Regular Exercise Helps Patients Combat Cancer


OUTRUNNING CANCER: Tumors on the lungs of sedentary mice (left) and animals that ran on wheels (right) after injection with melanoma cells.
L. PEDERSEN ET AL., CELL METAB, 2016

Bente Klarlund Pedersen

Mathilde was diagnosed with breast cancer at the age of 44. Doctors treated her with surgery, chemotherapy, and radiation, and Mathilde’s physician informed her that, among many other side effects of her cancer treatment, she could expect to lose muscle mass. To fight muscle wasting, Mathilde began the intensive physical training program offered to cancer patients at the Rigshospitalet University Hospital of Copenhagen. The program consists of 3.5-hour sessions of combined resistance and aerobic training, four times a week for six weeks. Although the chemotherapy made her tired, Mathilde (a friend of mine, not pictured, who requested I use her first name only) did not miss a single training session.

“In a way it felt counterintuitive to do intensive, hard training, while I was tired and nauseous, but I was convinced that the training was good for my physical and mental health and general wellbeing,” Mathilde told me in Danish. She followed the chemo- and radiotherapy strictly according to the prescribed schedule. She was not hospitalized, acquired no infections, and did not develop lymphedema, a failure of the lymphatic system that commonly occurs following breast cancer surgery and leads to swelling of the limbs.

Physical exercise is increasingly being integrated into the care of cancer patients such as Mathilde, and for good reason. Evidence is accumulating that exercise improves the wellbeing of these patients by combating the physical and mental deterioration that often occur during anticancer treatments. Most remarkably, we are beginning to understand that exercise can directly or indirectly fight the cancer itself.

An increasing amount of epidemiological literature strongly indicates that exercise training may lower the risk of cancer, control disease progression, amplify the effects of anticancer therapy, and improve physical function and psychosocial outcomes. For example, a 2016 study of more than 1.4 million individuals in the US and Europe found that people could reduce their cancer risk with moderate to vigorous leisure-time exercise training. The phenomenon held across several different cancers, including breast, colon, rectum, esophagus, lung, liver, kidney, bladder, and head and neck. And the combined results of approximately 700 unique exercise intervention trials, involving more than 50,000 cancer patients in total, leave little doubt that patients benefit from physical activity, showing improvements such as reduced toxicity of anticancer treatment, decreased disease progression, and enhanced survival. The same studies showed that exercise training improves mood, decreases loss of muscle mass, and helps cancer patients return to work earlier after successful treatment. Some studies show that 150 minutes per week of moderate exercise nearly double the chance of survival compared with breast cancer patients who don’t exercise during treatment.

Hundreds of animal studies, conducted over decades, suggest that the link is likely causal: in mice and rats, exercise leads to a reduction in the incidence, growth rate, and metastatic potential of cancer across a large variety of models of different human and murine tumor types. But how exercise helps fight cancer is a bit of a black box. Exercise may improve the efficacy of anticancer treatment by boosting the immune system and thereby attenuating the toxicity of chemotherapy and immunotherapy. Cancer patients are also likely to benefit from the overall health-promoting properties of physical activity, such as improved metabolism and enhanced cardiovascular function.

Uncovering the mechanisms whereby exercise induces anticancer effects is crucial to fighting the disease. Exercise-related factors that have a direct or indirect anticancer effect could serve as valuable biomarkers for monitoring the amount, intensity, and type of exercise required to best aid cancer treatment. Such research could also potentially highlight novel therapeutic targets.

Each workout matters

Regardless of the nature of the training, the primary setting of exercise’s effect on cancer is the bloodstream. Long-term training has been associated with a reduction in the blood levels of systemic risk factors, such as sex hormones, insulin, and inflammatory molecules. However, this effect is only seen if exercise training is accompanied by weight loss, and researchers have not yet established causal direct links between regular exercise training and the reductions in the basal levels of these risk factors. Alternatively, the anticancer effect of exercise could also be the result of something that occurs within individual sessions of exercise, during which muscles are known to release spikes of various hormones and other factors into the blood.

To learn more about the effects of individual bouts of exercise versus long-term training regimens, Christine Dethlefsen, a graduate student in my laboratory, incubated breast cancer cells with serum obtained from cancer survivors at rest before and after a six-month training intervention that began after patients completed primary surgery, chemotherapy, and radiotherapy. For comparison, she incubated other cells with serum obtained from blood drawn from these patients immediately after a two-hour acute exercise session during their weeks-long course of chemotherapy. Her study revealed that serum obtained following an exercise session reduced the viability of the cultured breast cancer cells, while serum drawn at rest following six months of training had no effect.

These data suggest that cancer-fighting effects are driven by repeated acute exercise, and each bout matters. In Dethlefsen’s study, incubation with serum obtained after a single bout of exercise (consisting of 30 minutes of warm-up, 60 minutes of resistance training, and a 30-minute high-intensity interval spinning session) reduced breast cancer cell viability by only 10 to 15 percent compared with control cells incubated with serum obtained at rest. But a reduction in tumor cell viability by 10 to 15 percent several times a week may add up to clinically significant inhibition of tumor growth. Indeed, in a separate study, my colleagues and I found that daily, voluntary wheel running in mice inhibits tumor progression across a range of tumor models and anatomical locations, typically by more than 50 percent.

Exercise’s molecular messengers

One prime candidate for helping to explain the link between exercise and anticancer effects is a group of peptides known as myokines, which are produced and released by muscle cells. Several myokines are released only during exercise, and some researchers have proposed that these exercise-dependent myokines contribute to the myriad beneficial effects of physical activity for all individuals, not just cancer patients, perhaps by mediating crosstalk between the muscles and other parts of the body, including the liver, bones, fat, and brain.

Exercise’s Anticancer Mechanisms

Researchers are beginning to understand that not only can exercise improve cancer patients’ overall wellbeing during treatment, but it may also fight the cancer itself. Experiments on cultured cells and in mice hint at some of the mechanisms that may be involved in these direct and indirect effects.

1) Exercising muscles release multiple compounds known as myokines. Several of these have been shown to affect cancer cell proliferation in culture, and some, including interleukin-6, slow tumor growth in mice.

2) Exercise stimulates an increase in levels of the stress hormones epinephrine and norepinephrine, which can both act directly on tumors and stimulate immune cells to enter the bloodstream.

3) Epinephrine also stimulates natural killer cells to enter circulation.

4) In mice, interleukin-6 appears to direct natural killer cells to home in on tumors.

5) In lab-grown cells and in mice, epinephrine, norepinephrine, and some myokines hinder tumor growth and metastasis.

The best-characterized myokine is interleukin-6, levels of which increase exponentially during exercise in humans. At least in mice, interleukin-6 is involved in directing natural killer (NK) cells to tumor sites. But there are approximately 20 known exercise-induced myokines, and the list continues to grow. Preliminary studies show that myokines can reduce cancer growth in cell culture and in mice. For example, when treated with irisin, a myokine best known for its ability to convert white fat into brown fat, cultured breast cancer cells were more likely to lose viability and undergo apoptosis than were control cells. A study I led found that oncostatin M, another myokine that is upregulated in murine muscles after exercise, also inhibits breast cancer proliferation in vitro. And a team led by Toshikazu Yoshikawa of Kyoto Prefectural University determined that in a mouse model of colon cancer, a myokine known as secreted protein acidic and rich in cysteine (SPARC) reduced tumorigenesis in the colon of exercising mice. Overall, skeletal muscle cells may be secreting several hundred myokine types, but of these, only about 5 percent have been investigated for their biological effects. And researchers have tested fewer for whether they regulate cancer cell growth.

Not all of the molecular messengers released in response to exercise come from the muscles. Notably, exercise induces acute increases in epinephrine and norepinephrine, stress hormones released from the adrenal gland that are involved in recruiting NK cells in humans. Murine studies show that NK cells can signal directly to cancer cells. In Dethlefsen’s study, when breast cancer cells incubated with serum obtained after a bout of exercise were then injected into mice, they showed reduced tumor formation. The exercise-induced suppression of breast cancer cell viability and tumor formation were, however, completely blunted when we blockaded β-adrenergic signaling, the pathway through which epinephrine and norepinephrine work. These findings suggested that epinephrine and norepinephrine are responsible for the cancer-inhibiting effects we observed. Epinephrine and norepinephrine, which activate NK cells, have also been shown to act on cancer cells through the Hippo signaling pathway, which is known for regulating cell proliferation and apoptosis. Exercise-induced spikes in these stress hormones activate this pathway, which somehow inhibits the formation of new malignant tumors associated with metastatic processes.

Calling the immune system

In addition to acting directly on tumors, the myokines released during and after exercise are known to mobilize immune cells, particularly NK cells, which appear to be instrumental to the exercise-mediated control of tumor growth in mice.

The late molecular biologist Pernille Højman of the Centre for Physical Activity Research at Rigshospitalet was a leader in discerning this mechanism. In the study described above that compared tumor growth in active and sedentary mice, on which I was also an author, Højman looked more closely at the tumors and found that the running mice had twice as many cytotoxic T cells and five times more NK cells than those animals housed without a wheel.

Højman repeated the experiment on mice that had been engineered to lack cytotoxic T cells. Again, she found that mice with access to running wheels had smaller tumors. When she performed the same test on mice that had intact T cells but lacked NK cells, the tumors of all the mice grew to the same size. This suggested that the NK cells, and not the T cells, were the link between exercise and tumor growth suppression.

Work by other groups had demonstrated that epinephrine has the potential to mobilize NK cells, and Højman and the rest of our team wondered if epinephrine had a role in mediating the anticancer effects of exercise. We injected mice that had malignant melanoma with either epinephrine or saline and found that the hormone indeed reduced the growth of tumors, but to a lesser degree than what was observed in the mice that had access to a wheel. Something else had to be involved.


AND STAY OUT: Exercise activates natural killer cells (purple) and helps them home to tumors.

To find out what, our team tested the effects of interleukin-6, which we suspected was the additional exercise factor involved in tumor homing of immune cells. When we exposed inactive mice to both epinephrine and interleukin-6, the rodents’ immune systems attacked the tumors as effectively as if the animals had been running.

While much remains to be learned about how physical exercise influences cancer, evidence shows that exercise training is safe and feasible for patients with the disease and contributes to their physical and psychosocial health. (See “Exercise and Depression” on page 44.) Being active may even delay disease progression and improve survival. A growing number of patients, including Mathilde, are undergoing exercise training to fight physical deterioration during cancer treatment. As they do so, scientists are working hard to understand the pathways by which physical activity results in anticancer activity.

Exercise and Depression

Depression is a severe adverse effect of cancer and cancer therapy. The risk of depression can be as high as 50 percent for some cancer diagnoses, although this number varies a great deal depending on cancer type and stage (J Natl Cancer Inst Monogr, 32:57–71, 2004). In addition to its effects on a patient’s quality of life, depression can hinder compliance with treatment, and it’s a risk factor for mortality in cancer patients (Lancet, 356:1326–27, 2000). In recent years, healthcare providers have increasingly integrated physical exercise into the care of cancer patients with the aim of controlling disease and lessening treatment-related side effects, while researchers have amassed evidence supporting the assertion that such training can lower symptoms of depression in these patients (Acta Oncol, 58:579–87, 2019). The biological mechanisms behind this beneficial effect remain to be determined, although some clues have emerged.

For example, a study in mice found that exercise-dependent changes in metabolism result in reduced accumulation of some neurotoxic products (Cell, 159:33-45, 2014). In cancer patients, systemic levels of kynurenine, a neurotoxic metabolite associated with fatigue and depression, are upregulated (Cancer, 121:2129-36, 2015). In mice, exercise enhances the expression of the enzyme kynurenine aminotransferase, which converts kynurenine into neuroprotective kynurenic acid, thereby reducing depression-like symptoms.

Findings such as these, together with exercise’s well-documented effects in alleviating depression among patients without cancer, suggest that incorporating exercise into cancer treatment may benefit mental as well as physical health.

https://www.the-scientist.com/features/regular-exercise-helps-patients-combat-cancer-67317?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=86607989&_hsenc=p2ANqtz-8W-OrX7bn_MULo5_Jx-u7E1c2gVfZwwWCD26RHtjZT7CoZ9KWhz0zOuCD53QkfOvre5WKYWWxP0plIm4Lf56uABjYb0A&_hsmi=86607989

Coronavirus Vaccine Could Be Ready in Six Months from Sarah Gilbert at Oxford University

By Olivia Konotey-Ahulu

A vaccine against the coronavirus could be ready by September, according to a scientist leading one of Britain’s most advanced teams.

Sarah Gilbert, professor of vaccinology at Oxford University, told The Times on Saturday that she is “80% confident” the vaccine would work, and could be ready by September. Experts have warned the public that vaccines typically take years to develop, and one for the coronavirus could take between 12 to 18 months at best.

In the case of the Oxford team, however, “it’s not just a hunch, and as every week goes by we have more data to look at,” Gilbert told the London newspaper.

Gilbert’s team is one of dozens worldwide working on a vaccine and is the most advanced in Britain, she told the Times. As the country looks set to begin its fourth week under lockdown, a vaccine could be fundamental in easing the measures and returning to normal life. Gilbert said human trials are due to start in the next two weeks.

Her remarks came as the death toll from the virus pushed past 100,000 globally. On Friday, the U.K. reported 980 fatalities, taking the total count from the virus to 8,958, and the government has repeatedly pleaded with the public to obey lockdown rules during the long Easter holiday weekend. As Prime Minister Boris Johnson begins his recovery after a spell in intensive care, Patrick Vallance, the government’s chief scientific adviser, warned he expects the number of deaths to increase for “a few weeks” yet.

Manufacturing the millions of vaccine doses necessary could take months. Gilbert said she’s in discussions with the British government about funding, and starting production before the final results are in, allowing the public to access the vaccine immediately if it proves to work. She said success by the autumn was “just about possible if everything goes perfectly.”

https://www.bloomberg.com/news/articles/2020-04-11/coronavirus-vaccine-could-be-ready-in-six-months-times

What Do Countries With The Best Coronavirus Reponses Have In Common? Women Leaders

Looking for examples of true leadership in a crisis? From Iceland to Taiwan and from Germany to New Zealand, women are stepping up to show the world how to manage a messy patch for our human family. Add in Finland, Iceland and Denmark, and this pandemic is revealing that women have what it takes when the heat rises in our Houses of State. Many will say these are small countries, or islands, or other exceptions. But Germany is large and leading, and the UK is an island with very different outcomes. These leaders are gifting us an attractive alternative way of wielding power. What are they teaching us?

Truth

Angela Merkel, the Chancellor of Germany, stood up early and calmly told her countrymen that this was a serious bug that would infect up to 70% of the population. “It’s serious,” she said, “take it seriously.” She did, so they did too. Testing began right from the get go. Germany jumped right over the phases of denial, anger and disingenuousness we’ve seen elsewhere. The country’s numbers are far below its European neighbours, and there are signs they may be able to start loosening restrictions relatively soon.

Decisiveness

Among the first and the fastest moves was Tsai Ing-wen’s in Taiwan. Back in January, at the first sign of a new illness, she introduced 124 measures to block the spread, without having to resort to the lockdowns that have become common elsewhere. She is now sending 10 million face masks to the US and Europe. Ing-wen managed what CNN has called “among the world’s best” responses, keeping the epidemic under control, still reporting only six deaths.

Jacinda Ardern in New Zealand was early to lockdown and crystal clear on the maximum level of alert she was putting the country under – and why. She imposed self-isolation on people entering New Zealand astonishingly early, when there were just 6 cases in the whole country, and banned foreigners entirely from entering soon after. Clarity and decisiveness are saving New Zealand from the storm. As of mid-April they have suffered only four deaths, and where other countries talk of lifting restrictions, Ardern is adding to them, making all returning New Zealanders quarantine in designated locations for 14 days.

Tech

Iceland, under the leadership of Prime Minister Katrín Jakobsdóttir, is offering free coronavirus testing to all its citizens, and will become a key case study in the true spread and fatality rates of Covid-19. Most countries have limited testing to people with active symptoms. Iceland is going whole hog. In proportion to its population the country has already screened five times as many people as South Korea has, and instituted a thorough tracking system that means they haven’t had to lockdown… or shut schools.

Sanna Marin became the world’s youngest head of state when she was elected last December in Finland. It took a millennial leader to spearhead using social media influencers as key agents in battling the coronavirus crisis. Recognising that not everyone reads the press, they are inviting influencers of any age to spread fact-based information on managing the pandemic.

Love

Norway’s Prime Minister, Erna Solberg, had the innovative idea of using television to talk directly to her country’s children. She was building on the short, 3-minute press conference that Danish Prime Minister Mette Frederiksen had held a couple of days earlier. Solberg held a dedicated press conference where no adults were allowed. She responded to kids’ questions from across the country, taking time to explain why it was OK to feel scared. The originality and obviousness of the idea takes one’s breath away. How many other simple, humane innovations would more female leadership unleash?

Generally, the empathy and care which all of these female leaders have communicated seems to come from an alternate universe than the one we have gotten used to. It’s like their arms are coming out of their videos to hold you close in a heart-felt and loving embrace. Who knew leaders could sound like this? Now we do.

Now, compare these leaders and stories with the strongmen using the crisis to accelerate a terrifying trifecta of authoritarianism: blame-“others”, capture-the-judiciary, demonize-the-journalists, and blanket their country in I-will-never-retire darkness (Trump, Bolsonaro, Obrador, Modi, Duterte, Orban, Putin, Netanyahu…).

There have been years of research timidly suggesting that women’s leadership styles might be different and beneficial. Instead, too many political organisations and companies are still working to get women to behave more like men if they want to lead or succeed. Yet these national leaders are case study sightings of the seven leadership traits men may want to learn from women.

It’s time we recognised it – and elected more of it.

https://www.forbes.com/sites/avivahwittenbergcox/2020/04/13/what-do-countries-with-the-best-coronavirus-reponses-have-in-common-women-leaders/#456c3af43dec

Humanity tested

Humanity tested
Nature Biomedical Engineering (2020)Cite this article

10 Altmetric

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The world needs mass at-home serological testing for antibodies elicited by SARS-CoV-2, and rapid and frequent point-of-care testing for the presence of the virus’ RNA in selected populations.

How did we end up here? Two ways. Gradually, then suddenly. Ernest Hemingway’s passage is a fitting description for humanity’s perception of the exponential growth of COVID-19 cases and deaths (Fig. 1). The worldwide spread of a highly infectious pathogen was only a matter of time, as long warned by many epidemiologists, public health experts, and influential and prominent voices, such as Bill Gates. Yet most of the world was unprepared for such a pandemic; in fact, most Western countries (prominently the United States1) fumbled their response for weeks. Singapore, Hong Kong and Taiwan have shown the world that, to contain the propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), governments need to quickly implement aggressive testing (by detecting the viral RNA through polymerase chain reaction (PCR)), the isolation of those infected and the tracing and quarantining of their contacts, while educating their citizens about the need for physical distancing and basic public health measures (in particular, frequent hand-washing and staying at home if feeling unwell). When outbreaks are not detected and acted upon sufficiently early, drastic physical distancing — of the sort implemented by China at the end of January and maintained for months — can eventually suppress the outbreak (Fig. 1). It is however unclear whether Western countries that have implemented strict physical-distancing measures later in their infection curve will be able to gradually release such lockdowns, let alone see their outbreaks controlled.

Fig. 1: Early mass testing and early containment measures save lives.
figure1
COVID-19 confirmed cases and deaths for selected countries in a 10-day window ending at each data point (successive data points on a line denote consecutive days). Numbers in colour are the estimated number of total PCR tests per million people up to the data point indicated; stars indicate when strict lockdowns were enacted. Deaths lag with respect to confirmed cases, according to the estimated two-to-three week interval10 between the onset of symptoms and death. Case fatality rates — that is, the fractions of total confirmed cases that become deaths — mostly depend on the extent of testing, on the capacity of a country’s healthcare system, on its demographics and on the availability of drugs that can significantly dampen the severity of COVID-19 in those infected. Even with mass testing, the case fatality rate of COVID-19 is expected to be a multiple of that for seasonal flu in the United States (0.1%). Countries that deployed tests for detecting SARS-CoV-2 RNA early and widely (such as South Korea), that applied contact tracing and targeted physical distancing measures for detected cases (such as South Korea and Japan), or that enacted early, strict lockdowns (such as China) are more likely to contain the disease outbreak earlier. In fact, Singapore, Hong Kong and Taiwan have contained COVID-19 outbreaks and have managed to limit COVID-19-related deaths to less than 10 (hence, these countries are not included in the figure). Data updated 6 April 2020. Individual data points can be affected by reporting errors and delays, by wilful underreporting and by location-specific definitions (and changes to them) for confirmed cases and deaths. Data sources: European Center for Disease Control and Prevention11 (cases and deaths); Our World in Data12, various government sources (tests). A regularly updated version of this graph is available13.

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Such non-pharmacological interventions aim to ‘flatten’ the infection curve by reducing the number of transmission chains and thus the virus’ basic reproduction number — that is, the average number of new cases generated by a case in an immunologically naive population. In the absence of a safe and effective vaccine — which, if current efforts end up being successful, is unlikely to become widely available within the next two years — non-pharmacological interventions will need to remain in place to reduce the threat of secondary outbreaks by maintaining the basic reproduction number below 1. However, the type and degree of the interventions could be better tailored if governments knew who are currently infected and who have been infected and recovered. For this, the world needs to see the mass deployment of serological testing for SARS-CoV-2 antibodies (which appear to be highly specific2), and frequent testing for SARS-CoV-2 RNA in those likely to be exposed to the virus (especially healthcare workers) or at a higher risk for severe respiratory disease (such as the elderly and younger individuals with relevant comorbidities).

Medical-device companies and government and research laboratories around the world have rushed to adapt and scale up nucleic acid tests (mostly employing PCR, but also CRISPR-based detection and loop-mediated isothermal amplification) to detect the virus’ RNA, and government agencies are scrambling to assess them via emergency routes (such as the Emergency Use Authorization program3 by the United States Food and Drug Administration (FDA)). Point-of-care PCR kits — based on lateral-flow technology or cartridge-based instruments for sample preparation, nucleic acid amplification and detection — also require RNA extraction from nasal or throat swabs (or both) but can speed up the time-to-result from a few hours to roughly 30 minutes4 (and in one test, positive results can be obtained in five minutes5), with near-perfect sensitivity and specificity if sample acquisition and preparation and device operation are carried out appropriately by trained personnel. This limits the usefulness of these kits for at-home use, which would significantly raise the fraction of false negatives. Immunoassays incorporating monoclonal antibodies specific for SARS-CoV-2 antigens (for instance, a domain of the virus’ spike protein) should be amenable to home use, yet they are more difficult to develop (the antibodies are typically obtained via the immunization of transgenic animals) and are less accurate than nucleic acid testing.

Lateral flow immunoassays (akin to the pregnancy test) and enzyme-linked immunosorbent assays to detect antibodies elicited by the virus are also being rapidly developed (mostly by Chinese companies thus far). Tens of at-home lateral-flow devices6 are already being commercialized, having obtained the European Union’s CE mark or been authorized for emergency use by the FDA or the Chinese FDA. In many of these kits, the recombinant viral antigens bind to SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) within 15 min; hence, these tests can also detect early-stage infection (of which IgM levels are a marker), but at the expense of sensitivity and accuracy (which can exceed 90% and 99% for IgG7. The real-world performance of such serology tests, which is currently unknown, will depend on the actual prevalence of COVID-19 in the population. For example, at a 5% pre-test probability of having the disease, a test with 99% sensitivity and 95% specificity would lead to as many true positives as false positives. Hence, before wide deployment, governments need to ensure that these finger-prick antibody tests are clinically validated8.

The world should roll out both antibody and nucleic acid tests on a wide scale. Widely available and inexpensive serological testing would help governments to tailor non-pharmacological interventions to specific locations and populations, to decide when to relax them and to permit citizens immune to the virus to help those who remain susceptible to it. Mass testing would also provide valuable data to pressing unknowns: what are the infection rates across locations and populations? What fraction of the population is immune? How long does immunity last and how does it depend on age and on the severity of infection? Wider deployment of nucleic acid tests would also provide clues about the prevalence of a wider range of COVID-19 symptoms, the role of children in spreading the disease, and the epidemiological characteristics of superspreaders9 and of those who were infected and asymptomatic. Testing should be complemented by privacy-minded digital surveillance, via phone apps, aiding contact tracing and permitting lighter levels of physical distancing — as done in Singapore, South Korea and Taiwan. The downside is that any invasion of privacy via the tracking of people can last longer than necessary. De-identified and aggregated health data, such as heart rate and activity levels collected via commercial wearables, might also predict (https://detectstudy.org) the emergence and location of outbreaks.

In our globalized world, the risk of further waves of COVID-19 outbreaks, and thus of prolonged drastic economic consequences, will remain substantial as long as any outbreak anywhere remains. It is in the world’s best interest that richer countries provide test kits, technical and public-health knowledge, personnel, personal protective equipment and, eventually, the necessary vaccine doses to poorer countries to assist them in their efforts to reduce and contain the spread of SARS-CoV-2. This is humanity’s next test.

References
1.
Shear, M. D. et al. The lost month: how a failure to test blinded the U.S. to Covid-19. The New York Times https://www.nytimes.com/2020/03/28/us/testing-coronavirus-pandemic.html (2020).

2.
Ju, B. et al. Preprint at https://doi.org/10.1101/2020.03.21.990770 (2020).

3.
Emergency Use Authorization (U.S. Food & Drug Administration, 2020); https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations

4.
Accula test: SARS-CoV-2 test. U.S. Food & Drug Administration https://www.fda.gov/media/136355/download (2020).

5.
Abbott realtime SARS-CoV-2 assay. Abbott https://www.molecular.abbott/us/en/products/infectious-disease/RealTime-SARS-CoV-2-Assay (2020).

6.
SARS-CoV-2 Diagnostic Pipeline (Find, 2020); https://www.finddx.org/covid-19/pipeline/

7.
COVID-19 Coronavirus rapid test casette. SureScreen Diagnostics https://www.surescreen.com/products/covid-19-coronavirusrapid-test-cassette (2020).

8.
The Associated Press. Virus test results in minutes? Scientists question accuracy. The New York Times https://www.nytimes.com/aponline/2020/03/27/world/europe/bc-virus-outbreakscramble-for-tests.html (2020).

9.
Hu, K. et al. Preprint at https://doi.org/10.1101/2020.03.19.20026245 (2020).

10.
Verity, R. et al. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(20)30243-7 (2020).

11.
Today’s Data on the Geographic Distribution of COVID-19 Cases Worldwide (European Centre for Disease Prevention and Control, 2020); https://www.ecdc.europa.eu/en/publications-data/download-todays-data-geographic-distribution-covid-19-cases-worldwide

12.
Roser, M., Ritchie, H. & Ortiz-Ospina, E. Coronavirus Disease (COVID-19) – Statistics and Research (Our World in Data, 2020); https://ourworldindata.org/coronavirus

13.
Pàmies, P. Tracking COVID-19 cases and deaths. Nature Research Bioengineering Community https://bioengineeringcommunity.nature.com/users/20986-pep-pamies/posts/64985-tracking-covid-19-cases-and-deaths (2020).

https://www.nature.com/articles/s41551-020-0553-6?utm_source=Nature+Briefing&utm_campaign=5907ab71f9-briefing-dy-20200408&utm_medium=email&utm_term=0_c9dfd39373-5907ab71f9-44039353

Eating too much salt seems to impair body’s ability to fight bacteria

By Michael Le Page

Eating too much salt may impair the body’s ability to fight bacterial infections, according to studies in mice and in 10 human volunteers.

Christian Kurts at the University Hospital of Bonn in Germany and his team first showed that mice given a high salt diet were less able to fight kidney infections caused by E. coli and body-wide infections caused by Listeria monocytogenes, a common cause of food poisoning.

“The bacteria caused more damage before the immune system got rid them,” says Kurts.

Next, the team gave 10 healthy women and men who were 20 to 50 years old an extra 6 grams of salt a day on top of their normal diet, in the form of three tablets a day. After a week, some of their immune cells, called neutrophils, had a greatly impaired ability to engulf and kill bacteria compared with the same tests done on each individual before they took extra salt.

The team didn’t examine the effect of high salt intake on the body’s ability to fight viral infections.

The World Health Organization recommends that people eat no more than 5 grams of salt a day to avoid high blood pressure, which can cause strokes and heart disease. In the UK, people eat 8 grams on average, suggesting many consume as much or more than the volunteers in the study.

The team thinks two mechanisms are involved. First, when we eat lots of salt, hormones are released to make the body excrete more salt. These include glucocorticoids that have the side effect of suppressing the immune system throughout the body.

Second, there is a local effect in the kidney. Kurts found that urea accumulates in the kidney when salt levels are high, and that urea suppresses neutrophils.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.aay3850

https://www.newscientist.com/article/2238629-eating-too-much-salt-seems-to-impair-bodys-ability-to-fight-bacteria/?utm_source=NSDAY&utm_campaign=8ea0a51a66-EMAIL_CAMPAIGN_2020_03_25_04_56&utm_medium=email&utm_term=0_1254aaab7a-8ea0a51a66-374123611

California teen donates more than 150 coronavirus sanitation kits to the homeless. Now she wants your help to distribute more.


Fifteen-year-old Shaivi Shah donated more than 150 hygiene kits to the homeless.

By Lauren Lee

The teenager and her parents made the purchases and now it was time to pack them up.

Shaivi Shah, 15, recruited her fellow Tesoro High School honor society members to assemble kits of hand sanitizer, antibacterial soap, lotion and reusable masks for distribution to help people experiencing homelessness in the middle of a pandemic.

“They don’t have necessities right now that are crucial to remain clean and stay germ-free,” Shaivi told CNN.


Shah assembles the kits at home.

California Gov. Gavin Newsom’s recent speech about the state’s homeless problem sparked her idea. So far, the efforts of the passionate student has led to the delivery of more than 150 low-cost sanitation kits to three Los Angeles shelters.

A vulnerable population

According to the US Interagency Council on Homelessness, on any given day, more than 150,000 Californians are living in homelessness — the most of any US state. Shaivi feared they might be forgotten in this time of social distancing.

“A lot of people are just focusing on themselves and their families,” she said.

The altruistic teen from Rancho Santa Margarita started a GoFundMe account to raise funds to expand her program throughout California and the US.

https://www.gofundme.com/f/covid19-sanitation-kit-for-the-homeless-community

“These people that are living on the streets, they have no protection, so even a small amount could help.”

A call to service

Shah hopes that her actions will encourage others to step in to help in their own ways during the pandemic.

“It’s important for people to step in and just do whatever they can, even if it helps just one person.”

Shah is no stranger to community service. Last year, she raised thousands of dollars for a homeless shelter through a dance recital. Her duty to help people experiencing homelessness comes from a feeling of gratitude.

“Imagine yourself in their shoes, without a house, without clothes, without any sanitation,” she says.

“That’ll make you be grateful for what you have, and possibly donate and do something good for the other people.”

https://www.cnn.com/2020/03/19/us/teen-donates-sanitization-kits-to-homeless-iyw-trnd/index.html

Children with less sleep experience increased depression and anxiety, and decreased cognitive performance

Shorter sleep duration among children was associated with increased risk for depression, anxiety, impulsive behavior and poor cognitive performance, according to study findings published in Molecular Psychiatry.

“Sleep disturbances are common among children and adolescents around the world, with approximately 60% of adolescents in the United States receiving less than 8 hours of sleep on school nights,” Jianfeng Feng, PhD, of the department of computer science at University of Warwick in the UK, told Healio Psychiatry. “An important public health implication is that psychopathology in both children and their parents should be considered in relation to sleep problems in children. Further, we showed that brain structure is associated with sleep problems in children and that this is related to whether the child has depressive problems.”

According to Feng and colleagues, the present study is the first large-scale research effort to analyze sleep duration in children and its impact on psychiatric problems including depression, brain structure and cognition. They analyzed measures related to these areas using data from the Adolescent Brain Cognitive Development Study, which included structural MRI data from 11,067 individuals aged 9 to 11 years.

The researchers found that depression, anxiety and impulsive behavior were negatively correlated with sleep duration. Dimensional psychopathology in participants’ parents was correlated with short sleep duration in the children. Feng and colleagues noted that the orbitofrontal cortex, prefrontal and temporal cortex, precuneus and supramarginal gyrus were brain areas in which higher volume was correlated with longer sleep duration. According to longitudinal data analysis, psychiatric problems, particularly depressive problems, were significantly associated with short sleep duration 1 year later. Moreover, they found that depressive problems significantly mediated these brain regions’ effect on sleep. Higher volume of the prefrontal cortex, temporal cortex and medial orbitofrontal cortex were associated with higher cognitive scores.

“Our findings showed that 53% of children received less than 9 hours of sleep per night,” Feng said. “More importantly, the behavior problems total score for children with less than 7 hours of sleep was 53% higher on average and the cognitive total score was 7.8% lower on average than for children with 9 to 11 hours of sleep. We hope this study attracts public attention to sleep problems in children and provides evidence for governments to develop advice about sleep for children.” – by Joe Gramigna

https://www.healio.com/psychiatry/depression/news/online/%7B7440e93a-fe6a-4154-88f4-a5858d16c4cb%7D/children-with-less-sleep-experience-increased-depression-anxiety-decreased-cognitive-performance

Novel drug therapy from University Hospitals of Cleveland shows promise for improving kidney transplants

Researchers from Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center (UH), Cleveland Clinic and Lifebanc (a Northeast Ohio organ-procurement organization) have developed a new way to preserve donated kidneys–a method that could extend the number and quality of kidneys available for transplant, saving more people with end-stage renal disease, more commonly known as “kidney failure.”

The team identified a drug–ethyl nitrite–that could be added to the preservation fluid to generate tiny molecules called S-nitrosothiols (SNOs), which regulate tissue-oxygen delivery. This, in turn, restored flow-through and reduced resistance within the kidney. Higher flow-rates and lower resistance are associated with better kidney function after transplantation.

Their research was funded by a grant from the Roche Organ Transplant Research Foundation and recently published in Annals of Surgery.

The United States has one of the world’s highest incidences of end-stage renal disease, and the number of afflicted individuals continues to increase. The prevalence of end-stage renal disease has more than doubled between 1990 and 2016, according to the Centers for Disease Control.

The optimal treatment is a kidney transplant, but demand far exceeds supply. Additionally, donation rates for deceased donors have been static for several years, despite various public-education campaigns, resulting in fewer kidneys available for transplant. And while the proportion and number of living donors has increased, this latter group still only makes up a small percentage of recovered kidneys for transplant.

Increasing the number of kidneys available for transplant benefits patients by extending lifespans and/or enhancing quality of life as well as the potential for reducing medical costs (a transplant is cheaper than ongoing dialysis). To help improve outcomes for kidney transplant patients, the team explored ways to extend the viability of donated kidneys.

Improvements in surgical techniques and immunosuppression therapies have made kidney transplants a relatively common procedure. However, less attention has been paid to maintaining/improving kidney function during the kidney-transport phase.

“We addressed this latter point through developing enhanced preservation methods,” said senior author James Reynolds, professor of Anesthesiology and Perioperative Medicine at Case Western Reserve School of Medicine and a member of the Harrington Discovery Institute at UH.

For decades, procured kidneys were simply flushed with preservation solution and then transported in ice-filled coolers to the recipient’s hospital. But advances in pumping technology slowly changed the field toward active storage, the preferred method for conveying the organ from donor to recipient.

“However, while 85% of kidneys are now pumped, up to 20% of kidneys are determined to be unsuitable for transplant during the storage phase,” said Kenneth Chavin, professor of surgery at the School of Medicine, chief of hepatobiliary and transplant surgery and director of the UH Transplant Institute.

“For several years, our team has directed research efforts toward understanding and improving the body’s response to medical manipulation,” Reynolds said. “Organ-donor physiology and ‘transport status’ fit well within this metric. We identified a therapy that might improve kidney perfusion, a significant factor in predicting how the organ will perform post-transplant.”

Previous work by Reynolds and long-time collaborator Jonathan Stamler, the Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation and president of the Harrington Discovery Institute, determined that brain death significantly reduces SNOs, which impairs blood-flow and tissue-oxygenation to the kidneys and other commonly transplanted organs. The loss of SNOs is not corrected by current preservation fluids, so impaired flow through the kidneys continues during storage and transport.

http://7thspace.com/headlines/1099047/novel_drug_therapy_shows_promise_for_quality__quantity_of_kidneys_available_for_transplant.html

Aerobic exercise limits risk of Alzheimer’s in vulnerable adults


A new study has found a new link between regular aerobic exercise and improved cognitive function in brain regions associated with Alzheimer’s disease.

By Nick Lavars

Previous research has shown us how regular exercise can be beneficial for cognitive function and help stave off the brain degeneration associated with dementia and Alzheimer’s, but scientists continue to learn more about the mechanisms at play. The latest discovery in this area comes courtesy of researchers from the University of Wisconsin (UW), who have published a new study describing a relationship between regular aerobic exercise and a reduced vulnerability to Alzheimer’s among high-risk adults.

More and more research is establishing stronger and stronger links between exercise and the prevention or slowing of Alzheimer’s and dementia. Last September, one study found that a regime of regular aerobic exercise could slow the degeneration of the hippocampus, while another from early in 2019 found that a hormone released during exercise can improve brain plasticity and memory.

For the new study, the UW researchers enlisted 23 subjects, with the participants all cognitively healthy young adults but with a heightened risk of Alzheimer’s due to family history and genetics. All lived what the researchers describe as a sedentary lifestyle and were first put through examinations to assess their cardiorespiratory fitness, cognitive function, typical daily physical activity, and brain glucose metabolism, which is considered a measure of neuronal health.

From there, half of the subjects were given information about how to lead a more active lifestyle, but were then left to their own devices. The other half of the group was given a personal trainer and put through a treadmill training program described as “moderate intensity,” involving three sessions a week across 26 weeks.

Unsurprisingly, the active group demonstrated improved cardio fitness and took on less sedentary lifestyles once the training program had finished. But in addition, they scored higher on cognitive tests of executive functioning, which is the capacity of the brain to plan, pay attention, remember instructions and multitask. Executive function is known to deteriorate during the onset of Alzheimer’s.

“This study is a significant step toward developing an exercise prescription that protects the brain against AD, even among people who were previously sedentary,” explains lead investigator Ozioma C. Okonkwo.

In addition to this improved executive function, brain scans also revealed some marked differences in brain glucose metabolism in the posterior cingulate cortex, a region again linked with Alzheimer’s.

“This research shows that a lifestyle behavior – regular aerobic exercise – can potentially enhance brain and cognitive functions that are particularly sensitive to the disease,” says Okonkwo. “The findings are especially relevant to individuals who are at a higher risk due to family history or genetic predisposition.”

With the sample size on the small side, the researchers are now working towards larger studies with more subjects to see if their findings can be replicated.

The research was published in the journal Brain Plasticity.

https://newatlas.com/medical/aerobic-exercise-risk-alzheimers-vulnerable-adults/

A single act of kindness affects millions

On a single summer day in 1990, Mahmoud Ghannoum’s life changed completely.

The research scientist was speaking at a conference in Washington, D.C., while his wife and children continued their family vacation in England.

But then, on Aug. 2, Saddam Hussein’s Iraqi forces invaded Kuwait. And Ghannoum, a professor at Kuwait University, suddenly lost his job, his home, and any way to access his bank accounts.

The conference was not the kind where he might land a job in the U.S. Another meeting, the following week, would be full of interview opportunities.

Problem was, Ghannoum had no money to stay—much less to pay to change his flight.

But then he met Jimmy Dorsey, a travel agent based in a local hotel. Dorsey not only changed his flight, but also arranged for a side trip to Milwaukee, where Ghannoum had a friend who could host him for a few days. Deeply grateful, Ghannoum began to leave. The agent stopped him, pulling $80 out of his wallet to give Ghannoum some spending money.

This past Sunday, Ghannoum was back in the greater D.C. area. Nearly 30 years later, he is globally recognized as the scientist who named the mycobiome—perhaps best known today in connection with gut health. He’s published hundreds of journal articles, been cited by other scientists thousands of times and, this summer, won a $3 million federal grant to build on earlier breakthroughs that hold promise for helping people with Crohn’s disease.

Ghannoum often told the story of his gratitude to the stranger whose kindness so profoundly affected his life—and, by extension, so many others. Because the travel agency had closed the following year, he’d never had the chance to thank him in person. It wasn’t until this fall, when Ghannoum’s son, Afif, put the story on Facebook, that the mystery was finally solved.

The Washington Post published a follow-up on Afif’s social media post, and soon after a reader wrote that the stranger sounded a lot like her boss at the time—Jimmy Dorsey, a Cleveland native, Vietnam veteran and volunteer firefighter. Sadly, cancer had taken his life the previous February, but Afif and the Post reporter eventually connected with his widow, Elaine.

Sure enough, she remembered Jimmy telling the very same story. The final proof came when she sent a photo of Dorsey as a young man. Ghannoum immediately recognized his rescuer, and the two families made plans to meet.

“He [gave] me the passion and the optimism that the world is good,” the elder Ghannoum said, “because people like him are out there.”

This weekend, the families came together for the first time. Ghannoum and his son decided they needed to do more than simply thank Elaine and her son Aaron. They came bearing gifts, specifically a plaque in Jimmy’s honor—and news that they had committed $25,000 to a scholarship fund at Case Western Reserve in his name.

“He was an outstanding man,” Elaine said of her late husband. “He was my knight in shining armor.”

On Monday, the Post recounted Sunday’s gathering, including mention of the new scholarship fund. People quickly began inquiring about how they too could give. Here’s the answer:

Visit the online giving site (https://tinyurl.com/z6xooba), choose “other area,” and in the “Special Instructions” box, write “Jimmy Dorsey Scholarship Fund.”
Mail: Checks should be made payable to “Case Western Reserve University” with a note “Jimmy Dorsey Scholarship Fund.” They should be sent to Case Western Reserve University, 11000 Cedar Avenue, #300, Cleveland, OH 44106-7035. Case Western Reserve University, Advancement Services

A single act of kindness affects millions