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Objective: In this study, we took advantage of a natural experiment that occurred within a substance use disorders (SUD) treatment setting which first saw the implementation of an evidence-based practice (EBP) for tobacco cessation, followed by the implementation of a tobacco-free policy (TFP) that included a campus-wide tobacco ban. We sought to examine how implementation of the EBP and TFP was associated with substances use outcomes, in addition to tobacco use, up to 3-months posttreatment., Methods: Data were collected from patients in a substance use disorders treatment program at baseline, discharge, 1-, and 3-months posttreatment. Using a quasi-experimental design and generalized estimating equations, we modelled how patients' (N = 480) exposure to one of 3 interventions (1: treatment as usual [TAU], 2: EBP, and 3: EBP + TFP) was associated with overall abstinence from tobacco, alcohol, and other substances over time. Measures of tobacco use frequency, amount, and quit attempts were also modelled among a sub-sample of participants who self-reported using tobacco before treatment., Result: Exposure to the EBP + TFP was associated with increased tobacco abstinence (odds ratio [OR] = 1.93, 95% confidence interval [CI] [1.29, 2.90]) over time, including decreases in tobacco use frequency (OR = 0.78, 95% CI [0.68, 0.89]) and amount (OR = 0.80, 95% CI [0.67, 0.96]), and increased in likelihood of making a quit attempt (OR = 1.75, 95% CI [1.10, 2.80]) compared to TAU. Exposure was not associated with alcohol and/or other substance use., Conclusions: Comprehensive tobacco interventions that include EBP + TFP can promote tobacco cessation and reduced tobacco use following inpatient SUD treatment, without adversely affecting the use of other substances., Competing Interests: The authors report no conflicts of interest, (Copyright © 2020 American Society of Addiction Medicine.)

Canada legalized recreational cannabis use for adults on October 17, 2018 with decision-makers emphasising the need to reduce cannabis use among youth. We sought to characterise trends of youth cannabis use before and after cannabis legalization by relying on a quasi-experimental design evaluating cannabis use among high school students in Alberta, British Columbia, Ontario, and Québec who participated in the COMPASS prospective cohort study. Overall trends in use were examined using a large repeat cross-sectional sample (n = 102,685) at two time points before legalization (16/17 and 17/18 school years) and one after (18/19 school year). Further differential changes in use among students affected by legalization were examined using three sequential four-year longitudinal cohorts (n = 5,400) of students as they progressed through high school. Youth cannabis use remains common with ever-use increasing from 30.5% in 2016/17 to 32.4% in 2018/19. In the repeat cross-sectional sample, the odds of ever use in the year following legalization were 1.05 times those of the preceding year (p = 0.0090). In the longitudinal sample, no significant differences in trends of cannabis use over time were found between cohorts for any of the three use frequency metrics. Therefore, it appears that cannabis legalization has not yet been followed by pronounced changes on youth cannabis use. High prevalence of youth cannabis use in this sample remains a concern. These data suggest that the Cannabis Act has not yet led to the reduction in youth cannabis use envisioned in its public health approach., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Objective: Lymphoedema is a debilitating condition that results in the swelling of one or more limbs, leading to a significant impairment of mobility. From a psychosocial perspective, body image and quality of life (QoL) are also adversely affected. To date, non-cancer lymphoedema has been under-researched. The primary objectives of this study were to explore QoL and limb volume in patients with primary and secondary non-cancer-related lower limb lymphoedema during the intensive, maintenance and self-care phases of complex decongestive therapy over a 24-week period. Secondary objectives included exploring patients' experiences of living with lymphoedema and the challenges of self-care maintenance., Method: A sequential mixed methodology, using quantitative and qualitative methods, was used. The quantitative part of the study involved the use of tape measurements at 4cm intervals to ascertain limb volume alterations. Measurements were taken during the intensive phase at weeks 1, 2, 3 and 4; and during the maintenance phase at weeks 8, 16 and 24. QoL was measured using the lymphoedema QoL (LYMQOL) leg, at baseline and weeks 8 and 24. The qualitative part of the study involved the use of semi-structured interviews with patients at week 8. Interviews explored the experiences of patients living with lymphoedema and their experiences of complex decongestive therapy., Results: A total of 20 patients were recruited, two male and 18 female, with a mean age of 58.8 years (standard deviation (SD): 16 years), and all receiving complex decongestive therapy. At baseline, for all patients, the mean QoL score was 4.3 (SD: 2.4); and 8 (SD: 1.5) after 8 weeks of complex decongestive therapy. Mean difference was 4.00 (95% confidence interval: 2.76-5.24; p=0.00001) indicating a positive treatment effect. Limb volume measurements demonstrated a reduction in oedema from baseline to week 8. However, there were fluctuations in limb volume over the maintenance period of four months after treatment as the patients endeavoured to engage in self-care. Analysis of the interviews identified themes pertaining to lack of knowledge of lymphoedema among health professionals, a negative impact of living with lymphoedema and the positive therapeutic effect of complex decongestive therapy., Conclusion: Lower limb lymphoedema is a chronic condition that impacts negatively on the individual. Complex decongestive therapy improves QoL and reduces oedema. However, given the fluctuations in oedema post-treatment, individuals need greater support to maintain active engagement in effective self-care strategies.

Purpose: Clinicians need a broad spectrum measurement of psychoactive substance craving (i.e., alcohol and/or drug) to assess collective treatment effects, especially in the context of polysubstance use. In three separate studies, we investigated the psychometric properties of an adapted version of the Penn Alcohol Craving Scale (PACS), designed to measure broad range substance craving., Design: In Study One, we examined the latent factor structure for craving, as well as concurrent validity with measures of frequency and severity of substance use. In Study Two, we examined the short-term test-retest reliability. In Study Three, we examined the long-term sensitivity to treatment effects at 12 month postdischarge., Setting: An inpatient SUD program in Guelph, Ontario, Canada., Participants: Adult patients receiving treatment for SUD: Study One, n = 971; Study Two, n = 35; Study Three, n = 191., Measurements: We used an adapted version of the PACS, termed the Aggregated Drug Craving Scale (ADCS), and measures of substance use frequency, severity, and abstinence., Findings: In Study One, confirmatory factor analysis supported the unidimensional structure of the craving scale (CFI: 0.994, RMSEA: 0.071, SRMR: 0.010). In addition, statistically significant, medium effect size associations provided evidence of concurrent validity with measures of substance use frequency and severity (CFI = 0.992; RMSEA = 0.054; SRMR = 0.015). In Study Two, the ADCS demonstrated good agreement over two time points (ICC = 0.82), exhibiting acceptable short-term retest reliability. In Study 3, the mean craving score decreased significantly from 19.6 at baseline to 7.5 at 12-month follow-up (t = -18.48, p < 0.001), demonstrating an ability to detect long-term sensitivity to treatment effects (Cohen's d = -1.54)., Conclusions: Together, these findings provide initial support for a concise, broad-spectrum measure of aggregated drug cravings among an SUD treatment population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Climate change is having a significant impact on biodiversity and increasing attention is therefore being devoted to identifying the behavioral strategies that a species uses to cope with climatic stress. We explore how wild vervet monkeys (Chlorocebus pygerythrus) respond to heat stress, and how behavioral adaptations are used to regulate body temperature., Materials and Methods: We implanted wild vervet monkeys with temperature-sensitive data loggers and related the body temperature rhythms of these animals to their use of thermoregulatory behaviors., Results: Environmental temperature had a positive effect on the mean, minima and maxima of daily body temperatures. Environmental temperature had a positive effect on the amount of time that vervet monkeys spent in the shade, and animals that spent more time in the shade had lower body temperature maxima. Drinking water did not have a proximate effect on body temperature, most likely a consequence of their regular access to drinking water. Body temperatures were observed to decrease after swimming events, but tended to return to pre-swim temperatures within 1 hr, suggesting a limited thermal benefit of this behavior., Conclusions: Our data support the view that vervet monkeys cope well in the heat, and use behavior as a means to aid thermoregulation. The ability of primates to be flexible in their use of thermoregulatory behaviors can contribute positively to their capacity to cope with environmental variability. However, given its broad effect on plant productivity and habitat loss, climate change is a major threat to species' biogeographical distribution and survival., (© 2019 Wiley Periodicals, Inc.)

Purpose: Tobacco use is highly prevalent within addiction treatment settings, despite the potential benefits that cessation may provide to patients' psychosocial functioning and overall sobriety. Moreover, tobacco cessation is often insufficiently addressed in addiction treatment programs, although evidence suggests that tobacco control policies, such as access to evidence-based treatment or tobacco-free policies, may be effective. The objective of our study was to evaluate the impact of the implementation of these two tobacco control policies in an inpatient addiction treatment centre., Methods: Using a 3-group quasi-experimental design, we examined how the implementation of the Ottawa Model for Smoking Cessation (OMSC) and a subsequent campus-wide tobacco ban influenced patients' overall smoking status, frequency, amount used per day, and quit attempts during treatment, compared to usual care. Participants (N = 397) responded to a comprehensive questionnaire upon admission and discharge from an addiction treatment program. We used generalized linear mixed modelling to measure changes over time while accounting for relevant sociodemographic covariates., Results: Patients exposed to a more comprehensive tobacco control environment (i.e., the OMSC, plus complete tobacco ban) were over 80% less likely to report having used tobacco during treatment, compared to patients exposed to usual care (AOR = 0.17, 95% CI [0.05-0.63]). Receiving treatment in this setting also contributed to a 35% decrease in the average number of days patients used tobacco compared to usual care (AOR = 0.65, 95% CI [0.53-0.98]), and a 27% decrease in the average number of cigarettes used per day compared to usual care (AOR = 0.73, 95% CI [0.58-0.93])., Conclusion: Comprehensive tobacco control policy interventions within inpatient addiction treatment hospitals promote tobacco cessation. Such interventions should include a combination of evidence-based treatment for patients and environmental restrictions to discourage tobacco use. The results of our study suggest that, within inpatient addiction treatment settings, use of the OMSC in combination with a campus-wide tobacco ban may be more effective than usual care or the OMSC alone., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Continuing care is increasingly prioritized in the treatment of substance use disorders (SUDs). Ongoing engagement in continuing care, including mutual support (e.g., 12-step groups) and/or professional outpatient services, may enhance treatment outcomes and facilitate recovery., Objective: This study investigates how engagement in 12-step mutual support and professional outpatient services is associated with short-term substance use outcomes in a sample of patients who completed inpatient SUDs treatment., Methods: As part of the Recovery Journey Project - a longitudinal cohort study - participants completed questionnaires upon admission to an inpatient SUDs treatment program, and at 1- and/or 3-months post-discharge (n = 379). Baseline data were collected by self-administered, electronic questionnaires. Follow up data were collected by phone or email. Analyses involved multivariate Generalized Estimating Equations separately modelling self-reported abstinence and percent days abstinent (PDA) over the three time periods., Results: Overall, rates of self-reported abstinence and PDA increased significantly from baseline to 1- and 3-months follow up. Engagement in 12-step activities (i.e., attended 30 meetings in 30 days, had a home group, had a sponsor, did service work) and professional outpatient substance use support were each significantly associated with abstinence and PDA. Participants who reported a higher degree of 12-step involvement (defined as engagement in more 12-step activities) were also more likely to report being abstinence and greater PDA., Conclusions: Engagement in continuing care, including 12-step activities and professional outpatient substance use support, was highly associated with substance use. Clinical teams should encourage participation in such activities to optimize treatment outcomes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype-disease associations are largely unknown. HLA alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and fecal microbiome signatures. Whether these changes are the cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examined the effect of HLA-B27 and HLA-DRB1 RA risk alleles on the composition of the intestinal microbiome in healthy individuals., Methods: Five hundred sixty-eight stool and biopsy samples from 6 intestinal sites were collected from 107 healthy unrelated subjects, and stool samples were collected from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S ribosomal RNA bacterial marker gene. All subjects were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data., Results: Associations were observed between the overall microbial composition and both the HLA-B27 genotype and the HLA-DRB1 RA risk allele (P = 0.0002 and P = 0.00001, respectively). These associations were replicated using the stool samples from the TwinsUK cohort (P = 0.023 and P = 0.033, respectively)., Conclusion: This study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects of HLA-B27 and HLA-DRB1 on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome and suggest that therapies targeting the microbiome may be effective in preventing or treating these diseases., (© 2019, American College of Rheumatology.)

The hearts of smaller mammals tend to operate at higher mass-specific mechanical work rates than those of larger mammals. The ultrastructural characteristics of the heart that allow for such variation in work rate are still largely unknown. We have used perfusion-fixation, transmission electron microscopy and stereology to assess the morphology and anatomical aerobic power density of the heart as a function of body mass across six species of wild African antelope differing by approximately 20-fold in body mass. The survival of wild antelope, as prey animals, depends on competent cardiovascular performance. We found that relative heart mass (g kg -1 body mass) decreases with body mass according to a power equation with an exponent of -0.12±0.07 (±95% confidence interval). Likewise, capillary length density (km cm -3 of cardiomyocyte), mitochondrial volume density (fraction of cardiomyocyte) and mitochondrial inner membrane surface density (m 2  cm -3 of mitochondria) also decrease with body mass with exponents of -0.17±0.16, -0.06±0.05 and -0.07±0.05, respectively, trends likely to be associated with the greater mass-specific mechanical work rate of the heart in smaller antelope. Finally, we found proportionality between quantitative characteristics of a structure responsible for the delivery of oxygen (total capillary length) and those of a structure that ultimately uses that oxygen (total mitochondrial inner membrane surface area), which provides support for the economic principle of symmorphosis at the cellular level of the oxygen cascade in an aerobic organ., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Following publication of the original article [1] it came to the attention of the Production Editor that Figs. 1 and 2 had not been replaced with the newly revised figures supplied by the authors (the originals being unusable due to poor quality image and text).

Background: Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Here, we have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort., Results: Through the analysis of five separate colonies of T1D susceptible NOD mice, we identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse., Conclusions: These findings demonstrate for the first time that type 1 diabetes-associated genetic variants that restore immune tolerance to islet antigens also result in functional changes in the gut immune system and resultant changes in the microbiota.

Background: The key role played by research nurses in coordinating clinical trials in a paediatric setting has developed in line with increasing complexities of trial design. A questionnaire-based survey was conducted to investigate the training of research nurses involved in paediatric trials across Europe, to identify potential training needs and compare roles across specialties and countries., Methods: A structured, cross-sectional questionnaire survey was used, with the aim of describing and quantifying research nurse experiences. The questionnaire was designed to cover four main areas of interest: demographics, training, clinical trial experience and research nurse roles/activities., Results: The questionnaire was completed by 341 respondents across 45 different specialties in 20 European countries. A higher percentage of research nurses within 3 years of taking up post were dissatisfied with the level of training received (16%), as compared with those in post for 3-6 years (8%) and >6 years (6%). There was a trend towards a higher percentage of respondents receiving self-funded training in mainland Europe, with reported values of 15%-20%, as compared with <5% in the UK and Ireland. Only 3% of research nurses prescribed investigational medicinal products in a clinical trial setting, with contrasting roles observed between countries., Conclusions: While high levels of training satisfaction were observed, 67% of respondents felt they would benefit from additional training in line with frequently changing practices. Currently, low levels of nurse prescribing are observed in a paediatric clinical trial setting across Europe. Appropriate research nurse training programmes should be promoted through national networks across Europe., Competing Interests: Competing interests: None declared.

Objectives: Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthropathy. Inflammation in AS is poorly understood. TBX21 encodes T-bet, a transcription factor, lying within a locus with genome-wide significant association with AS. T-bet is implicated in innate and adaptive immunity. However, the role of T-bet in AS pathogenesis is unclear., Methods: We assessed the importance of T-bet in disease development and progression in peripheral blood mononuclear cells from 172 AS cases and 83 healthy controls carrying either risk or protective alleles of the peak AS-associated TBX21 single nucleotide polymorphism. Kinetics and localisation of T-bet expression in the SKG mouse model of spondyloarthropathy was examined, along with the impact of Tbx21 knockout on arthritis development in SKG mice., Results: Patients with AS had higher T-bet expression than healthy individuals, driven predominantly by natural killer and CD8+ T cells, with expression levels in CD8+ T cells completely distinguishing AS cases from healthy controls. T-bet expression was increased in AS cases carrying risk compared with protective alleles of rs11657479. In curdlan-treated SKG mice, T-bet expression increased early after disease initiation and persisted throughout the course of disease. There was marked reduction in gut and peripheral joint inflammation, and less IFNγ-producing and IL-17-producing CD8+ T cells, in Tbx21-/- compared with wild-type SKG mice., Conclusions: AS-associated variants in TBX21 influence T-bet expression. T-bet+ innate and adaptive immune cells have altered IL-17 and IFNγ, and early activation marker CD69 expression than T-bet cells. This indicates that T-bet is a major component of inflammatory pathways of spondyloarthropathy in humans and mice., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway. The AS-genetic associations point to involvement of gut mucosal immunity in driving disease, and metagenomic studies have provided strong support that AS is a disease driven by interaction between the gut microbiome and host immune system, providing a rationale for the exploration of gut-targeted therapies for the disease.

This study presents a structure-function analysis of the mammalian left ventricle and examines the performance of the cardiac capillary network, mitochondria, and myofibrils at rest and during simulated heavy exercise. Left ventricular external mechanical work rate was calculated from cardiac output and systemic mean arterial blood pressure in resting sheep (Ovis aries; n = 4) and goats (Capra hircus; n = 4) under mild sedation, followed by perfusion-fixation of the left ventricle and quantification of the cardiac capillary-tissue geometry and cardiomyocyte ultrastructure. The investigation was then extended to heavy exercise by increasing cardiac work according to published hemodynamics of sheep and goats performing sustained treadmill exercise. Left ventricular work rate averaged 0.017 W/cm 3 of tissue at rest and was estimated to increase to ∼0.060 W/cm 3 during heavy exercise. According to an oxygen transport model we applied to the left ventricular tissue, we predicted that oxygen consumption increases from 195 nmol O 2 ·s -1 ·cm -3 of tissue at rest to ∼600 nmol O 2 ·s -1 ·cm -3 during heavy exercise, which is within 90% of the oxygen demand rate and consistent with work remaining predominantly aerobic. Mitochondria represent 21-22% of cardiomyocyte volume and consume oxygen at a rate of 1,150 nmol O 2 ·s -1 ·cm -3 of mitochondria at rest and ∼3,600 nmol O 2 ·s -1 ·cm -3 during heavy exercise, which is within 80% of maximum in vitro rates and consistent with mitochondria operating near their functional limits. Myofibrils represent 65-66% of cardiomyocyte volume, and according to a Laplacian model of the left ventricular chamber, generate peak fiber tensions in the range of 50 to 70 kPa at rest and during heavy exercise, which is less than maximum tension of isolated cardiac tissue (120-140 kPa) and is explained by an apparent reserve capacity for tension development built into the left ventricle., (Copyright © 2016 the American Physiological Society.)

Culture independent techniques, such as shotgun metagenomics and 16S rRNA amplicon sequencing have dramatically changed the way we can examine microbial communities. Recently, changes in microbial community structure and dynamics have been associated with a growing list of human diseases. The identification and comparison of bacteria driving those changes requires the development of sound statistical tools, especially if microbial biomarkers are to be used in a clinical setting. We present mixMC, a novel multivariate data analysis framework for metagenomic biomarker discovery. mixMC accounts for the compositional nature of 16S data and enables detection of subtle differences when high inter-subject variability is present due to microbial sampling performed repeatedly on the same subjects, but in multiple habitats. Through data dimension reduction the multivariate methods provide insightful graphical visualisations to characterise each type of environment in a detailed manner. We applied mixMC to 16S microbiome studies focusing on multiple body sites in healthy individuals, compared our results with existing statistical tools and illustrated added value of using multivariate methodologies to fully characterise and compare microbial communities.

Humans and microbes have developed a symbiotic relationship over time, and alterations in this symbiotic relationship have been linked to several immune mediated diseases such as inflammatory bowel disease, type 1 diabetes and spondyloarthropathies. Improvements in sequencing technologies, coupled with a renaissance in 16S rRNA gene based community profiling, have enabled the characterization of microbiomes throughout the body including the gut. Improved characterization and understanding of the human gut microbiome means the gut flora is progressively being explored as a target for novel therapies including probiotics and faecal microbiota transplants. These innovative therapies are increasingly used for patients with debilitating conditions where conventional treatments have failed. This review discusses the current understanding of the interplay between host genetics and the gut microbiome in the pathogenesis of spondyloarthropathies, and how this may relate to potential therapies for these conditions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Ankylosing spondylitis (AS) is a common, highly heritable immune-mediated arthropathy that occurs in genetically susceptible individuals exposed to an unknown but likely ubiquitous environmental trigger. There is a close relationship between the gut and spondyloarthritis, as exemplified in patients with reactive arthritis, in whom a typically self-limiting arthropathy follows either a gastrointestinal or urogenital infection. Microbial involvement in AS has been suggested; however, no definitive link has been established. The aim of this study was to determine whether the gut in patients with AS carries a distinct microbial signature compared with that in the gut of healthy control subjects., Methods: Microbial profiles for terminal ileum biopsy specimens obtained from patients with recent-onset tumor necrosis factor antagonist-naive AS and from healthy control subjects were generated using culture-independent 16S ribosomal RNA gene sequencing and analysis techniques., Results: Our results showed that the terminal ileum microbial communities in patients with AS differ significantly (P < 0.001) from those in healthy control subjects, driven by a higher abundance of 5 families of bacteria (Lachnospiraceae [P = 0.001], Ruminococcaceae [P = 0.012], Rikenellaceae [P = 0.004], Porphyromonadaceae [P = 0.001], and Bacteroidaceae [P = 0.001]) and a decrease in the abundance of 2 families of bacteria (Veillonellaceae [P = 0.01] and Prevotellaceae [P = 0.004])., Conclusion: We show evidence for a discrete microbial signature in the terminal ileum of patients with AS compared with healthy control subjects. The microbial composition was demonstrated to correlate with disease status, and greater differences were observed between disease groups than within disease groups. These results are consistent with the hypothesis that genes associated with AS act, at least in part, through effects on the gut microbiome., (Copyright © 2015 by the American College of Rheumatology.)

Abstract We evaluated the effectiveness of a ketamine-medetomidine-midazolam drug combination administered intramuscularly by remote injection followed by isoflurane anesthesia in free-living aardvarks (Orycteropus afer). Seven aardvarks weighing 33-45 kg were immobilized to perform surgical implantation of temperature loggers using 3.8 mg/kg ketamine, 0.1 mg/kg medetomidine, and 0.25 mg/kg midazolam. Immobilized aardvarks were transported to a surgical theater and received 0.5-1% isoflurane in oxygen after tracheal intubation. After surgery, medetomidine was antagonized with 0.5 mg/kg atipamezole, and aardvarks were released at the site of capture. We recorded induction and recovery times, clinical and physiologic parameters, and conducted blood gas analyses before and during isoflurane administration. Aardvarks showed initial effects within 3 min and reached lateral recumbency within 7 min after drug administration. Heart rate (50-67 beats/min), respiratory rate (10-15 breaths/min), oxygen hemoglobin saturation (SaO2; 90-97%), and rectal temperature (34.0-37.5 C) were within acceptable physiologic ranges. Mean arterial blood pressure was initially high (146 ± 12 mmHg), but the hypertension resolved over time. Rectal temperature dropped significantly during anesthesia. Four animals had to be treated to relieve apnea. Blood gas analyses revealed mild to moderate hypercapnia but no hypoxaemia. The ketamine-medetomidine-midazolam combination provided effective immobilization. Combined with a low concentration of isoflurane, it can be used for prolonged surgical procedures in wild aardvarks. However, caution is needed, and monitoring of clinical parameters is required.

It is increasingly clear that the interaction between host and microbiome profoundly affects health. There are 10 times more bacteria in and on our bodies than the total of our own cells, and the human intestine contains approximately 100 trillion bacteria. Interrogation of microbial communities by using classic microbiology techniques offers a very restricted view of these communities, allowing us to see only what we can grow in isolation. However, recent advances in sequencing technologies have greatly facilitated systematic and comprehensive studies of the role of the microbiome in human health and disease. Comprehensive understanding of our microbiome will enhance understanding of disease pathogenesis, which in turn may lead to rationally targeted therapy for a number of conditions, including autoimmunity.

Unlabelled: Pharmacists may be effective health care practitioners to deliver smoking cessation interventions. This paper examines the short-term outcomes of smokers randomized to one of two models of a pharmacist-led smoking cessation intervention., Methods: An open-label pragmatic randomized trial compared two models of a pharmacist-led behavioral intervention [Group A (3-sessions) vs. Group B (1-session)] in conjunction with 5 weeks of nicotine replacement therapy (NRT). Ninety-eight pharmacies in Ontario, Canada delivered the intervention. Baseline demographic and smoking behavior data were recorded, as were intervention characteristics. Self-reported, 7-day point prevalence quit rates were obtained 5-week postintervention start date., Results: 6,987 individuals participated; 51.4% (n = 3588) randomized to Group A; 48.6% (n = 3399) to Group B. Approximately, 50% of Group A participants completed all three sessions. Quit rates were significantly higher among Group A, 3-session completers (27.7%; n = 478) compared to Group B participants (18.0%; n = 604). Multivariable results suggest that even when controlling for possible confounders and clustering across pharmacies, Group A participants who completed all three sessions were more likely to quit compared to Group B [OR = 1.72 (95% CI: 1.53, 1.94)]., Conclusions: Cessation outcomes are higher among participants completing three intervention sessions compared to one session; however, many do not return for follow-up sessions.

To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio of haPer1, haPer2, and haBmal1 mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO). We also calculated expression on the sides ipsilateral vs. contralateral (I/C) to the side of the suprachiasmatic nucleus (SCN) expressing higher haPer1. The extent of asymmetry in split hamsters varied between specific genes, phases, and organs. Although the magnitude of asymmetry in peripheral organs was never as great as that in the SCN, we observed significantly greater lateralization of clock gene expression in the adrenal medulla and cortex, lung, and skeletal muscle, but not in liver or kidney, of split hamsters than of unsplit controls. We observed fivefold lateralization of expression of the clock-controlled gene, albumin site D-element binding protein (Dbp), in skeletal muscle (H/L: 10.7 +/- 3.7 at 3 h vs. 2.2 +/- 0.3 at 0 h pAO; P = 0.03). Furthermore, tyrosine hydroxylase expression was asymmetrical in the adrenal medulla of split (H/L: 1.9 +/- 0.5 at 0 h) vs. unsplit hamsters (1.2 +/- 0.04; P < 0.05). Consistent with a model of neurally controlled gene expression, we found significant correlations between the phase angle between morning and evening components (psi(me)) and the level of asymmetry (H/L or I/C). Our results indicate that neural pathways contribute to, but cannot completely account for, SCN regulation of the phase of peripheral oscillators.

Homozygous tau mutant (tau(ss)) hamsters show an extremely short (20 h) circadian period (tau) that is attributable to altered enzymatic activity of casein kinase 1epsilon. It has been proposed that coupling of constituent circadian oscillators is strengthened in tau(ss) hamsters, explaining their tendency to show strong resetting after prolonged exposure to constant darkness. To evaluate further the circadian organization of tau(ss) hamsters, the authors assessed the extent of shortening of period as an aftereffect of exposure to light:dark cycles whose period (T) is 91% of tau and the ability of constant light to induce splitting. They find that tau(ss) hamsters show aftereffects comparable to wild types, indicating that normal CK1epsilon activity is not required for T cycles to shorten tau. This finding also contradicts the proposal that circadian period is homeostatically conserved. However, the authors find that tau(ss) hamsters rarely show splitting in constant light. Furthermore, LL does not induce lengthening of tau or reduction of activity duration (alpha) in these mutants. The authors' findings support the conclusion that the tau mutation alters the coupling between constituent circadian oscillators.

Objectives: To examine the salience of tobacco marketing on postsecondary campuses and student support for tobacco control policies., Methods: Face-to-face surveys were conducted with 1690 students at 3 universities in southwestern Ontario., Results: Virtually all (97%) students reported noticing tobacco marketing in the past year, and 35% reported noticing marketing on campus. There was strong support for smoke-free restrictions on campus, including restaurants and bars (82%), and for prohibitions on campus marketing. The presence of campus policies was associated with reduced exposure to marketing and increased policy support., Conclusions: There is strong support among students to remove tobacco marketing from campus and to introduce comprehensive smoke-free restrictions.

The purpose of the study was to determine the effect of ethyl vinyl chloride vapocoolant spray on pain reported by children undergoing intravenous cannulation. A randomized, double-blinded, placebo-controlled trial was conducted on eligible children between the ages of 9 and 18 years seen in a pediatric emergency department and requiring intravenous cannulation. Informed consent was obtained, and children were randomized to receive ethyl vinyl chloride spray, isopropyl alcohol spray, or no spray (control group). Patient demographics and information pertaining to each intravenous cannulation were recorded. Children indicated the degree of pain associated with intravenous cannulation on a 100-mm visual analog scale (VAS) compared to a baseline pain score of "zero." Statistical analysis was performed by using Stata version 7. One hundred twenty-seven subjects were enrolled: 37 received ethyl vinyl chloride vapocoolant spray, 48 received isopropyl alcohol spray (placebo), and 42 received no pretreatment. Mean VAS scores for pain experienced during cannulation were 34, 33, and 31 mL for each group, respectively. Ethyl vinyl chloride vapocoolant spray failed to measurably reduce pain associated with intravenous cannulation when compared to those pretreated with isopropyl alcohol spray or receiving no intervention.

Dental dams, although in existence for over 100 years, are the most widely underused tool of infection control. This article addresses the many benefits of using dental dams and discusses simplified methods of incorporating dams into the dental practice.