A randomized controlled trial of inhibitory control training for smoking cessation and reduction

This is the author accepted manuscript. The final version is available from the American Psychological Association via the DOI in this recordObjective: The high rates of illness and mortality associated with cigarette smoking necessitate the development of novel reduction and cessation treatments. Inhibitory control training (ICT) has recently emerged as a potentially efficacious intervention to reduce the consumption of alcohol and unhealthy food. This randomized controlled trial was the first to investigate the effect of Internet-delivered ICT on cigarette consumption in a community sample of heavy smokers. Method: For the present study, 107 adult smokers (mean age = 46.15 years; 57 female) who smoked a minimum of 10 cigarettes per day and met criteria for a moderate or severe tobacco use disorder were recruited. Participants were randomly allocated to receive go/no-go training in which either smoking stimuli (intervention) or nonsmoking stimuli (control) were paired with no-go signals and were instructed to complete 1 training session per day over a 2-week period. This trial was preregistered with the Australian and New Zealand Clinical Trials Registry (Trial ID: ACTRN12617000252314). Results: We found no significant differences between conditions on percentage of days abstinent or daily cigarette consumption, although there was a significant decrease in daily cigarette consumption across both conditions. Further, we found no significant moderating effects of impulsivity on the relationship between cigarette consumption and the 2 tasks. Conclusions: Although participants in both conditions reduced their daily cigarette consumption, the intervention task was no more successful than the control task was in achieving cigarette abstinence or reduction.Deakin Universit

A randomised controlled trial examining the efficacy of smoking-related response inhibition training in smokers: A study protocol

This is the final version. Available on open access from BMC via the DOI in this recordsAvailability of data and materials: The syntax and full analysis plan will be made available on the Open Science Framework and the dataset made available by contacting the first author.Background: Smoking is one of the leading preventable causes of illness and premature death worldwide. Despite a variety of effective treatments, relapse rates remain high, and novel, innovative interventions are needed in order to reduce the global prevalence of smoking. Research has indicated that deficits in the ability to inhibit a response (referred to as response inhibition) is a predictor of relapse and subsequently, targeting this potentially modifiable risk factor may lead to improvements in smoking outcomes. Indeed, in recent years, stimulus-specific response inhibition training has emerged as a potentially efficacious intervention to reduce unwanted/unhealthy behaviours such as alcohol and unhealthy food consumption. As such, the present trial is the first to evaluate the real-world efficacy of response inhibition smoking training (INST) in a sample of adult heavy smokers. Methods/design: This randomised controlled trial will recruit nicotine dependent smokers aged between 18 and 60 using social media and advertisements in Victoria, Australia. The sample target was 150 to account for drop out and non-adherence. Once informed consent has been obtained, participants complete a range of baseline measures during a face to face interview. Participants are randomly allocated to one of two online training conditions: an intervention training group (INST), which requires participants to exercise response inhibition towards smoking-related stimuli; or an active control group, which requires participants to exercise response inhibition towards household items and does not include any smoking-related stimuli. They complete the first training session during the interview to ensure the training protocol is clear. Both groups are instructed to complete a further 13 training sessions (1 per day) at home on their computer and follow-up phone calls will be conducted at three time points: post-intervention, one-month and three months. The primary outcomes are: a) rates of smoking cessation and; b) reduction in the quantity of average daily smoking at post-intervention, one and three months follow-up. Discussion: There is a pressing need to develop novel and innovative smoking interventions. If proven to be effective, INST could make a highly cost-effective contribution to improvements in smoking intervention outcomes. Trial registration: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry 17th February 2017. Trial ID: ACTRN12617000252314.Deakin Universit

Self-Assessment of Competence and Referral Behavior for Musculoskeletal Injections among Dutch General Practitioners.

General practitioners (GPs) are qualified and trained to administer therapeutic musculoskeletal injections when indicated. However, it is unknown to what extend Dutch GPs feel competent to administer these injections in clinical practice. Reluctance among GPs to inject might lead to unnecessary and costly referral to secondary care. An online and offline questionnaire was spread among Dutch GPs, querying demographics, GPs' self-assessment of injection competence, the number of administered/referred injections and management strategy for musculoskeletal injections. A total of 355 GPs responded. In total, 81% of the GPs considered themselves competent in administering musculoskeletal injections. Self-assessed incompetent GPs performed less injections the last month than self-assessed competent GPs (1.2 ± 1.4 vs 4.8 ± 4.6 injections, P < 0.001). Additionally, they referred four times more often to a colleague GP (0.4 ± 1.0 vs 0.1 ± 0.6 injections per month, P < 0.001) and twice as often to secondary care (1.0 ± 1.3 vs 0.5 ± 0.9 injections per month, P = 0.001). Self-assessed incompetence was associated with female sex (OR [95% CI] = 4.94 [2.39, 10.21]) and part-time work (OR [95% CI] = 2.58 [1.43, 4.66]). The most frequently addressed barriers were a lack of confidence in injection skills, lack of practical training, and uncertainty about the effectiveness and diagnosis of musculoskeletal injections. Although most GPs considered themselves competent to administer musculoskeletal injections, the referral rate to secondary care for several injections was strikingly high. To decrease secondary care referrals, addressing some of the most frequently indicated barriers is highly recommended

Mathematical modeling of the metastatic process

Mathematical modeling in cancer has been growing in popularity and impact since its inception in 1932. The first theoretical mathematical modeling in cancer research was focused on understanding tumor growth laws and has grown to include the competition between healthy and normal tissue, carcinogenesis, therapy and metastasis. It is the latter topic, metastasis, on which we will focus this short review, specifically discussing various computational and mathematical models of different portions of the metastatic process, including: the emergence of the metastatic phenotype, the timing and size distribution of metastases, the factors that influence the dormancy of micrometastases and patterns of spread from a given primary tumor.Comment: 24 pages, 6 figures, Revie

A randomised controlled trial of inhibitory control training for smoking cessation: Outcomes, mediators and methodological considerations.

This is the final version. Available from Frontiers Media via the DOI in this record. The datasets presented in this article are not readily available because the authors do not have ethics approval to make the dataset public. Requests to access the datasets should be directed to PS, [email protected]: Inhibitory control training (ICT) has shown promise for improving health behaviours, however, less is known about its mediators of effectiveness. The current paper reports whether ICT reduces smoking-related outcomes such as craving and nicotine dependence, increases motivation to quit and whether reductions in smoking or craving are mediated by response inhibition or a devaluation of smoking stimuli. Method: Adult smokers (minimum 10 cigarettes per day; N = 107, M age = 46.15 years, 57 female) were randomly allocated to receive 14 days of smoking-specific ICT (named INST; a go/no-go task where participants were trained to not respond to smoking stimuli) or active control training (participants inhibited responding toward neutral stimuli). Participants were followed up to 3-months post-intervention. This trial was preregistered (Australian and New Zealand Clinical Trials Registry ID: ACTRN12617000252314; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370204). Results: There were no significant differences between ICT and active control training groups. Specifically, participants in both groups showed significant reductions in craving, nicotine dependence, motivation and a devaluation (reduced evaluation) of smoking-stimuli up to 3-months follow-up compared to baseline. Inhibition and devaluation of smoking stimuli did not act as mediators. Devaluation of smoking stimuli was an independent predictor of smoking and craving at follow-up. Conclusion: Inhibitory control training (ICT) was no more effective at reducing smoking-related outcomes compared to the active control group, however, significant improvements in craving, dependence indicators and evaluation of smoking stimuli were observed across both groups. A return to basic experimental research may be required to understand the most effective ICT approach to support smoking cessation.Deakin Universit

Mesenchymal stem cell secretome reduces pain and prevents cartilage damage in a murine osteoarthritis model

Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an osteoarthritis (OA)-modifying treatment. MSCs secrete factors that can counteract inflammatory and catabolic processes and attract endogenous repair cells. The effects of intra-articular injection of MSC secretome on OA-related pain, cartilage damage, subchondral bone alterations and synovial inflammation were studied in a mouse collagenase-induced OA model. The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). 54 mice were randomly assigned to injections with i) MSC secretome from 20,000 MSCs, ii) 20,000 MSCs or iii) medium (control). Pain was assessed by hind limb weight distribution. Cartilage damage, subchondral bone volume and synovial inflammation were evaluated by histology. MSC-secretome- and MSC-injected mice showed pain reduction at day 7 when compared to control mice. Cartilage damage was more abundant in the control group as compared to healthy knees, a difference which was not found in knees treated with MSC secretome or MSCs. No effects were observed regarding synovial inflammation, subchondral bone volume or the presence of different macrophage subtypes. Injection of MSC secretome, similarly to injection of MSCs, resulted in early pain reduction and had a protective effect on the development of cartilage damage in a murine OA model. By using the regenerative capacities of the MSC-secreted factors, it will be possible to greatly enhance the standardisation, affordability and clinical translatability of the approach. This way, this biological therapy could evolve towards a true disease-modifying anti-osteoarthritic drug

Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice

<p>Abstract</p> <p>Background</p> <p>The current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of <it>Tinospora cordifolia </it>extract that are exerted on circulating macrophages isolated from CCl₄(0.5 ml/kg body weight) intoxicated male albino mice.</p> <p>Methods</p> <p>Apart from damaging the liver system, carbon tetrachloride also inhibits macrophage functions thus, creating an immunocompromised state, as is evident from the present study. Such cell functions include cell morphology, adhesion property, phagocytosis, enzyme release (myeloperoxidase or MPO), nitric oxide (NO) release, intracellular survival of ingested bacteria and DNA fragmentation in peritoneal macrophages isolated from these immunocompromised mice. <it>T. cordifolia </it>extract was tested for acute toxicity at the given dose (150 mg/kg body weight) by lactate dehydrogenase (LDH) assay.</p> <p>Results</p> <p>The number of morphologically altered macrophages was increased in mice exposed to CCl₄. Administration of CCl₄(i.p.) also reduced the phagocytosis, cell adhesion, MPO release, NO release properties of circulating macrophages of mice. The DNA fragmentation of peritoneal macrophages was observed to be higher in CCl₄intoxicated mice. The bacterial killing capacity of peritoneal macrophages was also adversely affected by CCl_4.However oral administration of aqueous fraction of <it>Tinospora cordifolia </it>stem parts at a dose of 40 mg/kg body weight (<it>in vivo</it>) in CCl₄exposed mice ameliorated the effect of CCl₄, as the percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity of CCl₄intoxicated peritoneal macrophages came closer to those of the control group. No acute toxicity was identified in oral administration of the aqueous extract of <it>Tinospora cordifolia </it>at a dose of 150 mg/kg body weight.</p> <p>Conclusion</p> <p>From our findings it can be suggested that, polar fractions of <it>Tinospora cordifolia </it>stem parts contain major bioactive compounds, which directly act on peritoneal macrophages and have been found to boost the non-specific host defenses of the immune system. However, the molecular mechanism of this activity of <it>Tinospora cordifolia </it>on immune functions needs to be elucidated.</p

Bone Marrow–Harvesting Technique Influences Functional Heterogeneity of Mesenchymal Stem/Stromal Cells and Cartilage Regeneration

Background: Connective tissue progenitors (CTPs) from native bone marrow (BM) or their culture-expanded progeny, often referred to as mesenchymal stem/stromal cells, represents a promising strategy for treatment of cartilage injuries. But the cartilage regeneration capacity of these cells remains unpredictable because of cell heterogeneity. Hypothesis: The harvest technique of BM may highly influence stem cell heterogeneity and, thus, cartilage formation because these cells have distinct spatial localization within BM from the same bone. Study Design: Controlled laboratory study. Methods: CTPs obtained from the femur of patients undergoing total hip replacement by 2 harvest techniques—BM aspiration and BM collection—after bone rasping were immunophenotyped by flow cytometry and evaluated for chondrogenic ability. The spatial localization of different CTP subsets in BM was verified by immunohistochemistry. Results: Cells from the BM after rasping were significantly more chondrogenic than the donor-matched aspirate, whereas no notable difference in their osteogenic or adipogenic potential was observed. The authors then assessed whether distinct immunophenotypically defined CTP subsets were responsible for the different chondrogenic capacity. Cells directly isolated from BM after rasping contained a higher percentage (mean, 7.2-fold) of CD45–CD2711CD561 CTPs as compared with BM aspirates. The presence of this subset in the harvested BM strongly correlated with chondrogenic ability, showing that CD2711CD561 cells are enriched in chondroprogenitors. Furthermore, evaluation of these CTP subsets in BM revealed that CD2711CD561 cells were localized in the bone-lining regions whereas CD2711CD56– cells were found in the perivascular regions. Since the iliac crest remains a frequent site of BM harvest for musculoskeletal regeneration, the authors also compared the spatial distribution of these subsets in trabeculae of femoral head and iliac crest and found CD2711CD561 bone-lining cells in both tissues. Conclusion: Chondrogenically distinct CTP subsets have distinct spatial localization in BM; hence, the harvest technique of BM determines the efficiency of cartilage formation. Clinical Relevance: The harvest technique of BM may be of major importance in determining the clinical success of BM mesenchymal stem/stromal cells in cartilage repair

Quality control and beam test of GEM detectors for future upgrades of the CMS muon high rate region at the LHC

Gas Electron Multipliers (GEM) are a proven position sensitive gas detector technology which nowadays is becoming more widely used in High Energy Physics. GEMs offer an excellent spatial resolution and a high particle rate capability, with a close to 100% detection efficiency. In view of the high luminosity phase of the CERN Large Hadron Collider, these aforementioned features make GEMs suitable candidates for the future upgrades of the Compact Muon Solenoid (CMS) detector. In particular, the CMS GEM Collaboration proposes to cover the high-eta region of the muon system with large-area triple-GEM detectors, which have the ability to provide robust and redundant tracking and triggering functions. In this contribution, after a general introduction and overview of the project, the construction of full-size trapezoidal triple-GEM prototypes will be described in more detail. The procedures for the quality control of the GEM foils, including gain uniformity measurements with an x-ray source will be presented. In the past few years, several CMS triple-GEM prototype detectors were operated with test beams at the CERN SPS. The results of these test beam campaigns will be summarised

Presence of HIF-1 and related genes in normal mucosa, adenomas and carcinomas of the colorectum

Expression of the transcription factor hypoxia-inducible factor 1 (HIF-1), which plays a key role in cellular adaptation to hypoxia, was investigated in normal colorectal mucosa (ten), adenomas (61), and carcinomas (23). Tissue samples were analyzed for HIF-1α, its upstream regulators, von Hippel–Lindau factor, AKT, and mammalian target of rapamycin (mTOR) and its downstream targets glucose transporter 1 (GLUT1), carbonic anhydrase IX, stromal-cell-derived factor 1 (SDF-1) by immunohistochemistry. In normal colorectal mucosa, HIF-1α was observed in almost all nuclei of surface epithelial cells, probably secondary to a gradient of oxygenation, as indicated by pimonidazole staining. The same staining pattern was present in 87% of adenomas. In carcinomas, HIF-1α was present predominantly around areas of necrosis (78%). Active AKT and mTOR, were present in all adenomas, carcinomas, and in normal colorectal mucosa. GLUT1 and SDF-1 were present in the normal surface epithelium of all adenoma cases, whereas in the carcinoma GLUT1 was located around necrotic regions and SDF-1 was present in all epithelial cells. In conclusion, HIF-1α appears to be physiologically expressed in the upper part of the colorectal mucosa. The present observations support that upregulation of HIF-1α and its downstream targets GLUT1 and SDF-1 in colorectal adenomas and carcinomas may be due to hypoxia, in close interaction with an active phosphatidylinositol 3-kinases–AKT–mTOR pathway