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Objectives: Using high-performance liquid chromatography (HPLC), we developed and validated an in vitro assay for the quantitative determination of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity, supplementing limited current methodologies to assess the efficacy of BACE1 inhibitor compounds. A hexa-histidine tagged peptide substrate of BACE1 was used as the analyte for the determination of in vitro BACE1 activity; it was validated according to ICH guidelines. Methods: The HPLC analysis was performed on the Agilent 1290 Series Infinity II UHPLC System equipped with a Phenomenex Kinetex EVO C18 (100 × 3 mm) 5 µm column. The method was developed using a gradient programme comprising 10% aqueous acetonitrile (0.02 M TFA) to 30% aqueous acetonitrile (0.02 M TFA) for 5 min at a flow rate of 0.6 mL/min. Results: The method showed linearity over the range of 14.92 to 72 µM with r2=0.9997. The accuracy of the method in terms of mean recovery ranged between 96.62 and 98.38%. The %RSD for intra- and inter-day precision was less than 5%. Two commercial inhibitors, AZD3839 and OM99-2, were used to evaluate the performance of the method at their respective IC50, resulting in inhibition of 53.46 and 50.74%, respectively. The described method addresses the void for a practical and cheap alternative to quantitatively determine the activity of BACE1 compared to current commercially available detection assays. Conclusions: We have successfully developed an HPLC method to measure the inhibitory function of two commercial inhibitors of BACE1, indicating the suitability of the method for the identification and characterisation of novel BACE1 inhibitors.

Background: There have been 26 epidemic thunderstorm asthma (ETSA) events worldwide, with Melbourne at the epicentre of ETSA with 7 recorded events, and in 2016 experienced the deadliest ETSA event ever recorded. Health services and emergency departments were overwhelmed with thousands requiring medical care for acute asthma and 10 people died. Objectives: This multidisciplinary study was conducted across various health and science departments with the aim of improving our collective understanding of the mechanism behind ETSA. Design: This study involved time-resolved analysis of atmospheric sampling of the air for pollen and fungal spores, and intact and ruptured pollen compared with different weather parameters, pollution levels and clinical asthma presentations. Methods: Time-resolved pollen and fungal spore data collected by Deakin AirWATCH Burwood, underwent 3-h analysis, to better reflect the ‘before’, ‘during’ and ‘after’ ETSA time points, on the days leading up to and following the Melbourne 2016 event. Linear correlations were conducted with atmospheric pollution data provided by the Environment Protection Authority (EPA) of Victoria, weather data sourced from Bureau of Meteorology (BOM) and clinical asthma presentation data from the Victorian Agency for Health Information (VAHI) of Department of Health. Results: Counts of ruptured grass pollen grains increased 250% when the thunderstorm outflow reached Burwood. Increased PM10, high relative humidity, decreased temperature and low ozone concentrations observed in the storm outflow were correlated with increased levels of ruptured grass pollen. In particular, high ozone levels observed 6 h prior to this ETSA event may be a critical early indicator of impending ETSA event, since high ozone levels have been linked to increasing pollen allergen content and reducing pollen integrity, which may in turn contribute to enhanced pollen rupture. Conclusion: The findings presented in this article highlight the importance of including ruptured pollen and time-resolved analysis to forecast ETSA events and thus save lives.

Ocular allergy (OA) is a subtype of seasonal allergy that causes symptoms of itchiness, redness, swelling and irritation of the ocular surface and eyelids, often triggering allergy-induced eye rubbing and sustained inflammation for up to six months of the year during peak allergy season. These symptoms, coupled with reduced sleep quality, impaired daily productivity and decreased mood, highlight a significant yet underrepresented disease burden. Recent advances in tear-based multi-omics have enabled detailed characterisation of OA-associated biochemical changes on the ocular surface, highlighting human tears as a promising biospecimen for diagnostic biomarker and therapeutic target research. This review discusses emerging proteomic, lipidomic, metabolomic and miRNA findings comparing OA sufferers with healthy controls, and, where relevant, with comorbid conditions such as dry eye disease and keratoconus. Differential expression patterns across these analytes implicate key pathways involved in immune response, wound healing, angiogenesis, inflammation, oxidative stress and return to homeostasis on the ocular surface. By integrating these data into a stepwise model of OA biopathway activation, this review outlines candidate biomarkers and highlights methodological advances that may support translation of tear multi-omics into clinical tools for OA management.

Allergic rhinitis (hay fever) prevalence has increased in Australia. People with hay fever often experience many eye symptoms, especially itching. This study explores clinical correlations between tear IgE levels and ocular allergy signs in hay fever sufferers, focusing also on eyelid wiper friction damage from eye rubbing. In a cross-sectional study from November 2024 to January 2025, 16 individuals with self-reported hay fever and 17 healthy controls were recruited. Participants completed demographic and allergy-related questionnaires, including symptoms and quality of life assessments. Tear samples were analyzed for IgE and MMP-9 biomarkers. Ocular surface parameters-bulbar redness, palpebral roughness, and lid wiper epitheliopathy (LWE)-were graded. Corneal and conjunctival dendritic cells were also evaluated. Elevated tear IgE significantly correlated with self-reported hay fever, QUICK score, MiniRQLQ, eye rubbing frequency, and lower LWE grade. The hay fever group showed significantly higher LWE compared to healthy controls (p < 0.001), indicating frictional eyelid damage. ROC analysis of tear IgE yielded an AUC of 0.893 (cut-off 0.03 IU/mL; sensitivity 90%, specificity 85%). Tear IgE is a useful biomarker for ocular inflammation and may indicate friction-related eyelid damage in allergy sufferers. Incorporating LWE grading into clinical assessments of ocular allergy is recommended.

Grass pollen constitutes a significant public health concern in Australia, particularly for individuals with seasonal allergic rhinitis and asthma, due to its strong association with epidemic thunderstorm asthma (ETSA) events, which are getting more frequent due to climate change. The combined effects of humidity and lightning during ETSA events cause intact grass pollen to rupture and release small particles that can trigger severe asthma attacks, leading to increased hospital admissions. To help prevent this, researchers began collecting and monitoring local pollen data that contribute to ETSA warning systems. In Australia, expert pollen counters rely on Hirst-type traps, but these machines take 24 h to operate. Some modern machines have been designed to monitor pollen faster, but they are not able to determine the state of the pollen (i.e., intact or ruptured). The advent of artificial intelligence (AI) presents an opportunity to enhance pollen monitoring by accurately identifying not only pollen taxa but also the state of the pollen. Using AI to monitor ruptured pollen could improve the accuracy and efficiency of warning systems, thereby helping to prevent the severe outcomes associated with ETSA events.

Despite making up a significant proportion of airborne allergens, the relationship between fungal spores and asthma is not fully explored. Only 80 taxa of fungi have so far been observed to exacerbate respiratory presentations, with Cladosporium spp., Aspergillus spp., Penicillium spp., and Alternaria spp. found to comprise the predominant allergenic airborne spores. Fungal spores have been found in indoor environments, such as hospitals and housing due to poor ventilation. Meanwhile, outdoor fungal spores exhibit greater diversity, and higher abundance and have been associated with hospitalizations from acute asthma presentations. In addition, fungal spores may be the underlying, and perhaps the “missing link”, factor influencing the heightened rate of asthma presentations during epidemic thunderstorm asthma events. To improve our knowledge gap on fungal spores, airborne allergen monitoring must be improved to include not only dominant allergenic fungi but also provide real-time data to accurately and quickly warn the general public. Such data will help prevent future asthma exacerbations and thus save lives. In this review, we examine the health risks of prominent allergenic fungal taxa, the factors influencing spore dispersal and distribution, and why improvements should be made to current sampling methods for public health and wellbeing.

Survey studies have played a significant role in understanding the gaps in the knowledge and practices of health practitioners. However, there have been no such survey studies on Ocular Allergy (OA). Thus, the purpose of this study was to develop and validate a survey on OA to better understand the gaps in the diagnostic, treatment, and collaborative care approaches of health practitioners in OA. The survey is titled “Survey on Ocular Allergy for Health Practitioners (SOAHP)”. SOAHP was developed in a five-stage process. First, item extraction via the use of a literature review, second, face and content validity, third, a pilot study, fourth, test–retest reliability, and fifth, finalisation of the survey. 65 items under 6 domains were initially generated in the item extraction phase. Content validity was conducted on 15 experts in the field. This was conducted twice to reach consensus whereby items and domains were added, edited, kept, or removed, resulting in 50 items under 7 domains. The pilot study was conducted on 15 participants from the five relevant health practitioner fields (Allergists/Immunologists, General Practitioners (GPs), Ophthalmologists, Optometrists and Pharmacists). This altered the survey further to 40 items under 7 domains. Test–retest reliability was conducted on 25 participants from the five health practitioner fields. Reliability was moderate to almost perfect for most (97%) investigated items. The finalised survey was 40 items under 7 domains. SOAHP is the first survey created to assess diagnostic, treatment and collaborative care approaches of Allergists/Immunologists, GPs, Ophthalmologists, Optometrists and Pharmacists on OA. SOAHP will be a useful tool in clinical research on OA.

Although associations between airborne allergens, weather conditions and respiratory health have been established, the precise mechanisms that contribute to the onset and severity of epidemic thunderstorm asthma (ETSA) events remain poorly understood. One critical area of this research lies in understanding the role of fungal spores, which have not been extensively studied for their impact on asthma exacerbations compared to pollen, as well as the influence of certain pollutants like ozone on airborne allergens, which is not well documented. This study aimed to identify the environmental parameters that influence the dispersal & distribution of airborne allergens and how these factors are associated with asthma presentations. Analysis was conducted on 475 days of data collected over a 6-year period between October-December. Using eight global negative binomial generalised linear mixed model formulations combined with a model selection approach, we analysed airborne levels of grass pollen, Alternaria spp., and Cladosporium spp. from Metropolitan Melbourne, along with weather values from the Bureau of Meteorology (precipitation, temperature, humidity, dew point, wind direction, wind speed, air pressure) and pollution values from the Environmental Protection Authority (CO, NO 2 , O 3 , SO 2 ) to identify effects on asthma presentations from five emergency departments. Rainfall and O 3 levels had significant positive relationships with number of asthma presentations, with Incidence Response Ratios of 1.074–1.088 and 1.05–1.06, respectively. High allergen levels (allergenPC1, representing overall levels of grass pollen and fungal spores) had an interactive effect with high rainfall creating positive association with asthma cases. On days of low rainfall, allergen levels had minimal impact on asthma presentations, but on days of high rainfall, there were substantially greater numbers of presentations when allergen levels were also high (e.g. a predicted four-fold increase on days with 45 mm of rain). This impact of overall allergen count highlights the role of several prominent allergens in seasonal asthma, as well as potential cross reactivity between pollen and spores. The results of this study will inform researchers of several environmental monitoring parameters that should be included in risk forecasts for ETSA to allow for a more robust and accurate detection system and help improve public health responses across Australia.

Amyloid plaques, generated during the progression of Alzheimer's disease, cause major neurological deficits due to substantial cell toxicity and death. The underlying cause of plaque generation stems from cleavage of the amyloid precursor protein (APP) by β-secretase (BACE1). A resulting amyloid-β (Aβ) fragment forms aggregates to produce the main constituent of a plaque. Phage display and biopanning techniques were used to identify a 12-mer peptide that had a natural affinity for the BACE1 enzyme. The peptide was translated from phage DNA and synthetically produced. The peptide, at concentrations of 1nM, 10nM and 100nM, was used to confirm binding by direct assay. Non-specific binding to BACE2, renin and cathepsin D was tested by direct binding assay. A BACE1 activity assay was used to determine the peptide effect on cleavage of an APP substrate. Treatment of SY5Y cells with the peptide was used to determine toxicity and prevention of Aβ40 and Aβ42 production. After identification and synthetic production, the peptide exhibited a strong affinity for BACE1 at nanomolar concentrations in the direct assay. In case of non-specific binding to homologous BACE2, renin and cathepsin D, the peptide showed minor binding but was nullified when in solution with BACE1. The peptide addition to a BACE1 activity assay was able to significantly reduce the amount of substrate cleavage. SY5Y cells, when treated with the peptide, did not show any detrimental morphological changes while being able to reduce the production of natural Aβ40 and Aβ42. Even under stressed conditions (H O treatment) where the Aβ production was higher, the peptide was still able to significantly reduce the effect of BACE1 while not effecting cell viability. The identified peptide exhibited strong binding to BACE1 in vitro and was able to reduce production of Aβ, suggesting a favourable BACE1 inhibitor for future refining and characterisation.

Ocular allergy (OA) is a localized subset of allergy characterized by ocular surface itchiness, redness and inflammation. Inflammation and eye-rubbing, due to allergy-associated itch, are common in OA sufferers and may trigger changes to the ocular surface biochemistry. The primary aim of this study is to assess the differences in the human tear proteome between OA sufferers and Healthy Controls (HCs) across peak allergy season and off-peak season in Victoria, Australia. 19 participants (14 OA sufferers, 5 HCs) aged 18-45 were recruited for this study. Participants were grouped based on allergy symptom assessment questionnaire scoring. Proteins were extracted from human tear samples and were run on an Orbitrap Mass Spectrometer. Peaks were matched to a DIA library. Data was analyzed using the software MaxQuant, Perseus and IBM SPSS. 1267 proteins were identified in tear samples of OA sufferers and HCs. 23 proteins were differentially expressed between peak allergy season OA suffers vs HCs, and 21 were differentially expressed in off-peak season. Decreased proteins in OA sufferers related to cell structure regulation, inflammatory regulation and antimicrobial regulation. In both seasons, OA sufferers were shown to have increased expression of proteins relating to inflammation, immune responses and cellular development. Tear protein identification showed dysregulation of proteins involved in inflammation, immunity and cellular structures. Proteins relating to cellular structure may suggest a possible link between OA-associated itch and the subsequent ocular surface damage via eye-rubbing, while inflammatory and immune protein changes highlight potential diagnostic and therapeutic biomarkers of OA.