Body

In preclinical experiments, investigators restored p53 using synthetic mRNA nanoparticles, making lung and liver cancer cells susceptible to available cancer drugs

The tumor suppressor gene p53, also known as the guardian of the genome, plays a critical function in preventing cancer. Because of its powerful role, it is one of the most commonly compromised genes in cancer.

Investigators have long sought a way to restore the activity of tumor suppressor genes such as p53. Most recently, attention has turned to an approach developed at Brigham and Women's Hospital that uses nanotechnology to deliver synthetic messenger RNA (mRNA). Leveraging advancements in nanotechnology, investigators from the Brigham have found that restoring p53 not only delays the growth of p53-deficient liver and lung cancer cells but may also make tumors more vulnerable to cancer drugs known as mTOR inhibitors. The team's findings are published in Science Translational Medicine.

"mTOR inhibitors have been approved for the treatment of certain types of cancers but have not worked as well in clinical trials for many common cancers," said co-corresponding author Jinjun Shi, PhD, a faculty member in the Brigham's Center for Nanomedicine and Department of Anesthesiology. "We present evidence here that using the lipid-polymer hybrid mRNA nanoparticle platform we've developed to restore p53 may sensitize cancer cells to mTOR inhibitors. This represents a potentially powerful combination for cancer treatment."

Shi and colleagues, including co-corresponding authors Omid Farokhzad, MD, MBA, (director of Brigham's Center for Nanomedicine) and Wei Tao, PhD, (faculty in the Center), and first author Na Kong, MD, used a redox-responsive nanoparticle platform to deliver p53-encoding synthetic mRNA. The synthetic p53 caused cell cycle arrest, cell death and delayed the growth of liver cancer cells and lung cancer cells in which p53 had been depleted. In addition, synthetic p53 made the cells more sensitive to everolimus, a drug which is an mTOR inhibitor. The team reports successful results in multiple in vitro and in vivo models.

Past clinical trials of everolimus failed to show a clinical benefit in advanced cases of liver and lung cancer but found that response to the drug varied greatly between patients. Studies have also found that p53 is altered in approximately 36 percent of hepatocellular carcinomas (the most common form of liver cancer) and 68 percent of non-small cell lung cancers.

The authors note that further preclinical development and evaluation will be needed to explore that translational potential and scalability of the approach as well as its applicability to other p53 mutations and other cancers.

"We expect that this mRNA nanoparticle approach could be applied to many other tumor suppressors and rationally combined with other therapeutic modalities for effective combinatorial cancer treatment," the authors write.

A high fat diet limits the birth and growth of new neurons in adult female, but not male, mice, according to new research published in eNeuro. Further research could inspire metabolism-based preventions and treatments for brain disorders.

Metabolic disorders like obesity and type 2 diabetes are associated with an increased risk for brain disorders ranging from depression to Alzheimer's disease. The birth and development of new neurons - adult neurogenesis - may be a link between these two types of conditions. The hippocampus, an area of the brain implicated in memory and emotional processes, is a known site of adult neurogenesis.

Robison et al. fed one group of mice a high fat diet and another group a normal diet for eighteen weeks. The high fat diet caused weight gain and high blood sugar in both male and female mice, however, only female mice experienced impaired neurogenesis in the hippocampus. The female mice on the high fat diet had fewer newborn and developing neurons, while male mice on the high fat diet had the same number of new neurons as the control mice. This finding offers additional insight into why women are more at risk for greater cognitive decline during Alzheimer's disease and depression.

Metabolic diseases such as diabetes and obesity are ever more common globally. In addition to genetic disposition, lifestyle contributes strongly to the prevalence of these metabolic diseases. Precise monitoring methods are needed in order to, for example, evaluate how a change in diet or exercise affects disease and its metabolic characteristics. Now, a team from the Institute of Biological and Medical Imaging at Helmholtz Zentrum München and at the Chair of Biological Imaging at TranslaTUM at the Technical University of Munich has developed a technique that provides real-time images of biomolecules in living cells - without the need for labels or contrast agents. The evaluation of the imaging system was performed in collaboration with the Institute for Diabetes and Cancer at Helmholtz Zentrum München and the Heidelberg University Hospital.

Sound of light images biomolecules in cells and tissues

With this new technology, called Mid-infraRed Optoacoustic Microscopy, or MiROM for short, the researchers excite "fingerprint"-specific molecular vibrations with mid-infrared lasers. Selective absorption of transient mid-infrared light from different molecules triggers a thermoelastic expansion, i.e. a minute volumetric expansion that generates ultrasound waves. These waves are detected and processed to form an image of the distribution of specific molecules, depending on the wavelength(s) of excitation.

Compared to previous techniques, one outstanding advantage of this new method is that it is no longer limited to dry-fixed samples. By detecting acoustic waves, which pass easily through tissue rather than photons which are strongly absorbed by tissues and water, MiROM provides imaging features from metabolites beyond existing technologies. "MiROM offers a microscopy breakthrough. In conventional mid-IR imaging, higher biomolecule concentration leads to higher signal loss. Conversely, MiROM converts mid-IR imaging to a positive contrast modality, whereby higher concentration yields stronger signals. The technique demonstrated label-free imaging of biomolecules beyond the sensitivity limitations of Raman methods," explains Prof. Vasilis Ntziachristos, Director of the Institute of Biological and Medical Imaging and of the Chair of Biological Imaging.

A pioneering study that opens a new field in metabolic research

"MiROM provides novel insights into subpopulations of cells over time. Moreover, it enables us to detect not only lipids, but also carbohydrates and proteins in real-time", says Miguel Pleitez, who led the system development. Label-free imaging of metabolites can impact the ways we study molecular processes associated for example with fat storage and release due to the breakdown of white and brown fat cells, called lipolysis. However, a broader range of metabolic procedures and the interactions of different biomolecules can be studied as well.

Metabolic processes change in association with diabetes, obesity, or alterations of life style conditions including diet and exercise. However, observing many of these processes so far required the use of labels and contrast agents that were laborious and could affect the biological function studied. This new technology can revolutionize metabolism readings: "MiROM offers unique in-vivo label-free observations of metabolic processes in real-time, which can be applied to dynamically study the effects of different diets on the cellular level or evaluate the performance of new classes of drugs", says Miguel Pleitez. The team is working on a revised version of MiROM with enhanced speed, resolution, and sensitivity to boost discoveries in a broader spectrum of diseases including cancer.

Initial implementations of MiROM as a laboratory microscope demonstrated metabolic imaging in cells and excised tissues. "Our long-term vision is to adapt the technology to enable measurements in humans, so that we can study systemic processes associated with lifestyle changes and optimize disease prevention strategies", explains Ntziachristos.

ANN ARBOR--Leftover prescription opioids pose big risks to kids, yet most parents keep their own and their child's unused painkillers even after they're no longer medically necessary for pain.

But a new University of Michigan study suggests that convenient disposal paired with tailored risk education can improve those numbers.

Terri Voepel-Lewis, U-M associate professor of nursing, and colleagues, found that prompt disposal of leftover medications improved if parents received a disposal packet at the time the medications were prescribed. Further, parents who saw tailored online messages about the risks opioids pose to children and teens were less likely to report that they intended to keep leftover medications.

The study included 517 parents of children ages 7-17 who were prescribed a short course of opioids. Parents were placed in one of three groups: some received a take-home pill disposal packet; some received the packet and an interactive web-based program asking them to make opioid dosing decisions for their children in different real-life scenarios; and some received neither intervention.

Of the parents, 93% had leftover medications but only 19% in the control group promptly disposed of them. However, prompt disposal doubled (38.5%) for parents who received both interventions.

Further, the number of parents in the web intervention group who planned to keep leftover opioids was half the number in the control group. Higher risk perception lowered the odds of parents keeping the leftover opioids, while parental past opioid misuse increased them.

The takeaway for parents is that leftover opioids pose the risk of poisoning and death for children. The only way to completely avoid this risk is to get rid of leftovers as soon as possible, said Voepel-Lewis, principal investigator on the project.

The takeaway for prescribers is that the best way to improve prompt disposal rates is to give parents a simple way to dispose of the drugs, paired with information that boosts their understanding of the risk that keeping leftover medications poses to their children.

Several findings in the study surprised the researchers, Voepel-Lewis said.

"The high rate of parental misuse (11.8%) was a surprise--and that this and past retention behaviors were so predictive of intention to keep the drug around," she said. "This is something that prescribers need to know and assess for."

Nor did the team expect that intention-to-dispose rates would be as high, given past findings, Voepel-Lewis said.

"We believe that the opioid crisis awareness in our community may have falsely increased parents' reports of intention to dispose, knowing that many people in Michigan have died from accidental overdose," she said.

Though prescribing rates have recently decreased for opioids, leftover medications are still common for opioids and other risky drugs, like sedatives and stimulants.

"Many hospitals are now beginning to give disposal packets, mostly marketed and costly ones, with opioids," Voepel-Lewis said. "They are not doing this with other risky drugs and the risk enhancement information is lacking. We will make our educational information available at the end of our studies."

Mobile phone apps are increasingly being used to support breastfeeding decisions - sometimes at a cost, a Flinders University study indicates.

The objective approach of most infant feeding (IF) apps gives mothers a perception of greater control, confidence and efficiency at a time of transition and stress in the early stages of parenting an infant, the study found.

However, with more than 100 such apps available, the mobile content can also present new mums with another set of potential worries, including feeling overwhelmed by the information, concerns about over-reliance on the app, and even questioning the app's advice.

Overall the women interviewed in the study were positive about using such apps, says senior researcher Dr Jacqueline Miller, an expert in paediatric nutrition.

"Some apps provide information that is not always accurate and can't be tailored to the individual," she warns. "Information stored in the app can provide a useful history to discuss with health care providers who can then provide much more individualised advice, particularly with breastfeeding."

These targeted mobile apps can take the guesswork out of parenting.

"They are increasingly giving mothers a modern way of tracking aspects of baby care, including feeding regularly, sleep, growth and nappy changes," she says.

"A generation ago we used a safety pin to remind themselves which side to start feeding on. But these days we use apps to record all sorts of facts," Dr Miller says.

National Health and Medical Research Council guidelines in Australia recommend exclusive breastfeeding for approximately the first six months.

Community and health professional support is important for maternal decisions, with self and social perceptions, lifestyle choices as well as physical and psychological issues also playing a part, says Dr Carly Moores, who also contributed to the study.

Another co-author Kaitlyn Dienelt, who conducted detailed interviews with nine nursing mothers using eight different IF apps in South Australia over 12 months, says the study demonstrates how important the mobile apps can be in making mums feel encouraged and supported in their breastfeeding practices.

"This technology is helping mothers with everyday routines and decision-making which can be tiring and sometimes complex with breastfeeding - although some mobile apps are better than others."

"Overall, the participants were positive and some even felt they would have given up on breastfeeding without the app," she says.

"In a growing world of technology, studies like this are is important in shaping future research in providing the best health and self-management information via mobile devices to the wider population."

In one of the first studies of its kind, the study led by Flinders University College of Nursing and Health Sciences nutrition and dietetics experts sought to analyse the experience of mothers, the suitability of information and readability of the app material from an outside perspective.

With more than 100 apps to assist optimal infant feeding available on the market, many are free with in-app purchases, or some purchased of premium versions of free IF apps.

The mobile health app market is booming, expected to exceed $US30 billion by 2020. The World Health Organisation has forecast that mHealth apps will have a myriad of uses includes interventions and behaviour change, disease or condition self-management, data monitoring and e-information provision.

Hennigsdorf/Berlin, Germany, December 23, 2019 - Diagnostics company SphingoTec GmbH ("sphingotec", Hennigsdorf, Germany) today announced a publication in Critical Care1 with data on 2,000 ICU patients demonstrating that sphingotec's proprietary biomarker bio-ADM® (Bioactive Adrenomedullin) not only identifies high-risk patients for septic shock at admission but also identifies patients in the general ICU patient population who require immediate life-saving therapeutic intervention.

In an observational ancillary study to the FROG-ICU study, high blood levels of bio-ADM® at admission to the ICU were an early predictor of the requirement for organ support and treatment with ionotropes and vasopressors. Elevated bio-ADM® blood levels were also significantly associated with a prolonged length of ICU stay and fatal outcomes within 28 days post-admission, whereas low levels of bio-ADM® at admission were associated with positive outcomes.

This study is the largest published investigation on bio-ADM® in a patient cohort of which about 25% of patients suffered from sepsis and 75% of patients had conditions that were not sepsis-related. According to principal investigator Prof. Alexandre Mebazaa (Hôpital Lariboisière, Paris, France), the results demonstrate that bio-ADM® is not only a biomarker indicating impaired endothelial function in patients with septic shock as previously shown2, but also identifies further ICU patients who require rapid therapeutic intervention at admission due to distortion in endothelial function, which is independently associated with malperfusion of organs.

Previous data from more than 20,000 patients provide evidence, that high blood levels of bio-ADM® reflect impaired endothelial function independently from inflammation and other co-morbidities. High bio-ADM® blood levels indicate distortions in the barrier function of the endothelium before the patients progress to a critical stage. Failure of endothelial function has been demonstrated to precede the life-threatening blood pressure drop that causes shock and multiorgan failure e.g. in patients with sepsis at ICUs and in emergency departments (EDs) 2-3. Each year, 6 million people die from sepsis, one of the largest contributors to global disease burden causing $24 billion in direct annual costs to the U.S. healthcare system alone. As elevated bio-ADM® blood levels precede septic shock, bio-ADM® screening can identify risk patients who require early life-saving therapeutic intervention.

"The new study results add data to the broad body of existing evidence that our biomarker bio-ADM® can reliably support critical care physicians in identifying high-risk patients when they first present at the ICU," said Dr. Andreas Bergmann, founder and CEO of sphingotec. "We are set to launch the fully automated CE-IVD-marked point-of-care bio-ADM® assay on our widely established Nexus IB10 immunoassay platform by mid-2020. We are convinced that this rapid test for bio-ADM® will support earlier treatment decisions and improve outcomes of patients at ICUs and emergency departments."

Cumulative exposure to obesity could be at least as important as actually being obese in terms of risk of developing type 2 diabetes (T2D), concludes new research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]). The study is by Dr Juhua Luo, School of Public Health, Indiana University, Bloomington, IN, USA, and colleagues.

Although obesity is a well-established risk factor for T2D, little is known about the relationships between age of onset of obesity and cumulative exposure to obesity and risk of T2D, especially among young adults. In this study, the authors used data from the Australian Longitudinal Study on Women's Health (ALSWH) to identify body mass index (BMI) trajectories over the early adult life course. They then examined the relationship between distinct BMI trajectories and risk of T2D. Also investigated were the associations between timing of obesity onset, obese-years and T2D.

Women aged 18-23 years at baseline (n=11,192) enrolled in the ALSWH in 1996 were followed up about every three years via surveys for up to 19 years. Self-reported weights were collected up to seven times. New cases of T2D were self-reported. A total of 162 (1.5%) women newly developed T2D over an average of 16 years of follow-up. Six distinct BMI trajectories were identified, varying by different initial BMI and different rates of increase of obesity.

Higher initial BMI was associated with an increased risk of diabetes. Increased age at onset of obesity was associated with a lower risk of diabetes, with a 13% lower risk of developing T2D per one-year delay in onset. A higher number of obese-years was associated with increased risk of developing T2D. Obese years is calculated by person's BMI minus the BMI for obesity (30), then multiplying by the number of years of exposure. The authors estimate* that for each extra 10-obese years, the risk of diabetes increased by 25%.

Among 10,521 (94%) women who were not obese at baseline, the researchers observed that women who became obese during follow-up had a 3-fold increased risk of T2D compared to women who remained not obese. More specifically, compared with women who did not become obese during the follow-up, women who became obese and had obese-years of

Results of analysis using only the women's initial (baseline) BMI found that having baseline obesity (a BMI of 30 or more) was associated with a 7-times increased risk of developing diabetes, while overweight women (BMI 25.0 to 29.9) had a 2.3 times increased risk compared with women with normal weight.

Analysing how the women's BMI developed through the study, those who were already obese at baseline, but who continued to put on weight rapidly on top of this had 10-times increased risk of developing diabetes compared with normal weight women who remained stable; women who were overweight (rather than obese) at baseline, and who put on weight rapidly, had a 5-times increased risk of diabetes compared to the normal weight women who remained stable.

The authors found that further analysis adjusting the data for the number of children, dietary intake (including total energy intake), fibre intake, and dietary glycaemic index (how foods with different carbohydrate composition affect blood glucose levels) gave similar results.

The authors say: "More than half of the women experienced a rapid BMI increase from early (18-23 years old) to middle adulthood (37-42 years old). Our data confirmed that BMI in young adulthood played an important role in the subsequent risk of developing type 2 diabetes during adulthood. We also observed that women who were non-obese at baseline but became obese during follow-up had a higher risk of type 2 diabetes relative to women who stayed non-obese; the younger the age at onset of obesity or the greater the obese-years, the higher the risk of type 2 diabetes."

They add: "Our data also indicated that baseline BMI among young women was significantly associated with risk of developing type 2 diabetes...The results highlight the importance of overweight or obesity in early adulthood as risk factors for adult diabetes, indicating that weight control starting before early adulthood is critical for reducing type 2 diabetes risk in later life."

They conclude their work demonstrates "the importance of preventing or delaying the onset of obesity and reducing cumulative exposure to obesity to substantially lower the risk of developing diabetes. We recommend that people self-monitor weight change over time, and that health care providers look at weight change in addition to current weight as another risk factor for diabetes."

New Rochelle, NY, December 20, 2019--A new study shows that among a set of disadvantaged women, Medicaid managed care reduces the women's access to high-quality hospital services during pregnancy and delivery and was associated with worse birth outcomes, worse prenatal care, and a higher risk of inappropriate gestational weight gain. The specific results and their implications are reported in a study published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article on the Journal of Women's Health website through January 20, 2020.

Ji Yan, PhD, Appalachian State University, Boone, NC, was the author of the article entitled "The Impact of Medicaid Managed Care on Obstetrical Care and Birth Outcomes: A Case Study." Dr. Yan based his findings on a dataset of disadvantaged women who had singleton births over a 10-year period, resulting in more than 78,300 mother-infant observations. The Medicaid managed care program under which these women received health care achieved cost savings by reducing the use of some high-tech obstetrical services and limiting access to high-quality hospital services. There was a price to pay, however, in maternal health care utilization and infant well-being.

Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health and Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, states: "This study emphasizes the need to be cautious in designing and implementing lower cost managed care programs for low-income obstetrical patients, as it demonstrates the possible negative outcomes for both mothers and their infants."

A research team at Kobe University Hospital have further illuminated the likelihood of cancer drug side effects that can occur due to genetic mutations in the drug-metabolizing enzyme. The team led by Dr. TAKAOKA Yutaka also developed a mathematical model by using the results of molecular simulation analyses to predict the possibility of side effects.

It is hoped that this research will pave the way for effective predictions of cancer drug side effects and treatment results.

These research findings were first published in the American Scientific Journal 'PLOS ONE' on November 15 2019.

Research Background

Predictions regarding cancer treatment effectiveness and side effects can be made relating to 1. Drug metabolism and 2. Drug effectiveness on administration. However, how well drugs will be metabolized, their effectiveness and the likelihood of side-effects depends on individual differences. For example, before a patient with colon cancer is treated with the anti-cancer drug Irinotecan, a genetic analysis of their UGT1A1 must be performed. UGT1A1 is an enzyme found mainly in the liver which is responsible for processing many chemical substances, including Irinotecan. It is known that the patient with mutations in the UGT1A1 gene (in particular the mutations UGT1A1*6 and UGT1A1*28) have difficulty metabolizing this cancer drug, making severe side effects.

In recent years, genetic analysis technology has been advancing and new mutations in UGT1A1 are being discovered. To date, around 70 different mutations have been found. The ability of each of these newly discovered mutations to metabolize drugs is unknown, therefore it is difficult to accurately determine the likelihood of adverse reactions to anti-cancer agents.

Research Methodology

Professor Takaoka et al. used the results from molecular computer simulation analyses and wet laboratory experiments (using cells) to develop the following mathematical model for drug metabolism by the UGT1A1 (Figure 1).

They succeeded in using this mathematical model to predict the ability of UGT1A1 mutants to metabolize the anti-cancer agent with high accuracy- as shown in the bar graph (Figure 2). The predictions using the mathematical equation (gray bars) are very similar to the actual results (black bars).

Based on these results, this method was able to predict the drug metabolizing ability of UGT1A1 mutations. It is hoped that this methodology could be used to predict the possibility of cancer drug side-effects before they are prescribed- even for newly discovered mutations of UGT1A1.

Further Research

It is expected that further research using a similar methodology could be utilized to predict cancer drug effectiveness. Professor Takaoka et al. have already used RIKEN's K-computer to perform a basic analysis and they are currently working towards being able to predict the effectiveness of drugs utilized in lung cancer treatment.

High penKid® plasma levels identified all ED patients with hidden AKI and AKI at admission and reflected worsening of kidney function.

penKid® point-of-care (POC) implementation in EDs could eliminate current limitations of AKI prediction in septic patients allowing physicians to adjust treatment and therapy monitoring of patients with suspected AKI.

An automated CE-marked IVD penKid® assay running on sphingotec's POC platform Nexus IB10 will be launched in Q1 2020.

Hennigsdorf/Berlin, Germany, December 20, 2019 - Diagnostics company SphingoTec GmbH ("sphingotec", Hennigsdorf Germany) today reported on the publication of novel study results of its proprietary kidney function biomarker penKid® in BMC Emergency Medicine1. The data from a prospective study enrolling 588 septic patients demonstrate that penKid® accurately predicted acute kidney injury (AKI), multiorgan failure (MOF) and mortality in unselected sepsis patients at presentation to the emergency department (ED). Furthermore, increasing penKid® blood levels indicated worsening kidney function.

While organ dysfunction is a hallmark of sepsis, the renal system is being particularly susceptible. One in two patients with septic shock develop AKI and are at increased risk of both severe morbidity and higher mortality. In the current study, the admission levels of penKid® and serum creatinine (SCr) were corelated with patient outcomes. SCr is the current diagnostic standard and is used to calculate the estimated glomerular filtration rate (eGFR), a surrogate parameter quantifying kidney function. In the study, elevated penKid® blood levels at admission predicted all septic patients who developed AKI. Furthermore, high penKid® levels independently from eGFR, identified patients with subclinical AKI at ED admission, who could not be identified by SCr values. penKid® also predicted multiorgan failure and 28-day mortality.

Previously published clinical data from patients with sepsis admitted to intensive care units (ICUs) have provided evidence, that elevated blood levels of penKid® at admission predict AKI, worsening kidney function, organ failure and mortality independently from inflammation and other co-morbidities2. The new results demonstrate that penKid® can also identify AKI patients in a routine ED setting, in which therapy decision making is currently delayed due to the fact that eGFR assessment requires serial measurements2 and creatinine metabolism is affected by inflammation, fluid overload and the use of nephrotoxic agents3-4. Based on the study results, penKid® is a reliable marker for the detection and monitoring of subclinical AKI.

"These study results demonstrate for the first time that penKid® provides physicians at the emergency department with urgently needed information, which is complementary to the current diagnostic toolbox and enables the detection of AKI, particularly in patients with hidden AKI risk," said Dr. Andreas Bergmann, founder and CEO of sphingotec. "To support timely treatment decisions that are likely to improve outcomes in critical care patient, we will launch in Q1-2020 a fully automated CE-IVD-marked point-of-care penKid® assay on the established Nexus IB10 platform."

The end of 2019 brings with it holiday gatherings, school vacations, and the annual tradition of New Year's resolutions - with some of the most common resolutions being to exercise more and lose weight. Popular gym chains across the country capitalize on the broad desire to get healthy in the New Year with persuasive post-holiday marketing campaigns, but they're also undermining public health warnings about the dangers of indoor tanning, according to a new study from UConn researchers published today by the Journal of the American Medical Association (JAMA) Network Open.

"An interesting study was published a few years ago that found an association between physical activity and increased risk for melanoma," said Sherry Pagoto, a professor in the Department of Allied Health Sciences and director of the UConn Center for mHealth and Social Media who is the lead author of today's study. "Exercise is typically associated with reduced risk for cancer, so it was surprising to see an association with increased risk for melanoma. Around the same time we began to notice some of the large gym chains offering tanning beds. This got us wondering just how many gyms are offering tanning beds and about the implications of marketing tanning beds to physically active people who we now know are at increased risk for melanoma."

Little is known about how pervasive the presence of tanning beds is in gyms. In seeking better understanding, Pagoto's team sampled locations from three of the six largest national gym chains in the United States - Anytime Fitness, Gold's Gym, and Planet Fitness. Across all five regions of the country, the researchers identified 1,927 locations in 33 states and the District of Columbia, and then surveyed those locations to see if indoor tanning services were available for the location's clients. A total of 1,727 gyms responded to the survey calls and inquiries.

Over 78 percent of the gyms reached had tanning beds: a total of 4,660 tanning beds were found in the 1,727 gyms. Planet Fitness provided more tanning beds than the other gyms, followed by Anytime Fitness and then Gold's Gym. The Midwest region had the highest proportion of tanning beds in the sampled gyms when compared to the other four regions in the country - 87 percent of the locations surveyed in the Midwest had tanning beds.

"Gyms appear to be the new tanning salons," Pagoto said. "This is surprising because our sense had been that the tanning industry was on the decline. However, it appears that the industry is just moving tanning beds into novel environments - with gyms being the most common."

Pagoto continued, "Because people associate gyms with health, gyms are essentially putting a 'health halo' on tanning beds. The public health community has been trying to communicate the message to the public that tanning beds are not safe or healthy, but gyms with tanning beds are obstructing that message."

The surveys were conducted between June 2018 and February 2019, and focused on only the three gym chains, which are among the six largest gym chains in the United States. Only one other chain, SNAP Fitness, provides tanning beds; the remaining two chains - LA Fitness and 24 Hour Fitness - do not offer indoor tanning, according to their corporate offices.

"The good news is that there are gym chains that do not include tanning beds in their business model, and so consumers have a choice," Pagoto said. "I just have to question the motivation of any gym that uses a carcinogen to lure members. Is their priority really my health? Regardless of whether a consumer uses tanning beds, they should take pause when considering their choice of gym."

Skin cancer is the most commonly diagnosed cancer in the United States. Melanoma, the deadly form of skin cancer, is one of the most common types of cancer among women, especially young women, and exposure to ultraviolet (UV) rays is the most preventable cause. While exposure to UV rays from indoor tanning beds is particularly carcinogenic - more than 400,000 cases of skin cancer may be related to indoor tanning in the United States each year, according to a 2014 meta-analysis - it's also completely avoidable.

An educational outreach training package has shown to be effective for improving management of respiratory diseases in Brazil, raising hopes it could be rolled out to treat other common, severe diseases in low- and middle-income countries.

Researchers from the University of East Anglia (UEA) and the University of Cape Town, with partners from Brazil, the UK and South Africa, have created the Practical Approach to Care Kit (PACK) to provide basic, cost-effective ways to diagnose and treat diseases such as chronic obstructive pulmonary disease (COPD) and asthma.

The 'Effects of PACK guide training on the management of asthma and chronic obstructive pulmonary disease by primary care clinicians: a pragmatic cluster randomised controlled trial in Florianópolis, Brazil,' was published this week in the British Medical Journal Global Health.

Prof Max Bachmann, professor of health services research at UEA's Norwich Medical School, led the study in the Brazilian city of Florinópolis. PACK is now being used in all municipal clinics in Florinópolis, where doctors and nurses have been trained in the effective diagnosis and treatment of COPD and asthma, as well as other common diseases.

Prof Bachmann said: "Better primary care for these diseases will improve the health of whole populations of adult Brazilians, especially older people with multiple long-terms conditions.

"Respiratory diseases such as COPD and asthma are common and can be disabling or life-threatening, but are often under-recognised and under-treated or incorrectly treated in Brazil."

The Global Burden of Disease Study 2016 ranked COPD as the eighth-highest disease in Brazil in terms of disability-adjusted life years lost. Asthma was ranked 17th in terms of years lived with disability. WHO's World Health Survey found that 23 per cent of Brazilian adults aged 18 to 45 years reported wheezing in the last year, of whom only 12 per cent had a doctor diagnosis of asthma.

Florianópolis has a population of 486,000 and was the first Brazilian municipality to provide universal health coverage under the auspices of the national Family Health Strategy. Although it is one of the wealthiest cities in Brazil, with a large private health sector, a substantial proportion of its population has lower incomes and depends on free municipal primary care facilities.

Prof Bachmann said: "Provision of good-quality primary healthcare, including investigation, diagnosis and appropriate treatment of asthma, COPD and comorbid conditions, is a crucial part of the solution."

PACK gives doctors and nurses customised, up-to-date, evidence-based, point-of-care, clinical decision support. The Brazilian research found training improved cooperation between doctors and nurses, while expanding the nurses' roles and confidence. Nurses were not authorised to prescribe asthma or COPD medication or to request spirometry, but they were trained to refer patients whom they identified as needing these interventions to doctors in their primary care teams.

Prof Bachmann said: "Training doctors and nurses together aimed to align their clinical decision-making. These results add to previous evidence about interventions to promote inter-professional collaboration."

Previous research in South Africa found that earlier versions of PACK improved asthma treatment in primary health care clinics, while also improving diagnosis, treatment and health outcomes for other chronic diseases such as tuberculosis and HIV. The PACK programme is also being rolled out in Nigeria and Ethiopia, with plans to do the same in China and Vietnam. This is the first trial of PACK outside South Africa, and shows that it can work in different settings.

Oak Brook, IL - January's edition of SLAS Discovery features an analysis of two plated sets of synthetic compounds available from the National Cancer Institute (NCI), and the author's positive and negative results of using this type of collection in his lab's research.

Adam Zweifach, Ph.D., (The University of Connecticut) points out that NCI's compound collections are a valuable resource for academic scientists interested in assay development and drug discovery. The benefits, he concludes, are that the compounds provided were at a convenient size to screen manually; available at minimal (if any) cost; their property and activity data is readily available online, and acquiring a re-supply is easy and convenient.

However, he also noted that the collections did have a significant drawback: they can contain a large number of compounds that are pan assay interfering and nonspecific (PAINS), or contain other chemical liabilities revealed by tools like the rapid elimination of swill (REOS) software filters. This means that screening them is likely to generate hits in many assays; this is good, because it allows researchers to validate their assays and post-screening workflows, but also bad because the hits are unlikely to be attractive leads.

To solve this problem, Zweifach suggests that the NCI create a collection of 10,000 carefully selected lead-like compounds pooled into 1000 wells, which may help with the generation of more attractive hits in most assays. He believes that creating this kind of collection would exponentially help advance academic drug discovery efforts and efficiency.

Zweifach received his doctorate in physiology from Yale University and completed his postdoctoral fellowship at Stanford University. He then established his own lab in the Department of Physiology and Biophysics at the University of Colorado Health Sciences Center before moving to the Department of Molecular and Cell Biology at the University of Connecticut. Here, he became interested in phenotypic screening and has since focused on using high-throughput flow cytometry to discover immunologically active small molecules and on developing ways to use intramolecular FRET sensors based on fluorescent protein pairs for screening.

All print, broadcast and online journalists who receive the Obesity embargo alert agree to abide by the embargo and may not publish, post, broadcast or distribute details of the embargoed studies before the embargo date and time.

When writing about these studies, journalists are asked to attribute the source as the journal Obesity and to include the online link to the Obesity articles as provided below. Links become active when articles post at 3:00 a.m. (EST) on Dec. 20, 2019.

About the journal

- Obesity is the peer-reviewed, scientific journal of The Obesity Society.

Editors' Choice 1 - Special Section: Latest Research on Built Environment Interactions, including:

Embargoed Commentary, The Varying Effects of the Food, Built, and Socioeconomic Environment on BMI, Tony Kuo, tkuo@mednet.ucla.edu

(https://onlinelibrary.wiley.com/doi/10.1002/oby.22665)

Invited Review, Obesity and the Built Environment: A Reappraisal, Adam Drewnowski, James Buszkiewicz, buszkiew@uw.edu, Anju Aggarwal, Chelsea Rose, Shilpi Gupta, and Annie Bradshaw

(already online https://onlinelibrary.wiley.com/doi/10.1002/oby.22672)

Five Original Articles

Impact of Changes in the Food, Built, and Socioeconomic Environment on BMI in US Counties,

BRFSS 2003-2012, Pasquale E. Rummo, Justin M. Feldman, Priscilla Lopez, David Lee, Lorna E. Thorpe, and Brian Elbel, brian.elbel@nyumc.org

(already online https://onlinelibrary.wiley.com/doi/10.1002/oby.22603)

The Local Food Environment and Obesity: Evidence from Three Cities

Blake Byron Walker, Aateka Shashank, Danijela Gasevic, Nadine Schuurman, Paul Poirier, Koon Teo, Sumathy Rangarajan, Salim Yusuf, and Scott A. Lear, slear@providencehealth.bc.ca

(already online https://onlinelibrary.wiley.com/doi/10.1002/oby.22614)

Neighborhood Walkability and BMI Change: A National Study of Veterans in Large Urban Areas, Elizabeth Tarlov, etarlo1@uic.edu, Abigail Silva, Coady Wing, Sandy Slater, Stephen A. Matthews, Kelly K. Jones, and Shannon N. Zenk

(already online https://onlinelibrary.wiley.com/doi/10.1002/oby.22611)

Association of Food Access, Recreational Opportunities, and Natural Amenities with Engagement in the Veterans MOVE! Weight Management Program, Laura A. Graham, lauragraham@uabmc.edu, Emily B. Malone, Joshua S. Richman, April P. Carson, Olivia Affuso, Sara J. Knight, and Emily B. Levitan

(embargoed to Dec. 20, https://onlinelibrary.wiley.com/doi/10.1002/oby.22640)

Childhood Obesity and the Food Environment: A Population-Based Sample of Public School Children in New York City, Brian Elbel, brian.elbel@nyumc.org, Kosuke Tamura, Zachary T. McDermott, Erilia Wu, and Amy Ellen Schwartz

(already online https://onlinelibrary.wiley.com/doi/10.1002/oby.22663)

Editors' Choice 2 - Measuring the Carbon Footprint of the Planet's Obesity Epidemic, Faidon Magkos, fma@nexs.ku.dk, Inge Tetens, Susanne Gjedsted Bügel, Claus Felby, Simon Rønnow Schacht, James O. Hill,

Eric Ravussin, and Arne Astrup

(http://onlinelibrary.wiley.com/doi/10.1002/oby.22657)

Also see accompanying Commentary by Boyd Swinburn (http://onlinelibrary.wiley.com/doi/10.1002/oby.22708)

Editors' Choice 3 - Intrauterine Environment and Autonomic System Programming, Haliza Mat Husin, Franziska Schleger, Ilena Bauer, Ellen Fehlert, Isabelle Kiefer-Schmidt, Magdalene Weiss, Karl Oliver Kagan, Sara Brucker, Jan Pauluschke-Fröhlich, Hari Eswaran, Hans-Ulrich Häring, Andreas Fritsche, and Hubert Preissl, hubert.preissl@uni-tuebingen.de

(http://onlinelibrary.wiley.com/doi/10.1002/oby.22664)

Editors' Choice 4 - Role of Exposure to Stressors in Racial Disparities in BMI, Adolfo G. Cuevas, adolfo.cuevas@tufts.edu, Ruijia Chen, Natalie Slopen, Katherine A. Thurber, Norbert Wilson, Christina Economos, and David R. Williams

(http://onlinelibrary.wiley.com/doi/10.1002/oby.22648)

ADDITIONAL EMBARGOED RESEARCH

Weight History in Clinical Practice: The State of the Science and Future Directions, from The Obesity Society Clinical Committee, Robert F. Kushner, rkushner@northwestern.edu, John A. Batsis, W. Scott Butsch, Nicola Davis, Angela Golden, Florencia Halperin, Srividya Kidambi, Sriram Machineni, Marsha Novick, Ava Port, Domenica M. Rubino, Katherine H. Saunders, Linda Shapiro Manning, Taraneh Soleymani, and Scott Kahan (http://onlinelibrary.wiley.com/doi/10.1002/oby.22642)

Also see accompanying Commentary by Michelle Look (http://onlinelibrary.wiley.com/doi/10.1002/oby.22691)

Scroll down to find abstracts for each of the above papers. To request the full text of any of these studies and agree to the embargo policy, or to arrange an interview with a study's author or an obesity expert, please contact communications@obesity.org.

Editors' Choice Abstracts

Editors' Choice 1 - Special Section: Obesity--Environment Interactions

Please email Managing Editor Allison Templet, atemplet@obesity.org, for papers listed above.

Editors' Choice 2 - The Environmental Foodprint of Obesity

Emissions of greenhouse gases (GHG) are linked to global warming and adverse climate changes. Meeting the needs of the increasing number of people on the planet presents a challenge for reducing total GHG burden. A further challenge may be the size of the average person on the planet and the increasing number of people with excess body weight. We used data on GHG emissions from various sources and estimated that obesity is associated with ~20% greater GHG emissions compared with the normal-weight state. On a global scale, obesity contributes to an extra GHG emissions of ~49 megatons per year of CO2 equivalent (CO2eq) from oxidative metabolism due to greater metabolic demands, ~361 megatons per year of CO2eq from food production processes due to increased food intake, and ~290 megatons per year of CO2eq from automobile and air transportation due to greater body weight. Therefore, the total impact of obesity may be extra emissions of ~700 megatons per year of CO2eq, which is about 1.6% of worldwide GHG emissions. Inasmuch as obesity is an important contributor to global GHG burden, strategies to reduce its prevalence should prioritize efforts to reduce GHG emissions. Accordingly, reducing obesity may have considerable benefits for both public health and the environment.

Editors' Choice 3 - Maternal Weight, Weight Gain, and Metabolism are Associated with Changes in Fetal Heart Rate and Variability

Objective: Pre-pregnancy obesity and extensive weight gain can lead to diseases in the offspring later in life. The aim of this study was to evaluate the effect of anthropometric and metabolic factors on the fetal autonomic nervous system (ANS) in uncomplicated pregnancies.

Methods: A total of 184 pregnant women in the second or third trimester were included, and for 104 women, maternal insulin sensitivity (ISI) was determined. Fetal heart rate (HR) and heart rate variability (HRV) were determined by magnetic recording. Associations of maternal prepregnancy BMI, weight gain, and ISI with fetal HR and HRV were evaluated by ANCOVA, partial correlation, and mediation analysis.

Results: HR was increased and HRV decreased in fetuses of mothers with overweight or obesity in comparison to normal-weight mothers. Fetal HR was negatively correlated with maternal weight gain. Maternal pre-pregnancy BMI was positively correlated with fetal high frequency and was negatively correlated with low frequency and low/high frequency ratio. Maternal ISI showed a negative correlation with fetal HR.

Conclusions: The results show that the fetal ANS is sensitive to alterations of pre-pregnancy BMI, weight changes, and glucose metabolism. These findings highlight the importance of the intrauterine environment on the developing ANS and the possible programming of obesity.

Editors' Choice 4 - Assessing the Role of Health Behaviors, Socioeconomic Status, and Cumulative Stress for Racial/Ethnic Disparities in Obesity

Objective: This study aimed to examine the explanatory role of health behaviors, socioeconomic position (SEP), and psychosocial stressors on racial/ethnic obesity disparities in a multiethnic and multiracial sample of adults.

Methods: Using data from the Chicago Community Adult Health Study (2001-2003), Oaxaca-Blinder decomposition analysis was conducted to quantify the extent to which health behaviors (fruit and vegetable consumption and physical activity), SEP, and cumulative stressors (e.g., perceived discrimination, financial strain) each explained differences in obesity prevalence in Black, US-born Hispanic, and non-US-born Hispanic compared with non-Hispanic White participants.

Results: SEP and health behaviors did not explain obesity differences between racial/ethnic minorities and White individuals. Having high levels of stress in four or more domains explained 4.46% of the differences between Black and White individuals, whereas having high levels of stress in three domains significantly explained 14.13% of differences between US-born Hispanic and White. Together, the predictors explained less than 20% of differences between any racial/ethnic minority group and White individuals.

Conclusions: Exposure to stressors may play a role in obesity disparities, particularly among Black and US-born Hispanic individuals. Other obesity-related risk factors need to be examined to understand the underlying mechanisms explaining obesity disparities.

ADDITIONAL EMBARGOED RESEARCH

Weight History in Clinical Practice: The State of the Science and Future Directions

Eliciting a weight history can provide clinically important information to aid in treatment decision-making. This view is consistent with the life course perspective of obesity and the aim of patient-centered care, one of six domains of health care quality. However, thus far, the value and practicality of including a weight history in the clinical assessment and treatment of patients with obesity have not been systematically explored. For these reasons, the Clinical Committee of The Obesity Society established a task force to review and assess the available evidence to address five key questions. It is concluded that weight history is an essential component of the medical history for patients presenting with overweight or obesity, and there are strong and emerging data that demonstrate the importance of life stage, duration of exposure to obesity, maximum BMI, and group-based trajectory modeling in predicting risk for increased morbidity and mortality. Consideration of these and other patient-specific factors may improve risk stratification and clinical decision-making for screening, counseling, and management. Recommendations are provided for the key elements that should be included in a weight history, and several needs for future clinical research are outlined.

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PHOENIX -- A Mayo Clinic study involving 5,540 patients with metastatic colorectal cancer finds that maintenance chemotherapy after initial treatment is more beneficial for patients whose disease is under control, compared with more aggressive treatment.

A maintenance strategy with a fluoropyrimidine chemotherapy, such as 5-FU or capecitabine, is preferred, though observation with no chemotherapy is an acceptable option for some patients, according to the analysis of results from 12 randomized clinical trials. The study appears in JAMA Oncology.

"Based on these findings, switching to a lighter, maintenance regimen of chemotherapy or even taking a break in treatment for some patients is appropriate, with reintroduction of full chemotherapy when the disease progresses," says Mohamad Sonbol, M.D., a Mayo Clinic oncologist.

"The goal of therapy in metastatic colorectal cancer is to prolong life while preserving or improving quality of life. As most of these therapies are associated with side effects, it's important to use treatments that achieve a maximum benefit with the fewest side effects," says Dr. Sonbol, the study's first author.

Colorectal cancer is the third most common cancer in the U.S. At diagnosis, 1 in 4 patients will have cancer that already has spread to other organs. Randomized controlled trials have tested different strategies for continuing chemotherapy after initial treatment, compared with less-intensive maintenance chemotherapy and observation without chemotherapy.

The results of these trials have been inconsistent, making it challenging to draw conclusions. The Mayo Clinic study used a network meta-analysis of findings from the 12 trials to compare the treatment strategies used and the outcomes.

The analysis showed no benefit in continuing full chemotherapy until progression of the disease, compared to the other strategies. Also, all maintenance strategies showed significant improvement in disease control -- progression-free survival -- compared with observation. The investigators further compared different maintenance treatments used and found that the preferred regimen is fluoropyrimidine with or without the addition of bevacizumab, a medication used in combination with cancer-fighting drugs.

"Many chemotherapies that are used are initially beneficial in both shrinking and controlling the cancer," says Tanios Bekaii-Saab, M.D., a Mayo Clinic gastrointestinal oncologist and the study's senior author. "However, after a few months of therapy, the maximum benefit is usually achieved and the main focus should be on how to continue that benefit while minimizing side effects. This study confirms that switching to maintenance treatment is appropriate and beneficial, with introduction of full chemotherapy later upon progression of the disease."