Hospital for Sick Children

About: Hospital for Sick Children is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 4097 authors who have published 3746 publications receiving 129066 citations. The organization is also known as: Sick Kids Hospital & SickKids.

Active lysyl oxidase (LOX) correlates with focal adhesion kinase (FAK)/paxillin activation and migration in invasive astrocytes.

Abstract: The extracellular matrix (ECM) plays a critical role during the development and invasion of primary brain tumours. However, the function of ECM components and signalling between a permissive ECM and invasive astrocytes is not fully understood. We have recently reported the ECM enzyme, lysyl oxidase (LOX), in the central nervous system and observed up-regulation of LOX in anaplastic astrocytoma cells. While the catalytic function of LOX is essential for cross-linking of ECM proteins, we also reported that LOX induced invasive and metastatic properties in breast tumour epithelial cells through hydrogen peroxide-mediated FAK/Src activation. In this study, we tested the hypothesis that active LOX is expressed in anaplastic astrocytes and promotes FAK activation and invasive/migratory behaviour. Results demonstrate that increased expression and activity of LOX positively correlated with invasive phenotype of malignant astrocytoma cell lines. Immunohistochemistry detected increased LOX within tumour cells and ECM in grade I-IV astrocytic neoplasm compared with normal brain and coincidence of increased LOX with the loss of glial fibrillary acidic protein in higher-grade tumours. Increased active LOX in invasive astrocytes was accompanied by phosphorylation of FAK[Tyr576] and paxillin[Tyr118]; furthermore, both FAK and paxillin tyrosine phosphorylation were diminished by beta-aminopropionitrile inhibition of LOX activity and depletion of H(2)O(2) via catalase treatment. Additionally, we provide evidence that in astrocytes, LOX is likely processed by bone morphogenic protein-1 and LOX activity might be further stimulated by the expression of fibronectin in these cells. These results demonstrate an important LOX-mediated mechanism that promotes migratory/invasive behaviour of malignant astrocytes.

Stand Up and Be Counted: Measuring and Mapping the Rheumatology Workforce in Canada.

Abstract: Objective. To characterize the practicing rheumatologist workforce, the Canadian Rheumatology Association (CRA) launched the Stand Up and Be Counted workforce survey in 2015. Methods. The survey was distributed electronically to 695 individuals, of whom 519 were expected to be practicing rheumatologists. Demographic and practice information were elicited. We estimated the number of full-time equivalent rheumatologists per 75,000 population from the median proportion of time devoted to clinical practice multiplied by provincial rheumatologist numbers from the Canadian Medical Association. Results. The response rate was 68% (355/519) of expected practicing rheumatologists (304 were in adult practice, and 51 pediatric). The median age was 50 years, and one-third planned to retire within the next 5–10 years. The majority (81%) were university-affiliated. Rheumatologists spent a median of 70% of their time in clinical practice, holding 6 half-day clinics weekly, with 10 new consultations and 45 followups seen per week. Work characteristics varied by type of rheumatologist (adult or pediatric) and by practice setting (community- or university-based). We estimated between 0 and 0.8 full-time rheumatologists per 75,000 population in each province. This represents a deficit of 1 to 77 full-time rheumatologists per province/territory to meet the CRA recommendation of 1 rheumatologist per 75,000 population, depending on the province/territory. Conclusion. Our results highlight a current shortage of rheumatologists in Canada that may worsen in the next 10 years because one-third of the workforce plans to retire. Efforts to encourage trainees to enter rheumatology and strategies to support retention are critical to address the shortage.

A Systematic Literature Review of the Effectiveness of Community-Based Strategies to Increase Cervical Cancer Screening

Abstract: Objective: To evaluate and summarize evidence of the effectiveness of interventions available to public health staff that could be used to increase cervical cancer screening to women. Method: A thorough literature review was conducted, articles screened for relevance and assessed for quality. Results: Of 42 relevant studies, 1 was rated ‘strong’, 18 ‘moderate’ and 23 ‘weak’. Among the strong/moderate studies, 10 were aimed at disadvantaged women. The most frequently used intervention was mass media campaigns, alone or combined with individual strategies; followed by individual education using lay health educators; and last, letters of invitation. Thirteen of the moderate/strong studies evaluated strategies that reported statistically significant increases in Pap smear rates and other outcomes. Conclusions: Strategies that combined mass media campaigns with direct tailored education to women and/or health care providers seemed most successful. The importance of accurate centralized cytology databases for recall is underscored.

Valproic Acid Impairs Carnitine Uptake in Cultured Human Skin Fibroblasts. An In Vitro Model for the Pathogenesis of Valproic Acid–Associated Carnitine Deficiency

Abstract: The mechanisms of valproate-associated carnitine deficiency are controversial. The urinary excretion of valproylcarnitine is insufficient to account for tissue carnitine depletion. To explore this mechanism, we studied the effects of valproic acid (VPA) on carnitine uptake in cultured human skin fibroblasts by the method of Tein et al. (Pediatr Res 28:247-255, 1990). Fibroblasts were preincubated with varying concentrations (0-2000 microM) of VPA for 1, 3, 5, 7, 10, 14, 21, and 28 d and then incubated with fixed carnitine concentrations of 50 microM (normal physiologic concentration), 20 microM (as seen in secondary carnitine deficiency disorders), or 5 microM (as seen in the plasma membrane carnitine transport defect). There was an exponential dose-dependent decrease in carnitine uptake with increasing VPA concentrations, and the relative inhibitory effect was the same for all three carnitine concentrations. The mean percentages +/- SD (n-1) of residual carnitine uptake for all combined preincubation periods (1-28 d) and combined carnitine concentrations (5, 20, and 50 mumol/L) with increasing concentrations of VPA varied from 83.4 +/- 2.6% (10 microM VPA) to 56.7 +/- 0.1% (500 microM) to 19.8 +/- 1.3% (2000 microM). The degree of inhibition was directly proportional to the time of VPA preincubation and parallel for all three carnitine concentrations; the longer the preincubation period, the lower the toxic dose of VPA (to a minimum of 450 microM), resulting in a 50% suppression of carnitine uptake (TD50).(ABSTRACT TRUNCATED AT 250 WORDS)

Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5)

Abstract: The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age. A total of 1719 children, with the breakdown into groupings of <30, 30–36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis. Gestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037. Preterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research. This study has been registered at (identifier NCT00187382 )