Granulocyte-Colony Stimulating Factor (G-CSF) Improves Motor Recovery in the Rat Impactor Model for Spinal Cord Injury

Granulocyte-colony stimulating factor (G-CSF) improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function

Fas/FasL-mediated apoptosis and inflammation are key features of acute human spinal cord injury: implications for translational, clinical application

The Fas/FasL system plays an important role in apoptosis, the inflammatory response and gliosis in a variety of neurologic disorders. A better understanding of these mechanisms could lead to effective therapeutic strategies following spinal cord injury (SCI). We explored these mechanisms by examining molecular changes in postmortem human spinal cord tissue from cases with acute and chronic SCI. Complementary studies were conducted using the in vivo Fejota™ clip compression model of SCI in Fas-deficient B6.MRL-Fas-lpr (lpr) and wild-type (Wt) mice to test Fas-mediated apoptosis, inflammation, gliosis and axonal degeneration by immunohistochemistry, Western blotting, gelatin zymography and ELISA with Mouse 32-plex cytokine/chemokine panel bead immunoassay. We report novel evidence that shows that Fas-mediated apoptosis of neurons and oligodendrocytes occurred in the injury epicenter in all cases of acute and subacute SCI and not in chronic SCI or in control cases. We also found significantly reduced apoptosis, expression of GFAP, NF-κB, p-IKappaB and iba1, increased number of CD4 positive T cells and MMP2 expression and reduced neurological dysfunction in lpr mice when compared with Wt mice after SCI. We found dramatically reduced inflammation and cytokines and chemokine expression in B6.MRL-Fas-lpr mice compared to Wt mice after SCI. In conclusion, we report multiple lines of evidence that Fas/FasL activation plays a pivotal role in mediating apoptosis, the inflammatory response and neurodegeneration after SCI, providing a compelling rationale for therapeutically targeting Fas in human SCI

Enhanced Functional Recovery in MRL/MpJ Mice after Spinal Cord Dorsal Hemisection

Adult MRL/MpJ mice have been shown to possess unique regeneration capabilities. They are able to heal an ear-punched hole or an injured heart with normal tissue architecture and without scar formation. Here we present functional and histological evidence for enhanced recovery following spinal cord injury (SCI) in MRL/MpJ mice. A control group (C57BL/6 mice) and MRL/MpJ mice underwent a dorsal hemisection at T9 (thoracic vertebra 9). Our data show that MRL/MpJ mice recovered motor function significantly faster and more completely. We observed enhanced regeneration of the corticospinal tract (CST). Furthermore, we observed a reduced astrocytic response and fewer micro-cavities at the injury site, which appear to create a more growth-permissive environment for the injured axons. Our data suggest that the reduced astrocytic response is in part due to a lower lesion-induced increase of cell proliferation post-SCI, and a reduced astrocytic differentiation of the proliferating cells. Interestingly, we also found an increased number of proliferating microglia, which could be involved in the MRL/MpJ spinal cord repair mechanisms. Finally, to evaluate the molecular basis of faster spinal cord repair, we examined the difference in gene expression changes in MRL/MpJ and C57BL/6 mice after SCI. Our microarray data support our histological findings and reveal a transcriptional profile associated with a more efficient spinal cord repair in MRL/MpJ mice

Alexithymia in juvenile primary headache sufferers: a pilot study

Starting in the 1990s, there has been accumulating evidence of alexithymic characteristics in adult patients with primary headache. Little research has been conducted, however, on the relationship between alexithymia and primary headache in developmental age. In their research on alexithymia in the formative years, the authors identified one of the most promising prospects for research, as discussed here. The aim of this study was to verify whether there is: (a) a link between tension-type headache and alexithymia in childhood and early adolescence; and (b) a correlation between alexithymia in children/preadolescents and their mothers. This study was based on an experimental group of 32 patients (26 females and 6 males, aged from 8 to 15 years, mean 11.2 ± 2.0) suffering from tension-type headache and 32 control subjects (26 females and 6 males, aged from 8 to 15 years, mean 11.8 ± 1.6). Tension-type headache was diagnosed by applying the International Headache Classification (ICHD-II, 2004). The alexithymic construct was measured using an Italian version of the Alexithymia Questionnaire for Children in the case of the juvenile patients and the Toronto Alexithymia Scale (TAS-20) for their mothers. Higher rates of alexithymia were observed in the children/preadolescents in the experimental group (EG) than in the control group; in the EG there was no significant correlation between the alexithymia rates in the children/preadolescents and in their mothers

Extent and correlates of self-reported exposure to tobacco advertising, promotion and sponsorship in smokers: Findings from the EUREST-PLUS ITC Europe Surveys

Introduction: Tobacco advertising, promotion and sponsorship (TAPS) are known to promote tobacco consumption and to discourage smoking cessation. Consequently, comprehensive TAPS bans are effective measures to reduce smoking. The objective of this study was to investigate to what extent smokers are exposed to TAPS in general, and in various media and localities, in different European countries. Methods: A cross-sectional analysis of national representative samples of adult smokers in 2016 from Germany, Greece, Hungary, Poland, Romania, and Spain (EUREST-PLUS Project, n=6011), as well as England (n=3503) and the Netherlands (n=1213) (ITC Europe Surveys) was conducted. Prevalence of self-reported TAPS exposure is reported by country, and socioeconomic correlates were investigated using logistic regression models. Results: Self-reported exposure to TAPS varied widely among the countries, from 15.4 % in Hungary to 69.2 % in the Netherlands. In most countries, tobacco advertising was most commonly seen at the point of sale, and rarely noticed in mass media. The multivariate analysis revealed some variation in exposure to TAPS by sociodemographic factors. Age showed the greatest consistency across countries with younger smokers (18–24 years) being more likely to notice TAPS than older smokers. Conclusions: TAPS exposure tended to be higher in countries with less restrictive regulation but was also reported in countries with more comprehensive bans, although at lower levels. The findings indicate the need for a comprehensive ban on TAPS to avoid a shift of marketing efforts to less regulated channels, and for stronger enforcement of existing bans

Patterns of tobacco use, quit attempts, readiness to quit and self-efficacy among smokers with anxiety or depression: Findings among six countries of the EUREST-PLUS ITC Europe Surveys

Introduction: We compared smoking behaviors, past quit attempts, readiness to quit and beliefs about quitting among current cigarette smokers with probable anxiety or depression (PAD) to those without PAD, from six European Union (EU) Member States (MS). Methods: A nationally representative cross-sectional sample of 6011 adult cigarette smokers from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) was randomly selected through a multistage cluster sampling design in 2016. Respondents were classified as having PAD based on self-reported current diagnosis or treatment for anxiety or depression, or a positive screen for major depression, according to a validated two-item instrument. Sociodemographic characteristics, patterns of tobacco use, past quitting, readiness to quit, self-efficacy and beliefs about quitting were assessed for patients with and without PAD. Logistic regression was used to examine predictors of PAD. All analyses were conducted using the complex samples package of SPSS. Results: Among smokers sampled, 21.0% (95% CI: 19.3–22.9) were identified as having PAD. Logistic regression analyses controlling for socioeconomic variables and cigarettes smoked per day found smokers with PAD were more likely to have made an attempt to quit smoking in the past (AOR=1.48; 95% CI: 1.25–1.74), made a quit attempt in the last 12 months (AOR=1.75; 95% CI: 1.45–2.11), and report lower self-efficacy with quitting (AOR=1.83; 95% CI: 1.44–2.32) compared to smokers without PAD. Additionally, it was found that individuals with PAD were more likely to report having received advice to quit from a doctor or health professional and having used quitline support as part of their last quit attempt. Conclusions: Smokers with PAD report a greater interest in quitting in the future and more frequent failed quit attempts than smokers without PAD; however, the high rates of untreated anxiety or depression, nicotine dependence, low confidence in the ability to quit, infrequent use of cessation methods, as well as socioeconomic factors may make quitting difficult

Smoking in public places in six European countries: Findings from the EUREST-PLUS ITC Europe Survey

Introduction: Surveillance of tobacco consumption in public places is an important measure to evaluate the impact of tobacco control interventions over time. The objective of this study was to estimate the prevalence of smoking as seen by smokers and their smoking behaviour in public places, in six European countries. Methods: We used baseline data of the International Tobacco Control Six European countries (ITC 6E) Survey, part of the EUREST-PLUS Project, conducted in 2016 in national representative samples of about 1000 adult smokers aged 18 years and older in Germany, Greece, Hungary, Poland, Romania and Spain. For each setting (workplaces, restaurants, bars/pubs and discos) participants were asked whether they had seen someone smoking during their last visit there and whether they too had smoked there. We report the overall and by-country weighted prevalence of seeing someone smoking and the smokers’ own smoking behaviour at each setting. We also assess the relationship between seeing someone smoking and smoking themselves at these settings. Results: The prevalence of smoking as seen by smokers was 18.8% at workplaces, with high variability among countries (from 4.7% in Hungary to 40.8% in Greece). Among smokers visiting leisure facilities in the last year, during their last visit 22.7% had seen someone smoking inside restaurants and 12.2% had smoked themselves there, while for bars/pubs the corresponding prevalences were 33.9% and 20.4%, and inside discos 44.8% and 34.8%. Conclusions: Smoking is still prevalent at leisure facilities, particularly at discos in Europe, with high variability among countries. More extensive awareness campaigns and stricter enforcement are needed to increase the compliance of smokefree regulations, especially in leisure facilities

Social norms towards smoking and electronic cigarettes among adult smokers in seven European Countries: Findings from the EUREST-PLUS ITC Europe Surveys

Introduction: This study explores whether current smokers’ social norms towards smoking and electronic cigarettes (e-cigarettes) vary across seven European countries alongside smoking and e-cigarette prevalence rates. At the time of surveying, England had the lowest current smoking prevalence and Greece the highest. Hungary, Romania and Spain had the lowest prevalence of any e-cigarette use and England the highest. // Methods: Respondents were adult (≥18 years) current smokers from the 2016 EUREST-PLUS ITC (Romania, Spain, Hungary, Poland, Greece, Germany) and ITC 4CV England Surveys (N=7779). Using logistic regression, associations between country and (a) smoking norms and (b) e-cigarette norms were assessed, adjusting for age, sex, income, education, smoking status, heaviness of smoking, and e-cigarette status. // Results: Compared with England, smoking norms were higher in all countries: reporting that at least three of five closest friends smoke (19% vs 65–84% [AOR=6.9–24.0; Hungary–Greece]), perceiving that people important to them approve of smoking (8% vs 14–57% [1.9–51.1; Spain–Hungary]), perceiving that the public approves of smoking (5% vs 6–37% [1.7–15.8; Spain–Hungary]), disagreeing that smokers are marginalised (9% vs 16–50% [2.3–12.3; Poland–Greece]) except in Hungary. Compared with England: reporting that at least one of five closest friends uses e-cigarettes was higher in Poland (28% vs 36% [2.7]) but lower in Spain and Romania (28% vs 6–14% [0.3–0.6]), perceiving that the public approves of e-cigarettes was higher in Poland, Hungary and Greece (32% vs 36–40% [1.5–1.6]) but lower in Spain and Romania in unadjusted analyses only (32% vs 24–26%), reporting seeing e-cigarette use in public at least some days was lower in all countries (81% vs 12–55% [0.1–0.4]; Spain–Greece). // Conclusions: Smokers from England had the least pro-smoking norms. Smokers from Spain had the least pro-e-cigarette norms. Friend smoking and disagreeing that smokers are marginalised broadly aligned with country-level current smoking rates. Seeing e-cigarette use in public broadly aligned with countrylevel any e-cigarette use. Generally, no other norms aligned with product prevalence

Secondhand exposure to e-cigarette aerosols among smokers: A cross-sectional study in six European countries of the EUREST-PLUS ITC Europe Surveys

Introduction: Electronic cigarette (e-cigarette) use has grown significantly in some European Union (EU) Member States (MS). A better understanding of the exposure to secondhand e-cigarette aerosols (SHA) is necessary to develop and implement comprehensive regulations on e-cigarette use in public places. This study aims to assess the observation of e-cigarette use in public places, the self-reported exposure to SHA, and the level of users’ comfort using e-cigarettes in the presence of others. Methods: This is a cross-sectional study of the Wave 1 International Tobacco Control 6 European Countries Survey recruiting adult smokers (n=6011) across six EU MS: Germany, Greece, Hungary, Poland, Romania, and Spain, within the EURESTPLUS Project. A descriptive analysis was conducted to estimate the prevalence (%) of observed e-cigarette use in different places, frequency of self-reported exposure to SHA, and level of comfort using e-cigarettes in the presence of others. Results: In all, 31.0% of smokers observed others using e-cigarette in public places, 19.7% in indoor places where smoking is banned, and 14.5% indoors at work. Almost 37% of smokers reported to be ever exposed to SHA, ranging from 17.7% in Spain to 63.3% in Greece. The higher prevalence of observed e-cigarette use and passive exposure to SHA was reported by smokers of younger age, of higher educational level and those being current or former e-cigarette users. Part (8.8%) of the smokers who were also e-cigarette users reported feeling uncomfortable using e-cigarettes in the presence of others. Conclusions: A third of smokers from six EU MS reported being exposed to SHA. Prevalence differences were observed among the countries. In the context of scarce evidence on long-term health effects of exposure to SHA, precautionary regulations protecting bystanders from involuntary exposure should be developed

Receiving support to quit smoking and quit attempts among smokers with and without smoking related diseases: Findings from the EUREST-PLUS ITC Europe Surveys

Introduction: Having a chronic disease either caused or worsened by tobacco smoking does not always translate into quitting smoking. Although smoking cessation is one of the most cost-effective medical interventions, it remains poorly implemented in healthcare settings. The aim was to examine whether smokers with chronic and respiratory diseases were more likely to receive support to quit smoking by a healthcare provider or make a quit attempt than smokers without these diseases. Methods: This population-based study included a sample of 6011 adult smokers in six European countries. The participants were interviewed face-to-face and asked questions on sociodemographic characteristics, current diagnoses for chronic diseases, healthcare visits in the last 12 months and, if so, whether they had received any support to quit smoking. Questions on smoking behavior included nicotine dependence, motivation to quit smoking and quit attempts in the last 12 months. The results are presented as weighted percentages with 95% confidence intervals (CI) and as adjusted odds ratios with 95% CI based on logistic regression analyses. Results: Smokers with chronic respiratory disease, those aged 55 years and older, as well as those with one or more chronic diseases were more likely to receive smoking cessation advice from a healthcare professional. Making a quit attempt in the last year was related to younger age, high educational level, higher motivation to quit, lower nicotine dependence and having received advice to quit from a healthcare professional but not with having chronic diseases. There were significant differences between countries with smokers in Romania consistently reporting more support to quit as well as quit attempts. Conclusions: Although smokers with respiratory disease did indeed receive smoking cessation support more often than smokers without disease, many smokers did not receive any advice or support to quit during a healthcare visit