Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020.

Background: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland.

Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit.

Recommendations From Parents to Improve Health Services for Managing Pediatric Obesity in Canada.

Objective: Although parents are uniquely positioned to offer first-hand insights that can be used to improve health services for managing pediatric obesity, their perspective is underexplored. Our objective was to characterize parents' recommendations for enhancing tertiary-level health services for managing pediatric obesity in Canada.

Methods: Semistructured, one-on-one interviews were conducted with parents of children who initiated treatment at 1 of 4 Canadian tertiary-level, multidisciplinary weight management clinics.

Tools and resources for preventing childhood obesity in primary care: A method of evaluation and preliminary assessment.

Objectives: To pilot-test a mixed methods approach to evaluate tools and resources (TRs) that healthcare providers (HCPs) use for preventing childhood obesity in primary care, and report a preliminary descriptive assessment of commonly-used TRs.

Methods: This mixed methods study included individual, semi-structured interviews with purposefully-sampled HCPs in Alberta, Canada; interviews were digitally recorded and analyzed thematically (phase I). Two independent reviewers used three assessment checklists to evaluate commonly-used TRs (phase II).

Why do families enrol in paediatric weight management? A parental perspective of reasons and facilitators.

Background: Few children with obesity who are referred for weight management end up enroled in treatment. Factors enabling enrolment are poorly understood. Our purpose was to explore reasons for and facilitators of enrolment in paediatric weight management from the parental perspective.

The Development and Refinement of an e-Health Screening, Brief Intervention, and Referral to Treatment for Parents to Prevent Childhood Obesity in Primary Care.

Background: Nearly one-third of Canadian children can be categorized as overweight or obese. There is a growing interest in applying e-health approaches to prevent unhealthy weight gain in children, especially in settings that families access regularly. Our objective was to develop and refine an e-health screening, brief intervention, and referral to treatment (SBIRT) for parents to help prevent childhood obesity in primary care.

Mutational analysis of the Notch2 negative regulatory region identifies key structural elements for mechanical stability.

The Notch signalling pathway is fundamental to cell differentiation in developing and self-renewing tissues. Notch is activated upon ligand-induced conformational change of the Notch negative regulatory region (NRR), unmasking a key proteolytic site (S2) and facilitating downstream events. The favoured model requires endocytosis of a tightly bound ligand to transmit force to the NRR region, sufficient to cause a structural change that exposes the S2 site.

Developing and Pilot Testing the Readiness and Motivation Interview for Families in Pediatric Weight Management.

Clinical acumen is often used to assess families' motivation prior to initiating pediatric obesity management due to a lack of available tools. The purpose of this pilot study was to (i) develop and (ii) pilot test the "Readiness and Motivation Interview for Families" (RMI-Family) in pediatric weight management. We conducted 5 focus groups with parents (n = 15), youth with obesity (n = 11), and health care providers (n = 8) to explore perceptions of barriers to making healthy behaviour changes, which led to the creation of the RMI-Family as a semi-structured interview.

Lessons Learned From Using Focus Groups to Refine Digital Interventions.

There is growing interest in applying novel eHealth approaches for the prevention and management of various health conditions, with the ultimate goal of increasing positive patient outcomes and improving the effectiveness and efficiency of health services delivery. Coupled with the use of innovative approaches is the possibility for adverse outcomes, highlighting the need to strategically refine digital practices prior to implementation with patients. One appropriate method for modification purposes includes focus groups.

Inhibition of the Inositol Kinase Itpkb Augments Calcium Signaling in Lymphocytes and Reveals a Novel Strategy to Treat Autoimmune Disease.

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes.

Working With Parents to Prevent Childhood Obesity: Protocol for a Primary Care-Based eHealth Study.

Background: Parents play a central role in preventing childhood obesity. There is a need for innovative, scalable, and evidence-based interventions designed to enhance parents' motivation to support and sustain healthy lifestyle behaviors in their children, which can facilitate obesity prevention.

Objective: (1) Develop an online screening, brief intervention, and referral to treatment (SBIRT) eHealth tool to enhance parents' concern for, and motivation to, support children's healthy lifestyle behaviors, (2) refine the SBIRT eHealth tool by assessing end-user acceptability, satisfaction, and usability through focus groups, and (3) determine feasibility and preliminary effectiveness of the refined SBIRT eHealth tool through a randomized controlled trial.

Lifestyle Behaviors of Parents of Children in Pediatric Weight Management: Are They Meeting Recommendations?

Objective: Our objective was to examine the lifestyle behaviors of parents of children in pediatric weight management.

Methods: Parents were recruited upon presentation of their children (body mass index [BMI] ≥85th percentile) to a pediatric weight management clinic. Parents' demographic, anthropometric, and lifestyle habit data were collected by self-report.

Attrition and the management of pediatric obesity: an integrative review.

Background: A key challenge in managing pediatric obesity is the high degree of program attrition, which can reduce therapeutic benefits and contribute to inefficient health services delivery. Our aim was to document and characterize predictors of, and reasons for, attrition in pediatric obesity management.

Methods: We searched literature published until January 2014 in five databases (CINAHL, EMBASE, MEDLINE, PsycINFO, and Scopus).

It's like rocket science…only more complex: challenges and experiences related to managing pediatric obesity in Canada.

Pediatric obesity is an urgent and complex public health issue. Approximately one-third of Canadian children are overweight or obese, a proportion that highlights the need for effective and accessible services to improve short- and long-term health risks. In our experience, we have encountered a number of challenges common in pediatric obesity management across our clinical and research centers.

Modest treatment effects and high program attrition: The impact of interdisciplinary, individualized care for managing paediatric obesity.

Background: There is an urgent need to identify effective weight management interventions in real-world, clinical settings to improve the health of children with obesity.

Objectives: To determine the impact of individualized, interdisciplinary care on the weight status of children with obesity; to assess the relationship between clinical interactions and change in participants' weight status; and to document the degree of program attrition.

Methods: A retrospective medical record review of clinical and administrative data from a paediatric weight management clinic in Edmonton, Alberta, was performed, which included data from a group of five- to 18-year-olds (body mass index [BMI] ≥85th percentile) collected from 2008 to 2012.

Habitat quality affects early physiology and subsequent neuromotor development of juvenile black-capped chickadees.

In songbirds, the ability to learn and render the species-specific song is influenced by the development of both the song nuclei in the brain and the syrinx (bird's vocal apparatus) early in the bird's life. In black-capped chickadees (Poecille atricapillus), habitat quality is known to affect song structure, with birds in high-quality habitat (mature forest) having a higher song consistency than birds in low-quality habitat (young forest). Although this difference is suspected to stem from differences in development, the developmental status of juvenile birds in either habitat remains unexplored.

Cis-acting ribozymes for the production of RNA in vitro transcripts with defined 5' and 3' ends.

The use of in vitro transcribed RNA is often limited by sequence constraints at the 5'-end and the problem of transcript heterogeneity which can occur at both the 5'- and 3'-ends. This chapter describes the use of cis-acting ribozymes, 5'-end hammerhead (HH) and 3'-end hepatitis delta virus (HDV), for direct transcriptional processing to yield target RNAs with precisely defined ends. The method is focused on the use of the pRZ and p2RZ plasmids that are designed to simplify the production of such dual ribozyme templates.

Direct observation of proteolytic cleavage at the S2 site upon forced unfolding of the Notch negative regulatory region.

The conserved Notch signaling pathway plays crucial roles in developing and self-renewing tissues. Notch is activated upon ligand-induced conformation change of the Notch negative regulatory region (NRR) unmasking a key proteolytic site (S2) and facilitating downstream events. Thus far, the molecular mechanism of this signal activation is not defined.

Su(dx) E3 ubiquitin ligase-dependent and -independent functions of polychaetoid, the Drosophila ZO-1 homologue.

Zona occludens (ZO) proteins are molecular scaffolds localized to cell junctions, which regulate epithelial integrity in mammals. Using newly generated null alleles, we demonstrate that polychaetoid (pyd), the unique Drosophila melanogaster ZO homologue, regulates accumulation of adherens junction-localized receptors, such as Notch, although it is dispensable for epithelial polarization. Pyd positively regulates Notch signaling during sensory organ development but acts negatively on Notch to restrict the ovary germline stem cell niche.

Deletion of the potassium channel Kv12.2 causes hippocampal hyperexcitability and epilepsy.

We found the voltage-gated K+ channel Kv12.2 to be a potent regulator of excitability in hippocampal pyramidal neurons. Genetic deletion and pharmacologic block of Kv12.

The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease?

Objectives: During a reflux event the oesophagus is exposed to a heterogeneous mixture of gastric juice components. The role of non-acid components of the refluxate in causing damage to the oesophagus is now well established but no therapeutic option exists to address this.

Methods: The role of Gaviscon Advance (GA), a raft-forming alginate suspension, in protecting the oesophagus from damage by pepsin and bile acids (aggressors) was investigated using a series of in-vitro models.

Interactions between subunits of Saccharomyces cerevisiae RNase MRP support a conserved eukaryotic RNase P/MRP architecture.

Ribonuclease MRP is an endonuclease, related to RNase P, which functions in eukaryotic pre-rRNA processing. In Saccharomyces cerevisiae, RNase MRP comprises an RNA subunit and ten proteins. To improve our understanding of subunit roles and enzyme architecture, we have examined protein-protein and protein-RNA interactions in vitro, complementing existing yeast two-hybrid data.

Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex.

WW domains target proline-tyrosine (PY) motifs and frequently function as tandem pairs. When studied in isolation, single WW domains are notably promiscuous and regulatory mechanisms are undoubtedly required to ensure selective interactions. Here, we show that the fourth WW domain (WW4) of Suppressor of Deltex, a modular Nedd4-like protein that down-regulates the Notch receptor, is the primary mediator of a direct interaction with a Notch-PY motif.

Isotopically discriminated NMR spectroscopy: a tool for investigating complex protein interactions in vitro.

A new NMR approach is presented for observing in vitro multicomponent protein-protein-ligand(s) interactions, which should help to understand how cellular networks of protein interactions operate on a molecular level and how they can be controlled with drugs. The method uniquely allows at least two polypeptide components of the mixture to be simultaneously closely monitored in a single sample, without increased signal overlap, and can be used to study complex (e.g.