News

Two new studies from the University of Rochester Medical Center (URMC) have uncovered an association between vaping and mental fog. Both adults and kids who vape were more likely to report difficulty concentrating, remembering, or making decisions than their non-vaping, non-smoking peers. It also appeared that kids were more likely to experience mental fog if they started vaping before the age of 14.

While other studies have found an association between vaping and mental impairment in animals, the URMC team is the first to draw this connection in people. Led by Dongmei Li, Ph.D., associate professor in the Clinical and Translational Science Institute at URMC, the team mined data from two major national surveys.

"Our studies add to growing evidence that vaping should not be considered a safe alternative to tobacco smoking," said study author Li.

The studies, published in the journals Tobacco Induced Diseases and Plos One, analyzed over 18,000 middle and high school student responses to the National Youth Tobacco Survey and more than 886,000 responses to the Behavioral Risk Factor Surveillance System phone survey from U.S. adults. Both surveys ask similar questions about smoking and vaping habits as well as issues with mental function.

Both studies show that people who smoke and vape -- regardless of age -- were most likely to report struggling with mental function. Behind that group, people who only vape or only smoke reported mental fog at similar rates, which were significantly higher than those reported by people who don't smoke or vape.

The youth study also found that students who reported starting to vape early -- between eight and 13 years of age -- were more likely to report difficulty concentrating, remembering, or making decisions than those who started vaping at 14 or older.

"With the recent rise in teen vaping, this is very concerning and suggests that we need to intervene even earlier," said Li. "Prevention programs that start in middle or high school might actually be too late."

Adolescence is a critical period for brain development, especially for higher-order mental function, which means tweens and teens may be more susceptible to nicotine-induced brain changes. While e-cigarettes lack many of the dangerous compounds found in tobacco cigarettes, they deliver the same amount - or possibly more - nicotine.

While the URMC studies clearly show an association between vaping and mental function, it's not clear which causes which. It is possible that nicotine exposure through vaping causes difficulty with mental function. But it is equally possible that people who report mental fog are simply more likely to smoke or vape -- possibly to self-medicate.

Li and her team say that further studies that follow kids and adults over time are needed to parse the cause and effect of vaping and mental fog.

In addition to Li, authors of the youth study include Catherine Xie, and Zidian Xie, Ph.D. For the adult study, Li was joined by co-authors Zidian Xie, Ph.D., Deborah J. Ossip, Ph.D. Irfan Rahman, Ph.D., and Richard J. O'Connor, Ph.D. Both studies were funded by the National Cancer Institute and the U.S. Food and Drug Administration's Center for Tobacco Products.

Congratulations to Tim Smyth for his first authored publication "Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin", published in Particle Fibre Toxicology in October 2020. This research article reports the new finding that diesel exhaust particles lead to epithelial barrier dysfunction, and inhibit expression of the tight junction protein Tricellulin both in vitro and in vivo.

Ashley Rackow, current TOX PhD and Pulmonary T32 graduate student, has had a review article, "The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops," published in the European Respiratory Journal. Ashley currently works in Dr. Kottmann's Lab focusing on the endogenous function and manipulation of pH-sensing G-protein coupled receptors (GPCRs) in the context of pulmonary fibrosis. Congrats Ashley!

Rackow AR, Nagel DJ, McCarthy C, Judge J, Lacy S, Freeberg MAT, Thatcher TH, Kottmann RM, Sime PJ. The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops. Eur Respir J. 2020 Nov 26;56(5):2000075. doi: 10.1183/13993003.00075-2020. PMID: 32943406.

Abstract: Pulmonary fibrosis is a devastating, progressive disease and carries a prognosis worse than most cancers. Despite ongoing research, the mechanisms that underlie disease pathogenesis remain only partially understood. However, the self-perpetuating nature of pulmonary fibrosis has led several researchers to propose the existence of pathological signalling loops. According to this hypothesis, the normal wound-healing process becomes corrupted and results in the progressive accumulation of scar tissue in the lung. In addition, several negative regulators of pulmonary fibrosis are downregulated and, therefore, are no longer capable of inhibiting these feed-forward loops. The combination of pathological signalling loops and loss of a checks and balances system ultimately culminates in a process of unregulated scar formation. This review details specific signalling pathways demonstrated to play a role in the pathogenesis of pulmonary fibrosis. The evidence of detrimental signalling loops is elucidated with regard to epithelial cell injury, cellular senescence and the activation of developmental and ageing pathways. We demonstrate where these loops intersect each other, as well as common mediators that may drive these responses and how the loss of pro-resolving mediators may contribute to the propagation of disease. By focusing on the overlapping signalling mediators among the many pro-fibrotic pathways, it is our hope that the pulmonary fibrosis community will be better equipped to design future trials that incorporate the redundant nature of these pathways as we move towards finding a cure for this unrelenting disease.

A new grant from the National Institutes of Health (NIH) will provide support for the University of Rochester Medical Center's Preventive Care Asthma Program -- a program that has improved health outcomes for school children with asthma -- to help teenagers in Rochester who are suffering from significant asthma and related breathing problems.

The grant, which is funded for $4.3 million over 5 years, supports the "Telemedicine Enhanced Asthma Management-Uniting Providers for Teens (TEAM-UP for Teens)" program, which helps provide the following treatment support for teens with asthma:

• Telehealth visits with an asthma specialist to develop an optimized asthma management plan at the start of the school year
• School-based supervised therapy of preventive asthma medications -- providing support to teenagers with their treatment to ensure they are taking medicine consistently and correctly
• Follow-up telehealth visits with a nurse asthma educator to support teens and their caregivers with ongoing asthma management

The preventive asthma care program is led by Jill Halterman, M.D., M.P.H. Halterman is a general pediatrician, not an asthma specialist. But, when she saw how asthma disproportionately affected urban children, she was compelled help. A partnership with the city school district and school nurse program has allowed her and her team to reach hundreds of children with asthma in the community.

"My goal was to improve the delivery of care to children and teens who are suffering the greatest burden from asthma," said Halterman, Executive Vice Chair and Professor of Pediatrics.

The U.S. Department of Housing and Urban Development (HUD) has awarded a $927,069 grant to a partnership between the University of Rochester, Silent Spring Institute, the National Center for Healthy Housing, and the City of Rochester to study the impacts of home rehabilitation and resident engagement on exposures to harmful environmental chemicals within the home. This project will build on Rochester's nationally recognized lead poisoning prevention work to inform efforts to protect children and families from a wide range of home hazards.

The partners will work with the City of Rochester's highly successful Lead Hazard Control plus Healthy Homes program, which provides grants to low-income owner-occupants and landlords to address lead hazards in pre-1978 housing. The City of Rochester has received over $35 million in grant funding from HUD over the past 15 years to support lead hazard remediation in thousands of city homes.

This study will for the first time explore the potential of HUD-funded Lead Hazard Control grants to affect a wide range of other home-based exposures including pesticides, allergens, and endocrine disrupting chemicals such as flame retardants and phthalates. These chemical exposures contribute to a wide range of health concerns including asthma, learning disabilities, reproductive system problems, and cancer. The Lead Hazard Control grant program serves low-income families with young children, who are at particular risk from these environmental hazards.

Working with 100 owner-occupants over the next three years, the research team will study a wide range of chemicals in household dust before and after lead hazard control interventions. The project will engage with residents to educate them about how to maintain a healthy home, use safer consumer products (cleaners, air fresheners, pest control), and access additional community resources for support.

The University of Rochester has partnered with community stakeholders and the City of Rochester for several decades to develop childhood lead poisoning prevention efforts that are widely recognized as a national model. The new project builds on this collaboration and extends it to broader environmental health concerns by working with Silent Spring Institute, a non-profit research organization that studies environmental chemical exposures that harm human health and educates communities on how to reduce their exposures. Robin Dodson, Sc.D., the lead investigator from Silent Spring Institute, is an environmental exposure scientist with expertise in analyzing multiple chemical exposures in household dust. "With this grant, we will deepen our understanding of how to effectively create healthier homes, especially among the most vulnerable, by lowering indoor exposures to harmful endocrine disrupting chemicals, ," said Dobson.

"This grant will let us build on our longstanding partnership with the City of Rochester to learn how we can leverage childhood lead poisoning prevention efforts to maximize a wide range of lifelong health benefits for children and their families," said Katrina Smith Korfmacher, Ph.D., associate professor of Environmental Medicine at the University of Rochester Medical Center. Korfmacher has worked extensively with Rochester's community-based lead poisoning prevention efforts and is a co-principal investigator on the new HUD grant.

"I want to congratulate the University of Rochester Medical Center's Environmental Health Sciences Center on this award of a U.S. Department of Housing and Urban Development grant to study methods to improve environmental conditions in the home," said Rochester Mayor Lovely A. Warren. "Thanks in large part to our partnership with the Coalition to Prevent Lead Poisoning and our adoption of the Lead Ordinance, the City of Rochester has been cited as the national 'gold standard' for healthy housing policies. We are excited to partner with the University of Rochester and Silent Spring Institute to build on the success of these initiatives to find even more opportunities to provide all children and their families with access to homes that are healthy and safe."

The National Center for Healthy Housing is a national non-profit group that conducts research and promotes policies to promote health equity through improved housing quality. NCHH will inform the resident engagement component of the study, based on the New York State Healthy Neighborhoods Program and will disseminate results through its national networks of community groups, policymakers, and healthy homes professionals.

The research team expects that the findings will inform future HUD grant programs, policies, and practices to better protect children's environmental health. Efforts to cost-effectively address home environmental health hazards are particularly important now, as children and families spend more time at home due to the pandemic and associated stay-at-home orders, as well as the economic challenges facing many families. "This project builds on years of work on lead poisoning prevention in Rochester that has shown demonstrated success protecting children's health, has provided a model for other communities, and has informed federal programs and policies," said Korfmacher. "We hope that our findings will support efforts to protect children from other important hazards in their homes."

How do you make an impact when you are the only person in the room that looks like you? We hear the terms diversity and inclusion but forget that the term representation should be a reflection of diversity and inclusion combined. This isn't always the case. Dr. Grayson discusses her views on what it means to increase diversity and representation as an Individual Contributor. Learn more about her journey as the 2nd Black Woman to graduate with a PhD in Mechanical Engineering from her graduate institution. Hear about her current work as both an engineer, a STEM Advocate, and her most recent success as author of 'HOODED: A Black Girl's Guide to the PhD' where she highlights her time and lessons learned during her PhD Program.

 

What do vapers, smokers, and non-smokers with chronic conditions such as high blood pressure or diabetes have in common? They all are at higher risk for COVID-19.

The scientific explanation behind this is complex and not yet certain — but it may boil down to an enzyme known as ACE2, that lives on the surface of many cells in the lungs and serves as the entry point for the coronavirus.

Evidence shows that people with chronic inflammatory illnesses, vulnerable older adults, and those who smoke or vape, all have an abundance of ACE2 receptor proteins to serve as a gateway to the deadly virus.

A research team at the University of Rochester Medical Center, led by Irfan Rahman, Ph.D., published a series of studies during the pandemic that focus on the vital role of ACE2 — which is already at the center of many other scientific investigations — to shape a clearer picture of the critical cellular mechanisms that regulate the deadly virus and its link to vaping.

While Rochester investigators are working in lockstep with scientists around the world, Rahman's special interest is on the growing problem of young people who test positive and may be spreading coronavirus at alarming rates. Even some older children and teens who have higher levels of the ACE2 receptor seem to be more vulnerable to the virus.

"Our next step is to investigate whether ACE2 is normally low in young people, hence their relatively low infection and mortality rates from COVID-19, but to find out if ACE2 is increased by smoking or vaping rendering them more susceptible to the virus," said Rahman, Dean's Professor of Environmental Medicine, Medicine (Pulmonary), and Public Health Sciences. "This would be in contrast to older people with lung diseases such as COPD and pulmonary fibrosis, who we already know are at higher risk for severe viral illnesses and death."

At the start of the coronavirus pandemic, many people cleaned grocery-store purchases with disinfecting wipes before putting them away at home.

At that point, it was recommended as a best practice to avoid contagion. The thinking was that because the virus can survive on surfaces for short periods of time, someone could touch a contaminated item and then touch their eyes, nose, or mouth and possibly infect themselves.

Now, however, a lot more is known about how COVID-19 spreads -- primarily from person to person through droplets in the air. The risk of getting it from surfaces, including grocery packaging, is "exceedingly small," said Melissa Bronstein, senior director of infection prevention for Rochester Regional Health and a registered nurse.

The most up-to-date information on the website of the Centers for Disease Control and Prevention says that "because of the poor survivability of these coronaviruses on surfaces, there is likely a very low risk of spread from food products or packaging." In fact, it goes on to say that no cases of COVID-19 have been linked to people touching food or food packaging and then touching their faces.

"Some people are really scared, so if it makes them feel safer to wipe things down, then it's important for them to do that," said Katrina Korfmacher, a director at the University of Rochester Medical Center's Environmental Health Sciences Center. (She noted that it should be done safely, so that people don't end up ingesting disinfectants.)

The UR CTSI has selected two new awardees for its KL2 Career Development Award program, which supports the early career development of multidisciplinary clinical and translational scientists. The program provides two years of funding to help early-career scientists obtain independent funding for their innovative research.

Matthew D. McGraw, M.D.

Assistant Professor in the Department of Pediatrics, Division of Pulmonary Medicine

Project title:Basal Cell Dysfunction in Flavoring Induced Lung Disease

Inhaling certain chemicals, like diacetyl, which is found in foods, wine and e-cigarettes, is associated with a fibrotic lung disease called bronchiolitis obliterans. Currently, lung transplantation is the only treatment option for patients with bronchiolitis obliterans. Current therapies are limited due to our lack of knowledge of how certain chemicals exposures contribute to this devastating fibrotic lung disease.

McGraw will investigate the mechanisms by which this chemical causes airway stem cell death and will try to block cell death of this rare lung population to prevent the onset of fibrotic lung disease. His research will potentially identify new medical therapies for treatment of lung disease associated with inhalation of toxic flavoring chemicals found in e-cigarettes.

Ending Parkinson's Disease: A Prescription for Action," co-authored by University of Rochester Professor of Neurology Dr. Ray Dorsey, was featured in the New York Times. The book highlights the importance of reducing environmental exposures as part of efforts to address the disease.

National high priority program funds two projects to better understand how coronavirus interacts with proteins in human cells.

Two members of the University of Rochester's Department of Biology have received expedited funding awards from the National Science Foundation (NSF) to study biological processes involved in COVID-19.

As labs reopen across the University, Dragony Fu, an assistant professor of biology, and Jack Werren, the Nathaniel and Helen Wisch Professor of Biology, will apply their expertise in cellular and evolutionary biology to research proteins involved in infections from COVID-19, which is caused by the novel coronavirus SARS-CoV-2. The funding is part of the NSF's Rapid Response Research (RAPID) program to mobilize funding for high priority projects.

"At this point, combating this pandemic is an 'all-hands-on-deck' situation," says Elaine Sia, professor and chair of biology. "Researchers in the biology department at the University, like biologists everywhere, have been learning all we can about the SARS-CoV2 virus."

By better understanding the specific biological mechanisms and proteins involved in COVID-19 infection, scientists will better be able to develop effective treatments and vaccines to fight the disease.

When the first COVID-19 cases hit the University of Rochester Medical Center's ICU back in March of 2020, there were no proven treatments available, but experimental therapies were cropping up around the world. Quickly, a team of URMC clinicians and researchers mobilized to bring the most promising clinical trials - that address the broadest swath of patients' needs - to URMC. Since then, URMC has joined three clinical trials that provide extra treatment options for some of the sickest COVID-19 patients.

COVID-19 causes a wide range of outcomes: some infected people never show a single symptom, while many battle the disease for weeks in the ICU. The difference between those outcomes seems to lie in a careful balance of the immune response. In the beginning of the disease, the immune system helps fight off the virus. But for those who land in the hospital, this early, helpful immune response gives way to uncontrolled over-activation of the immune system, causing system-wide inflammation and severe complications.

The three COVID-19 inpatient clinical trials currently running at URMC attack the disease at both ends of this balance.

"Our goal has always been to promote effective therapies through clinical trials," said Martin Zand, M.D., Ph.D., senior associate dean for Clinical Research and co-director of the Clinical & Translational Science Institute. "Our team is working hard to make sure that the trials we bring to URMC have the greatest chance of benefiting our own patients, and significantly advancing the science of COVID-19 to benefit patients around the world."

Quieting Inflammation at All Ages

While researchers have high hopes that baricitinib can quell the over-exuberant immune activity of COVID-19, that trial is only open to patients who are 18 years old and up. Another trial, sponsored by Incyte Corp, is testing a very similar drug, called ruxolitinib, in patients as young as 12 who have very severe COVID-19 disease and need to be on a ventilator.

When the immune system runs amok in the late stages of COVID-19, the lining of the lungs can become leaky, allowing fluid to build up in the lungs' air sacs. This phenomenon, called acute respiratory distress syndrome, starves the body of oxygen and mechanical ventilation can even fail to rescue these patients.

The URMC team, led by Christopher Palma, M.D. and Steve Georas, M.D., expects to enroll up to 20 severely ill COVID-19 patients in the trial to see if ruxolitinib can keep them alive and get them off ventilators and out of the ICU sooner.

On 16 June 2020, EHP welcomed three Deputy Editors, Dana Boyd Barr, Manolis Kogevinas, and Paige Lawrence, on their first official day of service in their new positions. Editor-in-Chief (EIC) Joel Kaufman, MD, MPH, introduced the new Deputy Editor role and named the appointees in a recent webinar with the Board of Associate Editors.

As recognized leaders in their respective disciplines of exposure science, environmental epidemiology, and experimental toxicology, the Deputy Editors will act as ambassadors to colleagues in their scientific communities to ensure that EHP continues to publish the most influential environmental health research. With a wealth of leadership, editorial, and peer review experience at EHP and other journals, the new Deputy Editors are expected to complement existing editorial workflows.

Working closely with the EIC and EHP Science Editors, they will evaluate new and revised manuscripts, participate in triage and interim editorial decisions, and collaborate with Associate Editors to oversee peer review. The Deputy Editors will also provide leadership for the consideration of submissions in their areas of expertise.

The new Deputy Editor role represents the next step in changes to the journal's operating structure that began when Joel assumed the EIC role in February 2020. As the first offsite EIC, Joel maintains his faculty position at the University of Washington while serving the journal.

Although our annual Retreat and Awards Banquet were postponed due to the COVID-19 pandemic, we would still like to acknowledge the excellent work of our trainees. Please congratulate this year's recipients of the Toxicology Training Program awards:

Weiss Toxicology Scholar awards: Timothy Anderson (pre-doctoral); Thivanka Muthumalage, PhD (post-doctoral)

Tim is a student in Dr. Deborah Cory-Slechta's laboratory. He is studying the toxicokinetics of paraquat that is delivered via inhalation exposure and its associated neurobehavioral effects. This work has important implications for commonly-used agricultural pesticides. Thivanka is mentored by Dr. Irfan Rahman and studies cellular stress responses and lung injury following exposures to e-cigarette aerosols or specific components that are used in vaping. Both of these individuals are engaged, highly productive young scientists and exhibit strong leadership inside and outside of their respective laboratories.

Robert N. Infurna award for best scientific publication: Christina Post (pre-doctoral); Qixin Wang, PhD (post-doctoral)

Post CM, Boule LA, Burke CG, O'Dell CT, Winans B, Lawrence BP. The ancestral environment shapes antiviral CD8+ T cell responses across generations. iScience. 20:168-183, 2019.

This paper describes transgenerational impacts of an environmental toxicant, TCDD, on innate and adaptive immunity. This work was a complex, large undertaking and has significant implications for the way that we think about who is impacted by environmental exposures.

Wang Q, Khan NA, Muthumalage T, Lawyer GR, McDonough SR, Chuang TD, Gong M, Sundar IK, Rehan VK, Rahman I. Dysregulated repair and inflammatory responses by E-cigarette-derived inhaled nicotine and humectant propylene glycol in a sex-dependent manner in mouse lung. FASEB Bioadv 1(10): 609-623, 2019.

This paper combines in vivo and in vitro approaches to characterize the impact of e-cigarette vapors in the lungs upon acute inhalation exposure. In addition to demonstrating the pro-inflammatory effects of nicotine in lung, which is not new, it also demonstrates that the commonly-used solvent (humectant) has its own effects. It is comprehensive and timely.

Neuman award for exemplary scholarship and citizenship: Ashley Peppriell

Ashley is a mentored by Dr. Matt Rand and is studying the impacts on muscle development of methyl mercury exposure in a Drosophila model. In addition to working hard and making great strides in the laboratory, Ashley is a volunteer extraordinaire! She co-led the annual retreat planning team for two years, has served as a teaching assistant, is a peer mentor, and is a great ambassador for the Program. She certainly exhibits the high level of scholarship and citizenship that defined the lives and careers of Drs. Margaret and William Neuman.

Best Question awards: Janine Cubello and Ashley Fields

It was a tough call, so we decided to give out two awards this year! Janine is mentored by Dr. Margot Mayer-Pröschel and studies the effects of combined lead exposure and iron deficiency on the developing brain. Ashley's mentor is Dr. Martha Susiarjo and her project is focused on the impact of vitamin B6 deficiency on pregnancy outcomes in the context of diabetes mellitus.

Ian's virtual poster was presented last month as part of the competition, which was judged by a broad faculty pool. The title of the poster is "Establishing Tools to Investigate the Role of Microbes in Modulating Methylmercury Toxicokinetics". Please offer congratulations to Ian and his co-authors, Daria Vorojeikina, Tom Scrimale, and Matt Rand.

Research at the University of Rochester Medical Center has found evidence of why COVID-19 is worse for people who smoke and vape than for the rest of the population.

Irfan Rahman, who runs a lab at URMC that studies the effects of tobacco products on the lungs, said people who smoke and vape often have elevated levels of receptors for an enzyme called ACE2.

Those receptors also allow the novel coronavirus to enter lung cells. More receptors means more viral load, which means more severe infections, Rahman said.

"It's pretty bad, actually," he said.

Rahman said early evidence from novel coronavirus infections showed that smokers were particularly at risk from COVID-19, but the mechanism behind the vulnerability was unclear.

Now, Rahman and other researchers said, a growing body of evidence shows inhaling nicotine increases the lungs' receptiveness to the virus and the lethality of the disease.

Other articles on this topic:

https://www.rochestercitynewspaper.com/rochester/why-smokers-and-vapers-are-more-susceptible-to-covid-19/Content?oid=11961338

https://www.wxxinews.org/post/urmc-research-uncovers-links-between-covid-19-and-vaping-smoking#:~:text=Irfan%20Rahman%2C%20a%20researcher%20at,gain%20entry%20to%20the%20lungs.&text=Those%20receptors%20also%20allow%20the%20novel%20coronavirus%20to%20enter%20lung%20cells.

https://www.wxxi.org/category/tags/covid-19

The department is excited to share the news that Kadijah Abston, MS -- a fourth-year student working in Dr. Xin Li's laboratory -- has been selected to receive this year's University of Rochester Elon Huntington Hooker dissertation fellowship. Mr. Hooker was a graduate of the University and served as one of its trustees after founding the Hooker Chemical Company. The award is given to support student researchers who are primarily focused on chemistry or biochemistry. In her graduate work, Kadijah is exploring the novel hypothesis that lead can impact brain development across multiple generations via epigenetic modulations that are manifest at the level of DNA methylation changes and/or changes in small non-coding RNAs that get transmitted via the male line. This work will provide foundational knowledge about paternal information that gets transmitted across the generations and has implications regarding the broad human health impact of a wide-spread environmental toxicant.

Please congratulate Kadijah and Xin when you see them!

The Rahman lab has been highlighted in Nature journal for their work on discovery of exosomes in COPD. Read the article.