriophages.

In celebration of the National Institute on Aging's (NIA) 50th anniversary, this paper highlights the significant advances in cognitive aging research and the promotion of cognitive health among older adults. Since its inception in 1974, the NIA has played a pivotal role in understanding cognitive aging, including cognitive epidemiology, interventions, and methods, for measuring cognitive change. Key milestones include the shift toward understanding cognitive impairment and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), the development of large-scale longitudinal studies, and the incorporation of AD/ADRD-related biomarkers in cognitive aging cohorts. Additionally, NIA has championed diversifying the scientific workforce through initiatives, such as the Resource Centers for Minority Aging Research and the Butler-Williams Scholars Program. The next 50 years will continue to emphasize the importance of inclusion, innovation, and impactful research to enhance the cognitive health and well-being of older adults. [ABSTRACT FROM AUTHOR]