Body

The cover for issue 68 of Oncotarget features Figure 4, "Gene expression changes to the TME demonstrate sequential development of innate and adaptive immune responses," by Leong, et al.

Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade.

Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors.

Dr. Mary J. Janatpour from Dynavax Technologies, Inc., Emeryville, CA 94608,USA said, "It has long been appreciated by cancer researchers that the phenotypic heterogeneity and progressive evolution of malignant tumors minimizes the chance that any agent targeting a single molecular pathway could effectively cure advanced cancer."

The authors have previously demonstrated in mouse tumor models that employing the innate immune system to prime a T cell response, in combination with checkpoint blockade, results in deep and durable anti-tumor efficacy.

These high response rates were observed in both injected and non-injected tumor lesions and patients with PD-L1 negative tumors, indicating low levels of basal immune inflammation, responded as well as patients with PD-L1 positive tumors.

Intratumorally administered SD-101 exerts its priming activity and ultimate orchestration of a systemic anti-tumor T cell response through multiple mechanisms.

The production of interferon stimulates tumor cell killing by natural killer cells, with ensuing tumor antigen release, and induces chemokines that attract T cells back to the tumor bed.

Low-dose cyclophosphamide decreases Tregs. Additional impacted biological activities have been described, such as:

increased interferon production,
induction of immunogenic cell death,
increases in effector T cells, and
increases in functional NK cells,

...likely to be complementary to SD-101 activity by virtue of modulation of the TME. By administering SD-101 locally, rather than systemically, the researchers demonstrate that localized SD-101 injection combined with systemically administered low-dose cyclophosphamide confers an anti-tumor response at non-injected sites.

The Janatpour research Team concluded that, taken together, the intratumoral SD-101 plus low-dose CY combination may complement existing checkpoint blockade therapies in patients to improve efficacy in the clinic and extend the benefits of immunotherapy to more patients.

Adults living with HIV in Washington, D.C., were more likely to feel higher levels of emotional and physical well-being if they attended religious services regularly, prayed daily, felt "God's presence," and self-identified as religious or spiritual, according to research published online Jan. 29, 2020, in Psychology of Religion and Spirituality. By contrast, patients living with HIV who had the lowest levels of quality of life and more mental health challenges were privately religious, potentially eschewing organized religion due to fears about being stigmatized or ostracized.

"These findings are significant because they point to the untapped potential of encouraging patients living with HIV who are already religious to attend religious services regularly. Scientific evidence suggests that religions that present God as all-powerful, personal, responsive, loving, just and forgiving make a difference in health-related quality of life. By contrast, belief systems and religions that see God as punishing, angry, vengeful and distant and isolate members from their families and the larger community do not have health benefits or contribute to health-related quality of life. People who identify as spiritual also benefit from improved overall health-related quality of life," says Maureen E. Lyon, Ph.D., FABPP, a clinical health psychologist at Children's National Hospital, and senior study author.

"In general, patients living with HIV have reported that they wished their health care providers acknowledged their religious beliefs and spiritual struggles. Additional research is needed to gauge whether developing faith-based interventions or routine referrals to faith-based programs that welcome racial and sexual minorities improve satisfaction with treatment and health outcomes," Lyon adds.

More than 1 million people in the U.S. live with HIV, and in 2018, 37,832 people received an HIV diagnosis in the U.S., according to the Centers for Disease Control and Prevention (CDC). In 2017, the Washington, D.C., region recorded one of nation's highest rates of new cases of HIV: 46.3 diagnoses per 100,000 people, according to the CDC.

A research team that includes current and former Children's National faculty wanted to learn more about the degree of religiousness and spirituality reported by people living with HIV and the interplay between religion and health-related quality of life. They recruited patients to participate in a clinical trial about family-centered advance care planning and enrolled 223 patient/family dyads in this study.

Fifty-six percent of patients were male. Eighty-six percent were African American, and their mean age was 50.8. Seventy-five percent were Christian.

The researchers identified three distinct classes of religious beliefs:

Class 1, the highest level of religiousness/spirituality, applied to people more likely to attend religious services in person each week, to pray daily, to "feel God's presence" and to self-identify as religious and spiritual. Thirty-five percent of study participants were Class 1 and tended to be older than 40.

Class 2 applied to privately religious people who engaged in religious activities at home, like praying, and did not attend services regularly. Forty-seven percent of study participants were Class 2.

Class 3 participants self-identified as spiritual but were not involved in organized religion. Nearly 18 percent of study participants were Class 3, the lowest overall level of religiousness/spirituality.

Class 1 religiousness/spirituality was associated with increased quality of life, mental health and improved health status.

"Being committed to a welcoming religious group provides social support, a sense of identity and a way to cope with stress experienced by people living with HIV," Lyon says. "We encourage clinicians to capitalize on patients' spiritual beliefs that improve health - such as prayer, meditation, reading spiritual texts and attending community events - by including them in holistic treatment programs in a non-judgmental way."

What's more, the research team encourages clinicians to appoint a member of the team who is responsible for handling religiousness/spirituality screening and providing referrals to welcoming hospital-based chaplaincy programs or community-based religious groups.

"This is particularly challenging for HIV-positive African American men who have sex with men, as this group faces discrimination related to race and sexual orientation. Because HIV infection rates are increasing for this group, this additional outreach is all the more important," she adds.

FINDINGS

A study by researchers at the UCLA Jonsson Comprehensive Cancer Center suggests that using an immunotherapy drug called NKTR-214, also known as bempegaldesleukin, in combination with an infusion of anti-tumor immune cells, or T cells, may produce a stronger immune response that could help fight advanced melanoma.

When tested in mice with melanoma tumors that were unlikely to stimulate an immune response, the approach increased the number of anti-tumor immune cells, and those immune cells lived longer and functioned better than the standard therapy, empowering the cells to destroy the tumor.

BACKGROUND

Adoptive cell therapy is a type of immunotherapy that has had promising results for treating people with advanced cancers. The approach involves extracting and harvesting immune cells from a patient and engineering them in the laboratory to attack specific antigens on the surface of tumors. One challenge is that it requires giving patients interleukin 2, a protein signaling molecule in the immune system, to promote the development and expansion of the infused immune cells. But interleukin 2 can also activate cells to suppress the immune system, and because it is highly toxic, it can have serious adverse side effects.

Researchers have been seeking ways to produce large number of immune cells without exposing patients to those negative side effects -- including by combining adoptive cell therapy with other treatments.

METHOD

Researchers used mice to test NKTR-214 in combination with adoptive cell therapy. Using bioluminescence imaging, the researchers tracked the movement of T cells in the mice that received the combination therapy. The team observed an expansion of T cells in the spleen, the organ that helps accelerate the activation and expansion of T cells throughout the body. The T cells then migrated to the tumor, where they continued to have a long-lasting effect. The in vivo expansion and T cell accumulation in tumors was greatly improved when using NKTR-214 compared to using interleukin-2.

IMPACT

While immunotherapy has changed the face of cancer treatment for people with advanced cancers, it still only works in a small subset of patients. The results of the UCLA study suggest that using NKTR-214 in combination with adoptive cell therapy could be effective for more people with advanced solid tumors.

STONY BROOK, NY, January 29, 2020 - A new study led by Stony Brook University Cancer Center researchers to be published in Nature Communications suggests that the choice of anesthesia may change the metastatic process of breast cancer by affecting the cytokine and microenvironment.

Jun Lin, MD, PhD, of the Department of Anesthesiology in the Renaissance School of Medicine at Stony Brook University, and colleagues found that sevoflurane anesthesia leads to more metastatic burden in the lung after breast tumor resecting surgery than propofol in laboratory models.

The study findings may serve as a guide to design clinical trials for clinicians to optimize anesthesia choice for breast cancer surgery in order to achieve best long-term outcomes.

Babies born with low birth weights are more likely to have poor cardiorespiratory fitness later in life than their normal-weight peers. That is according to a study by researchers at Karolinska Institutet in Sweden published in the journal JAHA. The findings underscore the importance of prevention strategies to reduce low birth weights even among those carried to at term delivery.

Having a good cardiorespiratory fitness - that is ability of the body to supply oxygen to the muscles during sustained physical activity - is important for staying healthy and can reduce the risk of numerous diseases and premature death. Alarmingly, cardiorespiratory fitness is declining globally, both for youths and adults. A recent study showed that the proportion of Swedish adults with low cardiorespiratory fitness almost doubled from 27 percent in 1995 to 46 percent in 2017.

Given its implications for public health, there has been a growing interest in understanding the underlying causes of poor cardiorespiratory fitness. Researchers have identified both physical inactivity and genetic factors as important determinants. Preterm delivery, and the low birth weight associated with it, has also been linked to low cardiorespiratory fitness later in life. In this study, the researchers wanted to examine if low birth weights played a role for cardiorespiratory fitness in individuals born after pregnancy of 37-41 weeks.

They followed more than 280,000 males from birth to military conscription at age 17-24 using Swedish population-based registers. At conscription, the men underwent a physical examination that included an evaluation of their maximal aerobic performance on a bicycle ergometer. The researchers found that those born with higher birth weights performed significantly better on the cardiorespiratory fitness test. For every 450 grams of extra weight at birth, in a baby born at 40 weeks, the maximum work capacity on the bicycle increased by an average of 7.9 watts.

The association was stable across all categories of body mass index (BMI) in young adulthood and was largely similar in a subset analysis of more than 52,000 siblings, suggesting that BMI and shared genetic and environmental factors alone cannot explain the link between birth weight and cardiorespiratory fitness.

"The magnitude of the difference we observed is alarming," says Daniel Berglind, researcher at the Department of Global Public Health at Karolinska Institutet and corresponding author. "The observed 7.9 watts increase for each 450 grams of extra weight at birth, in a baby born at 40 weeks, translates into approximately 1.34 increase in metabolic equivalent (MET) which has been associated with a 13 percent difference in the risk of premature death and a 15 percent difference in the risk of developing cardiovascular disease. Such differences in mortality are similar to the effect of a 7-centimeter reduction in waist circumference."

The researchers believe the findings are of significance to public health, seeing as about 15 percent of babies born globally weigh less than 2.5 kilos at birth and as cardiorespiratory fitness have important implications for adult health.

"Providing adequate prenatal care may be an effective means of improving adult health not only through prevention of established harms associated with low birth weight but also via improved cardiorespiratory fitness," says Viktor H. Ahlqvist, researcher at the Department of Global Public Health and another of the study's authors.

A study published in The Lancet found that two ways of quickly restoring normal heart rhythm in patients with acute atrial fibrillation in the emergency department are equally safe and effective.

The large, randomized controlled trial looked at cardioversion, a medical procedure that quickly brings heart rhythm back to normal. Cardioversion can be done with a mild electric shock or with fast-acting drugs delivered through an IV.

"These methods allow us to quickly get patients back to their normal heart rate, and send them home after four to six hours in the emergency department," said Dr. Ian Stiell, lead author and senior scientist at The Ottawa Hospital and distinguished professor at the University of Ottawa.

Acute atrial fibrillation is a rapid, irregular heartbeat that must be treated within 48 hours to avoid complications like stroke and heart failure. The study team estimates that acute atrial fibrillation accounts for 430,000 emergency department visits every year in Canada and the United States.

The researchers recruited 396 patients with acute atrial fibrillation from 11 Canadian emergency departments. Cardioversion is a commonly used treatment in this country. Patients were randomly assigned to one of the two kinds.

The first group received only electrical cardioversion. Patients are sedated during this procedure, so they do not feel the shock.

The second group received a drug called procainamide through an IV. If the drug did not reset the patient's heart rhythm within 30 minutes, they received electrical cardioversion.

In the shock-only group (192 patients):

92 percent returned to their normal heart rhythm (176)

95 percent were discharged home (183)

In the drug-then-shock group (204 patients):

96 percent returned to their normal heart rhythm (196)

97 percent were discharged home (198)

52 percent recovered their normal heart rhythm with the drug alone (106)

Both kinds of cardioversion were equally good at restoring normal heart rhythm and getting patients home the same day. The drug-shock strategy was more effective for patients experiencing atrial fibrillation for the first time, and for patients younger than 70.

The two methods were equally safe -none of the patients had any serious side-effects. Two weeks after the treatment, no patients had had a stroke, 95 percent still had normal heart rhythm, 11 percent returned to the emergency department because of atrial fibrillation, three percent had an additional round of cardioversion, and two percent were admitted to hospital.

The researchers were interested to see that over half of the patients who received the drug did not need a shock to restore their regular heart rhythm. They recommend that physicians try the drug cardioversion first, to avoid unnecessary sedation.

"If I have a patient on a drug infusion, I can see other patients at the same time," said Dr. Jeffrey Perry, study co-author and senior scientist at The Ottawa Hospital and professor at the University of Ottawa. "To do an electrical cardioversion, I need to find another doctor, a nurse and a respiratory therapist, and it takes time to assemble those people."

The researchers note that patients often have a strong preference for one kind of cardioversion over the other, especially if they need it done regularly.

"While we believe that there are advantages to trying the drug infusion before the shock, the treatment choice is ultimately a shared decision between the patient and physician," said Dr. Perry.

While cardioversion is common in Canada, it isn't as well known in other parts of the world.

"In some countries, patients with acute atrial fibrillation are sent home with pills to slow their heart rate, while others are admitted to hospital," said Dr. Stiell. "Our study showed that cardioversion in the emergency department is safe and effective. We hope our results convince more physicians around the world to adopt these methods."

"Given the crowding which exists in the emergency health care setting, the Canadian Institutes of Health Research (CIHR) is proud to support this high-quality research that enhances evidence-informed clinical decisions in the transitions of care for patients with atrial fibrillation," said Dr. Brian Rowe, study co-author, Scientific Director of the CIHR's Institute of Circulatory and Respiratory Health, and professor of emergency medicine at the University of Alberta.

Researchers at the University of Birmingham and Tommy's National Centre for Miscarriage Research say giving progesterone to women with early pregnancy bleeding and a history of miscarriage could lead to 8,450 more babies being born each year.

The team have published two new studies evidencing both the scientific and economic advantages of giving a course of self-administered twice daily progesterone pessaries to women from when they first present with early pregnancy bleeding up until 16 weeks of pregnancy to prevent miscarriage.

Progesterone is a hormone that is naturally secreted by the ovaries and placenta in early pregnancy and is vital to the attainment and maintenance of healthy pregnancies.

Now the experts are calling for progesterone to be offered as standard in the NHS for women with early pregnancy bleeding and a history of miscarriage after their growing body of research has found it is both cost-effective and can increase women's chances of having a baby.

The first of the new studies, published today (31 Jan) in the American Journal of Obstetrics and Gynecology (i) examines the findings of two major clinical trials - PROMISE (ii) and PRISM (iii) - led by the University of Birmingham and Tommy's National Centre for Miscarriage Research and funded by the National Institute for Health Research (NIHR).

PROMISE studied 836 women with unexplained recurrent miscarriages at 45 hospitals in the UK and the Netherlands, and found a 3% higher live birth rate with progesterone, but with substantial statistical uncertainty. PRISM studied 4,153 women with early pregnancy bleeding at 48 hospitals in the UK and found there was a 5% increase in the number of babies born to those who were given progesterone who had previously had one or more miscarriages compared to those given a placebo. The benefit was even greater for the women who had previous 'recurrent miscarriages' (i.e., three or more miscarriages) - with a 15% increase in the live birth rate in the progesterone group compared to the placebo group.

The second of the new studies, published today (31 Jan) in BJOG: an international Journal of Obstetrics & Gynaecology (iv), evaluates the economics of the PRISM trial and, importantly, concludes that progesterone is cost-effective, costing on average £204 per pregnancy.

Meanwhile, an unpublished survey by the University of Birmingham of 130 healthcare practitioners in the UK found that prior to the results of the PRISM study just 13% offered women at threat of miscarriage progesterone, while post publication of the results in the New England Journal of Medicine in May 2019, 75% now offer the treatment.

Dr Adam Devall, Senior Clinical Trial Fellow at the University of Birmingham and Manager of Tommy's National Centre for Miscarriage Research, said: "Between 20 and 25 per cent of pregnancies end in a miscarriage, which has a major clinical and psychological impact on women and their families.

"The role of first trimester progesterone supplementation in the treatment of pregnancies at high risk of miscarriage is a long standing research question that has been debated in the medical literature for over 60 years.

"Thus far, policy makers have been unable to make evidence-based recommendations on the use of progesterone supplementation to improve outcomes.

"The PRISM and PROMISE Trials found a small but positive treatment effect, dependent on the number of previous miscarriages.

"We believe that the dual risk factors of early pregnancy bleeding and a history of one or more previous miscarriages identify high risk women in whom progesterone is of benefit. The question is, how should this affect clinical practice?"

Arri Coomarasamy, Professor of Gynaecology at the University of Birmingham and Director of Tommy's National Centre for Miscarriage Research, said: "Our suggestion is to consider offering to women with early pregnancy bleeding and a history of one or more previous miscarriages a course of treatment of progesterone 400mg twice daily, started at the time of presentation with vaginal bleeding and continued to 16 completed weeks of gestation.

"In the United Kingdom, we estimate that implementing this treatment strategy would result in an additional 8,450 live births per year.

"We believe that women at high risk of having a miscarriage may not need absolute scientific certainty to choose to have a treatment. We recommend that they are informed about the uncertainty around treatment effects, so they can then decide for themselves the right course of action.

"We now urge policy makers and guideline developers to consider the evidence carefully to make a balanced recommendation."

Tracy Roberts, Professor of Economics at the University of Birmingham, said: "Miscarriage is a significant economic burden, costing the UK's NHS around £350 million per year for the management of miscarriage and complications.

"Given the distress to women and families associated with miscarriage, and the subsequent resources that might be associated with counselling and close antenatal attention in the subsequent pregnancies of women who experience miscarriage, progesterone is likely to be considered good value for money in preventing miscarriage."

Faye Smith took part in the PRISM trial. The 40-year-old fundraiser lives in Solihull, UK, with her partner Dean and children Noah and Leila.

She said: "I experienced three miscarriages prior to participating in the PRISM trial. We were devastated and lost. The trial helped us to feel we were doing something positive and gave us hope that the outcome could be different. One of my miscarriages required additional hospital intervention due to complications and all of these experiences also led to anxiety for which I've received NHS treatment through cognitive behavioural therapy.

"The personal impact of miscarriage can be long term and far-reaching. It's clear that providing progesterone to those at risk would not only have significant benefits for women and their families, but also for the NHS."

Jane Brewin, Tommy's Chief Executive said: "Tommy's continues to hear from women who are being denied treatment and clinicians who seem unsure about the evidence. These thorough studies now provide women and their clinicians with an effective treatment option which women should be routinely offered. I'd like to call on NICE to amend the guidelines with this new information and for NHSE to encourage take up of this treatment across the country, preventing avoidable deaths."

Dr Pat O'Brien, Consultant and Vice President of The Royal College of Obstetricians and Gynaecologists, said: "Miscarriage can be a devastating loss for women, their partners and families. We, therefore, welcome the findings from this well-researched trial which supports the use of progesterone among women with early pregnancy bleeding and a history of miscarriage.

"This treatment offers an increased chance of a successful birth and appears to be cost effective for the NHS, so we hope NICE will consider this important research in their next update of the guidance.

"For women with no prior history of miscarriage, there does not appear to be any benefit of the treatment, and women with concerns about their pregnancy should contact their midwife or early pregnancy unit for care and support. Reassuringly, most women who have had a miscarriage will have a successful pregnancy and birth in the future."

Two new studies quantify, for the first time, how many cervical cancer cases could be averted and how many women's lives could be saved in 78 low-income and lower-middle income countries (LMICs), if proposed measures for eliminating the disease are implemented

The measures, proposed in the WHO's draft strategy towards eliminating cervical cancer, could avert 74 million cases and 62 million deaths over the next century, and reduce deaths by a third by 2030

The authors caution that this can only be achieved with considerable international financial and political commitment, in order to scale up vaccination, cervical screening and cancer treatment

The findings have informed the strategy for cervical cancer elimination, which will be presented to WHO Executive Board at its next meeting, 3-8 February, and considered for approval at the World Health Assembly in May 2020

Over the next 100 years, more than 74 million cervical cancer cases and 60 million deaths could be averted, and the disease eliminated in the 78 countries with the highest disease burden, according to two modelling studies published in The Lancet.

The first study modelled the progress that could be made towards eliminating new cervical cancer cases by introducing or increasing HPV vaccination coverage, or by combining high levels of vaccination with cervical screening once, or twice, in a woman's lifetime. The second study included cancer treatment in its models alongside other variables, and analysed the impact of vaccination, screening and treatment on reducing deaths. Both studies focused on 78 low-income and lower-middle income countries (LMICs).

Cervical cancer is the second most common cancer in LMICs and the most common cause of death from cancer in women in 42 LMICs. In high-income countries, vaccination against HPV has dramatically improved the outlook for cervical cancer prevention among women, but the uptake of HPV vaccination and cervical screening remains very low in most LMICs. In 2018, 88% of 570 000 new cervical cancer cases worldwide and 91% of 311,000 deaths occurred in low, low-middle or upper middle income countries.

The disparity in the burden of disease between high income countries and LMICs prompted the WHO to call for action in 2018 to eliminate cervical cancer as a public health problem. They proposed a threshold for which cervical cancer would be considered to be eliminated as a public health problem (4 per 100,000 women-years) and drafted a strategy to put countries on the path to achieving it, with three main targets for 2030: to increase vaccination to 90% coverage, to ensure 70% of women are screened twice in their lives around the ages of 35 and 45, and to ensure 90% of women diagnosed with cervical cancer receive the treatment they need.

To examine whether elimination can be achieved and what the impact of the elimination strategy might be beyond 2030, WHO established the Cervical Cancer Elimination Modelling Consortium (CCEMC), which includes modelling teams from Laval University in Canada, Harvard University in the USA, and Cancer Council NSW in Australia. The two new studies were carried out by researchers for the CCEMC.

"For the first time, we've estimated how many new cases of cervical cancer could be averted if WHO's triple intervention strategy is rolled out and when elimination could be achieved" says Professor Marc Brisson from Laval University, Canada, who co-led both studies. "Our results suggest that to eliminate cervical cancer by the end of the century it will be necessary to achieve both high HPV vaccination coverage and high uptake of screening, especially in countries with the highest rates of the disease." [1]

The first of the current studies focused on whether and by when it might be feasible to eliminate cervical cancer cases in LMICs according to different scenarios and different definitions of elimination. The scenarios modelled were HPV vaccination of girls, vaccination combined with screening of women aged 35, and vaccination combined with screening twice in a woman's lifetime.

The results predict that vaccination alone could reduce the number of cervical cancer cases by 89% over the next century, averting 60 million cases in LMICs. However, countries with an incidence today of more than 25 cases per 100,000 women could not eliminate the disease with HPV vaccination alone, using WHO's proposed threshold of cervical cancer elimination (four or fewer cases per 100,000 women). For example, in sub-Saharan Africa, elimination would only be possible in 27% of countries.

If twice-lifetime screening is scaled-up in addition to HPV vaccination, then 100% of countries could reach elimination, reducing cervical cancer cases by 97% and averting 74 million cases by 2120. Such a strategy would also accelerate elimination by 11-31 years.

For the second modelling study, the authors analysed the impact of all three elements of the WHO triple strategy on deaths from cervical cancer, modelling the impact of scaling up cancer treatment as well as vaccination and screening. In 2020, there will be an estimated 13 deaths from cervical cancer per 100,000 women in LMICs. By 2030, the triple strategy could avert around 300,000 deaths, a reduction of 34%. By 2070, it could avert 14.6 million deaths, reducing mortality by 92%, compared to a reduction of 62% (4.8 million deaths) with vaccination alone. By 2120, the triple strategy could avert 62 million deaths, reducing mortality by 99%, compared to 90% (45.8 million deaths) with vaccination alone.

"Our findings emphasise the importance of acting immediately to combat cervical cancer on all three fronts," says Adjunct Professor Karen Canfell from Cancer Council NSW and the University of Sydney, Australia, who co-led both studies. "In just 10 years, it's possible to reduce deaths from the disease by a third and, over the next century, more than 60 million women's lives could be saved. This would represent an enormous gain in terms of both quality of life and lives saved." [1]

The authors highlight several limitations to the studies. For example, the quality of data from LMICs on cervical cancer incidence, access to treatment and survival are poor, so the numbers of cases and deaths might be higher, making elimination take longer. Neither study explicitly modelled the interaction between HIV infection and HPV, which can increase the risk of cervical cancer after HPV infection, so the impact of HPV vaccination might be overestimated in countries with a high prevalence of HIV.

Despite these limitations, the authors highlight the strengths of the approach and the importance of using multiple models. Professor Jane Kim from Harvard University, USA, who co-led both studies said: "Our finding show close concordance in predictions from three independently developed models, and highlight the very substantial health gains that could be achieved if the WHO strategy can be implemented successfully."

Writing in a linked Comment, Professor Vivien Tsu (who was not involved in the studies) from the University of Washington, USA, says: "These two papers show us that considerable progress can be made in reducing the intolerable and preventable burden of cervical cancer. We now need to take the next steps of making the difficult choices of what to do first, building on what exists, laying foundations where even basic infrastructures are lacking, putting locally tailored plans in place that move us expeditiously towards the goal of making cervical cancer the rare disease it should be."

Time spent playing video games is often seen as time stolen from physical activities. Research has shown that exercise has many physical and cognitive benefits. But what if exercise could benefit video game performance as well? A new study led by neuroscientist Dr. Marc Roig and his research team from the School of Physical & Occupational Therapy at McGill University, found, for the first time, that it can. The results of this study challenge the preponderant view that video gaming and physical activity are antagonistic activities. The findings were published online in the journal Medicine & Science in Sports & Exercise.

"The idea for the study actually came from two of my students in The Memory Lab , Bernat de Las Heras and Orville Li," explains Dr. Roig, the study's senior author. "They devoted so much time and effort investigating the impact of exercise on brain plasticity and cognition in people who have various conditions such as stroke or Parkinson's Disease, that they were curious to also explore the relationship between exercise and video game performance, a leisure activity that some of them are very familiar with. The question was whether a single bout of exercise could improve video game performance?"

Several studies have shown that increased screen time, including video gaming is associated with low levels of physical activity and that video gamers who exceed screen-time limits are at greater risk of experiencing health issues associated to physical inactivity. The evidence also reveals that a lack of physical activity combined with increased sedentary activity puts people at a greater risk of experiencing health issues including cardiometabolic clinical conditions such as hyperlipidemia, coronary heart disease and diabetes as well as psychosocial issues. Participating in an exercise program can improve overall health, reduce the risk of developing these sedentary-related cardiometabolic health problems and is also shown to have positive effects on cognition.

Discovering the benefits of exercise to gaming

Conducting their work at The Memory Lab, the researchers showed that as little as 15 minutes of intense cardiovascular exercise, performed immediately before playing a video game, improved the performance of the popular online video game, League of Legends (LoL). To complete the study, a group of young individuals were asked to either perform intense cardiovascular exercise, or rest, immediately before playing the same customized mission in LoL. Their performance in the video game was observed and documented and found to improve after exercise in comparison with rest. The research group was excited to find these results not only because exercise can have a positive effect on video gaming performance but also because this is the first time this has been demonstrated.

This positive relationship of exercise and video gaming could have an important impact on the growing number of people who play video games worldwide. The latest statistics show that there are 2.3 billion video game players in the world and this number is expected to increase to 2.7 billion by 2021. Online video game platforms such as League of Legends or Fortnite have 67 and 78.3 million players monthly respectively. At the same time as video game use is increasing, as a society we are failing to promote physical activity in younger individuals. The findings in this study could produce a dramatic shift in the video game discussion as the results provide a strong argument to convince the rapidly growing number of video gamers in the world to become more active physically.

"It was surprising that most participants benefited from the effects of exercise regardless of their fitness level and their emotional response to exercise," notes Dr. Roig. "It was striking to see that those participants who were not in exceptionally good shape or were not particularly crazy about exercise also improved their video game skill level after the single bout of exercise. This suggests that this intervention could be suitable for many individuals in our society. Video gamers could potentially integrate exercise into their training routines not only to enhance their video game performance but also to benefit from the well-known effects of exercise on physical and cognitive health."

Plans to expand on this research in the future

Looking ahead, the group would be interested to see whether these findings can be extrapolated to other video games and whether other exercise modalities would show similar effects. It would also be interesting to look into potential underlying mechanisms and whether multiple exercise sessions would have summative effects on video gaming skills. Finally, but not the least important, one could ask whether the results of this study will be enough to change the habits of sedentary video gamers and their views on physical activity.

Dr. Roig says that one of the main challenges of the study was to create a video game task that was close enough to real video gaming but that also allowed the researchers to measure the performance of players reliably. That is why the research group is thinking about partnering with a company to create a video game platform for research purposes. The idea would be to create a video game that could be used to study the effects of different interventions (e.g. exercise) on different cognitive and motor skills. They would also like to explore the combined effects of exercise and video gaming as a multimodal intervention to improve cognition in non-disabled individuals but also those suffering from clinical conditions.

January has been an exciting month at The Jackson Laboratory (JAX). With this surplus of news, we wanted to share three major stories from the past week:

Shriners Hospitals for Children and The Jackson Laboratory announced research affiliation for genomic studies of pediatric patients. The goal is to identify advanced treatment approaches for children with genetic orthopedic conditions such as clubfoot, scoliosis, and osteogenesis imperfecta. "Harnessing the power of genomics to understand the basis for orthopedic and other pediatric diseases is of the utmost importance," said Charles Lee, Ph.D., FACMG, scientific director and professor, JAX. (https://www.jax.org/news-and-insights/2020/january/pioneers-in-recombination)

Recombination is a vital process in sexual reproduction in which DNA is exchanged, usually in "hot spots," between parental chromosomes. JAX's Chris Baker identified two proteins that allow recombination at these hot spots, as shared in a Genes & Development paper. These proteins are "pioneer factors," meaning they are needed for successful meiosis and fertility. Please review our research highlight (https://www.jax.org/news-and-insights/2020/january/pioneers-in-recombination) for more information.

Assessing the effect of the microbiome--all the microbes on and within our bodies--is challenging for many reasons. There are huge numbers of microbial species to identify, and often sub-strains of the same species can colonize a single individual in both beneficial and virulent ways. In a Cell paper published today, JAX's Julia Oh led a team to analyze S. epidermidis sub-strains to underscore the role of strain genetic diversity in skin health. (https://www.jax.org/news-and-insights/2020/january/taking-a-strain-level-look-at-skin-bacteria)

WASHINGTON (Jan. 30, 2020) -- The dermatology community is inadequately prepared for a biological disaster and would benefit from a formal preparedness training program, according to a study from the George Washington University (GW). The article is published in the Journal of Drugs in Dermatology.

Natural and man-made disasters can cause a range of dermatologic conditions due to environmental exposures, such as secondary infections following a flood, irritation from blistering agents used in chemical warfare, and acute and chronic effects of cutaneous radiation syndrome. A 2003 survey revealed that 88% of dermatologists felt unprepared to respond to a biological attack -- this new survey shows that the need for training still exists.

"Recognizing and diagnosing the conditions that can arise following a disaster requires diagnostic acumen, knowledge on reporting, and short- and long-term management strategies," said Adam Friedman, MD, interim chair of the Department of Dermatology at the GW School of Medicine and Health Sciences and senior author on the study.

This current survey from an interdisciplinary team of dermatology and emergency medicine researchers, led by Emily Murphy, a research fellow in the GW Department of Dermatology, examines whether the field of dermatology has advanced in its bioterrorism preparedness.

The survey, disseminated via the Orlando Dermatology Aesthetic and Clinical Conference listserv, found that only 28.9% of respondents received training in disaster preparedness and response. The respondents to the survey frequently commented that they felt dermatologists should be prepared for bioterrorism-related cutaneous diseases, such as anthrax or smallpox-related diseases, as well as infections resulting from natural disasters.

Similar to the 2003 survey, the authors found that few dermatologists received adequate bioterrorism preparedness training. Even among those who had reported training, many indicated they felt ill prepared to manage patients affected by disasters, especially biological attacks and nuclear or radiological events.

"While few respondents to the survey were trained in disaster preparedness, it is encouraging that 75% reported that it should be included in dermatology training," Friedman said. "It is a necessary tool to advance the field."

James Phillips, MD, section chief of disaster and operational medicine in the GW Department of Emergency Medicine, director of the GW Disaster Medicine Fellowship, and co-author on the study, agreed: "My fellows and I found great value in partnering with our dermatology colleagues for this project. It is my firm belief that, while disaster medicine and emergency management primarily fall within the scope of emergency medicine and trauma surgery, education, and training for other specialties is of great value and is virtually unexplored. In an increasingly complex disaster environment, we welcome such research collaborations with other GW specialists."

Nearly 37 percent of electronic dance music (EDM) party attendees test positive for ketamine use when samples of their hair are tested--despite only 14.6 percent disclosing that they have used the drug in the past year.

The study--published in the Journal of General Internal Medicine--suggests that ketamine use is extensively underreported and EDM party attendees may be unintentionally exposed to the drug.

Individuals who frequent EDM parties report higher levels of recreational drug use compared to the general population. They are also at high risk for unknown exposure to drugs, which occurs when drugs such as ecstasy (also known as MDMA and Molly) are adulterated with other substances. However, little is known about how ketamine is intentionally or unintentionally used in this population.

Ketamine is a dissociative anesthetic that has long been used in operating rooms and was approved by the FDA in 2019 as a fast-acting treatment for depression delivered as a nasal spray. It also has a long history as a club drug (known as Special K), recreationally used for producing feelings of detachment and hallucinations.

To better understand ketamine use in this high-risk scene, in 2019, the researchers surveyed hundreds of adults entering EDM parties in New York City about their past-year drug use. In addition, 216 participants provided hair samples, which were analyzed to detect drug use in the past 12 months using ultra-high performance liquid chromatography-tandem mass spectrometry.

While 14.6 percent of EDM party attendees reported using ketamine in the past year, hair analyses revealed that 36.7 percent tested positive for any level of ketamine. This suggests that, when taking into consideration both self-reported use and hair testing, the prevalence of ketamine use is closer to 40.6 percent among EDM party attendees--2.8 times higher than self-reported use.

"Intentional underreporting of drug use is common, but the underreporting we found here is higher than expected, considering that many party attendees reported use of other synthetic drugs," said Joseph Palamar, PhD, MPH, an associate professor of population health at NYU Grossman School of Medicine, an affiliated researcher with the Center for Drug Use and HIV/HCV Research at NYU School of Global Public Health, and the study's lead author. "Since it is unlikely that someone would disclose the use of drugs such as ecstasy and intentionally not report using ketamine, we believe many cases of positive detection may be due to unknown exposure through the use of adulterated drugs."

In further analyses, testing positive for ketamine after not reporting using the drug was associated with biologically confirmed exposure to MDMA. "Ecstasy has a long history of being adulterated with other drugs--including ketamine--but people who use ecstasy or other synthetic drugs may now be at an even higher likelihood of being exposed to ketamine without realizing it," said Palamar. "While ketamine is by no means the most dangerous drug, accidentally being exposed to the drug can lead to a pretty unpleasant dissociative experience."

The authors note that more research on both intentional and unintentional ketamine use is warranted.

"In addition, we feel it is important to determine whether extensive media coverage about ketamine's ability to treat depression influences recreational use," said Palamar.

Sweet soft drinks and lots of sugar increase the risk of both dental cavities and inflammation of the gums - known as periodontal diseases - and if this is the case, then healthy eating habits should be prioritised even more. This is the conclusion of a research result from Aarhus University.

Most of us are aware that sweets and other sugary food and drink increase the risk of dental cavities. A new research result now suggests that a sugary diet can also promote periodontal diseases.

The results have been obtained in connection with a critical review of the literature over the past fifty years, and have just been published in the international scientific journal Journal of Oral Microbiology.

"Sugar hasn't traditionally been associated with the development of periodontal diseases. It's true that back in the 1970s two American researchers suggested that a diet which was high in carbohydrates could be a common risk factor for both dental diseases and inflammatory diseases such as diabetes, obesity and heart disease, but this knowledge was largely forgotten again," says Professor, Dr. Odont. Bente Nyvad from the Department of Dentistry and Oral Health at Aarhus University, who has headed the research.

"Today, there is general agreement that the above-mentioned diseases are associated with a high sugar intake. However, a hypothesis that could link and explain the two major dental diseases, caries and periodontitis, has been lacking," she says.

In the new research project, the researchers have arrived at a common hypothesis for the development of the two major dental diseases. The hypothesis is based on the biochemical processes that take place in the bacterial deposits on teeth when you add copious amounts of nutrients to the bacteria - particularly when you eat sugar.

"In other words, we revive the 'forgotten' hypothesis that sugar can promote both dental cavities and periodontal diseases," says Bente Nyvad, and emphasises the importance of continuing to brush your teeth with fluoride toothpaste, even if you cut down on sugar.

The researchers assumption is that periodontal diseases caused by sugar belong to the group of inflammatory diseases in line with diabetes, obesity and heart disease. Bente Nyvad therefore recommends that healthy eating habits should be given much higher priority if the goal is to avoid expensive treatments in the healthcare system.

Health insurance purchased by state AIDS Drug Assistance Programs for people living with HIV in states that did not expand Medicaid are improving outcomes and have the potential to save millions in healthcare costs, a new study suggests.

The researchers are urging efforts to increase enrollment in the programs, believing that they can even reduce new HIV transmissions.

"Increased enrollment in state-funded Qualified Health Plans was found to be associated with improved rates of viral suppression for people living with HIV in three states. State AIDS Drug Assistance Programs, especially those in the South and those in states without Medicaid expansion, could consider investing in purchasing Qualified Health Plans because increased enrollment could improve viral suppression rates," said researcher Kathleen A. McManus, MD, of the University of Virginia School of Medicine and UVA Health. "This evidence-based intervention could contribute to the federal government's Ending the HIV Epidemic Initiative."

Qualified Health Plans and HIV

The researchers examined Affordable Care Act Qualified Health Plans to determine if people living with HIV who enrolled in them have better outcomes. Specifically, they looked at the percentage of patients who reached what is known as "viral suppression," in which the presence of HIV is reduced to undetectable levels in the blood. They found that 86% of enrollees reached that desirable health benchmark, while only 80% of non-enrollees did so.

To make that assessment, the researchers looked at 7,776 patients in Nebraska, South Carolina and Virginia - all states that had not expanded Medicaid during the time period studied. The patients were 18 to 64 years old, did not have Medicare and were eligible to enroll under their state's guidelines. More than 70% had incomes less than 138% of the federal poverty line, meaning they would have been eligible for Medicaid had their state expanded it at that time.

Overall, 52% of the patients were enrolled in Qualified Health Plans by Jan. 1, 2015. In Virginia, 63% of patients enrolled, while 51% enrolled in Nebraska and only 34% enrolled in South Carolina. The researchers speculated that the high rate in Virginia may have resulted from centralized efforts by the state Department of Health.

There were no significant differences in enrollment based on age, gender, race/ethnicity, income and other such factors, which the researchers called "reassuring." "This is a key finding showing that this structural system-level intervention benefited people living with HIV across demographic groups and was not found to be contributing to disparities in outcomes," McManus said.

Increasing Enrollment in Qualified Health Plans

The researchers say increasing enrollment in Qualified Health Plans would be beneficial. Their findings suggest that for every 20 new people enrolled, one likely will reach viral suppression - at which point the virus is difficult to transmit. "This could translate into benefits for the individual in terms of living longer and healthier lives and for public health in terms of decreasing HIV transmission," the researchers write in a paper outlining their findings.

They note that every averted HIV case saves up to $402,000 in healthcare costs.

"If all eligible people living with HIV who are receiving support from a state AIDS Drug Assistance Program were enrolled in Qualified Health Plans, an additional 2.4% of AIDS Drug Assistance Program clients could achieve viral suppression. This could also avert 103 HIV infections and avoid more than $41 million dollars in healthcare costs," McManus said. "As the United States focuses on ending HIV as an epidemic, we need to ensure that our health policies and laws support the goal of getting to zero new HIV diagnoses."

Findings Published

The researchers have published their findings in the scientific journal Clinical Infectious Diseases. The research team consisted of McManus, Bianca Christensen, V. Peter Nagraj, Renae Furl, Lauren Yerkes, Susan Swindells, Sharon Weissman, Anne Rhodes, Paul Targonski, Elizabeth Rogawski McQuade and Rebecca Dillingham. McManus reported an investigator-initiated research grant from and stock ownership in Gilead Sciences Inc. Swindells reported research grants to her institution, the University of Nebraska, from ViiV Healthcare. Dillingham reported an investigator-initiated research grant from Gilead and consulting for Warm Health Technology Inc.

BUFFALO, N.Y. -- Researchers quizzed cannabis enthusiasts at a marijuana advocacy event about their beliefs on whether the drug is effective in treating certain medical conditions.

The majority of the nearly 500 people surveyed failed the quiz, according to the best science available.

"There is a big discrepancy between what the empirical evidence is saying and what people believe," said Daniel Kruger, PhD, the lead author of the study, which was published this month in the American Journal of Health Promotion.

"We've gone back to the 19th century miracle cure," added Kruger, a research associate professor of community health and health behavior in the University at Buffalo's School of Public Health and Health Professions and research investigator with the Population Studies Center at the University of Michigan.

"People are using cannabis and cannabinoids for everything and anything, and we don't have enough systematic research on whether it's effective for these conditions. People are stopping or reducing prescription drugs to use medical cannabis. It's a serious issue," he said.

And that's exactly why researchers felt it was important to survey marijuana users.

Researchers set up a table during Hash Bash, an annual marijuana advocacy event that has taken place on the campus of the University of Michigan for the past several decades.

The research team -- which included Jessica Kruger, PhD, a clinical assistant professor in UB's School of Public Health and Health Professions -- has conducted several previous studies with data collected at Hash Bash.

Among them was a paper published last spring that showed that the munchies exist, and that there's a need for tailored nutrition education as the population of marijuana users grows.

For the current study, nearly 500 Hash Bash participants completed surveys that asked about their cannabis use and where they obtained their information about marijuana.

They were also asked to respond to questions such as, "Which of the following conditions do you think marijuana is effective in treating (check all that apply)?" and "Which of the following conditions/events do you think marijuana use increases the risk for (check all that apply)?"

Participants' knowledge was compared with National Academies of Sciences, Engineering and Medicine (NASEM) conclusions regarding medical effectiveness and risk related to cannabis use.

In addition to revealing a disconnect between mainstream health and medicine and the medicinal use of marijuana, the study results also identified a lack of awareness of the potential risks involved.

For example, only 22% of respondents thought that cannabis use during pregnancy could be risky.

"That was really striking," Daniel Kruger said, adding that "there is evidence that marijuana use could lead to lower birth weights."

In addition, the majority of survey respondents said cannabis was effective in treating cancer, depressive symptoms and epilepsy. The NASEM assessment, however, concludes there is limited evidence that cannabis or cannabinoids effectively reduce depressive symptoms, and no or insufficient evidence that it works for cancer and epilepsy.

Participants also said marijuana can treat irritable bowel syndrome, despite, again, a lack of empirical data supporting that conclusion.

Kruger is quick to note the following caveat: Marijuana remains a Schedule I substance, which prohibits scientists from conducting the clinical trials necessary for properly informing NASEM conclusions.

The majority of study participants reported using marijuana every day, and 85% said they use it for health or medical reasons. About 78% said their knowledge of cannabis stemmed from personal experience, compared to just 23% from a medical cannabis caregiver or dispensary and 18% from a primary care provider.

The knowledge gap identified in the study is significant from a public health perspective, researchers say, adding that as a growing number of states legalize -- or consider legalizing -- adult recreational marijuana use, the conversation needs to shift.

"These results highlight the disconnect between marijuana advocacy and policies and the lack of scientific evidence. We need more scientifically rigorous research to inform health messages that provide guidance about the use and effectiveness of cannabis and cannabinoids for a wide range of medical conditions," said study co-author R. Lorraine Collins, PhD, associate dean for research in UB's School of Public Health and Health Professions and a contributor to the NASEM report.

The issue is moving at a rapid pace due to citizen-driven ballot initiatives and pushes from public officials, Daniel Kruger added. For example, New York Governor Andrew M. Cuomo in his recent State of the State Address again called for legalizing marijuana for adult recreational use. Michigan voters passed a bill in 2018 approving legalizing, regulating and taxing marijuana there.

Given these efforts, it's time for public health to get up to speed, Daniel Kruger says. "Abstinence won't work as the only goal anymore. We need to maximize the benefits and minimize the costs, risks and harms to individuals and society. We hope our study broadens the conversation."