Clinical Trial

Scientists Have Identified Four Distinct Types of Alzheimer’s And What They Do to Us

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The more we understand about Alzheimer’s, the faster we can work towards better treatments and ultimately a cure, which makes discovering four distinct subtypes of the brain disease an important one.

Using machine learning algorithms trained at brain scans of 1,143 people either with healthy brains or brains affected by Alzheimer’s, scientists have identified four distinct ways tau proteins get tangled up among neurons.

Misshapen tau proteins are closely linked to the development and progression of Alzheimer’s, but it was thought that the pattern of tau entanglement in the brain was more or less the same in everyone with the disease.

“We identified four clear patterns of tau pathology that became distinct over time,” says neurologist Oskar Hansson from Lund University in Sweden.

“The prevalence of the subgroups varied between 18 and 30 percent, which means that all these variants of Alzheimer’s are actually quite common and no single one dominates as we previously thought.”

alz 2Images of the four variants. (Jacob Vogel)

The first variant, discovered in 33 percent of cases, sees tau spreading mainly within the temporal lobe and affecting patient memory. The second, found 18 percent of the time, spreads across the other parts of the cerebral cortex – memory problems are less common, but difficulties in planning and performing actions are more common.

The third variant, found in 30 percent of all cases, is where tau spreads in the visual cortex (used for processing sight) – patients have trouble orienting themselves, judging distance, and identifying shapes. The fourth and final variant, seen in 19 percent of cases, spreads asymmetrically in the brain’s left hemisphere and affects language processing.

The discoveries were made possible by detailed, 3D Positron Emission Tomography (PET) scans. Follow-up analysis over two years confirmed the presence of these four distinct patterns in people with Alzheimer’s, and it could help explain why different people show different symptoms as the disease progresses.

“This would suggest that Alzheimer’s is an even more heterogeneous disease than previously thought,” says neuroscientist Jacob Vogel from McGill University in Canada.

“We now have reason to reevaluate the concept of typical Alzheimer’s, and in the long run also the methods we use to assess the progression of the disease.”

Alzheimer’s is already the leading form of dementia worldwide, and the number of affected people continues to rise sharply as populations age. We know that it causes a steady loss of neurons, but it’s still not clear exactly why that happens – and as yet, there’s no known cure.

Progress is being made, though. Previous studies have also looked at splitting Alzheimer’s up until subtypes to give us a better understanding of the disease, while we’re also learning more about neurons vulnerable to Alzheimer’s, and how its effects might be reversed.

The next step is to extend the analysis across a longer time period – up to 10 years, suggest the researchers. Knowing which subtype is present in a patient could, for example, give them a better idea of which symptoms to expect and when, as well as opening up options for new treatments.

“This knowledge is important for doctors who assess patients with Alzheimer’s, and it also makes us wonder whether the four subtypes might respond differently to different treatments,” says Hansson.

The research has been published in Nature Medicine.

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CCMB study reveals N440K variant of cornavirus 10 times more infectious than others

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Revealing their latest research findings, scientists from the Centre for Cellular and Molecular Biology (CCMB) have found that the N440K mutant variant of Covid-19 virus is 10 times more infectious compared to the other prevailing viruses in India.

According to the scientists, the N440K variant Covid virus is mainly witnessed in southern states of Telangana, Andhra Pradesh, Karnataka, parts of Maharashtra and Chhattisgarh, and is the major cause of widespread corona infections in the region.

Explaining about the high spreading characteristics of the Covid-19 virus, Dr. Rakesh Mishra, director of CCMB said that the ability of N440k mutant variant to generate large amounts of infectious virus articles within a short time period is very high.

Not only that, but these particles also have the ability to spread rapidly across the population and causing large number of people getting infected with the deadly disease. “Unlike in the first wave, where the Covid variants of B1.617 and B1.618 were prevailing and did not show very high rate of infections, however the current prevailing variant of N440k Covid virus is found to be generating 10 times more number of virus particles compared to the previous once. The main reason for high rate of infections during the second wave can be attributed to N440k variant as this virus is having an edge over the other mutant variants prevailing currently in the country,” observed the CCMB director.

The CCMB geneticists also explained that 50 per cent samples they collected from various centers have found to be having the N440K variant of virus. It is also revealed that this virus is spreading among a certain section of population and it is more localized compared to other variants.

For instance, this virus variant is more found to be spreading in Telangana, parts of Maharashtra, Chhattisgarh and Karnataka. The rapid surge of Covid-19 cases in Telangana during the past one month is also attributed to this variant of Covid strain. During the second wave, Telangana state has witnessed more than 100 per cent surge of Covid cases. The number of active cases which were about 6,159 in the beginning of April, had jumped to about 80,000 cases in just one month until 1st May.

“The N440k mutant variant has the ability to generate 10 times more virus articles than the A2a prototype strain which is in circulation worldwide. This ability to generate large amounts of infectious virus articles in a short time makes N440K variant distinctive compared to other prevailing viruses,” revealed study by the CCMB scientists.

Revealing their latest research findings, scientists from the Centre for Cellular and Molecular Biology (CCMB) have found that the N440K mutant variant of Covid-19 virus is 10 times more infectious compared to the other prevailing viruses in India.

According to the scientists, the N440K variant Covid virus is mainly witnessed in southern states of Telangana, Andhra Pradesh, Karnataka, parts of Maharashtra and Chhattisgarh, and is the major cause of widespread corona infections in the region.

Explaining about the high spreading characteristics of the Covid-19 virus, Dr. Rakesh Mishra, director of CCMB said that the ability of N440k mutant variant to generate large amounts of infectious virus articles within a short time period is very high.

Not only that, but these particles also have the ability to spread rapidly across the population and causing large number of people getting infected with the deadly disease. “Unlike in the first wave, where the Covid variants of B1.617 and B1.618 were prevailing and did not show very high rate of infections, however the current prevailing variant of N440k Covid virus is found to be generating 10 times more number of virus particles compared to the previous once. The main reason for high rate of infections during the second wave can be attributed to N440k variant as this virus is having an edge over the other mutant variants prevailing currently in the country,” observed the CCMB director.

The CCMB geneticists also explained that 50 per cent samples they collected from various centers have found to be having the N440K variant of virus. It is also revealed that this virus is spreading among a certain section of population and it is more localized compared to other variants.

For instance, this virus variant is more found to be spreading in Telangana, parts of Maharashtra, Chhattisgarh and Karnataka. The rapid surge of Covid-19 cases in Telangana during the past one month is also attributed to this variant of Covid strain. During the second wave, Telangana state has witnessed more than 100 per cent surge of Covid cases. The number of active cases which were about 6,159 in the beginning of April, had jumped to about 80,000 cases in just one month until 1st May.

“The N440k mutant variant has the ability to generate 10 times more virus articles than the A2a prototype strain which is in circulation worldwide. This ability to generate large amounts of infectious virus articles in a short time makes N440K variant distinctive compared to other prevailing viruses,” revealed study by the CCMB scientists.

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Is COVID-19 Here to Stay For Good? Here’s What Experts Think

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Now, over a year since the World Health Organization (WHO) announced the beginning of the COVID-19 pandemic, we are starting to look forward to a reduced spread of the virus. With the rollout of several effective vaccines and the enforcement of safety measures such as travel bans and quarantine, coronavirus cases are reducing in some parts of the world.

Will it be possible to eliminate COVID-19 at some point in the future, or will it always remain endemic in some regions? We asked eight experts in epidemiology whether COVID-19 will become endemic – 75 percent said ‘yes’.

What does endemic mean?

Endemic “means that there are always people who are infected, who pass infection to somebody else and then recover. Over a long time, each person infects on average one other person, so that the number infected remains approximately the same,” says Professor Graham Medley, an expert in disease modeling from the London School of Hygiene and Tropical Medicine.

This is very different from the high level of transmission we have seen during the pandemic.

Many common diseases are endemic, including the coronaviruses that cause colds. Prof Medley says, “Endemic infections are usually in children causing mild symptoms. Endemic coronaviruses are not associated with significant disease. By the time children are adults they will have been exposed, and potentially infected, many times, and are immune.”

How have previous pandemics ended?

Professor James Wood, an expert in disease modeling and epidemiology from the University of New South Wales (UNSW) Sydney, says, “When pH1N12009 (swine flu) emerged in 2009, it became endemic within a year of the initial pandemic and also pushed the existing H1N1 influenza strain circulating in humans to extinction.”

Many viruses that were responsible for previous pandemics, including the 1918 flu pandemic, are still circulating today.

Completely eradicating a disease is not easy. To date, the WHO has only declared two diseases that have been eradicated worldwide: smallpox and rinderpest. Both required a large, worldwide vaccine campaign to reach herd immunity.

The two options for how a pandemic can end: either the virus is eradicated, or it becomes endemic.

Could we eradicate COVID-19 using the new vaccines?

Smallpox and rinderpest were eradicated using vaccines; now that several COVID-19 vaccines exist, could we use them to wipe out this disease?

Dr Lee Riley from UC Berkeley highlights one key obstacle to eliminating COVID – the responsible virus could mutate to become resistant to the vaccines.

He says that “in places where there is a mixture of vaccinated and unvaccinated populations, the vaccines may exert selective pressures on the virus to undergo further mutations, and these variants will spread among the unvaccinated people. Some of the variants may also infect vaccinated people”.

Another difficulty in reaching herd immunity is that some of the currently available vaccines do not offer 100 percent immunity against getting COVID-19.

Professor Jane Heffernan, an expert in epidemiology from York University, says, “COVID-19 infection and vaccination can induce high levels of protective immunity in individuals. The immunity gained can protect against infection, or, if infected, will lessen the severity of disease”.

There is also the challenge of vaccinating so many people across so many countries.

Professor Wood from UNSW, highlights that “the limitations in our ability to produce vaccine (15-20 million doses per day) mean that high global coverage with 2 doses will take well over a year even with relatively equitable supply of vaccines”.

Dr David Hayman from Massey University adds that “there is enormous inequality in vaccine distribution, with just a few percent of the world currently vaccinated. This means that unless this is resolved the virus will likely become endemic in those countries.”

Despite these challenges, it could still be theoretically possible to vaccinate enough of the world’s population to reach herd immunity and eradicate COVID-19.

Interestingly, however, Professor Wood points out that “elimination and eradication may not remain as priorities if residual protection from vaccines against severe disease remains strong”.

If we can protect people from becoming severely ill with COVID-19, there may be no reason to eradicate it completely.

The takeaway

Whilst public health measures and vaccine campaigns will hopefully end the current COVID-19 pandemic, it is likely that it will remain endemic in some countries rather than being totally eradicated.

Article based on 8 expert answers to this question: Will COVID-19 become endemic?

This expert response was published in partnership with independent fact-checking platform Metafact.io. Subscribe to their weekly newsletter here.

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Ayush researchers find Ayush 64 useful for treating mild and moderate Covid-19 infection

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The scientists of Ayurevda research institutions in the country have found that Ayush 64, a poly herbal formulation developed by the Central Council for Research in Ayurvedic Sciences (CCRAS), under the Union Ministry of Ayush is useful in the treatment of asymptomatic, mild and moderate Covid-19 infection as an adjunct to standard care. Initially the drug was developed for malaria in the year 1980 and now is repurposed for Covid-19.

The Union Ministry of Ayush-Council of Scientific and Industrial Research (CSIR) collaboration has recently completed a robust multi-centre clinical trial to evaluate the safety and efficacy of Ayush 64 in the management of mild to moderate Covid-19 patients.

Ayush 64 comprises of Alstonia scholaris (aqueous bark extract), Picrorhiza kurroa (aqueous rhizome extract), Swertia chirata (aqueous extract of whole plant) and Caesalpinia crista (fine-powdered seed pulp). It is extensively studied, scientifically developed, safe and effective ayurveda formulation. This medicine is also recommended in National clinical management protocol based on Ayurveda and Yoga which is vetted by National taskforce on Covid-19 management of Indian Council of Medical Research (ICMR).

Dr N Srikanth, director general, CCRAS elaborated that additional studies on Ayush 64 are underway at reputed research institutes including CSIR-Indian Institute of Integrative Medicine (IIIM), Department of Biotechnology- Translational Health Science and Technology Institute (DBT-THSTI), ICMR-National Institute of Nutrition (NIN), All India Institute of Medical Science (AIIMS) Jodhpur and Medical Colleges including Post Graduate Institute of Medical Education & Research, Chandigarh; King George’s Medical University, Lucknow; Government Medical College, Nagpur; Datta Meghe Institute of Medical Sciences, Nagpur.

He further stated that results received so far have shown the usefulness of Ayush 64 in dealing with mild and moderate Covid-19. He also added that the outcome of the seven clinical studies has revealed that Ayush 64 exhibits early clinical recovery in Covid-19 cases without further progression. In all clinical studies, Ayush 64 was found to be well tolerated and found clinically safe.

Dr Arvind Chopra, director, Centre for Rheumatic Diseases, Pune and chief clinical coordinator of Ayush–CSIR collaboration stated that Ayush 64 as an adjunct to standard of care (SoC) showed significant improvement and thus lesser period of hospitalization as compared SoC alone. He concluded that this controlled drug trial study has provided substantial evidence that Ayush 64 can be effectively and safely used to treat mild to moderate cases of Covid-19 as adjuvant to SoC.

Dr V M Katoch, chairman of the joint monitoring committee, informed that the committee has carefully reviewed the outcome of Ayush 64 study and recommended Ayush 64 in the management of asymptomatic, mild to moderate Covid-19. It is worthwhile to note that this committee has also recommended Ministry to communicate to the state licensing authorities/regulators regarding adding new indication of Ayush 64 for repurposing in the management of mild to moderate Covid-19.

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There’s One Really Unhealthy Effect of Cold Offices, According to Science

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With millions of Americans vaccinated against COVID-19, many who have worked from home over the past year will be heading back into the office. Adjusting to new routines is challenging and can affect our health and fitness. We’ve been more sedentary or more active, gained weight or dropped pounds.

As part of my work as a biomedical engineer, I study how physical factors influence human metabolism. This includes height and weight, gravity – and air temperature.

My research colleagues and I have found that living or working in a cool environment for extended periods can lower core body temperature. That decreases metabolic rate – how fast we burn calories – and commonly causes weight gain.

Maintaining core body temperature

Humans are homeotherms – that is, we maintain a relatively constant core body temperature. Specifically, we keep our body temperature in the range of 97 °F to 101 °F (36 to 38 °C) even in cool environments. Three different types of metabolic activity keep our body warm.

The first is basal metabolism. About two-thirds of the calories we burn each day fuel basic bodily functions, all of which generate heat: breathing, blood circulation, cell growth, brain function and food digestion. Any kind of physical movement also generates heat through chemical reactions that make muscles contract.

A third heat-generating process happens within specialized tissue called “brown fat.” It’s a leftover evolutionary adaptation that kept us from freezing during the ice ages. It kicks in when our core temperature drops to very low levels, but most people lose their brown fat as they age. https://8ce752daf8e692d9b5cf9eab787f9cda.safeframe.googlesyndication.com/safeframe/1-0-38/html/container.html

With increasing body temperature, our metabolic rate rises and we burn more calories. This generates more heat and further raises our body temperature, creating a positive feedback process which usually keeps our body temperature in the healthy range.

But this process is remarkably sensitive to temperature. For every 1-degree drop in body temperature, our metabolic rate can decrease by more than 7 percent. This means that the resting metabolic rate for someone at a body temperature of 101 °F (38.3 °C, the high end of normal) is up to 30 percent higher than if their temperature were 97 °F (36.1 °C, the low end).

Increasing body temperature by four degrees can burn more calories during the course of the day than the average person burns as a result of all of their daily physical activity.

body temp graph(Schwetana Sunkari/Author provided)

Above: Working in a chilly office lowers core body temperature, pushing body temperature below the normal range, as shown in this chart plotting women’s body temperature and age for a typically cooled office at 70 °F.

Body temperature versus physical exercise

This is why changing your physical environment can substantially alter the way your body works – and impacts both health and fitness. If you’re gaining weight and aren’t sure why, check the thermostat where you live or work.

Most offices tend to be kept near 70 °F (21.1 °C). That’s why so many of your co-workers are complaining of being cold, wearing sweaters or jackets, or using a space heater. This tends to be too cold for most women – and many men – who sit at a desk all day. But it’s more than uncomfortable; it’s not healthy.

The “correct” room temperature is where you are comfortable: not too hot, not too cold. That’s generally between 72 and 81 °F (22.2 and 27.2 °C) at moderate humidity, but may range as low as 65 or up to 85 °F (18.3 °C to 29.4 °C).

Working in a cold office slows your metabolism. In addition to making weight management challenging, sluggish metabolic rates are linked to lowered immune response, heart damage and increased risk of developing Type 2 diabetes.

If you don’t have control over the thermostat, you still have a few options besides wearing a coat all day.

New technologies include a wearable personal device which changes your perception of warmth and cold; a passive exercise device that increases your metabolic rate by increasing cardiac output (I have an equity stake in this company); and a “smart” version of the traditional space heater. However you achieve it, do your best to stay comfortably warm in your future workplace.

Kenneth McLeod, Professor of Systems Science and Director, Clinical Science and Engineering Research Laboratory, Binghamton University, State University of New York.

This article is republished from The Conversation under a Creative Commons license. Read the original article. 

Editor’s note (1 May 2020): This article was updated to indicate the author has an equity stake in Sonostics, one of the companies linked to in the article.

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