Biopsychosocial Predictors of Quality of Life in Paediatric Patients With Sickle Cell Disease

Sickle cell disease (SCD) refers to a group of inherited blood disorders with considerable morbidity that causes severe pain, reduces life expectancy, and requires significant self-management. Acute painful episodes are the hallmark of SCD, but persistent daily pain is also highly prevalent in this population. Characterising the impact and experience of SCD-related morbidity (i.e., sleep disruption, frequent emergency department visits, cognitive dysfunction) on health-related quality of life (HRQOL) requires multiple assessment methods to best capture the underlying mechanisms. To gain a greater understanding of the effect of common symptom categories on HRQOL and to determine potential pain coping targets, the present study investigated whether demographic, socioeconomic, sleepiness, pain burden, frequency of emergency department (ED) visits, and cognition predicted HRQOL in a paediatric sample of patients with SCD. Our study was a secondary analysis of baseline assessment data of children with SCD aged 8-15 years (n = 30) in the Prevention of Morbidity in Sickle Cell Anaemia Phase 2b (POMSb2) randomised controlled clinical trial of auto-adjusting continuous positive airways pressure. Patients completed cognitive testing (IQ, Processing Speed Index, Delis-Kaplan Executive Function Scale (DKEFS) Tower, Conner's Continuous Performance Test), sleepiness (Epworth Sleepiness Scale), and HRQOL (PedsQL Sickle Cell Module) at baseline. Patients reported pain burden (Sickle Cell Pain Burden Inventory-Youth) each month over 8 visits. Caregivers provided demographic information and reported their child's executive function (Behavioural Rating Inventory of Executive Function) at baseline. Data from our analysis demonstrated that demographic factors (i.e., age, gender, level of neighbourhood deprivation) and treatment variables (i.e., hydroxyurea use) did not independently predict HRQOL, and laboratory values (i.e., haemoglobin, haematocrit, mean oxygen saturation) were not significantly correlated with HRQOL (ps > 0.05). However, sleepiness, pain burden, ED visits, and executive dysfunction independently predicted HRQOL (R 2 = 0.66) with large effects (η2 = 0.16 to 0.32). These findings identify specific, measurable symptom categories that may serve as targets to improve HRQOL that are responsive to change. This knowledge will be useful for multimodal interventions for paediatric patients with SCD that include sleep management, pain coping strategies, and executive function training

Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial

BACKGROUND: Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA. METHODS: The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3-7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry. DISCUSSION: Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA. TRIAL REGISTRATION: ClinicalTrials.gov NCT04351698 . Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020

Non-escaping frost tolerant QTL linked genetic loci at reproductive stage in six wheat DH populations

Reproductive stage frost poses a major constraint for wheat production in countries such as Australia. However, little progress has been made in identifying key genes to overcome the constraint. In the present study, a severe frost event hit two large-scale field trials consisting of six doubled haploid (DH) wheat populations at reproductive stage (young microspore stage) in Western Australia, leading to the identification of 30 robust frost QTL on 17 chromosomes. The major 18 QTL with the phenotype variation over 9.5% were located on 13 chromosomes including 2A, 2B, 2D, 3A, 4A, 4B, 4D, 5A, 5D, 6D, 7A, 7B and 7D. Most frost QTL were closely linked to the QTL of anthesis, maturity, Zadok stages as well as linked to anthesis related genes. Out of those, six QTL were repetitively detected on the homologous regions on 2B, 4B, 4D, 5A, 5D, 7A in more than two populations. Results showed that the frost damage is associated with alleles of Vrn-A1a, Vrn-D1a, Rht-B1b, Rht-D1b, and the high copy number of Ppd-B1. However, anthesis QTL and anthesis related genes of Vrn-B1a and TaFT3-1B on chromosomes 5B and 1B did not lead to frost damage, indicating that these early-flowering phenotype related genes are compatible with frost tolerance and thus can be utilised in breeding. Our results also indicate that wild-type alleles Rht-B1a and Rht-D1a can be used when breeding for frost-tolerant varieties without delaying flowering time

Physiological models of body composition and human obesity

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Synthesis of ZnO nanoparticles by flame spray pyrolysis and characterisation protocol

There is uncertainty concerning the potential toxicity of zinc oxide (ZnO) nanoparticles, which may be attributed in part to a lack of understanding with regard to the physiochemical properties of the nanoparticles used in toxicological investigations. This paper reports the synthesis of a ZnO nanopowder by flame spray pyrolysis and demonstrates that the typically employed characterisation techniques such as specific surface area measurement and X-ray diffraction provide insufficient information on the sample, especially if it is intended for use in toxicity studies. Instead, a more elaborate characterisation protocol is proposed that includes particle morphology as well as detailed compositional analysis of the nanoparticle surface. Detailed transmission electron microscopy analysis illustrated the polydispersity within the sample: particles were elongated in the c-crystallographic direction, with average Ferret length ∼23 nm and Ferret width ∼14 nm. Dynamic light scattering (0.1 w/v% in deionised water, pH 7.4) revealed the particles were agglomerated with a modal secondary particle size of ∼1.5 μm. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy indicated the presence of carbonate and hydroxide impurities on the surface of the ZnO nanoparticles and an increase of such impurities was observed as the sample was aged, which might influence the nanoparticle dissolution and/or cellular uptake behaviour. These data will be utilised, in order to facilitate the interpretation and understanding of results from toxicological investigations using in vitro cell lines

Auto-adjusting positive airway pressure in children with sickle cell anemia: results of a phase I randomized controlled trial

Low nocturnal oxygen saturation (SpO2) is implicated in complications of Sickle Cell Anemia (SCA). Twenty-four children with SCA were randomized to receive overnight auto-adjusting continuous positive airway pressure (auto-CPAP) with supplemental oxygen, if required, to maintain SpO2 94% or as controls. We assessed adherence, safety, sleep parameters, cognition and pain. Twelve participants randomized to auto-CPAP (3 with oxygen) showed improvement in Apnea/Hypopnea Index (p<0.001), average desaturation events >3%/hour (p=0.02), mean nocturnal SpO2 (p=0.02) and cognition. Primary efficacy endpoint (Processing Speed Index) showed no group differences (p=0.67), but a second measure of processing speed and attention (Cancellation) improved in those receiving treatment (p=0.01). No bone marrow suppression, rebound pain or serious adverse event resulting from auto-CPAP use was observed. Six weeks of auto-CPAP therapy is feasible and safe in children with SCA, significantly improving sleep-related breathing disorders and at least one aspect of cognition