COVID-19 in New South Wales children during 2021: severity and clinical spectrum.

OBJECTIVES: To describe the severity and clinical spectrum of coronavirus disease 2019 (COVID-19) in children during the 2021 New South Wales outbreak of the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN, SETTING: Prospective cohort study in three metropolitan Sydney local health districts, 1 June - 31 October 2021. PARTICIPANTS: Children under 16 years of age with positive SARS-CoV-2 nucleic acid test results admitted to hospital or managed by the Sydney Children's Hospital Network (SCHN) virtual care team. MAIN OUTCOME MEASURES: Age-specific SARS-CoV-2 infection frequency, overall and separately for SCHN virtual and hospital patients; rates of medical and social reason admissions, intensive care admissions, and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 per 100 SARS-CoV-2 infections; demographic and clinical factors that influenced likelihood of hospital admission. RESULTS: A total of 17 474 SARS-CoV-2 infections in children under 16 were recorded in NSW, of whom 11 985 (68.6%) received SCHN-coordinated care, including 459 admitted to SCHN hospitals: 165 for medical reasons (1.38 [95% CI, 1.17-1.59] per 100 infections), including 15 admitted to intensive care, and 294 (under 18 years of age) for social reasons (2.45 [95% CI, 2.18-2.73] per 100 infections). In an analysis that included all children admitted to hospital and a random sample of those managed by the virtual team, having another medical condition (adjusted odds ratio [aOR], 7.42; 95% CI, 3.08-19.3) was associated with increased likelihood of medical admission; in univariate analyses, non-asthmatic chronic respiratory disease was associated with greater (OR, 9.21; 95% CI, 1.61-174) and asthma/viral induced wheeze with lower likelihood of admission (OR, 0.38; 95% CI, 0.18-0.78). The likelihood of admission for medical reasons declined from infancy to 5-11 years, but rose again for those aged 12-15 years. Sex and Indigenous status did not influence the likelihood of admission. CONCLUSION: Most SARS-CoV-2 infections (Delta variant) in children were asymptomatic or associated with mild disease. Hospitalisation was relatively infrequent, and most common for infants, adolescents, and children with other medical conditions. More children were hospitalised for social than for medical reasons.

Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability.

Medical research is developing an ever greater need for comprehensive high-quality data generation to realize the promises of personalized health care based on molecular biomarkers. The nucleic acid proximity-based methods proximity ligation and proximity extension assays have, with their dual reporters, shown potential to relieve the shortcomings of antibodies and their inherent cross-reactivity in multiplex protein quantification applications. The aim of the present study was to develop a robust 96-plex immunoassay based on the proximity extension assay (PEA) for improved high throughput detection of protein biomarkers. This was enabled by: (1) a modified design leading to a reduced number of pipetting steps compared to the existing PEA protocol, as well as improved intra-assay precision; (2) a new enzymatic system that uses a hyper-thermostabile enzyme, Pwo, for uniting the two probes allowing for room temperature addition of all reagents and improved the sensitivity; (3) introduction of an inter-plate control and a new normalization procedure leading to improved inter-assay precision (reproducibility). The multiplex proximity extension assay was found to perform well in complex samples, such as serum and plasma, and also in xenografted mice and resuspended dried blood spots, consuming only 1 µL sample per test. All-in-all, the development of the current multiplex technique is a step toward robust high throughput protein marker discovery and research.

The role of parental control and modelling in predicting a child's diet and relationship with food after they leave home. A prospective study.

Research indicates that parental control and parental modelling are key factors in shaping a child's eating behaviour. To date, however, little is known about how these factors influence a child's diet once they have left home. This prospective study evaluated the extent to which a parent's own behaviour and their use of control over food whilst their child was still living at home predicted their child's relationship with food once they had begun to live independently. Parent/child dyads (n=93) took part in the study. Parents completed baseline measures of parental control practices (overt control, covert control and pressure to eat), their own diet (unhealthy snacks, unhealthy meals, healthy foods) and eating behaviours (emotional, uncontrolled and restrained eating). At one year follow up, once their child had left home, the child completed measures of their own diet and eating behaviours. The results showed a clear role for modelling with concordance between a child's intake of unhealthy snacks and emotional eating and their parents' own reports of these behaviours. Furthermore, the child's intake of healthy foods was also predicted by their parent's behaviour although there was both concordance and discordance between parents and their children. No role for parental control was found for any measure of diet or eating behaviour. It is concluded that a parent's own behaviour rather than parental control has a stronger longer lasting influence once a child has left home and that although this mostly involves a child copying their parent's behaviour (action) at times it also involves the opposite (reaction).

Cellular mechanisms of nitric oxide-induced relaxation of corporeal smooth muscle in the guinea-pig.

The cellular mechanism of nitric oxide (NO)-induced relaxation in corporeal smooth muscle (CSM) of the guinea-pig was investigated. Changes in the intracellular concentration of calcium ions ([Ca(2+)](i)), membrane potential and isometric tension were measured. CSM cells exhibited spontaneous depolarizations and transient increases in [Ca(2+)](i) (Ca(2+) transients) which were accompanied by contractions. This spontaneous activity was abolished by nifedipine (10 microM). NO released by 3-morpholino-sydnonimine (SIN-1, 10 microM) hyperpolarized the membrane and prevented the generation of spontaneous depolarizations. SIN-1 also abolished Ca(2+) transients and associated contractions. These effects of SIN-1 were blocked by 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10 microM), an inhibitor of guanylate cyclase. Noradrenaline (NA, 1 microM) increased [Ca(2+)](i) to levels similar to those produced by high potassium-containing solution (high K(+) solution, [K(+)](o) = 40 mM), however, NA-induced contractions were three times greater in amplitude than those induced by high K(+) solution. In NA precontracted preparations, SIN-1 inhibited 80 % of the contraction and decreased [Ca(2+)](i) by 20 %. In contrast, nifedipine reduced [Ca(2+)](i) by 80 %, while the level of contraction was decreased by only 20 %. SIN-1-induced reduction in [Ca(2+)](i) but not the tension effect, was abolished by pretreatment with cyclopiazonic acid (CPA, 10 microM). In high K(+) precontracted preparations, SIN-1 inhibited 80 % of the contraction and reduced [Ca(2+)](i) by 20 %. Nifedipine, however, largely abolished increases in both [Ca(2+)](i) and tension under these circumstances. These results suggest that decreasing the sensitivity of contractile proteins to Ca(2+) is probably the key mechanism of NO-induced relaxation in CSM of the guinea-pig.