Gene therapy and genome editing for primary immunodeficiency diseases

In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells (HSCs) transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases (PIDs). Despite of some pitfalls at early stage clinical trials, the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety, preparatory regime for manufacturing high quality virus, automated CD34 cell purification. Hence, the overall outcome from the clinical trials for the different PIDs has been very encouraging. In addition to the viral vector based gene therapy, the recent fast moving forward developments in genome editing using engineered nucleases in HSCs has provided a new promising platform for the treatment of PIDs. This review provides an overall outcome and progress in gene therapy clinical trials for SCID-X, ADA-SCID, WAS, X- CGD, and the recent developments in genome editing technology applied in HSCs for developing potential therapy, particular in the key studies for PIDs

Estimating the Impact of Food and Drug Administration Regulation of Cigarette Package Warning Labels and the Potential Added Impact of Plain Packaging: Evidence From Experimental Auctions Among Adult Smokers

Objective: To estimate differences in demand for cigarette packages with different packaging and health warning label formats. Methods: Adult smokers (n=404) in four states participated in experimental auctions. Participants bid on two of four experimental conditions, each involving a different health warning label format but with the same warning message: 1. text on 50% of pack side; 2. text on 50% of the pack front and back; 3. text with a graphic picture on 50% of the pack front and back; and 4. same as previous format, but without brand imagery. Results: Mean bids decreased across conditions (1. $3.52; 2.$3.43; 3. $3.11; 4.$2.93). Bivariate and multivariate random effects models indicated that there was no statistically significant difference in demand for packs with either of the two text only warnings; however, demand was significantly lower for both packs with prominent pictorial warnings, with the lowest demand associated with the plain, unbranded pack. Conclusions: Results suggest that prominent health warnings with graphic pictures will reduce demand for cigarettes. Regulators should not only consider this type of warning label, but also plain packaging policies for tobacco products.experimental auctions, cigarette labels, grotesque images, Food Consumption/Nutrition/Food Safety, Health Economics and Policy, C93,

Impaired bone marrow homing of cytokine-activated CD34⁺ cells in the NOD/SCID model

The reduced engraftment potential of hematopoietic stem/progenitor cells (HSPCs) after exposure to cytokines may be related to the impaired homing ability of actively cycling cells. We tested this hypothesis by quantifying the short-term horning of human adult CD34+ cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals. We show that the loss of engraftment ability of cytokine-activated CD34+ cells is associated with a reduction in homing of colony-forming cells (CFCs) to bone marrow (BM) at 24 hours after transplantation (from median 2.8% [range, 1.9%-6.1%] to 0.3% [0.0%-0.7%]; n = 3; P < .01), coincident with an increase in CFC accumulation in the lungs (P < .01). Impaired BM homing of cytokine-activated cells was not restored by using sorted cells in G 0G1 or by inducing cell cycle arrest at the G 1/S border. Blocking Fas ligation in vivo did not increase the BM homing of cultured cells. Finally, we tested cytokine combinations or culture conditions previously reported to restore the engraftment of cultured cells but did not find that any of these was able to reverse the changes in homing behavior of cytokine-exposed cells. We suggest that these changes in homing and, as a consequence, engraftment result from the increased migratory capacity of infused activated cells, leading to the loss of selectivity of the homing process. © 2004 by The American Society of Hematology

The impact of anti-tobacco industry prevention messages in tobacco producing regions: evidence from the US truth(R) campaign

Background: Adolescents who live in tobacco producing regions may not respond favourably to anti-industry ads

Exposure to Smoking Imagery in Popular Films and Adolescent Smoking in Mexico

Background: Exposure to smoking imagery in films in consistently associated with smoking behavior and its psychological antecedents among adolescents in high-income countries, but its association with adolescent smoking in middle-income countries is unknown. Methods: In 2006, a cross-sectional sample of 3876 Mexican adolescents in secondary school was surveyed on smoking behavior, smoking risk factors, and exposure to 42 popular films that contained smoking. Participants were classified into quartiles of exposure to smoking imagery across all films they reported having seen. Models were estimated to determine associations among quartiles of film-smoking exposure, smoking behavior, and the psychological antecedents of smoking, adjusting for age, gender, sensation seeking, self-esteem, parental smoking, sibling smoking, best-friend smoking, having a bedroom TV, and private versus public school attendance. Analyses were conducted in 2007. Results: Adolescents were exposed to an average of 51.7 (SE=1.3) minutes of smoking in the films they viewed. Crude and adjusting ORs indicated positive associations between quartiles of film-smoking exposure and both current smoking (AOR4v1=3.13; p\u3c0.0001) and having ever smoked (AOR4v1=2.42;p\u3c0.0001). Data from never-smokers (n=2098) were analyzed to determine associations between film-smoking exposure and psychological antecedents of smoking uptake. Crude and adjusted coefficients indicated significant, positive associations between exposure and susceptibility to smoking (AOR4v1=1.66; p\u3c0.05); favorable attitudes toward smoking (Adjusted B4v1=0.44;p\u3c0.0001); and perceived peer prevalence of smoking (Adjusted B4v1=0.26; p\u3c0.0001). Conclusions: Exposure to smoking in films appears associated with smoking among Mexican adolescents. Policies could aim to decrease youth exposure to smoking in nationally and internationally distributed

Predictive and External Validity of a Pre-Market Study to Determine the Most Effective Pictorial Health Warning Label Content for Cigarette Packages

INTRODUCTION: Studies examining cigarette package pictorial health warning label (HWL) content have primarily used designs that do not allow determination of effectiveness after repeated, naturalistic exposure. This research aimed to determine the predictive and external validity of a pre-market evaluation study of pictorial HWLs. METHODS: Data were analyzed from: (1) a pre-market convenience sample of 544 adult smokers who participated in field experiments in Mexico City before pictorial HWL implementation (September 2010); and (2) a post-market population-based representative sample of 1765 adult smokers in the Mexican administration of the International Tobacco Control Policy Evaluation Survey after pictorial HWL implementation. Participants in both samples rated six HWLs that appeared on cigarette packs, and also ranked HWLs with four different themes. Mixed effects models were estimated for each sample to assess ratings of relative effectiveness for the six HWLs, and to assess which HWL themes were ranked as the most effective. RESULTS: Pre- and post-market data showed similar relative ratings across the six HWLs, with the least and most effective HWLs consistently differentiated from other HWLs. Models predicting rankings of HWL themes in post-market sample indicated: (1) pictorial HWLs were ranked as more effective than text-only HWLs; (2) HWLs with both graphic and "lived experience" content outperformed symbolic content; and, (3) testimonial content significantly outperformed didactic content. Pre-market data showed a similar pattern of results, but with fewer statistically significant findings. CONCLUSIONS: The study suggests well-designed pre-market studies can have predictive and external validity, helping regulators select HWL content

Use of cigarettes with flavor-changing capsules among smokers in the United Kingdom: An online survey

Introduction Cigarettes with flavour-changing capsules in the filter have experienced phenomenal global growth in the last decade. We explore socio-demographic and smoking-related factors associated with using capsule cigarettes, how frequently users burst the capsule, and reasons for using them. Methods An online survey was conducted in the United Kingdom between April-May 2016 with 6234 factory-made and/or hand-rolled cigarette smokers. This analysis focuses on 3620 factory-made cigarette smokers, aged 18 years and over, who had smoked in the past month. Results Thirteen percent smoked capsule cigarettes, with younger smokers more likely than older smokers to do so. Capsule use was significantly more common among white non-British than white British, and among those planning to quit in the next six months than those not planning to quit. Most capsule users who crushed the capsule did so always (51%) or most of the time (18%), with more frequent crushing of capsules more common among females, younger and middle-aged participants, white-British and those with a lower score on the Heaviness of Smoking Index. The most common reasons for using capsule cigarettes were that they taste better (52%), are smoother (41%), provide a choice of flavours (32%) and the enjoyment of clicking the capsule (25%). Capsule and non-capsule smokers did not differ significantly in their perceptions of the harmfulness of their brand relative to other brands. Conclusions Our study provides an insight into how and why smokers of capsule cigarettes use these products, with the key drivers of use being taste, flavour choice and interactivity

Flavour capsule cigarettes continue to experience strong global growth

First paragraph: Cigarettes with flavour-changing capsules in the filter, a continuing success story for tobacco companies, have grown exponentially since being introduced in 2007. The global capsule market is estimated to be 150 billion sticks in 2017. We provide an update on the capsule market since 2014. From this time capsule cigarettes have been introduced in new markets in Europe (Croatia, Spain), Africa (Tunisia), Latin America (Bolivia, Ecuador, Uruguay) and Asia (China, India, Philippines, Thailand, Vietnam). They are the fastest growing segment of the combustible market, with market share increasing between 2014 and 2017 in 52 of the 67 countries where they are sold and monitored by tobacco analyst Euromonitor. These products now have market share greater than 10% in four European countries (UK, Hungary, Ireland, Poland), and have increased 12% in the Middle East and Africa. The five most popular capsule markets remain in Latin America (see Figure 1), with market share increasing by at least 40% in each of these countries since 2014

Smokers\u27 Neurological Responses to Novel and Repeated Health Warning Labels (HWLs) From Cigarette Packages

Graphic health warning labels (HWLs) depicting bodily injury due to smoking are effective for producing changes in affect, cognition and smoking behavior in adult smokers. However, little is known about the effects of repeated presentation of graphic HWL’s on the aforementioned processes. The goal of this study was to examine neural and behavioral responses to graphic HWL’s and evaluate whether the repeated presentation of graphic HWL’s leads to repetition suppression (RS). Smokers (N = 16) performed an event-related HWL cue task while blood oxygen level dependent (BOLD) signal was collected during a functional magnetic resonance imaging (fMRI) experimental session. Consistent with prior literature, graphic HWL’s, as compared to scrambled images, elicited increased BOLD response in brain regions involved in self-referential and emotion processing. Importantly, BOLD response at sites in this network diminished during repeated presentation of the same HWL. These findings suggest that while novel graphic HWL’smay have a significant effect on smokers’ brain activity, repeated presentationmay lead to muted responses and thus limit their potential to induce behavioral change