Local modulation of steroid action: rapid control of enzymatic activity.

peer reviewedEstrogens can induce rapid, short-lived physiological and behavioral responses, in addition to their slow, but long-term, effects at the transcriptional level. To be functionally relevant, these effects should be associated with rapid modulations of estrogens concentrations. 17beta-estradiol is synthesized by the enzyme aromatase, using testosterone as a substrate, but can also be degraded into catechol-estrogens via hydroxylation by the same enzyme, leading to an increase or decrease in estrogens concentration, respectively. The first evidence that aromatase activity (AA) can be rapidly modulated came from experiments performed in Japanese quail hypothalamus homogenates. This rapid modulation is triggered by calcium-dependent phosphorylations and was confirmed in other tissues and species. The mechanisms controlling the phosphorylation status, the targeted amino acid residues and the reversibility seem to vary depending of the tissues and is discussed in this review. We currently do not know whether the phosphorylation of the same amino acid affects both aromatase and/or hydroxylase activities or whether these residues are different. These processes provide a new general mechanism by which local estrogen concentration can be rapidly altered in the brain and other tissues

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol

From July 1990 to March 1996, 112 children with stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) with up to 70% FAB L3-type blasts (n= 42) in the bone marrow without central nervous system (CNS) disease were treated on the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol (identical to the French LMB 84). The median age was 8.3 years. There were 81 boys and 31 girls. According to the extent of the primary disease, patients were sub-staged into three groups: IIIA with unresectable abdominal tumour (n= 39); IIIB with abdominal multiorgan involvement (n= 57) and IIIX with extra-abdominal primary lymphoma often presenting as pleural effusion (n= 16). Univariate and multivariate analyses were carried out to evaluate the prognostic significance of lactate dehydrogenase (LDH) level at diagnosis, the sub-stage and the time to achieve complete remission (CR). With a median follow up of 48 months (range 12–92), the overall and event free survival (EFS) is 87% (95% confidence interval (CI) 79.2–92.1%) and 83.7% (95% CI 76.3–89.2%) respectively. Six patients (5.4%) never achieved CR, of whom one is alive following high-dose therapy. Eight patients (7.1%) relapsed after achieving CR, three are alive after second-line therapy. There were three early toxic deaths (2.7%), mainly from infection, and one late death from a second cancer. There was no significant difference in EFS according to LDH level at diagnosis, the sub-stage or the time to CR. This study confirms the overall good prognosis and low rate of toxic deaths in patients with advanced B-NHL treated with this intensive regimen. No significant difference in EFS according to the sub-stage, the time to achieve CR or LDH level at diagnosis making it difficult to identify a group that should not receive intensive therapy. © 2000 Cancer Research Campaig

Optimizing outcomes for children with non-Hodgkin lymphoma in low- and middle-income countries by early correct diagnosis, reducing toxic death and preventing abandonment

In high-income countries, more than 90% of children with mature B-cell lymphomas are cured with frontline therapy. However, cure requires prompt and correct diagnosis, careful risk stratification, very intense chemotherapy and meticulous supportive care, together with logistical support for patients who live far from the cancer centre or face financial barriers to receiving care. In low- and middle-income countries (LMIC), cure rates range from 20% to 70% because of lack of diagnosis, misdiagnosis, abandonment of treatment, toxic death and excess relapse with reduced-intensity regimens. Fortunately, a wide range of successful interventions in LMIC have reduced these causes of avoidable treatment failure. Public awareness campaigns have led to societal awareness of childhood cancer; telepathology has improved diagnosis, even in remote areas; subsidized chemotherapy, transportation, housing and food have reduced abandonment; and hand hygiene, nurse training programmes and health system improvements have reduced toxic death. These interventions can be deployed everywhere and at low cost, so are highly scalable. Children and adolescents with Burkitt lymphoma can be cured in all countries by making a timely correct diagnosis, applying protocols adapted to the local context, preventing abandonment of therapy and avoiding toxic death. Reducing these causes of treatment failure is feasible and highly cost-effective everywhere.Fil: Chantada, Guillermo Luis. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lam, Catherine G.. St. Jude Children's Research Hospital; Estados UnidosFil: Howard, Scott C.. University of Tennessee; Estados Unido

Interrelationships among depression, anxiety, flourishing, and cannabis use in youth

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.addbeh.2018.10.007 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Aims The objective of the study was to examine if depression or anxiety was associated with youth cannabis use; and investigate whether flourishing moderates these associations. Methods Students (N = 8179) were recruited from 10 secondary schools (grade 9–12) in Ontario and British Columbia, Canada Self-report questionnaires were used to assess symptoms of depression [CESD-R-10], anxiety [GAD-7], flourishing [Deiner's Flourishing Scale] and cannabis consumption using measures that assess cannabis ever use and frequency of use. Logistic regression and product-term interactions were used to examine the associations between mental health and youth cannabis use, and the potential moderating effect(s) of flourishing. Results In our sample, 33% of participants had ever used cannabis, 51% and 38% reported elevated depressive and anxiety symptoms, respectively. Associations between depression, anxiety, and cannabis use were no longer significant when flourishing was added to the models. In addition, there was no evidence suggesting a moderating effect of flourishing as all interactions were not statistically significant. Instead, robust associations were found between flourishing and cannabis use: mental health and cannabis ever use, mental health and cannabis use frequency. Conclusions Indicators of mental wellbeing, such as flourishing, appear to be associated with a lower likelihood of cannabis use, even after controlling for depression and anxiety. Results suggest prevention strategies for youth cannabis use should aim to foster mental wellbeing among all youth, rather than exclusively targeting those experiencing mental health problems. Future longitudinal studies should test the sequential relationship between cannabis use and changes in both positive and negative mental health

Do weight perception and bullying victimization account for links between weight status and mental health among adolescents?

Background: The purpose of this study was to explore whether the way youth perceive their weight and their experiences of bullying victimization account for the increased risk of depression and anxiety symptoms, and poor psychosocial well-being, associated with overweight/obesity in a large sample of Canadian secondary school students. We also explored if associations differed by gender. Methods: We used cross-sectional survey data from year 7 (2018–19) of the COMPASS study. The sample included 57,059 students in grades 9–12 (Secondary III-V in Quebec) at 134 Canadian secondary schools (Alberta, British Columbia, Ontario, Quebec). First, multiple regression models tested associations between body mass index (BMI) classification and mental health outcomes (anxiety [GAD-7] and depression [CESD-10] symptoms, and psychosocial well-being [Diener’s Flourishing Scale]). Second, weight perception and bullying victimization were added to the models. Models were stratified by gender and controlled for sociodemographic covariates and school clustering. Results: When weight perception and bullying victimization were added to the models, obesity BMI status no longer predicted internalizing symptoms and flourishing scores relative to normal-weight BMIs. Students with ‘overweight’ or ‘underweight’ perceptions, and experiences of bullying victimization in the past month, reported higher anxiety and depressive symptomatology, and lower flourishing levels, in comparison to students with ‘about right’ weight perceptions and without experiences of bullying victimization, respectively, controlling for BMI status. Results were largely consistent across boys and girls. Conclusions: Results suggest perceptions of weight and experiences of bullying independently contribute to differences in mental health outcomes by weight status among youth. Continued efforts targeting weight-based bullying and weight bias, and the promotion of body size acceptance and positive body image, may help reduce the risk of mental illness and poor mental health among adolescents.Brock Library Open Access Publishing Fun

Etude préliminaire d’un virus hémadsorbant-hémagglutinant isolé d’une lésion de pneumonie du veau

Charton André, Faye P., Lecoanet Jean, Le Layec Cl., Patte F. Etude préliminaire d’un virus hémadsorbant-hémagglutinant, isolé d’une lésion de pneumonie du veau. In: Bulletin de l'Académie Vétérinaire de France tome 118 n°5, 1965. pp. 195-199

Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

School start time changes in the COMPASS study: associations with youth sleep duration, physical activity, and screen time

The final publication is available at Elsevier via https://doi.org/10.1016/j.sleep.2018.09.020� 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background To date, no longitudinal population-based studies of school start times have been conducted within Canada. School schedule changes provided an opportunity to examine start times in association with youth sleep, physical activity, and screen use over time. Methods This longitudinal study included grade 9�12 students attending 49 Ontario secondary schools that participated in at least two consecutive years of the COMPASS study (2012�2017). Fixed effects models tested whether differences in within-student change in self-reported sleep duration, moderate-to-vigorous physical activity, and screen time were associated with school start time changes, adjusting for student- (grade, sex, ethnicity, spending money) and school-level covariates (median income, urbanicity, geographical area). Results Thirteen start time changes of 5�10�min were reported. Ten-minute advances at earlier clock times (8:30 AM�8:20 AM; 8:40 AM�8:30 AM) were associated with steeper sleep duration declines than schools with consistent start times but had no effect at later times (9:00 AM�8:50 AM). While sleep change did not differ with 5-min�delays, 10-min�delays (8:50 AM�9:00 AM) were associated with additional sleep (23.7�min). Apart from one school that shifted from 8:30 AM to 8:35 AM, in which screen time and physical activity decreased more steeply, no effect was found for screen time, and 5-min�delays were associated with more physical activity (10.9�min) and advances with less activity (_8.0�min). Conclusions Results support start time delays as a valuable strategy to help ameliorate sleep debt among youth. Interference with physical activity or increased screen time appear unlikely with modest schedule changes. Potential adverse impacts on sleep require consideration with 10-min�advances.Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes [grant OOP-110788]Canadian Institutes of Health Research Institute of Population and Public Health [grant MOP-114875]Canadian Institutes of Health Research Project Grant [grant PJT-148562]Canadian Institutes of Health Research New Investigator Salary AwardCanadian Institutes of Health Research Doctoral Research Awar