Medical Students in Canadian Universities: Report of Statistics, 1966-67

Enrolment in the 13 Canadian medical schools in 1966-67 reached a new high of 4230, an increase of 5.1% over 1965-66. The percentage of women among medical students (12.1%) was close to that of the preceding three years. There has been a levelling off in the decline of students from outside Canada in 1966-67, when 9.5% of medical students were non-Canadian. The decline had been primarily in the number of American students, which continues. The number of students from Commonwealth countries has shown a steady increase during the eight-year period under review; in 1966-67, they make up nearly one-half of all non-Canadian students. It was noted that 18.5% of overseas students came to Canada under governmental or intergovernmental sponsorship. Of the Canadian students, 94% came from the “home” provinces of the medical schools.     

Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand

The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer.     

Characterization of the enzymatic activity of human kallikrein 6: Autoactivation,substrate specificity,and regulation by inhibitors

Human kallikrein 6 (hK6) is a trypsin-like serine protease, member of the human kallikrein gene family. Studies suggested a potential involvement of hK6 in the development and progression of Alzheimer's disease. The serum levels of hK6 might be used as a biomarker for ovarian cancer. To gain insights into the physiological role of this enzyme, we sought to determine its substrate specificity and its interactions with various inhibitors. We produced the proform of hK6 and showed that this enzyme was able to autoactivate, as well as proteolyse itself, leading to inactivation. Kinetic studies indicated that hK6 cleaved with much higher efficiency after Arg than Lys and with a preference for Ser or Pro in the P2 position. The efficient degradation of fibrinogen and collagen types I and IV by hK6 indicated that this kallikrein might play a role in tissue remodeling and/or tumor invasion and metastasis. We also demonstrated proteolysis of amyloid precursor protein by hK6 and determined the cleavage sites at the N-terminal end of the protein. Inhibition of hK6 was achieved via binding to different serpins, among which antithrombin III was the most efficient.     

Attention, the presolution period, and choice accuracy in pigeons

Six pigeons were trained first on a color then on a form discrimination; four other pigeons were trained first on form and then on color. One of two colors or one of two forms (sample stimuli) appeared in the center of a touch sensitive monitor for 5 pigeons and in the center and in 16 other locations for 5 other pigeons. A peck anywhere within the region in which the sample stimuli appeared produced two white disks (comparison stimuli), one on the left and one on the lower right corners of the screen. Correct left-right choices provided food. Although of no consequence, the location of pecks in presence of the sample was predictive of the pigeon's subsequent choice. Accuracy, choice of the correct comparison stimulus, was greater when the sample stimuli appeared in the center as well as 16 other locations than when it appeared only in the center. The presolution period, the period of chance accuracy prior to evidence of discrimination learning, was decreased on each task following training on the other task. This evidence of facilitation following an extra-dimensional shift was attributed to continued relevance of the conditions under which the first task was learned. The duration of the presolution period was inversely related to asymptotic accuracy-data accounted for by Heinemann's (1983) theory of information processing during the presolution period.     

Trauma-Related Mortality among Adults in Rural Western Kenya: Characterising Deaths Using Data from a Health and Demographic Surveillance System

Background

Information on trauma-related deaths in low and middle income countries is limited but needed to target public health interventions. Data from a health and demographic surveillance system (HDSS) were examined to characterise such deaths in rural western Kenya.

Methods And Findings

Verbal autopsy data were analysed. Of 11,147 adult deaths between 2003 and 2008, 447 (4%) were attributed to trauma; 71% of these were in males. Trauma contributed 17% of all deaths in males 15 to 24 years; on a population basis mortality rates were greatest in persons over 65 years. Intentional causes accounted for a higher proportion of male than female deaths (RR 2.04, 1.37-3.04) and a higher proportion of deaths of those aged 15 to 65 than older people. Main causes in males were assaults (n=79, 25%) and road traffic injuries (n=47, 15%); and falls for females (n=17, 13%). A significantly greater proportion of deaths from poisoning (RR 5.0, 2.7-9.4) and assault (RR 1.8, 1.2-2.6) occurred among regular consumers of alcohol than among non-regular drinkers. In multivariate analysis, males had a 4-fold higher risk of death from trauma than females (Adjusted Relative Risk; ARR 4.0; 95% CI 1.7-9.4); risk of a trauma death rose with age, with the elderly at 7-fold higher risk (ARR 7.3, 1.1-49.2). Absence of care was the strongest predictor of trauma death (ARR 12.2, 9.4-15.8). Trauma-related deaths were higher among regular alcohol drinkers (ARR 1.5, 1.1-1.9) compared with non-regular drinkers.

Conclusions

While trauma accounts for a small proportion of deaths in this rural area with a high prevalence of HIV, TB and malaria, preventive interventions such as improved road safety, home safety strategies for the elderly, and curbing harmful use of alcohol, are available and could help diminish this burden. Improvements in systems to record underlying causes of death from trauma are required.     

Oral but Not Intravenous Glucose Acutely Decreases Circulating Interleukin-6 Concentrations in Overweight Individuals

Background

Plasma interleukin-6 (IL-6) concentrations decrease acutely 1 h after ingestion of a glucose load or mixed meals and this may be mediated by an anti-inflammatory effect of insulin. The aim of the present study was to compare the effect of higher versus lower insulin levels on plasma IL-6 concentrations following oral compared with intravenous glucose administration in overweight/obese subjects.

Methods and Findings

Fifteen subjects (12 women and 3 men) with BMI >28 kg/m² were given an oral glucose load (75g) followed a week later by an intravenous infusion of glucose aimed at matching plasma glucose concentrations during the oral glucose load. A week later, they drank a volume of water equivalent to the volume consumed with the oral glucose load. Plasma glucose, insulin, nonesterified fatty acids, and IL-6 concentrations and blood hematocrit were measured at 30 minute intervals for 2 h following each intervention. Plasma IL-6 decreased (13–20%) significantly (P = 0.009) at 30 min to 90 min following the oral glucose load and did not change significantly following the other two interventions. The incremental area under the curve for plasma IL-6 concentrations following oral intake of glucose was significantly lower compared with concentrations following intravenous glucose (P = 0.005) and water control (P = 0.02). Circulating insulin concentrations were significantly (P<0.001) and 2.8 fold higher following oral compared with intravenous glucose administration.

Conclusions

These data show that plasma IL-6 concentrations did not decrease during isoglycemic, intravenous glucose administration suggesting that the markedly higher circulating insulin levels and/or gut-related factors may mediate the acute decrease in plasma IL-6 after oral glucose intake in overweight/obese subjects.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12612000491864     

Pollen influx values measured in different sedimentary environments and their palaeoecological implications

Aspects which need to be considered when calculating pollen influx values in three sedimentary environments (pollen traps, peats and lake sediments) are reviewed. Examples of influx values (grains cm^-2 year^-1) in northern Fennoscandia for two arboreal taxa Betula and Pinus, calculated from these three different environments are presented. Such long term average pollen influx values can be used to indicate the presence/absence and density of the species within the vicinity of the sampling site. Contrary to expectations, conditions do exist in which numerically comparable values are obtained from all three environments. Using these pollen influx values to interpret forest and woodland history in tree-line situations, from both peats and lake sediments, a higher degree of precision can be obtained than through the more classical pollen percentage method alone.