372 results match your criteria: "and Murdoch Children's Research Institute[Affiliation]"

Perioperative Management of Patients with Preeclampsia: A Comprehensive Review.

Anesthesiology

February 2025

Division of Obstetric Anesthesiology, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Preeclampsia is a common condition of pregnancy characterized by hypertension complicated by cerebral, cardiac, hepatic, renal, hematologic, and placental dysfunction. Patients with preeclampsia frequently undergo cesarean delivery, the most common major surgical procedure in the world. They represent a high-risk perioperative cohort suffering significant preventable morbidity and mortality.

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Background: A MenABCWY vaccine containing 4CMenB and MenACWY-CRM vaccine components has been developed to protect against the five meningococcal serogroups that cause most invasive disease cases.

Methods: In this phase 3 study (NCT04707391), healthy participants aged 15-25 years, who had received MenACWY vaccination ≥4 years previously, were randomized (1:1) to receive two MenABCWY doses six months apart or one MenACWY-CRM dose. Primary objectives were to demonstrate the non-inferiority of MenABCWY 1 month post-vaccination versus MenACWY-CRM, with a lower limit of 2-sided 95% confidence interval above -10% for group differences in 4-fold rise in human serum bactericidal antibody (hSBA) titers against serogroups ACWY, and to evaluate reactogenicity and safety.

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Global burden of tuberculous meningitis in children aged 0-14 years in 2019: a mathematical modelling study.

Lancet Glob Health

January 2025

Sheffield Centre for Health and Related Research, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.

Background: Tuberculous meningitis is fatal if untreated and can lead to lifelong neurological sequelae. However, to our knowledge, there are no data on the number of children affected by this disease. We aimed to estimate the global disease burden and attributable mortality of childhood tuberculous meningitis by WHO regions, age groups, treatment status, and HIV status in 2019.

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A substantial proportion of people with tuberculosis (TB)-one of the world's deadliest infectious diseases-live in resource-poor, food insecure settings. It is widely recognised that undernutrition significantly heightens vulnerability to TB, as well as contributes to poor treatment adherence and outcomes. However, more attention is needed to understand what shapes food insecurity and undernutrition in a particular setting.

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Article Synopsis
  • The study evaluates a new meningococcal vaccine (MenABCWY) that combines components of the existing MenB vaccine (4CMenB) and the MenACWY vaccine, aiming to provide broad immunization against various meningococcal strains and ease vaccination schedules.
  • Conducted as a phase 3 randomized trial across multiple countries, healthy participants aged 10-25 were assigned to receive different vaccine schedules to assess safety, immune response, and consistency of vaccine lots.
  • The trial primarily focused on the immune response to MenB strains, comparing MenABCWY's effectiveness to 4CMenB and evaluating the consistency of immune responses among different production lots of the vaccines.
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Article Synopsis
  • Meningococcal serogroup B (MenB) vaccination with the 4CMenB vaccine was tested for its effectiveness and safety among 3,651 healthy participants aged 10 to 25, using different dosing schedules (0-2, 0-6, and 0-2-6 months).
  • The study measured the immune response through two methods: a test-based approach showing high immune breadth (over 78%) and a responder-based approach indicating a significant percentage of participants achieved strong responses (up to 93.4% for the 0-2-6 schedule).
  • The results showed no major differences in effectiveness across the dosing schedules, confirming that the simpler 2-dose regimen (0-2)
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Impaired Muscle Parameters in Individuals With Premature Ovarian Insufficiency: A Pilot Study.

J Endocr Soc

October 2024

Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.

Context: Although bone loss is a recognized consequence of premature ovarian insufficiency (POI), the impact on skeletal muscle health is less well-defined.

Objective: To compare muscle mass and function parameters between women with POI and controls.

Methods: Cross-sectional study from a tertiary health network and community between 2017 and 2023.

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Mitochondrial DNA (mtDNA) has been widely used in genetics research for decades. Contamination from nuclear DNA of mitochondrial origin (NUMTs) can confound studies of phylogenetic relationships and mtDNA heteroplasmy. Homology searches with mtDNA are widely used to detect NUMTs in the nuclear genome.

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Globally, more than 1.2 billion inhalers are purchased for asthma and chronic obstructive pulmonary disease (COPD) annually. In Australia and New Zealand, pressurized metered dose inhalers (pMDIs) are the leading delivery device prescribed and pMDI salbutamol can be purchased over the counter in Australia.

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Combined education and counselling can contribute to person-centred care for tuberculosis (TB), improving uptake, adherence, and outcomes of treatment for TB disease and TB infection. Though strongly recommended by the World Health Organization for all people diagnosed with TB, education and counselling is not widely implemented in TB programs around the world. In 2016, a pilot TB education and counselling program, delivered by trained professionals and peers, was initiated to support people on TB treatment in the South Fly District of Papua New Guinea.

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Given the increased prevalence of mental health problems during adolescence, there is considerable interest in understanding potential biological mechanisms including the contribution of pubertal hormones. This systematic review of 55 papers aimed to synthesize the evidence for the effect of pubertal hormones on the risk for mental health problems in children and adolescents. The pattern of findings from included studies suggested associations of testosterone and estradiol with certain types of mental health problems, but with inconsistencies relating to DHEA and DHEA-S.

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Article Synopsis
  • Pain is a significant issue for individuals with epidermolysis bullosa (EB), impacting their quality of life and identified as a priority for improved treatments.
  • The Prospective EB Longitudinal Evaluation Study (PEBLES) gathered data over eight years from 61 participants to evaluate pain characteristics and treatments in different RDEB subtypes.
  • Results showed that 93% of participants experienced pain, with a median background pain score of 40 and procedural pain score of 52; many did not use medication for pain management despite its severity.
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Early mortality in STXBP1-related disorders.

Neurol Sci

October 2024

Department of Epilepsy Genetics and Personalized Treatment, Danish Epilepsy Center, Member of the European Reference Network EpiCARE, University of Southern Denmark, Dianalund, Denmark.

Article Synopsis
  • Pathogenic variants in the STXBP1 gene are linked to developmental and epileptic encephalopathy (DEE), often resulting in drug-resistant epilepsy and increased mortality risk, primarily from sudden unexpected death in epilepsy (SUDEP).
  • A study analyzed data from 40 individuals with STXBP1 variants who died, revealing a mortality rate of 3.2% and median age of death at 13 years; the leading causes were SUDEP (36%) and respiratory complications (33%).
  • Findings highlight the importance of understanding mortality risks in STXBP1-related disorders, aiding in prognostic evaluations, genetic counseling, and the development of preventative strategies for affected families.
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Somatic instability of the FGF14-SCA27B GAA•TTC repeat reveals a marked expansion bias in the cerebellum.

Brain

October 2024

Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC H3A 2B4, Canada.

Article Synopsis
  • Spinocerebellar ataxia 27B (SCA27B) is a disease that affects balance and coordination, caused by a genetic change in a specific part of a gene called FGF14.
  • Research shows that most brain damage from this disease happens mainly in the cerebellum, which controls movement.
  • In a study of blood samples and brain tissue, scientists found that the genetic change was mostly stable over time, but it exhibited more growth in the cerebellum than in other brain areas, helping to explain why SCA27B mainly affects that part of the brain.
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Purpose: Pathways and Resources for Engagement and Participation (PREP) is an intervention to optimise individuals' participation by building problem-solving capacity and addressing environmental barriers. We investigated the feasibility of implementing PREP with young adults (18-30 years) with complex disability in Australia.

Materials And Methods: Explanatory sequential mixed methods study in three stages.

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This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 μg (Tdap-1018 1500 μg) or 3000 μg (Tdap-1018 3000 μg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 μg, Tdap-1018 3000 μg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination.

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Inflation of polygenic risk scores caused by sample overlap and relatedness: Examples of a major risk of bias.

Am J Hum Genet

September 2024

Population Health and Immunity Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia. Electronic address:

Polygenic risk scores (PRSs) are an important tool for understanding the role of common genetic variants in human disease. Standard best practices recommend that PRSs be analyzed in cohorts that are independent of the genome-wide association study (GWAS) used to derive the scores without sample overlap or relatedness between the two cohorts. However, identifying sample overlap and relatedness can be challenging in an era of GWASs performed by large biobanks and international research consortia.

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Motivation: Nanopore sequencing current signal data can be 'basecalled' into sequence information or analysed directly, with the capacity to identify diverse molecular features, such as DNA/RNA base modifications and secondary structures. However, raw signal data is large and complex, and there is a need for improved visualization strategies to facilitate signal analysis, exploration and tool development.

Results: Squigualiser (Squiggle visualiser) is a toolkit for intuitive, interactive visualization of sequence-aligned signal data, which currently supports both DNA and RNA sequencing data from Oxford Nanopore Technologies instruments.

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Patient, Parental, and Health Professional Perspectives on Growth in Children With CKD.

Am J Kidney Dis

January 2025

Sydney School of Public Health, University of Sydney, Sydney, Australia; Centre for Kidney Research, Children's Hospital at Westmead, Sydney, Australia.

Rationale & Objective: Growth failure is a common problem among children with chronic kidney disease (CKD). Reduced height is associated with psychosocial burden, social stigma, and impaired quality of life. This study describes the aspects of growth impairment that are most impactful from the perspectives of children with CKD, their parents, and health professionals.

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Article Synopsis
  • Sequence-based genetic testing finds causative variants in about 50% of cases of developmental and epileptic encephalopathies (DEEs), but DNA methylation changes in these cases have not been thoroughly explored.
  • This study analyzed genome-wide DNA methylation in blood samples from 582 individuals with unresolved DEEs, identifying rare methylation patterns and potential genetic causes in 12 of these cases.
  • The research highlights the effectiveness of DNA methylation analysis in diagnosing DEEs, showing a 2% diagnostic yield, and provides insights into the CHD2 gene's pathophysiology using advanced sequencing methods.
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Article Synopsis
  • Oculopharyngodistal myopathy (OPDM) is a genetic muscle disease that causes drooping eyelids, trouble swallowing, and weakness in the arms and legs.
  • Recent research found repeating sequences in a gene called ABCD3 in people with OPDM from European backgrounds, while similar repeats were only discovered in certain Asian groups before.
  • These long repeats in the ABCD3 gene might play a role in the muscle problems seen in OPDM, suggesting a link between these repeats and the weakness that affects patients.
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Background: In children with severe acute malnutrition (SAM) tuberculosis is common, challenging to diagnose, and often fatal. We developed tuberculosis treatment decision algorithms (TDAs) for children under the age of 5 years with SAM.

Methods: In this prospective diagnostic study, we enrolled and followed up children aged <60 months hospitalised with SAM at three tertiary hospitals in Zambia and Uganda from 4 November 2019 to 20 June 2022.

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The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents.

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