👤 Manvir Ahluwalia

Parents play a critical role in influencing their young children's physical activity (PA) and sedentary time (ST). Despite this, many young children (aged 3-4y) and their parents are insufficiently active and engage in high amounts of ST. M-health interventions targeting PA and ST have seldom been tested in this population. The objective of this study was to examine the effectiveness and acceptability of the Active Family m-health intervention on the PA and ST of young children and their parents. Twenty-five stay-at-home parent-child dyads from Canada took part in the 2-week just-in-time micro-randomized controlled trial. Parents received seven text message prompts per day, where they were randomized to receive either a micro-intervention (activity suggestion) or control (no suggestion). Parents and children wore ActiGraph accelerometers to measure ST, light [LPA], and moderate-to-vigorous physical activity [MVPA]. Parents also completed a short online acceptability survey. A centred and weighted least square regression was used to analyze the effect of activity suggestions on the 60-min ST, LPA, and MVPA of parents and children following suggestion randomization. Descriptive statistics and content analysis were used to analyze acceptability survey responses. Micro-interventions were not effective at changing children's or parent's proximal ST (d = 0.01, p = .878; d = -0.09, p = .485, respectively), LPA (d = 0.03, p = .714; d = 0.03, p = .729, respectively), or MVPA (d = -0.05, p = .511; d = 0.10, p = .480, respectively). Interventions became more effective at increasing MVPA over time for parents (b = 0.47, 95%CI = 0.12, 0.83, p = .013). Among children, intervention effectiveness varied by contextual factors (e.g., weather). The intervention was largely acceptable, appropriate, and feasible for parents, though they did offer suggestions for improvement. Overall, micro-interventions did not significantly change parents or young children's proximal movement. Though, this approach showed promise for increasing parent's MVPA over time and for supporting children's activity under specific conditions. Show less

Bladder cancer, primarily urothelial carcinoma, is an important global health issue given its high recurrence and poor prognosis. Tumour invasion into the muscularis propria is a crucial prognostic indicator, distinguishing muscle-invasive bladder carcinoma (MIBC) from non-muscle-invasive carcinoma. Epithelial-mesenchymal transition (EMT) promotes tumour aggressiveness and metastasis and is marked by key transcription factors, such as SNAIL, SLUG and TWIST. This study investigates the association between the expression of EMT markers and histopathological features of bladder carcinoma. This retrospective study included 36 newly diagnosed cases of urothelial carcinoma at a tertiary care centre. Immunohistochemistry was conducted to assess SNAIL-SLUG and TWIST expression. Scoring was performed on the basis of staining intensity and extent. Statistical analysis was conducted to evaluate the associations amongst EMT markers, tumour grade, muscle invasion and clinical stage. MIBC was present in 58.3% of cases, with 80.6% of cases having high-grade tumours. TWIST expression was significantly higher in MIBC ( Elevated TWIST expression is correlated with high-grade and muscle-invasive urothelial carcinoma, suggesting its prognostic importance. Show less

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci. Show less

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index. Show less