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The Toronto protocol for cancer surveillance in children with Li-Fraumeni syndrome has been adopted worldwide.To assess the diagnostic accuracy of the imaging used in this protocol.We conducted a blinded retrospective review of imaging modalities in 31 pediatric patients. We compared imaging findings with the reference standards, which consisted of (1) histopathological diagnosis, (2) corresponding dedicated imaging or subsequent surveillance imaging or (3) clinical outcomes. We individually analyzed each modality's diagnostic performance for cancer detection and assessed it on a per-study basis for chest and abdominal regional whole-body MRI (n=115 each), brain MRI (n=101) and abdominal/pelvic US (n=292), and on a per-lesion basis for skeleton/soft tissues on whole-body MRI (n=140).Of 763 studies/lesions, approximately 80% had reference standards that identified 4 (0.7%) true-positive, 523 (85.3%) true-negative, 5 (0.8%) false-positive, 3 (0.5%) false-negative and 78 (12.7%) indeterminate results. There were 3 true-positives on whole-body MRI and 1 true-positive on brain MRI as well as 3 false-negatives on whole-body MRI. Sensitivities and specificities of tumor diagnosis using a worst-case scenario analysis were, respectively, 40.0% (95% confidence interval [CI]: 7.3%, 83.0%) and 38.2% (95% CI: 29.2%, 48.0%) for skeleton/soft tissues on whole-body MRI; sensitivity non-available and 97.8% (95% CI: 91.4%, 99.6%) for chest regional whole-body MRI; 100.0% (95% CI: 5.5%, 100.0%) and 96.8% (95% CI: 90.2%, 99.2%) for abdominal regional whole-body MRI; sensitivity non-available and 98.3% (95% CI: 95.3, 99.4) for abdominal/pelvic US; and 50.0% (95% CI: 2.7%, 97.3%) and 93.8% (95% CI: 85.6%, 97.7%) for brain MRI.Considerations for optimizing imaging protocol, defining criteria for abnormalities, developing a structured reporting system, and practicing consensus double-reading may enhance the diagnostic accuracy for tumor surveillance.

To assess the prevalence of visual impairment and unmet eye care needs of the Syrian adult refugee population in Canada.Cross-sectional descriptive study.Enrolment was offered to all Syrian refugees 18 years or older, with 248 patients enrolled.Five clinics were organized from July 2016 to November 2017 in Toronto, Ontario. A vision screening and dilated retinal examination was performed on all participants. Prevalence of visual impairment and nonrefractive pathologies as well as information on sociodemographics and subjective visual acuity were obtained.The mean age of participants was 36 years (interquartile range, 30-35) and 53% were females. The prevalence of reported uncorrected vision problems was 22.2% for distance vision, 6.5% for near vision, and 5.6% for both distance and near vision, including loss of vision. Compared with the Canadian population, Syrian adult refugees were 19.04 times more likely to report uncorrected vision problems (34.4% vs 1.8%, p0.01). The presenting visual acuity in the better-seeing eye was 20/50 or worse in 19.4%. Pinhole improved this to 12.5% (95% confidence interval [CI], 8.7%-17.3%). Compared with the Canadian population (0.95%), Syrian adult refugees were 13 times more likely to have 20/50 vision or worse (p0.01). The most common finding was refractive error in 46.0% (95% CI, 39.6%-52.4%) followed by nonrefractive error in 30.2% (95% CI, 24.9%-36.2%).This is the first study to assess ocular health in a refugee population in Canada. Syrian adult refugees have a high prevalence of visual impairment, even when living within a system of universal health care.

To assess the ocular health status of Syrian pediatric refugees in Canada and report the prevalence of vision impairment within this population.Cross-sectional descriptive study.Syrian refugees 18 years old or younger.Five clinic days were organized from July 2016 to November 2017 in Toronto, Ontario. A total of 274 patients were enrolled. Data collection involved surveys, vision screening, and ocular examinations. χThe prevalence of uncorrected vision was 17.2% for distance, 4.7% for near, and 0.7% for both distance and near vision, including loss of vision. Of these, 95.3% had not visited an eye specialist in the past year, and 25.2% of parents were dissatisfied with their children's vision. The presenting visual acuity in the better-seeing eye was 20/50 or worse in 5.8% (95% confidence interval [CI] 3.6%-9.3%), and this did not correct with pinhole. This rate is 32 times (p0.01) higher than the prevalence rate in the average Canadian pediatric population (0.17%). Uncorrected refractive error prevalence was 26.3% (95% CI 21.2%-31.9%), with the most common etiology being myopia (19.7% CI 15.2%-24.9%). Myopia was 17.9 times (p0.0001) more prevalent among our Syrian refugee children compared with the average Canadian pediatric population (1.1%).Syrian pediatric refugees residing in Canada have a high prevalence of vision problems. Comprehensive vision screening, improved access to eye clinics, and developing evidence-based guidelines may help address the unmet eye care needs of this vulnerable population.

Aims Transforming growth factor β1 (TGF-β1) is a prosclerotic cytokine involved in cardiac remodelling leading to heart failure (HF). Acetylation/de-acetylation of specific lysine residues in Smad2/3 has been shown to regulate TGF-β signalling by altering its transcriptional activity. Recently, the lysine de-acetylase sirtuin 1 (SIRT1) has been shown to have a cardioprotective effect; however, SIRT1 expression and activity are paradoxically reduced in HF. Herein, we investigate whether pharmacological activation of SIRT1 would induce cardioprotection in a pressure overload model and assess the impact of SIRT1 activation on TGF-β signalling and the fibrotic response. Methods and results Eight weeks old male C57BL/6 mice were randomized to undergo sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Post-surgery, animals were further randomized to receive SRT1720 or vehicle treatment. Echocardiography, pressure-volume loops, and histological analysis revealed an impairment in cardiac function and deleterious left ventricular remodelling in TAC-operated animals that was improved with SRT1720 treatment. Genetic ablation and cell culture studies using a Smad-binding response element revealed SIRT1 to be a specific target of SRT1720 and identified Smad2/3 as a SIRT1 specific substrate. Conclusion Overall, our data demonstrate that Smad2/3 is a specific SIRT1 target and suggests that pharmacological activation of SIRT1 may be a novel therapeutic strategy to prevent/reverse HF via modifying Smad activity.

The capacity of stem and progenitor cells to stimulate cardiac regeneration has been studied for almost 20 years, with very promising preclinical data and mixed clinical results. Several cell types have been studied, identified by their cell surface markers, differentiation capacity and their secreted growth factors. Bone marrow derived mesenchymal stem cells (MSCs) have been found to have potent regenerative capacity, through multiple mechanisms, including mesoderm lineage differentiation, immunomodulation, and paracrine stimulation. MSCs also secrete exosomes and microvesicles, which themselves contain potent angiogenic cytokines or mRNA molecules with effects on their local milieu. This concise review summarizes the mechanisms of MSC-based cardiac regeneration and highlighting results from molecular and preclinical studies. We also discuss clinical trial results to date, and ongoing studies. Furthermore, we discuss novel approaches for the enhancement of MSC based cardiac regeneration, such as genetic modification.

Mechanisms for visuospatial cognition are often inferred directly from errors in behavioral reports of remembered target direction. For example, gaze-centered target representations for reach were first inferred from reach overshoots of target location relative to gaze. Here, we report evidence for the hypothesis that these gaze-dependent reach errors stem predominantly from misestimates of hand rather than target position, as was assumed in all previous studies. Subjects showed typical gaze-dependent overshoots in complete darkness, but these errors were entirely suppressed by continuous visual feedback of the finger. This manipulation could not affect target representations, so the suppressed gaze-dependent errors must have come from misestimates of hand position, likely arising in a gaze-dependent transformation of hand position signals into visual coordinates. This finding has broad implications for any task involving localization of visual targets relative to unseen limbs, in both healthy individuals and patient populations, and shows that response-related transformations cannot be ignored when deducing the sources of gaze-related errors.