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Research

The unmet clinical needs of children with developmental coordination disorder

The aim of this study was to understand the challenges experienced by families obtaining a diagnosis and therapy for developmental coordination disorder (DCD). Parents of 435 children aged 4-18 years with persistent motor difficulties consistent with a diagnosis of DCD completed an online survey. Diagnostic timeline and diagnostic label/s received were examined, along with therapies accessed.

Research

Converting the maybes: Crucial for a successful COVID-19 vaccination strategy

Broad community acceptance of a COVID-19 vaccination will be critical for effectively halting the spread of the virus. In this study, we focus on factors that differentiate those who are undecided from those who are either willing or unwilling to accept a prospective COVID-19 vaccine. An online survey in May 2020 assessed Australian adults' willingness to receive a COVID-19 vaccine (yes, maybe, no). A multinomial logistical regression of responses (N = 1,313) was used to identify correlates of vaccine willingness between the three groups.

Research

Maternal prenatal stress exposure and sex-specific risk of severe infection in offspring

Maternal stressful life events during pregnancy have been associated with immune dysregulation and increased risk for asthma and atopy in offspring. Few studies have investigated whether prenatal stress is associated with increased overall or specific infectious diseases in childhood, nor explored sex differences. We sought to examine the relationship between the nature and timing of maternal stress in pregnancy and hospitalisation with infection in offspring.

Research

The Role of Cannabinoids as Anticancer Agents in Pediatric Oncology

Cannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant Cannabis sativa L. Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects, including memory, pain, reproduction, bone remodeling or immunity, to name a few. Unsurprisingly, given these broad physiological effects, alterations of the ECS have been found in different diseases, including cancer.

Research

Time spent outdoors through childhood and adolescence - assessed by 25-hydroxyvitamin D concentration - and risk of myopia at 20 years

To investigate the relationship between time spent outdoors, at particular ages in childhood and adolescence, and myopia status in young adulthood using serum 25-hydroxyvitamin D [25(OH)D] concentration as a biomarker of time spent outdoors. Participants of the Raine Study Generation 2 cohort had 25(OH)D concentrations measured at the 6-, 14-, 17- and 20-year follow-ups. Participants underwent cycloplegic autorefraction at age 20 years, and myopia was defined as a mean spherical equivalent -0.50 dioptres or more myopic. Logistic regression was used to analyse the association between risk of myopia at age 20 years and age-specific 25(OH)D concentrations. Linear mixed-effects models were used to analyse trajectory of 25(OH)D concentrations from 6 to 20 years.

Research

Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts.

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Biogeography of the Relationship between the Child Gut Microbiome and Innate Immune System

The gut microbiome is a well-recognized modulator of host immunity, and its compositions differ between geographically separated human populations. Systemic innate immune responses to microbial derivatives also differ between geographically distinct human populations. However, the potential role of the microbiome in mediating geographically varied immune responses is unexplored. We here applied 16S amplicon sequencing to profile the stool microbiome and, in parallel, measured whole-blood innate immune cytokine responses to several pattern recognition receptor (PRR) agonists among 2-year-old children across biogeographically diverse settings. Microbiomes differed mainly between high- and low-resource environments and were not strongly associated with other demographic factors. We found strong correlations between responses to Toll-like receptor 2 (TLR2) and relative abundances of Bacteroides and Prevotella populations, shared among Canadian and Ecuadorean children.

Research

ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma

COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC.

Research

Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour Immunosuppression

Immunotherapy has revolutionised the treatment of cancers by harnessing the power of the immune system to eradicate malignant tissue. However, it is well recognised that some cancers are highly resistant to these therapies, which is in part attributed to the immunosuppressive landscape of the tumour microenvironment (TME). The contexture of the TME is highly heterogeneous and contains a complex architecture of immune, stromal, vascular and tumour cells in addition to acellular components such as the extracellular matrix. While understanding the dynamics of the TME has been instrumental in predicting durable responses to immunotherapy and developing new treatment strategies, recent evidence challenges the fundamental paradigms of how tumours can effectively subvert immunosurveillance. Here, we discuss the various immunosuppressive features of the TME and how fine-tuning these mechanisms, rather than ablating them completely, may result in a more comprehensive and balanced anti-tumour response.

Research

Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).