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Why Michigan experts say monkeypox is next pandemic, but not next COVID

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ANN ARBOR – As cases of monkeypox continue to grow worldwide, the United States recently declared a national public health emergency amid the outbreak.

According to the Centers for Disease Control and Prevention, there were 31,800 cases around the world as of Aug. 9. Nearly 99% of those cases were found in countries that had not historically reported monkeypox, according to the CDC.

Two epidemiologists at the University of Michigan recently discussed the disease and the implications of its spread.

Joseph Eisenberg is a professor of epidemiology and an infectious disease epidemiologist who studies environmental determinants of infectious diseases, specifically those that are vector borne or waterborne. Andrew Brouwer is an assistant research scientist in epidemiology who uses statistical and mathematical models to address how infectious disease, cancer and tobacco control impact public health.

The university released the following Q&A with Eisenberg and Brouwer on the topic.

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Should we be worried now that the monkeypox virus (MPV) has been declared a public health emergency in the United States?

Brouwer: MPV has been declared a public health emergency by the World Health Organization, the U.S. Department of Health and Human Services, and some states and localities. These declarations serve to bring attention to the topic, enhance coordinated responses, and make money and resources available. It does not mean that we’re all in imminent danger of being infected.

Is monkeypox going to be the next pandemic?

Eisenberg: Monkeypox is the next pandemic. It is spreading globally through several countries, including the U.S. In the U.S., cases are rapidly increasing into the thousands. It’s a different kind of pandemic than what we see in COVID, however, because it is much less infectious and it is currently affecting a specific risk group that involves very close, intimate contact. And so, yes, it’s a pandemic, but it’s not anything like the COVID pandemic.

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Brouwer: The COVID-19 pandemic has sensitized us to disease transmission. Other outbreaks, such as the hepatitis A epidemic (predominantly 2016-2018, with more than 30,000 cases in the U.S.), received much less attention. That is not to say that we should let the MPV and other outbreaks fly under the radar, but we should have some perspective that outbreaks of various diseases happen all the time and not all are existential threats.

It is good that there is a lot of attention being paid to MPV so that transmission can be interrupted and those infected can be treated. But MPV is not the next COVID.

Unlike SARS-CoV-2, MPV is not spread by casual contact. It is primarily sexually transmitted. It is unlikely to become a widespread epidemic in the broader public, and we should not be too worried about catching it when we’re in public. However, the virus has likely spread to many localities throughout the country, so sexually active individuals should be aware of the signs and discuss MPV with their sexual partners.

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What is monkeypox?

Eisenberg: Monkeypox is a viral disease related to smallpox. It’s different from smallpox in that the disease primarily is spread among nonhuman animals like rodents and primates—what we call a zoonotic disease—and historically has been endemic in central and west Africa, primarily in rainforest areas.

Historically, monkeypox is able to be transmitted from animals to humans with some limited person to person spread. But this new strain is different in that it is now spreading more rapidly through close person-to-person contact and spreading globally throughout different countries in the world. We don’t fully understand why this strain is spreading globally.

How is monkeypox spread?

Eisenberg: This virus is spread through very close contact, often skin to skin. Monkeypox causes lesions and rashes, and the fluid from the lesions and rashes are infectious. It also can be through droplets, that is, droplets that are released through your mouth, through even just talking.

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The virus can, in addition, contaminate objects like fabrics and it can survive there for a period of time, and people can be exposed through touching those objects, but this mode of transmission seems to be rare.

Brouwer: The vast majority of monkeypox transmission is through skin-to-skin sexual contact. Transmission can also occur through nonsexual close contacts and from contaminated objects, typically within a home.

Should we be worried that this is going to spread like COVID-19?

Eisenberg: No. The big difference between monkeypox and COVID is that monkeypox is much less effective in spreading. First of all, it can’t aerosolize into the air and therefore stay in the air for hours or even days like COVID. Second of all, it requires a much higher dose to become infected. So the fact that it’s much less infectious is one reason why monkeypox will not spread in the way we see something like COVID spreading.

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Also, it is thought that only symptomatic individuals that have these rashes and lesions are infectious. As far as we know, people that are infected but presymptomatic cannot transmit the disease. And that’s also very different from COVID, as somebody could be walking around with COVID without any symptoms and be infectious and spread the disease.

What are the symptoms?

Eisenberg: A lot of the initial symptoms of monkeypox are what we call broad spectrum, symptoms like fever, headache, muscle ache, typical respiratory symptoms—types of symptoms that don’t necessarily tell you that it’s monkeypox as opposed to COVID, the flu or common cold. The lesions are what’s the most characteristic symptom of monkeypox. And those lesions are what is diagnostic for a clinician to say, oh, this is monkeypox and not COVID. And that comes sometimes a little later than the first phase of just having your general fever and headache and respiratory symptoms.

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What should someone do if they are experiencing these symptoms?

Eisenberg: If they’re experiencing these symptoms, they should isolate themselves. If they’ve got lesions and rashes, they should separate even within their house, separate themselves from animals, because this can be transmitted to animals as well as family members. And then contacting their physician would be also prudent to see whether or not there are treatments that are available for them.

There’s been some confusion about the spread of this disease, and there has been a lot of focus on the gay and queer communities. Is MPV an STI? Should we be focusing on those communities?

Brouwer: MPV is a sexually transmitted infection. Sexual transmission is not the only mode of transmission, but it is by far the most important one right now. The fact is that 98% of cases worldwide in this epidemic have been in men who have sex with men. To gloss over this fact creates incorrect risk perceptions for both low- and high-risk individuals.

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It is possible to be forthright about who is currently at highest risk and what precautions can be taken without stigmatizing whole populations. In general, public health messaging needs to do a better job of recognizing that diseases create fear responses and that people with infections (of any kind) are often blamed for their infection. We saw this in the COVID-19 pandemic, too.

And how concerned should the public be? Should everyone get the vaccine?

Eisenberg: Only people that have been potentially exposed or have high-risk behaviors or are immunocompromised should be considering getting a vaccine. It’s just not widespread enough to make it something that everybody should be getting.

Brouwer: No, at this point the vaccine should be targeted to high-risk individuals. There is little indication that the outbreak will become epidemic in the larger population. It may become an endemic sexually transmitted infection, however, so continued awareness and education is important.

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So if I go to the grocery store, I most likely won’t get monkeypox?

Eisenberg: Exactly. So that is not the kind of casual contact that can occur and cause transmission for, again, COVID, the flu, common cold, those are all things that you could get if you just went to the grocery store. Monkeypox is much less infectious.

Can you talk about zoonotic diseases and how climate change might impact how often we see these types of diseases coming up?

Eisenberg: Zoonotic diseases are diseases that are coming from nonhuman animals, livestock and even wild animals. Most of the emerging and reemerging pathogens that become human diseases, including all the childhood diseases like measles and smallpox and such, were originally zoonotic. That is, pathogens have been emerging from animals into human populations, ever since the development of agriculture. Agriculture created a situation where there is much more intimate contact with animals.

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What climate change has done is exacerbate the risk of new emerging or reemerging pathogens that we’ve always had. For some pathogens, we will see an expansion of transmission and more intense transmission. For other pathogens, we’ll just see geographic shifts. That is, some locations will have less transmission and in some locations we will have an increasing amount of transmission.

This geographic shift in transmission will be challenging to address. Public health infrastructures will have to be much more nimble and flexible in addressing future risks that may be different than what the risks were in the past. So, again, we should not only be focused on the idea that climate change is going to be increasing the risk of disease, rather that it’s going to be shifting where the high-risk locations are over time.

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Clinical Trial Restored Sight to 20 People With Corneas Made From An Unlikely Source : ScienceAlert

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Implants made from pig skin have restored sight to 20 people with diseased corneas, in an exciting pilot clinical trial. Many of the patients were blind before receiving the help of this bioengineered tissue.

Incredibly, after two years, all 14 of those blind people had their vision restored and three of them, and three of them now have perfect 20/20 vision.

“This gets us around the problem of [a] shortage of donated corneal tissue and access to other treatments for eye diseases,” says Linköping University ophthalmology researcher Neil Lagali.

While around 12.7 million people suffer vision loss due to problems with their corneas, only 1 in 70 manage to receive a cornea transplant – the only way to restore their vision.

As the means to provide these transplants are costly, and donated corneas are in short supply, most people in the world do not have access to effective treatments.

“We’ve made significant efforts to ensure that our invention will be widely available and affordable by all and not just by the wealthy. That’s why this technology can be used in all parts of the world,” says Linköping University biomedical engineer Mehrdad Rafat.

To achieve this, Rafat and colleagues developed a new technique that requires no stitches so doctors can perform the implant procedure with less specialized conditions and equipment.

“A less invasive method could be used in more hospitals, thereby helping more people. With our method, the surgeon doesn’t need to remove the patient’s own tissue. Instead, a small incision is made, through which the implant is inserted into the existing cornea,” explains Lagali.

What’s more, the material used to create the implant is a byproduct of the food industry and, thanks to specially developed packaging and sterilization processes, the final product can be stored for up to two years. In contrast, donated human corneas must be used within two weeks.

Our cornea – the clear screen over the front part of our eye that shields our iris and pupil – is mostly composed of different types of collagen. This structure can gradually thin out over time, causing it to bulge outwards and distort our vision in a condition called keratoconus.

While the exact cause of this thinning isn’t known, genetics, vigorous eye rubbing, and conditions including hay fever, asthma, Down syndrome, and Ehlers-Danlos syndrome can increase the chances of developing keratoconus.

So the researchers purified collagen from pig skin to create a new cornea layer. They used chemical and photochemical methods to strengthen this usually soft material, making it more stable, resulting in a hydrogel they’ve called a bioengineered porcine construct, double crosslinked (BPCDX).

Changes in corneal thickness with arrows indicating the implant outline post operation (bottom). (Rafat et al, Nature Biotechnology, 2022)

Refining their techniques in animal models, researchers then developed a simple method to insert BPCDX into the recipient’s cornea, eliminating the need to remove the existing tissue.

Here, the implant flattens the cornea’s buckling and provides the lost thickness, repairing the eye’s capacity to focus.

The minimally invasive surgery leaves the corneal nerves and cell layers intact, allowing the wound to rapidly heal.

Following implantation through a 2-millimeter incision, the BPCDX successfully remained transparent. There was no scar formation or adverse reaction, and no intensive therapy or further surgery was required; just an eight-week treatment with immunosuppressive eye drops and a bandage.

The bioengineered cornea checked all the safety boxes.

After two years, the participants from Iran and India experienced an average increase of more than 200 micrometers in their cornea’s thickness, and a decrease in its curvature, improving their vision at least to the extent of traditional corneal transplants.

Previously attempted biomaterial implants into the eye ended up thinning, but the fortified pig cell collagen held strong and kept the implant stable, even after eight years, the team reported based on their previous studies and unpublished data.

“No previous study has, to our knowledge, achieved full corneal transparency in vivo with sufficient corneal thickening and flattening, or with significant visual acuity gains as reported here,” the researchers wrote in their paper.

A larger clinical trial is now being planned, but if the pilot is any indication the researchers are hopeful for additional promising results that will help the new procedure meet regulatory approvals.

“The results show that it is possible to develop a biomaterial that meets all the criteria for being used as human implants, which can be mass-produced and stored up to two years and thereby reach even more people with vision problems,” Lagali concludes.

This research was published in Nature Biotechnology.

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Polio virus reappears in rich economies, exposing gaps in immunisation

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Public health authorities in wealthy economies are racing to head off a return of polio, after the virus has turned up in several countries where it had been all but stamped out.

Health authorities in New York City on Friday said they detected polio in samples taken from the sewage system. Last month a man in suburban New York was diagnosed with the US’s first case since 2013.

In London, health officials this week said they would offer polio vaccine boosters to hundreds of thousands of children after the virus was detected in London waste water. Israel earlier identified its first cases since 1988 and there has been a cluster in war-torn Ukraine, where health services are under huge strain.

The situation is raising concerns that vaccine hesitancy and global conflicts could allow a disease that was on the brink of global eradication to make a comeback.

For much of the 20th century polio, which is short for poliomyelitis, was one of the most feared childhood diseases, killing and disabling tens of thousands of people every year. But vaccine development in the 1950s and a global campaign against the disease begun in 1988 slashed the number of infections to just 175 cases by 2019 and reduced the number of countries where it is endemic to two — Pakistan and Afghanistan.

But its re-emergence in Europe and the US, along with the disruption of inoculation programmes — by the Covid-19 pandemic, and by war in places such as Ukraine and Afghanistan — have caused public health officials to raise the alarm.

“There has been a huge dip globally in the routine immunisation coverage, as countries were engaged in the Covid-19 pandemic response. If you scratch the surface, this shows the vulnerability of countries’ immunisation systems,” said Siddhartha Datta, the World Health Organization’s regional adviser for vaccine-preventable diseases in the European region.

Last month the WHO and Unicef released data showing the largest sustained decline in childhood vaccinations in three decades, with at least 25mn infants missing out on life-saving jabs in 2021. Slightly less than 7mn children missed their third dose of polio vaccine last year when compared to 2019, before the coronavirus pandemic.

New York health officials warned on Friday that hundreds of people may have already contracted the virus following a diagnosis of polio on July 21 in an unvaccinated man who developed paralysis in Rockland county, about 30 miles north-west of New York City.

The suburban county has one of the lowest immunisation rates in the US. Authorities have set up vaccination hubs, distributed leaflets urging people to get jabs and are considering offering polio booster shots to top up people’s immunity.

Dr Mary Leahy, chief executive of Bon Secours Charity Health System, one of the largest hospital groups in Rockland, said the virus had probably infected a lot of people without their knowledge because three-quarters of those with infections do not show any symptoms.

“They have polio, but they’re walking around and do not know that they have it. Only about 25 per cent develop flu-like symptoms . . . less than 1 per cent go on to develop paralysis.”

Genetic studies of the New York case have linked it to the polio viruses in Israel and London, suggesting ties across borders. The detected viruses are examples of vaccine-derived polio, which is a strain related to the weakened live poliovirus contained in the oral polio vaccine. They can cause illness and paralysis if they are allowed to circulate in populations with unvaccinated people for long enough and then mutate.

Rockland county has a vaccination rate of 60 per cent for children at two years of age, well below the statewide average of 78 per cent. The WHO says 95 per cent vaccination coverage is required to provide herd immunity.

Rockland is home to a large and growing Orthodox Jewish population. Dorrit Reiss, professor of law at the University of California, Hastings College of Law, said the Orthodox community in the Rockland area had been actively sought out by national anti-vaccine campaigners, who have held rallies and distributed leaflets raising fears about immunisation.

“There is nothing in Judaism that is against vaccines, but some specific Jewish Orthodox communities have concerns. They live a closed life in multigenerational homes with large numbers of kids, so in a very real sense it is an area that is vulnerable to an outbreak,” she said.

Local tensions over vaccination remain high after a measles outbreak in 2018 and 2019 which infected hundreds of people, centred in Rockland’s ultra-Orthodox community.

New York Jewish Week and other local publications have reported the man who contracted polio in Rockland is Orthodox, although local health officials have not confirmed this due to concerns about stigmatising the community.

A New York state senator last month also identified the infected polio patient as an Orthodox Jew and alleged that some private Jewish schools had a history of non-compliance with vaccination requirements. He later retracted his statement following objections from Jewish groups.

“One thing about this polio case is it’s in Rockland country, which had a massive measles outbreak two years ago — so that suggests there is vaccine hesitancy,” said Dr Marny Eulberg, a retired physician and polio survivor who has studied the disease for decades.

“That’s a problem because these days many young parents haven’t seen polio, it isn’t part of their consciousness. And the reality is once you get polio, the treatment now is no better than it was in the 1950s: so the best response is to get vaccinated.”

Health providers in Rockland say fears about polio are prompting some previously hesitant people to come forward to get vaccinated.

“We have seen one mother who was anti-vax and has not given other vaccinations, that brought her two children in for the polio vaccine, because the paralysis scares her,” said Amanda Salzman, director of communications at Refuah Health in Rockland.

Salzman said the clinic had administered almost 500 polio vaccines so far, out of a total of 2,000 across the county.

Health experts say the latest cases demonstrate the need for vigilance on vaccination efforts and for governments to support global eradication efforts on polio. This programme is seeking $4.6bn in funds to complete vaccination efforts in Afghanistan and Pakistan.

“There is a huge need to identify funding,” said Dr Jay Wenger, who leads a polio eradication programme at the Bill & Melinda Gates Foundation. “The importance of getting that is then we won’t have these episodes of viruses in New York, in London or anywhere.”

Additional reporting by Donato Paolo Mancini in London

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Epilepsy drug ‘doubles children’s autism risk’ if their mother takes it while pregnant 

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Epilepsy drug ‘doubles children’s autism risk’ if their mother takes it while pregnant

By Martyn Halle and Stephen Adams for The Mail on Sunday

Published: | Updated:

A drug used to prevent epileptic seizures and migraine has been found to double the chances of a child developing autism if their mother takes it while pregnant.

An urgent review has been launched into topiramate, known by the brand name Topamax, which has been prescribed for decades.

The Medicines and Healthcare products Regulatory Agency (MHRA) has begun a safety review to assess the ‘benefits and risks’ of the drug, which is likely to raise the odds of other intellectual impairments, as well as congenital birth defects. 

A drug used to prevent epileptic seizures and migraine has been found to double the chances of a child developing autism if their mother takes it while pregnant. A file photo is used above

It follows warnings about another epilepsy drug, sodium valproate, marketed as Epilim, which has been linked to higher-than-normal rates of the same conditions.

Seven years ago the MHRA ordered that women of child-bearing age should be warned about sodium valproate’s risks. However, pregnant women were still being prescribed it earlier this year. Experts believe 20,000 babies have been harmed as a result.

The MHRA launched its investigation late last month, after Scandinavian scientists conducted an observational study looking at rates of autism and intellectual disability in children whose mothers took topiramate while pregnant.

They found that about three per cent of such children had an autism spectrum disorder (ASD) diagnosis – double the 1.5 per cent rate among those not exposed to the drug.

An urgent review has been launched into topiramate, known by the brand name Topamax, which has been prescribed for decades. A file photo is used above

Some 3.5 per cent of children whose mothers took it while pregnant were diagnosed with an intellectual disability – about four times higher than the rate of 0.8 per cent among those unexposed. The results were derived from looking at patient records from 4.5 million children across five Nordic countries, of which almost 25,000 had been exposed to topiramate in the womb.

Writing in the Journal Of The American Medical Association Neurology, the scientists warned: ‘Our results do not suggest that topiramate is a safe alternative to sodium valproate (Epilim).’

Drugs firm Janssen, which makes topiramate / Topamax, said packs already contained a warning that it ‘should not be used during pregnancy unless the potential benefit outweighs the potential risk’.

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Vitamin D Supplements Help Alleviate Depression, According to Research Meta-Analysis

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A new study finds that vitamin D supplementation may alleviate depressive symptoms in adults with depression.

Vitamin D supplementation may alleviate depressive symptoms in adults with depression, according to an extensive meta-analysis. Conducted by an international team of scientists, the meta-analysis included dozens of research studies from around the world. It has been published in the journal Critical Reviews in Food Science and Nutrition.

Depressive symptoms cause a significant global disease burden. The therapeutic efficacy of current antidepressants is often insufficient to effectively treat depression. This is why further ways to alleviate the symptoms of depression have been sought, for example, from nutritional research.

Vitamin D is thought to regulate central nervous system functions. Disturbances of these functions have been linked with depression. Additionally, cross-sectional studies have observed an association between vitamin D deficiency and depressive symptoms. However, previous meta-analyses on the effects of vitamin D supplementation on depression have been inconclusive. In a meta-analysis, results from multiple different studies are combined and analyzed statistically.

The new meta-analysis on the association of vitamin D supplementation with depression is the largest one published so far. In fact, it included results from 41 studies from around the world. These studies have investigated the efficacy of vitamin D in alleviating depressive symptoms in adults by randomized placebo-controlled trials in different populations. The studies included those carried out in patients with depression, in the general population, and in people with various physical conditions.

The results of the meta-analysis show that vitamin D supplementation is more effective than a placebo in alleviating depressive symptoms in people with depression. There were major differences in the vitamin D doses used, but typically the vitamin D supplement was 50–100 micrograms (2,000–4,000 IU) per day.

“Despite the broad scope of this meta-analysis, the certainty of evidence remains low due to the heterogeneity of the populations studied and the due to the risk of bias associated with a large number of studies,” Doctoral Researcher and lead author Tuomas Mikola of the Institute of Clinical Medicine at the University of Eastern Finland says. The meta-analysis is part of Mikola’s PhD thesis.

“These findings will encourage new, high-level clinical trials in patients with depression in order to shed more light on the possible role of vitamin D supplementation in the treatment of depression,” Mikola concludes.

Reference: “The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta‐analysis of randomized controlled trials” by Tuomas Mikola, Wolfgang Marx, Melissa M. Lane, Meghan Hockey, Amy Loughman, Sanna Rajapolvi, Tetyana Rocks, Adrienne O’Neil, David Mischoulon, Minna Valkonen-Korhonen, Soili M. Lehto and Anu Ruusunen, 11 July 2022, Critical Reviews in Food Science and Nutrition.
DOI: 10.1080/10408398.2022.2096560

The meta-analysis was carried out in international collaboration between Finnish, Australian and US researchers.



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‘Abnormal’ Protein Could Be Common Link Between All Forms of Motor Neuron Disease

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Summary: A new study reports that abnormalities in the SOD1 protein are a common factor in all types of motor neuron diseases.

Source: University of Sydney

Researchers have found an abnormal protein usually linked to a rare inherited form of motor neuron disease is present in all types of motor neuron disease, suggesting a common link between the different forms of the disease.

The study, published in the neuroscience journal Brain, is the first to confirm toxic changes to the protein in individuals with genetic or non-genetic forms of motor neuron disease.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease. Ten percent of ALS cases are hereditary, with remaining cases lacking an apparent genetic cause.

“The results suggest this abnormal protein contributes to cell death in many forms of motor neuron disease, not just rare genetic cases of motor neuron disease,” says senior author Professor Kay Double from the Brain and Mind Center, Faculty of Medicine and Health.

“It is a big step in advancing our understanding of motor neuron disease. Our findings will direct further research and could ultimately lead to more effective treatments.”

Normally, the protein superoxide dismutase 1 (SOD1) protects cells, but a mutation in its gene is thought to make the protein “toxic”; this toxic protein form is associated with hereditary forms of ALS. Abnormal mutant SOD1 is only found in regions of the spinal cord where nerve cells die, implicating this abnormal protein in cell death.

Abnormal SOD1 protein detected in human spinal cord tissue (dark spots). Credit: Trist et al

Previous investigations into the role of toxic forms of SOD1 protein largely focused on mutant forms of the protein and were primarily conducted using animal and cellular models of ALS.

The study, led by a team from the University of Sydney’s Brain and Mind Center, advances our understanding of the causes of motor neuron disease by studying this abnormal protein in post-mortem tissues from patients with ALS.

“We have shown for the first time that mechanisms of disease long hypothesized to occur in animal and cellular models are present in patients with motor neuron disease,” says lead author Dr. Benjamin Trist from the Brain and Mind Center, Faculty of Medicine and Health.

“This is a significant milestone in our understanding of ALS and motor neuron disease more broadly.”

In related experiments, Professor Double and her team are also currently studying how abnormal SOD1 interacts with other disease-linked proteins in motor neuron disease. This work is in press and will be published in Acta Neuropathologica Communications.

About this motor neuron disease research news

Author: Press Office
Source: University of Sydney
Contact: Press Office – University of Sydney
Image: The image is credited to Trist et al.

Original Research: Open access.
“Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord” by Benjamin G Trist et al. Brain

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Abstract

Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord

Aberrant self-assembly and toxicity of wild-type and mutant superoxide dismutase 1 (SOD1) has been widely examined in silico, in vitro, and in transgenic animal models of amyotrophic lateral sclerosis (ALS). Detailed examination of the protein in disease-affected tissues from ALS patients, however, remains scarce.

We employed histological, biochemical and analytical techniques to profile alterations to SOD1 protein deposition, subcellular localization, maturation and post-translational modification in post-mortem spinal cord tissues from ALS cases and controls. Tissues were dissected into ventral and dorsal spinal cord grey matter to assess the specificity of alterations within regions of motor neuron degeneration.

We provide evidence of the mislocalization and accumulation of structurally-disordered, immature SOD1 protein conformers in spinal cord motor neurons of SOD1-linked and non-SOD1-linked familial ALS cases, and sporadic ALS cases, compared with control motor neurons. These changes were collectively associated with instability and mismetallation of enzymatically-active SOD1 dimers, as well as alterations to SOD1 post-translational modifications and molecular chaperones governing SOD1 maturation.

Atypical changes to SOD1 protein were largely restricted to regions of neurodegeneration in ALS cases, and clearly differentiated all forms of ALS from controls. Substantial heterogeneity in the presence of these changes was also observed between ALS cases.

Our data demonstrates that varying forms of SOD1 proteinopathy are a common feature of all forms of ALS, and support the presence of one or more convergent biochemical pathways leading to SOD1 proteinopathy in ALS. The majority of these alterations are specific to regions of neurodegeneration, and may therefore constitute valid targets for therapeutic development.

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Blood clots: Risk factors may include over-consumption of diet drink

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The study, co-authored by Shirley Beresford, senior associate dean and professor of epidemiology at the University of Washington School of Public Health, and co-author of the study, said: “Part of what makes this study important is that people who regularly drink soda or other sugary beverages tend to switch to artificially sweetened beverages to lose weight when the ideal is to substitute with water.”

This formation of blood clots in the small arteries is dangerous because it sets the stage for further complications such as stroke.

In fact, the findings showed that compared with women who consumed diet drinks less than once a week or not at all, women who consumed to or more per day were 23 percent more likely to have a stroke.

What’s more, they were 31 percent more likely to have a clot-caused ischaemic stroke.



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Letter obtained by CNN shows FDA defended new monkeypox vaccine strategy to vaccine maker

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In a letter Friday to Bavarian Nordic CEO Paul Chaplin, two top FDA officials responded to concerns Chaplin had raised earlier this week. They wrote that the agency recently determined that the benefits of stretching its limited supply of the two-dose Jynneos vaccine by giving individuals smaller doses outweighed the known possible risks.

The decision came after the FDA ruled out — at least for now — the use of alternative vaccines, as well as the option of delaying the second vaccine dose by three to six months, the agency said.

The FDA’s letter, obtained by CNN Saturday, was signed by FDA Commissioner Dr. Robert Califf and Dr. Peter Marks, the director of the FDA’s Center for Biologics and Evaluation Research.

The letter cited a 2015 clinical study, which Chaplin co-authored, in which “individuals who received the vaccine intradermally received a lower volume (one fifth) than individuals who received the vaccine subcutaneously.”

“The results of this study demonstrated that intradermal administration produced a very similar immune response to subcutaneous (SC) administration,” the letter said. While the intradermal injection method “did result in more redness, firmness, itchiness and swelling at the injection site, but less pain,” the letter continued, “these side effects were manageable.”

The FDA also detailed other options that the agency had considered. But the use of alternative vaccines to prevent monkeypox “was determined to be either impractical or inadvisable at this time,” according to the letter. Specifically, the ACAM2000 vaccine, which is FDA approved for prevention of smallpox, “may not be appropriate now for a potentially immunocompromised population,” the letter said.

The FDA also looked into the option of delaying the second vaccine doses by three to six months, rather than giving the second dose the recommended 28 days after the first.

But the agency ultimately determined that there was not any data to demonstrate that this method would provide sufficient protection, and that delaying the second dose could also give people “a false sense of reassurance that they were protected against monkeypox when the actual level of protection would be unknown and quite possibly inadequate,” the letter said.

The federal government’s announcement this week authorizing health care providers to give smaller doses of Jynneos came in an attempt to better meet the high demand for the vaccine. Top Biden administration health officials have made clear in recent days that given the speed of the spread of monkeypox — which it earlier this month declared a public health emergency — the US did not have enough vaccine supply to meet demand. This week’s decision to stretch out the available Jynneos vaccines was aimed at addressing the limited supply.

Dr. Marks of the FDA said Thursday that there were an estimated 1.6 million to 1.7 million people in the US who are now eligible for the two-dose Jynneos vaccine. According to the US Department of Health and Human Services, around 634,213 vials have been sent to jurisdictions as of Friday.

The low-dose intradermal strategy immediately prompted concern among some public health experts, including about the limited amount of research surrounding the new method.

“This approach raises red flag after red flag, and appears to be rushed ahead without data on efficacy, safety, or alternative dosing strategies,” David Harvey, executive director of the National Coalition of STD Directors, said in a statement this week.

Chaplin, the CEO of Bavarian Nordic, also raised concerns. CNN reported that Chaplin wrote in a letter Tuesday to Califf and HHS Secretary Xavier Becerra that he had concerns about the “very limited safety data available” on the newly announced vaccination strategy, and that a relatively high percentage of people in the clinical study — 20% — did not get their second shot.

“While we have certain reservations, we are trying to find the best way to support the [emergency use authorization] by collecting additional data and aligning on the responses to assist state officials in the rollout,” Chaplin wrote. “We are also investing in expanding the manufacturing capacity at both BN and external facilities, with likely more announcements soon to come.”

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Early-Term Births Associated With Higher Rate of ADHD as Reported by Teachers

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Summary: Children born at 37-38 weeks gestation scored significantly higher on teacher rating scales for ADHD, inattention, and cognitive problems than children born between 39-41 weeks.

Source: Rutgers University

Among children born at term (37–41 weeks), those born before 39 weeks are more likely to experience symptoms associated with attention-deficit/hyperactivity disorder (ADHD), according to a study by Rutgers Robert Wood Johnson Medical School.

ADHD, which affects more than 10 percent of U.S. school-age children, according to the Centers for Disease Control and Prevention, manifests early in childhood with symptoms of hyperactivity, impulsivity or inattention, and has known links to preterm birth (less than 37 weeks gestation).

The study, published in the Journal of Pediatrics, is one of only a few to investigate the associations between gestational age at term (37–41 weeks) and a diagnosis or symptoms of ADHD. It is the first to include reports from teachers.

“Teachers’ reports, in conjunction with maternal reports and physician evaluations, provide valuable input for the diagnosis of ADHD,” said Nancy Reichman, author of the study and a professor of pediatrics at Rutgers Robert Wood Johnson Medical School.

“Mother-reported symptoms generally reflect behaviors in the home or in small family or social groups, while teacher-reported symptoms reflect behaviors in a structured educational setting by professionals who work with a large number of children and observe the range of behaviors that students exhibit in classrooms.”

Reichman and her team, which included Rutgers Robert Wood Johnson Medical School neonatology fellow Geethanjali Linguasubramanian, sought to estimate the associations between gestational age at term and 9-year-old children’s symptoms of ADHD reported by their teachers.

They analyzed data on about 1,400 children in the Fragile Families and Child Wellbeing study, a U.S. birth cohort study that randomly sampled births in 75 hospitals in 20 large U.S. cities from 1998 to 2000 and re-interviewed mothers over nine years.

ADHD, which affects more than 10 percent of U.S. school-age children, according to the Centers for Disease Control and Prevention, manifests early in childhood with symptoms of hyperactivity, impulsivity or inattention, and has known links to preterm birth (less than 37 weeks gestation). Image is in the public domain

During the nine-year follow-up, consent was obtained to contact the children’s teachers, who were asked to evaluate their students using the Conners’ Teacher Rating Scale–Revised Short Form, which includes symptoms of hyperactivity, ADHD, oppositional behavior and cognitive problems or inattention.

Overall, the Rutgers researchers found that children born early-term (37–38 weeks) had significantly higher scores on the teacher rating scales than children who were full-term (39–41 weeks) for hyperactivity, ADHD and cognitive problems or inattention, but that gestational age wasn’t significantly associated with oppositional behavior.

Specifically, the researchers found that each week of gestational age at term was associated with 6 percent lower hyperactivity scores and 5 percent lower ADHD and cognitive problems or inattention scores, and that birth at 37 to 38 weeks was associated with 23 percent higher hyperactivity scores and 17 percent higher ADHD scores when compared with birth at 39 to 41 weeks.

“The findings add to growing evidence supporting current recommendations for delaying elective deliveries to at least 39 weeks and suggest that regular screenings for ADHD symptoms are important for children born at 37 to 38 weeks,” Reichman said.

Preterm infants are at increased risk for ADHD because of immature brain development, she said. “Significant growth and development in various kinds of brain cells are observed between 34 and 40 weeks of gestation,” said Reichman. “Infants born at full-term likely benefit from the additional one to two weeks of brain growth in utero compared with those born early-term.”

About this ADHD research news

Author: Patti Verbanas
Source: Rutgers University
Contact: Patti Verbanas – Rutgers University
Image: The image is in the public domain

See also

Original Research: Closed access.
“Gestational Age at Term and Teacher-Reported ADHD Symptom Patterns” by Nancy Reichman et al. Journal of Pediatrics

Abstract

Gestational Age at Term and Teacher-Reported ADHD Symptom Patterns

Objective

To estimate associations between gestational age (GA) and teacher-reported ADHD- related symptom patterns at age 9 among children born at term (37–41 weeks).

Study design

A secondary data analysis of approximately 1,400 children in the Fragile Families and Child Wellbeing study, a U.S. birth cohort study that oversampled non-marital births, was conducted. At age 9, students were evaluated by their teachers using the Conners Teacher Rating Scale–Revised Short Form that included subscales for symptoms of hyperactivity, ADHD, oppositional behavior, and cognitive problems/inattention. Unadjusted and adjusted negative binomial and logistic regression models of associations between GA and teacher-reported scores were estimated.

Results

Each week of GA at term was associated with hyperactivity scores that were 6% lower (adjusted IRR: 0.94; 95% CI: 0.89–0.99) and ADHD and cognitive problems/inattention scores that were 5% lower (adjusted IRR: 0.95; 95% CI: 0.91–0.98 in both cases). Early-term birth (37–38 weeks) was associated with 23% higher hyperactivity scores (adjusted IRR: 1.23; 95% CI:1.07–1.41), 17% higher ADHD scores (adjusted IRR: 1.17; 95% CI: 1.05–1.30), and ∼50% higher odds of scoring 1.5+ standard deviations above the sample mean for hyperactivity (adjusted OR: 1.51; 95% CI: 1.05–2.18) when compared to birth at 39-41 weeks. There were no significant associations between GA and oppositional behavior scores.

Conclusion

The findings add to growing evidence supporting current recommendations for delaying elective deliveries to at least 39 weeks and suggest that regular screenings for ADHD symptoms are important for children born at 37-38 weeks GA.

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Health

WHO to rename monkeypox to avoid discrimination and stigmatization

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The World Health Organization says it’s holding an open forum to rename monkeypox, after some critics raised concerns the name could be considered discriminatory and stigmatizing.

WHO said the decision was made after meeting with the Food and Agriculture Organization of the United Nations (FAO), which helps identify best practices for naming new human diseases to “avoid causing offense to any cultural, social, national, regional, professional, or ethnic groups, and minimize any negative impact on trade, travel, tourism or animal welfare.”

In a statement Friday, the U.N. health agency said it has also renamed two families, or clades, of the virus, using Roman numerals instead of geographic areas, to avoid stigmatization. 

MONKEYPOX: WHAT YOU MUST KNOW AOBUT THE VIRUS – AND HOW TO PROTECT YOURSELF

The version of the disease formerly known as the Congo Basin will now be known as Clade one or I and the West Africa clade will be known as Clade two or II.

WHO said that the new names for the clades will take effect immediately while a new name for the disease and virus will be worked on. The WHO said that anyone who wishes to submit a name suggestion can do so on their website. 

The decision comes after a group of scientists in June proposed an “urgent” name change, calling the current name “discriminatory and stigmatizing.”

The new name, they proposed, would minimize the “negative impacts on nations, geographic regions, economies and people and that considers the evolution and spread of the virus.”

The scientists proposed a neutral name that accounts for the evolution of the virus.

“In the context of the current global outbreak, continued reference to, and nomenclature of this virus being African is not only inaccurate but is also discriminatory and stigmatizing. The most obvious manifestation of this is the use of photos of African patients to depict the pox lesions in mainstream media in the global north” they said in a joint statement. 

NEW YORK GOVERNOR: MONKEYPOX IS A ‘DISASTER EMERGENCY’

The Center of Disease Control notes that the source of monkeypox is unknown, despite the virus being named in 1958 when two outbreaks of a pox-like disease occurred in colonies where monkeys were kept for research. 

Prior to 2022, monkeypox cases almost always linked to international travel to countries where the disease is common or through imported animals. The first human case was in 1970.

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“What people need to know very clearly is the transmission we are seeing is happening between humans to humans. It’s close contact transmission. So the concern should be about where it’s transmitting in the human population, and what humans can do to protect themselves from getting it and transmitting it. They should certainly not be attacking any animals,” WHO spokesperson Margaret Harris said on Tuesday.

Sarah Rumpf is a Fox News Digital Production Assistant. You can reach her on Twitter at @rumpfsarahc 

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