Body

Fibromyalgia is one of many chronic pain conditions that remains stubbornly difficult to treat.

As the ravages of the opioid epidemic lead many to avoid these powerful painkillers, a significant number of people with fibromyalgia are finding an effective replacement in CBD-containing products, finds a new Michigan Medicine study.

CBD, short for cannabidiol, is the second most common cannabinoid in the cannabis plant, and has been marketed for everything from mood stabilization to pain relief, without the intoxicating effects produced by the most common cannabinoid, THC. THC, which stands for delta-9-tetrahydrocannabinol, is the ingredient in marijuana that causes people to feel high.

The cannabis industry has exploded, aided by the legalization of medical and recreational marijuana in states around the United States and the removal of hemp-derived CBD from Schedule 1 status--reserved for drugs with no currently accepted medical use and a high potential for abuse--at the federal level.

Previous research shows that some people substitute medical cannabis (often with high concentrations of THC) for opioids and other pain medications, reporting that cannabis provides better pain relief and fewer side effects. However, there is far less data on CBD use.

"CBD is less harmful than THC, as it is non-intoxicating and has less potential for abuse," said Kevin Boehnke, Ph.D., a research investigator in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center. "If people can find the same relief without THC's side effects, CBD may represent a useful as a harm reduction strategy."

Boehnke and his team surveyed people with fibromyalgia about their use of CBD for treatment of chronic pain.

"Fibromyalgia is not easy to treat, often involving several medications with significant side effects and modest benefits," Boehnke explained. "Further, many alternative therapies, like acupuncture and massage, are not covered by insurance."

For this study, the team focused on 878 people with fibromyalgia who said they used CBD to get more insight into how they used CBD products.

The U-M team found that more than 70% of people with fibromyalgia who used CBD substituted CBD for opioids or other pain medications. Of these participants, many reported that they either decreased use or stopped taking opioids and other pain medications as a result.

"I was not expecting that level of substitution," said Boehnke, noting that the rate is quite similar to the substitution rate reported in the medical cannabis literature. People who said they used CBD products that also contained THC had higher odds of substitution and reported greater symptom relief.

Yet the finding that products containing only CBD also provided pain relief and were substituted for pain medications is promising and merits future study, noted Boehnke.

The team noted that much of the widespread use of CBD is occurring without physician guidance and in the absence of relevant clinical trials. "Even with that lack of evidence, people are using CBD, substituting it for medication and doing so saying it's less harmful and more effective," he said.

Boehnke stressed the need for more controlled research into how CBD may provide these benefits, as well as whether these benefits may be due to the placebo effect.

Clinically, opening up lines of discussion around CBD use for chronic pain is imperative, said Boehnke, for medication safety reasons as well as for "enhancing the therapeutic alliance and improving patient care."

INDIANAPOLIS -- A new study demonstrates that many younger adult dental patients are taking medications and highlights the importance of dental providers reviewing medication histories regardless of age.

The study from Regenstrief Institute and the Indiana University School of Dentistry looked at dental records from 11,220 dental patients over the age of 18. The results showed:

53 percent of all patients reported taking at least one medication

12 percent of those age 18-24 were taking at least one medication

20 percent of those age 25-34 were taking at least one medication

"The number of younger adults on medication really surprised us," said senior author Thankam Thyvalikakath, DMD, PhD, director of the Regenstrief and IU School of Dentistry Dental Informatics Program. "Often dentists will assume individuals this age aren't on medications, but these results underscore the importance of paying attention to medical histories of all patients, because medications can play a significant role in oral health."

Younger adults were most likely to be taking antidepressants, which can cause dry mouth, and opioids, which carry the risk of addiction.

"We need to be aware of these possibilities, because dry mouth increases risk for tooth decay and tooth loss, and dental professionals should be proactive with preventive measures," said Dr. Thyvalikakath. "In the same way, if someone is taking an opioid, we as dentists need to make sure we are not overprescribing these medications to that patient and possibly contributing to dependence or substance use disorder."

The study showed that older patients were more likely to be taking medications to treat chronic conditions like high cholesterol, hypertension and diabetes. Across all ages, white patients were more likely to be on a medication.

In the future, Dr. Thyvalikakath hopes to develop and test an intervention to alert dental care providers about medicines and medical history because a more complete picture of a person's health can lead to better care and prevention.

"Differences in medication usage of dental patients by age, gender, race/ethnicity and insurance status" was published online ahead of print in Technology and Health Care, the official journal of the European Society for Engineering and Medicine. This project was made possible by Dr. Thyvalikakath's start-up funds through the Indiana University School of Dentistry.

Leukemia is a group of blood cancers that affects thousands of people worldwide. However, with advances in medicine, several different types of leukemia can be effectively treated with donor stem cells through allogenic stem cell transplantation (allo-SCT). One such type of leukemia is B-cell acute lymphoblastic leukemia (B-ALL), which is caused by uncontrolled proliferation and prolonged existence of cancerous B-cells. While allo-SCT can 'cure' B-ALL in several cases, there are also cases of failure, characterized by deterioration in health after a period of recovery--a phase medically known as relapse. Early prediction of this unfavorable outcome can have several medical advantages for the corresponding patients and the healthcare system.

To address this challenge, a group of medical researchers from Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, and Chinese Academy of Medical Sciences successfully developed an effective risk score that can accurately predict leukemia relapse, after allo-SCT. Their findings have been published as a research article in Chinese Medical Journal.

Detailing the comprehensive methodology used in the study, Dr. Xiao-Jun Huang from Peking University Institute of Hematology, Peking University People's Hospital, who led the study, explains, "We enrolled 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT and establish a risk score to identify patients with different probabilities of relapse. We performed univariate and multivariate analyses with the Cox proportional hazards model using time-dependent variables to analyze our data."

As mentioned by Dr. Huang, some of the analyzed factors associated with allo-SCT transplant outcomes included engraftment of white blood cell like neutrophils, and platelets, in the patients; presence of residual cancer cells, measured as minimal residual disease (MRD); occurrence of chronic graft-versus-host disease (cGVHD); and decrease in leukemia symptoms, medically known as remission, after the procedure. Then, the researchers went on to identify if these factors could be used to determine outcomes like 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality, in the patients. Finally, these results were used to formulate the risk score.

In the patients assessed for the different factors previously described, the researchers notably observed that all of them achieved neutrophil engraftment, and 95.4% of them achieved platelet engraftment. Also, they observed that 20.7% of the patients showed CIR, 70.4% of them survived overall, 65.6% endured LFS, and 13.9% succumbed to non-relapse mortality.

Further statistical analysis allowed the researchers to observe distinct associations between the analyzed factors and evaluated outcomes. In this regard, Dr. Huang, excitedly explains, "Our analysis showed that patients with positive post-transplantation MRD, transplanted beyond the first complete remission (?CR2), and without cGVHD, had higher CIR and worse LFS, and OS , than did patients without MRD after transplantation, transplanted in CR1, and with cGVHD." With such apparent observations, as explained by Dr. Huang, the researchers immediately went on to devising their risk score.

The novel risk score pinned 5-year relapse rates of 6.3%, 16.6%, 55.9%, and 81.8%, as 0, 1, 2, and 3, respectively. The researchers also added that, with increasing risk score, the 5-year LFS and OS values correspondingly decreased.

Overall, the researchers hope that the risk score that they have devised will serve as a guide for leukemia treatment, by allowing stratification of patients with different risks of relapse. They also hope that this will allow for better medical intervention. Indeed, the world can hope that this risk score serves a milestone in leukemia relapse prediction.

(Denver)-Patients with primary lung cancer detected using low-dose computed tomography screening are at reduced risk of developing brain metastases after diagnosis, according to a study published in the Journal of Thoracic Oncology.

JTO is an official journal of the International Association for the Study of Lung Cancer. The full study is available here: Impact of Low-Dose Computed Tomography Screening for Primary Lung Cancer on Subsequent Risk of Brain Metastasis - Journal of Thoracic Oncology (jto.org)

The researchers, led by Summer Han, PhD, from Stanford University School of Medicine in Palo Alto, Calif., used the National Lung Screening Trial data to identify 1502 participants who were diagnosed with lung cancer between 2002 to 2009 and have follow-up data for brain metastases.

Of 1502 participants, 41.4% had lung cancer detected through LDCT screening versus 58.6% detected through other methods, for example, chest radiograph or incidental detection. Patients whose lung cancer was detected with LDCT screening had a significantly lower three-year incidence of brain metastases (6.5%) versus those without (11.9%), with a cause-specific hazard ratio (HR) of 0.53 (p = 0.001), adjusting for age at lung cancer diagnosis, stage, histology, and smoking status. This significant reduction in brain metastases risk among patients with lung cancer detected through LDCT screening persisted in subgroups of participants with early-stage primary lung cancer (HR = 0.47, p = 0.002) and those who underwent surgery (HR = 0.37, p = 0.001).

To investigate potential explanations for an association between brain metastases risk and lung cancer detected by LDCT screening, the researchers explored LDCT imaging data using a subset of patients (n = 552) who were randomized to the LDCT arm and have LDCT imaging data available. The researchers then compared the characteristics of the nodules that were LDCT screen-detected versus those that were missed by LDCT screening among the patients who were interval detected in the LDCT screening arm.

Given the observed high rate of brain metastases among patients with lung cancer in stage I in NLST (32.4%), the research group further evaluated and compared the characteristics of the nodules of the patients who developed brain metastases (n = 12) versus those who did not develop brain metastases (n = 350) within the patients whose lung cancer was LDCT screen detected in stage I (n = 362).

"This reduction in risk for brain metastases among LDCT screen-detected lung cancer--which persisted in subgroup analyses of patients with early-stage lung cancer and those who underwent surgery for lung cancer--may not be fully explained by stage shift nor curative treatment for PLC," said Han. "The reduction in brain metastases risk may be because of a potentially different tumor biology of the tumors detected by LDCT screening that are less aggressive and slow growing, which needs to be confirmed by further investigation."

"To the best of our knowledge, our study presents the first effort investigating the potential impact of LDCT lung screening on subsequent risk of metastasis," said Han. She pointed out that using the NLST data with a long follow up period provided sufficient time to observe the development of brain metastases.

DUARTE, Calif. -- City of Hope, a world-renowned cancer research and treatment center, has identified how cancer cells in patients with early-stage breast cancer change and become resistant to hormone or combination therapies, according to a new study published in Nature Cancer.

About 80% of breast cancer cases are hormone receptor positive, meaning that these cancer cells need estrogen or progesterone to grow, according to the American Cancer Society. Doctors currently treat people with estrogen receptor positive (ER+) breast cancer using therapy that inhibits both estrogen levels and cell cycle activity. While these therapies often initially shrink tumors, about 90% of metastatic patients and 50% of Stage 2 and 3 breast cancer patients develop resistance.

A research team led by Andrea Bild, Ph.D., a professor in City of Hope's Department of Medical Oncology & Therapeutics Research, used single-cell RNA sequencing to identify resistant traits cancer cells acquire; these cancer cells are able to persist despite therapy. The team also identified when these resistant traits are acquired and found them as early as two weeks after the start of a treatment regimen, which is months faster than current methods used to measure treatment response.

"If health care providers are able to identify the development of tumor resistance earlier, then they can quickly switch gears and offer a different treatment regimen that could eventually bring the breast cancer patient into remission rather than continuing on a path that may fail to achieve a positive outcome," Bild said. "With the current available set of precision medicine tools, medical professionals could measure patient response to treatment earlier to offer treatment options that are more likely to work for each individual patient."

Bild and her colleagues studied the evolution of the DNA and RNA in breast tumor cells of postmenopausal women with ER+ breast cancer who were enrolled in the FELINE trial. These patients were treated with endocrine therapy (letrozole) alone and in combination with cyclin-dependent kinase (CDK) inhibitor therapy (ribociclib), a treatment that restrains tumor cells from growing. Patients were treated with targeted therapy in a neoadjuvant setting, meaning prior to surgery to remove the tumor, to assess response. Biopsies from over 40 patients' tumors were processed and analyzed from cells taken prior to, two weeks after and six months from the start of endocrine and combination treatments.

City of Hope researchers found that resistant cells that persist even after endocrine and cell cycle (CDK4/6) inhibition therapy tend to shift their growth engine from using estrogen signaling to using alternative growth factor receptors and to rewiring cell cycle pathways. For example, resistant cells bypass the blocked pathways by turning on alternative signaling pathways such as growth receptors and MAPK signaling; this rewiring enables cancer cells to continue growing despite the estrogen and cell cycle drug inhibitors. Targeting these acquired resistance pathways with appropriate therapies may help doctors in the future treat patients with resistant ER+ early-stage breast cancer.

"The study is impressive in its scope, presenting comprehensive genomic profiling of the longitudinal samples from multiple patients," said Suwon Kim, Ph.D., who was not involved in the research and is an associate professor at Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and a faculty member of the University of Arizona College of Medicine. "The results are significant, revealing the emergence of the alternate specific pathways in single tumor cells as they become resistant to CDK inhibitors and endocrine therapy. The study findings offer opportunities for evidence-guided therapeutic intervention for therapy-resistant breast cancer."

Understanding how tumor cells quickly change and rewire signaling pathways so that they can persist after combination neoadjuvant cancer treatment will enable scientists to design novel treatment regimens that target tumor resistance. Bild and colleagues are now identifying drugs that block the traits found specifically in resistant cancer cells.

"Early-stage ER+ and PR+ (progesterone receptor positive) breast cancer is often curable, and we need to continue down this line of research to design therapy strategies that provide a positive patient outcome that lasts," Bild said. "I recommend that, when possible, clinicians continue to collect tumor biopsies so we can measure cancer cell responses during treatment to understand how the patient's tumors are responding. In addition, we need to look at RNA changes and not just DNA modifications, as these changes may more broadly capture resistance mechanisms."

She added, "I am grateful to patients who participate in clinical trials so that scientists can continue to find better ways to treat this disease."

A growing trove of data to help scientists understand the biology of Alzheimer's disease among diverse populations within the context of sociocultural, behavioral and environmental factors is now available through the Institute for Translational Research at The University of North Texas Health Science Center at Fort Worth (HSC).

The research data is the result of the Health and Aging Brain among Latino Elders (HABLE) study launched in 2017 with $12 million in funding from the National Institutes of Health and headed by Sid O'Bryant, PhD, Executive Director of the Institute.

In 2020, the HABLE study received an additional $45 million from National Institute on Aging, part of the National Institutes of Health.

Dr. O'Bryant announced the availability of the research data in article published June 21 in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, a national journal published by the Alzheimer's Association.

"The data from this study is a first-of-a-kind for the field," Dr. O'Bryant said. "We will for the first time be able to examine the biology of Alzheimer's among Mexican Americans as well as non-Hispanic whites all within the context of sociocultural, environmental and behavioral factors. Scientists from across the globe can use this data to address health disparities and define new diagnostic and treatment opportunities for underserved communities."

The percentage of Hispanics 65 and above in the U.S. will triple by the year 2050 and, when compared to other racial or ethnic groups, are expected to experience the largest increase in Alzheimer's disease related dementias by 2060, according to the paper. About 65 percent of U.S. Hispanics are of Mexican decent.

However, Mexican Americans are severely underrepresented in Alzheimer's research, resulting too few comprehensive studies of the biomarkers of the disease among this population. Early findings suggest that beta amyloid protein -- one of the biomarkers of Alzheimer's -- is less common among Mexican Americans yet Mexican Americans seem to have a younger onset of cognitive loss.

About 1,000 Mexican Americans and 1,000 non-Latino whites over 50 from North Texas have enrolled in the study that gives participants reoccurring and free comprehensive interviews, functional exams, clinical laboratory tests, a brain MRI and state-of-the-art PET Scans.

The PET Scans allow researchers to observe the differences over time in the development of the biomarkers between Mexican Americans and non-Latino whites.

In December, HSC announced an additional $7 million investment that to add 1,000 African Americans to the study. Among people 65 and older,?African Americans have the highest prevalence of Alzheimer's disease, followed by Hispanics and non-Latino?whites, according to the U.S. Center for?Disease Control and Prevention.

The project is the only comprehensive, large-scale Alzheimer's research study into the three largest ethnic groups in the U.S. - Non-Hispanic whites, Mexican Americans and African Americans.

Niigata, Japan - An estimated 1.13 billion people worldwide have hypertension or high blood pressure, and two-thirds of these individuals are living in low- and middle-income countries. Blood pressure is the force manifested by circulating blood against the walls of the body's arteries, the major blood vessels in the body. Hypertension is when blood pressure is too high.

Blood pressure is written as two numbers. The first (systolic) number represents the pressure in blood vessels when the heart contracts or beats. The second (diastolic) number represents the pressure in the vessels when the heart rests between beats. Hypertension is diagnosed if, when it is measured on two different days, the systolic blood pressure (SBP) readings on both days is ≥140 mmHg and/or the diastolic blood pressure (DBP) readings on both days is ≥90 mmHg.

Worldwide, high blood pressure is a common and strong risk factor for the development of cardiovascular disease. As reported by previous studies in Asia and elsewhere, as the level of SBP rises, the risk of developing cardiovascular disease increases, too. Similarly, the likelihood of dying from a cardiovascular event increases as the SBP rises. However, whether these observations hold for increases in DBP is not known. Moreover, although a high blood glucose status is itself associated with a high likelihood for the development of cardiovascular disease, it is not known whether the blood glucose status plays any role in the relationship between high blood pressure and cardiovascular events.

This theory led the authors to propose a hypothesis for their study. Commenting further, Dr. Kazuya Fujihara of the Department of Internal Medicine, Faculty of Medicine, Niigata University, said "The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline defined blood pressure >130/80 mm Hg as hypertension. This guideline showed that the normal level is less than 120/80 mm Hg and SBP 120-129 mm Hg and DBP

In the Diabetes Care paper, the authors addressed these research questions using a nationwide claims-based database that included information on 805,992 people enrolled with a health insurance provider for company employees and their dependents in Japan. In one arm of the study, they compared the cumulative incidence of coronary artery disease according to their SBP in individuals with normal, borderline and elevated blood glucose, separately (Figure). The authors reported that, "a linear relationship was observed between cumulative incidence rates of coronary artery disease and SBP categories across all glucose tolerance status designations using SBP below 119 mmHg as the reference". In another arm of the study, the investigators compared the cumulative incidence of cerebrovascular disease according to their SBP in individuals with normal, borderline and elevated blood glucose, separately (Figure). Similarly, the authors observed a linear dose-response relationship between cumulative incidence rates of cerebrovascular disease and SBP categories across all glucose tolerance status. Furthermore, the investigators repeated similar analyses using the DBP and reported that "Similar to the relationship between SBP and coronary artery disease and cerebrovascular disease; the coronary artery disease and cerebrovascular disease risk concurrently increased with higher DBP categories".

The study also found that combined together, the blood glucose status and blood pressure values had a synergistic effect on the incidence of coronary artery disease and cerebrovascular disease. Commenting on the significance of their findings, Prof. Sone said, "Compared to Westerners, Asians have significantly less coronary artery disease, but more stroke. In addition, Asians have a much lower obesity level than Westerners, and the pathogenesis of diabetes mellitus is also very different between the two. Therefore, this data should be an important reference for determining blood pressure thresholds for guidelines for Asians". Commenting further, Dr. Fujihara said "Recent study [the Systolic Blood Pressure Intervention Trial (SPRINT) Final Report] showed that intensive treatment (SBP,

While the findings of these analytical study are impressive and provide new insight on what blood pressure targets in patients with hypertension according to glucose status should be, the authors recommended that "Further trials to examine strict BP interventions for preventing cardiovascular diseases should focus on patients with borderline glycemia and diabetes to confirm findings from the current cohort study and apply them to clinical practice".

Current American Heart Association, European Society of Cardiology, and UK National Health Service guidelines recommend a 5-yearly health checks for screening of individuals at high cardiovascular disease risk. These health checks include measurement of major risk factors, such as systolic blood pressure, cholesterol profile, blood glucose, and smoking status.

If lifestyle interventions are unsuccessful in reducing risk factor levels, prevention guidelines recommend initiation of preventive medication therapies such as statins. However, current guidelines advice only using the latest risk measurement and do not use information from individual's risk factor history.

Faster risk progression should be identified in health checks

According to a Finnish-English study published in the Lancet Digital Health, individuals whose risk levels increase faster than expected based on ageing should be identified to inform decisions on preventive interventions. If the initiation of preventive interventions was delayed, these individuals can lose 2 to 6 cardiovascular disease free life-years, depending on their risk progression rate.

"Our study shows that individual risk history may provide important information for primary care to better identify individuals at high risk of cardiovascular diseases. Similarly, information allows to identify individuals who manage to reduce their risk levels between the health check and thus are at lower risk of cardiovascular diseases. In the UK, approximately 160,000 die from cardiovascular disease every year and it has been estimated that 80% of them would be preventable by timely interventions, so even small improvements in the prevention system can have large impact", says lead author Joni Lindbohm MD, PhD at University College London and University of Helsinki.

The study followed over 7000 men and women over two decades

The study was based on the Whitehall II cohort of 7000 British adults. Following current guidelines, their risk factor levels were screened every five years over a 22-year follow-up. The participants were linked to electronic health records from NHS registries including records on cardiovascular disease events. The investigators found that accelerated risk progression was most detrimental among the youngest participants aged between 40 and 50. Similarly, the benefits of risk reduction were highest in this group.

Based on their results the researchers developed an online tool that can be used to study how risk history modifies estimated cardiovascular disease risk.

Additional study is needed

"These results are promising, but national guidelines are rarely changed based on a single study. The benefits of using additional information on risk history in health checks should be further studied in randomized control trials, emphasises Professor Mika Kivimäki, University College London, who is director of the Whitehall II study and one of the study authors.

Cardiovascular disease risk can be easily estimated with an internet-based risk calculator

Currently UK residents can determine their individual cardiovascular disease risk with the QRISK3 calculator that includes questions about age, sex, smoking, total cholesterol, HDL-cholesterol, systolic blood pressure, antihypertensive medication, diabetes status, and variety of medical conditions.

Everybody from a child knows that elephants trumpet. Over the past decades research in general and at the University of Vienna has mainly studied the elephants low-frequency rumble. Its fundamental frequency reaches into the infrasonic range below the human hearing threshold. This call is produced by the elephant´s massive vocal folds. Much less was known about how elephants produce their higher pitched sounds, trumpets and squeaks.

The following rule generally applies to sound production in mammals: the larger the vocal fold, the lower the calls fundamental frequency. Conversely the size of the vocal folds sets an upper limit to the fundamental frequencies that can be reached. The high-pitched squeak only Asian but not African elephants produce when aroused, do not fit within that spectrum.

In her recent study Veronika Beeck, who is part of the FWF doctorate school Cognition and Communication at the Department of Behavioural and Cognitive Biology at the University of Vienna and her supervisor Angela Stöger, together with Gunnar Heilmann and Micheal Kerscher from gfai tech, Berlin, studied the squeak sounds of Asian elephants in Nepal.

The researchers used an acoustic camera with an array of 48 microphones that visualises sounds in colours similar to a thermic camera. In this way the sound source was precisely located. "Our images clearly demonstrate that the squeaks are emitted by the mouth and not the trunk", Veronika Beeck explains.

According to the researcher's theory the Asian elephants produce squeaks by pressing air through their tensed lips inducing the lip´s vibration. This technique equals the human brass players lip buzzing to produce a complex sound whose harmonic overtones are subsequently resonated by the instrument, resulting in its characteristic brassy sound. "Apart from human brass players this technique of lip buzzing to produce sounds has, to our knowledge, not been described in any other animal species and is thus considered unique in the animal kingdom", says Veronika Beeck.

The elephants iconic trumpet on the other hand is produced by a blast of air through the trunk. Here again, however, the vibrating anatomic sound source is not yet conclusively studied.

This new evidence further highlights the elephant´s flexibility in sound production. A few years ago, Angela Stöger-Horwath showed that elephants are capable of learning novel sounds. An Asian elephant in a Korean Zoo, by imitating his trainer, learned to speak some words in Korean. Since only a few elephants in this recent study squeaked the researchers suggest that squeaks might be learned, too.

An accurate, non-invasive, and low-cost method of testing for COVID-19 using samples taken from the screens of mobile phones has been developed by a team led by UCL researchers at Diagnosis Biotech.

The study, published in eLife and led by Dr Rodrigo Young (UCL Institute of Ophthalmology), analysed swabs from smartphone screens rather than directly from people, and found that people who tested positive by the regular nasal swabbing PCRs were also positive when samples were taken from phone screens.

The new method - known as Phone Screen Testing (PoST) - detected the COVID-19 virus on the phones of 81 to 100% of contagious people with a high viral load, suggesting it is as accurate as antigen lateral flow tests.

Globally active screening for COVID-19 is still a priority as new variants keep emerging and the vaccination rollout is not guaranteed in many countries. However, testing is expensive and can be physically unpleasant, both of which are significant hurdles on the road to an effective test and trace system.

As PoST is an environmental test, rather than a clinical test, it is both non-invasive and less expensive that a traditional nasal swabbing PCR. This means not only is it suitable for rollout in lower-income countries, but it also removes the discomfort of current COVID-19 testing options, potentially increasing take-up of regular testing among the general population. In addition, PoST sampling takes less than a minute and does not require medical personnel, which eases mass adoption in big facilities and large-scale applications.

Dr Rodrigo Young said: "Like many, I was very worried about the economic and social impact that the pandemic would leave behind, particularly in lower-income countries. We knew that the only effective way to stop the spreading is to regularly test as many people as possible, but this was not happening because it's too expensive and uncomfortable.

"We immediately knew this was something special, as PoST is a method that would not only make COVID-19 mass testing much easier but could also be used to contain outbreaks of new naturally occurring and man-made viruses, to avoid future pandemics."

Diagnosis Biotech, a Chilean startup founded by UCL's Dr Young, has been performing COVID-19 screenings in companies and schools in Chile to avoid outbreaks and maintain operational continuity, as frequent measurement of all workers or students allows the early identification of asymptomatic people and helps to control the spread of the virus.

A machine is currently under development by Diagnosis Biotech which will build on this research, safely taking a phone for PoST sampling and deliver the results directly via SMS to minimise contact.

Children with obstructive sleep apnea are nearly three times more likely to develop high blood pressure when they become teenagers than children who never experience sleep apnea, according to a new study funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. However, children whose sleep apnea improves as they grow into adolescence do not show an increased chance of having high blood pressure, which is a major risk factor for heart disease.

The long-term study, one of the largest of its kind in the pediatric population, underscores the seriousness of sleep apnea in children and the importance of early treatment, the researchers said. Their findings appear online in the journal JAMA Cardiology.

Obstructive sleep apnea, a common sleep disorder that affects millions worldwide, causes people to briefly and repeatedly stop breathing during sleep. While it occurs mostly in adults, an estimated 10% of school-aged children can also suffer from it. Although almost half of them outgrow the disorder by the time they reach adolescence, another half remain with a chronic and persistent problem. As physicians cannot accurately predict who will outgrow sleep apnea, early treatment may be beneficial to the long-term cardiovascular health of children, the researchers suggest.

While past studies have linked sleep apnea to high blood pressure and an increased risk of heart disease in adults, few have examined the long-term health impact of the disorder in children as they transition to adolescence, said lead study author Julio Fernandez-Mendoza, Ph.D., an associate professor at the Sleep Research and Treatment Center at Penn State College of Medicine in Hershey, Pennsylvania.

"Our study showed that pediatric sleep apnea can act as a gateway to future hypertension," Fernandez-Mendoza said. "Because most cases of sleep apnea go undiagnosed in adults and children alike the problem needs more attention. Sleep apnea and its risk factors should be screened for, monitored, and targeted early in life to prevent future cardiovascular disease."

Marishka Brown, Ph.D., director of the NHLBI's National Center on Sleep Disorders Research, noted that most of the sleep apnea findings in pediatric patients focus on the disorder's behavioral effects, such as sleepiness, hyperactivity, and cognition.

"There is limited data on either the short- or long-term impact on cardiovascular risk in this population," she said. "The new findings address this knowledge gap and raise awareness of sleep-disordered breathing in children as a public health problem."

In the study, the researchers enrolled 421 children ages 5 to 12 years and monitored them overnight in a sleep lab. They found that about 12% had obstructive sleep apnea according to pediatric diagnostic criteria. The researchers also measured blood pressure levels in this group.

After eight years, the researchers evaluated these children again for sleep apnea and high blood pressure. At this point, the participants were on average 16 years old (ages 12 to 23 years).

The researchers found that children whose sleep apnea continued into adolescence were nearly three times more likely to develop high blood pressure compared to those who never had sleep apnea. Those whose sleep apnea began as teenagers and met adult diagnostic criteria were nearly twice as likely to develop high blood pressure than those without sleep apnea. In addition, these teens were also more likely to have a specific form of high blood pressure called orthostatic hypertension, which occurs when standing up rapidly from a prone position and is considered a strong risk factor for heart disease in adulthood.

The exact biological mechanisms underlying the link between childhood sleep apnea and elevated blood pressure in adolescence are unclear. Obesity is a driving factor of sleep apnea even in the young, the researchers said. Growing evidence also suggests that increased inflammation, oxidative stress, and impaired heart function caused by changes in the sympathetic nervous system may be at play, given the independent contribution of sleep apnea to high blood pressure and orthostatic hypertension observed, they added.

Like adult sleep apnea, pediatric sleep apnea can be treated. For some specific cases, surgical removal of the tonsils and adenoids can help. Other cases may require the use of a CPAP machine (continuous positive airway pressure), a device that delivers air through a mask to keep the airway open when worn during sleep. For children with obesity, adopting a healthy eating and exercise plan that leads to weight loss can also help. Fernandez-Mendoza encourages parents to talk to their child's pediatrician if they suspect sleep apnea and encourages clinicians to integrate behavioral weight loss in their management of overweight youth with sleep apnea.

Fernandez-Mendoza is currently conducting another follow-up study of these youth, now aged 20 to 31 years old, to better understand the long-term impact of childhood sleep apnea on cardiovascular health in adulthood.

COLUMBIA, Mo. - Throughout her 20-year career as a nurse practitioner, Jennifer Hulett noticed survivors of breast cancer would often express gratitude for being alive and mention God or a divine acknowledgement that had improved their health and well-being.

Now an assistant professor at the University of Missouri Sinclair School of Nursing, Hulett is researching the benefits of spirituality on improving immune health and reducing stress, as well as the chances of cancer reoccurrence, among breast cancer survivors.

In a recent study, Hulett collected and froze samples of saliva from 41 breast cancer survivors at MU's Ellis Fischel Cancer Center. She identified breast cancer survivors' reports of practicing forgiveness and receiving positive social support from their congregation or other social support network were linked with two specific biomarkers, alpha-amylase and interleukin-6. The findings lay the foundation for further examining the role spirituality plays in the health and well-being of both cancer survivors and individuals managing chronic disease.

"Breast cancer survivors are often a highly spiritual group given the trauma they have been through, and we found they often have more positive spiritual beliefs in a loving God or higher power rather than a punitive, punishing God," Hulett said. "This confirmed what I had previously experienced anecdotally as a nurse. Breast cancer survivors would often express gratitude and contribute their health and well-being to a higher power, and they tended to have better health outcomes as well."

Hulett's research builds off previous findings indicating positive spiritual beliefs are associated with healthier levels of cortisol, a biomarker commonly associated with stress, among breast cancer survivors.

"Cortisol and stress suggest chronic inflammation, and anything we can do to lower levels of stress and inflammation will have a good effect on a patient's longevity, health outcomes and reduced risk of reoccurring disease," Hulett said. "We often hear about diet and exercise in promoting physical health, but we rarely hear about the importance of managing stress, and all three are connected with well-being."

One in eight women develop breast cancer at some point in their lives, and previous studies show chronic stress in breast cancer survivors is linked with increased inflammation and risk for cancer reoccurrence.

"We know cortisol is linked with stress, and elevated levels of the immune biomarker interleukin 6 suggests inflammation," Hulett said. "By first finding out which biomarkers are meaningful to look at, we can then see how they are potentially influenced by various spiritual or mindfulness practices aimed at reducing inflammation."

Hulett's research sets the foundation for future research that evaluates the effectiveness of spiritual and mindfulness interventions, including daily prayer, mediation, yoga and relaxation, on health outcomes among cancer survivors and individuals with chronic disease.

"We already know these interventions improve mental health, but they might also improve physical health as well, and we can try to prove it by looking at these physiological biomarkers," Hulett said. "These spiritual interventions are what nurses can use at the bedside to quickly implement if they see patients struggling to cope with their illness. Any evidence-based solutions we can equip nurses with will help improve patient health outcomes, and that is where these mind-body interventions can play a role going forward."

SAN FRANCISCO, CA--June 23, 2021--A healthy heart is a pliable, ever-moving organ. But under stress--from injury, cardiovascular disease, or aging--the heart thickens and stiffens in a process known as fibrosis, which involves diffuse scar-like tissue. Slowing or stopping fibrosis to treat and prevent heart failure has long been a goal of cardiologists.

Now, researchers at Gladstone Institutes have discovered a master switch for fibrosis in the heart. When the heart is under stress, they found, the gene MEOX1 is turned on in cells called fibroblasts, spurring fibrosis. Their new study, published in the journal Nature, suggests that blocking this gene could prevent fibrosis in the heart--and other organs that can similarly fail from stiffening over time.

"With these findings, we may have an entirely new way to stop that slow but steady progression of heart failure that affects 24 million people worldwide," says Deepak Srivastava, MD, president and senior investigator at Gladstone and senior author of the study. "Right now, we don't have any drugs that effectively prevent fibrosis."

Fibroblasts are key to normal organ repair and integrity; they're the most abundant cell in connective tissue and congregate at sites of bodily damage or disease. In many cases, their presence is beneficial. They help launch immune responses, mediate inflammation, and rebuild tissue. But in chronic disease, activated fibroblasts can continuously create scar tissue, impeding normal organ function.

Researchers knew that in mice with heart disease, blocking a class of proteins known as BET proteins slowed fibrosis and improved heart function, although it wasn't clear which cell type in the heart was being affected. They also knew that BET proteins are needed throughout the body for many important functions, including normal immunity.

"To treat a heart failure patient with a BET inhibitor is a sledgehammer approach, because we might prevent fibrosis, but we'd likely also disrupt many other critical cellular functions throughout the body in the process," says Srivastava, who is also a pediatric cardiologist and a professor in the Department of Pediatrics at UC San Francisco (UCSF). "Our hope was that if we could understand the precise mechanism through which BET works in the heart, we could home in on a narrower target with fewer side effects."

Srivastava's group studied mice who developed heart failure, and treated them daily with a BET inhibitor for 1 month. The researchers used single-cell RNA sequencing and single-cell epigenomics--which can reveal which genes in a cell are accessible and being turned on at any given time--to compare heart cells from mice before, during, and after the treatment, and correlate those results with heart function.

These technologies allowed the researchers to analyze thousands of cells at once, and separate them based on their specific cell type. Thanks to a close collaboration with the laboratory of Katie Pollard, PhD, at Gladstone, they developed new computational methods to learn from the vast amount of data generated by their analysis.

While the scientists didn't find significant changes to heart muscle cells, they observed that the treatment induced striking changes in cardiac fibroblasts, which represent more than half the cells in the human heart.

In particular, the researchers discovered that the gene MEOX1 was highly active in the mice with heart failure and that its levels dramatically dropped when the mice were treated with the BET inhibitor. Moreover, the levels of MEOX1 correlated with activation of the fibroblasts; when the gene was switched on, the fibroblasts were better at making scar tissue. In fact, MEOX1 seemed to be a "master regulator" of fibroblast activation, controlling thousands of other genes that contribute to fibrosis.

"MEOX1 is a gene known to be important in early development, but not much was known about it in adult disease, so our findings were quite surprising," says Michael Alexanian, PhD, a Gladstone postdoctoral scholar and first author of the new study.

The findings point to the precise part of the DNA, regulated by BET, that is responsible for MEOX1 to be turned on in disease states. Using CRISPR genome-editing technology, the scientists showed that deleting this small part of the DNA prevented MEOX1 from being activated, even under stress.

The team went on to show that blocking MEOX1 from being switched on had the same effects as a BET inhibitor--it blocks the activation of fibroblasts. The researchers also studied other organs that commonly become fibrotic with disease, and found that cellular stress led to higher levels of MEOX1 in human lung, liver, and kidney fibroblasts.

"Fibrosis is much broader than just the heart; it affects many other organs," says Srivastava. "We hope this discovery provides an avenue to slow down or stop fibrosis in many settings."

More studies are needed to show whether blocking MEOX1 could have therapeutic value in humans. Srivastava and his colleagues are now conducting additional studies to better understand the long-term role of MEOX1 in heart disease and heart failure.

"In a coordinated effort to design novel therapies for heart failure, researchers are looking for molecular clues to use as therapeutic targets," says Bishow Adhikari, PhD, a program officer in the heart failure and arrhythmias branch, located within the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute. "These findings are highly informative and bring researchers closer to advancing new therapeutic strategies to better predict and treat heart disease."

Microscopy is an essential tool in many fields of science and medicine. However, many groups have limited access to this technology due to its cost and fragility. Now, researchers from the Universities of Göttingen and Münster have succeeded in building a high-resolution microscope using nothing more than children's plastic building bricks and affordable parts from a mobile phone. They then went on to show that children aged 9-13 had significantly increased understanding of microscopy after constructing and working with the LEGO® microscope. Their results were published in The Biophysicist.

The researchers designed a fully functional, high-resolution microscope with capabilities close to a modern research microscope. Apart from the optics, all parts were from the toy brick system. The team realized that the lenses in modern smartphone cameras, which cost around €4 each, are of such high quality that they can make it possible to resolve even individual cells. The scientists produced instructions for building the microscope as well as a step-by-step tutorial to guide people through the construction process whilst learning about the relevant optical characteristics of a microscope. The researchers measured children's understanding through questionnaires given to a group of 9-13 year olds. The researchers found that children given the parts and plans to construct the microscope themselves significantly increased their knowledge of microscopy. For this particular study, the researchers, whose day-to-day research focusses on fundamental biophysical processes, benefitted from the input and enthusiasm of their 10-year-old co-author.

"An understanding of science is crucial for decision-making and brings many benefits in everyday life, such as problem-solving and creativity," says Professor Timo Betz, University of Göttingen. "Yet we find that many people, even politicians, feel excluded or do not have the opportunities to engage in scientific or critical thinking. We wanted to find a way to nurture natural curiosity, help people grasp fundamental principles and see the potential of science." The researchers stayed in contact with the children and monitored their progress: after they had constructed the main parts, they discovered that the lenses can act as magnifying glasses. After exploring this, and realizing that a good light source was important, they initially found it tricky to align two magnifying glasses. However, once they had achieved this, the lenses generated tremendous magnification. This enabled the children to literally "play" with the microscope: make their own adaptations; explore how the magnification works; and discover the exciting world of the micro-cosmos for themselves.

"We hope that this modular microscope will be used in classrooms and homes all over the world to excite and inspire children about science," continues Betz. "We have shown that scientific research does not need to be separate from everyday life. It can be enlightening, educational and fun!"

Two mRNA vaccines against COVID-19 have proven safe and effective in clinical trials, as well as in the millions of people who have been vaccinated so far. But how prior SARS-CoV-2 infection affects vaccine response, and how long that response lasts, are still uncertain. Now, a new study in ACS Nano supports increasing evidence that people who had COVID-19 need only one vaccine dose, and that boosters could be necessary for everyone in the future.

In clinical trials, the Pfizer-BioNTech and Moderna COVID-19 vaccines were about 95% effective in protecting against symptomatic infections. Both mRNA vaccines trigger the immune system to produce antibodies against the SARS-CoV-2 spike protein receptor binding domain (RBD), and two doses are necessary to provide immunity in people who haven't previously had COVID-19. However, the clinical trials included very few people who had already recovered from the disease, so the immune response of these individuals is less well known. Also, the time course of antibody development in both groups, and how long virus-neutralizing antibodies persist, haven't been well characterized. So Otto Yang and colleagues wanted to compare antibody levels, quality and persistence after one and two doses of mRNA vaccine in people with or without prior SARS-CoV-2 infection.

The researchers used an enzyme-linked immunosorbent assay (ELISA) to measure antibodies against the RBD in people who received the Pfizer-BioNTech or Moderna vaccine, and in unvaccinated people soon after mild or severe COVID-19 cases. In the 28 participants without prior infection, one dose of either vaccine triggered antibody levels similar to those seen after mild COVID-19 infections, whereas two doses were required to obtain anti-RBD antibodies approaching those observed after severe cases. In contrast, in 36 participants who had COVID-19 prior to vaccination, the first dose produced a vigorous antibody response similar to severe natural infection, but the second dose provided no additional increase in antibody levels. The quality of antibodies, indicated by their ability to neutralize the SARS-CoV-2 spike protein and their potency, followed similar patterns. After the second vaccine dose, antibody levels waned in both groups comparably to natural infection, resulting in an average loss of 90% within 85 days. Although more research on T cell responses to the vaccines is needed, this result suggests that booster vaccinations will likely be required for everyone, the researchers say.