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Reconsidering Canadian curriculum studies : provoking historical, present, and future perspectives
\"Reconsidering Canadian Curriculum Studies is a thought-provoking book, where curriculum scholars at different stages in their academic careers experiment with innovating theoretical and methodological ways to research the concept of \"curriculum.\" Each chapter showcases examples of the dynamic intellectual work being done within the international field of curriculum studies across the diverse geographical and cultural regions here in Canada and the United States. In this book, the authors provoke us to ask more of curriculum studies in relation to other fields of study like environmental education, anti-racist education, multicultural education, internationalization, indigenousness, cultural studies, cultural geography, interdisciplinary studies, phenomenology, hermeneutics, and poststructuralism. This book is an excellent introductory text for any curriculum studies course either here in Canada or abroad\"-- Provided by publisher.
Book
Promoter hypermethylation of tumour suppressor genes as potential biomarkers in colorectal cancer
Colorectal cancer (CRC) is a common malignancy and the fourth leading cause of cancer deaths worldwide. It results from the accumulation of multiple genetic and epigenetic changes leading to the transformation of colon epithelial cells into invasive adenocarcinomas. In CRC, epigenetic changes, in particular promoter CpG island methylation, occur more frequently than genetic mutations. Hypermethylation contributes to carcinogenesis by inducing transcriptional silencing or downregulation of tumour suppressor genes and currently, over 600 candidate hypermethylated genes have been identified. Over the past decade, a deeper understanding of epigenetics coupled with technological advances have hinted at the potential of translating benchtop research into biomarkers for clinical use. DNA methylation represents one of the largest bodies of literature in epigenetics, and hence has the highest potential for minimally invasive biomarker development. Most progress has been made in the development of diagnostic markers and there are currently two, one stool-based and one blood-based, biomarkers that are commercially available for diagnostics. Prognostic and predictive methylation markers are still at their infantile stages.
Journal Article
Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer
The term metastasis is widely used to describe the endpoint of the process by which tumour cells spread from the primary location to an anatomically distant site. Achieving successful dissemination is dependent not only on the molecular alterations of the cancer cells themselves, but also on the microenvironment through which they encounter. Here, we reviewed the molecular alterations of metastatic gastric cancer (GC) as it reflects a large proportion of GC patients currently seen in clinic. We hope that further exploration and understanding of the multistep metastatic cascade will yield novel therapeutic targets that will lead to better patient outcomes.
Journal Article
Psychometric Testing of Three Chinese Online-Related Addictive Behavior Instruments among Hong Kong University Students
Given that there is a lack of instruments assessing internet-related addictions among Chinese population, this study aimed to validate the Chinese version of the nine-item Internet Gaming Disorder Scales- Short Form (IGDS-SF9), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application-Based Addiction Scale (SABAS) among Hong Kong university students. Participants aged between 17 and 30 years participated in the present study (n = 307; 32.4% males; mean [SD] age = 21.64 [8.11]). All the participants completed the IGDS-SF9, BSMAS, SABAS, and the Hospital Anxiety and Depression Scale (HADS). Confirmatory factor analyses (CFAs) were used to examine the factorial structures and the unidimensionality for IGDS-SF9, BSMAS, and SABAS. CFAs demonstrated that the three scales were all unidimensional with satisfactory fit indices: comparative fit index = 0.969 to 0.992. In addition, the IGDS-SF9 and BSMAS were slightly modified based on the modification index in CFA. The Chinese IGDS-SF9, BSMAS, and SABAS are valid instruments to assess the addiction levels of internet-related activities for Hong Kong university students.
Journal Article
Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study
Background
Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies.
Methods
This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints.
Results
PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (
p
= 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (
p
= 0.0197) and Total (
p
= 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo.
Conclusions
Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis.
Trial registration
This trial is registered at the Australian New Zealand Clinical Trials Registry #
ACTRN12617000893303
.
Journal Article
Off-Pump or On-Pump Coronary-Artery Bypass Grafting at 30 Days
A total of 4752 patients for whom CABG was planned were randomly assigned to undergo the procedure on-pump or off-pump. At 30 days, the rates of death, myocardial infarction, stroke, or renal failure requiring dialysis did not differ significantly between the two groups.
Coronary-artery bypass grafting (CABG) reduces mortality in patients with extensive coronary artery disease.
1
CABG has generally been performed with the use of cardiopulmonary bypass (on-pump). With this approach, perioperative mortality is about 2%, with an additional 5 to 7% of patients having complications such as myocardial infarction, stroke, and renal failure requiring dialysis. The technique of operating on a beating heart (off-pump) for CABG was developed to decrease perioperative complications, some of which may be related to the use of cardiopulmonary bypass and to cross-clamping of the aorta associated with the on-pump CABG procedure.
Several previous trials have compared off-pump . . .
Journal Article
Serum 21-Deoxycortisol for Diagnosis of Nonclassic Congenital Adrenal Hyperplasia in Women With Androgen Excess
Abstract
Context
Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies.
Objective
We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17-hydroxyprogesterone (17OHP).
Methods
A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by receiver operating characteristic analysis.
Results
Basal 17OHP, stimulated 17OHP, and 21DF were measured in 99, 85, and 42 participants, respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L, and 13.6 for stimulated 17OHP, 21DF, and the ratio (21DF + 17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5%, and 85.0%, respectively.
Conclusion
LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS.
Journal Article
Googling for a diagnosis—use of Google as a diagnostic aid: internet based study
Objective To determine how often searching with Google (the most popular search engine on the world wide web) leads doctors to the correct diagnosis. Design Internet based study using Google to search for diagnoses; researchers were blind to the correct diagnoses. Setting One year's (2005) diagnostic cases published in the case records of the New England Journal of Medicine. Cases 26 cases from the New England Journal of Medicine; management cases were excluded. Main outcome measure Percentage of correct diagnoses from Google searches (compared with the diagnoses as published in the New England Journal of Medicine). Results Google searches revealed the correct diagnosis in 15 (58%, 95% confidence interval 38% to 77%) cases. Conclusion As internet access becomes more readily available in outpatient clinics and hospital wards, the web is rapidly becoming an important clinical tool for doctors. The use of web based searching may help doctors to diagnose difficult cases.
Journal Article
Association between day of the week of elective surgery and postoperative mortality
In prior studies, higher mortality was observed among patients who had elective surgery on a Friday rather than earlier in the week. We investigated whether mortality after elective surgery was associated with day of the week of surgery in a Canadian population and whether the association was influenced by surgeon experience and volume.
We conducted a population-based retrospective cohort study in the province of Ontario, Canada. We included adults who underwent 1 of 12 elective daytime surgical procedures from Apr. 1, 2002, to Dec. 31, 2012. The primary outcome was 30-day mortality. We used generalized estimating equations to compare outcomes for surgeries performed on different days of the week, adjusting for patient and surgeon factors.
A total of 402 899 procedures performed by 1691 surgeons met our inclusion criteria. The median length of hospital stay was 6 (interquartile range 5–8) days. Surgeon experience varied significantly by day of week (p < 0.001), with surgeons operating on Fridays having the least experience. Nearly all of the patients who had their procedure on a Friday had postoperative care on the weekend, as compared with 49.1% of those whose surgery was on a Monday (p < 0.001). We found no difference in the 30-day mortality between procedures performed on Fridays and those performed on Mondays (adjusted odds ratio 1.08, 95% confidence interval 0.97–1.21).
Although surgeon experience differed across days of the week, the risk of 30-day mortality after elective surgery was similar regardless of which day of the week the procedure took place.
Journal Article
Heterozygosity for Lmna Deficiency Eliminates the Progeria-Like Phenotypes in Zmpste24-Deficient Mice
Zmpste24 is a metalloproteinase required for the processing of prelamin A to lamin A, a structural component of the nuclear lamina. Zmpste24 deficiency results in the accumulation of prelamin A within cells, a complete loss of mature lamin A, and misshapen nuclear envelopes. Zmpste24-deficient (Zmpste24-/-) mice exhibit retarded growth, alopecia, micrognathia, dental abnormalities, osteolytic lesions in bones, and osteoporosis, which are phenotypes shared with Hutchinson-Gilford progeria syndrome, a human disease caused by the synthesis of a mutant prelamin A that cannot undergo processing to lamin A. Zmpste24-/- mice also develop muscle weakness. We hypothesized that prelamin A might be toxic and that its accumulation in Zmpste24-/- mice is responsible for all of the disease phenotypes. We further hypothesized that Zmpste24-/- mice with half-normal levels of prelamin A (Zmpste24-/- mice with one Lmna knockout allele) would be subjected to less toxicity and be protected from disease. Thus, we bred and analyzed Zmpste24-/-Lmna+/- mice. As expected, prelamin A levels in Zmpste24-/-Lmna+/- cells were significantly reduced. Zmpste24-/-Lmna+/- mice were entirely normal, lacking all disease phenotypes, and misshapen nuclei were less frequent in Zmpste24-/-Lmna+/- cells than in Zmpste24-/- cells. These data suggest that prelamin A is toxic and that reducing its levels by as little as 50% provides striking protection from disease.
Journal Article