Posts Tagged ‘health’

Humanity tested
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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

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


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

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

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


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/

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