Publications by authors named "David Broderick"

Objective: Influenza reemerged after a 2020-2021 hiatus in 2022, but understanding the resurgence needs pre-COVID era surveillance. We compared age- and ethnicity-specific incidence of severe acute respiratory infection (SARI) from a hospital network in Auckland, New Zealand, in 2022 against a baseline, 2012-2019.

Methods: Annual and monthly influenza SARI incidence per 1000 persons by age and ethnic group between 2012 and 2022 was calculated using resident population as the denominator.

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Background: Forecasting models predicting trends in hospitalization rates have the potential to inform hospital management during seasonal epidemics of respiratory diseases and the associated surges caused by acute hospital admissions. Hospital bed requirements for elective surgery could be better planned if it were possible to foresee upcoming peaks in severe respiratory illness admissions. Forecasting models can also guide the use of intervention strategies to decrease the spread of respiratory pathogens and thus prevent local health system overload.

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The aim of this study was to investigate both the microbial composition and absolute abundance of clinically relevant bacteria in tissue specimens from patients with chronic suppurative otitis media with cholesteatoma (CSOM with cholesteatoma). Mastoid mucosa and cholesteatoma tissue from eleven subjects with CSOM with cholesteatoma, and mastoid mucosa from ten controls were examined using standard hospital culture swabs, Gram staining, bacterial 16S rRNA gene sequencing, Droplet Digital PCR (ddPCR), and multiplex PCR. Positive results from culture swabs were reported in half the CSOM with cholesteatoma samples and 1 control sample.

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Novel topical therapeutics require extensive pre-clinical testing to assess efficacy and safety. Antibiofilm or immunosuppressant agents can utilize ex vivo models to measure ciliotoxicity. Agents that are found to be effective and non-toxic ex vivo warrant further investigation in vivo.

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Background: Changes in the epidemiology of illnesses caused by respiratory syncytial virus (RSV) infection following the COVID-19 pandemic are reported. The New Zealand (NZ) COVID-19 situation was unique; RSV community transmission was eliminated with the 2020 border closure, with a rapid and large increase in hospitalizations following the relaxation of social isolation measures and the opening of an exclusive border with Australia.

Methods: This active population-based surveillance compared the age-specific incidence and seasonality of RSV-associated hospitalizations in Auckland, NZ, for 2 years before and after the 2020 border closures.

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The discovery of bacterial microcolonies in tonsillar tissue of patients with tonsillar hyperplasia has raised the question of their role in provoking the local immune response. Tonsils collected from patients undergoing tonsillectomy were stained for three clinically relevant bacterial taxa and lymphocytes. The bacterial composition and abundance of microcolonies was investigated using a combination of laser-microdissection, amplicon sequencing and Droplet Digital polymerase chain reaction.

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In microbiome fields of study, meta-analyses have proven to be a valuable tool for identifying the technical drivers of variation among studies and results of investigations in several diseases, such as those of the gut and sinuses. Meta-analyses also represent a powerful and efficient approach to leverage existing scientific data to both reaffirm existing findings and generate new hypotheses within the field. However, there are currently limited data in other fields, such as the paediatric respiratory tract, where extension of original data becomes even more critical due to samples often being difficult to obtain and process for a range of both technical and ethical reasons.

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Cultivation-independent (molecular) analysis of the oral microbiota can provide a comprehensive picture of microbial community composition, yet there is an at-times bewildering array of approaches that can be employed. This chapter introduces some of the key considerations when undertaking microbiota research and describes two alternative bioinformatic pipelines for conducting such studies. The descriptions are based on analysis of bacterial 16S ribosomal RNA gene sequences, but can be easily adapted for analysis of other microbial taxa such as fungi.

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Background: Low-energy diets (LEDs) comprise commercially formulated food products that provide between 800 and 1200 kcal/day (3.3-5 MJ/day) to aid body weight loss. Recent small-scale studies suggest that LEDs are associated with marked changes in the gut microbiota that may modify the effect of the LED on host metabolism and weight loss.

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Introduction: Non-cystic fibrosis bronchiectasis is a respiratory health condition with many possible aetiologies, some of which are potentially reversible in childhood with early diagnosis and appropriate treatment. It is important to understand factors which contribute to progression or potential resolution of bronchiectasis. It is evident that respiratory exacerbations are a key feature of bronchiectasis disease progression.

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The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.

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Introduction: Despite the rich history and progression of mental health assets and their utilization within the Marine Corps, the implementation of these assets has been varied and inconsistent. This article strives to take the lessons learned from the past and improve on them. The goal is to develop a consistent program focused on resiliency and retention, and propose an integrated organized structure across all the Marine Expeditionary Forces (MEF).

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We report on the molecular interactions of the farnesoid X receptor (FXR) with prenylflavonoids, an emerging class of FXR modulators. FXR is an attractive therapeutic target for mitigating metabolic syndromes (MetS) because FXR activates the inhibitory nuclear receptor, small heterodimer partner (SHP), thereby inhibiting both gluconeogenesis and de novo lipogenesis. We and others have shown that xanthohumol (XN), the principal prenylflavonoid of the hop plant (Humulus lupulus L.

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Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of transcription factors that plays a key role in the regulation of bile acids, lipid and glucose metabolisms. The regulative function of FXR is governed by conformational changes of the ligand binding domain (LBD) upon ligand binding. Although FXR is a highly researched potential therapeutic target, only a limited number of FXR-agonist complexes have been successfully crystallized and subsequently yielded high resolution structures.

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The retinoid X receptor (RXR) is a ligand-activated transcription factor that plays an important role in growth and development and the maintenance of cellular homeostasis. A thermodynamic ultraviolet circular dichroism, tryptophan fluorescence and ligand binding activity with guanidine as a chemical denaturant are consistent with a two step mechanism. The dimeric LBD equilibrates with a monomeric intermediate (DeltaG(0)(H(2)O) equal to 8.

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Retinoid X receptors (RXRs) function as ligand-activated transcription factors and are obligatory components of a large number of nuclear receptor heterodimers. RXRs help regulate diverse physiological responses including the cancer prevention responses of cell proliferation, inflammation, cell differentiation, and apoptosis. Since RXRs represent important targets for cancer chemoprevention, an ultrafiltration mass spectrometry-based assay was developed to facilitate the discovery of potential chemoprevention agents that bind to human RXRalpha.

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Several different agonists of the retinoic X receptor alpha (hRXRalpha) were examined for their effects on the amide H/D exchange kinetics of the homodimeric protein using mass spectrometry. Some agonists, LG 100268, SR11246, and DHA, bind such that slower deuterium exchange-in occurs compared with 9-cis-retinoic acid (9-cis-RA), whereas others, fenretinide and methoprenic acid, result in poorer protection during binding and hence faster exchange-in. Protection against H/D exchange by different agonists and the inhibition of H/D exchange kinetics relative to 9-cis-RA varies markedly in different regions of the protein.

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Receptors for retinoic acid act as ligand activated transcription factors. The three-dimensional structure of the retinoid X receptor (RXR) ligand binding domain has been determined, but little information is available concerning the properties of the protein in solution. Hydrogen/deuterium exchange followed by electrospray ionization mass spectrometry was used to probe the solution conformation of the recombinant human RXRalpha homodimer ligand binding domain in the presence and absence of 9-cis-retinoic acid (9-cis-RA).

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