The LUNCHES Study: Elementary School Children\u27s Packed Lunch Contents and Intake in the Traditional vs. Balanced School Day Schedule

The Balanced School Day (BSD), an alternative to the Traditional Schedule (TS), provides two 20-minute eating periods during the school day, rather than a midday lunch break. Widespread implementation of the BSD schedule has occurred across Ontario with limited systematic evaluation of potential health outcomes. The purpose of this study was to compare the food and nutrient value of grade 3 and 4 students’ packed lunch contents and consumption in the BSD versus TS, by direct observation. When compared to the TS, more BSD students had a sugar-sweetened beverage packed in their lunch. Greater portions of snack items were also packed and consumed in the BSD. Correspondingly, children in the BSD consumed more energy, carbohydrates, saturated fatty acids, total sugar, and percent energy from total sugar than in the TS. These findings suggest the BSD may negatively affect the quality of packed lunches, increasing the risk of adverse health outcomes

Biomarkers of oesophageal neoplasia

Background. Symptomatic oesophageal cancer is usually advanced and terminates fatally. There is a need for biomarkers to help pathologists recognise patients at increased risk of squamous and glandular oesophageal cancers (in the case of Barrett's oesophagus). The work described in this thesis looks at four topics: cytokeratin 7 and 20 phenotypes in Barrett's intestinal metaplasia; the distribution of cardiac, cardio-oxyntic and 'specialised' intestinal-type Barrett's mucosa in relation to glandular dysplasia; dysregulated expression of the proliferation marker Ki67 and the DNA replication-licensing proteins Mcm2 and Mcm5 in glandular and squamous dysplasia; and relates different types of complete (type I) and incomplete (types IIA/IIB) intestinal metaplasia to dysplasia/neoplasia in Barrett's esophagus. Results. Cytokeratin 7 and 20 phenotypes are complex and variable, so likely clinical utility is not immediately obvious. The ubiquitous presence of intestinal metaplasia (IM) in Barrett's mucosa is confirmed, and a very strong association of IM with dysplasia. A positive association exists between dysplasia and type IIB intestinal metaplasia, and an even stronger negative association with type I intestinal metaplasia. This identifies a possibility that robust markers of (complete) small intestinal metaplasia may be associated with low dysplasia risk in Barrett's oesophagus, whereas a potentially colonic phenotype (type IIB IM) is associated with greater risk. Over-expression of the cell-proliferation related antigen Ki67 and the DNA replication licensing proteins Mcm2 and Mcm5 in the differentiated surface compartment of squamous oesophageal epithelium and Barrett's mucosa confirm the Mem proteins are promising markers of oesophageal dysplasia meriting further evaluation, e.g. in the field of non-endoscopic oesophageal cytology

In-depth proteomics identifies a role for autophagy in controlling reactive oxygen species mediated endothelial permeability

Endothelial cells (ECs) form the inner layer of blood vessels and physically separate the blood from the surrounding tissue. To support tissues with nutrients and oxygen, the endothelial monolayer is semipermeable. When EC permeability is altered, blood vessels are not functional, and this is associated with disease. A comprehensive knowledge of the mechanisms regulating EC permeability is key in developing strategies to target this mechanism in pathologies. Here we have used an in vitro model of human umbilical vein endothelial cells mimicking the formation of a physiologically permeable vessel and performed time-resolved in-depth molecular profiling using stable isotope labeling by amino acids in cell culture mass spectrometry (MS)-proteomics. Autophagy is induced when ECs are assembled into a physiologically permeable monolayer. By using siRNA and drug treatment to block autophagy in combination with functional assays and MS proteomics, we show that ECs require autophagy flux to maintain intracellular reactive oxygen species levels, and this is required to maintain the physiological permeability of the cells

Picky eating is associated with lower nutrient intakes from children’s home‐packed school lunches

The objective was to assess the relationship between children’s picky eating (PE) status and nutrient intake from home‐packed school lunches. The lunches of 321 students, aged 7–10 years, were quantified via cross‐sectional direct observation. Children were classified as having PE (n = 155) or not (non‐PE; n = 166) based on food neophobia scores and parental perceptions of PE. The PE group consumed significantly less protein, folate, magnesium, potassium, zinc, and vitamins B1, B2, B3, B6, D, and E than the non‐PE group; however, both groups consumed amounts exceeding Dietary Reference Intakes (DRIs) for protein, carbohydrates, sugar, sodium, iron, and vitamins B1, B2, B3, B6, B12, and C. Conversely, both groups consumed amounts significantly lower than DRIs for calcium, fibre, folate, magnesium, potassium, zinc, and vitamins A, D, E, and K. The PE group ate significantly less meat and alternatives, vegetables and fruit, and fruit than the non‐PE group, and did not meet any of Canada’s Food Guide (2007) recommendations. The non‐PE group met recommendations for meat and alternatives only. PE impacts the dietary intake of children’s homepacked lunches; however, many packed lunches were of low nutritional quality. Focus should be placed on provision of nutritionally complete school lunches for all children

Mitogen-activated protein kinase kinase 5 regulates proliferation and biosynthetic processes in procyclic forms of Trypanosoma brucei

The pathogenic protozoan T. brucei alternates into distinct developmental stages in the mammalian and insect hosts. The mitogen-activated protein kinase (MAPK) signaling pathways transduce extracellular stimuli into a range of cellular responses, which ultimately lead to the adaptation to the external environment. Here, we combined a loss of function approach with stable isotope labeling with amino acids in cell culture (SILAC)-based mass spectrometry (MS) to investigate the role of the mitogen-activated protein kinase kinase 5 (MKK5) in T. brucei. The silencing of MKK5 significantly decreased the proliferation of procyclic forms of T. brucei. To shed light on the molecular alterations associated with this phenotype, we measured the total proteome and phosphoproteome of cells silenced for MKK5. In the total proteome, we observed a general decrease in proteins related to ribosome and translation as well as down-regulation of several components of the fatty acids biosynthesis pathway. In addition, we observed alterations in the protein levels and phosphorylation of key metabolic enzymes, which point toward a suppression of the oxidative metabolism. Taken together, our findings show that the silencing of MKK5 alters cell growth, energy metabolism, protein and fatty acids biosynthesis in procyclic T. brucei

Children’s School-Day Nutrient Intake in Ontario: A Cross-Sectional Observational Study Comparing Students’ Packed Lunches from Two School Schedules

This study compared the caloric and nutrient values of packed lunch contents and consumption in the Balanced School Day (BSD) (two 20 min eating periods) versus the Traditional Schedule (TS) (one 20 min lunch). Foods consumed during school were assessed by direct food observation in 321 grade 3 and 4 students, aged 7–10 years, at 9 BSD and 10 TS elementary schools in Ontario. Packed lunch contents in the BSD were significantly higher than the TS in energy (3128.14 ± 1100.36 vs. 2658.98 ± 951.34 kJ, p \u3c 0.001, respectively). Similarly, carbohydrates, total sugar, protein, fat, saturated fatty acids (SFA), calcium, iron, and sodium were significantly higher in the BSD versus TS packed lunches. Correspondingly, students in the BSD consumed significantly more energy, carbohydrates, total sugar, and SFA compared to the TS. Overall, lunches brought by students in the BSD schedule provided more energy across all macronutrients, with only a few micronutrients showing increased amounts, suggesting two 20 min eating opportunities could contribute to excess caloric intake during school, potentially contributing to the prevalence of childhood overweight and obesity in Canada. Furthermore, packed lunches in both schedules had excess amounts of nutrients of concern and much work is needed to ensure that children in Canada receive nutritious lunches at school

Patterns and trends among physicians-in-training named in civil legal cases: a retrospective analysis of Canadian Medical Protective Association data from 1993 to 2017

BACKGROUND: Medico-legal data show opportunities to improve safe medical care; little is published on the experience of physicians-in-training with medical malpractice. The purpose of this study was to examine closed civil legal cases involving physicians-in-training over time and provide novel insights on case and physicians characteristics. METHODS: We conducted a retrospective descriptive study of closed civil legal cases at the Canadian Medical Protective Association (CMPA), a mutual medico-legal defence organization for more than 105 000 physicians, representing an estimated 95% of physicians in Canada. Eligible cases involved at least 1 physician-in-training and were closed between 1993 and 2017 (for time trends) or 2008 and 2017 (for descriptive analyses). We analyzed case rates over time using Poisson regression and the annualized change rate. Descriptive analyses addressed case duration, medico-legal outcome and patient harm. We explored physician specialties and practice characteristics in a subset of cases. RESULTS: Over a 25-year period (1993-2017), 4921 physicians-in-training were named in 2951 closed civil legal cases, and case rates decreased significantly (β = -0.04, 95% confidence interval -0.05 to -0.03, where β was the 1-year difference in log case rates). The annualized change rate was -1.1% per year. Between 2008 and 2017, 1901 (4.1%) of 45 967 physicians-in-training were named in 1107 civil legal cases. Cases with physicians-in-training generally involved more severe patient harm than cases without physicians-in-training. In a subgroup with available information (n = 951), surgical specialties were named most often (n = 531, 55.8%). INTERPRETATION: The rate of civil legal cases involving physicians-in-training has diminished over time, but more recent cases featured severe patient harm and death. Efforts to promote patient safety may enhance medical care and reduce the frequency and severity of malpractice issues for physicians-in-training

A Critical Appraisal of Guidelines for Antenatal Care: Components of Care and Priorities in Prenatal Education

There are a variety of published prenatal care (PNC) guidelines that claim a scientific basis for the information included. Four sets of PNC guidelines published between 2005 and 2009 were examined and critiqued. The recommendations for assessment procedures, laboratory testing, and education/counseling topics were analyzed within and between these guidelines. The PNC components were synthesized to provide an organized, comprehensive appendix that can guide providers of antepartum care. The appendix may be used to locate which guidelines addressed which topics to assist practitioners to identify evidence sources. The suggested timing for introducing and reinforcing specific topics is also presented in the appendix. Although education is often assumed to be a vital component of PNC, it was inconsistently included in the guidelines that were reviewed. Even when education was included, important detail was lacking. Addressing each woman\u27s needs as the first priority was suggested historically and remains relevant in current practice to systematically provide care while maintaining the woman as the central player. More attention to gaps in current research is important for the development of comprehensive prenatal guidelines that contribute effectively to the long‐term health and well‐being of women, families, and their communities

Hypoxic cancer–associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling

Intratumoral hypoxia causes the formation of dysfunctional blood vessels, which contribute to tumor metastasis and reduce the efficacy of therapeutic treatments. Blood vessels are embedded in the tumor stroma of which cancer-associated fibroblasts (CAFs) constitute a prominent cellular component. We found that hypoxic human mammary CAFs promoted angiogenesis in CAF-endothelial cell cocultures in vitro. Mass spectrometry–based proteomic analysis of the CAF secretome unraveled that hypoxic CAFs contributed to blood vessel abnormalities by altering their secretion of various pro- and anti-angiogenic factors. Hypoxia induced pronounced remodeling of the CAF proteome, including proteins that have not been previously related to this process. Among those, the uncharacterized protein NCBP2-AS2 that we renamed HIAR (hypoxia-induced angiogenesis regulator) was the protein most increased in abundance in hypoxic CAFs. Silencing of HIAR abrogated the pro-angiogenic and pro-migratory function of hypoxic CAFs by decreasing secretion of the pro-angiogenic factor VEGFA and consequently reducing VEGF/VEGFR downstream signaling in the endothelial cells. Our study has identified a regulator of angiogenesis and provides a map of hypoxia-induced molecular alterations in mammary CAFs