Body

BOSTON - (July 20, 2020) - Every doctor recommends regular aerobic exercise, since greater aerobic fitness is important for achieving better overall health. But Joslin Diabetes Center scientists now have discovered that some benefits of aerobic exercise may be dampened by higher-than-normal blood sugar levels, a condition known as hyperglycemia.

These diminished gains are seen in mouse models and humans with chronic hyperglycemia that is in the "prediabetes" range, says Sarah Lessard, PhD, a Joslin assistant investigator in the section of Clinical, Behavioral and Outcomes Research and senior author on a paper in Nature Metabolism that presents the work. The study also showed that this maladaptive trait is independent of obesity and insulin levels in the blood.

Clinical studies have demonstrated that people with diabetes or chronically high levels of blood sugar struggle to improve their aerobic exercise capacity compared to people with normal blood sugar levels. "The idea behind this study was to see if we induce high blood sugar in mice, will we impair their ability to improve their aerobic fitness?" says Lessard, who is an assistant professor of medicine at Harvard Medical School. The study also aimed to uncover the mechanisms that may lead to low fitness levels in people with hyperglycemia.

Her team used two mouse models that reflect the two major causes of hyperglycemia in humans. One group of mice consumed a Western diet, high in sugar and saturated fat, which caused some weight gain in addition to hyperglycemia. The other group was modified to produce less insulin, which caused similar increases in blood sugar as the Western diet, even though the mice ate a diet lower in sugar and fat, and maintained normal body weight. Both groups were subjected to a training protocol in which they ran in wheels in their cages to boost their aerobic fitness.

In both hyperglycemic groups, animals ran around 500 kilometers over the course of the study but, on average, failed to improve their aerobic exercise capacity compared to mice with lower blood sugar levels, Lessard says.

Looking in more detail at skeletal muscle in these mice, she and her colleagues saw that the muscle was not adapting to the aerobic challenge as muscle normally would.

Muscle tissue can remodel itself, which is one reason why exercise becomes easier when we do it regularly, Lessard says. Over time, aerobic exercise such as running or swimming can alter muscle fibers to become more efficient at using oxygen during exercise. "We also grow new blood vessels to allow more oxygen to be delivered to the muscle, which helps to increase our aerobic fitness levels," she says.

The scientists propose that high levels of blood sugar may prevent muscle remodeling in part by modifying the "extracellular matrix" proteins in the space between the muscle cells, where blood vessels are formed.

Earlier work by Lessard's lab had demonstrated that a biological pathway known as the "JNK" signaling pathway can act as a kind of molecular switch to tell muscle cells to adapt to either aerobic or strength training. The scientists found that these JNK pathway signals were getting crossed in the hyperglycemic mice, by activating pathways associated with strength training, even though the mice were performing aerobic exercise. "As a result, the muscles of hyperglycemic animals have bigger fibers and fewer blood vessels, which is more typical of strength training, rather than aerobic training," Lessard says.

Following up on these animal findings in clinical tests with young adult volunteers, the Joslin scientists found that those who had higher blood sugar levels in response to ingesting glucose, a condition known as impaired glucose tolerance, showed the lowest aerobic exercise capacity. "Looking at how their muscles responded to a single bout of typical aerobic exercise, we also saw that those with the lowest glucose tolerance had the highest activation of the JNK signaling pathway, which blocks aerobic adaptations," she says.

"The good news is, although our mouse models of hyperglycemia failed to improve aerobic fitness with training, they still achieved other important health benefits from the exercise including decreased fat mass and improved glucose metabolism," Lessard says. "So, regular aerobic exercise is still a key recommendation for maintaining health in people with or without hyperglycemia." It is important to note that people with hyperglycemia also can benefit from other forms of exercise, such as strength training, which is recommended for maintaining health, she says.

Overall, the study suggests several approaches that might help people with chronic hyperglycemia eventually overcome the obstacles to building aerobic capacity. One is to adopt a diet designed to keep blood sugar levels low. Another is to take existing diabetes drugs designed to keep blood sugar levels in normal ranges.

"We often think of diet and exercise as separate ways to improve our health," Lessard says. "But our work shows that there is more interaction between these two lifestyle factors than what was previously known, and suggests that we may want to consider them together in order to maximize the health benefits of aerobic exercise."

New Rochelle, NY, July 20, 2020--A new study has shown that although 86% of women seen at an outpatient gynecology clinic had a cardiovascular risk factor and 40.1% had at least one cardiovascular symptom, the awareness of cardiovascular risk factors and symptoms was low. The study, which showed the feasibility of using a simple screening tool in the outpatient gynecology setting for cardiovascular risk assessment, is published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article on the Journal of Women's Health website through August 20, 2020.

Roxana Mehran, MD, Mount Sinai Medical Center (New York, NY), and an international team of researchers found the need for improved screening for cardiovascular risk factors and symptoms, both among women who had a history of adverse pregnancy outcomes (APO) and those who did not. The level of awareness of risk factors, including high blood pressure, high cholesterol, and obesity, was somewhat higher among those who had had adverse pregnancy outcomes. The no-APO group was more likely to have risk factors and cardiovascular symptoms such as angina and dyspnea. For many women, a visit to the gynecologist serves as their only form of primary health care. Mehran concluded that improved screening in ob/gyn clinics may enhance the detection of cardiovascular issues in women. They present their findings in the article entitled "Feasibility and Utility of a Cardiovascular Risk Screening Tool in Women Undergoing Routing Gynecology Evaluation."

Gina Lundberg, MD, applauds the simple questionnaire used by Yu et al. to assess cardiovascular disease risk during routine office appointments in the editorial entitled "Beyond the Bikini." She states: "This compelling paper emphasizes how far we are from achieving optimal cognizance of CVD risk factors in addition to identifying symptoms of angina among all women, particularly perimenopausal women and those with a history of adverse pregnancy outcomes."

Phase 2 randomised controlled trial of a recombinant adenovirus type-5-vectored COVID-19 vaccine (Ad5-vectored COVID-19 vaccine) was conducted in China in April 2020 and involved more than 500 people

The primary objective of the study was to evaluate the immune response and safety of the vaccine, and to determine the most suitable dose for a phase 3 trial

Phase 3 trials are needed to confirm whether the vaccine candidate effectively protects against SARS-CoV-2 infection

A phase 2 trial of an Ad5 vectored COVID-19 vaccine candidate, conducted in China, has found that the vaccine is safe and induces an immune response, according to new research published in The Lancet.

The randomised trial sought to evaluate the safety and immunogenicity of the vaccine candidate and follows a phase 1 trial published in May 2020 [1]. The results provide data from a wider group of participants than their phase 1 trial, including a small sub-group of participants aged over 55 years and older, and will inform phase 3 trials of the vaccine.

However, the authors note that it is important to stress that no participants were exposed to SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine whether the vaccine candidate effectively protects against SARS-CoV-2 infection.

Professor Feng-Cai Zhu, Jiangsu Provincial Center for Disease Control and Prevention, China, says: "The phase 2 trial adds further evidence on safety and immunogenicity in a large population than the phase 1 trial. This is an important step in evaluating this early-stage experimental vaccine and phase 3 trials are now underway." [2]

Currently, there are about 250 candidate vaccines against SARS-CoV-2 in development worldwide, including mRNA vaccines, replicating or non-replicating viral vectored vaccines, DNA vaccines, autologous dendritic cell-based vaccine and inactive virus vaccines. At least 17 of them are currently under evaluation in clinical trials.

The vaccine in this trial uses a weakened human common cold virus (adenovirus, which infects human cells readily but is incapable of causing disease) to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight off the coronavirus.

508 participants took part in the trial of the new vaccine. Of these, 253 received a high dose of the vaccine (at 1×1011 viral particles/1.0mL), 129 received a low dose (at 5×1010 viral particles/1.0mL) and 126 received placebo. Approximately two thirds of participants (309; 61%) were aged in 18-44 years, a quarter (134; 26%) were aged 45-54 years, and 13% (65) were 55 years or older.

Participants were monitored for immediate adverse reactions for 30 minutes after injection and were followed for any injection-site or systemic adverse reactions within 14- and 28-days post-vaccination. Serious adverse events reported by participants during the whole study period were documented. Blood samples were taken from participants immediately before the vaccination and 14- and 28-days post-vaccination to measure antibody responses.

The trial found that 95% (241/253) of participants in the high dose group and 91% (118/129) of the recipients in the low dose group showed either T cell or antibody immune responses at day 28 post-vaccination.

The vaccine induced a neutralising antibody response in 59% (148/253) and 47% (61/129) of participants, and binding antibody response in 96% (244/253) and 97% (125/129) of participants, in the high and low dose groups, respectively, by day 28. The participants in the placebo group showed no antibody increase from baseline.

Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with geometric mean titres of 19.5, and 18.3 in participants receiving the high and low dose, respectively. The binding antibody response peaked at 656.5 ELISA units and 571 ELISA units for the high and low dose of the vaccine, respectively.

T cell responses were also found in 90% (227/253) and 88% (113/129) of participants receiving the vaccine at high and low dose, respectively. A median of 11 spot-forming cells and 10 spot-forming cells per 1 × 10? peripheral blood mononuclear cells in participants in the high dose and low dose groups, respectively, were observed at day 28.

The proportions of participants who had any adverse reactions such as fever, fatigue and injection-site pain were significantly higher in vaccine recipients than those in placebo recipients (72% [183/253] in the high dose group, 74% [96/129] in the low dose group, 37% [46/126] in the placebo group). However, most adverse reactions were mild or moderate. Within 28 days, 24 (9%) participants in the high dose group had severe (grade 3) adverse reactions, which was significantly higher than in those receiving the low dose or placebo (one (1%) participant in the low dose group, and 2 people (2%) in the placebo group). The most common severe reaction was fever.

The authors note that pre-existing immunity to the human adenovirus which was used as the vector (ie, the Ad5 vector) for this vaccine and increasing age could partially hamper the specific immune responses to vaccination, particularly for the antibody responses. Among the 508 participants, 266 (52%) participants showed a high pre-existing immunity to Ad5 vector, while 242 (48%) had low pre-existing immunity to Ad5 vector. Those with a higher pre-existing anti-Ad5 immunity showed an inferior immune response (the binding and neutralising antibody levels were around two times larger in people with low pre-existing anti-Ad5 immunity, compared to those with high pre-existing immunity). Compared with the younger population, older participants generally had significantly lower immune responses and higher tolerability to the Ad5 vectored COVID-19 vaccine.

Professor Wei Chen, Beijing Institute of Biotechnology, China, says: "Since elderly individuals face a high risk of serious illness and even death associated with COVID-19 infection, they are an important target population for a COVID-19 vaccine. It is possible that an additional dose may be needed in order to induce a stronger immune response in the elderly population, but further research is underway to evaluate this." [2]

The authors note that the trial was conducted in Wuhan, China, and the baseline immunity is representative of Chinese adults at that time, but other countries may have different rates of immunity which should be considered. Additionally, the trial only followed participants for 28 days and no data about the durability of the vaccine-induced immunity is available from this study. Importantly, no participants were exposed to SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine the efficacy of the candidate vaccine or any immunological risk associated with antibody induced by vaccination when having a virus exposure.

(Edmonton, AB) A new blood test that reliably predicts outcomes for heart failure patients could lead to new diagnostics and treatments for COVID-19 patients as well, according to newly published research from cardiologists at the University of Alberta.

The researchers examined circulating angiotensin peptide levels in the blood of 110 people who were experiencing heart failure due to a heart attack or stroke at the University of Alberta Hospital emergency department and the Mazankowski Alberta Heart Institute in Edmonton. Angiotensin peptides are short proteins that regulate the cardiovascular system and are altered in patients with heart failure--and those with COVID-19.

The researchers found that a high ratio between beneficial peptides (angiotensin 1-7) and harmful peptides (angiotensin II) led to better outcomes, including a lower risk of death and shorter hospital stays, no matter how severe their symptoms were. It was determined that measuring levels of either type of peptide on its own did not provide enough information.

"What our study shows is that you have to look at both sides of it, so it's a balance between the good guy and the bad guy," said Gavin Oudit, a professor of cardiology, Canada Research Chair in Heart Failure and director of the Heart Function Clinic at the Mazankowski. "This is very relevant for heart failure because we can now target this pathway, but it also has implications for COVID-19 patients."

Oudit recently published another paper explaining that the link between heart failure and COVID-19 is the key role played in each disease by the enzyme ACE2 (angiotensin-converting enzyme 2), which is produced in many parts of the body, including the heart, lungs, kidneys and gut. The enzyme protects the heart by increasing production of angiotensin 1-7 (the "good guy" peptide) and suppressing the renin-angiotensin system that produces angiotensin II (the "bad guy" peptide).

ACE2 has also been identified as the receptor for SARS-CoV-2, the virus that causes COVID-19 and has infected millions of people worldwide. Severe disease symptoms can include pneumonia, heart failure, neural problems and failure of other organs.

"This is why SARS-CoV-2 is such a problem," Oudit said. "It's evolved to bind to the right target.

"It picked the perfect receptor to bind to, this key enzyme that protects the cardiovascular system, the lungs, the kidneys, the gut and the central nervous system, and hence these are the type of symptoms our patients are having.

Oudit noted that cardiovascular disease is a key feature in patients with COVID-19, especially those who are hospitalized, are sicker and end up in intensive care units.

The test to determine the ratio between good and bad peptides in the cardiovascular system involves taking a single blood draw and analyzing it with a liquid chromatography-mass spectrometry technique that requires specialized instruments available in most analytic labs.

Oudit proposes the test should be used routinely to determine the risk of adverse outcomes in both heart failure and COVID-19 patients. A precision medicine approach could then be taken to target poor ratios and improve them with either traditional or new drug therapies.

He said the discovery of the ratio test highlights the bridge between cardiovascular disease and COVID-19 and the pivotal role ACE2 plays in both diseases.

"We are fortunate that we have the understanding of ACE2, and we have both the research and therapeutic tools to target this pathway for patients with heart failure, and also now patients with COVID-19," he said. "The crisis is an opportunity to better help all of our patients."

Oudit has been studying the role of ACE2 in heart failure for 20 years, but this research has been cited hundreds of times since the connection between ACE2 and COVID-19 was uncovered.

He explained that traditional heart failure treatments that block the bad peptides in the renin-angiotensin system--such as ACE inhibitors and angiotensin receptor blockers--might be beneficial for COVID-19 patients who experience similar symptoms. Clinical trials to determine their effectiveness are already underway in North America, Europe and China.

"In cardiovascular patients, the renin-angiotensin system makes the disease worse, so blocking the system has always been beneficial for patients with cardiovascular disease, including those with heart failure," Oudit said.

He also suggested that new biologic therapies that boost the good peptides--synthetic human molecules such as recombinant human ACE2 or angiotensin 1-7 analogues--may also be beneficial for both cardiovascular and COVID-19 patients.

"We make large amounts of the human molecules that are shown to be pure and effective, and they can be given at high levels to replenish a system that's relatively deficient in them," he explained.

Oudit said trials giving peptide boosters to COVID-19 patients are starting in Europe, and his team intends to apply for Health Canada permission to study the effect of these treatments in both heart failure and COVID-19 patients as well.

Early on in the COVID-19 pandemic, medical researchers feared that boosting ACE2 in patients might make them more susceptible to the virus, but that has now been shown to be incorrect.

"We now know that whatever baseline ACE2 levels you have, whether you're healthy or have cardiovascular disease, that's more than enough for the virus to get into your body if you encounter the virus," he said. "So changing the level with these drugs does not change your risk, and in fact it may actually improve your outcome."

He explained that SARS-CoV-2 aids the harmful renin-angiotensin system by tying up the ACE2 regulator function, so the hope is that boosting ACE2 in COVID-19 patients can override that effect to better fight the disease.

"In heart failure patients, when your ACE2 is working well, your mortality is much lower, hospitalization is reduced," he said. "Now we need to see the parallels in patients with COVID-19."

A replicating RNA vaccine, formulated with a lipid-based nanoparticle emulsion that goes by the acronym LION, produces antibodies against the COVID-19 coronavirus in mice and primates with a single immunization. These antibodies potently neutralize the virus.

The effects occurred within two weeks after administration through injection into a muscle. The level of antibodies generated was comparable to those in people who are recovering from COVID-19.

The vaccine induced coronavirus-neutralizing antibodies robustly in both younger and older mice. This hopeful finding was well-received by the researchers, because of the concern that the elderly are less likely to respond to vaccination due to their aging immune systems.

Vulnerability to severe COVID-19 in older people increases with age; a vaccination suitable for this high-risk population is a key goal of the scientists.

This vaccine design, as shown in lab studies, is designed to avoid immune responses that could enhance a respiratory disease induced by the coronavirus. Instead, it directs the immune response toward more protective antiviral measures. In addition to antibody production that can block the infection, the vaccine induces T cells, a type of white blood cell that provides a second line of defense if antibodies don't completely block the infection.

The methods and results of animal tests of the replicating RNA coronavirus vaccine candidate vaccine are published July 20 in Science Translational Medicine.

The lead author of the paper is Jesse H. Erasmus, a Washington Research Foundation Postdoctoral Fellow in the laboratory of Deborah Heydenberg Fuller. She is a professor of microbiology at the University of Washington School of Medicine and division chief of Infectious Diseases and Translational Medicine at the Washington National Primate Research Center.

As COVID-19 continues to spread, the discovery and widespread distribution of safe and effective vaccines are essential for slamming down the pandemic. Scores of vaccine candidates are in various stages of testing around the world, from preclinical studies to human trials.

"A vaccine that can stop COVID-19," Fuller wrote, "will ideally induce protective immunity after only a single immunization, avoid immune responses that could exacerbate virus-induced pathology, be amenable to rapid and cost-effective scale-up and manufacturing, and be capable of inducing immunity in all populations including the elderly who typically respond poorly to vaccines."

"That's a tall order," she added. She sees conventional nucleic acid vaccines as promising, but at least two immunizations are needed to instill immunity in people.

Most DNA vaccines require high doses to achieve protective levels of immunity in humans. Traditional messenger RNA vaccines formulated with lipid nanoparticles to increase their effectiveness may face obstacles of mass-production and shelf life.

To try to overcome these limitations, the labs of Fuller and her collaborators at the National Institutes of Health Rocky Mountain Laboratories and HDT Bio Corp. have developed a replicating RNA version of a coronavirus vaccine.

Replicating RNA vaccines for other infectious diseases and cancers are in the pipeline at several institutions.

Replicating RNA expresses a greater amount of protein, and also triggers a virus-sensing stress response that encourages other immune activation.

In the case of the COVID-19 vaccine candidate, the RNA enters cells and instructs them to produce proteins that teach the body to recognize coronaviruses and attack them with antibodies and T cells.

This blockade might keep the viruses from fusing to cells and injecting their genetic code for commandeering cellular activities.

These antibodies induced by the vaccine provide protection by interfering with the protein machinery on the spikes of the coronavirus.

This replicating RNA vaccine contains the novel Lipid InOrganic Nanoparticle (LION) developed by Seattle-based biotechnology company HDT Bio Corp.

"We are pleased with the collaboration with UW to move our RNA vaccine platform forward," said the company's CEO, Steve Reed.

Amit P. Khandhar, the lead formulation developer, added, "RNA molecules are highly susceptible to degradation by enzymes. LION is a next-generation nanoparticle formulation that protects the RNA molecule and enables in vivo delivery of the vaccine after a simple mixing step at the pharmacy."

The nanoparticle enhances the vaccine's ability to provoke the desired immune reaction, and also its stability. This vaccine is stable at room temperature for at least one week. Its components would allow it to be rapidly manufactured in large quantities, should it prove safe and effective in human trials.

The scientists anticipate that lower and fewer doses would need to be made to immunize a population.

A key differentiating factor between LION and the lipid nanoparticle delivery vehicle used in other mRNA COVID-19 vaccines is its ability to be formulated with mRNA by simple mixing at the bedside.

The two-vial approach enabled by LION allows for manufacturing of the formulation independently from the mRNA component.

The research team is working to advance the vaccine to Phase 1 testing in people, in which it would be introduced into a small group of healthy volunteers to gather preliminary data on whether it is safe and generates the desired immune response.

Scientists report a change in why men seek help for sexual problems, with fewer men complaining about impotence (erectile dysfunction) and premature ejaculation, and more men, especially younger men, complaining about low sexual desire and curvature of the penis (Peyronie's disease).

Presenting the work at the European Association of Urology (virtual) Congress, after recent acceptance for publication, research leader Dr Paolo Capogrosso (San Raffaele Hospital, Milan, Italy) said:

"Over a 10 year period we have seen a real change in what concerns men when they attend sexual health clinics. This is probably driven by greater openness, and men now accepting that many sexual problems can be treated, rather than being something they don't want to talk about".

The success of erectile dysfunction treatments such as Viagra and Cialis, and the availability of new treatments, means that men facing sexual problems have now have treatments for sexual problems which weren't available a generation ago. Now researchers at San Raffaele Hospital in Milan have studied why men come to sexual health clinics, and how this has changed over a 10-year period.

In what is believed to be the first research of its kind, the scientists questioned 3244 male visitors to the San Raffaele Hospital Sexual Health Clinic in Milan over a 10 year period (2009 to 2019), and classified the main reason for the visit. They found that the number of patients visiting with erectile dysfunction problems increased from 2009 to 2013, then started to decrease.

There were comparatively few patients complaining of low sex drive or Peyronie's disease in 2009, but complaints about both of these conditions grow from 2009 to the end of the study. In 2019 men were around 30% more likely to report Peyronie's disease than in 2009, and around 32% more likely to report low sexual desire.

The amount of men complaining of premature ejaculation dropped by around 6% over the 10-year period. The average age of first attendance at the clinical also dropped, from a mean of 61 to 53 years.

"Erectile dysfunction is still the main reason for attending the clinic, but this number is dropping, whereas around 35% of men attending the clinic now complain of Peyronie's disease, and that number has shown steady growth" said Paolo Capogrosso. "Our patients are also getting younger, which may reflect a generational change in attitude to sexual problems".

Dr Capogrosso continued "We need to be clear about what these figures mean. They do not indicate any change in the prevalence of these conditions, what they show is why men came to the clinic. In other words, it shows what they are concerned about. The changes probably also reflect the availability of treatments; as treatments for sexual conditions have become available over the last few years, men are less likely to suffer in silence".

These are results from a single centre, so they need to be confirmed by more inclusive studies. "Nevertheless there seems to be a growing awareness of conditions such as Peyronie's disease, with articles appearing in the popular press**. In addition, we know that the awareness of this condition is increasing in the USA and elsewhere, so this may be a general trend*** " said Dr Capogrosso.

Commenting, Dr Mikkel Fode (Associate Professor of Urology at University of Copenhagen), said:

"Although these data are somewhat preliminary as they stem from single institution they are interesting because they allow us to formulate several hypothesis. For example the drop in men presenting with erectile dysfunction may mean that family physicians are becoming more comfortable addressing this issue and that the patients are never referred to specialized centres. Likewise the simultaneous drop in age at presentation and increase in Peyronie's disease and low sex drive could indicate that both men and their partners are becoming more mindful to optimizing their sex lives. I will be very interesting to see if these trends are also present in other centres around the world."

Dr Fode was not involved in this work, this is an independent comment.

BOSTON - Lowering the cost of magnetic-resonance imaging (MRI) could revolutionize how doctors diagnose and screen for many diseases. In a study published in the journal Science Advances, a researcher at Massachusetts General Hospital (MGH) and colleagues in Australia identify the missing piece needed to generate high-quality imaging using low-cost MRI scanners, which could expand the role of this powerful technology in medicine.

A typical MRI scanner carries a price tag of up to $3 million or more, which is why the machines are primarily found in imaging clinics and are typically unaffordable for hospitals in remote areas with small patient populations. Finding a way to make MRI scanners more affordable has long been the objective of physicist Matthew Rosen, PhD, director of the Low-field MRI and Hyperpolarized Media Laboratory at the MGH Martinos Center for Biomedical Imaging. "The focus of my lab is to deconstruct the MRI scanner," says Rosen.

The cost of an MRI scanner is largely driven by its superconducting magnet, explains Rosen: The stronger the magnetic field it produces, the more expensive the machine. A typical MRI machine generates a magnetic field of 1.5 Tesla (T), though increasingly machines reach 3 T. However, a new generation of portable "low-field" MRI scanners that operate at 0.064 T and cost between $50,000 and $100,000 has recently become available.

While low-field MRIs are growing in popularity, radiologists frequently ask Rosen if an injectable contrast agent is available to improve the images they produce. Doctors occasionally inject patients with a contrast agent based on the heavy metal gadolinium before performing a conventional MRI to enhance image quality, though concerns about long-term toxicity now limit that practice.

For gadolinium to be used with low-field MRI, a doctor would have to administer 1,000 times more than the amount approved by the Food and Drug Administration (FDA), explains Rosen.

To solve the problem, physicists David Waddington, PhD, the lead author of the Science Advances study, and Zdenka Kuncic, PhD, both from the University of Sydney, suggested testing superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent with low-field MRI.

SPIONs are safe and approved by the FDA for treating some cases of anemia, or iron-deficiency, but they have another desirable quality. "SPIONs essentially amplify low magnetic fields," says Waddington, noting that SPIONs are 3,000 times more magnetic than conventional MRI contrast agents.

In the study, healthy lab rats were scanned with Rosen's homemade ultralow field (ULF) MRI (0.0065 T), then injected with SPIONs and rescanned. A comparison of pre- and post-injection images shows a striking difference, with kidneys, livers, and other organs glowing brightly following administration of SPIONs.

While SPIONs need to be approved by the FDA for use as contrast agents, doctors can use them now "off label" with low-field MRI. Rosen and Waddington believe the combination of portable low-field MRIs and SPIONs will bring this valuable imaging technology to emergency rooms, intensive care units, and doctors' offices for routine screenings.

Waddington and Kuncic are also investigating the use of specially coated SPIONs that could allow MRI to be used for detecting malignant tumors. "This is an enabling technology that will make low-cost MRI a reality," says Rosen.

OAK BROOK, Ill. (July 17, 2020) - Private radiology practices have been especially hard hit by the COVID-19 pandemic, and the steps they take to mitigate the impact of the pandemic on their practice will shape the future of radiology, according to a special report from the Radiological Society of North America (RSNA) COVID-19 Task Force, published today in the journal Radiology.

The COVID-19 pandemic resulted in widespread disruption to the global economy. The resulting reduction in demand for imaging services had an abrupt and substantial impact on private radiology practices, which are heavily dependent on examination volumes for practice revenues. Examination volumes in radiology practices have decreased by 40%-90%. The volume reduction is anticipated to persist for anywhere from a few months to a few years.

Private practice radiologists make up a substantial proportion of the specialty, accounting for approximately 83% of all practicing radiologists in 2019.

The report describes specific experiences of radiologists working in various types of private practices during the initial peak of the COVID-19 pandemic and presents a detailed case study of a private radiology practice impacted by the pandemic. The authors outline factors determining the impact of the pandemic on private practices, the challenges practices have faced, and the financial adjustments made to mitigate losses.

"For many practices, caring for patients with COVID-19 increased the complexity of the financial impact," said lead author Richard E. Sharpe Jr., M.D., M.B.A., senior associate consultant at Mayo Clinic in Scottsdale, Arizona. "Volumes of advanced imaging, a higher reimbursement service for many practices, were reduced while low reimbursement services, such as radiography, often increased. At the same time, performing these low reimbursement services in ways that minimized the risk of virus transmission to staff and other patients increased the time and resources required to perform these services. These challenges were often most pronounced in private practices that included a hospital-based component to their practice, and which cared for COVID-19 patients with moderate and severe symptoms."

In addition to financial burdens, tremendous variability in interpretations of state-level practice guidance existed, even in the early affected Seattle area. For example, some practices in Seattle maintained elective imaging appointments, while other groups only indicated plans to reschedule screening examinations. Still others requested that patients postpone all elective imaging. One group directed patients to reschedule only if they were symptomatic for coronavirus.

In the report, Dr. Sharpe, along with coauthors Brian S. Kuszyk, M.D., and Mahmud Mossa-Basha, M.D., lay out strategic efforts that practices are making to their mid- and long-term plans to pivot for long-term success while managing the COVID-19 pandemic.

Private radiology practices have crafted tiered strategies to respond to the impact of the pandemic by pulling various cost levers to adjust service availability, staffing, compensation, benefits, time off and expense reductions. In addition, they have sought additional revenues, within the boundaries of their practice, to mitigate ongoing financial losses.

Some practices may opt to adjust employed physician contracts to better mitigate practice risk from potential future volume disruptions. Base salary may comprise a smaller portion of overall compensation, with the balance dependent on the overall financial performance of the organization and/or individual productivity.

The longer-term impact of the pandemic will alter existing practices, making some of them more likely to succeed in the years ahead.

Some groups may prove unable to survive the COVID-19 pandemic, potentially fueling trends either toward consolidation into larger radiology groups or toward increased employment by hospitals.

"We anticipate that small radiology practices may be at greatest risk for consolidation with larger radiology groups that have a more diversified practice model regarding inpatient-outpatient mix, subspecialty service lines, and geography," said Dr. Kuszyk, president of Eastern Radiologists in Greenville, North Carolina.

RSNA is committed to providing trusted resources to the radiology community as they prepare for and manage patient surges caused by the spread of COVID-19. RSNA established the COVID-19 Task Force to lead RSNA's efforts in educating radiologists and health care professionals about the impact of COVID-19 and develop needed tools to help radiology departments handle the crisis. RSNA's COVID-19 Resources page houses the latest guidance, original research, image collection and more.

MANHATTAN, KANSAS -- A new study by Kansas State University researchers is the first to confirm that SARS-CoV-2 cannot be transmitted to people by mosquitoes.

Stephen Higgs, associate vice president for research and director of the university's Biosecurity Research Institute, or BRI, together with colleagues from the BRI and the College of Veterinary Medicine had the findings published July 17 by Scientific Reports.

The article, "SARS-CoV-2 failure to infect or replicate in mosquitoes: an extreme challenge," details the study's findings, which provide the first experimental investigation on the capacity of SARS-CoV-2, the virus that causes COVID-19 disease, to infect and be transmitted by mosquitoes.

"While the World Health Organization has definitively stated that mosquitoes cannot transmit the virus, our study is the first to provide conclusive data supporting the theory," said Higgs, Peine professor of biosecurity and university distinguished professor of diagnostic medicine and pathobiology.

The study, which was done at the BRI, a biosecurity level-3 facility, ultimately found that the virus is unable to replicate in three common and widely distributed species of mosquitoes -- Aedes aegypti, Aedes albopictus and Culex quinquefasciatus -- and therefore cannot be transmitted to humans.

"I am proud of the work we are doing at K-State to learn as much as we can about this and other dangerous pathogens," said Higgs. "This work was possible because of the unique capabilities of the BRI and the dedicated BRI and institutional staff."

Colleagues involved with the study include Yan-Jang Huang, research assistant professor of diagnostic medicine and pathobiology; Dana Vanlandingham, professor of diagnostic medicine and pathobiology; Ashley Bilyeu and Haelea Sharp, research assistants in diagnostic medicine and pathobiology; and Susan Hettenbach, research assistant at the BRI.

Researchers at the BRI have completed four additional studies on COVID-19 since March and this is the first peer-reviewed publication based on SARS-CoV-2 experiments wholly conducted at K-State.

Research at the Biosecurity Research Institute has been ongoing with other animal pathogens that can be transmitted from animals to people, including Rift Valley fever and Japanese encephalitis, as well as diseases that could devastate America's food supply, such as African swine fever and classical swine fever. The research was in part supported by the National Bio and Agro-Defense Facility Transition Fund provided by the state of Kansas.

"We have remarkable talent and capabilities working within our research and training facility at the BRI," said Peter Dorhout, K-State vice president for research. "The BRI is one of the critical anchor facilities in the North Campus Corridor, which serves as our growing research and development space for private sector and government agency partnerships with K-State."

Irvine, Calif. - Cannabis appears to be a safe and potentially effective treatment for the chronic pain that afflicts people with sickle cell disease, according to a new clinical trial co-led by University of California, Irvine researcher Kalpna Gupta and Dr. Donald Abrams of UC San Francisco. The findings appear in JAMA Network Open.

"These trial results show that vaporized cannabis appears to be generally safe," said Gupta, a professor of medicine on the faculty of UCI's Center for the Study of Cannabis. "They also suggest that sickle cell patients may be able to mitigate their pain with cannabis - and that cannabis might help society address the public health crisis related to opioids. Of course, we still need larger studies with more participants to give us a better picture of how cannabis could benefit people with chronic pain."

Opioids are currently the primary treatment for the chronic and acute pain caused by sickle cell disease. But the rise in opioid-associated deaths has prompted physicians to prescribe them less frequently, leaving sickle cell patients with fewer options.

The double-blind, placebo-controlled, randomized trial was the first to employ such gold-standard methods to assess cannabis's potential for pain alleviation in people with sickle cell disease. The cannabis used in the trial was obtained from the National Institute on Drug Abuse - part of the National Institutes of Health - and contained equal parts of THC and CBD.

"Pain causes many people to turn to cannabis and is, in fact, the top reason that people cite for seeking cannabis from dispensaries," Gupta said. "We don't know if all forms of cannabis products will have a similar effect on chronic pain. Vaporized cannabis, which we employed, may be safer than other forms because lower amounts reach the body's circulation. This trial opens the door for testing different forms of medical cannabis to treat chronic pain."

Twenty-three patients with sickle cell disease-related pain completed the trial, inhaling vaporized cannabis or a vaporized placebo during two five-day inpatient sessions that were separated by at least 30 days. This allowed them to act as their own control group.

Researchers assessed participants' pain levels throughout the treatment period and found that the effectiveness of cannabis appeared to increase over time. As the five-day study period progressed, subjects reported that pain interfered less and less with activities, including walking and sleeping, and there was a statistically significant drop in how much pain affected their mood. Although pain levels were generally lower in patients given cannabis than in those given the placebo, the difference was not statistically significant.

BUFFALO, N.Y. -- A new study reveals intricate details about the biology of the huntingtin protein (HTT), which is responsible for Huntington's disease.

The research focuses on axonal transport -- the way in which vital materials travel along pathways called axons inside nerve cells, or neurons.

Scientists found that HTT sometimes journeys along these roadways in cellular vehicles (called vesicles) that also carry freight including a protein called Rab4. Other materials that may be present in these shipments include proteins essential to the health and function of nerve cells, scientists conclude.

The findings also point to a potential treatment avenue: In fruit fly larvae, a mutated form of HTT that causes Huntington's disease disrupted the normal movement of vesicles holding HTT and Rab4. This led to problems such as defects in a part of the nerve cell called the synapse; difficulties with crawling; and decreased lifespan, the study found. But when larvae carrying the HTT mutation were engineered to also produce excess Rab4, some of these symptoms -- including abnormalities in synapses, crawling and lifespan -- were less pronounced.

"When it comes to finding therapies for neurological diseases, a lot of the research focuses on the pathology and aggregation of proteins, but that may not be the actual cause," says Shermali Gunawardena, PhD, associate professor of biological sciences in the University at Buffalo College of Arts and Sciences. "We want to try to figure out what might be going on earlier. We want to come in from a different angle and say, 'OK, are huntingtin and Rab4 normally present together in healthy neurons? And then, what are they doing in the context of a disease state?' "

"This research helps shed light on the normal function of huntingtin and how it is altered in disease," says co-first author Joseph A. White II, a UB biological sciences PhD graduate who is now a postdoctoral researcher at Duke University. "Based on what we're seeing, HTT seems to be important for the transport of a particular type of vesicle known as endosomes within neurons. We believe this presents a potential avenue for therapeutics aimed at improving endosomal transport in Huntington's disease patients."

Gunawardena led the study with first authors White and Thomas J. Krzystek, a UB PhD student in biological sciences.

The research, published on July 1 in Acta Neuropathologica Communications, builds on past work in Gunawardena's lab. Previously, her team showed that mutated HTT can also perturb the movement of some other Rab proteins. The findings suggest that potential treatments focusing on axonal pathways may also need to be multifaceted, involving a number of drugs targeting different problems, Gunawardena says.

"The idea behind our work is to tease out these details about what's going on inside neurons," she says. "It's really difficult to isolate what's going on inside the organism. But from what we have done in the lab, we can say now that huntingtin is in these different, specific kinds of cargoes. I think the bottom line is that this protein is doing a lot of different things."

"Model organisms, like the fruit fly, are excellent tools we can use to quickly investigate a variety of proteins and pathways related to human diseases," Krzystek says. "Our study highlights the advantage of using these simpler organisms to discover new information that we can then test directly in more complex systems. Through this, we learned about what huntingtin might be doing with Rab4 in healthy neurons, and how this role may become disrupted in Huntington's disease."

July 16, 2020-- An American Thoracic Society-led international task force has released a guidance document to help guide clinicians on restoring elective in-person pulmonary and sleep services as COVID-19 incidence decreases in their communities. The new guidance, published online in the Annals of the American Thoracic Society, is titled "Restoring Pulmonary and Sleep Services as the COVID-19 Pandemic Lessens."

The task force, comprised of clinicians who are members of the Association of Pulmonary, Critical Care, and Sleep Division Directors and/or the American Thoracic Society who are actively engaged in COVID-19 patient care, developed a consensus approach on how and when to restart services that were put on hold due to the Centers for Disease Control and Prevention (CDC) March 2020 recommendations to cancel elective services. Specific guidance is provided regarding elective services in outpatient pulmonary and sleep medicine clinics, pulmonary function testing laboratories, bronchoscopy and procedural suites, polysomnography laboratories, and pulmonary rehabilitation facilities.

"This document provides important guidance to health care institutions about when it is reasonable to begin resuming elective in-person clinical services in pulmonary and sleep medicine, as well as strategies to mitigate the risk of viral transmission as those services are resumed," said Kevin C. Wilson, MD, chief of Guidelines and Documents at the American Thoracic Society and Professor of Medicine at Boston University School of Medicine. "To facilitate implementation of the guidance, we aimed to account for limitations in staff, equipment and space that are essential for the care of COVID-19 patients and provide access to care for patients with acute and chronic conditions."

The main recommendations for resuming outpatient clinical services are:

to ensure that the local new case rate has a downward trajectory for at least 14 days before resuming clinical testing, assuming that the volume of testing remains relatively constant;

to resume elective clinical services when one's institution has the capacity for implementing patient prioritization, screening, diagnostic testing, physical distancing, infection control and follow-up surveillance;

to prioritize outpatient services on the basis of patient acuity, and tailor services to institutional resources, patient and provider preferences, and community disease prevalence;

to identify patients with SARS-CoV-2, the virus caused by COVID-19, by following a multi-phased screening schedule to mitigate the possibility of viral transmission from such patients;

to use physical distancing strategies, which should vary depending on COVID-19 community prevalence, and should also account for visitor policies;

to institute appropriate infection control and personal protective equipment protocols, such as requiring that all patients wear a surgical mask and cleaning rooms between patients;

to instruct patients to contact the clinic if they develop new respiratory symptoms within 14 days of their visit, and/or are diagnosed with COVID-19;

to, periodically, critically assess the success (or lack thereof) of resuming pulmonary and sleep medicine clinical services and adjust accordingly, and

to give staff either COVID-19 or non-COVID assignments, with no rotations through both clinical settings.

Guidance for specific services include, for example, evaluating how important pulmonary function testing is for making a diagnosis or decision, relative to the risk of exposing staff and cross-contaminating equipment. For bronchoscopy and procedure suites, a priority scoring system such as the Medically Necessary and Time-Sensitive instrument might be used to determine procedure scheduling. The guidance recommends that polysomnography services reopen in a phased manner, to allow staff time to acclimate to a new workflow, with the preferred first step being home sleep apnea testing.

Dr. Wilson added, "A static plan is unlikely to be maximally effective in the context of a dynamic process like SARS-CoV-2 transmission. The operational strategy should be frequently assessed and modified as needed to emphasize strengths and correct faults."

Kanazawa, Japan - Tens of millions of people worldwide have chronic heart failure, and only a little over half of them survive 5 years beyond their diagnosis. Now, researchers from Japan are helping doctors to assign patients into groups based on their specific needs, to improve medical outcomes.

In a study recently published in the Journal of Nuclear Cardiology, researchers from Kanazawa University have used computer science to disentangle patients most at risk of sudden arrhythmic cardiac death from patients most at risk of heart failure death.

Doctors have many methods at their disposal for diagnosing chronic heart failure. However, there's a need to better identify what treatment to pursue, in accordance with the risks of each approach. When combined with conventional clinical tests, a molecule known as iodine-123 labelled MIBG can help discriminate between high-risk and low-risk patients. However, there is no way to assess the risk of arrhythmic death separately from the risk of heart failure death, something the researchers at Kanazawa University aimed to address.

"We used artificial intelligence to show that numerous variables work in synergy to better predict chronic heart failure outcomes," explains lead author of the study Kenichi Nakajima. "Neither variable, in and of itself, is quite up to the task."

To do this, the researchers examined the medical records of 526 patients with chronic heart failure and who underwent consecutive iodine-123-MIBG imaging and standard clinical testing. Conventional medical care proceeded as normal after imaging.

"The results were clear," says Nakajima. "Heart failure death was most common in older adult patients with very low MIBG activity, worse New York Heart Association class, and comorbidities."

Furthermore, arrhythmia was most common in younger patients with moderately low iodine-123-MIBG activity and less serious heart failure. Doctors can use the Kanazawa University researchers' results to tailor medical care; for example, the type of implantable defibrillator most likely to meet the needs of the patient.

"It's important to note that our results need to be confirmed in a larger study," explains Nakajima. "In particular, the arrhythmia outcomes were perhaps too infrequent to be clinically reliable."

Given that chronic heart failure is a global problem that frequently kills within a few years after diagnosis, if not treated appropriately, it's essential to start the most appropriate medical care as soon as possible. With a reliable test that predicts which patients most likely need which treatments, a greater number of patients are likely to live longer.

A novel mouse model of the protective effects of contained tuberculous infection could lead to the development of a more effective vaccine, according to a study published July 16 in the open-access journal PLOS Pathogens by Alan Diercks of Seattle Children's Research Institute, and colleagues.

Tuberculosis, which is caused by the bacterium Mycobacterium tuberculosis (Mtb), is the deadliest infectious disease worldwide. But the vast majority of individuals with an intact immune system contain the infection indefinitely with no clinical symptoms. Prior infection with Mtb protects against the development of active tuberculous after re-exposure. Understanding the elusive mechanisms underlying this natural protection would inform vaccine design efforts - an important goal, given the lack of a highly effective vaccine against adult tuberculosis. Unfortunately, progress toward this goal has been hampered by the lack of a small animal model of the protective effects of contained Mtb infection -- a critical feature of the human disease.

Using a mouse model, Diercks and colleagues showed that contained and persistent yet non-pathogenic infection with Mtb rapidly and durably reduces tuberculosis disease burden after re-exposure. Previous studies attributed the protective effects of contained Mtb infection to adaptive immune responses, which unfold over a longer timescale, but target pathogens more accurately. By contrast, the new study reveals an important role for innate immune responses - nonspecific defense mechanisms that are quickly activated. Specifically, the researchers found that the protective effects of contained Mtb infection is associated with amplified innate immune activation, which is dependent on low blood levels of a signaling molecule called interferon-?. The findings suggest that the continuous interaction of the immune system with Mtb benefits the host by maintaining elevated innate immune responses. According to the authors, a deeper understanding of the protective mechanisms generated by contained Mtb infection could substantially inform clinical practice.

The authors conclude, "This study highlights the continued and evolving role of the mouse model in TB vaccine development."

A study has shown that the amount of porn a man watches is linked to worse erectile function. Watching porn is also associated with greater dissatisfaction with "normal" sex, with only 65% of respondents rating sex with a partner to be more stimulating than porn. This work is presented at the EAU virtual Congress.

Pornography has been increasingly available via the internet since around 2007. This has led to a rapid uptake in use, but there is little information on how increasing porn use might affect erectile function. Researchers from Belgium, Denmark and the UK established an online questionnaire, which was advertised mainly to men in Belgium and Denmark through social media, posters and flyers. 3267 men replied to the 118 questions, answering questions about masturbation, frequency of porn watching, and sexual activity with partners. The questionnaire concentrated on men who had had sex within the previous 4 weeks, which allowed the team to relate the effect of porn watching on sexual activity. The questionnaire incorporated questions from standard erectile function and sexual health surveys (see notes).

Head researcher, Professor Gunter de Win (University of Antwerp and University Hospital Antwerp) said:

"We found that there was a big range of responses. In our sample, men watch quite a lot of porn, on average around 70 minutes per week, normally for between 5 and 15 minutes per time, with obviously some watching very little and some watching much, much more".

They also found that around 23% of men under-35 who responded to the survey had some level of erectile dysfunction when having sex with a partner.

Professor de Win commented:

"This figure was higher than we expected. We found that there was a highly significant relationship between time spent watching porn and increasing difficulty with erectile function with a partner, as indicated by the erectile function and sexual health scores. People who watch more porn also scored high on porn addiction scales.

"We need to keep understand what this work means and doesn't mean. It is a questionnaire rather than a clinical trial, and it could be that the people who have responded are not completely representative of the whole male population. However, the work was designed to unpick any relationship between porn and erectile dysfunction, and given the large sample size we can be pretty confident about the findings".

We found that 90% of men fast-forward to watch the most arousing pornographic scenes. There's no doubt that porn conditions the way we view sex; in our survey only 65% of men felt that sex with a partner was more exciting than watching porn. In addition, 20% felt that they needed to watch more extreme porn to get the same level of arousal as previously. We believe that the erectile dysfunction problems associated with porn stem from this lack of arousal.

Our next step in this research to identify which factors lead to erectile dysfunction, and to conduct a similar study on the effects of porn on women. In the meantime, we believe that doctors dealing with erectile dysfunction should also be asking about watching pornography".

Commenting, Professor Maarten Albersen (University of Leuven, Belgium) said:

"This is an interesting study by prof. De Win and colleagues. The sample consisted mainly of younger men recruited via (social) media and posters, which may result in a sample biased towards higher online porn consumption rates". All-in-all, the study raises interesting insights in the fact that porn consumption by men may lead to impaired erectile function and/or sexual satisfaction or confidence during partner-sex. As Professor De Win says, the running hypothesis is that the type of porn watched may come more explicit over time and partner-sex may not lead to the same level of arousal as the pornographic material does. The study contributes to an ongoing debate on the topic; experts have highlighted that porn may have both positive and negative effects, and could for example be used as an aid in the treatment of sexual dysfunctions, so this is a controversial area and the last words have not been said on this topic".

Professor Albersen was not involved in this work, this is an independent comment.

The 35th European Association of Urology conference takes place online from 17-19 July, 2020. This replaces the physical conference which was scheduled to take place in Amsterdam. The EAU conference is the largest and most important urology congress in Europe, with up to 14,000 attendees. Conference website https://eaucongress.uroweb.org/