Day: May 13, 2021

Bulimia Experience as a Teen Shaped Man’s Healthy Recipe Project

A UK man who started a project coming up with gut-healthy-recipes said that it was “shaped” by his having had bulimia in his teenage years.

Clinician and scientist Dr Sunni Patel, 35, said as a teen he thought he was “chubby” and experienced the eating disorder when he was aged 15 to 18.

Binge eating was his “solace” he said, and he used religious fasting “as a cover”.

Dr Patel started a website sharing recipes, and he urged people not to underestimate how gut health affects mental health.

“I’d find comfort and my escapism via food.”
Dr Sunni Patel

He said he would fast for four days a week, eating fruit at the end of the day.

Being from a traditional Asian background, the way “one looks and acts tends to be judged a lot more”, he said.

“Because I’d got bulimia as a get out, I’d binge eat. I might eat six or seven crisp packets at one sitting. I’d find comfort and my escapism via food.”

Suffering bullying at school, Dr Patel said that there was “pressure as a teenager to look cool”. He said that “the thinner I got, the more attractive I felt”. Bulimia became the “solution”, he added.

As he lost weight, he began receiving compliments which would “feed the beast”.

At least 1.5 million people in the UK have an eating disorder, experts estimate, with 25% being male. Bulimia nervosa is a condition that occurs most commonly in adolescent females, though it can appear in just about any patient. It is characterised by indulgence in binge-eating, and inappropriate compensatory behaviours to prevent weight gain.

Dr Patel said after he went to university he stopped, “I wasn’t able to find the safe space to have the… episodes, I didn’t want the truth to come out.”

From around the age of 24, he received cognitive behavioural therapy and in recent years has had psychotherapy.

“I was diagnosed with gut issues in 2014 and that’s when I started exploring the link between gut health and depression. As my diet became healthier so did my mind.”

A business director as well as a clinician, he now comes up with gut-healthy-recipes that are shared on his Dish Dash Deets website, set up during the COVID pandemic, where he also keeps a blog.

Included in his recipes are his top foods to combat depression and low mood, such as bananas, berries, beans and lentils.

He said to anyone that is in a similar position to his, “find a safe person to talk to”, who would not judge, adding: “Don’t feel any shame. You’re human.”

“The more that you rely on it, you use it as your way of escaping, the more it becomes your norm,” he said.

He also currently does live cook-alongs on Instagram with invited celebrities and chefs.

“Food is still my escapism. Now I enjoy being in the kitchen and making things that will serve my needs, not make things worse.”

Source: BBC News

Fat Cells Tapped for Spinal Fusion

Photo by cottonbro from Pexels

Researchers at Johns Hopkins Medicine have come up with a method that uses adipose cells, better known as fat, as a practical and plentiful source of stem cells for use in spinal fusion surgeries.

Spinal fusion ‘welds’ two or more vertebrae together so that they heal into a single, solid bone. Unfortunately, the surgery — using bone taken from other parts of the patient’s body — fails in up to a fifth of procedures. Stem cells, harvested from a patient’s marrow and allowed to mature into bone cells, can improve the outcome of spinal fusions. However, the aspiration method for getting stem cells out of the marrow carries an infection risk and often is painful.

In a study published in the journal Spine, researchers sought to try out adipose cells rather than bone marrow as a source for the stem cells.

Performing spinal fusion procedures in rats, the researchers found that freshly isolated stem cells from fat worked just as well as the more commonly used bone marrow stem cells. The researchers say this suggests the technique could be a candidate for human clinical trials.

“Bone marrow stem cells are isolated in human patients from the hip,” said Christina Holmes, PhD, a former Johns Hopkins Medicine postdoctoral fellow now at Florida State University. “But using a huge needle to take out bone marrow is a painful procedure, and we can only get a limited number of cells, so we’ve found an alternative source by using stem cells from fat.”

Alexander Perdomo-Pantoja, MD, a postdoctoral fellow at the Johns Hopkins University School of Medicine, said spinal fusion procedures are used to treat many different conditions.

“Spinal fusions are used for anything that causes spinal instability, which usually produces significant mechanical pain,” he says. “You see it frequently when we get older as the intervertebral discs, ligaments and muscles in the spine deteriorate. But these procedures can also be used to treat instability when it is caused by tumors, fractures, deformities or trauma.”

The researchers isolated stem cells from fat and bone marrow, and implanted them into rat spines. For the adipose-derived stem cells, the researchers used freshly isolated cells to see if they could speed up and simplify the procedure.

Stem cells are currently sourced either from bone marrow or fat and are often grown in a lab culture to mature them enough for spinal fusion. During culturing, there is a risk of contamination or transformation into unusable bone. Holmes said that freshly isolating cells avoids these problems, along with reducing labour and material costs.

While stem cells from fat are commonly used in cosmetic procedures, they are not often used in spinal fusions, she adds.

“We feel that fat cells are a logical alternative to bone marrow cells because most patients have an adequate supply of fat cells,” Tsaid imothy Witham, MD, director of the Johns Hopkins Neurosurgery Spinal Fusion Laboratory. ”Fat also is much more accessible during surgery and can be harvested with less stem cell death than bone marrow. Spinal fusion is a very common procedure, and we feel this approach could be applied across a wide cohort of spinal fusion patients.”

The researchers found significantly more bone formation and blood supply in the fresh adipose-derived stem cells compared with what they saw in previous studies with cultured cells from both fat and bone marrow.

The next step for Witham and his team is identifying which cells are the most advantageous for spinal fusions and then characterising them.

Source: John Hopkins University

Journal information: Alexander Perdomo-Pantoja et al. Comparison of Freshly Isolated Adipose Tissue-derived Stromal Vascular Fraction and Bone Marrow Cells in a Posterolateral Lumbar Spinal Fusion Model, Spine (2020). DOI: 10.1097/BRS.0000000000003709

Scientists Find How Enriched Environments Boost Brains

Image by Colin Behrens from Pixabay

A recent study in Frontiers in Molecular Neuroscience has shown how environmental enrichment ‘opens up’ chromosomes through the action of ‘master switches’.

Environmental enrichment, that is, making stimulating and interesting surroundings, is often used in zoos, laboratories, and farms to stimulate animals and increase their wellbeing.

Stimulating environments are better for mental health and cognition because they boost the growth and function of neurons and their connections, the glia cells that support and feed neurons, and blood vessels within the brain. But what are the deeper molecular mechanisms that first set in motion these large changes in neurophysiology? 

The study investigators utilised a large molecular toolbox to map how environmental enrichment leads to changes in the 3D organisation of chromosomes in neurons and glia cells of the mouse brain, which change the activation of some genes within the genome. 

They show that genes which in humans are important for cognitive mental health are particularly affected, possibly leading to new treatments.

Chromosome ‘opens up’ with enrichment

“Here we show for the first time, with large-scale data from many state-of-the-art methods, that young adolescent mice that grew up in an extra stimulating environment have highly specific ‘epigenetic’ changes—that is, molecular changes other than in DNA sequence—to the chromosomes within the cells of the brain cortex,” said corresponding author Dr Sergio Espeso-Gil from the Centre for Genomic Regulation in Barcelona, Spain.

He continued, “These increase the local ‘openness’ and ‘loopiness’ of the chromosomes, especially around DNA stretches called enhancers and insulators, which then fine-tune more ‘downstream’ genes. This happens not only in neurons but also in the supportive glia cells, too often ignored in studies about learning.”

The team raised mice for the first month after birth in social groups inside housing with Lego blocks, ladders, balls, and tunnels that were frequently changed and moved around. As a control, other mice were raised in smaller groups inside standard housing. The researchers then used a variety of tools to pick up molecular changes in neurons and glia cells within the brain cortex. These included alterations in the 3D structure of chromosomes, particularly the local “chromatin accessibility” (openness) and “chromatin interactions” (where distant genes are brought together through loops, to coordinate activity). Chromatins are the proteins which make up chromosomes, carrying DNA and the proteins to package them.

Epigenetic ‘master’ switches

They show that two ‘master’ switches operational after environmental enrichment increase chromatin interactions and another increases chromatin availability, important for the pyramidal neurons involved in cognition. A third works on a key chromosomal protein histone H3, activating nearby genes as a result.

These switches mainly occur around genomic regions that contain enhancers, regulatory DNA that (when bound to proteins called transcription factors) can activate neighboring genes. Also affected were genomic regions with insulators, regulatory DNA that can override the gene-activating effect of neighboring enhancers.

The team concluded that growing up in an enriched environment causes highly local and specific epigenetic changes in neurons and glia cells. These then mostly increase the activity of a few genes within the genome.

Mental health in humans

“Our results show that many of the genes involved are known to play a role in the growth and differentiation of neurons, the development of blood vessels, the formation and patterning of new synaptic connections on neurons, and molecular pathways implicated in memory and learning in mice,” said Dr Espeso-Gil.

“And when we look for parallel regions in the human genome, we find many regions that are statistically associated with differences in complex traits such as insomnia, schizophrenia, and Alzheimer’s in humans, which means that our study could inform future research on these disorders. This points to the potential of environmental enrichment in therapies for mental health. Our research could also help to guide future research on chromatin interactions and the poorly known importance of glial cells for cognitive mental health.”

Source: Medical Xpress

Journal information: Sergio Espeso-Gil et al, Environmental Enrichment Induces Epigenomic and Genome Organization Changes Relevant for Cognition, Frontiers in Molecular Neuroscience (2021). DOI: 10.3389/fnmol.2021.664912

New Antimalarial Compound Traps Parasites in Cells

Photo by Егор Камелев on Unsplash

To combat the growing resistance of malaria to current treatments, researchers at the Francis Crick Institute and the Latvian Institute of Organic Synthesis have designed a new antimalarial compound which interrupts the malaria parasite life cycle by trapping them in their host cells.

While drugs and mosquito control have reduced levels of malaria over recent decades, with malaria being effectively wiped out in North America by the 1950s, the parasite still kills over 400 000 people every year, 90% of whom live in sub-Saharan Africa. It has now developed resistance to many existing antimalarial drugs, meaning new treatments that work in different ways are urgently needed.

If we can effectively trap malaria in the cell by blocking the parasite’s exit route, we could stop the disease in its tracks and halt its devastating cycle of invading cells.
Mike Blackman

The researchers developed an array of compounds designed to prevent the parasites bursting out of blood cells, a vital replication step. One compound in particular was found to be very effective in human cell tests.

“Malaria parasites invade red blood cells where they replicate many times, before bursting out into the bloodstream to repeat the process. It’s this cycle and build-up of infected red blood cells which causes the symptoms and sometimes fatal effects of the disease,” says Mike Blackman, lead author and group leader of the Malaria Biochemistry Laboratory at the Crick.  

“If we can effectively trap malaria in the cell by blocking the parasite’s exit route, we could stop the disease in its tracks and halt its devastating cycle of invading cells.”

Blocking the parasite’s emergence

The compound works by blocking an enzyme called SUB1, needed for them to burst out of cells. Current antimalarials kill the parasite within the cell, so the researchers hope this alternative drug action will overcome the resistance the parasite has acquired.

The compound can penetrate both the cell wall and the compartment within where the parasites reside.

The researchers are further refining the compound making it smaller and more potent. Further tests are needed before it can be trialled in humans.

Study author Chrislaine Withers-Martinez and researcher in the Malaria Biochemistry Laboratory, said: “Many existing antimalarial drugs are plant derived and while they’re incredibly effective, we don’t know the precise mechanisms behind how they work. Our decades of research have helped us identify and understand pathways crucial to the malaria life cycle allowing us to rationally design new drug compounds based on the structure and mechanism of critical enzymes like SUB1.

“This approach, which has already been highly successful at finding new treatments for diseases including HIV and Hepatitis C, could be key to sustained and effective malaria control for many years to come.” 

Source: Francis Crick Institute

Immune Cells Respond to Threats with Six ‘Words’

Scanning electron microscope of a dead yeast cell being engulfed by a macrophage. Credit: National Institute of Allergy and Infectious Diseases (NIAID)

A new study has identified six ‘words’ that certain immune cells use to turn on defence genes, an important step towards discovering how the immune system coordinates itself to handle threats.

In addition, they discovered that using two of these words incorrectly can activate the wrong genes, resulting in the autoimmune disease known as Sjögren’s syndrome.

“Cells have evolved an immune response code, or language,” said senior author Alexander Hoffmann, a professor at UCLA. “We have identified some words in that language, and we know these words are important because of what happens when they are misused. Now we need to understand the meaning of the words, and we are making rapid progress. It’s as exciting as when archeologists discovered the Rosetta stone and could begin to read Egyptian hieroglyphs.”

Listening in on macrophages

Immune cells constantly assess their external environment, and communicate with signalling codons (‘words’) to tell the nucleus which genes to turn on in response to invading pathogens. These codons consist of a sequence of actions by a DNA binding protein that produces a word, like typing letters in sequence on a keyboard.

The researchers focused on words used by macrophages, which clear up harmful substances, pathogens and dead cells. ‘Listening’ to macrophages in healthy mice, they identified six specific codon-words that correlated to immune threats. They repeated this with mice that contained a mutation akin to Sjögren’s syndrome in humans to see if this disease is caused by the defective use of these words.

“Indeed, we found defects in the use of two of these words,” Prof Hoffmann said. “It’s as if instead of saying, ‘Respond to attacker down the street,’ the cells are incorrectly saying, ‘Respond to attacker in the house.'”

According to the researchers, the findings suggest that Sjögren’s doesn’t result from chronic inflammation as it has been thought to, but rather from a codon-word confusion that leads the body to attack itself. New treatments could focus on correcting the miscommunication.

Cracking the code

According to Prof Hoffman, the reason immune cells can mount a specific response to each pathogen is due to ‘signalling pathways’. These link receptor molecules on the immune cells with different defence genes. The transcription factor NFκB is one such pathway, acting as a central regulator of immune cell responses to pathogen threats.

“The macrophage is capable of responding to different types of pathogens and mounting different kinds of defences. The defence units—army, navy, air force, special operations—are mediated by groups of genes,” he said. “For each immune threat, the right groups of genes must be mobilised. That requires precise and reliable communication with those units about the nature of the threat. NFκB dynamics provide the communication code. We identified the words in this code, but we don’t yet fully understand how each defense unit interprets the various combinations of the codon-words.”

Calling up the wrong units can not only be ineffective but destructive as in Sjögren’s.

To crack the language, researchers studied how 12 000 cells communicated in response to 27 immune threat conditions. Based on possible arrangements of NFκB dynamics, they drew up a list of over 900 possible ‘words’, resembling three-letter words.

Then, using a telecommunications industry algorithm developed in the 1940s, they monitored the rate at which each of the potential words came up when macrophages responded to threats. They discovered that six specific dynamical features, or ‘words,’ were most frequently correlated with that response.

This would be like listening to a conversation and finding that certain three-letter words tend to be used, such as “the,” “boy,” “toy,” and “get,” but not “biy” or “bey,” explained lead author Adewunmi Adelaja, who earned his PhD in Hoffmann’s laboratory and is now pursuing his MD at UCLA.

The researchers found that teaching a machine learning algorithm the six words, it was able to recognise the stimulus when simulated cells were ‘talking’. They then explored what would happen if the computer only had five words available. They found that the algorithm made more errors in recognising the stimulus, which led the team to conclude that all six words are required for reliable cellular communication.

The scientists also used calculus to study the biochemical molecular interactions inside the immune cells that produce the words.

Source: UCLA

Journal information: Adewunmi Adelaja et al. Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses, Immunity (2021). DOI: 10.1016/j.immuni.2021.04.011

SA on The Brink of Third Wave, Says Health Department

COVID heat map. Photo by Giacomo Carra on Unsplash

The health department called the increasing number of COVID cases across South Africa “worrying” on Wednesday night, adding that although close, the requirements had not yet been met for a third wave.

In a statement, the department said that it had observed an increase in the weekly number of new cases over the past seven and 14 days compared to the previous corresponding periods. Increases have been seen in all provinces — particularly the North West and Gauteng. There was also an increase in the number of COVID-related deaths over the past seven days.

However the department maintained that these increases had not yet met the requirements of the “resurgence threshold”. Dr Zweli Mkhize however said that numbers would not go down unless containment measures were put in place.

“There was an increase in new cases from 8593 cases in the preceding seven days (April 26-May 2) to 12 531 cases in the past seven days (May 3-9), constituting a 46% increase. The 14-day comparisons also showed that the cases increased from 17 017 in the preceding 14 days to 21 124 cases in the past 14 days, an overall 24% increase. All provinces showed a positive percentage increase, with Northern Cape 68% up in the past seven  days followed by Gauteng at 63%, Limpopo at 47%, North West at 42% and Western Cape at 39%.

“The new Covid-19 related deaths increased by 18.22% in the past seven days (May 3-9) to 318 from 269 in the preceding seven days (April 26-May 2). However, the 14-day comparison showed the deaths decreased by 28.93% to 587 in the past 14 days compared to 826 in the preceding 14 days. The cumulative case fatality ratio is 3.43% (54 735 of 1 596 595),” the department said.

Hospital admissions fortunately “have not shown an increase”. As of Wednesday, the detection rate for COVID tests was 7.45%. Adam Lowe, a member of the ASSA COVID working group, said that based on modelling and historical parallels, three scenarios are possible for a third wave: an early, less severe, wave in May driven by school holidays; a later, more severe third wave; or a sudden and severe, but unlikely, third wave.

“As much as these figures are worrying, our resurgence dashboard, which was developed by the South African Covid-19 Modelling Consortium, which is updated thrice a week, still shows that we have not as a country reached a resurgence threshold, though some districts in the country are fast approaching the threshold,” the department said.

The department of health added that it was working with provinces to update their resurgence plans, which mainly focus on case management, contract tracing, oxygen availability, bed capacity, respiratory support equipment and human resources.

It also said that the main drivers of the new wave will be one or both of the resurgence of new variants and growing fatigue to measures such as social distancing and masking. Genomic surveillance is being conducted to catch the emergence of new variants.

“So we want to assure South Africans that we have not yet hit the third wave, however we are at risk and we hence need to be on heightened vigilance,” the department said.

Source: Times Live