Month: April 2021

Categories : PaediatricsTags :

New ADHD Drug Gets FDA Approval for Children

On By ModernMedia

US regulators have approved the first new ADHD drug for children in over a decade.

The Food and Drug Administration last week approved  viloxazine (Qelbree) for the treatment of attention deficit hyperactivity disorder in children ages 6 to 17. It was developed by  Supernus Pharmaceuticals. The drug’s price was undisclosed but is likely to be higher than the generic ADHD pills.

In Europe, viloxazine was sold as an antidepressant for several decades, but never received FDA approval. It was discontinued nearly two decades ago, due to competition from popular pills like Zoloft and Prozac.

ADHD affects about 6 million American children and adolescents. For many, problems include trouble paying attention and completing tasks, fidgeting and impulsiveness.  

Earlier ADHD treatments like Ritalin, nearly all of which contain the stimulants amphetamine or methylphenidate, which create the potential for abuse. Viloxazine however is not a stimulant or a controlled substance. It carries a warning of potential for suicidal thoughts and behaviour, which occurred in fewer than 1% of volunteers in studies of the drug.

Qelbree could be an option for children with substance use disorders, who do not cope well with stimulant side effects or who need more therapy, said Dr David W. Goodman, director of Suburban Psychiatric Associates near Baltimore and an assistant professor of psychiatry at Johns Hopkins School of Medicine.

Goodman said that long-acting stimulants prescribed to ADHD patients currently are harder to abuse to get a high than the older fast-acting versions.

In a late-stage study, 477 children ages 6 to 11 took viloxazine for six weeks. Compared to placebo, Inattention and hyperactivity symptoms were reduced by about 50%. Symptom reduction was seen within a week in some participants. Its common side effects include sleepiness, lethargy, decreased appetite and headache.

Supernus is in late-stage testing for adults with ADHD, who represent a small but growing market as adult treatment of the condition expands.

Source: Medical Xpress

Categories : Cancer Cardiovascular DiseaseTags :

Antihypertensive Drugs Not Linked to Cancer Risk

On By ModernMedia

A review of 33 clinical studies  showed that antihypertensive drugs did not have a consistent association with cancer risk.

Patients treated with any of five different classes of antihypertensive drugs had essentially the same cancer risk as those receiving placebo. Comparisons of each antihypertensive class against all the others showed no association with an increased risk of cancer, save for calcium channel blockers (CCBs), which had only a modestly higher risk versus the other drug classes (HR 1.06, 95% CI 1.01-1.11).

The data do not conclude the issue, since some comparisons had insufficient data to exclude the possibility of excess cancer risk, reported Kazem Rahimi, DM, of the University of Oxford in England, and colleagues in Lancet Oncology.

“Our study has addressed an ongoing controversy about the safety of blood pressure-lowering medication with respect to cancer risk, using the largest sample of individual-level randomized evidence on blood pressure-lowering treatment to date, to our knowledge,” they wrote. “The main implication of our study is that patients using antihypertensive medication should continue to take their medications because concerns about increased cancer risk seem to be unfounded.”

The author of an accompanying commentary noted that the findings could have been due to chance. The number of trials per drug class varied greatly, and small sample sizes were used in analyses by type of cancer.

“Taken together, these limitations raise a more fundamental question about how the findings of randomised controlled trials should be interpreted,” wrote Laurent Azoulay, PhD, of McGill University in Montreal.

Randomised trials are the “gold standard” for assessing drug efficacy, but are not typically designed to assess safety, he continued. This is especially important for outcomes like cancer, which have a delayed onset. Since the median follow-up was only 4.2 years , “a potential association between cancer and the long-term use of antihypertensive drugs cannot be ruled out.”

“Such analyses are necessary to understand the short-term effects of these drugs on cancer incidence,” Azoulay concluded. “However, moving forward, these studies will need to be complemented with well-designed, real-world studies in heterogeneous patient populations who are followed up for extended periods of time to fully understand their carcinogenic potential.”

Several meta-analyses have yielded conflicting evidence, Rahimi and colleagues stated. The Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) is the world’s largest individual patient-level data on blood pressure-lowering trials, and data from this formed the basis for the meta-analysis.

The authors identified 33 trials for inclusion in the meta-analysis, which comprised 260 447 patients with available data on cancer outcomes. CCBs were the antihypertensive class most commonly represented in the trials (n=19), followed by ACE inhibitors (15), angiotensin-receptor blockers (ARBs, 11), thiazide diuretics (six), and beta-blockers (five). Median follow-up ranged from 4 to 5 years across the trials, grouped by drug class.

Patient age ranged between 64 and 68 by drug class, and pretreatment systolic blood pressure ranged from 147mm Hg (ACE inhibitors) to 166mm Hg (beta-blockers).

Across the five classes of antihypertensive drugs, individual comparisons for cancer risk versus the other drug classes yielded only a maximum hazard ratio of 1.06 for CCBs.

“We found no consistent evidence that antihypertensive medication use had any effect on cancer risk,” the authors stated.

Source: MedPage Today

Journal information 1: Copland E, et al “Antihypertensive treatment and risk of cancer: An individual participant data meta-analysis” Lancet Oncol 2021; DOI: 10.1016/S1470-2045(21)00033-4.

Journal information 2: Azoulay L “Elucidating the association between antihypertensive drugs and cancer: A need for real-world studies” Lancet Oncol 2021; DOI: 10.1016/S1470-2045(21)00085-1.

Categories : COVIDTags :

South African Volunteers Battle Vaccine Misinformation

On By ModernMedia
Man with LED mask reading a burning newspaper. Photo by Connor Danylenko from Pexels.

As the long-delayed vaccine rollout in South Africa has begun, the government has run a public campaign to tackle prevalent health myths. But there are also volunteers who are waging an online battle against COVID and vaccine misinformation, as reported by the BBC.

Sarah Downs, who is studying molecular biology and infectious diseases, debunks false claims under the alias Mistress of Science and is fighting a surge of misinformation in South Africa. A relatively small collection of Facebook groups and users are responsible for promoting this misinformation. When she tweeted about her grandmother’s passing, a COVID denier questioned whether an autopsy had been performed. 
“We estimate that it’s about 20 000 South Africans who are actually active on anti-vax Facebook pages,” said Prof Hannelie Meyer, a pharmacist and adviser to the South African Vaccine and Immunisation Centre (Savic).

Most anti-vaccine claims in South Africa actually originate in the United States, according to a 2015 study. Anecdotal evidence, such as the spread of false claims about vaccines and DNA by an American osteopath, show this trend still holds in the pandemic.

Prof Meyer said that while data on vaccine hesitancy in SA are limited, studies indicate that more wealthy and educated groups, particularly among whites, are less willing to be vaccinated.

Leading virologist Prof Jeffrey Mphahlele has also pushed back against rumours, such as COVID and its vaccines being a Western plot to reduce Africa’s population and control its natural resources. He called the misinformation “mind boggling” – pointing out the supposed plot would require the West to create a virus that killed millions of its own people.

Even authority figures have promulgated falsehoods: South Africa’s top judge was recently criticised after a video showed him linking vaccines to a “Satanic agenda.”

One of the most prominent groups on Facebook, with some 10 000 members, seeks to spread “awareness” about vaccines but the members’ hard-line anti-vaccine attitude is very clear, ridiculing or dismissing vaccines. One video posted in the group – originally aired on an evangelical US Christian television programme – suggested getting a jab could lead to “a lifetime of illness”.

Sarah Downs stepped in to help answer questions amidst the deluge of misinformation, and one person she helped was Sheona Lottering, a swimming teacher.

“I had a friend that forwarded me a German article,” Sheona said. “She was trying to convince me that death was one of the side-effects [of a COVID vaccination].

“And I was a little bit freaked out about that.”

Sarah explained the subtleties around adverse events to her, and now Sheona keeps in contact with Sarah over difficult vaccine-related questions.

Lisa (not her real name) spends hours lurking in Facebook groups to guide people towards trusted sources of health information.

“The claims are so bizarre I could hardly believe there are people believing these things,” she said. “I don’t like misinformation, so when I see something, I just try to correct it.”

Doing this for over a decade, she’s seen communities grow and knows their tactics. She said that young mothers are a particular target in Facebook groups, where posts are coordinated to try and convince them not to vaccinate their children., which is when Lisa steps in. She keeps her inbox open and believes gentle communication works best – asking about people’s concerns rather than shouting statistics at them.

But Sarah, Lisa and other volunteers we spoke to risk exposing themselves to online abuse, and the prospects of persuasion can often seem slim. It’s difficult, pro-health work – that isn’t paid. So do they judge success?

“I think if I can just help one person be a little bit less terrified… that’s what I aim to get out of it,” Sarah says. “And if they’re willing to take the vaccine, even more so.”

Source: BBC News

Categories : COVIDTags :

South African Variant Escapes Sputnik Vaccine

On By ModernMedia

A study on COVID variants using in vitro tests, available on the preprint server medRXiv, has shown that the South African variant escapes the Sputnik V vaccine.

This study is the first of its kind to show Sputnik V vaccine recipients had reduced neutralising capacity against the B.1.351 and E484K mutant spikes.

When it comes to vaccine design, the most effective vaccines use a stabilised form of the spike protein, while others use the wildtype spike, protecting against severe disease but not infection because of lower levels of neutralising antibodies. A number of SARS-CoV-2 variants of concern (VOC) have mutations on the spike protein, or the E484K mutation, which allows it to escape vaccines and prior immunity. 

In South Africa, where 93% of infections are due to B.1.351, the AstraZeneca vaccine, based on the wild-type spike, failed to prevent mild-to-moderate COVID. The Sputnik V or Gam-COVID-Vac vaccine is also based on the wild-type spike. Interim Phase 3 trial results reported an efficacy of 92%, but this excludes current variants and any lineage containing E484K. 
The current study examined serum neutralisation activity in samples obtained from 12  recipients of the Sputnik V vaccine in Argentina. This country has already detected many independent variants with E484K, with or without N501Y substitutions.

The researchers found that pseudoviruses bearing either the wildtype D614G spike, and the B.1.1.1.7 spike were effectively neutralised by the vaccine sera, in live virus plaque reduction neutralisation assays. The geometric mean titer of neutralising titers was 49, similar to that of the phase III trial.

However, these sera showed moderate to a marked reduction in neutralisation titers against spike protein bearing E484K, and the UK variant. Even at the highest serum concentration used, 9 of the 12 serum samples could not inhibit 50% of B.1351 viral particles, and only half the sera did so against the E484K mutant.

The researchers concluded that, relative to the wildtype spike virus neutralising titers, were reduced by seven-fold against the B.1.351 lineage and three-fold against the E484K spike. They also found that the VOCs with the different spikes showed different modes of escape from antibody-mediated neutralisation by sera elicited by the Sputnik V vaccine. This means that resistance to neutralisation offered by the South African variant occurs by a different mechanism than that of the E484K mutant.

The UK VOC has low resistance to pre-existing or vaccine-induced antibodies, but the B.1.351 variant shows marked resistance. In fact, 8 of 12 samples were unable to reach IC90 at the highest possible serum concentration.

One neutralised the UK variant but none of the other three variants. These findings are of particular concern because all three VOCs carry the N501Y RBD substitution that confers increased affinity for the ACE2 receptor.

This resistance is competitive and is not present at higher serum concentrations. However, this is not true for the mutations in the B.1.351 variant, which escapes neutralisation with undiluted serum.

Though the Sputnik V vaccine likely protects against severe COVID from VOCs, it is troubling that B1.351, as well as all E484K-bearing mutants, is resistant to neutralisation by sera elicited by this vaccine.

However, antibody functions may be different in vivo, and this study does not cover cell-mediated immunity to multiple antigen sites.
“Taken together, our data argue that surveillance of the neutralizing activity elicited by vaccine sera will be necessary on an ongoing basis,” the authors wrote.

The knowledge of which variants can still spread among vaccinated and naturally immune individuals will help decide how to contain them with vaccine upgrades.

Source: News-Medical.Net

Preprint information: Ikegame, S. et al. (2021). Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants. medRxiv preprint. doi: https://doi.org/10.1101/2021.03.31.21254660. https://www.medrxiv.org/content/10.1101/2021.03.31.21254660v2

Categories : NeurologyTags :

Shared Neural System May Be Used for Different Memory Stores

On By ModernMedia

The brain may have a shared neural system that is involved in the retrieval of facts and personal memories used in everyday life, new research has found.

Factual memory had long been categorised into two stores; factual memory and memory of personal experiences. These two repositories in concert enable people to make sense of the world around them. Individuals with retrograde amnesia can fail to remember personal experiences, but still recall factual knowledge. These two stores have been shown by decades of clinical and experimental research to be stored across two separate regions of the brain.

But the new study suggests that a shared set of brain regions play an important role in controlling the successful retrieval of weak memories.

When participants were asked to retrieve fact memories and personal memories, researchers used functional MRI imaging to study how these regions changed in activity levels.

Lead researcher Dr Deniz Vatansever, formerly of the University of York and now working for the Institute of Science and Technology for Brain-inspired Intelligence, Fudan University said: “The new research suggests that despite their functional differences, successfully retrieving weak information from these two memory systems might be dependent upon a shared brain mechanism.

“Our memories allow us to make sense and flexibly interact with the world around us. Although in most cases, our strongly encoded memories might be sufficient for the task at hand, remembering to pack a beach towel for an upcoming seaside holiday, this strong memory may be irrelevant in other instances, such as when packing for a business trip. As such, we need to tightly control the retrieval of relevant memories to solve different tasks under different circumstances. Our results indicate that this control process might be shared across both factual and personal memory types.”

The researchers said their findings may be applicable to memory disorders, including dementia, where patients’ quality of life is affected by being unable to remember important information. The findings could also be relevant in the development of a new generation of AI, which use long-term memory in solving computational problems. 

“In order to generate appropriate thoughts and behaviors, we have to draw on our memory stores in a highly flexible way,” said senior author Elizabeth Jefferies, and professor, Department of Psychology, University of York. “This new study highlights control processes within the brain that allow us to focus on unusual aspects of the meanings of words and to retrieve weakly encoded personal experiences. This control over memory allows us to be creative and to adapt as our goals or circumstances change.”

Source: News-Medical.Net

Journal information: Vatansever, D., et al. (2021) Varying demands for cognitive control reveals shared neural processes supporting semantic and episodic memory retrieval. Nature Communications. doi.org/10.1038/s41467-021-22443-2.

Categories : GenderTags :

Evidence for Puberty Blockers is ‘Very Low’ Says UK Guidance Body

On By ModernMedia

In an official review of studies, the UK’s National Institute of Health and Care Excellence (NICE) said that the evidence for puberty blockers is “very low”.

In an assessment of the evidence for puberty blockers commissioned by NHS England, the guidance body said that existing studies of the drugs were small and “subject to bias and confounding”. The assessment forms part of a review into gender identity services for children and young people.

NHS England said the advice would be considered by the review and it would not be commenting further.

Gonadotrophin-releasing hormone (GnRH) analogues, popularly known as puberty blockers, are prescribed to some young people with gender dysphoria – distress caused by a discrepancy between a person’s gender identity (how they see themselves regarding their gender) and their sex at birth.

The NICE evidence review looked at what impact puberty blockers had on gender dysphoria, mental health – such as depression, anger and anxiety – and quality of life.

NICE, which provides national guidance and advice to improve health and social care, said: “The quality of evidence for these outcomes was assessed as very low certainty.”

The review sought to find out how treatment with GnRH analogues compared in terms of clinical effectiveness with other interventions that may be offered to young people with gender dysphoria. These include psychological support, social transitioning to the desired gender – such as changing pronouns and clothes but without medication – or no intervention at all.

NICE found it was difficult to draw conclusions from existing studies because they were “all small” and lacked control groups. They found other issues with the studies too, such as not describing what other physical and mental health problems a young person may have alongside gender dysphoria.

The review said there was “very little data” on any additional interventions, such as counselling or other drug treatments, that the young people may have received alongside taking puberty blockers, leading to possible bias in results. Impacts of puberty blockers on bone density were another concern.

However without a “comparator group”, it was not known whether bone density changes observed “are associated with GnRH analogues or due to changes over time”.

It is argued by some that it is difficult to withhold support to create a comparator group because it would mean unfairly disadvantaging some. NICE accepted this, but said offering psychological support to compare puberty blockers “may reduce ethical concerns in future trials”.

No evidence of cost-effectiveness of treatment was found by the review.

NICE also reviewed the evidence base for gender-affirming hormones, which can be given to young people with gender dysphoria from age 16 in the NHS. These start the development of the physical sex characteristics of the gender with which they identify with the aim of improving mental health, quality of life and body image.

The review found the evidence of clinical effectiveness and safety of gender-affirming hormones was also of “very low” quality.

“Any potential benefits of gender-affirming hormones must be weighed against the largely unknown long-term safety profile of these treatments in children and adolescents with gender dysphoria,” NICE said.

Source: BBC News

Categories : Neurodegenerative DiseasesTags :

Exercise Slows Cognitive Decline in APOE4-related Parkinson’s Disease

On By ModernMedia

Results from a longitudinal study showed physical activity reduced  cognitive decline in early APOE4-related Parkinson’s disease.

Jin-Sun Jun, MD, of Hallym University in Seoul, and colleagues in Neurology presented the findings of a longitudinal study on a group of 173 recently diagnosed Parkinson’s patients. Of this group, those who with an apolipoprotein E ε4 (APOE4) allele had faster cognitive decline on the 30-point Montreal Cognitive Assessment (MoCA) scale than noncarriers (estimate -1.33, 95% CI -2.12 to -0.47, P=0.002). However, among the APOE4 carriers, higher physical activity was related to slower cognitive decline (estimate 0.007, 95% CI 0.003-0.011, P=0.001)..

Dr Jun noted that this reflects a number of studies that have demonstrated that Parkinson’s patients who exercise regularly show better clinical outcomes, including motor and cognitive function.

“These observations are supported by epidemiological data showing a link between physical activity and decreased risk for Parkinson’s disease,” Dr Jun told MedPage Today. “Because previous data indicate that physical activity modifies the APOE4 effect on the development and progression of Alzheimer’s disease, we hypothesized that physical activity also plays a role in modulating the association between APOE4 and cognition in Parkinson’s disease.”

Genetic factors interact with physical activity on other health outcomes, noted Jacob Raber, PhD, of Oregon Health and Science University in Portland, and colleagues, in an accompanying editorial.

“If similar gene-by-physical activity interactions were identified in Parkinson’s disease, they could pave the way for personalized treatment,” Raber and colleagues wrote. “While the effects of APOE4 on promoting beta-amyloid and tau pathology are well-established, recent studies show that APOE4 is also associated with more profound pathology of alpha-synuclein and higher measures of cognitive burden, both in mouse models and in humans with Parkinson’s disease.”

In their study, the researchers followed recently diagnosed patients in the Parkinson’s Progression Markers Initiative cohort who were not treated for Parkinson’s and who had abnormal dopamine transporter (DAT) imaging.

Self-reported physical activity was begun 2 years after enrollment and scored on the Physical Activity Scale of the Elderly. Cognitive function was measured annually with the MoCA, which is well-suited for Parkinson’s patients, and DAT imaging was performed at years 2 and 4. Assessments performed at years 2, 3, and 4 were used for analysis.

There was no significant interaction seen between physical activity and APOE4 involving change in striatal DAT activities. This suggests that striatal dopaminergic function may not be a major factor in physical activity’s protective effect on APOE4-related cognitive decline, Dr Jun and colleagues noted. “These negative results may be explained by the modest effect of APOE4 on the nigrostriatal dopaminergic system,” they wrote. “Furthermore, our follow-up duration may be too short to comprehend the impact of APOE4 on this system, considering the slow progressive nature of alpha-synucleinopathy.”

The researchers also pointed out that the exercise could offer benefits through mechanisms unrelated to the disease. “Although we cannot conclude what types or amounts of exercise help to slow progression from this study design, even non-high-intensity physical activity positively modified the impact of APOE4 on cognitive function,” Jun said.

The study’s limitations included physical activity being self-reported, cognitive function being based only on MoCA scores, and a short follow-up time. Though motor scores in the off-medication state were adjusted for, physical activity may have been less due to disease progression.

Source: MedPage Today

Categories : NeurologyTags :

Sugar-sweetened Drinks During Adolescence Impacts Cognition in Adulthood

On By ModernMedia

New research has shown that, in rats, daily consumption of sugar-sweetened drinks during adolescence impairs performance on a learning and memory task during adulthood. 

The researchers also demonstrated that changes in the bacteria in the gut may be the key to the sugar-induced memory impairment. Evidence in support of this comes from the observation of similar memory deficits even when the bacteria, called Parabacteroides, were experimentally enriched in the guts of animals that had never consumed sugar.

“Early life sugar increased Parabacteroides levels, and the higher the levels of Parabacteroides, the worse the animals did in the task,” said first author Emily Noble, assistant professor, College of Family and Consumer Sciences, University of Georgia. “We found that the bacteria alone was sufficient to impair memory in the same way as sugar, but it also impaired other types of memory functions as well.”

Data from the Centers for Disease Control and Prevention show American children between the ages 9-18 exceed the recommendation of limiting added sugars to less than 10 percent of calories per day, with the bulk of the calories coming from sugar-sweetened beverages.

Since the hippocampus is still developing into late adolescence and plays a role in a variety of cognitive functions, researchers sought to understand more about its susceptibility to a high-sugar diet via gut microbiota.

Juvenile rats were given their normal chow and an 11% sugar solution, comparable to commercially available sugar-sweetened beverages. Researchers then had the rats perform a hippocampus-dependent memory task designed to measure episodic contextual memory, or remembering the context where they had seen a familiar object before.

“We found that rats that consumed sugar in early life had an impaired capacity to discriminate that an object was novel to a specific context, a task the rats that were not given sugar were able to do,” Prof Noble said.

A second memory task measured basic recognition memory, a hippocampal-independent memory function that involves the animals’ ability to recognise something they had seen previously. Sugar had no effect on the animals’ recognition memory.

“Early life sugar consumption seems to selectively impair their hippocampal learning and memory,” Prof Noble said.

Further analysis revealed that high sugar consumption led to elevated levels of Parabacteroides in the gut microbiome, the more than 100 trillion microorganisms in the gastrointestinal tract that play a role in human health and disease.

To determine the mechanism by which bacteria impacted memory and learning, researchers experimentally increased levels of Parabacteroides in the microbiome of rats that had never consumed sugar. Those animals showed impairments in both hippocampal dependent and hippocampal-independent memory tasks.

“(The bacteria) induced some cognitive deficits on its own,” Prof Noble said.

Future research is needed to better identify these gut-brain signaling specific pathways.

“The question now is how do these populations of bacteria in the gut alter the development of the brain?” Prof Noble said. “Identifying how the bacteria in the gut are impacting brain development will tell us about what sort of internal environment the brain needs in order to grow in a healthy way.”

Source: News-Medical.Net

Journal information: Noble, E. E., et al. (2021) Gut microbial taxa elevated by dietary sugar disrupt memory function. Translational Psychiatry. doi.org/10.1038/s41398-021-01309-7.

Categories : Cancer PaediatricsTags :

Blood Mutation Explains High Leukaemia Rates in Children with Down’s

On By ModernMedia

According to a new study by researchers at the Linda Crnic Institute for Down Syndrome, the reason that children with Down syndrome have a drastically elevated risk of leukaemia is due to a more prevalent condition increasing blood stem cell mutation.

Children with Down syndrome are 20-times more likely to develop acute lymphocytic leukaemia (ALL) and 150-times more likely to develop acute myeloid leukaemia (AML) compared to their typical peers. The researchers found that the reason for this is that they are more likely to present with clonal haematopoiesis (CH), a process in which a blood stem cell acquires a genetic mutation that promotes replication.  

The findings add to a growing body of evidence linking immune dysregulation to a very different disease spectrum, whereby people with Down syndrome are highly predisposed to certain diseases such as leukaemia and autoimmune disorders, while being highly protected from others, such as solid tumours.

“We found a higher-than expected rate of CH in individuals with Down syndrome between the age of one to 20 years old,” said study author Dr Alexander Liggett, who as a doctoral candidate led the study in the lab of Dr James DeGregori, Professor of Biochemistry and Molecular Genetics. “It is a surprising finding, as the phenomenon is typically only observed in elderly people.”

The researchers used an advanced sequencing technique that they had developed, called FERMI, to blood samples from the Crnic Institute Human Trisome Project Biobank. Mutations were more likely to be detected in Down’s syndrome and also more likely to be oncogenic. In elderly people, oncogenic mutations are commonly found in the genes DNMT3A, TET2, ASXL1, TP53, and JAK2. In people with Down’s syndrome, oncogenic CH was found to be dominated by mutations of the TET2 gene.

“Given the increased risk of leukaemia that accompanies clonal expansion of blood cells carrying oncogenic mutations, these expansions may become an important biomarker of cancer risk in the future,” said Dr Liggett.

The study also found that CH in Down syndrome is associated with immune dysregulation biosignatures linked to diseases co-occurring with Down’s syndrome, including thyroiditis, Alzheimer’s disease, and leukaemia. This discovery opens new avenues in understanding the way CH impacts an array of health outcomes in Down syndrome and how to potentially counteract its effects.

“This is truly transformative. This team has identified a new trait of Down syndrome that has strong implications for understanding the appearance of comorbidities more common in this population, such as leukaemia and premature ageing,” said Dr. Joaquin Espinosa, Executive Director of the Crnic Institute. “The next step is to define the long-term impacts of this precocious clonal hematopoiesis and how to prevent its harmful effects.”

Source: News-Medical.Net

Journal information: Liggett, L.A., et al. (2021) Precocious clonal hematopoiesis in Down syndrome is accompanied by immune dysregulation. Gut. doi.org/10.1182/bloodadvances.2020003858.

Categories : COVIDTags :

COVID Surges Driven by New Variants

On By ModernMedia

A study of SARS-CoV-2 genomes and epidemic case data has shown that COVID outbreaks emerge with new variants.

“As variants emerge, you’re going to get new outbreaks,” said Bart Weimer, professor of population health and reproduction at the UC Davis School of Veterinary Medicine. The study combined classical epidemiology with genomics, providing a tool for public health authorities to predict the course of pandemics.

SARS-CoV-2  only has 15 genes, but is mutating constantly. The majority of these changes have little impact, but occasionally they result in the virus becoming more or less transmissible.

Together with graduate student DJ Darwin R Bandoy, Prof Weimer at first analysed the genomes of 150 SARS-CoV-2 strains, mostly from outbreaks in Asia prior to March 1, 2020, along with epidemiology and transmission information on those outbreaks. 

The classified outbreaks by stage: index (no outbreak), takeoff, exponential growth and decline. Virus transmissibility is set by the value R, or reproductive number, where R is the average number of new infections caused by each infected person.

They combined all this information into a metric called GENI, for pathogen genome identity. Comparing GENI scores with epidemic phases showed that an increase in genetic variation immediately preceded exponential growth in cases, for example in South Korea in late February. In Singapore, however, bursts of variation were associated with smaller outbreaks that were quickly brought under control.

Prof Weimer and Bandoy then looked at 20 000 sequences of SARS-CoV-2 viruses collected over February to April 2020 in the United Kingdom, and compared them with COVID cases data.

They found that the GENI variation score rose steadily with the number of cases. When a national lockdown was imposed in late March, the number of new cases stabilised but the GENI score continued to rise. This shows that control measures such as banning gatherings, mask mandates and social distancing are effective in controlling spread of disease in the face of rapid virus evolution.

It could also help explain “superspreader” events when large numbers of infections result from relaxed precautions at an event.

Prof Weimer said he hopes that health authorities will adopt this method of measuring virus variation and linking it to the local transmission rate, R.

“In this way you can get a very early warning of when a new outbreak is coming,” he said. “Here’s a recipe for how to go about it.”

Source: Medical Xpress

Journal information: Scientific Reports (2021). DOI: 10.1038/s41598-021-86265-4