A predicted dimer-based polymorph of 10,11-dihydrocarbamazepine (Form IV)

A novel polymorph of 10,11-dihydrocarbamazepine (form IV), which had been predicted to be thermodynamically feasible, was obtained from the vapour phase and displays an R22(8) hydrogen bonded dimer motif in contrast to the catemeric motifs in forms I–III

Root-Associated Streptomyces Isolates Harboring melC Genes Demonstrate Enhanced Plant Colonization

Streptomycetaceae assemble into the internal, root endophytic compartment of a wide variety of plants grown in soils worldwide, suggesting their ability to survive during root microbiome assembly. A previous study found that among four nonpathogenic, root-isolated Streptomyces strains (303, 299, CL18, and 136), only 303 and 299 colonized endophytic root tissue of the majority of Arabidopsis thaliana roots when inoculated with 34 other bacterial isolates. Here we demonstrate that 303 and 299 also colonize significantly more in singly inoculated A. thaliana seedlings. The genomes of melanin-producing 303 and 299 each contain two copies of the gene encoding tyrosinase (melC2 and melD2), an enzyme necessary for melanin biosynthesis in Streptomyces. These genes were not found in the genomes of 136 or CL18. Tyrosinase activity was detected in 303 and 299 whole cell and supernatant protein extracts, suggesting functional intracellular and extracellular enzymes.. Because tyrosinase oxidizes phenolic compounds and Streptomyces colonization of A. thaliana appears to be influenced by the phenolic compound salicylic acid (SA), we measured direct sensitivity of Streptomyces isolates to the phenolic compounds catechol, ferulic acid (FA), and SA in vitro. While both 303 and 299 showed higher numbers of surviving colonies than CL18 and 136 in the presence of catechol, only 303 demonstrated a higher number of surviving colonies when isolates were challenges with FA and SA. Finally, when seedlings were singly inoculated with a collection of related plant-associated Streptomyces isolates, colonization was significantly higher in isolates possessing two tyrosinase gene copies than isolates with zero or one gene copy. Overall, we describe a connection between microbial tyrosinase activity and increased seedling colonization of nonpathogenic Streptomyces isolates in A. thaliana. We propose tyrosinase activity in Streptomyces partially protects against harmful plant-produced phenolic compounds as they transition into an endophytic lifestyle

EnROL: A multicentre randomised trial of conventional versus laparoscopic surgery for colorectal cancer within an enhanced recovery programme

BACKGROUND: During the last two decades the use of laparoscopic resection and a multimodal approach known as an enhanced recovery programme, have been major changes in colorectal perioperative care. Clinical outcome improves using laparoscopic surgery to resect colorectal cancer but until recently no multicentre trial evidence had been reported regarding whether the benefits of laparoscopy still exist when open surgery is optimized within an enhanced recovery programme. The EnROL trial (Enhanced Recovery Open versus Laparoscopic) examines the hypothesis that laparoscopic surgery within an enhanced recovery programme will provide superior postoperative outcomes when compared to conventional open resection of colorectal cancer within the same programme. METHODS/DESIGN: EnROL is a phase III, multicentre, randomised trial of laparoscopic versus open resection of colon and rectal cancer with blinding of patients and outcome observers to the treatment allocation for the first 7 days post-operatively, or until discharge if earlier. 202 patients will be recruited at approximately 12 UK hospitals and randomised using minimization at a central computer system in a 1:1 ratio. Recruiting surgeons will previously have performed >100 laparoscopic colorectal resections and >50 open total mesorectal excisions to minimize conversion. Eligible patients are those suitable for elective resection using either technique. Excluded patients include: those with acute intestinal obstruction and patients in whom conversion from laparoscopic to open procedure is likely. The primary outcome is physical fatigue as measured by the physical fatigue domain of the multidimensional fatigue inventory 20 (MFI-20) with secondary outcomes including postoperative hospital stay; complications; reoperation and readmission; quality of life indicators; cosmetic assessments; standardized performance indicators; health economic analysis; the other four domains of the MFI-20. Pathological assessment of surgical quality will also be undertaken and compliance with the enhanced recovery programme will be recorded for all patients. DISCUSSION: Should this trial demonstrate that laparoscopic surgery confers a significant clinical and/or health economic benefit this will further support the transition to this type of surgery, with implications for the training of surgeons and resource allocation. TRIAL REGISTRATION: ISRCTN48516968

Clinical teaching: An evidence-based guide to best practices from the Council of Emergency Medicine Residency Directors

Clinical teaching is the primary educational tool use to train learners from day one of medical school all the way to the completion of fellowship. However, concerns over time constraints and patient census have led to a decline in bedside teaching. This paper provides a critical review of the literature on clinical teaching with a focus on instructor teaching strategies, clinical teaching models, and suggestions for incorporating technology. Recommendations for instructor-related teaching factors include adequate preparation, awareness of effective teacher attributes, using evidence-based-knowledge dissemination strategies, ensuring good communication, and consideration of environmental factors. Proposed recommendations for potential teaching strategies include the Socratic method, the One-Minute Preceptor model, SNAPPS, ED STAT, teaching scripts, and bedside presentation rounds. Additionally, this article will suggest approaches to incorporating technology into clinical teaching, including just-in-time training, simulation, and telemedical teaching. This paper provides readers with strategies and techniques for improving clinical teaching effectiveness

AMP-activated protein kinase complexes containing the β2 regulatory subunit are upregulated during and contribute to adipogenesis

AMP-activated protein kinase (AMPK) is a heterotrimer of α catalytic and β and γ regulatory subunits that acts to regulate cellular and whole-body nutrient metabolism. The key role of AMPK in sensing energy status has led to significant interest in AMPK as a therapeutic target for dysfunctional metabolism in type 2 diabetes, insulin resistance and obesity. Despite the actions of AMPK in liver and skeletal muscle being extensively studied, the role of AMPK in adipose tissue and adipocytes remains less well characterised. Small molecules that selectively influence AMPK heterotrimers containing specific AMPKβ subunit isoforms have been developed, including MT47-100, which selectively inhibits complexes containing AMPKβ2. AMPKβ1 and AMPKβ2 are the principal AMPKβ subunit isoforms in rodent liver and skeletal muscle respectively, yet the contribution of specific AMPKβ isoforms to adipose tissue function, however, remains largely unknown. This study therefore sought to determine the contribution of AMPKβ subunit isoforms to adipocyte biology, focussing on adipogenesis. AMPKβ2 was the principal AMPKβ isoform in 3T3-L1 adipocytes, isolated rodent adipocytes and human subcutaneous adipose tissue, as assessed by the contribution to total cellular AMPK activity. Downregulation of AMPKβ2 with siRNA inhibited lipid accumulation, cellular adiponectin levels and adiponectin secretion during 3T3-L1 adipogenesis, whereas downregulation of AMPKβ1 had no effect. Incubation of 3T3-L1 cells with MT47-100 selectively inhibited AMPK complexes containing AMPKβ2 whilst simultaneously inhibiting cellular lipid accumulation as well as cellular levels and secretion of adiponectin. Taken together, these data indicate that increased expression of AMPKβ2 is an important feature of efficient adipogenesis

School-based physical activity intervention for older adolescents: rationale and study protocol for the Burn 2 Learn cluster randomised controlled trial

Introduction This trial aims to investigate the impact of a school-based physical activity programme, involving high-intensity interval training (HIIT), on the physical, mental and cognitive health of senior school students. Methods and analysis The Burn 2 Learn (B2L) intervention will be evaluated using a two-arm parallel group cluster randomised controlled trial with allocation occurring at the school level (to treatment or wait-list control). Schools will be recruited in two cohorts from New South Wales, Australia. The trial will aim to recruit ∼720 senior school students (aged 16-18 years) from 20 secondary schools (ie, 10 schools per cohort). A range of implementation strategies will be provided to teachers (eg, training, equipment and support) to facilitate the delivery of HIIT sessions during scheduled classes. In phase I and II (3 months each), teachers will facilitate the delivery of at least two HIIT sessions/week during lesson-time. In phase III (6 months), students will be encouraged to complete sessions outside of lesson-time (teachers may continue to facilitate the delivery of B2L sessions during lesson-time). Study outcomes will be assessed at baseline, 6 months (primary end point) and 12 months. Cardiorespiratory fitness (shuttle run test) is the primary outcome. Secondary outcomes include: vigorous physical activity, muscular fitness, cognition and mental health. A subsample of students will (i) provide hair samples to determine their accumulated exposure to stressful events and (ii) undergo multimodal MRI to examine brain structure and function. A process evaluation will be conducted (ie, recruitment, retention, attendance and programme satisfaction)

Process evaluation of a school-based high-intensity interval training program for older adolescents : the Burn 2 Learn cluster randomised controlled trial

Process evaluations can help to optimise the implementation of school-based physical activity interventions. The purpose of this paper is to describe the process evaluation of a school-based high-intensity interval training (HIIT) program for older adolescent students, known as Burn 2 Learn (B2L). B2L was evaluated via a cluster randomised controlled trial in 20 secondary schools (10 intervention, 10 control) in New South Wales, Australia. Teachers (n = 22 (55% female)) from the 10 intervention schools, delivered the program over three phases (Phases 1 and 2, 6 months; Phase 3, 6 months) to older adolescent students (n = 337 (50% female); mean ± standard deviation (SD) age = 16.0 ± 0.4 years). Process evaluation data were collected across the 12-month study period. Teachers delivered 2.0 ± 0.8 and 1.7 ± 0.6 sessions/week in Phases 1 and 2 respectively (mean total 25.9 ± 5.2), but only 0.6 ± 0.7 sessions/week in Phase 3. Observational data showed that session quality was high, however heart rate (HR) data indicated that only half of the students reached the prescribed threshold of ≥85% predicted HRmax during sessions. Over 80% of teachers reported they intended to deliver the B2L program to future student cohorts. Almost 70% of students indicated they intended to participate in HIIT in the future. Teachers considered the program to be adaptable, and both students and teachers were satisfied with the intervention. B2L was implemented with moderate-to-high fidelity in Phases 1 and 2, but low in Phase 3. Our findings add to the relatively scant process evaluation literature focused on the delivery of school-based physical activity programs

Feasibility of a school-based physical activity intervention for adolescents with disability

Background: Adolescents with disability are less active and have lower levels of physical fitness than their typically developing peers. Schools are ideal settings to address this; however, few school-based interventions have been designed and evaluated among this group. Therefore, the aim of this pilot study was to determine the feasibility of a time-efficient school-based physical activity intervention for adolescents with disability. Methods: A non-randomized pilot trial was conducted with adolescents in the special education unit at one secondary school in New South Wales, Australia. Sixteen grade 11 and 12 students (aged 17.3 ± 0.7 years) participated in the 2-month physical activity intervention. Two classroom teachers were trained to facilitate the delivery of a high-intensity interval training (HIIT) program, known as Burn 2 Learn adapted (B2La). Teachers were asked to deliver 2–3 weekly HIIT sessions for a period of 2 months. Four domains of feasibility (acceptability, implementation, adaptability, and practicality) were assessed using quantitative measures at the student and teacher levels (e.g., observations, process evaluation questionnaires, and heart rate [HR] monitoring). Data were also collected from three learning and support teachers who assisted classroom teachers with intervention delivery. Preliminary efficacy of the intervention on measures of adolescents’ functional capacity (6-min walk/run test) and muscular fitness (sit-to-stand test and modified push-up test) were analyzed using paired sample t-tests. Results: Moderate-to-high levels of program satisfaction were reported by both students (80% rated “Good” or “Excellent”) and teachers (100% rated “Good” or “Excellent”). Teachers reported delivering 2.5 ± 0.7 sessions per week during the study. Based on researcher session observations, the program was delivered effectively by teachers (14/20). However, HR data indicated session intensity was lower than intended. The program was considered “adaptable” by teachers, with several observed modifications to HIIT sessions to cater for the needs of adolescents with disability. No adverse events were reported. We observed improvements in preliminary efficacy measures. Conclusions: Our findings suggest it is feasible to train teachers to deliver a school-based HIIT program for adolescents with disability. Evaluation of B2La within a larger-scale effectiveness trial is warranted

Understanding Cultivar-Specificity and Soil Determinants of the <i>Cannabis</i> Microbiome

Understanding microbial partnerships with the medicinally and economically important crop Cannabis has the potential to affect agricultural practice by improving plant fitness and production yield. Furthermore, Cannabis presents an interesting model to explore plant-microbiome interactions as it produces numerous secondary metabolic compounds. Here we present the first description of the endorhiza-, rhizosphere-, and bulk soil-associated microbiome of five distinct Cannabis cultivars. Bacterial communities of the endorhiza showed significant cultivar-specificity. When controlling cultivar and soil type the microbial community structure was significantly different between plant cultivars, soil types, and between the endorhiza, rhizosphere and soil. The influence of soil type, plant cultivar and sample type differentiation on the microbial community structure provides support for a previously published two-tier selection model, whereby community composition across sample types is determined mainly by soil type, while community structure within endorhiza samples is determined mainly by host cultivar.</p