Functional assessment of IDUA variants of uncertain significance identified by newborn screening.

With the expansion of newborn screening efforts for MPS disorders, the number of identified variants of uncertain significance in IDUA continues to increase. To better define functional consequences of identified IDUA variants, we developed a HEK293-based expression platform that can be used to determine the relative specific activity of variant α-iduronidases by combining a fluorescence-based activity assay and semi-quantitative western blotting. We employed the current platform to characterize over thirty different IDUA variants, including known benign and pathogenic variants, as well as multiple variants of uncertain significance identified through newborn screening.

Spatial and temporal transmission dynamics of respiratory syncytial virus in New Zealand before and after the COVID-19 pandemic.

Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns.

Tube voltage in chest and abdomen DR imaging: Which settings return maximal non-prewhitening model observer with eye filter (NPWE) detectability?

Background: The non-prewhitening computational model observer with eye filter (NPWE) has been shown to reasonably predict human observer performance in general radiography and is an appropriate substitute when real clinical trials are not feasible. In this study, the NPWE model observer is used to detect specific tasks (circular designer nodules) ranging between 1 and 30 mm in diameter using chest and abdomen phantom images acquired across the diagnostic energy range (60-125 kVp) with and without an anti-scatter grid.

Purpose: The aim of this study was to derive tube voltage (kVp) settings that return maximal NPWE detectability (d') of designer nodules, for digital radiography (DR) chest and abdomen imaging.

An integrated multi-omics approach allowed ultra-rapid diagnosis of a deep intronic pathogenic variant in PDHX and precision treatment in a neonate critically ill with lactic acidosis.

The diagnosis of mitochondrial disorders is complex. Rapid whole genome sequencing is a first line test for critically ill neonates and infants allowing rapid diagnosis and treatment. Standard genomic technology and bioinformatic pipelines still have an incomplete diagnostic yield requiring complementary approaches.

Change in Age profile of Respiratory Syncytial Virus disease over the course of annual epidemics: a multi-national study.

Objectives: We aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics.

Methods: We used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into "epidemic quarters", i.

Mindfulness Teacher Trainees' Experiences (MTTE): An investigation of intense experiences in mindfulness-based interventions.

With the increasing interest in mindfulness practices within clinical as well as non-clinical settings and the increasing body of research on the positive effects of mindfulness, concerns have been raised that mindfulness might also produce adverse effects including intense experiences and psychosis. The aim of this study was to investigate if intense experiences occur as a natural part of mindfulness practice, and if so to examine the characteristics of such experiences. We conducted a qualitative analysis based on fortnightly meditation reports from 13 mindfulness teacher trainees for 4 months.

How Surgeons Think to Avoid Error: A Case Study of the Neurovascular Bundle Sparing During a Robotic Prostatectomy.

Objective: To illustrate how experts efficiently navigate a "slowing down moment" to obtain optimal surgical outcomes using the neurovascular bundle sparing during a robotic prostatectomy as a case study.

Design: A series of semistructured interviews with four expert uro-oncologists were completed using a cognitive task analysis methodology. Cognitive task analysis, CTA, refers to the interview and extraction of a general body of knowledge.

Impact of the COVID-19 related border restrictions on influenza and other common respiratory viral infections in New Zealand.

Background: New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID-19 elimination measures, provided a rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years.

Methods: We collected the data from multiple surveillance systems, including hospital-based severe acute respiratory infection surveillance, SHIVERS-II, -III and -IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza-like illness surveillance and SHIVERS-V sentinel GP-based ARI surveillance, SHIVERS-V traveller ARI surveillance and laboratory-based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions.

A comparison of physical image quality of two hologic digital mammography systems that utilise linear and 2D anti-scatter grids.

. Full-field digital mammography (FFDM) systems manufactured by Hologic that utilise either a 2D or linear anti-scatter grid have recently been installed in our clinic. The manufacturer advise that for matched dose, both grids deliver comparable image quality.

Triamterene Functions as an Effective Nonsense Suppression Agent for MPS I-H (Hurler Syndrome).

Mucopolysaccharidosis I-Hurler (MPS I-H) is caused by the loss of α-L-iduronidase, a lysosomal enzyme that degrades glycosaminoglycans. Current therapies cannot treat many MPS I-H manifestations. In this study, triamterene, an FDA-approved, antihypertensive diuretic, was found to suppress translation termination at a nonsense mutation associated with MPS I-H.

Functional assessment of homozygous ALDH18A1 variants reveals alterations in amino acid and antioxidant metabolism.

Mono- and bi-allelic variants in ALDH18A1 cause a spectrum of human disorders associated with cutaneous and neurological findings that overlap with both cutis laxa and spastic paraplegia. ALDH18A1 encodes the bifunctional enzyme pyrroline-5-carboxylate synthetase (P5CS) that plays a role in the de novo biosynthesis of proline and ornithine. Here we characterize a previously unreported homozygous ALDH18A1 variant (p.

"I see beauty, I see art, I see design, I see love." Findings from a resident-driven, co-designed gardening program in a long-term care facility.

Background: Engagement with the natural environment is a meaningful activity for many people. People living in long-term care facilities can face barriers to going outdoors and engaging in nature-based activities. In response to needs expressed by our long-term care facility resident partners, we examined the feasibility and benefits of a co-designed hydroponic and raised-bed gardening program.

RNA analysis of the GALNS transcript reveals novel pathogenic mechanisms associated with Morquio syndrome A.

Morquio syndrome A (Mucopolysaccharidosis IVA, MPS IVA) is an autosomal recessive lysosomal storage disorder caused by deficiency of -acetyl-galactosamine-6-sulfatase (GALNS) which catabolizes the glycosaminoglycans (GAG), keratan sulfate and chondroitin-6-sulfate. Homozygous or compound heterozygous pathogenic variants in the result in the deficiency of the enzyme and consequent GAG accumulations. DNA sequence and copy number analysis of the coding region fails to identify biallelic causative pathogenic variants in up to 15% of patients with Morquio syndrome A.

Clinical outcomes of campylobacteriosis: a case series analysis of hospitalisations associated with the Havelock North Campylobacter outbreak.

Aim: In August 2016, a large waterborne campylobacteriosis outbreak occurred in Havelock North, New Zealand. This analysis describes the clinical complications of cases admitted to hospital as a result of acute infection, identifies risk factors for hospitalisation and compares deaths between hospitalised and non-hospitalised cases. Hospital admissions with post-infectious sequelae were excluded as they are the subject of a separate analysis.

Reactive arthritis incidence in a community cohort following a large waterborne campylobacteriosis outbreak in Havelock North, New Zealand.

Objectives: In August 2016, Campylobacter spp contaminated an untreated reticulated water supply resulting in a large-scale gastroenteritis outbreak affecting an estimated 8320 people. We aimed to determine the incidence of probable reactive arthritis (ReA) cases in individuals with culture-confirmed campylobacteriosis (CC), self-reported probable campylobacteriosis (PC) and those reporting no diarrhoea (ND).

Design: We conducted a retrospective cohort study to identify incidence of probable ReA cases.

Measurement of lysosomal enzyme activities: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Assays that measure lysosomal enzyme activity are important tools for the screening and diagnosis of lysosomal storage disorders (LSDs). They are often ordered in combination with urine oligosaccharide and glycosaminoglycan analysis, additional biomarker assays, and/or DNA sequencing when an LSD is suspected. Enzyme testing in whole blood/leukocytes, serum/plasma, cultured fibroblasts, or dried blood spots demonstrating deficient enzyme activity remains a key component of LSD diagnosis and is often prompted by characteristic clinical findings, abnormal newborn screening, abnormal biochemical findings (eg, elevated glycosaminoglycans), or molecular results indicating pathogenic variants or variants of uncertain significance in a gene associated with an LSD.

Hematopoietic cell transplantation for sialidosis type I.

We report the clinical and laboratory follow-up data of an adolescent female with Type I Sialidosis who underwent bone marrow transplant (BMT). After BMT, plasma and urine biomarkers responded concurrently with engraftment. Neuropsychiatry data showed preservation in some domains, but she did have overall decline in motor performance.

Conservation of vaccine antigen sequences encoded by sequenced strains of Streptococcus equi subsp. equi.

Background: Streptococcus equi subspecies equi (S equi) is the cause of Strangles, one of the most prevalent diseases of horses worldwide. Variation within the immunodominant SeM protein has been documented, but a new eight-component fusion protein vaccine, Strangvac, does not contain live S equi or SeM and conservation of the antigens it contains have not been reported.

Objective: To define the diversity of the eight Strangvac antigens across a diverse S equi population.

3-Methylglutaconic aciduria in carriers of primary carnitine deficiency.

The etiology of secondary 3-methylglutaconic aciduria (3-MGA-uria) is not well understood although is thought to be a marker of mitochondrial dysfunction. For this reason, suspicion for a secondary 3-MGA-uria often leads to an extensive clinical and laboratory work-up for mitochondrial disease, although in many cases evidence for mitochondrial dysfunction is never found. 3-methylglutaconic aciduria in healthy individuals without known metabolic disease has not been well described.

Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants.

Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. We collected, analyzed, and uniformly summarized all published GALNS gene variants, thus updating the previous mutation review (published in 2014). In addition, new variants were communicated by seven reference laboratories in Europe, the Middle East, Latin America, Asia, and the United States.

The Global Epidemiology of RSV in Community and Hospitalized Care: Findings From 15 Countries.

Background: Respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infections. To optimize control strategies, a better understanding of the global epidemiology of RSV is critical. To this end, we initiated the Global Epidemiology of RSV in Hospitalized and Community care study (GERi).

Defining the seasonality of respiratory syncytial virus around the world: National and subnational surveillance data from 12 countries.

Background: Respiratory syncytial virus (RSV) infections are one of the leading causes of lower respiratory tract infections and have a major burden on society. For prevention and control to be deployed effectively, an improved understanding of the seasonality of RSV is necessary.

Objectives: The main objective of this study was to contribute to a better understanding of RSV seasonality by examining the GERi multi-country surveillance dataset.