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Saturday, October 30, 2021

Injecting Trouble

 Plans to open “safe injection sites” in New York City, long stalled, appear to be moving forward, though not at the speed that advocates would prefer. These sites, which Mayor Bill de Blasio prefers to call “overdose prevention centers,” will provide a place for drug addicts to inject themselves with narcotics, under medical supervision. When opioid users overdose, for example, medical personnel will be standing by to revive them.

Assuming de Blasio announces an inaugural date for the program before he leaves office at the end of 2021, New York will be the first municipality in the United States to sponsor “safe injection” as a city service, though Rhode Island is making similar plans at the state level. Philadelphia licensed an injection-site program, but it was blocked after the Trump administration opposed it in court. It remains unclear where the Biden Justice Department stands on the issue, but advocates appear hopeful that it will permit the program to launch.

Proponents say that safe injection sites are an obvious solution to the horrific problem of drug overdoses, which now kill more than 90,000 Americans annually. In 2020, the 30 percent leap in drug-overdose fatalities nearly matched the 40 percent increase in the nation’s homicide rate. Opioids killed 69,000 people that year, most of whom died after either injecting or insufflating synthetic opioids, whose hyper-concentrated nature makes it nearly impossible to titrate.

Establishing safe spaces for addicts to inject themselves, says city councilman Stephen Levin, “saves lives.” He explains that “these centers keep people from dying. The medical data is very clear. Any public health expert says it is not a controversial issue at all. Of course you want supervised injection facilities.” De Blasio echoes this premise. Taking issue with a reporter’s nomenclature, the mayor explained, “I call it overdose prevention centers, because I think it gets to the heart of what this is. It’s to save lives, stop people from overdosing, who could be saved and of course, to in every way, help them towards treatment and support. So, this is an idea that has worked in Canada. It’s worked in Europe. It’s an idea whose time has come.”

Advocates of safe injection sites, whether in government, the media, or in the nonprofit sector, all point to the Canadian experience as positive proof that such programs are a life saver. Insite, which opened in Vancouver, British Columbia, in 2003 as North America’s “first sanctioned supervised drug injection site,” is considered the gold standard of care from the perspective of “harm reduction.”

The principle of harm reduction is that society should ensure that all dangerous, dysfunctional behavior—drug abuse, unsafe sexual practices, failure to comply with psychiatric medical orders, living on the street—happens in as safe a manner as possible. People will not stop using drugs just because they are told not to, so the best way to manage the various side effects of drug abuse—overdose, festering wounds, poverty, crime, child neglect, despair—is to make using drugs as easy as possible. And in addition to preventing death or disease, harm-reduction programs create an opportunity for government social-service providers to conduct outreach, helping addicts or other people in need of services get in touch with care in a trusting, non-stigmatized environment.

It’s not hard, though, to see that harm reduction can be a long, dark tunnel to the light of the prosocial day. At Vancouver’s Insite, “when somebody’s struggling with their injection, like we can see they’re getting frustrated, agitated, poking or stabbing away at themselves, it’s our responsibility to see if we can help make that safer for them, to find a safer vein,” says Tim Gauthier, a nurse and the clinic’s coordinator. The staff at Insite don’t actively inject anyone, but it’s hard philosophically to explain why not, if it would be safer to do so. Similarly, if it is dangerous for an addict to have to go buy impure drugs on the street, how is it not morally justifiable for a harm-reduction center to offer to sell pure drugs on site, at cost? Or to give them out for free?

Advocates would surely object that these thought experiments don’t relate to the real-world work of saving lives. So how are Vancouver and Toronto doing in regard to overdoses? Not so well, it turns out. The British Columbia coroner reports at least 1,200 overdose deaths in the first half of 2021, “the highest ever recorded in the first seven months of a calendar year and . . . a 28% increase over the number of deaths recorded between January and July 2020 (941).” Toronto is doing no better: the Ontario coroner reported a record 521 opioid overdose deaths in the city in 2020, and the situation this year is much worse: one day in early May saw five deaths, the highest ever recorded. Even if, for the sake of argument, one wanted to concede the possibility that these numbers might be even higher in the absence of safe-injection sites, the difference made is on the margins. As Christopher Rufo wrote last year in a City Journal story on Vancouver’s program: “It’s not that addicts who use the safe-injection site are achieving sobriety; they’re just not dying on the floor of the Insite injection room.”

And none of this raises the other problems associated with “safe injection sites,” which are necessarily located in the areas where the scourge is the most acute, and which essentially make the blight permanent by encouraging drug dealers to prey on the sites’ users. Robbery of dealers and users will follow, as will street crime and associated dysfunctionality.

The presumptive next mayor of New York, Eric Adams, has said that he is in favor of the program. If he permits its introduction, he will be living up to the promise that de Blasio has said he sees in him.

Seth Barron is managing editor of The American Mind.

https://www.city-journal.org/nyc-safe-injection-sites-a-dangerous-plan

CDC clarifies unvaccinated young foreign travelers do not need to quarantine

 The Centers for Disease Control and Prevention (CDC) said on Saturday that unvaccinated foreign nationals under the age of 18 traveling to the United States by air do not have to self-quarantine upon arrival.

CDC Director Rochelle Walensky on Saturday signed a revised order c https://www.cdc.gov/quarantine/cruise/pdf/Vax-Order-10-30-21-p.pdflarifying that foreign national children who have not been vaccinated against COVID-19 do not need to isolate for seven days upon arrival in the United States. A CDC order issued on Monday had raised alarm among some foreign travelers that their children would need to quarantine for that long after arriving.

On Nov. 8, the United States is lifting the extraordinary travel restrictions that have barred most non-U.S. citizens who within the last 14 days have been in the United Kingdom, the 26 Schengen countries in Europe without border controls, Ireland, China, India, South Africa, Iran and Brazil. It is also imposing new rules requiring nearly all foreign adult air visitors to be vaccinated against COVID-19.

https://www.marketscreener.com/news/latest/CDC-clarifies-unvaccinated-young-foreign-travelers-do-not-need-to-quarantine--36848674/

China's Xi calls for COVID-19 vaccine mutual recognition

 Chinese President Xi Jinping on Saturday called for mutual recognition of COVID-19 vaccines based on the World Health Organization's emergency use list, according to a transcript of his remarks published by the official Xinhua news agency.

Speaking to the Group of 20 Leaders' Summit in Rome via video link, Xi said China had provided more than 1.6 billion COVID shots to the world, and was working with 16 nations to cooperate on manufacturing doses.

"China is willing to work with all parties to improve the accessibility and affordability of COVID-19 vaccines in developing countries," Xi said.

Xi reiterated China's support of the World Trade Organization (WTO) making an early decision on waiving intellectual property rights for COVID-19 vaccines, and he called for vaccine companies to be encouraged to transfer technology to developing countries.

Two Chinese vaccines, one from Sinovac Biotech and one from Sinopharm, have been included in the WHO's emergency use list.

Xi also called for policies to maintain global economic and financial stability, saying China will strengthen macroeconomic policy coordination and maintain policy continuity, stability and sustainability.

"Major economies should adopt responsible macroeconomic policies to avoid negative spillover effects to developing countries and maintain the steady operation of the international economic and financial system," he said.

Xi reiterated that China would work to hit a carbon emissions peak by 2030, with the goal of reaching carbon neutrality by 2060.

https://www.marketscreener.com/quote/stock/SINOVAC-BIOTECH-LTD-5714593/news/China-s-Xi-calls-for-COVID-19-vaccine-mutual-recognition-36845559/

How COVID-19 alters the immune system

 COVID-19 reduces the numbers and functional competence of certain types of immune cells in the blood, say LMU researchers. This could affect responses to secondary infections.

The SARS-CoV-2 coronavirus causes moderate to severe disease in 3–10% of those infected. In such cases, the  overreacts to the virus, triggering an aberrant innate  that is characterized by systemic inflammation, intravascular blood clotting and damage to the cardiovascular system. A team led by immunology professor Anne Krug at LMU's Biomedical Center (BMC), which included many researchers based at the BMC and the LMU Medical Center, has carried out a comprehensive study of this phenomenon, and uncovered hitherto unknown effects of the virus on the immune system. In the journal PLOS Pathogens, they report that, following infection with SARS-CoV-2, the numbers of immune  called  in the circulation decline, while the functionality of the remaining fraction is impaired. The authors believe that this could make patients more susceptible to secondary infections during, and immediately after recovery from a bout of COVID-19.

Dendritic cells (DCs) are responsible for initiating immune responses against invasive pathogens. They do so by activating helper T cells, which in turn stimulate B cells to secrete antibodies directed against the invader. Krug and her colleagues set out to determine the effects of moderate to severe coronavirus infection on this process. They analyzed  obtained from 65 COVID-19 patients who had been treated at the LMU Medical Center. They found that there were fewer DCs in these samples than in the blood of healthy controls. Furthermore, DCs isolated from the blood of patients showed a reduced ability to activate T cells. "We had actually expected that DCs isolated from patients infected with SARS-CoV-2 would activate T cells more potently than DCs obtained from healthy donors," says Krug. "However, we discovered that, in the course of the disease, the proteins present on the surface of the DCs in patients' blood were altered in a way that made them more likely to inhibit T cell responses." In spite of this, by 15 days after diagnosis 90% of these patients had generated antibodies directed against the SARS-CoV-2 spike protein, and many of them had also activated a T cell response. – these responses are the hallmarks of a robust immune reaction against the virus. "So, the drop in the numbers and reduced functionality of DCs does not seem to have a negative impact on the immune response to the coronavirus itself," Krug says.

However, she is convinced that the reduced number and altered function of DCs is significant. It is conceivable that this might cause the immune system to react less strongly than expected to bacterial or other viral infections following recovery from COVID-19, but this possibility will require further clinical investigation.

What might account for the depletion of DCs in the blood and the decrease in their capacity to stimulate T cells? – Krug has several hypotheses to offer. It could in fact represent an appropriate regulatory process, she suggests. COVID-19 is often associated with vigorous inflammation reactions—so the phenomenon might be part of an attempt to downregulate inflammatory processes. Dendritic cells might migrate from the  into inflamed tissues, such as the lung, which could explain the fall in the numbers of DCs in the circulation. "However, we also found that the regeneration of dendritic cells is delayed," Krug points out. The authors of the study believe that this phenomenon could weaken the ability of patients to mount effective immune responses to other pathogens during, and in the immediate aftermath of a symptomatic COVID-19 infection. The team will now explore this issue further in an effort to determine whether the effects of SARS-CoV-2 on DCs play a role in long-term COVID.


Explore further

Cancer patients with poor antibody response to COVID-19 vaccines also lack secondary immune response

More information: Elena Winheim et al, Impaired function and delayed regeneration of dendritic cells in COVID-19, PLOS Pathogens (2021). DOI: 10.1371/journal.ppat.1009742
https://medicalxpress.com/news/2021-10-covid-immune.html

Potential new treatment for COVID-19 identified

 Researchers have identified a potential new treatment that suppresses the replication of SARS-CoV-2, the coronavirus that causes COVID-19. In order to multiply, all viruses, including coronaviruses, infect cells and reprogram them to produce novel viruses. The research revealed that cells infected with SARS-CoV-2 can only produce novel coronaviruses when their metabolic pentose phosphate pathway is activated.

With the application of the drug benfooxythiamine, an inhibitor of this pathway, SARS-CoV-2 replication was suppressed and infected cells did not produce coronaviruses.

The research from the University of Kent's School of Biosciences and the Institute of Medical Virology at Goethe-University, Frankfurt am Main, found the drug also increased the antiviral activity of '2-deoxy-D-glucose'; a drug which modifies the host cell's metabolism to reduce virus multiplication.

This shows that  pathway inhibitors like benfooxythiamine are a potential new  option for COVID-19, both on their own and in combination with other treatments.

Additionally, benfooxythiamin's antiviral mechanism differs from that of other COVID-19 drugs such as remdesivir and molnupiravir. Therefore, viruses resistant to these may be sensitive to benfooxythiamin.

Professor Martin Michaelis, University of Kent, said, "This is a breakthrough in the research of COVID-19 treatment. Since resistance development is a big problem in the treatment of viral diseases, having therapies that use different targets is very important and provides further hope for developing the most effective treatments for COVID-19."

Professor Jindrich Cinatl, Goethe-University Frankfurt, said, "Targeting virus-induced changes in the host cell metabolism is an attractive way to interfere specifically with the virus replication process."


Explore further

New drug candidate for the treatment of COVID-19

More information: Denisa Bojkova et al, Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy, Metabolites (2021). DOI: 10.3390/metabo11100699
https://medicalxpress.com/news/2021-10-potential-treatment-covid-.html

Fast-food restaurant availability across US linked to higher rates of type 2 diabetes

 An increasing number of studies suggest a link between a neighborhood's built environment and the likelihood that its residents will develop chronic diseases such as heart disease, type 2 diabetes (T2D) and certain types of cancers. A new nationwide study led by researchers from NYU Grossman School of Medicine published online today in JAMA Network Open suggests that living in neighborhoods with higher availability of fast-food outlets across all regions of the United States is associated with higher subsequent risk of developing type 2 diabetes.

Findings also indicated that the availability of more supermarkets could be protective against developing T2D, particularly in suburban and rural neighborhoods.

The study -- notable for its large geographic breadth -- uses data from a cohort of more than 4 million veterans living in 98 percent of U.S. census tracts across the country. It counted fast-food restaurants and supermarkets relative to other food outlets, and is the first, according to the researchers, to examine this relationship in four distinct types of neighborhoods (high-density urban, low-density urban, suburban, and rural) at the hyperlocal level nationwide.

"Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas," said Rania Kanchi, MPH, a researcher in the Department of Population Health at NYU Langone and lead author of the study. "Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not."

How the Study was Conducted

The research team used data from the U.S. Veterans Health Administration (the largest single-payer healthcare system in the country) that captures more than 9 million veterans seen at more than 1,200 health facilities around the country. Using this data, the researchers then constructed a national cohort of more than 4 million veterans without diabetes from the VA electronic health records (EHR) between 2008 and 2016. Each veteran's health status was followed through 2018 or until the individual either developed diabetes, died, or had no appointments for more than two years.

Within each of four distinct neighborhood types, the proportion of restaurants that were fast food, and the proportion of food outlets that were supermarkets were tabulated within a one-mile walk in high- density urban neighborhoods, a two-mile drive in low-density urban neighborhoods, a six-mile drive in suburban communities, and a 10-mile drive in rural communities.

Veterans were followed for a median of five and a half years. During that time, 13.2 percent of the cohort were newly diagnosed with T2D. Males developed T2D more frequently than females (13.6 versus 8.2 percent). Non-Hispanic Black adults had the highest incidence (16.9 percent), compared to non-Hispanic Whites (12.9 percent), non-White Asian and Hispanics (12.8 percent), Native Hawaiian and Pacific Islanders (15 percent), and Native American and Alaskan Indians (14.2 percent).

When stratifying by community types, 14.3 percent of veterans living in high density urban communities developed T2D, while the lowest incidence was among those living in suburban and small town communities (12.6 percent).

Overall, the team concluded that the effect of the food environment on T2D incidence varied by how urban the community was, but did not vary further by region of the country.

"The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents," said Lorna Thorpe, PhD, MPH, professor in the Department of Population Health at NYU Langone and senior author of the study.

One limitation of the study, according to the authors, is that the study may not be fully generalizable to non-veteran populations, as U.S. veterans tend to be predominantly male and have substantially greater health burdens and financial instability than the civilian population. They are also at greater risk of disability, obesity, and other chronic conditions.

The next phase of the research, say Thorpe and Kanchi, will be to better understand the impacts of the built environment on diabetes risk by subgroups. They plan to examine whether or not the relationships between fast-food restaurants, supermarkets and community types vary by gender, race/ethnicity, and socioeconomic status.

Funding for the study was provided by the Centers for Disease Control and Prevention.

In addition to Thorpe and Kanchi, other NYU Langone researchers include Priscilla Lopez, MPH; Pasquale E. Rummo, PhD; David C. Lee, MD; Samrachana Adhikari, PhD; Mark D. Schwartz, MD, and Brian Elbel, PhD. Other research support was provided by Sanja Avramovich, PhD, Department of Health Administration and Policy, George Mason University; Karen R. Siegel, PhD; Deborah B. Rolka, MS and Giuseppina Imperatore from the Division of Diabetes Translation at the Centers for Disease Control and Prevention.


Story Source:

Materials provided by NYU Langone Health / NYU Grossman School of MedicineNote: Content may be edited for style and length.


Journal Reference:

  1. Rania Kanchi, Priscilla Lopez, Pasquale E. Rummo, David C. Lee, Samrachana Adhikari, Mark D. Schwartz, Sanja Avramovic, Karen R. Siegel, Deborah B. Rolka, Giuseppina Imperatore, Brian Elbel, Lorna E. Thorpe. Longitudinal Analysis of Neighborhood Food Environment and Diabetes Risk in the Veterans Administration Diabetes Risk CohortJAMA Network Open, 2021; 4 (10): e2130789 DOI: 10.1001/jamanetworkopen.2021.30789

Cause of Alzheimer’s progression in the brain

 For the first time, researchers have used human data to quantify the speed of different processes that lead to Alzheimer’s disease and found that it develops in a very different way than previously thought. Their results could have important implications for the development of potential treatments.

The international team, led by the University of Cambridge, found that instead of starting from a single point in the brain and initiating a chain reaction which leads to the death of brain cells, Alzheimer’s disease reaches different regions of the brain early. How quickly the disease kills cells in these regions, through the production of toxic protein clusters, limits how quickly the disease progresses overall.

The researchers used post-mortem brain samples from Alzheimer’s patients, as well as PET scans from living patients, who ranged from those with mild cognitive impairment to those with full-blown Alzheimer’s disease, to track the aggregation of tau, one of two key proteins implicated in the condition.

In Alzheimer’s disease, tau and another protein called amyloid-beta build up into tangles and plaques – known collectively as aggregates – causing brain cells to die and the brain to shrink. This results in memory loss, personality changes and difficulty carrying out daily functions.

By combining five different datasets and applying them to the same mathematical model, the researchers observed that the mechanism controlling the rate of progression in Alzheimer’s disease is the replication of aggregates in individual regions of the brain, and not the spread of aggregates from one region to another.

The results, reported in the journal Science Advances, open up new ways of understanding the progress of Alzheimer’s and other neurodegenerative diseases, and new ways that future treatments might be developed.

For many years, the processes within the brain which result in Alzheimer’s disease have been described using terms like ‘cascade’ and ‘chain reaction’. It is a difficult disease to study, since it develops over decades, and a definitive diagnosis can only be given after examining samples of brain tissue after death.

For years, researchers have relied largely on animal models to study the disease. Results from mice suggested that Alzheimer’s disease spreads quickly, as the toxic protein clusters colonise different parts of the brain.

“The thinking had been that Alzheimer’s develops in a way that’s similar to many cancers: the aggregates form in one region and then spread through the brain,” said Dr Georg Meisl from Cambridge’s Yusuf Hamied Department of Chemistry, the paper’s first author. “But instead, we found that when Alzheimer’s starts there are already aggregates in multiple regions of the brain, and so trying to stop the spread between regions will do little to slow the disease.”

This is the first time that human data has been used to track which processes control the development of Alzheimer’s disease over time. It was made possible in part by the chemical kinetics approach developed at Cambridge over the last decade which allows the processes of aggregation and spread in the brain to be modelled, as well as advances in PET scanning and improvements in the sensitivity of other brain measurements.

“This research shows the value of working with human data instead of imperfect animal models,” said co-senior author Professor Tuomas Knowles, also from the Department of Chemistry. “It’s exciting to see the progress in this field – fifteen years ago, the basic molecular mechanisms were determined for simple systems in a test tube by us and others; but now we’re able to study this process at the molecular level in real patients, which is an important step to one day developing treatments.”

The researchers found that the replication of tau aggregates is surprisingly slow – taking up to five years. “Neurons are surprisingly good at stopping aggregates from forming, but we need to find ways to make them even better if we’re going to develop an effective treatment,” said co-senior author Professor Sir David Klenerman, from the UK Dementia Research Institute at the University of Cambridge. “It’s fascinating how biology has evolved to stop the aggregation of proteins.”

The researchers say their methodology could be used to help the development of treatments for Alzheimer’s disease, which affects an estimated 44 million people worldwide, by targeting the most important processes that occur when humans develop the disease. In addition, the methodology could be applied to other neurodegenerative diseases, such as Parkinson’s disease.  

“The key discovery is that stopping the replication of aggregates rather than their propagation is going to be more effective at the stages of the disease that we studied,” said Knowles.

The researchers are now planning to look at the earlier processes in the development of the disease, and extend the studies to other diseases such as Frontal temporal dementia, traumatic brain injury and progressive supranuclear palsy where tau aggregates are also formed during disease.

The study is a collaboration between researchers at the UK Dementia Research Institute at the University of Cambridge, University of Cambridge and Harvard Medical School. Funding is acknowledged from the Sidney Sussex College Cambridge, the European Research Council Grant Number, the Royal Society, JPB foundation, the Rainwater foundation, the NIH and the NIHR Cambridge Biomedical Research Centre which supports the Cambridge Brain Bank.


Story Source:

Materials provided by University of Cambridge. The original text of this story is licensed under a Creative Commons LicenseNote: Content may be edited for style and length.


Journal Reference:

  1. Georg Meisl, Eric Hidari, Kieren Allinson, Timothy Rittman, Sarah L. DeVos, Justin S. Sanchez, Catherine K. Xu, Karen E. Duff, Keith A. Johnson, James B. Rowe, Bradley T. Hyman, Tuomas P. J. Knowles, David Klenerman. In vivo rate-determining steps of tau seed accumulation in Alzheimer’s diseaseScience Advances, 2021; 7 (44) DOI: 10.1126/sciadv.abh1448