Year: 2022

Categories : Cancer UrogenitalTags :

Focus on Urinary Problems Clouds Early Prostate Cancer Detection

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Credit: Darryl Leja / National-Human-Genome Research Institute / National Institutes of Health

Diagnoses of early, curable stages of prostate cancer are being missed because national guidelines and media health campaigns in the UK focus on urinary symptoms despite a lack of scientific evidence, according to University of Cambridge researchers.

Prostate cancer is the most common type of cancer in men. And while 78% of men diagnosed with this cancer survive for over ten years, this proportion has barely changed over the past decade in the UK, largely because the disease is detected at a relatively late stage. In England, for example, nearly half of all prostate cancers are picked up at stage three of four (stage four being the latest stage).

Despite no evidence of a link between urinary symptoms and prostate cancer, national guidelines, health advice and public health campaigns continue to promote this link. In a review published in BMC Medicine, Cambridge researchers argue that not only is this unhelpful, but it may even deter men from coming forward for early testing and detection of a potentially treatable cancer.

“When most people think of the symptoms of prostate cancer, they think of problems with peeing or needing to pee more frequently, particularly during the night,” said Vincent Gnanapragasam, Professor of Urology at the University of Cambridge. “This misperception has lasted for decades, despite very little evidence, and it’s potentially preventing us picking up cases at an early stage.”

Prostate enlargement can cause the urinary problems often included in public health messaging, but evidence suggests that this is rarely due to malignant prostate tumours. Rather, research suggests that the prostate is smaller in cases of prostate cancer.  A recent study – the UK PROTECT trial – even went as far as to say that a lack of urinary symptoms may in fact be an indicator of a higher likelihood of cancer.

Screening programmes are one way that cancers are often detected at an early stage, but in the case of prostate cancer, some argue that such programmes risk overwhelming health services and leading to men being treated for relatively benign disease.

Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. PSA density is significantly more accurate than PSA alone in predicting a positive biopsy and is used in everyday clinical practice.

The researchers point to evidence that there is a misconception that prostate cancer is always symptomatic: a previous study found that 86% of the public associated prostate cancer with symptoms, but only 1% were aware that it could be asymptomatic.

“We urgently need to recognise that the information currently given to the public risks giving men a false sense of security if they don’t have any urinary symptoms,” said Prof Gnanapragasam.

“We need to emphasise that prostate cancer can be a silent or asymptomatic disease, particularly in its curable stages. Waiting out for urinary symptoms may mean missing opportunities to catch the disease when it’s treatable.

“Men shouldn’t be afraid to speak to their GP about getting tested, and about the value of a PSA test, especially if they have a history of prostate cancer in their family or have other risk factors such as being of Black or mixed Black ethnicity.”

The researchers say they are not advocating for an immediate screening programme, and acknowledge that changes in messaging could mean more men approaching their GPs for a PSA test, potentially resulting in unnecessary investigations and treatment. However, they argue that there are ways to reduce the risk of this happening. These include the use of algorithms to assess an individual’s risk and whether they need to be referred to a specialist, and for those who are referred, MRI scans could help rule out ‘indolent’ (mild) disease or negative findings, reducing the risks of an unnecessary biopsy.

“We’re calling on organisations such as the NHS, as well as patient charities and the media, to review the current public messaging,” said Prof Gnanapragasam.

“If men were aware that just because they have no symptoms doesn’t necessarily mean they are cancer free, then more might take up offers for tests. This could mean more tumours identified at an earlier stage and reduce the numbers of men experiencing late presentation with incurable disease.”

Source: University of Cambridge

Categories : VaccinesTags :

New Tuberculosis Vaccine Passes Safety Hurdle in SA Trial

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Tuberculosis bacteria
Tuberculosis bacteria. Credit: CDC

The only vaccine currently available against tuberculosis, Bacillus Calmette Guérin (BCG), is not equally effective against all types of tuberculosis. A clinical trial in South Africa has now shown that the new vaccine candidate VPM1002, decades in development, is equally safe for newborns with and without HIV exposure and has fewer side effects compared to BCG.

First used 100 years ago, the BCG vaccine against the disease contains attenuated pathogens of cattle tuberculosis. “We know that BCG can prevent so-called tuberculous meningitis and miliary tuberculosis in infants with a 75 to 86 percent effectiveness rate. But this is not the case for the most common form of the disease, pulmonary tuberculosis, in all age groups. Here, BCG is only insufficiently effective,” explained Max Planck researcher Stefan H.E. Kaufmann, who developed the vaccine with his team.

Since the 1990s, the infection biologist and his team have been working on an improved next-generation vaccine, called VPM1002. To achieve this, the researchers genetically modified the attenuated BCG vaccine strain so that immune cells can better recognise the pathogens. “We developed VPM1002 in no small part to combine increased safety with improved efficacy for immunocompromised children,” Kaufmann said.

Vaccine candidate VPM1002 is safe

The group of immunocompromised children includes, for example, HIV-exposed infants born to HIV-positive mothers. In a clinical trial in South Africa, researchers compared VPM1002 with BCG in HIV-exposed and non-HIV-exposed newborns. The study examined both the safety and the immunogenicity associated with the formation of immune cells and immunostimulatory proteins. The study, published in Lancet Infectious Diseases, concluded that VPM1002 is safe in both HIV-exposed and non-HIV-exposed newborns, has fewer side effects than BCG, and elicits a similar immune response.

In the randomised phase II double-blind study in South Africa, 416 eligible newborns were randomly selected and vaccinated before day 12 of life. 312 of them received VPM1002, and 104 received the BCG vaccine. As the study showed, VPM1002 triggered fewer vaccine-related adverse reactions than BCG. This was true for reactions occurring at the injection site, such as scarring and abscess formation, as well as enlargement of lymph nodes. This finding is important because local and regional reactions after vaccination are among the limitations of the BCG vaccine, Kaufmann points out.

Newborns with or without HIV exposure showed similar immunogenicity with both vaccines, though starting at six weeks of age, the BCG-triggered immune response was greater than in even younger infants.

Phase III study investigates protection

“Studies such as those described here examine a vaccine’s immunogenicity, but not its protection. For the latter, we have already developed a larger phase III clinical trial and have successfully enrolled mothers with their newborns to participate. Now the clock is ticking,” Kaufmann said. He expects initial results showing whether VPM1002 can provide comparable or better protection than existing BCG vaccines in about three years. In addition, VPM1002 vaccine is currently in two other phase III clinical trials in India for protection against tuberculosis, which expected to be completed in 2023 and 2024.

Source: Max-Planck-Gesellschaft

Categories : Cardiovascular DiseaseTags :

Gout Flare-ups Linked to Increased MI and Stroke Risk

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The risk of myocardial infarction (MI) and strokes temporarily increases in the four months after a gout flare, suggests a study published in the journal JAMA.

The findings showed that gout patients who suffered from an MI or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the 61-120 days prior.

Gout is a common form of arthritis that is caused by high levels of uric acid, a chemical produced by breakdown of body tissues and present in certain foods and drinks.

At high levels, uric acid is deposited in and around joints as needle shaped urate crystals. Once released from their deposits, these crystals cause severe inflammation that manifest as joint pain, swelling, redness, and tenderness that often lasts for 1–2 weeks. These episodes, called gout flares, often recur. Inflammation is also a risk factor for heart attack and stroke.

While gout patients tend to have more cardiovascular risk factors, there have been no previous studies about whether gout flares are linked with an increased risk of MI and stroke.

To address this, the team used data from 62 574 patients with gout treated in the NHS. Of these, 10 475 experienced heart attack or stroke after the diagnosis of gout, while matched controls did not experience such events. They evaluated the association between heart attacks or strokes and recent gout flares and adjusted these results for possible confounding factors. They found that gout patients who suffered an MI or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the preceding 61–120 days.

They found a similar high rate of MI or stroke in the 0–60 and 61–120 days after gout flares compared with other time periods, when they used information from only patients who consulted for a gout flare and also experienced either MI or stroke. This further strengthened the finding that gout flares are associated with a transient increase in cardiovascular events following flares. The increased odds and rates persisted when people with pre-existing heart disease or stroke before their gout diagnosis were excluded, and when shorter exposure periods such as 0-15 and 16-30 days prior to MI or stroke, were considered.

Gout patients who died from a MI or stroke had over four times the odds of experiencing a gout flare in the preceding 0-60 days and over twice the odds of gout flare in the preceding 61-120 days.

The study’s lead author, Professor Abhishek at the University of Nottingham, said: “This is the first study of its kind to examine whether there is an association between recent gout flares and heart attacks and strokes.

“The results show that among patients with gout, patients who experienced a heart attack or stroke had significantly increased odds of a gout flare during the preceding 120-days compared with patients who did not experience such events. These findings suggest that gout flares are associated with a transient increase in cardiovascular events following flares.

“People with recurrent gout flares should be considered for long-term treatment with urate lowering treatments such as allopurinol. This is a reliable way of removing urate crystal deposits and providing freedom from gout flares. Patients should also be considered for concurrent treatment with anti-inflammatory medicines such as colchicine for the first few months because urate lowering treatments may trigger gout flares in the short term.

“People with gout should be encouraged to adopt a healthy lifestyle with appropriate treatment of conditions such as high blood pressure, high cholesterol, obesity and diabetes to minimise their background risk of heart attack and stroke.”

Source: University of Nottingham

Categories : COVID PaediatricsTags :

Children’s Nasal Epithelium Protective against Older COVID Variants

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An Australian study published in PLOS Biology suggests the nasal epithelium of children inhibits infection and replication of the ancestral strain of the SARS-CoV-2 virus and also the Delta variant, but not the Omicron variant.

Children are in general less susceptible to COVID, with a lower infection rate and milder symptoms than adults. However, the factors driving this apparent paediatric resistance to COVID infections remained unknown.

In order to better understand infection and replication of SARS-CoV-2 in children, Kirsty Short at University of Queensland, and colleagues, obtained samples of primary nasal epithelium cells from twenty-three healthy children aged 2–11 and fifteen healthy adults aged 19–66 in Australia. They exposed the cells of adults and children to SARS-CoV-2 and then observed the infection kinetics and antiviral responses in children compared to adults.

The researchers found that ancestral SARS-CoV-2 replicated less efficiently and was associated with a heightened antiviral response in the nasal epithelial cells of children. This lower viral replication rate was also observed with the Delta variant, but not the Omicron variant.

Study limitations included a small sample size, so future clinical studies will be needed to validate these preliminary findings in a larger population and to determine the role of other factors, such as antibodies in protecting children from SARS-CoV-2 infection. Additionally, paediatric protection from emerging variants has yet to be quantified.

The authors wrote, “We have provided the first experimental evidence that the paediatric nasal epithelium may play an important role in reducing the susceptibility of children to SARS-CoV-2. The data strongly suggest that the nasal epithelium of children is distinct and that it may afford children some level of protection from ancestral SARS-CoV-2.”

Short added, “We use nasal epithelial cells from children and adults to show that the ancestral SARS-CoV-2 and Delta, but not Omicron, replicate less efficiently in paediatric nasal epithelial cells.”

Source: Science Daily

Categories : Cardiovascular DiseaseTags :

Gut Microbes Could Explain Some of Red Meat’s Added Cardiovascular Risk

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Part of the higher risk of cardiovascular disease associated with red meat consumption could be from metabolites produced by gut microbes, suggests new research published in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

“Most of the focus on red meat intake and health has been around dietary saturated fat and blood cholesterol levels,” said co-lead author of the study Meng Wang, PhD. “Based on our findings, novel interventions may be helpful to target the interactions between red meat and the gut microbiome to help us find ways to reduce cardiovascular risk.”

Previous research has found that certain metabolites are associated with a greater risk of cardiovascular disease. One of these is trimethylamine N-oxide (TMAO), which is produced by gut bacteria to digest red meat that contains high amounts of the chemical L-carnitine.

High blood levels of TMAO in humans may be linked to increased risks of CVD, chronic kidney disease and Type 2 diabetes. However, whether TMAO and L-carnitine-derived metabolites was linked to cardiovascular disease and to what extent, are still unknown.

To find out, the study researchers measured levels of the metabolites in blood samples. They also examined whether blood sugar, inflammation, blood pressure and blood cholesterol may account for the elevated cardiovascular risk associated with red meat consumption.

Study participants included nearly 4000 of the 5888 adults initially recruited from 1989 to 1990 for the Cardiovascular Health Study (CHS). The participants selected for the current study were free of clinical cardiovascular disease at time of enrolment in the CHS, an observational study of risk factors for cardiovascular disease in adults aged 65 or older. The CHS follows 5 888 participants, whose average age at enrolment was 73; nearly two-thirds were female and 88% of participants self-identified as white. The median follow-up time for participants was 12.5 years, and up to 26 years in some cases.  At follow-up appointment, participants’ medical history, lifestyle, health conditions and sociodemographic characteristics were assessed.

Several blood biomarkers were measured at the start of the study and again in 1996–1997. The fasting blood samples stored frozen at -80°C were tested for levels of several gut-microbiome linked to red meat consumption including TMAO, gamma-butyrobetaine and crotonobetaine.

Additionally, all study participants answered two validated food-frequency questionnaires about their usual dietary habits, including intake of red meat, processed meat, fish, poultry and eggs, at the start of the study and again from 1995 to 1996. For the first questionnaire, participants indicated how often, on average in the previous 12 months, they had eaten given amounts of various foods, ranging from “never” to “almost every day or at least five times per week,” based on medium portion sizes, which varied based on the food source. The second questionnaire used a ten-category frequency of average intake over the past 12 months, ranging from “never or less than once per month” to “six+ servings per day,” with defined standard portion sizes.

For the current analyses, the researchers compared the risk of cardiovascular disease among participants who ate different amounts of animal source foods (ie, red meat, processed meat, fish, chicken and eggs). They found that eating more meat, especially red meat and processed meat, was linked to a higher risk of atherosclerotic cardiovascular disease, an increased risk of 22% for 1.1 serving per day.

The increase in TMAO and related metabolites explained roughly one-tenth of this elevated risk, the authors said. They also noted that blood sugar and general inflammation pathways may help explain the links between red meat intake and cardiovascular disease. Blood sugar and inflammation also appear to be more important in linking red meat intake and cardiovascular disease than pathways related to blood cholesterol or blood pressure. Intake of fish, poultry and eggs were not significantly linked to higher risk of cardiovascular disease.

“Research efforts are needed to better understand the potential health effects of L-carnitine and other substances in red meat such as heme iron, which has been associated with Type 2 diabetes, rather than just focusing on saturated fat,” Dr Wang said. 

Source: American Heart Association

Categories : NeurologyTags :

Stimulating the Vagus Nerve Boosts the Brain’s Learning Centres

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Source: Pixabay

Researchers have shown a direct link between vagus nerve stimulation and its connection to the brain’s learning centres. The discovery, reported in the journal Neuron, may lead to treatments that will improve cognitive retention in both healthy and injured nervous systems.

“We concluded that there is a direct connection between the vagus nerve, the cholinergic system that regulates certain aspects of brain function, and motor cortex neurons that are essential in learning new skills,” said Cristin Welle, PhD, senior author of the paper. “This could provide hope to patients with a variety of motor and cognitive impairments, and someday help healthy individuals learn new skills faster.”

Researchers taught healthy mice a difficult task to see if it could help boost learning. Stimulating the vagus nerve during the process was found to help the mice learn the task much faster and achieve a higher performance level. This showed that vagus nerve stimulation can increase learning in a healthy nervous system.

The vagus nerve regulates internal organ functions like digestion, heart rate and respiration, as well as helping control reflex actions like coughing and sneezing.

The study also revealed a direct connection between the vagus nerve and the cholinergic system, which is essential for learning and attention. Each time the vagus nerve was stimulated, researchers could observe the neurons that control learning activated within the cholinergic system. Damage to this system has been linked to Alzheimer’s disease, Parkinson’s disease and other motor and cognitive conditions. Now that this connection has been established in healthy nervous systems, Dr Welle said it could lead to better treatment options for those whose systems have been damaged.

“The idea of being able to move the brain into a state where it’s able to learn new things is important for any disorders that have motor or cognitive impairments,” she said. “Our hope is that vagus nerve stimulation can be paired with ongoing rehabilitation in disorders for patients who are recovering from a stroke, traumatic brain injury, PTSD or a number of other conditions.”

In addition to the study, Dr Welle and her team have applied for a grant that would allow them to use a non-invasive device to stimulate the vagus nerve to treat patients with multiple sclerosis who have developed movement deficits. She also hopes that this device could eventually help speed up skill learning in healthy people.

“I think there’s a huge untapped potential for using vagus nerve stimulation to help the brain heal itself,” she said. “By continuing to investigate it, we can ultimately optimise patient recovery and open new doors for learning.”

Source: University of Colorado Anschutz Medical Campus

Categories : Genetics Medical Research & TechnologyTags :

Quantum Leap for Genetic Disease Therapy with Baculovirus DNA Repair Kit

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DNA repair
Source: Pixabay/CC0

Genetic mutations behind a genetic kidney disease affecting children and young adults have been fixed in patient-derived kidney cells with a high-capacity DNA ‘repair kit’. The advance, developed by University of Bristol scientists, is published in Nucleic Acids Research.

In this new study, the international team describe how they created a DNA repair vehicle to genetically fix faulty podocin, a common genetic cause of inheritable Steroid Resistant Nephrotic Syndrome (SRNS).

Podocin is a protein normally located on the surface of specialised kidney cells and is essential for kidney function. Faulty podocin, however, remains stuck inside the cell and never makes it to the surface, terminally damaging the podocytes. Since the disease cannot be cured with medications, gene therapy which repairs the genetic mutations causing the faulty podocin offers hope for patients.

Typically, human viruses have been utilised in gene therapy applications to carry out genetic repairs. These are used as a ‘Trojan Horse’ to enter cells carrying the errors. Currently dominating systems include lentivirus (LV), adenovirus (AV) and adeno-associated virus (AAV), which are all relatively harmless viruses that readily infect humans. Their viral shells however restrict the amount of cargo they can carry and deliver, namely the DNA kit necessary for efficient genetic repair. This limits the scope of their application in gene therapy.

By applying synthetic biology techniques, the team led by Dr Francesco Aulicino and Professor Imre Berger, re-engineered baculovirus, a insect virus which has a nearly unlimited cargo capacity.

“What sets apart baculovirus from LV, AV, and AAV is the lack of a rigid shell encapsulating the cargo space.” said Dr Francesco Aulicino, who led the study. The shell of baculovirus resembles a hollow stick, simply lengthening when the cargo increases. This allows a much more sophisticated tool-kit can be delivered by the baculovirus.

First, baculovirus had to be equipped to penetrate human cells which it normally would not do. “We decorated the baculovirus with proteins that enabled it to enter human cells very efficiently.” explained Dr Aulicino. The scientists then used their engineered baculovirus to deliver much larger DNA pieces than was previously possible, and build these into the genomes of a whole range of human cells.

The DNA in the human genome comprises 3 billion base-pairs making up ~25,000 genes, which encode for the proteins that are essential for cellular functions. If faulty base-pairs occur in our genes, faulty proteins are made which can make us ill, resulting in hereditary disease. Gene therapy promises repair of hereditary disease at its very root, by rectifying such errors in our genomes. Gene editing approaches, in particular CRISPR/Cas-based methods, have greatly advanced the field by enabling genetic repair with base-pair precision.

The team used patient-derived podocytes carrying the disease-causing error in the genome to demonstrate the aptitude of their technology. By creating a DNA repair kit, comprising protein-based scissors and the nucleic acid molecules that guide them – and the DNA sequences to replace the faulty gene, the team delivered with a single engineered baculovirus a healthy copy of the podocin gene concomitant with the CRISPR/Cas machinery to insert it with base-pair precision into the genome. This was able to reverse the disease-causing phenotype and restore podocin to the cell surface.

Professor Imre Berger explained: “We had previously used baculovirus to infect cultured insect cells to produce recombinant proteins for studying their structure and function.” This method, called MultiBac, has been highly successful to make very large multiprotein complexes with many subunits, in laboratories world-wide. “MultiBac already exploited the flexibility of the baculovirus shell to deliver large pieces of DNA into the cultured insect cells, instructing them to assemble the proteins we were interested in.” When the scientists realised that the same property could potentially transform gene therapy in human cells, they created this new DNA repair kit.

Dr Aulicino added: “There are many avenues to utilise our system. In addition to podocin repair, we could show that we can simultaneously correct many errors in very different places in the genome efficiently, by using our single baculovirus delivery system and the most recent editing techniques available.”

Source: University of Bristol

Categories : Cardiovascular DiseaseTags :

Beta Blockers and Antiplatelet Drugs Tied to Heat-related MI Risk

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During hot weather events, people taking beta blockers and antiplatelet medications such as aspirin could be at increased risk of a myocardial infarction (MI), amplifying the risk already present from hot weather.

A new study published in Nature Cardiovascular Research found that, among people suffering non-fatal MI associated with hot weather, a greater portion are taking these heart drugs.

“Patients taking these two medications have higher risk,” said Assistant Professor Kai Chen, first author of the study. “During heat waves, they should really take precautions.”

External environmental factors like air pollution and cold weather can trigger MIs, and there is growing evidence to suggest that hot weather can do so, too. But epidemiologists are still working to identify which groups of people are most vulnerable to these environmental extremes.

The authors looked at 2494 cases sourced from a registry, in which individuals experienced a non-fatal MI in Augsburg, Germany during the hot-weather months (May–September) between 2001 and 2014.

In previous research, they had shown that exposure to either heat or cold made heart attacks more likely, and they calculated that heat-related MI rates would rise once the planet has warmed by 2–3°C.

The current study built on that research by examining patients’ medication use prior to their MI.

They analysed the data in a way that let patients serve as their own controls, by comparing heat exposure on the day of the MI versus the same days of the week within the same month. That is, if a person had an NI on the third Thursday in June, the authors compared their temperature exposure that day to their temperature exposure on other, “control” Thursdays in June.

It turned out that users of beta-blockers or antiplatelet medications were likelier to have an MI during the hottest days compared to control days. Antiplatelet medication use was associated with a 63% increase in risk and beta-blockers with a 65% increase. People taking both drugs had a 75% higher risk. Non-users of those medications were not more likely to have a heart attack on hot days.

When researchers compared younger patients (25–59 years) to older ones (60–74 years), they found, as expected, that the younger ones were a healthier group, with lower rates of coronary heart disease. Yet younger patients taking beta-blockers and antiplatelet medications were more susceptible to heat-related heart attack than older patients, despite the older ones having more heart disease.

Another clue that these two medication types may render people more vulnerable is that, other heart medications generally didn’t show a connection to heat-related heart attacks. An exception was statins, which taken by younger people, were associated with an over threefold risk of a heart attack on hot days.

“We hypothesise that some of the medications may make it hard to regulate body temperature,” Asst Prof Chen said. He plans to find out why in future studies.

The results suggest that as climate change progresses, heart attacks might become a greater hazard to some people with cardiovascular disease.

Source: Yale School of Public Health

Categories : COVIDTags :

Research Throws Cold Water on COVID ‘Lab Leak’ Theory

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The source of the COVID pandemic likely is down to live animals sold at the Huanan Seafood Wholesale Market, according to an international team of researchers.

The researchers traced the start of the pandemic to the market in Wuhan, China, where animals susceptible to the virus were sold live immediately before the pandemic began. Their findings were published in a pair of papers in the journal Science.

The publications all but rule out other explanations for the start of the pandemic, such as the ‘lab leak’ hypothesis. The authors further conclude that the first spread to humans from animals likely occurred in two separate transmission events in the Huanan market in late November 2019.

The first study looked at the locations of the first known COVID cases, as well as swab samples taken various places in the market. The second study examined genomic sequences of SARS-CoV-2 from samples collected from COVID patients during the first weeks of the pandemic in China.

The first paper, led by University of Arizona virus evolution expert Michael Worobey and Professor Kristian Andersen, was able to determine the locations of almost all of the 174 COVID cases identified by the World Health Organization in December 2019, 155 of which were in Wuhan.

A ‘bullseye’ on the market

Analyses showed that these cases were clustered tightly around the Huanan market, whereas later cases were dispersed widely throughout Wuhan. A striking percentage of early COVID patients had not visited there but turned out to live near the market. This suggests that vendors got infected first and set off a chain of infections among community members in the surrounding area, said Worobey.

“In a city covering more than 3000 square miles, the area with the highest probability of containing the home of someone who had one of the earliest COVID cases in the world was an area of a few city blocks, with the Huanan market smack dab inside it,” said Worobey.

This conclusion was supported by another finding: When the authors looked at the geographical distribution of later COVID cases, from January and February 2020, they found a “polar opposite” pattern, Worobey said. While the cases from December 2019 mapped “like a bullseye” on the market, the later cases coincided with areas of the highest population density in Wuhan.

“This tells us the virus was not circulating cryptically,” Worobey said. “It really originated at that market and spread out from there.”

Worobey and collaborators also addressed the question of whether health authorities found cases around the market simply because that is where they looked.

To rule out bias even more, from the market outwards the team removed cases ran the stats again. They found that even when two-thirds of cases were removed, the findings remained the same.

“Even in that scenario, with the majority of cases, removed, we found that the remaining ones lived closer to the market than what would be expected if there was no geographical correlation between these earliest COVID cases and the market,” Worobey said.

The study also looked at swab samples taken from market surfaces like floors and cages after Huanan market was closed. SARS-CoV-2-positive samples were significantly associated with stalls selling live wildlife.

The researchers determined that mammals now known to be susceptible to SARS-CoV-2, including red foxes, hog badgers and raccoon dogs, were sold live at the Huanan market in the weeks preceding the first recorded COVID cases. The scientists developed a detailed map of the market and showed that SARS-CoV-2-positive samples reported by Chinese researchers in early 2020 showed a clear association with the western portion of the market, where live or freshly butchered animals were sold in late 2019.

“Upstream events are still obscure, but our analyses of available evidence clearly suggest that the pandemic arose from initial human infections from animals for sale at the Huanan Seafood Wholesale Market in late November 2019,” said Prof Andersen at Scripps Research, co-senior author of both studies.

Virus likely jumped from animals to humans more than once

The second study, was an analysis of SARS-CoV-2 genomic data from early cases.

The researchers combined epidemic modeling with analyses of the virus’s early evolution based on the earliest sampled genomes. They determined that the pandemic, which initially involved two subtly distinct lineages of SARS-CoV-2, likely arose from at least two separate infections of humans from animals at the Huanan market in November 2019 and perhaps in December 2019. The analyses also suggested that, in this period, there were many other animal-to-human transmissions of the virus at the market that failed to manifest in recorded COVID-19 cases.

Using molecular clock analysis, which relies on the natural pace with which genetic mutations occur over time, researchers established a framework for the evolution of the SARS-CoV-2 virus lineages. They found that a scenario of a singular introduction of the virus into humans rather than multiple introductions would not align with molecular clock data. Earlier studies had suggested that one lineage of the virus – named A and closely related to viral relatives in bats – gave rise to a second lineage, named B. The more likely scenario in which the two lineages jumped from animals into humans on separate occasions, both at the Huanan market, Worobey said.

“Otherwise, lineage A would have had to have been evolving in slow motion compared to the lineage B virus, which just doesn’t make biological sense,” said Worobey.

The two studies provide evidence that COVID originated via jumps from animals to humans at the Huanan market, likely following transmission to those animals from coronavirus-carrying bats in the wild or on farms in China. Moving forward, the researchers say scientists and public officials should seek better understanding of the wildlife trade in China and elsewhere and promote more comprehensive testing of live animals sold in markets to lower the risk of future pandemics.

Source: University of Arizona

Categories : Ethics and Law PaediatricsTags :

UK Children’s Gender Identity Clinic to Close after Controversies

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Following a highly critical independent report and accusations of inadequate and unsafe care, the UK will shut down the Tavistock gender identity clinic for children – the only one in the country. It will be replaced by a number of smaller facilities with closer links with mental health care.

The Tavistock and Portman NHS Foundation Trust clinic, named the Gender Identity Development Service (GIDS), had faced complaints of both long waiting lists for a burgeoning number of referrals, as well as rushing to assign puberty-blocking drugs and cross-sex hormones to children experiencing gender dysphoria.

Concerns had been voiced as early as 2005, when a nurse working at the clinic said that patients were being assessed too quickly and giving in to pressure from interest groups. Nevertheless, demand for its services skyrocketed in later years, from less than 100 per year in 2010 to nearly 2500 by 2018. In 2018, concerns were raised anew, with staff going on to make serious public accusations.

In July 2019, Dr Kirsy Entwhisle, a psychologist at GIDS Leeds hub, said that staff misled patients and made decisions about young people’s “bodies and lives” without “robust evidence”. Some of the children had suffered “very traumatic early experiences” which had not been addressed by the staff. The trust’s safeguarding lead, Sonia Appleby, won a claim from an employment tribunal after trust managers tried to stop her from carrying out her role when staff raised concerns.

One of the loudest critics of Tavistock Centre is Keira Bell, who at 16 was assigned puberty blockers, then cross-sex hormones at 17, and had a double mastectomy at 20 before later de-transitioning.

The former patient, who said she was suffering from anxiety and depression at the time she received treatment, said medics should have considered her mental health issues, “not just reaffirm my naïve hope that everything could be solved with hormones and surgery”.

Along with the unnamed parent of an autistic girl at the clinic, she won a ruling against the NHS assigning cross-sex hormones to children under 16 – but was overturned on appeal.

Helen, a parent of a patient at the clinic, welcomed its closure, but expressed concern for the future of her son’s treatments, according to LGBT site Pink News. While she said her son was treated quickly and received puberty blocking drugs, “From that point on, it felt like it was a little bit like they were winging it,” she said.

During therapy sessions at Tavistock, she said her son was asked a lot of questions and treated “almost like a little bit of an academic curiosity”. She criticised the fact that the same staff evaluated children for medical interventions and also offered therapy session, creating “a fear that they would stop access to medical support”. In contrast to the legal claims of Keira Bell’s and the unnamed patient, she said that GIDS refused to even discuss cross-sex hormones.

Dr David Bell (no relation to Keira Bell) welcomed the closure of Tavistock, telling the BBC: “Some children have got the double problem of living with the wrong treatment, and the original problems weren’t addressed – with complex problems like trauma, depression, large instances of autism.”