Tag: 26/8/21

Categories : Cancer PaediatricsTags :

Existing Drug Could Target Childhood Leukaemia

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Existing Drug Could Target Childhood Leukaemia

A new study published in PNAS has shown that the tumour-inhibiting gene TET2 is silenced in a large fraction of cases of acute lymphoblastic leukaemia (ALL) in children. The scientists show that the gene can be reactivated by an existing drug, 5-azacytidine, suggesting that it could be used a as targeted therapy for ALL in children.

“T-cell acute lymphoblastic leukaemia (T-ALL) is a devastating disease for the affected children and their families. One of five children affected do not survive the disease. The ultimate goal of my research is to ensure that all children can be cured. Our discovery may pave the way for clinical studies of 5-azacytidine as a new therapy for this poorly understood disease. The more treatment options we have for T-ALL the more chance we have of beating this aggressive cancer,” explained study leader Colm Nestor, senior lecturer in the Department of Biomedical and Clinical Sciences .

One of the characteristics of cancer cells is that they lose their cellular identity. One of the reasons for this is certain genes being silenced while others are activated. Switching genes on and off is controlled by epigenetic modification, where small chemical groups are attached to and removed from DNA, such as DNA methylation. The pattern of DNA-methylation is often altered in cancer cells, making them attractive targets for cancer drug research.

In the recently published study, the researchers were interested in an enzyme, TET2, that removes methyl groups from DNA. The gene that codes for TET2 is often affected by mutations in adult leukaemias. In children however, harmful mutations in TET2 are very rare, which led the researchers to speculate whether TET2 function is affected differently in child leukaemias. They analysed the gene expression patterns in cancer cells from more than 300 patients with T-ALL, and found that in many cases the TET2 gene was silenced.

It turned out that  methylation often silenced the TET2 gene. The scientists therefore decided to treat tumour cells in culture with a drug, 5-azacytidine, that removes methyl groups from DNA. This drug is used to treat certain leukaemias in adults.

“We found that one type of T-ALL cell, whose DNA seems to be highly methylated, is more sensitive to azacytidine than other cells that are not highly methylated. The drug actually turns silenced TET2 back on by demethylating it, so this might be a targeted therapy for a subset of cases. We suggest that azacytidine may have a doubled effect in these cells, since both the drug itself and TET2 kill cancer cells by demethylating the genome,” explained Colm Nestor.

Since 5-azacytidine is an approved drug, the researchers hope that it will be a much quicker path to treatment than when developing a novel drug.

“Chemotherapy agents have a broad effect and can be used for many patients, but they also kill healthy cells and can give rise to serious undesired effects. Targeted treatment, on the other hand, only works for a small fraction of patients, but is extremely specific. We need an arsenal of drugs to use for patients who experience relapses, and for those whose cancer does not respond to chemotherapy,” said Colm Nestor.

The researchers will continue with experiments to determine the effects of activating TET2 in these cancer cells, and to see if 5-azacytidine can function as targeted therapy in other types of cancer.

“The fact that we can target the loss of TET2 using the drug 5-azacytidine makes me hopeful that this treatment can help T-ALL patients in the future,” said researcher Maike Bensberg, PhD student at Linköping University.

Source: Linköping University

Categories : COVIDTags :

COVID Most Contagious 2 Days Before to 3 Days After Symptoms Start

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A new study published in JAMA Internal Medicine has found that individuals infected with the virus are most contagious two days before, and three days after, they develop symptoms.

The study also found that infected individuals were more likely to be asymptomatic if they contracted the virus from a primary case (the first infected person in an outbreak) who was also asymptomatic.

“In previous studies, viral load has been used as an indirect measure of transmission,” explained Dr Leonardo Martinez, assistant professor of epidemiology at BUSPH, and who co-led the study with Dr Yang Ge, research assistant in the Department of Epidemiology & Biostatistics at the University of Georgia College of Public Health. “We wanted to see if results from these past studies, which show that COVID cases are most transmissible a few days before and after symptom onset, could be confirmed by looking at secondary cases among close contacts.”

The investigators performed contact tracing and studied COVID transmission among approximately 9000 close contacts of primary cases in the Zhejiang province of China from January 2020 to August 2020. ‘Close’ contacts included household contacts (individuals living in the same household or who dined together), co-workers, people in hospital settings, and riders in shared vehicles. The researchers monitored infected individuals for at least 90 days after their initial positive COVID test results to distinguish between asymptomatic and pre-symptomatic cases.

Of the primary cases, 89 percent developed mild or moderate symptoms, and only 11 percent were asymptomatic — and none developed severe symptoms. Household members of primary cases, as well as those exposed to primary cases more often or for longer time, had the highest infection rates among close contacts. But regardless of these risk factors, close contacts were more likely to contract COVID from the primary infected individual if they were exposed shortly before or after the individual developed noticeable symptoms.

“Our results suggest that the timing of exposure relative to primary-case symptoms is important for transmission, and this understanding provides further evidence that rapid testing and quarantine after someone is feeling sick is a critical step to control the epidemic,” Dr Martinez said.

Compared to mild and moderate symptomatic individuals, asymptomatic primary individuals were much less likely to transmit COVID to close contacts — but if they did, the contacts were also less likely to experience noticeable symptoms.

Source: Newswise

Categories : Addiction GenderTags :

Despite Smoking Less, Women Find it Harder to Quit

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A large study has found that women smoke fewer cigarettes than men but are less likely to quit.

Study author Ms Ingrid Allagbe, PhD student at the University of Burgundy, said: “In our study, women who used smoking cessation services had higher rates of overweight or obesity, depression, and anxiety compared to men and kicked the habit less often. Our findings highlight the need to provide smoking cessation interventions tailored to the needs of women.”

This study, presented at ESC Congress 2021, compared characteristics and abstinence rates of men and women visiting smoking cessation services between 2001 and 2018 in France, obtained from a nationwide database. The participants were smokers with at least one additional risk factor for cardiovascular disease: overweight/obese (body mass index [BMI] 25 kg/m² or above); high cholesterol; diabetes; high blood pressure; history of stroke, heart attack or angina.

Participants were classified as having mild, moderate, or severe nicotine dependence. Smoking abstinence (at least 28 consecutive days) was self-reported and confirmed by measurement of exhaled carbon monoxide less than 10 parts per million (ppm).

Participant height, weight, age, education level, chronic conditions, and number of cigarettes smoked each day were recorded. Participants were classified as having anxiety and depression symptoms or not according to their medical history, use of anti-anxiety medication or antidepressants, and the Hospital Anxiety and Depression Scale (HADS).

A total of 37 949 smokers were included in the study, of whom 43.5% were women. The average age of women in the study was 48 years, while the average age of men was 51 years. More women (55%) reported a bachelor’s degree level of education or higher compared to men (45%).

Both men and women had a high burden of cardiovascular risk factors. High cholesterol was more common in men (33%) than women (30%), as was high blood pressure (26% vs 23%, respectively) and diabetes (13% vs 10%, respectively).

Women were more likely (27%) to be overweight or obese compared to men (20%), and more likely (37.5%) to have symptoms of anxiety or depression than men (26.5%). Chronic obstructive pulmonary disease was more common in women (24%) compared to men (21%) as was asthma (16% vs 9%, respectively).

However, women smoked fewer cigarettes per day (23) than men (27). Severe nicotine dependence was less common, 56% of women compared to 60% of men, and abstinence was less common in women (52%) than men (55%).

Ms Allagbe said: “The findings suggest that despite smoking fewer cigarettes and being less nicotine dependent than men, women find it more difficult to quit. Possible contributors could be the higher prevalence of anxiety, depression and overweight or obesity among women. It has previously been reported that women may face different barriers to smoking cessation related to fear of weight gain, sex hormones, and mood.”

She concluded: “The results indicate that comprehensive smoking cessation programmes are needed for women that offer a multidisciplinary approach involving a psychologist, dietitian, and physical activity specialist.”

Source: European Society of Cardiology

Categories : NeurologyTags :

Why REM Sleep is Important in Animals

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Photo by Bruce Christianson on Unsplash

Researchers in Japan have discovered that capillary blood flow in the brain is increased in mice during the dream-active REM phase of sleep, possibly preventing a buildup of waste products.

Scientists have long wondered why almost all animals sleep, despite the disadvantages to survival of being unconscious. Now, researchers led by a team from the University of Tsukuba have found new evidence of brain refreshing that takes place during a specific phase of sleep: rapid eye movement (REM) sleep, where dreaming occurs.

Previous studies have seen conflicting results when measuring differences in blood flow in the brain between REM sleep, non-REM sleep, and wakefulness using various methods. For this study, the investigators used a technique to directly visualise red blood cell movement in the brain capillaries of mice during awake and asleep states.

“We used a dye to make the brain blood vessels visible under fluorescent light, using a technique known as two-photon microscopy,” explained the senior study author, Professor Yu Hayashi. “In this way, we could directly observe the red blood cells in capillaries of the neocortex in non-anaesthetised mice.”

The researchers also measured electrical activity in the brain to identify REM sleep, non-REM sleep, and wakefulness, and looked for differences in blood flow between these phases.

“We were surprised by the results,” said Professor Hayashi. “There was a massive flow of red blood cells through the brain capillaries during REM sleep, but no difference between non-REM sleep and the awake state, showing that REM sleep is a unique state”

The research team then disrupted the mice’s sleep, resulting in ‘rebound’ REM sleep, which is a stronger form of REM sleep to compensate for the earlier disruption. During rebound REM sleep, blood flow was increased even further, suggesting an association between blood flow and REM sleep strength. However, when the researchers repeated the same experiments in mice without adenosine A2a receptors (blocking these receptors makes you feel more awake after a coffee), there was less of an increase in blood flow during REM sleep, even during rebound REM sleep.

“These results suggest that adenosine A2a receptors may be responsible for at least some of the changes in blood flow in the brain during REM sleep,” said Professor Hayashi.

Given that reduced blood flow in the brain and decreased REM sleep are correlated with the development of Alzheimer’s disease, in which waste products are seen to build up in the brain, this increased blood flow in the brain capillaries during REM sleep could be important for waste removal from the brain. This study highlights the role of adenosine A2a receptors in this process, perhaps leading to the development of new treatments for Alzheimer’s disease and other conditions.

Source: University of Tsukuba

Categories : Obstetrics & GynaecologyTags :

Taking Action Before and Between Pregnancies Reduces Risk of Preeclampsia

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In a new study, John Hopkins researchers have found that the periods before pregnancy and in between pregnancies are crucial times to address preeclampsia risk factors like obesity, diabetes and hypertension.

Preeclampsia, a common pregnancy complication, is characterised by high blood pressure and signs of damage to the liver, kidneys or other organs. It usually starts after 20 weeks of pregnancy in women whose blood pressure had previously been normal. .

The team, led by S. Michelle Ogunwole, MD, a fellow in the Division of General Internal Medicine, and Wendy Bennett, MD, MPH, associate professor of medicine, both at the Johns Hopkins University School of Medicine, published their findings in the Journal of the American Heart Association.

Dr Ogunwole said: “Preconception health care is really important as it’s a window of opportunity to think about your future health. We encourage patients to work on chronic disease issues before their pregnancies and between their pregnancies.”

A woman who develops preeclampsia during her first pregnancy has a higher risk of the condition recurring in a second or any successive pregnancies, she said.

“As an internist concerned about maternal outcomes, I am interested in what health care providers can do to help women reduce their risk of preeclampsia, including being a big proponent of preconception counseling,” said Dr Ogunwole.

The team compared two sets of women who were participating in the Boston Birth Cohort. Since 1998, the cohort has looked at a broad array of early life factors and their effects on pregnancy, infancy and child health outcomes. The researchers wanted to understand the differences between women who developed preeclampsia and those who did not, and how a first case of the condition affects subsequent pregnancies. Dr Ogunwole’s team studied 618 women to gain “rich maternal health data among racially and ethnically diverse pregnant women.”

“We wanted to make sure that we’re asking questions in a population that looks like the populations we serve,” she says. “I’m interested in the life course of women and pregnancy complications that can shape the trajectory of their future health.”

The researchers found that obesity, diabetes, high blood pressure, gestational diabetes and preterm birth were common factors in women who had preeclampsia during both first and second pregnancies, or who developed the condition during gestation with a second or later child.

“We know that improving weight will improve other conditions, so we advise that women create healthier lifestyles before and between pregnancies,” said Dr Ogunwole. “Whether you have another pregnancy again or not, you can still improve your overall health.”

Future research should hopefully include larger trials to confirm their results. Dr  Ogunwole  also plans to study the structural barriers that may prevent women from engaging in healthy lifestyles and develop strategies to improve long-term health outcomes for women.

Source: John Hopkins Medicine

Categories : COVIDTags :

Govt Switches COVID Focus to Vaccine Access and Hesitancy

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As the official COVID death toll in South Africa passes the 80 000 mark, the Department of Health is now shifting focus to addressing flagging vaccine demand.

The department said this will include making access easier, such as vaccinating at shops or places of work.

Another change would be providing transportation to vaccine sites to help those in underprivileged areas. One option being looked into is the introduction of home vaccinations and ‘pop-up’ sites in rural areas where travel is harder to come by and at busy commercial areas such as shopping centres.

The government also hopes for assistance from the religious sector, with the possibility of churches offering vaccines on a Sunday. Mosques, synagogues and other places of worship would also offer a ‘familiar environment’ where people feel comfortable receiving a vaccine.

Public awareness
Social media will be heavily employed for vaccine promotion, and could incude online influencers and ambassadors to encourage vaccination.
This could extend to identifying ‘apolitical’ vaccine champions relevant to the target group who have also great influence, such as celebrities and traditional leaders.

A number of awareness initiatives are being considered, including making use of channels such as social media and teachers to provide information to young people and counteract misinformation, as well as more traditional media efforts such as radio slots and signage.

Vaccine skepticism high in men
Department of Health Deputy director-general Dr Nicholas Crisp, pointed out that South Africa has a particular problem with men not wanting to be vaccinated.

“This is not good,” Dr Crisp said. “It means that men are going to end up very sick and in hospital, and we don’t want that to happen just before Christmas.”

An Africa Centres for Disease Control and Prevention (ACDC) study found that 66% of men in South Africa were sceptical about vaccine safety compared to 74% of women.

Mandatory vaccinations on the cards
Health minister Dr Joe Phaahla warned of a very long road ahead as new cases continue to spike.

The ministerial advisory committee on COVID is now discussing the possibility of mandatory vaccination for certain groups of people, which could include healthcare workers and those professions spending time indoors with other people, according to the Sunday Times.

Scientists and health activists told the paper that the right to refuse a vaccine is outweighed by the health hazard of the pandemic.

The country would then be able to reopen and operate in a way as close as possible to the pre-COVID era, said leading vaccinologist Professor Shabir Madhi.

“In these settings, if people choose not to be vaccinated, they should be compelled to undergo testing every three or four days at their own expense,” he said.

While vaccinations don’t confer complete COVID protection, it is still significant, and more impactful if a greater proportion are vaccinated, Prof Madhi said.

Source: BusinessTech