May 2017

Nicotine, aerosol particles, carbonyls and volatile organic compounds in tobacco- and menthol-flavored e-cigarettes

In this study, we aimed to assess the content of electronic cigarette (EC) emissions for five groups of potentially toxic chemical compounds that are known to be present in tobacco smoke: nicotine, particles, carbonyls, volatile organic compounds (VOCs), and trace elements by flavor. We used ECs containing a common nicotine strength and the most popular flavors, tobacco and menthol. An automatic multiple smoking machine was used to generate EC emissions under controlled conditions. The chemical compounds were extracted from EC aerosols into a solid or liquid phase and analyzed. We found that EC aerosols contained toxic compounds including nicotine, fine and nanoparticles, industrial chemicals known as carbonyls, and some industrial solvents such as benzene and toluene. Higher concentrations of particles were generated from tobacco-flavored ECs than from menthol-flavored ECs. We concluded that machine-generated EC aerosols contain some industrial pollutants that may pose significant health risks to users as well as persons exposed to second hand emissions.

Summary provided by David Christopher Christiani, MD, MPH, Physician in the Pulmonary and Critical Care Unit at Massachusetts General Hospital, and senior author of the study.

CIRCLE-seq: A highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets

CRISPR-Cas9 nucleases are proteins that function as molecular scissors that can change the DNA in the genomes of living cells. These molecular scissors can be programmed to make beneficial changes or mutations to specific regions of the genome, but can also cut cellular DNA in other places unintentionally. We have recently developed a method, called CIRCLE-seq, that enables the sensitive detection of which parts of a cells genome can be inadvertently cut by CRISPR-Cas9. CIRCLE-seq will be an important tool to help scientists and researchers who wish to use CRISPR-Cas9 nucleases for research and therapeutic applications.

Summary provided by J. Keith Joung, MD, PhD, Associate Chief of Pathology for Research at Massachusetts General Hospital, and senior author of the study.

In the face of pain: The choice of visual cues in pain conditioning matters

In pain research, investigators often create an association between an arbitrary cue, e.g. a picture, and a painful stimulus. When the association is learned, presentation of the cue can make pain more or less intense. We investigated whether seeing an abstract image, a face or a pseudo-word would influence how well the association is learned. When the cues could be perceived consciously, there was no difference between the cues. When the cues could not be perceived consciously, only face cues effected pain intensity; equally only the association with face cues did not disappear after un-learning the association. We conclude that face-related associations to pain might be stronger than other visual cues. This information that can be harnessed in placebo/nocebo research.

Summary provided by Jian Kong, MD, Associate Researcher in the Martinos Center for Biomedical Imaging at Massachusetts General Hospital, and senior author of the study.

KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients

Chronic neuroinflammation and oxidative stress contribute to the development of neurodegenerative disorders like Huntington’s disease (HD). In our study we identified the molecule that activates the NRF2 pathway, the key regulator of cellular anti-inflammatory and antioxidant defense genes, and discovered that this compound was able to repress the excessive inflammatory responses in mouse glial cells and in HD patients’ monocytes (a type of white blood cell). We also showed that NRF2-activation responses are muted in neural stem cells from patients with HD, suggesting increased susceptibility of this critical renewable cell population to oxidative stress in HD brain. Our results suggest multiple protective benefits of NRF2 activation for HD patients.

Summary provided by Aleksey G. Kazantsev, PhD, formerly of the Mass General Institute for Neurodegenerative Disease (MIND), and senior author of the study. Luisa Quinti, PhD, of the Mass General Institute for Neurodegenerative Disease (MIND), is lead author of the study.

Empathic nonverbal behavior increases ratings of both warmth and competence in a medical context

New research reveals that empathic nonverbal behavior (good eye contact, open body posture, equal eye level, and no physical barrier such as computer screen or desk) increased ratings of physicians on scales of both warmth and competence in a medical setting. Additionally, compared with male participants, female participants perceived physicians displaying unempathic nonverbal behavior as less empathic. Given the significant consequences of clinician empathy, it is critically important for clinicians to learn how nonverbal behavior contributes to perceptions of warmth, and use it as another tool to improve their patients’ emotional and physical health.

Summary provided by Helen Riess, MD, Director of the Empathy and Relational Science Program at Massachusetts General Hospital, and senior author of the study.

Microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases

Crohn’s disease and ulcerative colitis, together termed inflammatory bowel diseases (IBD) commonly affect the gastrointestinal tract. Many different treatments are available but existing tools have not been able to reliably predict whether a patient is going to respond to a particular treatment before they have been initiated on it. Recent studies have shown that intestinal bacterial composition is an important determinant of inflammation in IBD. In this study, lead authors Ananthakrishnan and Luo and colleagues studied the bacterial composition in stool from 85 patients with IBD initiating treatment with a targeted therapy known as vedolizumab. They showed that it is possible to predict who has achieved remission from their symptoms by 14 weeks based on the composition of their intestinal bacteria. As characterizing the stool microbiome becomes more efficient and less expensive, the authors propose that it may become a valuable tool to personalize therapy, matching the right treatment to the right patient, ensuring quick response and minimizing unnecessary exposure.

Summary provided by Ashwin Ananthakrishnan, MBBS, MPH, of the Digestive Healthcare Center at Massachusetts General Hospital, and lead author of the study. Ramnik Xavier, MD, PhD, Director of the Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital, is senior author of the study.

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