Cure for HIV moves closer as scientists find potential genetic switch

Agencies
December 7, 2018

Washington, Dec 7: A genetic switch that causes HIV hidden inside the cells to replicate can be manipulated to completely eradicate the virus from the human body, a study has found.

Cells harbouring latent HIV are "invisible" to the natural defences of the immune system, said researchers from the University of Illinois at Chicago in the US.

During infection, the DNA of HIV makes its way into the host cell's nucleus and integrates itself into the host genome.

The Tat gene circuit is a key piece of HIV DNA that controls the HIV gene transcription and activation, according to the study published in the journal Proceedings of the National Academy of Sciences.

When activated, it initiates a takeover of the cell's machinery to churn out new copies of the HIV virus, which eventually burst from the cell and infect neighbouring cells.

HIV-specific immune effector cells kill cells infected with HIV, but only when the cells are being used to produce more of the virus, meaning that the Tat gene circuit is switched on.

In cells that are latently infected, the Tat gene circuit is off, and the cell goes about its normal business all the while harbouring quiescent HIV.

"By targeting the Tat gene circuit with drugs or small molecules to activate it, we would be able to cause latently-infected cells to start producing more virus, and then they can be destroyed by the immune system," said Jie Liang, a professor at the University of Illinois.

So far, there are no drugs successfully targeting this circuit, researchers said.

People infected with the HIV virus can live relatively normal lives with exceedingly low or even undetectable viral loads thanks to powerful antiretroviral therapies that work to suppress viral replication.

However, even in people where the virus is undetectable, it doesn't mean it's completely absent.

The HIV virus can hide in cells in an inactivated state, meaning it isn't actively replicating.

This is a dire situation and makes life-long antiretroviral therapy the only option for HIV infected patients.

"It is extremely difficult to flush latently-infected cells out of their latency," Liang said.

Techniques developed to reactivate latent HIV-infected cells so that they become susceptible to the body's natural immune response or to drug therapies have had mixed results.

This is mostly because the technique, known as "shock and kill," relies on a class of drugs called HDAC inhibitors that come with severe adverse effects, researchers said.

"We need to better understand the mechanisms that regulate HIV latency so we can identify new opportunities for intervention and develop better drugs that can either lock viral particles in a latent state, or kill latent cells, or both," Liang said.

The Tat gene circuit has a random probability of being active or inactive, and the switch from inactive to active can happen spontaneously.

"In HIV-infected cells, reactivation of the Tat gene circuit is still a very rare event," Liang said.

The researchers developed advanced computational algorithms to study the Tat gene circuit under different conditions.

"Using different models and algorithms, we were able to accurately map a 'probability landscape' of the cellular reactions that can impact Tat gene circuit reactivation, and our results suggest new ways of targeting latent cells that may lead to the eradication of the HIV virus from a host," Liang said.

Researchers identified ways to manipulate the Tat gene circuit so that the "shock and kill" technique would be more effective.

They also looked at a "block and lock" strategy, where latent viral particles are locked into latency by permanently blocking activation of the Tat gene circuit.

"Our results suggest that by controlling HIV latency through manipulation of the Tat gene circuit, effective therapeutic strategies can be identified that would one day provide a cure for HIV," Liang said.

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Agencies
February 27,2020

Washington D.C, Feb 27: New research shows that adults who have low fruit and vegetable intake are more likely to be diagnosed with an anxiety disorder.

"For those who consumed less than 3 sources of fruits and vegetables daily, there was at least at 24% higher odds of anxiety disorder diagnosis," says the lead author of the Canadian Longitudinal Study, Karen Davison, who is a health science faculty member, nutrition informatics lab director at Kwantlen Polytechnic University, (KPU) and North American Primary Care Research Group Fellow.

"This may also partly explain the findings associated with body composition measures. As levels of total body fat increased beyond 36%, the likelihood of anxiety disorder was increased by more than 70%," states co-author Jose Mora-Almanza, a Mitacs Globalink intern who worked with the study at KPU.

"Increased body fat may be linked to greater inflammation. Emerging research suggests that some anxiety disorders can be linked to inflammation," says Davison.

In addition to diet and body composition measures, the prevalence of anxiety disorders also differed by gender, marital status, income, immigrant status and several health issues.

An important limitation of the study was that the assessment of anxiety disorders was mostly based upon self-reporting of a medical diagnosis.

"It is estimated that 10% of the global population will suffer from anxiety disorders which are a leading cause of disability," says Karen Davison

"Our findings suggest that comprehensive approaches that target health behaviours, including diet, as well as social factors, such as economic status, may help to minimize the burden of anxiety disorders among middle-aged and older adults, including immigrants," she concluded.

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Agencies
June 12,2020

Global poverty could rise to over one billion people due to the COVID-19 pandemic and more than half of the 395 million additional extreme poor would be located in South Asia, which would be the hardest-hit region in the world, according to a new report.

Researchers from King's College London and Australian National University published the new paper with the United Nations University World Institute for Development Economics Research (UNU-WIDER) said that poverty is likely to increase dramatically in middle-income developing countries and there could be a significant change in the distribution of global poverty.

The location of global poverty could shift back towards developing countries in South Asia and East Asia, the report said.

The paper, 'Precarity and the Pandemic: COVID-19 and Poverty Incidence, Intensity and Severity in Developing Countries,' finds that extreme poverty could rise to over one billion people globally as a result of the crisis.

The cost of the crisis in lost income could reach USD 500 million per day for the world's poorest people, and the intensity and severity of poverty are likely to be exacerbated dramatically.

The report said that based on the USD 1.90 a day poverty line and a 20 per cent contraction, more than half of the 395 million additional extreme poor would be located in South Asia, which would become the hardest hit region in the world mainly driven by the weight of populous India followed by sub-Saharan Africa which would comprise 30 per cent, or 119 million, of the additional poor.

The report added that as the value of the poverty line increases, a larger share of the additional poor will be concentrated in regions where the corresponding poverty line is more relevant given the average income level.

For instance, the regional distribution of the world's poor changes drastically when looking at the USD 5.50 a day poverty line the median poverty line among upper-middle-income countries.

At this level, almost 41 per cent of the additional half a billion poor under a 20 per cent contraction scenario would live in East Asia and the Pacific, chiefly China; a fourth would still reside in South Asia; and a combined 18 per cent would live in the Middle East and North Africa (MENA) and in Latin America and the Caribbean (LAC), whose individual shares are close to that recorded for sub-Saharan Africa.

India plays a significant role in driving the potential increases in global extreme poverty documented previously, comprising almost half the estimated additional poor regardless of the contraction scenario, the report said.

Nonetheless, there are other populous, low and lower-middle- income countries in South Asia, sub-Saharan Africa, and East Asia and the Pacific accounting for a sizeable share of the estimates: Nigeria, Ethiopia, Bangladesh, and Indonesia come next, in that order, concentrating a total of 18 19 per cent of the new poor, whereas the Democratic Republic of Congo, Tanzania, Pakistan, Kenya, Uganda, and the Philippines could jointly add 11 12 per cent.

Taken together, these figures imply that three quarters of the additional extreme poor globally could be living in just ten populous countries.

The report added that this high concentration of the additional extreme poor is staggering , although not necessarily unexpected given the size of each country's population.

On one hand, data shows that three of these ten countries (Ethiopia, India, and Nigeria) were among the top ten by number of extreme poor people in 1990 and remained within the ranks of that group until 2018.

Despite this crude fact, two of these countries have managed to achieve a sustained reduction in their incidence of poverty since the early 1990s, namely Ethiopia and India, reaching their lowest poverty headcount ratio ever recorded at about 22 and 13 per cent, respectively. Nonetheless, the potential contraction in per capita income/consumption imposed by the pandemic's economic effects could erase some of this progress.

The researchers are now calling for urgent global leadership from the G7, G20, and the multilateral system, and propose a three-point plan to address the impact of the COVID-19 on global poverty quickly.

Professor of International Development at King's College London and a Senior Non-Resident Research Fellow at UNU-WIDER Andy Sumner said the COVID-19 crisis could take extreme poverty back over one billion people because millions of people live just above poverty.

Millions of people live in a precarious position one shock away from poverty. And the current crisis could be that shock that pushes them into poverty.

Professor Kunal Sen, Director of UNU-WIDER said the new estimates about the level of poverty in the world and the cost of the COVID-19 pandemic to the world's poor are sobering.

We cannot stand by and see the hard work and effort of so many be eradicated. We will know what the real impact is in time, but the necessary action to ensure we achieve the Sustainable Development Goals by 2030 needs to be planned now, Sen said.

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Agencies
July 21,2020

New Delhi, Jul 21: The Centre has written to all states and union territories warning against the use of N-95 masks with valved respirators by people, saying these do not prevent the virus from spreading out and are "detrimental" to the measures adopted for its containment.

The Director General of Health Services (DGHS) in the Ministry of Health, in a letter to the Principal Secretaries of health and medical education of states, said it has been observed that there is "inappropriate use" of N-95 masks, particularly those with valved respirators, by the public other than designated health workers.

The DGHS referred to the advisory on the use of homemade protective cover for face and mouth available on the website of the Ministry of Health.

"It is to bring to your knowledge that the use of valved respirator N-95 masks is detrimental to the measures adopted for preventing the spread of coronavirus as it does not prevent the virus from escaping out of the mask. In view of the above, I request you to instruct all concerned to follow the use of face/mouth cover and prevent inappropriate use of N-95 masks," DGHS Rajiv Garg said in the letter.

The government had in April issued an advisory on the use of homemade protective cover for face and mouth, asking people to wear it, particularly when they step out of their residences.

The advisory stressed such face covers must be washed and cleaned each day, as instructed, and stated that any used cotton cloth can be used to make this face cover.

The colour of the fabric does not matter but one must ensure that the fabric is washed well in boiling water for five minutes and dried well before making the face cover. Adding salt to this water is recommended, it said.

It also listed the procedures of making such homemade masks, asking to ensure it fits the face well and there are no gaps on the sides.

It urges people to wash hands thoroughly before wearing the face cover, switching to another fresh one as the face cover becomes damp or humid, and never reusing it after single use without cleaning it.

"Never share the face cover with anyone. Every member in a family should have separate face cover," the advisory stated.

India's COVID-19 case tally crossed the 11-lakh mark on Monday, while the total number of recovered patients increased to over seven lakh, according to Union health ministry data.

The death toll due to the disease rose to 27,497 with 681 fatalities reported in one day.

The ministry data updated at 8 am on Monday showed that a record single-day jump of 40,425 COVID-19 cases had taken the total number of cases to 11,18,043.

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