Author Archives: Sci Club

It is always said that the “health is wealth”. But have you ever, thought what if that wealth turned out to be Brutus to your mental health Caesar. Yes!!!! You may be astonished on hearing this, but this how hypochondria or health anxiety feels like. The hypochondria or health anxiety is a mental condition which is categorized under obsessive compulsive disorder (OCD) yeah!!! You heard it right!!! Come on, OCD is not just washing hands it is lot more pain than repeated hand washing. The person who has hypochondria is often obsessed with intrusive thoughts of concerns about their health and constantly thinks about infections, heart attacks, organ failure without any rational cause.

We had interviewed a victim who has been bashed hardly by this monster hypochondria. The victim’s name was kept secret for his privacy. Victim words “That day, I remember it was May 8, 2018, I had to encounter with a person with mouth sore. I accidentally got physical touch on it, there started my evil nightmare. From next day, it started to feel like some infection has entered into my body. I started to repeatedly check for symptoms like fever, pulse rate, lesions etc., day by day I started doubting myself whether I’m missing something which is internally eating me badly. Then I started to take several tests to check infections such as HIV/AIDS, Herpes, Syphilis, Hepatitis etc., all turned out negative. Still, I had intrusive thoughts like what if the test missed something, what if the testing center is fake blah blah … again I started testing for time being after testing it feels good after that it starts again…. Finally, I got into severe depression, had repeated anxiety attacks with additionally my partner also broke with me. I reached to such an extent that I felt like why I’m I even living, I started to think of killing myself…my weight got reduced abruptly, I had very less to zero hunger, severe dizziness, no happiness finally one day by my God’s grace I was admitted for dizziness in a neurology care. In the hospital, they just took my brain MRI and CT, reports reviewed and I was found  all fine. Then, the turning point came as blessings when the doctor found that… I’m not laughing, but continued to be depressed and anxious about my health. The doctor then… sent me for Psychological assessment where they found that I was having severe health anxiety or health OCD and the symptoms are all the consequences of the anxiety. Still I’m on anti-depressants and SSRIs now I learnt how to control my anxiety and health related thoughts…” It may sound like the person is exaggerating but in reality, he lost his admission in the prestigious National Institute of Technology (NIT), spent more than a 1 lakh for treatment and still he is relying on his pills. This makes sense that mental health and inclusive support from the loved ones is very crucial in determining the quality of life. Often, Yoga and holistic health practices can be of great help for such people/patients.

Symptoms: Symptoms of illness anxiety disorder involve preoccupation with the idea that you're seriously ill, based on normal body sensations (such as a noisy stomach) or minor signs (such as a minor rash). Signs and symptoms may include:

• Being preoccupied with having or getting a serious disease or health condition





• Worrying that minor symptoms or body sensations mean you have a serious illness





• Being easily alarmed about your health status





• Finding little or no reassurance from doctor visits or negative test results





• Worrying excessively about a specific medical condition or your risk of developing a medical condition because it runs in your family





• Having so much distress about possible illnesses that it's hard for you to function





• Repeatedly checking your body for signs of illness or disease





• Frequently making medical appointments for reassurance — or avoiding medical care for fear of being diagnosed with a serious illness





• Avoiding people, places or activities for fear of health risks





• Constantly talking about your health and possible illnesses





• Frequently searching the internet for causes of symptoms or possible illnesses
  
  
  

Treatment options:

The disorder can be very difficult to treat. This is due, in part, to the fact that people who have it refuse to believe their symptoms and distress are the result of mental or emotional rather than physical causes.

Treatment for somatic symptom disorder most often includes a combination of the following options:

• Supportive care: In most cases, the best course of action is for the person to stay in regular contact with a trusted health care provider. Within this doctor-patient relationship, the doctor can monitor the symptoms and stay alert to any changes that might signal a real medical illness. The doctor's main approach is likely to focus on reassuring and supporting the person, and preventing unnecessary tests and treatments. It might be necessary, however, to treat some of the symptoms, such as severe pain.





• Medications: Antidepressant or anti-anxiety drugs are sometimes used if a person with somatic symptom disorder also has a mood disorder or anxiety disorder.





• Psychotherapy: Psychotherapy (a type of counselling), particularly cognitive therapy, can be helpful in changing the thinking pattern and behaviour that contribute to the symptoms. Therapy also can help the person learn better ways to deal with stress, and improve their social and work functioning. Unfortunately, most people with somatic symptom disorder deny there are any mental or emotional problems, making them fairly resistant to psychotherapy.





• Alternative medicines and holistic health practices: Ayurvedic health formulations and homeopathic potencies can also help to ease this disorder. Moreover, consuming organic foods, probiotics, avoiding oily, junk and canned foods can also help in proper functioning of gut thereby influencing the brain. “Gut-brain” connection has been well established and hence, gut can always be kept at best of its condition.   Finally, Yoga and meditation as holistic health practices, can be of great help to unlearn the health anxiety and associated stress.

This blog has been written by Pavan who is an ICMR-Senior Research Fellow/PhD student working in the Yenepoya Research Centre. Pavan works on nanotechnology based targeted drug delivery for cancer therapeutics. Pawan can be reached at srpavan1997@gmail.com

This blog has been edited by Dr Bipasha Bose, Associate Professor, Stage II (Senior), Stem Cells and Regenerative Medicine Centre, Yenepoya (Deemed to be University), Mangalore-575018, Karnataka, India. Dr Bipasha Bose can be reached at Bipasha.bose@yenepoya.edu.in

Well, nobody is keen on seeing a doctor. So, every morning, I wish myself and all my near-dear ones and colleagues the best of their health because I do not want them to see a doctor. Indeed, we all grew up with this common 19^th-century proverb, “An apple……………away”. Being a kid, I always pondered, is it true? Now, here I am to profess the same because an apple can reduce low-grade inflammation in people.

In the current times of McDonald’s, Pizza Hut, Burger King and joints like that, the younger population is much more inclined to such kinds of high-fat foods. Besides, processed and high sugary foods and beverages are also in vogue. The increased consumption of high-fat, ready to eat foods/drinks is culture, mindset, taste, and peer-group motivation. Lack of exercise, a sedentary lifestyle, mainly due to mobile phone addictions, and laziness in cooking fresh food are also the reasons. As a result, most of the city-dwelling populations in the world are becoming obese. What happens to the physiology of such obese people? Yes, low-grade chronic inflammation leads to various metabolic disorders such as type II diabetes, cardiovascular diseases (CVD), cancer and so on. Hence, the solution to curb such metabolic disorders is to reduce low-grade chronic inflammation. The critical protein responsible for low-grade inflammation is the C-reactive protein (Trumann et al., 2022).

An Apple can reduce C-reactive protein in people

Apples are rich in anti-inflammatory bioactives with polyphenols and fibre. In overweight and obese conditions, the circulating inflammatory biomarker C-reactive protein (CRP) is increased. Epidemiological data revealed that plant-based foods reduce CVD risk. Regular consumption of whole apples in individuals reportedly reduced the levels of CRP ≥ 3.0mg/mL. Polyphenols have anti-inflammatory effects, antioxidative actions and modulation of cell signalling cascades related to inflammatory cytokine produced. Apples are the largest sources of phenolic compounds in the Western diet and also in Northern Himalayan India, especially in apple growing belts. Apples have the highest proportion of free phenolics compared to other fruits. Red apples, particularly Gala and Royal varieties, are the primary source of polyphenols, harbouring ~ 2-6 times more polyphenols as compared to other apple varieties. A randomized, controlled, parallel-arm trial was conducted with 46 participants. Human intervention studies have suggested potential health benefits of apples, mainly anti-inflammatory effects. The study has shown that consuming three small Gala apples daily for six weeks alleviated circulating biomarkers of inflammation and endotoxin exposure, including CRP, IL-6 and LBP.

Till now, as per the best of our knowledge, only two human studies have investigated the effects of whole apples on inflammatory biomarkers, neither of which focused on obese or overweight participants. In the study by Liddle et al. (2021), TNF-𝛼, however, remained unaffected till six weeks of daily Gala apple consumption. The anti-inflammatory effects of daily consumption of Gala apple are supported by findings in isolated PBMCs, which are mainly composed of lymphocytes and monocyte cells involved in chronic low-grade inflammation in overweight and obese individuals. Forty-four participants completed the trial (30 female, 14 male; mean ± SEM age: 45.4 ± 2.2y; BMI: 33.4 ± 0.9kg/m2). This was the first study to show that 6wk consumption of whole Gala apple might effectively appease inflammation in overweight and obese individuals. However, apples did not alter the anthropometric risk markers. Moreover, regular consumption of apples alleviates the occurrence of comorbidities associated with excess adiposities, such as CVD.

The consumption of apples, especially the Gala/Royal Gala, can also be recommended for people suffering/ recovering/recovering from COVID-19 infections, a present-day problem. As COVID-19 conditions are associated with elevated CRP levels leading the secondary infections/complications (Kooistra et al., 2021), either immediately or over some time, the reduction of CRP levels might help such individuals to return to normal physiology. Finally, a message to all: “Choose the Gala/Royal apple variety, eat one apple daily and keep CRP away”.

References:

1. Liddle, Danyelle M et al. “Daily apple consumption reduces plasma and peripheral blood mononuclear cell-secreted inflammatory biomarkers in adults with overweight and obesity: a 6-week randomized, controlled, parallel-arm trial.” The American journal of clinical nutrition vol. 114,2 (2021): 752-763. doi:10.1093/ajcn/nqab094.
2. Truman, S. C., Wirth, M. D., Arp Adams, S., Turner-McGrievy, G. M., Reiss, K. E., & Hébert, J. R. (2022). Meal timing, distribution of macronutrients, and inflammation among African-American women: A cross-sectional study. Chronobiology international, 39(7), 976–983. https://doi.org/10.1080/07420528.2022.2053702.
3. Kooistra, E. J., van Berkel, M., van Kempen, N. F., van Latum, C., Bruse, N., Frenzel, T., van den Berg, M., Schouten, J. A., Kox, M., & Pickkers, P. (2021). Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients. Critical care (London, England), 25(1), 281. https://doi.org/10.1186/s13054-021-03717-z

This blog has been written by Mr Sumit Mallick. Sumit is a PhD student/Junior Research Fellow, in the Stem Cells and Regenerative Medicine Centre, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, Pincode-575018 Karnataka, India. He can be reached at the electronic address: 19466@yenepoya.edu.in

Edited by: Dr Bipasha Bose, Associate Professor (Senior/Grade II), Stem Cells and Regenerative Medicine Centre, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore-575 018, Karnatka, India. Dr Bose can be reached at the electronic address: bipasha.bose@yenepoya.edu.in

The biology behind Procrastination and possible solutions to curb the same………..

Procrastination is voluntarily delaying or putting off tasks until the last minute or at the end of the deadline despite knowing that it will lead to discomfort. It can be job-related work or daily chores like leaving the shopping to the last minute, planning to study the night before the exam, submitting a report at the deadline, etc. People consider procrastination due to laziness or just plain incompetence. Indeed, there’s much more science behind procrastination than you would expect! Most of us tend to procrastinate thinking that we will do it later or the next day and finally end up in getting nothing done on time. It’s an incredibly common human experience to put off the things and leave the stuff to the very last moment. Some people procrastinate because of not  knowing what to do, fear of failure, fear of being judged by others, perfectionism, etc.

And there is another group, the thrill-seekers! Who think that they work better under pressure, they just don’t start a task unless they get the pressure of approaching a deadline.

Now, lets see, why do we procrastinate?

What’s it that drives our mind to put off important stuff, despite knowing its consequences?

It’s just a simple thing - the wiring of our brain! In that case, there is something serious going inside our brain which prompts us to procrastinate.

Science behind procrastination

Procrastination is the result of the constant battle between two parts of our brain, the limbic system and prefrontal cortex. In Sanskrit this terminology is called "Dwanda”

The limbic system is a group of structures in the brain that is located on both sides of the thalamus,  just beneath the cerebrum. It’s one of the well-developed and dominant parts of the brain which controls all our moods and emotions like fear, anxiety, anger, behavior. For example, when you accidentally place your hand near a cactus plant it is the limbic system that urges you to move your hand away from an unpleasant task.

The Prefrontal cortex is a part of the cerebral cortex which is less developed and weak. It is located right behind the forehead. The prefrontal cortex controls all our brain activities such as planning, decision making, problem-solving, self-controlling, etc. This is the part of the brain that eventually forces us to do our task. But this part does not function on its own, since it’s less developed and week; we need to put some effort to make it work.

At times we have to deal with many tasks, particularly when we have to go with difficult stuff; a tug of war will be constantly going on betwixt the limbic system and prefrontal cortex. The moment when you lose focus on that certain work,  limbic system takes over and you stop doing that important task which you have to finish and become more interested in preferring things that please you, like watching Netflix, scrolling Facebook, sleeping etc…and thus, procrastination kicks in!

When procrastination kicks in, a whole cascade of chemicals alter our brain chemistry. In such a case,our brain considers all the tasks as a threat. Amygdala is a section of the limbic system, controlling our survival mechanism our emotional behavior and motivation. In fact, amydgala scans our environment and helps us to coordinate the response to anything that threatens us. When it detects something unpleasant (in this case, the work in hand), the neurotransmitter norepinephrine takes over, thereby,  increasing the levels of anxiety and fear. Subsequently,, the hormone adrenaline gets pumped into the picture altering our physiology to make us emotionally to fight (resistant) or flight (ignore) the task.

Dopamine, on the other hand, is a feel-good neurotransmitter. It is released in pleasurable situations like watching movies, having food, etc. Human beings are addicted to dopamine. It stimulates our brain to seek out the pleasurable activity by actively neglecting other important stuff. That’s why you choose something else instead of doing something really important. This is the scientific explanation behind procrastination.

Types of procrastination

Researchers classified procrastination mainly into two types:

• Active procrastinators: Delay the task because of having trouble in making a decision and acting on them
• Delayed procrastinators: Delay the task purposefully because working under pressure makes them to “feel challenged and motivated”

Reasons for procrastination:

Consistent with recent researchers, there are some reasons for procrastination;

• Lacking the initiative to get started
• Fear of being rejected
• Not knowing what should be done
• Not in a mood to do the task
• Thinking that they work better under pressure
• Thinking they can complete in the last moment

To a certain degree, it's normal to procrastinate. You procrastinate about something because you are not sure that you’ve made the right decision and your mind tries to weigh up all the pros and cons and gather the necessary information to ensure your decision is right, rather than jumping into action without thinking properly. But chronic procrastination will result in a sense of guilt, crisis, stress, anxiety, and loss of personal productivity.

How can we stop procrastination?

There are several tips that you can use to avoid procrastination and start actively working on your task.

1. Create a to-do list: It will help to keep you on track by prioritizing which is important
2. Chunk the work: Rather than seeing it as one big task, chunk it into small, manageable steps so that it does not seem so overwhelming
3. Do difficult task first: Keeping the dreadful task last in the list will erode your mental energy, seeing it completed will make you feel more productive
4. Artificial deadlines: The problem with any task is that the due date is far away, to counteract this procrastination inducing delay, consider placing the due date next to each one
5. Eliminate distraction: Turn off the phone when you sit to work, because the most distracting thing today is a quick jump into social media. You can stay more focused on the work when you don’t use phones.
6. Work in a different place: We usually sit and work in the same place, instead if you have an important task to do, go to a strange location and start working, it will help you to focus more on your task.
7. Use Apps: Some apps can help you stop procrastination like,
   • AppDetox
   • Detox Procrastination Blocker
   • YourHour
   • Beeminder
   • Focus to do, etc.

“Life would be less stressful if you handle things when they show up, instead of when they blow up!” (Mohammed Ali)

Written by: Ashaiba Asiamma. She is an ICMR Senior Research Fellow at Yenepoya Research Centre (YRC), Yenepoya (Deemed to be University), Mangalore. Her research area includes Medical Microbiology and Nanotechnology".

Artwork: Ashaiba Asiamma

Edited by: Dr. Bipasha Bose, Associate Professor (Senior/GradeII), Stem Cells and Regenerative Medicine Centre, YRC

Stress is an emotion that you experience when
you fail to cope up with the demands. It reflexes the pressure put on the body
and brain. Thus, it is an adaptive response of the body that is controlled by
the brain.

Stress occurs when you encounter a sudden
danger or before a challenge, such as job interviews, presentations at work,
financial obligations, or a shocking event.

During a stressful situation, your brain floods chemicals and hormones that are responsible for stress to your body. 

How it works, and what are the hormones?

The front-line hormones responsible for stress
are adrenaline, along with norepinephrine (noradrenalin), and cortisol.

The stress activates the central stress
response system, known as the hypothalamic-pituitary-adrenocortical (HPA) axis,
as it is comprised of the hypothalamus, pituitary gland, and the adrenal
cortex.

During fight or flight response to acute
stress, nervous systems stimulate the adrenal glands triggering the release of
catecholamines, which include adrenaline and noradrenaline.
Their release into the bloodstream causes increased blood pressure, heart rate,
breathing rate, trembling, and sweating.

Once the amygdala, a part of the brain
realizes the fear, it activates the hypothalamus to release
corticotropin-releasing hormone (CRH). It further triggers the pituitary gland
to release another hormone called adrenocorticotropic (ACTH), which tells
adrenal glands to release cortisol.

The level of various other hormones changes to
stress that include prolactin, and growth hormones.

Though, the optimal amounts
of cortisol can be life-saving. Too much cortisol can suppress the immune
system, increase blood pressure and sugar, produce acne, contribute to obesity,
and more.

Stress is good or bad!

Not all stress is bad. In scientific terms,
good stress is called eustress. During low-level stress, in the case of
non-life-threatening situations, your brain uses more oxygen, and increases
activity which supports creativity, positive feelings of excitement,
satisfaction, and keeps you motivated.

But the long-term stress is harmful to your
health. The episodes of acute stress may lead to chronic stress, with the
symptoms of headaches, sleeplessness, sadness, anger, or irritability. Overtime
it contributes to serious health issues that include, heart disease, high blood
pressure, diabetes, and mental disorders such as depression and anxiety.

To maintain good physical and mental health,
stress management is very essential. Involving yourself in creative aspects,
regular exercise, relaxing activity, setting goals, stay connected, and even
good eat and sleep are the effective practices that may help you to cope with
stress.

The happy hormones such as dopamine, serotonin, oxytocin, and endorphins act positively and aids to overcome stress.

Written by: Yashaswini Devi G. V., JRF, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore-575018, Karnataka, India.

Artwork: Yashaswini Devi G. V.

Edited by: Dr. Venkatesan Jayachandran

What
Is Multitasking? Multitasking refers to performing several tasks at a time or
in other words, switching back and forth from one task to another. If we are
involved in two or more tasks at once, we can call ourselves as a multitasker. Sometimes
our job demands multitasking under pressure to complete work in a predefined
time schedule.

Take
a moment and think, are you multitasking right now? Along with reading this write-up,
perhaps you are engaged in other activities such as talking to your friends, checking
emails, browsing on your computer, writing any article, listening to music, or eating.

Numerous
research studies have been conducted to understand the effect of multitasking
on brain damage, memory, productivity etc. While
multitasking we are bombarded with too much information at a time, so it
weakens the power of our brain to process information in an effective way. Studies
from Wanger’s lab on media multitasking and memory reported that heavy
multitasking lowers the working memory (ability to hold information
temporarily), long-term memory and also affects the attentional scope. Researchers
carried out number of tests to check the working memory ability in heavy media
multitasker and they found that, the performance of heavy media multitasker is
worse compared to light media multitasker. Many of the studies reported a
negative relationship between media multitasking and working memory, it is
because of lack of attention while doing several works at a time. In another study by Joshua
Rubinstein et.al., observed that switching between multiple tasks
resulted in the significant loss of time.

However,
there are studies which report no performance difference between multitasker
and other group who are not engaged in multitasking. Of
course, it’s very hard to say whether multitasking is good or bad. So, more
evident studies are required to understand the effect of multitasking.

Now
let’s delve into how our brain manages multitasking. As we all know, the information
that we are getting from the outside world is processed, interpreted and stored
by our brain. Like any other activity, proper processing of all information
that we are exposed to each and every minute into a meaningful form is
necessary.

Stages of information processing

Several
theories have been proposed regarding the information processing stages.
Generally, the information processing consists of three key stages such as
input, storage and output. In the input stage external stimuli reaches the
brain through various sense organs and it undergoes preliminary evaluation. In
the second stage, the information is stored as short-term or long-term memory
depending upon our focus. There is a chance to forget the information if it is
not reinforced. The last stage is output, in this stage brain give instructions
to respond to the stimuli on the basis of stored information.

Posterior
lateral prefrontal cortex (pLPFC) is the part of cerebral cortex and is
responsible for routing the information input to corresponding centers for
processing and storage. This region plays an important role when we are multitasking.
During simultaneous arrival of information, pLPFC keeps them in a queue rather
than sending them for processing and storage.  If it continues to happen, pLPFC queues two of
them for processing and ignores the rest. This ignored information slip past to
the striatum. Which is a part of subcortical basal
ganglia and plays a pivotal role in the sequential representation of actions. As
this information are not processed and stored, we fail to recall it later.

Multitasking it seems is like a better way to finish all our work at once, but research has shown that it can actually reduce the productivity. So, to avoid this it’s better to reduce the simultaneous work burden to our brain by prioritising our work and allocating enough time in between each task.

Written by: Akhina P., UGC-JRF, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore-575018, Karnataka, India.

Artwork: Akhina P.

Edited by: Saketh Kapoor

Antibiotics work effectively in most people
but not for all. The same antibiotic does not work for all individuals. One may
ponder about the differences in antibiotic sensitivity among various
individuals? Could genetic variations lead to variations in antibiotic
sensitivity? Not genetics rather, overexposure to antibiotics make bacteria
increases the probability of bacteria to become resistant to it. According to reports,
India tops the list of
countries with the highest incidence of antibiotic resistance. Awareness in
this aspect is essential to avoid hassles in treatment strategies. It is the
responsibility of every country, to enlighten citizens about the serious impact
of antibiotic resistance and to educate the population regarding the proper use
of antibiotics. 

How does antibiotic resistance occur?

Well,
there are many possible reasons for it.

Taking antibiotics without prescription from professional expert. This constitutes as one of the main reasons for development of antibiotic resistance. Considering anexample, the causative organism for common cold are viruses. Consuming antibiotics to treat common cold makes no or little  difference to the affected individual but rather it may prompt the bacterial population to become resistant to a particular antibiotic. So remember, take only prescribed course of drugs else it may give way to antibiotic resistance. Avoid buying or selling antibiotics over the counter without proper prescription. Additionally, sometimes antibiotics are prescribed due to wrong diagnosis. This clinical misdiagnosis leads to unnecessary consumption of antibiotics often leading to development of antibiotic resistance.

Low grade of antibiotics. In several developing nations, antibiotics are of substandard quality, may not be stored properly and some are consumed even after the actual expiration dates. Continuous intake of such antibiotics in doses lower than what is recommended to treat the disease also leads to development of antibiotic resistance.

Antibiotics used as prophylactics. In several developed countries antibiotics are given to individuals with low immune conditions such as those who have recently undergone operation or those undergoing chemotherapy. These factors may also contribute to resistance and ease of international travel facilitates the transfer of antibiotic resistant bacteria to several places in a short span of time.

Nosocomial infections. Hospital-acquired antibiotic resistance contributes largely to the number of antibiotic resistant infections. The excessive use of antibiotic for multiple purposes often leads to development of resistant bacteria. The resistant bacteria quickly cross-contaminate patients thereby increasing their numbers. Use of antibiotics based on rotations may reduce the development of such resistant bacteria.

Antibiotic resistance is through poultry
or animal husbandry. Here, in
addition to use of antibiotics to treat disease conditions, they are also used to
avoid the spread of diseases. In some cases, antibiotics are also used as
growth stimulators in animals. The resistant bacteria can be introduced into
the human body through consumption of food derived from animals infected with the
resistant bacteria. The later impact of it is the failure of an individual to
fight against bacterial diseases. 

Stance of World Health Organization (WHO) on antibiotic resistance 

Considering the importance of antibiotics WHO has labelled antibiotic resistance as a global threat. This highlights the importance of creating awareness in this aspect. WHO has launched Global Antimicrobial Resistance Surveillance System (GLASS) that supports global surveillance and research related to antibiotic resistance. In the future, a growing number of infections like pneumonia, tuberculosis, gonorrhoea, and salmonellosis that we can control today with the help of antibiotics will become extremely difficult to treat tomorrow.

Written by: Apoorva H. N., DST-JRF, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore-575018, Karnataka, India.

Artwork: Apoorva H. N

Edited by: Saketh Kapoor

How to introduce stem cells to a layperson? If they are not up to date with the recent advances in science, they might think we are talking about plants. First usage of the word “stem cell” was seen in the literature dated back to 1868 in the works of evolutionary biologist Ernst Haeckel. He used the word “Stammzelle” to describe the unicellular ancestor from which all multicellular organisms have evolved according to his presumption. Not to go too deep into the history, let us focus on the matter at hand – what are stem cells? 

To put it straight we can say - stem cells are babies! A baby has the potential to become whoever he wants to be when he grows up - a doctor, an engineer, a scientist, a techie, an entrepreneur, an artist, a movie star, a singer, or anyone. As he grows up, the choices he makes further narrows down this fate. For instance, choosing biological science over computer science or commerce for the higher secondary education and doing undergraduate courses in the preferred stream. Anyway, you get the picture. Just like a baby, stem cells can become whatever cell it wants when grown up (differentiated to be specific). 

Now let us get a little technical. Stem cells are the cells which can self-renew (make identical copies of themselves) and differentiate into other cells types. During the early development, when the egg is fertilized, the cells thus formed are totipotent stem cells. Each cell can grow into a new individual, if separated. These cells can give rise to embryonic as well as extra embryonic structures. The first segregation of stem cell fate begins at blastulation – formation of blastula. In mammals, blastulation is the formation of a hollow sphere of cells with a fluid filled cavity and group of cells in one corner named inner cell mass. The totipotency is lost at this stage and the cells now become pluripotent. The cells in the inner cell mass of the blastula can give rise to all three germ layers (ectoderm, endoderm, and mesoderm) of the embryo proper but not the extraembryonic membranes. As the growth and differentiation progresses, the pluripotent stem cells become multipotent and limits the differentiation to fewer lineages. The mesenchymal stem cells present in adult tissues such as bone marrow, adipose tissue as well as the umbilical cord of the foetus and the haematopoietic stem cells present in bone marrow and peripheral circulation are multipotent. Further the progenitors of these multipotent stem cells are oligopotent. They can only give rise to fewer cell types. For instance, haematopoietic stem cells, which are multipotent, can differentiate into oligopotent myeloid or lymphoid progenitors. The myeloid progenitors can only differentiate into the blood cells (RBCs and WBCs) whereas the lymphoid progenitors can give rise to B cells, T cells and NK cells. Then there are unipotent stem cells, whose potency is limited to one lineage. Muscle stem cells or myosatellite cells are one of the examples for unipotent stem cells. They can only differentiate into skeletal muscle cells. Thus, the potency of stem cells varies depending on the site or stage at which they are isolated. As for the therapeutic research, the choice of stem cells depends on the abundance of the source and the feasibility of differentiating them into the cell type of interest. 

What we discussed are the naturally occurring stem cells. Understanding the genetics of embryonic stem cells (ESCs) have made it possible to induce a differentiated cell of an adult body to become pluripotent. These induced pluripotent stem cells (iPSCs) were made by introducing four genes – Oct3/4, Sox2, Myc and Klf4, known as Yamanaka factors, to a differentiated cell such as a skin cell. Shinya Yamanaka discovered this for which he shared the Nobel Prize in Physiology or Medicine in 2012 with John B. Gurdon who had earlier proved in 1962 that specialisation of cells is reversible. These iPSCs are equivalent to ESCs in their properties and they do not cause any ethical issues that pertains in the isolation of ESCs from human embryos. Around the world scientists have created neurons, blood cells, egg and sperm precursors, liver cells, pancreatic beta islets, cardiomyocytes, bone precursors and a whole lot of cell types from iPSCs for the therapeutic research. Clinical trials are underway in using iPSCs for Parkinson’s disease, heart diseases, macular degeneration, spinal cord injury, diabetes, osteoarthritis, and the list keeps on increasing. The advent of iPSCs have revolutionized stem cell research by creating a new platform to study diseases and introduce patient specific regenerative therapies.

Having said that, we cannot just do stem cell therapy for anything everything like those quackery advertisements claim. There are strict regulations put forward by the health authorities. The Indian Council of Medical Research only permits the transplantation of haematopoietic stem cells from bone marrow and umbilical cord blood to treat cancers and different blood disorders. Therapies involving other stem cells or other diseases are still being researched and yet to be approved officially. Any other treatment or therapy violates the NGSCR 2017 (National Guidelines for Stem Cell Research) is considered unethical and a malpractice. Unproven stem cell treatments may have health benefits as they claim, but there are greater risks associated with it. The transplanted cells may not stay at the site in the body where we intent it to be and it might differentiate into some other cell type and multiply. Sometimes it may not work or worst case it will develop into a tumour. What we can do is wait for the day when all the clinical trials are done with and stem cell therapy for other diseases are approved by the authorities. 

In case you are wondering if stem cells can be of any use in the fight against the SAR-CoV-2 virus and the COVID-19 disease – Yes, they can! Stem cells can help us learn a lot about the virus as well as heal the damage done by the virus. iPSCs can be used to create lung organoids to study how the virus infects the cell and find an effective way to fight it. The damages in the lungs and other organs of the COVID-19 patients can be healed with stem cells and the quality of life can be improved. As of now these, treatments can only be done under the strict guidelines of clinical trials. There are still a few challenges that needs to be tackled so that stem cells can reach its full potential in therapeutic research. Immunogenicity and tumorigenicity are the major risks associated with the transplantation of stem cells and their derivatives. Researchers are still finding ways to improve the quality and safety of stem cells. Hopefully, within the next decade, we might find stem cell transplantation facilities in most of our hospitals. 

Written by: Muhammad Nihad A. S., JRF, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore-575018, Karnataka, India.

Artwork: Muhammad Nihad A. S

Edited by: Dr. Raghu Bhushan

Sanitizers are
one of frequently purchased products world-wide especially due to the current
COVID-19 pandemic. The efficacy of the hand hygiene product determines its
activity against bacteria, yeasts, and coated
viruses.

Among the
available products, alcohol-based sanitizers are in trend due to its active
action against germs such as bacteria, fungi and viruses. Alcohol is treated as
a good antiseptic and does not show toxic effect on human skin however,
continuous use may cause irritation and dryness. Different concentrations of
alcohol are available in the market. Although a higher concentration of alcohol
acts effectively against germs, the best efficacy can be achieved by using
ethanol (60-85%), isopropanol (60-80%), and n-propanol (60-80%) based
sanitizers. As per literature, 95% ethanol has the highest action against naked
viruses. Moreover, the synergistic action could be seen by mixing a different
combination of alcohols. As proof, propanol and isopropanol are presently
available as good disinfectants in the market.

Why alcohol is so important in
sanitizer?

A bacterial
membrane entails basic compounds such as phospholipids and lipopolysaccharides
and their interactions are alleviated by Mg²⁺ and Ca²⁺
ions. When ionized, disinfecting molecules are absorbed or repelled by
electrical charges at the initial contact and absorption stage, leading to cell
membrane damage and the electrolyte leakage which can activate cell death pathways.

Alcohol is a
combination of organic molecules such as carbon, oxygen, and hydrogen. Alcohol
clears most of the disease-causing pathogens by breaking the protein-lipid and
dissolving their membranes. The bacterial membrane contains hydrophobic or
lipophilic tails and a hydrophilic head phosphate group. Sanitizers act at
lipophilic ends to break the cell membranes by rupturing its structure and
denaturing the proteins. The novel SARS-CoV-2 virus is surrounded by a ‘fatty’
membrane layer, which can also be disrupted by using alcohol-based sanitizers.
In particular, when the concentration of alcohol exceeds 60%, it has high
efficiency to kill certain bacteria and viruses. In addition to alcohol,
limited concentrations of hydrogen peroxide are added to avoid the growth of
microbes and glycerol or caprylyl glycol or isopropyl myristate is added to
moisturize the skin and prevents dermatitis. Moreover, water acts as a catalyst
in sanitizer, which helps to improve penetration and leads to cell membrane
rupture. Besides, fragrances are also used to give a pleasant odour. When
sanitizer is rubbed on hands, ethanol evaporates and leaving behind soothing
compounds.

Not only
alcohol-based sanitizers, even less concentrated i.e., 0.3% of benzalkonium
chloride or triclosan based sanitizers also kill germs. However, the
effectiveness is lower compared to alcohol-based sanitizers. So, alcohol and
its percentage are very important in sanitizer preparation and purchase.

Written by: Kumara B N, DST-SERB-JRF, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore-575018, Karnataka, India.

Artwork: Kumara B N

Edited by: Dr. Pratigya Subba

Diagnostic and therapeutic advancements are among the key factors in improving the quality of living. An advanced health care system is a cardinal scale for measuring the development of a country. Till date, the discovery of vaccines is one of the most remarkable advancements in modern medicine. Vaccines enabled humans to eradicate some of the most life-threatening diseases. Rather than finding an external agent to kill the pathogen, the immune system is trained to fight off the pathogens. The diverse and complex nature of the immune system, remarkable specificity and an efficient regulatory system makes it a powerful target for the development of modern therapeutics.

The Nobel Prize in Physiology or Medicine, 2018 was jointly awarded to Dr. James P. Allison and Dr. Tasuku Honjo for the discovery of immune checkpoint molecule CTLA4 and PD1, which act as a molecular brake in anticancer immune response. But the concept of targeting the immune system to treat cancer is not a new idea. In the late 1800s, a physician Dr. William B. Coley observed that patients with cancer underwent spontaneous remission after erysipelas development. Upon injecting mixtures of live and inactivated Streptococcus pyogenes and Serratia marcescens into patients’ tumors Dr. Coley observed a complete durable remission in several types of malignancies. Lack of known mechanisms about how the cancers were affected by such infection and ethical issues related to deliberately infecting patients with potential bacteria hindered the adoption of this strategy over surgery and radiotherapy. After a century, the Bacille Calmette-Guerin (BCG) was tested for preventing the recurrence of nonmuscle-invasive bladder cancer. The successful trials led to worldwide usage of BCG as a preventive therapy against several cancers.

The original concept underlining cancer immunotherapy was proposed by Thomas and Burnet in 1957. The immune cells function as a surveillance system to find mutated, abnormal cells, or cancer cells. Lack of scientific evidence to support the theory due to the inability to culture immune cells impeded the field of cancer research until the T cell growth factor Interleukin-2 (IL-2) was identified in 1976. Ability to culture immune cells using IL-2 led to the understanding of immune surveillance capability and cancer-killing action of T cells. Effectiveness of large quantities of IL-2 in patients with metastatic cancers led to the expansion of lymphocytes and increased the survival of patients. IL-2 as an immunotherapeutic was eventually granted FDA approval for treating metastatic kidney cancer in 1991 and against metastatic melanoma in 1998. In 1984 Dr. Niels K. Jerne, Dr. Georges J.F. Kohler and Dr. Cesar Milstein were awarded the Nobel Prize for Physiology and Medicine for the theories concerning the specificity in development and control of the immune system and generation of monoclonal antibodies. Research on antibody-based therapeutics opened a new arena for targeted therapies. The development of the first monoclonal antibody Rituximab approved by FDA for the treatment of non-Hodgkin’s lymphoma in 1997. Rituximab antibody binds to CD20 receptors on immature B cells and eventually induces elimination by natural killer (NK) cells. 

The concept of cancer vaccine emerged after the identification of tumor antigens. Even though the cancer cells contain the same genetic material like normal cells, the adapted mutations, alteration of the protein expression and change in cellular metabolism differentiate them from the normal cells. Such alterations generate tumor antigens which can be used to target cancer and also develop a vaccine approach to treat efficiently and prevent any chance of relapse. In 1991 researchers cloned a melanoma derived antigen that was successful in generating an anticancer response from cytotoxic T cells. In recent years the tumor antigen-based anticancer immunotherapies have evolved. The development of antigen-activated allogenic and autologous T cells has shown promising responses in both, laboratory studies and clinical trials. The process of mass expansion of T cells, dendritic cells and NK cells collected from patients or healthy donors and their expansion into target tumor cells using specific antigens are the current cell-based vaccine approaches. The development of genetically modified Chimeric antigen receptor T cells (CAR T cells) has shown significant responses against various cancers. Currently, multiple CAR T cell therapies have been approved by FDA for the treating various types of leukemia. Identification of immune checkpoint inhibitory molecules CTLA4, PD1 and its ligand PDL1 are a potential target anticancer therapy. Ipilimumab an antibody targeted against CTLA-4 is approved by FDA for use in melanoma patients. Antibodies that inhibit PD1 and PDL1 are currently in phase III clinical trials and reportedly showing a promising response. 

Even though immunotherapies are promising and efficient in providing long-term protection from cancer relapse, the humongous costs involved for the treatment make it unaffordable for major affected populations. Many undergoing studies are refurbishing conventional therapies such as chemotherapy, radiotherapy and modern advancements such as photodynamic therapy, radiofrequency hyperthermia, etc. along with immunotherapeutic methods will hopefully lower the costs. The potential of the immune system, diversity of different immune subpopulations and heterogeneity of patient groups is opening up a modern era for research to fight cancer. The major challenge in treating solid tumors is the harsh tumor microenvironment, which enables the rapid evolution of cancer cells to develop therapy resistance and immune escape. Identifying the potential modulators of immune microenvironments in various cancers and targeting such mechanisms to reactivate the immune surveillance is possibly what lies ahead for cancer therapy.

Written by: Sooraj M, ICMR-JRF, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore-575018, Karnataka, India.

Artwork: Sooraj M
Edited by: Saketh Kapoor