The Smoking Gun: Can We Do for Gun Control What We Are Doing to Control the Vaping and E-Cigarettes Epidemic?

An editorial by UMass Medical School public health experts calls for legislators and policymakers to take bold action on gun control, similar to the recent ban in Massachusetts on vaping products in response to lung illnesses in vaping device and e-cigarette users

Teen Distracted Reality an Interactive Virtual Education (D.R.I.V.E.): Experience and Impact on Teenage Drivers

Introduction: In 2013, 2,163 teens in the United States ages 16–19 were killed and 243,243 were treated in emergency departments for injuries from motor vehicle crashes. distracted driving (i.e. texting, loud music, or phone conversations) and impaired driving (driving under the influence) play a role in these motor vehicle crashes. Prevention efforts aimed at high-risk teenager driving behavior may encourage safe driving habits. Methods: The Teen D.R.I.V.E. program is a mobile driving simulator that provides teenagers with distracted and impaired driving scenarios. We administered anonymous surveys from April 2015-April 2016 to obtain demographic data and evaluate the program’s impact on their driving behavior. We retrospectively analyzed survey responses using univariate and multivariate statistical analysis. Results: A total of 1374 participants in the survey, however, 50 did not respond to the driving experience portion of the survey. Most participants (70%) were between 16-17 years of age years old and 51% were males. A majority (76%) of respondents had driving experience (26% permit, and 46% license) or had attended a driver’s education course (67%). After experiencing the simulation respondents felt that the consequences of driving distracted (53%) and driving impaired (61%) were worse than previously expected. In addition, participants said that they would never drive distracted (70%) or drive impaired (90%). A majority of participants (72%) feel that simulation is the most effective way to teach driving related topics. Conclusion: Teen D.R.I.V.E. offers a valuable experience to teenagers, teaching them about the dangers of driving distracted and impaired. Participants are likely to never drive impaired compared or distracted. Most teenagers feel simulation teaches these driving lessons most effectively

Are Goods for Guns Good for the Community? An Update of a Community Gun Buyback Program

BACKGROUND: Gun violence remains a leading cause of death in the United States. Community gun buyback programs provide an opportunity to dispose of extraneous firearms. The purpose of this study was to understand the demographics, motivation, child access to firearms and household mental illness of buyback participants in hopes of improving the program\u27s effectiveness. METHODS: A 2015 Injury Free Coalition for Kids gun buyback program which collaborated with local police departments was studied. We administered a 23-item questionnaire survey to gun buyback participants assessing demographic characteristics, motivation for relinquishing firearms, child firearm accessibility, and mental illness/domestic violence history. RESULTS: A total of 186 individuals from Central/Western Massachusetts turned in 339 weapons. Participants received between $25 and$75 in gift cards dependent on what type of gun was turned in, with an average cost of $41/gun. A total of 109 participants (59%) completed the survey. Respondents were mostly white (99%), male (90%) and first-time participants in the program (85.2%). Among survey respondents, 54% turned in firearms for safety reasons . Respondents reported no longer needing/wanting their weapons (47%) and approximately one in eight participants were concerned the firearm(s) were accessible to children. Most respondents (87%) felt the program encouraged neighborhood awareness of firearm safety. Three out of every five participants reported that guns still remained in their homes, additionally; 21% where children could potentially access them and 14% with a history of mental illness/suicide/domestic violence in the home. CONCLUSIONS: Gun buybacks can provide a low-cost means of removing unwanted firearms from the community. Most participants felt their homes were safer after turning in the firearm(s). In homes still possessing guns, emphasis on secure gun storage should continue increasing the safety of children and families. The results of this survey also provided new insights into the association between mental illness/suicide and gun ownership. LEVEL OF EVIDENCE: Level III, Prognostic and Epidemiological

Oncogenic D816V-KIT signaling in mast cells causes persistent IL-6 production

Persistent dysregulation of IL-6 production and signaling have been implicated in the pathology of various cancers. In systemic mastocytosis, increased serum levels of IL-6 associate with disease severity and progression, although the mechanisms involved are not well understood. Since systemic mastocytosis often associates with the presence in hematopoietic cells of a somatic gain-of-function variant in KIT, D816V-KIT, we examined its potential role in IL-6 upregulation. Bone marrow mononuclear cultures from patients with greater D816V allelic burden released increased amounts of IL-6 which correlated with the percentage of mast cells in the cultures. Intracellular IL-6 staining by flow cytometry and immunofluorescence was primarily associated with mast cells and suggested a higher percentage of IL-6 positive mast cells in patients with higher D816V allelic burden. Furthermore, mast cell lines expressing D816V-KIT, but not those expressing normal KIT or other KIT variants, produced constitutively high IL-6 amounts at the message and protein levels. We further demonstrate that aberrant KIT activity and signaling are critical for the induction of IL-6 and involve STAT5 and PI3K pathways but not STAT3 or STAT4. Activation of STAT5A and STATB downstream of D816V-KIT was mediated by JAK2 but also by MEK/ERK1/2, which not only promoted STAT5 phosphorylation but also its long-term transcription. Our study thus supports a role for mast cells and D816V-KIT activity in IL-6 dysregulation in mastocytosis and provides insights into the intracellular mechanisms. The findings contribute to a better understanding of the physiopathology of mastocytosis and suggest the importance of therapeutic targeting of these pathwaysThis work was supported by the Division of Intramural Research within the National Institute of Allergy and Infectious Diseases (NIAID), at the National Institutes of Health.S

Integrated Assessment of Genomic Correlates of Protein Evolutionary Rate

Rates of evolution differ widely among proteins, but the causes and consequences of such differences remain under debate. With the advent of high-throughput functional genomics, it is now possible to rigorously assess the genomic correlates of protein evolutionary rate. However, dissecting the correlations among evolutionary rate and these genomic features remains a major challenge. Here, we use an integrated probabilistic modeling approach to study genomic correlates of protein evolutionary rate in Saccharomyces cerevisiae. We measure and rank degrees of association between (i) an approximate measure of protein evolutionary rate with high genome coverage, and (ii) a diverse list of protein properties (sequence, structural, functional, network, and phenotypic). We observe, among many statistically significant correlations, that slowly evolving proteins tend to be regulated by more transcription factors, deficient in predicted structural disorder, involved in characteristic biological functions (such as translation), biased in amino acid composition, and are generally more abundant, more essential, and enriched for interaction partners. Many of these results are in agreement with recent studies. In addition, we assess information contribution of different subsets of these protein properties in the task of predicting slowly evolving proteins. We employ a logistic regression model on binned data that is able to account for intercorrelation, non-linearity, and heterogeneity within features. Our model considers features both individually and in natural ensembles (“meta-features”) in order to assess joint information contribution and degree of contribution independence. Meta-features based on protein abundance and amino acid composition make strong, partially independent contributions to the task of predicting slowly evolving proteins; other meta-features make additional minor contributions. The combination of all meta-features yields predictions comparable to those based on paired species comparisons, and approaching the predictive limit of optimal lineage-insensitive features. Our integrated assessment framework can be readily extended to other correlational analyses at the genome scale

No Evidence That Gratitude Enhances Neural Performance Monitoring or Conflict-Driven Control

It has recently been suggested that gratitude can benefit self-regulation by reducing impulsivity during economic decision making. We tested if comparable benefits of gratitude are observed for neural performance monitoring and conflict-driven self-control. In a pre-post design, 61 participants were randomly assigned to either a gratitude or happiness condition, and then performed a pre-induction flanker task. Subsequently, participants recalled an autobiographical event where they had felt grateful or happy, followed by a post-induction flanker task. Despite closely following existing protocols, participants in the gratitude condition did not report elevated gratefulness compared to the happy group. In regard to self-control, we found no association between gratitude--operationalized by experimental condition or as a continuous predictor--and any control metric, including flanker interference, post-error adjustments, or neural monitoring (the error-related negativity, ERN). Thus, while gratitude might increase economic patience, such benefits may not generalize to conflict-driven control processes

An Experimental Approach to Examining Psychological Contributions to Multisite Musculoskeletal Pain.

The present study examined the prospective value of pain catastrophizing, fear of pain, and depression in the prediction of multisite musculoskeletal pain following experimentally induced delayed-onset muscle soreness (DOMS). The study sample consisted of 119 (63 females, 56 males) healthy university students. Measures of pain catastrophizing, fear of pain, and depression were completed prior to the DOMS induction procedure. Analyses revealed that pain catastrophizing and fear of pain prospectively predicted the experience of multisite pain following DOMS induction. Analyses also revealed that women were more likely to experience multisite pain than men. There was no significant relation between depressive symptoms and the experience of multisite pain. The discussion addresses the mechanisms by which pain catastrophizing and fear of pain might contribute to the spreading of pain. Clinical implications of the findings are also addressed. Perspective: The results of this experimental study suggest that pain catastrophizing and fear of pain might increase the risk of developing multisite pain following musculoskeletal injury

A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus

In this study, genome-wide expression profiling based on Affymetrix ATH1 arrays was used to identify discriminating responses of Arabidopsis thaliana to five herbicides, which contain active ingredients targeting two different branches of amino acid biosynthesis. One herbicide contained glyphosate, which targets 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), while the other four herbicides contain different acetolactate synthase (ALS) inhibiting compounds. In contrast to the herbicide containing glyphosate, which affected only a few transcripts, many effects of the ALS inhibiting herbicides were revealed based on transcriptional changes related to ribosome biogenesis and translation, secondary metabolism, cell wall modification and growth. The expression pattern of a set of 101 genes provided a specific, composite signature that was distinct from other major stress responses and differentiated among herbicides targeting the same enzyme (ALS) or containing the same chemical class of active ingredient (sulfonylurea). A set of homologous genes could be identified in Brassica napus that exhibited a similar expression pattern and correctly distinguished exposure to the five herbicides. Our results show the ability of a limited number of genes to classify and differentiate responses to closely related herbicides in A. thaliana and B. napus and the transferability of a complex transcriptional signature across species

SLI-1 Cbl Inhibits the Engulfment of Apoptotic Cells in C. elegans through a Ligase-Independent Function

The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.National Cancer Institute (U.S.) (Award K08CA104890

Differential Gene Repertoire in Mycobacterium ulcerans Identifies Candidate Genes for Patho-Adaptation

The emerging human disease Buruli ulcer, caused by Mycobacterium ulcerans, is of increasing challenge for public health systems in many countries, mainly in West and Central sub-Saharan Africa. Genetic differentiation of patient isolates, a prerequisite for scientific studies on and intervention of disease transmission and dispersal, is hampered by an exceptional lack of genetic diversity within this species. Comparative genomics on M. ulcerans of worldwide geographical origin has already allowed for distinguishing several haplotypes separated into two distinct lineages. Differences in prevalence and incidence of Buruli ulcer were already suspected, but biological relevance for this was unclear. Here, we show newly identified hot spot regions of genomic instability, a biased silencing of coding sequences belonging to distinct functional groups, and a differential gene repertoire across M. ulcerans strains. Gene inactivation mediated by different mechanisms in M. ulcerans adds to the concept of anti-virulence genes observed in an increasing number of bacterial species. According to this concept, loss of such genes—in addition to gain of function—may confer a selective advantage for a pathogen radiating into a new niche. In the case of M. ulcerans, a distinct set of disrupted genes may enhance virulence, particularly in the classical lineage