Timescales for pluton growth, magma-chamber formation and super-eruptions.

Generation of silicic magmas leads to emplacement of granite plutons, huge explosive volcanic eruptions and physical and chemical zoning of continental and arc crust1-7. Whereas timescales for silicic magma generation in the deep and middle crust are prolonged8, magma transfer into the upper crust followed by eruption is episodic and can be rapid9-12. Ages of inherited zircons and sanidines from four Miocene ignimbrites in the Central Andes indicate a gap of 4.6 Myr between initiation of pluton emplacement and onset of super-eruptions, with a 1-Myr cyclicity. We show that inherited zircons and sanidine crystals were stored at temperatures <470 °C in these plutons before incorporation in ignimbrite magmas. Our observations can be explained by silicic melt segregation in a middle-crustal hot zone with episodic melt ascent from an unstable layer at the top of the zone with a timescale governed by the rheology of the upper crust. After thermal incubation of growing plutons, large upper-crustal magma chambers can form in a few thousand years or less by dike transport from the hot-zone melt layer. Instability and disruption of earlier plutonic rock occurred in a few decades or less just before or during super-eruptions.

Investigation of microglial diversity in a LRRK2 G2019S mouse model of Parkinson's disease.

Microglia contribute to the outcomes of various pathological conditions including Parkinson's disease (PD). Microglia are heterogenous, with a variety of states recently identified in aging and neurodegenerative disease models. Here, we delved into the diversity of microglia in a preclinical PD model featuring the G2019S mutation in LRRK2, a known pathological mutation associated with PD. Specifically, we investigated the 'dark microglia' (DM) and the 'disease-associated microglia' (DAM) which present a selective enrichment of CLEC7A expression. In the dorsal striatum - a region affected by PD pathology - extensive ultrastructural features of cellular stress as well as reduced direct cellular contacts, were observed for microglia from old LRRK2 G2019S mice versus controls. In addition, DM were more prevalent while CLEC7A-positive microglia had extensive phagocytic ultrastructural characteristics in the LRRK2 G2019S mice. Furthermore, our findings revealed a higher proportion of DM in LRRK2 G2019S mice, and an increased number of CLEC7A-positive cells with age, exacerbated by the pathological mutation. These CLEC7A-positive cells exhibited a selective enrichment of ameboid morphology and tended to cluster in the affected animals. In summary, we provide novel insights into the occurrence and features of recently defined microglial states, CLEC7A-positive cells and DM, in the context of LRRK2 G2019S PD pathology.

Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions.

The hippocampus is a plastic brain area that shows functional segregation along its longitudinal axis, reflected by a higher level of long-term potentiation (LTP) in the CA1 region of the dorsal hippocampus (DH) compared to the ventral hippocampus (VH), but the mechanisms underlying this difference remain elusive. Numerous studies have highlighted the importance of microglia-neuronal communication in modulating synaptic transmission and hippocampal plasticity, although its role in physiological contexts is still largely unknown. We characterized in depth the features of microglia in the two hippocampal poles and investigated their contribution to CA1 plasticity under physiological conditions. We unveiled the influence of microglia in differentially modulating the amplitude of LTP in the DH and VH, showing that minocycline or PLX5622 treatment reduced LTP amplitude in the DH, while increasing it in the VH. This was recapitulated in Cx3cr1 knockout mice, indicating that microglia have a key role in setting the conditions for plasticity processes in a region-specific manner, and that the CX3CL1-CX3CR1 pathway is a key element in determining the basal level of CA1 LTP in the two regions. The observed LTP differences at the two poles were associated with transcriptional changes in the expression of genes encoding for Il-1, Tnf-α, Il-6, and Bdnf, essential players of neuronal plasticity. Furthermore, microglia in the CA1 SR region showed an increase in soma and a more extensive arborization, an increased prevalence of immature lysosomes accompanied by an elevation in mRNA expression of phagocytic markers Mertk and Cd68 and a surge in the expression of microglial outward K+ currents in the VH compared to DH, suggesting a distinct basal phenotypic state of microglia across the two hippocampal poles. Overall, we characterized the molecular, morphological, ultrastructural, and functional profile of microglia at the two poles, suggesting that modifications in hippocampal subregions related to different microglial statuses can contribute to dissect the phenotypical aspects of many diseases in which microglia are known to be involved.

The patient advisor, an organizational resource as a lever for an enhanced oncology patient experience (PAROLE-onco): a longitudinal multiple case study protocol.

BACKGROUND: Quebec is one of the Canadian provinces with the highest rates of cancer incidence and prevalence. A study by the Rossy Cancer Network (RCN) of McGill university assessed six aspects of the patient experience among cancer patients and found that emotional support is the aspect most lacking. To improve this support, trained patient advisors (PAs) can be included as full-fledged members of the healthcare team, given that PA can rely on their knowledge with experiencing the disease and from using health and social care services to accompany cancer patients, they could help to round out the health and social care services offer in oncology. However, the feasibility of integrating PAs in clinical oncology teams has not been studied. In this multisite study, we will explore how to integrate PAs in clinical oncology teams and, under what conditions this can be successfully done. We aim to better understand effects of this PA intervention on patients, on the PAs themselves, the health and social care team, the administrators, and on the organization of services and to identify associated ethical and legal issues. METHODS/DESIGN: We will conduct six mixed methods longitudinal case studies. Qualitative data will be used to study the integration of the PAs into clinical oncology teams and to identify the factors that are facilitators and inhibitors of the process, the associated ethical and legal issues, and the challenges that the PAs experience. Quantitative data will be used to assess effects on patients, PAs and team members, if any, of the PA intervention. The results will be used to support oncology programs in the integration of PAs into their healthcare teams and to design a future randomized pragmatic trial to evaluate the impact of PAs as full-fledged members of clinical oncology teams on cancer patients' experience of emotional support throughout their care trajectory. DISCUSSION: This study will be the first to integrate PAs as full-fledged members of the clinical oncology team and to assess possible clinical and organizational level effects. Given the unique role of PAs, this study will complement the body of research on peer support and patient navigation. An additional innovative aspect of this study will be consideration of the ethical and legal issues at stake and how to address them in the health care organizations.

Glutamate-induced excitotoxicity in Parkinson's disease: The role of glial cells.

Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamate transmission efficiency depends on the correct functionality and expression of a plethora of receptors and transporters, located both on neurons and glial cells. Of note, glutamate reuptake by dedicated transporters prevents its accumulation at the synapse as well as non-physiological spillover. Indeed, extracellular glutamate increase causes aberrant synaptic signaling leading to neuronal excitotoxicity and death. Moreover, extrasynaptic glutamate diffusion is strongly associated with glia reaction and neuroinflammation. Glutamate-induced excitotoxicity is mainly linked to an impaired ability of glial cells to reuptake and respond to glutamate, then this is considered a common hallmark in many neurodegenerative diseases, including Parkinson's disease (PD). In this review, we discuss the function of astrocytes and microglia in glutamate homeostasis, focusing on how glial dysfunction causes glutamate-induced excitotoxicity leading to neurodegeneration in PD.

The ß-adrenoceptor blocker propranolol ameliorates compulsive-like gambling behaviour in a rodent slot machine task: implications for iatrogenic gambling disorder.

Previous work has shown that chronic administration of the dopamine D2/3 receptor agonist ropinirole invigorates performance on a rodent slot machine task (rSMT). This behavioural change appears superficially similar to the iatrogenic gambling disorder (GD) observed in a sub-set of patients with Parkinson's disease (PD), and has been associated with increased activation of the intra-cellular signalling proteins GSK3ß and CREB in the striatum. Here, we wanted to determine whether this response to ropinirole could be attenuated by targeting these signalling proteins, and if the loss of dopaminergic innervation characteristic of PD would alter ropinirole's effects on the rSMT. Male Long Evans rats were trained on the rSMT. Dopaminergic terminals innervating the dorsolateral striatum were then lesioned bilaterally using the neurotoxin 6-hydroxydopamine hydrochloride (6-OHDA). Subsequently animals were implanted with osmotic mini-pumps delivering ropinirole. Lastly, animals were given dietary lithium (Li+ ), to inhibit the activation of GSK3ß, or injections of the ß-adrenoceptor antagonist propranolol, which potently inhibits CREB as a secondary mechanism of action, and any changes in ropinirole-induced increases in compulsive-like engagement in the rSMT evaluated. Chronic ropinirole increased the number of trials animals completed, reproducing our original finding. This increase in task engagement was not altered in animals with 6-OHDA lesions, a putative model of early PD. In addition, the effects of ropinirole were not attenuated by administration of Li+ , but were ameliorated by propranolol. These data suggest that propranolol may represent a potential pharmacotherapy for the treatment of iatrogenic gambling.

Sources of variability in childhood obesity indicators and related behaviors.

The purpose of this study was to describe sources of variability in obesity-related variables in 6022 children aged 9-11 years from 12 countries. The study design involved recruitment of students, nested within schools, which were nested within study sites. Height, weight and waist circumference (WC) were measured and body mass index (BMI) was calculated; sleep duration and total and in-school moderate-to-vigorous physical activity (MVPA) and sedentary time were measured by accelerometry; and diet scores were obtained by questionnaire. Variance in most variables was largely explained at the student level: BMI (91.9%), WC (93.5%), sleep (75.3%), MVPA (72.5%), sedentary time (76.9%), healthy diet score (88.3%), unhealthy diet score (66.2%), with the exception of in-school MVPA (53.8%) and in-school sedentary time (25.1%). Variance explained at the school level ranged from 3.3% for BMI to 29.8% for in-school MVPA, and variance explained at the site level ranged from 3.2% for WC to 54.2% for in-school sedentary time. In general, more variance was explained at the school and site levels for behaviors than for anthropometric traits. Given the variance in obesity-related behaviors in primary school children explained at school and site levels, interventions that target policy and environmental changes may enhance obesity intervention efforts.

The short-term effects of a mass reach physical activity campaign: an evaluation using hierarchy of effects model and intention profiles.

BACKGROUND: Mass reach physical activity campaigns are designed to deliver physical-activity related messages to a large population across different media including print, television, radio, and websites. Few evaluations have examined the short-term effects of a mass reach campaign on participants who were engaged with the campaign. The current research examined the short-term effects of the ParticipACTION 150 Play List, a mass reach physical activity campaign, on participants who registered with the campaign website. METHODS: Participants (N = 7801) completed a registration questionnaire measuring demographic information, awareness and recall of physical activity and sport advertising, and self-reported number of activities tried or planned to try from the 150 Play List. A follow-up survey was completed by 1298 participants from the original sample. Additional questions assessed experience with the 150 Play List and attitudes towards campaign advertisements. RESULTS: Approximately 14.5% of participants cited the ParticipACTION 150 Play List and 23.6% mentioned a 'getting active' message when recalling advertisements. Those who named the 150 Play List or getting active reported more activities tried and more activities planned than those who did not. They were also more likely to say they had tried a new activity and planned ongoing participation. It was also found that participants with a disability were more likely to have tried a new activity compared to those not in a minority group. Other correlates of trying new activities at follow-up were younger age, more positive reported experience with the 150 Play List, and more favourable attitudes towards campaign advertisements. Those who did not intend continued participation, or who were unsure at baseline and then decided against continued participation at follow-up, reported they were less sedentary or encouraging others to be active. CONCLUSIONS: This research addresses the gap in evidence regarding the efficacy of mass reach physical activity campaigns by informing whether a year-long campaign like the 150 Play List can be effective in influencing the behavior of those engaged with the campaign. The results reinforce the idea that 'top of mind' awareness should be measured. Investigating intention profiles can help inform campaign impacts and continuation intentions.

Identifying poor metabolic adaptation during early lactation in dairy cows using cluster analysis.

Currently, cows with poor metabolic adaptation during early lactation, or poor metabolic adaptation syndrome (PMAS), are often identified based on detection of hyperketonemia. Unfortunately, elevated blood ketones do not manifest consistently with indications of PMAS. Expected indicators of PMAS include elevated liver enzymes and bilirubin, decreased rumen fill, reduced rumen contractions, and a decrease in milk production. Cows with PMAS typically are higher producing, older cows that are earlier in lactation and have greater body condition score at the start of lactation. It was our aim to evaluate commonly used measures of metabolic health (input variables) that were available [i.e., blood ß-hydroxybutyrate acid, milk fat:protein ratio, blood nonesterified fatty acids (NEFA)] to characterize PMAS. Bavarian farms (n = 26) with robotic milking systems were enrolled for weekly visits for an average of 6.7 wk. Physical examinations of the cows (5-50 d in milk) were performed by veterinarians during each visit, and blood and milk samples were collected. Resulting data included 790 observations from 312 cows (309 Simmental, 1 Red Holstein, 2 Holstein). Principal component analysis was conducted on the 3 input variables, followed by K-means cluster analysis of the first 2 orthogonal components. The 5 resulting clusters were then ascribed to low, intermediate, or high PMAS classes based on their degree of agreement with expected PMAS indicators and characteristics in comparison with other clusters. Results revealed that PMAS classes were most significantly associated with blood NEFA levels. Next, we evaluated NEFA values that classify observations into appropriate PMAS classes in this data set, which we called separation values. Our resulting NEFA separation values [<0.39 mmol/L (95% confidence limits = 0.360-0.410) to identify low PMAS observations and ≥0.7 mmol/L (95% confidence limits = 0.650-0.775) to identify high PMAS observations] were similar to values determined for Holsteins in conventional milking settings diagnosed with hyperketonemia and clinical symptoms such as anorexia and a reduction in milk yield, as reported in the literature. Future studies evaluating additional clinical and laboratory data, breeds, and milking systems are needed to validate these finding. The aim of future studies would be to build a PMAS prediction model to alert producers of cows needing attention and help evaluate on-farm metabolic health management at the herd level.

Can reflexivity be learned? An experience with tobacco control practitioners in Canada.

Summary: To explore an example of a reflexive intervention with health professionals working in tobacco control (TC). This study reports the perceived intervention effects regarding: (i) participants' understanding of reflexivity and personal learning and (ii) conditions needed in order to integrate reflexivity into professional and organizational practices. This is a qualitative study using an interpretative evaluation framework to assess the perceived effects of a reflexive intervention in Montréal, Québec. Semi-structured qualitative interviews (n = 8) gathered data. Data analysis began deductively, guided by the broad categories found in research questions. Sub-categories to populate these broad categories captured the inhibitors and facilitators through an inductive thematic analysis. Our study reveals that, following the intervention, most participants had a generally good understanding of reflexivity and described concrete learning in association with the intervention. Main facilitators and inhibitors to conducting a reflexive workshop pertained to the organizational context as well as to the professional and individual characteristics of the participants. Some participants implemented sustainable changes as a result of the intervention, such as creating a tool, reviewing work plans and developing new mechanisms to integrate the voice of their clientele in the planning process. The need and interest for dialogue among health professionals about how TC intervention activities may inadvertently contribute to social inequalities in smoking is apparent. While there appears to be potential for reflexive practice, the integration of reflexivity into practice is reliant upon the organizational context (financial and time constraints, culture, support, and climate) and the reflexivity concept itself (intangibility, complexity and fuzziness).

Associations between meeting combinations of 24-h movement guidelines and health-related quality of life in children from 12 countries.

OBJECTIVES: To examine whether meeting vs not meeting movement/non-movement guidelines (moderate-to-vigorous physical activity [MVPA], screen time, sleep duration), and combinations of these recommendations, are associated with health-related quality of life (HRQoL) in children from 12 countries in five major geographic regions of the world and explore whether the associations vary by study site. STUDY DESIGN: Observational, multinational cross-sectional study. METHODS: This study included 6106 children aged 9-11 years from sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. Participants completed the KIDSCREEN-10 to provide a global measure of their HRQoL. Sleep duration and MVPA were assessed using 24-h accelerometry. Screen time was assessed through self-report. Meeting the recommendations was defined as ≥60 min/day for MVPA, ≤2 h/day for screen time, and between 9 and 11 h/night for sleep duration. Age, sex, highest parental education, unhealthy diet pattern score, and body mass index z-score were included as covariates in statistical models. RESULTS: In the full sample, children meeting the screen time recommendation, the screen time + sleep recommendation, and all three recommendations had significantly better HRQoL than children not meeting any of these guidelines. Differences in HRQoL scores between sites were also found within combinations of movement/non-movement behaviors. For example, while children in Australia, Canada, and USA self-reported better HRQoL when meeting all three recommendations, children in Kenya and Portugal reported significantly lower HRQoL when meeting all three recommendations (relative to not meeting any). CONCLUSIONS: Self-reported HRQoL is generally higher when children meet established movement/non-movement recommendations. However, differences between study sites also suggest that interventions aimed at improving lifestyle behaviors and HRQoL should be locally and culturally adapted.

Comparison of ActiGraph GT3X+ and Actical accelerometer data in 9-11-year-old Canadian children.

Accelerometry is the gold standard for field-based physical activity assessment in children; however, the plethora of devices, data reduction procedures, and cut-points available limits comparability between studies. This study aimed to compare physical activity variables from the ActiGraph GT3X+ and Actical accelerometers in children under free-living conditions. A cross-sectional study of 379 children aged 9-11 years from Ottawa (Canada) was conducted. Children wore the ActiGraph GT3X+ and Actical accelerometers on the hip simultaneously for 7 consecutive days (24-h protocol). Moderate-to-vigorous (MVPA), vigorous (VPA), moderate (MPA), and light (LPA) physical activity, as well as sedentary time, (SED) were derived using established data reduction protocols. Excellent agreement between devices was observed for MVPA (ICC = 0.73-0.80), with fair to good agreement for MPA, LPA and SED, and poor agreement for VPA. Bland-Altman plots showed excellent agreement for MVPA, LPA, and SED, adequate agreement for MPA, and poor agreement for VPA. MVPA derived from the Actical was 11.7% lower than the ActiGraph GT3X+. The ActiGraph GT3X+ and Actical are comparable for measuring children's MVPA. However, comparison between devices for VPA, MPA, LPA, and SED are highly dependent on data reduction procedures and cut-points, and should be interpreted with caution.

Chloral hydrate for sedation of children with asthma during dental treatment.

AIM: We hypothesised that chloral hydrate is safe and effective for sedation during dental treatments for children with mild asthma. We evaluated the safety and efficacy of chloral hydrate by measuring changes in heart rate (HR), transcutaneous oxygen saturation, (SpO2), asthma score, behaviour, types and frequency of adverse reactions associated with chloral hydrate were assessed throughout treatment. MATERIALS AND METHODS: Children (<10 years old) with mild asthma undergoing dental treatments received a single 65 mg/kg oral dose of chloral hydrate liquid 1 hour prior to treatment in an open label trial. Heart rate (HR), SpO2, asthma score, behaviour, types and frequency of adverse reactions associated with chloral hydrate were assessed throughout treatment. Asthma score was obtained before and after treatment. Thirty minutes after treatment, SpO2, HR, and level of consciousness was assessed. RESULTS: Twenty four children were enrolled and 92% (22/24) recovered from sedation without respiratory depression. Two experienced mild respiratory depression related to chloral hydrate. Asthma was not a contributing factor as they did not experience wheezing, cough, tachypnoea, or retractions. Inhaled nitrous oxide supplemented chloral hydrate sedation in 63% (15/24) children to achieve effective cooperation. Three children had a SpO2 <95% (2 during treatment, 1 during recovery). CONCLUSION: Chloral hydrate 65 mg/kg administered a as single oral dose appears to be safe with respect to disease exacerbation for children with mild asthma undergoing dental treatment. Due to ineffective sedation and mild respiratory depression associated with chloral hydrate, newer, easily titrated medications, such as midazolam, may offer advantages.

Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya.

Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization.

Overnight storage of whole blood: cooling and transporting blood at room temperature under extreme temperature conditions.

BACKGROUND AND OBJECTIVES: Many countries allow the overnight storage of whole blood (WB) at ambient temperature. Some countries, such as Canada, also require a rapid cooling of WB with an active cooling system. Given the significant operational constraints associated with current cooling systems, an alternative method for cooling and transporting WB at 20-24°C was evaluated. MATERIALS AND METHODS: Phase 22 cooling packs (TCP Reliable Inc., USA) were used in combination with vacuum-insulated panel (VIP) boxes. Temperature profiles of simulated WB units were studied in extreme temperatures (-35 and 40°C). The quality of blood components prepared using Phase 22 packs and CompoCool-WB (Fresenius HemoCare, Germany) was studied. RESULTS: Phase 22 packs reduced the temperature of simulated WB bags from 37 to 24°C in 1·7 ± 0·2 h. Used in combination with VIP boxes, Phase 22 packs maintain the temperature of bags between 20 and 24°C for 15 and 24 h, compared to 2 and 11 h with CompoCool-WB, when exposed at -35 and 40°C, respectively. The quality of platelet concentrates and plasma was comparable, regardless of the cooling system used. For red blood cell units, per cent haemolysis on day 42 was slightly higher in products prepared after cooling with Phase 22 packs compared to CompoCool-WB (0·33 ± 0·15% vs. 0·21 ± 0·06%; P < 0·05). CONCLUSIONS: Phase 22 packs combined with VIP boxes are an acceptable alternative to butane-1,4-diol cooling systems. This system allows blood manufacturers to transport WB to processing facilities in a broad range of environmental conditions.

Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase sigma.

Protein tyrosine phosphatase sigma (PTP-sigma, encoded by the Ptprs gene) is a member of the LAR subfamily of receptor-like protein tyrosine phosphatases that is highly expressed during mammalian embryonic development in the germinal cell layer lining the lateral ventricles of the developing brain, dorsal root ganglia, Rathke's pouch, olfactory epithelium, retina and developing lung and heart. On the basis of its expression and homology with the Drosophila melanogasterorthologues DPTP99 and DPTP100A (refs 5,6), which have roles in the targeting of axonal growth cones, we hypothesized that PTP-sigma may also have a modulating function in cell-cell interactions, as well as in axon guidance during mammalian embryogenesis. To investigate its function in vivo, we generated Ptprs-deficient mice. The resulting Ptprs-/-animals display retarded growth, increased neonatal mortality, hyposmia and hypofecundity. Anatomical and histological analyses showed a decrease in overall brain size with a severe depletion of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cells in Ptprs-/- hypothalamus. Ptprs-/- mice have an enlarged intermediate pituitary lobe, but smaller anterior and posterior lobes. These results suggest that tyrosine phosphorylation-dependent signalling pathways regulated by PTP-sigma influence the proliferation and/or adhesiveness of various cell types in the developing hypothalamo-pituitary axis.

Nurse Preceptors' Experiences of an Online Strength-Based Nursing Course in Clinical Teaching.

Background: Online educational programs for nurse preceptors have been created based on various theoretical frameworks; however, no programs using a Strengths-Based Nursing (SBN) approach could be located. Purpose: This qualitative descriptive study explored the nurse preceptors' experiences in using a SBN approach to provide clinical teaching to nursing students after completing an online SBN clinical teaching course. Methods: Semi-structured interviews were conducted with six nurses. Data was thematically analyzed. Findings: Although their levels of familiarity with SBN varied, all preceptors acknowledged that using a SBN approach in clinical teaching benefits both students and educators. They reported that it empowered students and that it allowed them to discover their strengths. Getting to know their students helped the preceptors provide tailored learning experiences and feedback. Using the SBN approach simultaneously enhanced the preceptors' self-confidence and created opportunities for shared learning. Conclusion: Using a strengths' approach offers nurse preceptors a powerful tool to facilitate student learning and skills development in clinical practice.

Brother of CDO (BOC) expression in equine articular cartilage.

Brother of CDO (BOC) is a cell surface receptor that derives its name from the structurally related protein, cell adhesion molecule-related/down-regulated by oncogenes (CDO, sometimes CDON). High levels of BOC mRNA and protein expression have been described in embryonic tissues with active cell proliferation and ongoing cellular differentiation(1,2). A microarray-based screen of RNA isolated from 11 different adult equine tissues unexpectedly identified BOC as having an expression pattern restricted to articular cartilage. The objective of this study was to further investigate BOC expression in adult articular cartilage relative to other tissues. Both RT-qPCR and mRNA sequencing confirmed the microarray data. Steady state BOC mRNA levels in articular cartilage were substantially higher than in the other adult tissues tested, neonatal tendon, placenta, and whole embryo. The expression of BOC displayed a pattern of tissue specificity comparable to well established cartilage matrix protein biomarkers. BOC mRNA levels in articular cartilage increased with age, but were rapidly down-regulated when chondrocytes were enzymatically isolated from the cartilage matrix and expanded in monolayer culture. Relative expression patterns of CDO were broadly similar, but displayed lower fold change differences. A functional role in articular cartilage that involves Hedgehog signaling is suggested by the known binding affinity of BOC for all three Hedgehog ligands. These data also extend BOC and CDO biology to a post-mitotic and highly differentiated cell type within a mature tissue.

The effect of smoking cessation counselling in pregnant women: a meta-analysis of randomised controlled trials.

BACKGROUND: Pregnant smokers are often prescribed counselling as part of multicomponent cessation interventions. However, the isolated effect of counselling in this population remains unclear, and individual randomised controlled trials (RCTs) are inconclusive. OBJECTIVE: To conduct a meta-analysis of RCTs examining counselling in pregnant smokers. SEARCH STRATEGY: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline and PsycINFO databases for RCTs evaluating smoking cessation counselling. SELECTION CRITERIA: We included RCTs conducted in pregnant women in which the effect of counselling could be isolated and those that reported biochemically validated abstinence at 6 or 12 months after the target quit date. DATA COLLECTION AND ANALYSIS: Overall estimates were derived using random effects meta-analysis models. MAIN RESULTS: Our search identified eight RCTs (n = 3290 women), all of which examined abstinence at 6 months. The proportion of women that remained abstinent at the end of follow up was modest, ranging from 4 to 24% among those randomised to counselling and from 2 to 21% among control women. The absolute difference in abstinence reached a maximum of only 4%. Summary estimates are inconclusive because of wide confidence intervals, albeit with little evidence to suggest that counselling is efficacious at promoting abstinence (odds ratio 1.08, 95% confidence interval 0.84-1.40). There was no evidence to suggest that efficacy differed by counselling type. CONCLUSIONS: Available data from RCTs examining the isolated effect of smoking cessation counselling in pregnant women are limited but sufficient to rule out large treatment effects. Future RCTs should examine pharmacological therapies in this population.