Author Interviews, CDC, HIV, Sexual Health, Technology / 15.06.2016
HIV Can Be Prevented in Monkeys With New Vaginal Ring That Dispenses Topical Meds
MedicalResearch.com Interview with:
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Dr. James M. Smith[/caption]
Dr. James M. Smith Ph.D
Laboratory Branch, Division of HIV/AIDS Prevention
Centers for Disease Control and Prevention
Atlanta, Georgia
MedicalResearch.com: What is the background for this study?
Dr. Smith: Our laboratory has been developing a macaque model for testing drug release, safety and efficacy of intravaginal rings (IVR) for preexposure prophylaxis (PrEP) against HIV for several years. The initial studies involved both matrix rings, where the drug is dispersed in the silicone matrix of the device, and reservoir rings, which are essentially a polymer tube filled with drug. In collaboration with the Oak Crest Institute of Science and Auritec Pharmaceuticals, Inc., we began testing a new type of intravaginal ring, the pod-IVR. In this innovative design the ring itself is a scaffold that contains compressed polymer-coated drug tablets, or pods, within the ring. Each pod is separate, allowing for a customizable release rate for each drug by varying the number and diameter of the drug release ports for each individual pod. The macaque pod-IVR can accommodate up to six pods whereas the human pod-IVR can accommodate up to 10 pods. The IVR design was developed to allow the delivery of drug combinations and for simple, cost-effective manufacturing.
Dr. James M. Smith[/caption]
Dr. James M. Smith Ph.D
Laboratory Branch, Division of HIV/AIDS Prevention
Centers for Disease Control and Prevention
Atlanta, Georgia
MedicalResearch.com: What is the background for this study?
Dr. Smith: Our laboratory has been developing a macaque model for testing drug release, safety and efficacy of intravaginal rings (IVR) for preexposure prophylaxis (PrEP) against HIV for several years. The initial studies involved both matrix rings, where the drug is dispersed in the silicone matrix of the device, and reservoir rings, which are essentially a polymer tube filled with drug. In collaboration with the Oak Crest Institute of Science and Auritec Pharmaceuticals, Inc., we began testing a new type of intravaginal ring, the pod-IVR. In this innovative design the ring itself is a scaffold that contains compressed polymer-coated drug tablets, or pods, within the ring. Each pod is separate, allowing for a customizable release rate for each drug by varying the number and diameter of the drug release ports for each individual pod. The macaque pod-IVR can accommodate up to six pods whereas the human pod-IVR can accommodate up to 10 pods. The IVR design was developed to allow the delivery of drug combinations and for simple, cost-effective manufacturing.
Dr. Joseph Alvarnas[/caption]
Joseph Alvarnas, MD
Associate clinical professor
Department of hematology and Director of value-based analytics
City of Hope National Medical Center
Duarte, CA
MedicalResearch.com: What is the background for this study?
Dr. Alvarnas: Patients with HIV infection have a significantly increased risk of non-Hodgkin lymphoma and Hodgkin lymphoma. Prior to the availability of effective anti-retroviral therapy, HIV-infected patients with lymphoma had very poor treatment outcomes. Following the availability of effective anti-HIV therapy, patient outcomes for HIV-infected patients now parallel those of non-infected patients. Historically, however, HIV infection has been used as a criterion for not offering patients autologous blood stem cell transplantation outside of centers with unique expertise. The purpose of this trial was to evaluate outcomes, complication rates, and immunological reconstitution of HIV-infected patients following autologous blood stem cell transplantation.
Dr. Donald Burke[/caption]
Donald S. Burke, M.D.
Dean of the University of Pittsburgh Graduate School of Public Health
Director of the University of Pittsburgh Center for Vaccine Research
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Burke: At the University of Pittsburgh we developed a unique method for detecting antibodies in the blood of patients in a proof-of-principle study that opens the door to development of simple diagnostic tests for diseases for which no microbial cause is known, including auto-immune diseases, cancers and other conditions.
We used a technique pioneered by co-author Thomas Kodadek, Ph.D., of the Scripps Research Institute, that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody.
My team chemically generated a huge library of random molecular shapes. Then, using blood from HIV-infected patients and from non-infected people, we screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies.
We then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), a confidential research study of the natural history of treated and untreated HIV/AIDS in men who have sex with men (supported by the National Institutes of Health). Study co-author Charles Rinaldo, Ph.D., chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology and director of the Pittsburgh arm of the MACS, selected the samples, but blinded the testers to which samples were HIV-positive or -negative. The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.
Dr. Jesper Smit[/caption]
Jesper Smit, MD
Department of Clinical Microbiology
Aalborg University Hospital
Aalborg, Denmark
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Smit: Use of glucocorticoids have been suggested to be associated with increased risk of blood infections by Staphylococcus aureus, but the existing evidence is sparse. Therefore, we conducted a large case-control study to investigate this topic in detail.
We found that the risk of staphylococcal blood infections was more than doubled in users of systemic glucocorticoids compared with non-users and that the risk of infection escalated with increasing dose.
Dr. Mary Forhan[/caption]
Dr. Mary Forhan OT Reg (Alberta), PhD, Assistant Professor ad
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Dr-Tasuku-Terada[/caption]
Dr. Tasuku Terada, post-doctoral research fellow
Faculty of Rehabilitation Medicine
University of Alberta
MedicalResearch.com: What is the background for this study?
Response: The prevalence of obesity has increased. Notably, a proportion of severe obesity (body mass index: body weight [kg] divided by height squared [m2]: >40kg/m2) has shown the most significant increase. Greater body mass increases the risk of cardiovascular disease and referrals for coronary artery graft surgery (CABG) have increased in patients with severe obesity. Interestingly, while obesity is often considered to increase the risk of complications and associated health care costs, many studies have reported better prognosis in patients with obesity compared to patients with normal weight, a phenomenon referred to as the obesity paradox. Therefore, it was not clear if patients with severe obesity were at higher risk of complications and contributed to greater resource use. A better understanding of the relationship between obesity and post-surgical adverse outcomes was needed to provide quality and efficient care.
Dr. Sanjay Saint[/caption]
MedicalResearch.com Interview with:
Sanjay Saint, MD, MPH
Chief of Medicine
VA Ann Arbor Healthcare System
George Dock Professor of Internal Medicine & Senior Associate Chair -
Department of Internal Medicine
University of Michigan Medical School
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Saint: Catheter-associated urinary tract infection (CAUTI) is a common, costly, and morbid complication of hospitalization. Urinary tract infection (UTI) is one of the most common device-related infections in the United States. CAUTI rates rose nationally between 2009 and 2013.
We put in place a national program to reduce CAUTI. Specifically, we enrolled 926 intensive care unit (ICU) and non-ICU hospital units in 603 hospitals spread over 32 states, the District of Columbia and Puerto Rico between March 2011 and November 2013.
By the end of the 18-month program, UTI rates among hospital patients in general wards had dropped by a third. Specifically:
• The rate of CAUTIs dropped from 2.40 per 1000 days of catheter use to 2.05 (a ~14 percent overall drop).
• Nearly all of the decrease in CAUTI rates was due to changes in infection rates in non-ICUs, which went from 2.28 to 1.54 infections per 1,000 catheter-days – a drop of 32 percent. In non-ICUs, the overall use of catheters decreased by 7%.
• ICUs didn’t see a substantial change in either CAUTI or catheter use, likely because the nature of patients treated in ICUs means more frequent urine output monitoring and culturing of urine, so UTIs are more likely to be spotted.
Dr. Markus Juonala[/caption]
Markus Juonala, MD, PhD
Murdoch Childrens Research Institute, Parkville
Victoria, Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Juonala: This is an epidemiological follow-up study investigating whether childhood infections and socieconomic status are associated with cardiovasular risk factor and early chances in vasculature.
The main finding was that childhood infections were associated with obesity and impaired vascular function in adulthood among those individuals with low socioeconomic status.
Dr. Steven Kyle Grinspoon[/caption]
Steven Grinspoon, MD
Professor of Medicine, Harvard Medical School
MGH Endowed Chair in Neuroendocrinology and Metabolism
Director, MGH Program in Nutritional Metabolism
and Nutrition Obesity Research Center at Harvard
MGH
Boston, MA 02114
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Grinspoon: Numerous epidemiologic studies have shown that people living with HIV face a 1.5 to 2-fold increased risk of heart attack, or myocardial infarction, as compared to individuals without the virus. Mechanisms underlying the increased risk of myocardial infarction in HIV are incompletely understood. It is possible that among people living with HIV, increased systemic immune activation fuels arterial inflammation. Arterial inflammation may, in turn, promote the development of high-risk morphology coronary atherosclerotic plaque, which is liable to rupture and result in myocardial infarction.
For people diagnosed with HIV, the overall health benefits of immediate antiretroviral therapy (ART) are clear. However, the effects of newly-initiated antiretroviral therapy on arterial inflammation have not previously been studied. In this study, we set out to assess among a cohort of treatment-naive HIV-infected subjects, the effects of newly-initiated ART with a contemporary regimen on both immune function and arterial inflammation. We found that among treatment-naive HIV-infected individuals without clinical cardiovascular disease, newly initiated combined antiretroviral therapy has discordant effects to restore immune function without reducing the degree of arterial inflammation.
Jennifer Mahony, PhD and Prof Douwe Van Sinderen[/caption]
Jennifer Mahony, PhD and
Prof Douwe Van Sinderen
Dept of Microbiology
University College Cork
Cork, Ireland
MedicalResearch.com Editor's note: Dr Jennifer Mahony & Prof Douwe van Sinderen, of the APC (Alimentary Pharmbiotic Center) Microbiome Institute, University College Cork, Ireland, have received a Grand Challenges Explorations Grant from the Bill & Melinda Gates Foundation to study the microbiota (bacteria and viruses) of infants in developing countries. This study seeks to improve the gut health of infants which could potentially prevent/reduce the estimated 0.8 million infants who die annually in developing countries.
Dr. Mahony & Prof. van Sinderen answered several questions about the upcoming study for the MedicalResearch.com audience.
MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by a microbiome?
Response: The World Health Organisation promotes exclusive breast-feeding in infants until they are at least 6 months old. Early weaning in developing countries where sanitary conditions may be poor may lead to the introduction of microorganisms such as Shigella, which can cause intestinal infections and in extreme cases may be fatal. 0.8 million infant deaths in developing countries could be avoided annually according to UNICEF if exclusive breast-feeding is continued to the sixth month of life. Our intestinal tracts naturally contain many bacteria, called our microbiota, and the composition of this microbiota may have implications for our health and well-being. Just in the same way that drinking a probiotic drink every day is reported to promote a healthy gut microbiota, we will investigate how bacterial viruses (that specifically infect bacteria and not humans!) can change the gut bacterial population.
Dr. Nicole Shen[/caption]
Dr. Nicole Shen
New York-Presbyterian/Weill Cornell Medical College
MedicalResearch.com: What is the background for this study?
Dr. Shen: Clostridium difficile infection (CDI) is a persistent, healthcare associated infection with significant morbidity and mortality that costs the US billions of dollars annually. Prevention is imperative, particularly for patients at high risk for infection – hospitalized adults taking antibiotics. Trials have suggested probiotics may be useful in preventing CDI. We conducted a systematic review with meta-analysis in this high-risk population, hospitalized adults receiving antibiotics, to evaluate the current evidence for probiotic use for prevention of CDI.
Dr. Nombela Franco[/caption]
Luis Nombela-Franco, MD, PhD
Structural cardiology program.
Interventional Cardiology department.
Hospital Clínico San Carlos, Cardiovascular Institute
Madrid, Spain
(Dr. Nombela-Franco, has a special interest in interest on percutaneous treatment of structural heart disease and coronary interventions with special focus on chronic total occlusion)
MedicalResearch.com: What is the background for this study?
Dr. Nombela-Franco: In-hospital infections are one of the most common complications that may occur following medical and surgical admissions, significantly impacted length of hospital stay, costs and clinical outcomes. In addition, approximately one third of hospital-acquired infections are preventable.
Transcatheter aortic valve replacement (TAVR) is currently the standard of care for symptomatic patients with severe aortic stenosis deemed at high surgical risk or inoperable. Patients undergoing TAVR have several comorbidities and the invasive (although less invasive the surgical treatment) nature of the procedure and peri-operative care confers a high likelihood in-hospital infections in such patients. This study analyzed the incidence, predictive factors and impact of in-hospital infections in patients undergoing transcatheter aortic valve implantation.
Mille Feuille Paper Filter[/caption]
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mihranyan: We describe for the first time a paper filter that can remove even the worst-case viruses from water with high efficiency and at industrially relevant rates. The filter is produced from 100% naturally derived cellulose and is formed into paper sheets using very simple processing, which is essentially the same as that for making paper on a large scale. Filter paper is used ubiquitously in every day life from coffee filters to chemistry classrooms but these filters have normally too large pores to retain microbes, let alone viruses.
We show for the first time that we can remove viruses as small as 20 nm! How is it possible? We use cellulose nanofibers from green algae and we possess know-how to control the distribution of the pores inside the paper to be able to remove such small particles. One important aspect, which we discuss in detail in the article, is the special internal layered structure of the filter, which is remarkably similar to French pastry mille-feuille- hence, the name mille-feuille filter.
Dr. Sushanta Mitra[/caption]
Sushanta K. Mitra, PhD, PEng
Associate Vice-President Research
Kaneff Professor in Micro & Nanotechnology for Social Innovation
FCSME, FASME, FEIC, FRSC, FCAE, FAAAS Y
York University Toronto
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mitra: As a mechanical engineer I got interested in the water problem when I had discussions with Tata Consultancy Services (TCS), India and the tertiary public health centre doctors near Mumbai, where the doctors had to deal with large number of patients with water-borne diseases. This was hugely a challenge from resource point of view as the doctors would much preferred to have their attention focused on more pressing diseases. They approached me about developing tools for rapid detection of water-borne pathogen in drinking water. Hence, my journey started on water quality monitoring.
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mitra: Here, we have developed a low-cost compact E. coli and total coliform detection system, which uses commercially available plunger-tube assembly. We incorporate a hydrogel (porous matrix) inside the tube so that the plunger-tube assembly act as a concentrator and a detector at the same time. Specially formulated enzymatic substrates are caged inside the hydrogel so that an E. coli cell trapped within the hydrogel will be lysed and react with the enzymatic substrates to produce a red color.
Dr. Andreas Bäumler[/caption]
Andreas J. Bäumler, Ph.D
Editor, Infection and Immunity
Associate Editor, PLOS Pathogens
Section Editor, EcoSal Plus
Professor, Department of Medical Microbiology and Immunology
Vice Chair of Research
University of California, Davis School of Medicine
Davis, California
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Bäumler: Antibiotics are generally beneficial for treating bacterial infection, but paradoxically a history of antibiotic therapy is a risk factor for developing Salmonella food poisoning. Our study reveals the mechanism by which antibiotics increase susceptibility to Salmonella infection.
Antibiotics deplete beneficial microbes from the gut, which normally provide nutrition to the cells lining our large bowel, termed epithelial cells. Depletion of microbe-derived nutrients causes our epithelial cells to switch their energy metabolism from respiration to fermentation, which in turn increases the availability of oxygen at the epithelial surface. The resulting increase in oxygen diffusion into the gut lumen drives a luminal expansion of Salmonella by respiration. Through this mechanism, antibiotics help Salmonella to breath in the gut.
Dr. Gabriele Messina[/caption]
Gabriele Messina, MD Dr.PH MSc
Research Professor of Public Health
University of Siena
Department of Molecular and Developmental Medicine
Area of Public Health. Room: 2057
Siena, Italy
MedicalResearch.com: What is the background for this study?
Dr. Messina: Studies conducted in the 1970s and 1980s conferred to environmental surfaces a marginal role in the transmission of health care associated infections (HAIs). Today, it is demonstrated that several pathogens such as C. difficile, VRE (Vancomycin-resistant Enterococcus) and MRSA (Methicillin-resistant Staphylococcus aureus) can survive even for months on inanimate surfaces. Up to 40% of HAIs can be spread by the hands of doctors and hospital staff after touching infected patient and/or contaminated surfaces; furthermore, people hospitalized in rooms previously occupied by patients infected by microorganism that can persist on surfaces present an increased risk to develop HAIs.
Dr. Julie Shakib[/caption]
Julie H. Shakib, DO, MS, MPH
Assistant Professor of Pediatrics | University of Utah
Medical Director | Well Baby and Intermediate Nursery
Salt Lake City
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Shakib: Immunization against influenza in the first six months of life is ineffective due to an immature immune response. Passive protection via maternal immunization offers an alternative but only a few studies have evaluated the efficacy of this immunization strategy. We found that in infants born to women immunized against influenza during pregnancy, the risk of laboratory-confirmed influenza and influenza-related hospitalization were reduced by 70% and 81% in their first 6 months of life, respectively.This large study provides more evidence that when women are immunized against influenza during pregnancy, their infants are much less likely to be diagnosed with influenza in their first 6 months.
Dr. Charu Kaushic[/caption]
Charu Kaushic. PhD.
Professor
OHTN Applied HIV Research Chair
Department of Pathology and Mol. Medicine
McMaster Immunology Research Center,
McMaster University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kaushic: Female sex hormones, estradiol and progesterone have been shown to regulate immune responses in many experimental and clinical studies. We and others have shown previously that these hormones also regulate susceptibility to and outcome of sexually transmitted infections (STIs), including Chlamydia, HSV-2, SIV and HIV-1. Most studies show that progesterone generally increases susceptibility while estradiol generally confers protection against STIs. This has recently gained much more widespread attention because of the controversy surrounding use of injectable hormonal contraceptives in geographical areas where there is high prevalence of HIV-1. The most frequently used injectable contraceptive uses a progestin-based formulation which has been correlated with 2-fold increase in HIV acquisition and transmission in epidemiological studies. Oral contraceptives that contain a combination of estradiol and progesterone do not show similar correlation with increased infection. This is currently a very important women’s health issue, which is being carefully monitored by many public health agencies, including WHO. Many researchers are focusing efforts in understanding how sex hormones can increase or decrease susceptibility of women to STIs.
We have published in this area for more than a decade, including a series of papers showing that in a mouse model, the outcome of genital herpes (HSV-2) infection can depend on which hormone we treat the mice with. A few years ago, we showed for the first time that mice that received an HSV-2 vaccine under the influence of estradiol were much better protected and showed less disease pathology (Bhavanam et al, Vaccine 2008). These results were reproduced a year later by another group, using an actual HSV-2 vaccine formulation. Since then, we have been working to understand at a cellular level, the underlying mechanism of estradiol-mediated enhanced protection. In this PLOS Pathogens paper, we report for the first time a cellular mechanism by which estradiol was seen to enhance immune protection against HSV-2 infection in mice.
The main findings are that estradiol primes dendritic cells in the vaginal tract to induce enhanced anti-viral T cell responses. Dendritic cells are key immune cells that decide what type of immune responses will be mounted against an infection. Under the influence of estradiol, the dendritic cells in the vaginal tract of mice induced Th17 cells which in turn helped enhance anti-viral T cell responses (Th1), resulting in better protection against genital HSV-2. This regulation of anti-viral immunity was seen only in the reproductive tract.
Robert Bonacci[/caption]
Robert Bonacci MPH, MD Candidate’16
University of Pennsylvania School of Medicine
MedicalResearch.com: What is the background for this study?
Response: During the mid-2000’s, the HIV incidence rate stubbornly persisted around 50,000 infections per year. Responding to this trend, President Obama released the first comprehensive US National HIV/AIDS Strategy (NHAS) in 2010. The NHAS hoped to spur a more coordinated national response and set ambitious targets for reducing HIV incidence (25 percent) and the transmission rate (30 percent), among other goals, by 2015.
To evaluate whether the U.S. achieved the NHAS goals by 2015, we used mathematical models drawing on data from the U.S. Centers for Disease Control and Prevention (CDC) on HIV prevalence and mortality for 2007 to 2012, and our own previously published incidence estimates from 2008-2012. Changes seen from 2010 through 2012 were extrapolated for the time period 2013 through 2015.
Dr. Emily Severance[/caption]
Emily G. Severance, Ph.D
Stanley Division of Developmental Neurovirology
Department of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Severance: This research stems in part from anecdotal dialogues that we had with people with psychiatric disorders and their families, and repeatedly the issue of yeast infections came up. We found that Candida overgrowth was more prevalent in people with mental illness compared to those without psychiatric disorders and the patterns that we observed occurred in a surprisingly sex-specific manner. The levels of IgG antibodies directed against the Candida albicans were elevated in males with schizophrenia and bipolar disorder compared to controls. In females, there were no differences in antibody levels between these groups, but in women with mental illness who had high amounts of these antibodies, we found significant memory deficits compared to those without evidence of past infection.
Dr. Fleming Dutra[/caption]
MedicalResearch.com: What is the background for this study?
Dr. Fleming-Dutra: One of the most urgent public health threats of our time is the emergence of antibiotic-resistant bacteria. The use of antibiotics is the single most important factor leading to antibiotic resistance around the world. Simply using antibiotics creates resistance. To combat antibiotic resistance we have to use antibiotics appropriately — only when needed and, if needed, use them correctly. In 2015, the White House released the National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB), which set a goal for reducing inappropriate outpatient antibiotic use by 50% by 2020. However, the amount of antibiotic use in the outpatient setting that is inappropriate was unknown.
MedicalResearch.com: What are the main findings?
Dr. Fleming-Dutra: In this study, we estimate that at least 30% of antibiotics prescribed in doctors’ offices, emergency departments and hospital-based clinics are unnecessary—meaning that no antibiotic was needed at all, which equates to 47 million unnecessary antibiotic prescriptions written annually in these outpatient settings. Most of those unnecessary antibiotic prescriptions were written for acute respiratory conditions, a key driver of antibiotic overuse. Thus, in order to reach the White House goal of reducing inappropriate outpatient antibiotic use by 50%, a 15% reduction in overall antibiotic use in outpatient settings is needed by 2020.
Dr. Anna Phillips[/caption]
Dr Anna C. Phillips PhD CPsychol AFBPsS
Reader in Behavioural Medicine
School of Sport, Exercise & Rehabilitation Sciences
University of Birmingham
Edgbaston Birmingham
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Phillips: We know that various factors can affect the response to vaccination and that older adults have a poorer response than younger people, i.e. they produce fewer antibodies. We also know that many immune messengers and important hormones have daily rhythms in their levels and wanted to test whether the antibody response to vaccination might also be affected by time of day. We randomised surgeries to giving morning or afternoon vaccinations and tested before and one month after the vaccination for levels of antibodies.
Two of the three flu strains (viruses) contained in the vaccine showed a higher antibody response in the morning than in the afternoon, up to 4 x higher to one of the strains (A/California) and 1.5 x higher to the B strain. None of the potential mechanisms we measured (immune messengers, hormones) seemed to be driving this effect.
