How does loneliness affect your brain?

Spreng et al. The default network of the human brain is associated with perceived social isolation. Nature Communications. December 2020.

A recent study found fundamental structural and functional differences in the brains of lonely people. Researchers examined the magnetic resonance imaging (MRI) data, genetics, and psychological self-assessments of over 40,000 middle-aged and older adults in the UK Biobank medical database. They then compared the MRI data of participants who reported often feeling lonely with those who did not. There were several major differences in the brains of lonely people which were primarily found in what is called the “default brain network,” a group of brain regions that are involved in inner thoughts such as remembering, future planning, imagining, and thinking about others. Detailed analyses of these regions showed that surprisingly, the default networks of lonely people were more strongly wired together and their grey matter volume in regions of the default network was greater. Moreover, bundles of nerve fibers called fornix that connects the hippocampus to the default network were better preserved in the brains of lonely people. These findings suggest that since lonely people are more likely to use imagination, memories of the past, or envisioning the future to overcome their social isolation they strengthen memory-based functions of their default networks through internally-directed thoughts and imagining social experiences. Loneliness has been increasingly turned into a major health problem, as other studies showed that older people who experience loneliness have a higher risk of cognitive decline and dementia. As COVID-19 related social distancing continues, isolation and loneliness could affect our society even more dramatically. Understanding how loneliness manifests itself in the brain at the structural and functional level, and how these paradoxical findings translate into late-onset brain pathologies, would be critical to prevent both neurological diseases and related social problems.

Human-made mass is about to exceed total global living biomass

Elhacham et al. Global human-made mass exceeds all living biomass. Nature. December 2020.

Humanity is rapidly approaching a new milestone in the history of our planet. The amount of manmade objects on Earth will soon outweigh all living biomass. A new study finds that each person alive today produces approximately the amount of manmade mass equivalent to their bodyweight every week. Our daily life objects such as roads, houses, cars, and clothes now weigh in at around 1.1 trillion metric tons, which is equal to the combined dry weight of all plants, animals and microorganisms on the planet. The production and accumulation of manmade objects, also known as anthropogenic mass, has accelerated since the early 1900s. The world’s plastics alone now weigh twice as much as the planet’s marine and terrestrial animals.

About 50% of the current anthropogenic mass is concrete. Bricks, asphalt, metals, plastic, and other materials make up about 19% of the total. Three major problems will arise from the outproduction of antropogenic mass. First, manufacturing consumes resources which will not be available for future generations unless objects are recycled or new raw materials are discovered. Second, even if we can achieve 100% recycling, pollution is generated and energy is used during manufacturing, so resources are still consumed. Third, many of the manufactured items will eventually be discarded which will cause serious disposal issues in the future. This is particularly alarming for the future. Nature is not infinite like so many of us would like to believe. If the current trend continues, anthropogenic mass will grow to three times the world’s biomass by 2040. In the next 20 years, we will generate as much waste as from the last 110 years together. These huge waste flows could lead to massive environmental catastrophes. This study demonstrates the brutal scale and impact of human activities on our planet. Humans are modifying the planet to such an extent that we might have already started a new geologic epoch likely called the Anthropocene.

Drug repurposing by artificial intelligence

Liu et al. A deep learning framework for drug repurposing via emulating clinical trials on real-world patient data, Nature Machine Intelligence. January 2021.

Researchers have developed a machine-learning method that analyzes very large datasets to discover which existing medications could work for diseases for which they were not prescribed. This process is called “drug repurposing,” a popular strategy to find new purposes for existing drugs that offers a rapid transition from research to clinical care. Drug repurposing can lower the risk associated with safety testing of new medications and dramatically reduce the time and money required to get a drug into the marketplace for clinical use. However, discovering new uses for existing medications still requires time-consuming and expensive randomized controlled trials to prove that a drug that is effective for one disorder will also be useful to treat another disorder. To overcome this challenge, a team designed a computational framework that works in two steps. First, it searches enormous patient care-related datasets with high-powered computation to arrive at repurposed drug candidates for a given disease. Second, it calculates and estimates effects of those existing medications on a defined set of clinical outcomes. As a proof-of-principle, researchers decided to focus on repurposing of drugs to prevent heart failure and strokes in patients with coronary artery disease. The edge of the machine learning approach is that it can analyze and compare thousands of human differences within a large population that could influence how a drug will work in the body. These confounding factors such as age, gender, race, and disease severity function as parameters in the deep learning computer algorithm on which the framework is based. This information is streamed from “real-world evidence,” which consists of longitudinal observational data about millions of patients captured by various sorts of electronic medical records. The team used insurance data for more than 1.2 million heart-disease patients. The algorithm analyzed each patient’s drug prescriptions and diagnostic tests for every visit and models input for drugs based on their active ingredients. The model yielded a total of 9 drugs with potential therapeutic benefits, three of which are currently in use and six new candidates for drug repurposing. Interestingly, two diabetes medications, metformin and escitalopram, have been found to lower the risk of heart failure and stroke in the model patient population. This study shows how artificial intelligence can speed up hypothesis generation and clinical trial processes. While this study focused on heart failure and stroke, the framework is flexible and could be applied to most complex diseases.

Athlete’s foot is a frequent infection that millions of people suffer from annually. I once had it during my military service where we had to wear boots almost an entire day. Once during a noon intercession, I performed my ablutions to pray and I placed my feet under the sunlight to dry them. I was also hoping that ultraviolet rays from the sun would be good for the infection. Soon, flies swarmed in between my toes. When I could not bear the excessive itching, I tried to kill the flies until I was stopped by a friend who reminded me of the great sage Bediuzzaman’s comments where he called flies “cleaning workers.” At that time, I also remembered Prophet Muhammad’s (peace be upon him) words on flies. So, I patiently endured the nuisance, and repeated the same procedure for the next three or four days. Eventually, my feet were healed and there was no trace of the fungi.

In one of his very interesting hadiths, the Prophet, peace and blessings be upon him, is reported to have said the following about flies: “If a fly falls into your drink, dip it into your drink, then throw it away, for on one of its wings is a disease, and on the other is a cure. It dips the wing with the disease to protect itself” [1]. This hadith has been a reason for much controversy mainly due to germ disease theory.  According to Jonathan C. Brown, “even before modern medicine, the Hadith of the Fly was raising skeptical eyebrows and prompting Sunni defensiveness as early as the writings of Ibn Qutayba (d. 276/889)” [2]. Brown also mentions that this hadith “could be false or it could be true, since scientists used the flesh of a snake to help prepare antidotes to its poison” [3].

Before the microscope was invented it was impossible to define microbes or talk about the anatomy or microbiology of flies as we can today. However, the introduction of experimentation and observation as an important scientific method with the Renaissance served as a turning point in Western scientific revolution. Thus, the “proof-based medicine” conception that relies on experimentation and observation emerged as a precursor to today’s medicinal and scientific research. The importance of perceptions that rely on causes relating to the material world in persuading the human mind cannot be denied. It is harder to make people believe in something unless they are provided with concrete results that appeal to our five senses. We should not rush to deny any claim solely based upon our preconceptions and prior knowledge without doing any research about it; rather, we should pass our judgment on it after experimentation and observation.

Some people may automatically reject the idea that when a fly falls in our food or drink that we should immerse this microbe-carrying insect completely and they may say that this would not eliminate the microbes. Indeed, it may sound reasonable to assume that this disgusting insect that feeds on all sorts of dirt would cause only diseases. If you have an ample supply of food or water and if you do not have the stomach for it, you can of course refrain from eating or drinking such a food or drink. But, you can hardly advise someone who has very little water or food in a desert or at the time of famine to throw away what they have because of a fly.

We should examine different types of flies in laboratory settings using the method of experimentation and observation. First of all, it is very difficult to prove that someone can contract an illness from eating food in which a fly had fallen into although he or she had immersed that fly completely in that food. If it is proven that someone becomes ill due to a fly’s alighting in their food, then strong objections can be raised. If it is said that there many diseases caused by flies, no one will deny it. The point is not whether flies carry germs, but whether this advice for being protected from the germs carried by flies is correct or not. As a matter of fact, the advice by the Prophet seeks to protect us from diseases that may be caused by germs carried by flies. The great scholar Bediuzzaman’s words on flies also give us an alternative perspective to consider about these “tiny birds”:

“…Flies are dutiful about cleaning away noxious substances or germs that cause disease. By sucking up and absorbing harmful germs, they destroy them, and they cause noxious or poisonous substances to change into other harmless forms, thus preventing the spread of many contagious diseases. A sign that they are both laborers for health and cleansing operatives and chemists, serving many instances of wisdom, is the fact that they exist in extremely great numbers. For the things that are valuable and beneficial are multiplied.” [4]

The hadith of the Prophet and Bediuzzaman’s commentary encourage us to explore more about flies and whether they can be a source of healing in any way.

Flies are very ubiquitous on earth. There are approximately 125,000 species of flies, but only ten species live in our homes and are of concern to us. They feed on garbage and organic waste materials that act as a breeding ground for microbes such as bacteria, fungi, and viruses. The female fly lays down more than 100 eggs in the dung of some animals or in garbage. After one day, the larva emerges to feed on the surrounding organic materials. In two weeks, they become full-grown flies. In four generations, one female fly can lay 1.5 million eggs, but fortunately the majority die due to weather circumstances or become food for birds, reptiles, amphibians, and other insects. A fly can live for 60 days at most.

Given the ecological balance in nature, one comes to accept that there should be species that will remove all sorts of organic waste, garbage, dead animals or plants, and similar things by eating them. Houseflies feed on the rotting corpses of animals while female horseflies suck blood. How can flies, which act as health workers that are charged with the duty of cleaning the world, digest so many diverse amounts of garbage and waste?

Flies get their nourishment differently from other animals. What other animals do for digestion is done by flies outside their bodies. They do not have teeth-like structures in their mouths in order to chew solid, dry food and therefore have to turn such food into liquid form or split it into 0.45-mm or smaller pieces. In this liquid form, flies can easily suck up their food using their suitably shaped mouths. To do this, flies vomit a saliva-like liquid, containing enzymes and acids, and that disintegrates the solid food into something that can easily be digested in a couple of seconds. In this process, some of the microbes in that waste food can be disintegrated while the rest will be sent to the stomach.

These foods and microbes taken inside in the form of vomit are sent to a sac called a “crop” if they are not small enough to go through the digestive tract. Flies produce fresh saliva regularly during which the vomit moves between their mouths and crops. Eventually, the sufficiently liquefied food is sent to the stomach which contains enzymes and acidic content as well as partially disintegrated microorganisms.

What does scientific research tell us?

Based on the theory that flies must have remarkable antimicrobial defenses and resistance to survive the bacteria from rotting dung, meat, and fruit, a team at the department of biological sciences at Macquarie University in Australia set out to identify those antibacterial properties.

“Our research is a small part of a global research effort for new antibiotics, but we are looking where we believe no one has looked before,” said Joanne Clarke, who presented the group’s findings at the Australian Society for Microbiology Conference in Melbourne.

Clarke’s research showed that flies produce their own antibiotics, and this was tested on four different fly species. Such research may lead to better treatments for human infections from Escherichia coli and other virulent bacteria even, perhaps, Staphylococcus aureus (MRSA).

Upon preliminary results, a global pharmaceutical company decided to support the research over the next six months by trying to isolate antibiotic compounds from the material collected from the flies. The research team is trying to identify the specific antibacterial compounds. As antibiotics that will eventually be invented and chemically synthesized come from the body surface of flies, not from other fungi or bacteria, it is believed that any gene that gives resistance to microbes will not be easily transferred to pathogens and the new antibiotic form will have longer and more effective treatment duration [5].

Later, Russian doctors had developed interest in this topic and observed that flies contain many substances that can be more effective than traditional medications and certain fly larvae have very strong therapeutic effects [6].

Noting that flies should be kept away from hospitals, Professor Juan Alvarez Bravo at the University of Tokyo expressed his support for such research, saying, “But soon we will witness a rapid treatment for many diseases, which consists of extracts from flies” [7].

Some researchers at Auburn University of the United States discovered a protein in the fly’s saliva which can accelerate the lengthy process of healing wounds and chronic skin cracking. Entomologists Ed and Mary Cupp managed to isolate the protein which houseflies inject into their prey to increase blood flow in the skin of their prey. Mary Cupp and surgeon Steven Swaim demonstrated that surgical incisions, skin ulceration, and diabetic foot lesions treated with solutions that combine antibiotics and this protein heal faster and stronger than incisions treated with antibiotics alone [8, 9].

In another study, it was found that epithelial cells forming the inner layers of the front and back intestines of the fly protect it from the bacteria it swallows thanks to a special cuticular lining, and in this way, bacteria never directly touch the intestinal epithelium and cannot give any damage to it. In this study, it was noted that people nurtured a radical approach to flies and that fly control has been abused for the sake of human health, suggesting that flies may be the source of novel germicides that make use of their antimicrobial digestive enzymes, lysozyme, and antimicrobial peptides [10].

Viruses cause many diseases in cattle, sheep, and birds. These diseases include encephalitis, aphthous fever (foot and mouth diseases), and duck plague which can be transferred to people through infected animals. Some crops such as potatoes, tomatoes, bananas, and sugarcane can also be destroyed by viral infections.

Flies carry the viruses of many diseases which are consequently transferred to man’s food, drink, and body. Of these viral diseases are common flu, measles, mumps, chickenpox, warts, yellow fever, infectious liver diseases, some cases of paralysis, some types of cancer, and some chronic diseases of the central nervous system.

El-Naggar, Zaghloul, from Egypt, indicates that some of the disease-causing viruses may directly infect living beings and cause damage to their cells, while there is a type of virus which infects bacteria cells known as “bacteriophage.” These viruses, which can kill the bacteria they infect in a short time, are known as “virulent bacteriophage.” Those viruses that do not kill the bacteria they infect are called “temperate bacteriophage” [11].

After a bacteriophage infects a bacterium, more than 100 viruses are released from that bacterium and each of these viruses can infect new bacteria. The spreading of infection may continue until all vulnerable bacteria cells die. After it was discovered that bacteriophages are parasites of bacteria, they started to be used in treating the diseases caused by bacteria. However, their use in this manner declined after the discovery of antibiotics. Yet, the interest in phage treatment was revived after the emergence of bacterial resistance to antibiotics [12].

Researchers from Stanford University announced that they found a substance in flies that can improve the human immune system [13].

The work by Rehab Mohammed Atta from the Microbiology and Immunology Department, National Research Center, Cairo, Egypt, is quite remarkable [14]. In this research, the extracts taken separately from the left and right wings of flies were used against the bacteria and fungi calculated on nutrient “agar” media in the laboratory. It was demonstrated there was both bacterial and fungal growth for the left wing extract plates while no bacterial or fungal growth was reported for the right ones.

Given the fact that the garbage and rotting corpses on which flies feed from contain numerous dangerous bacteria, it is quite reasonable that it contains antibacterial materials necessary for its survival. In this case, the fly’s needs might be of service as sources of antibiotics that can prevent epidemics among human beings, and this may be the reason why they were created in the first place: not to be a source of nuisance but a source of healing for us.

Aj-Taili, et al., from the department of medical microbiology, Qassim University in Saudi Arabia, conducted an experiment using water, honey, and various fruit juices in different cups. They found no germ in the solution in which the whole body of fly was immersed while the solution in which only one wing of the fly was dipped indicated the presence of germs [15].

In sum, we can say that antibacterial materials produced in the bodies of flies protect them against the microbes in their environments and that these microbes can prevent epidemics among human beings. At the very least, this topic deserves in-depth research. Atta’s study confirms the virtue of the hadith that says, “The best way to release this vital antidote is to dip the fly in a liquid because these substances are concentrated on the outer surface of the fly body and wing.” Abduldaem al-Kaheel refers to this study in his website: “This is logical because the fly has a lot of harmful bacteria on the outside of her body and therefore in order to continue in her life, it should also carry anti-bacterial materials; these materials were furnished by God to protect it from viruses and diseases.” In the light of these studies, the need for conducting more research for obtaining antibiotics from the right wing of the fly is clear [16].

References

1. Abu Dawud, At’imah, 49. Also see Bukhari, Tib, 57, Bed’u al-Khalk 17; Ibn Majah, Tib, 31, Nasa’i, Far’, 11.
2. Brown, Jonathan A. C. 2009. Hadith: Muhammad’s Legacy in the Medieval and Modern World, p. 264.
3. Ibid. p. 255.
4. Nursi, Bediuzzaman Said. 2008. The Gleams. The Light, Inc. p. 376.
5. Danny Kingsley, ABC Science Online, 1 October 2002, The new buzz on antibiotics. Clarke, J., Gillings, M. and Beattie, A. (2002). Hypothesis-driven drug discovery. Microbiology Australia, pp. 8–10.
6. Petersburg State University, (2006). The fly effect: Russian Scientists Invent new medicine with the help of flies.
7. Bravo, J. A. (1994). The ointment in the fly: antibiotics. New antibiotic derived from a common fly. The Economist (US).
8. Ed and Mary Cupp (2005). Protein in Fly Saliva Speeds Healing of Incisions Wounds. Auburn University. R Am Ex Ars Medica, Inc., 7:23.
9. Protein in Fly Saliva Speeds Healing of Incisions, Wounds 20-Jan-2005. www.newswise.com/articles/protein-in-fly-saliva-speeds-healing-of-incisions-wounds
10. Nayduch, D. and Burrus, R.G. (2017). Flourishing in Filth: House Fly–Microbe Interactions Across Life History. Special Collection: Filth Fly–Microbe Interactions. Annals of the Entomological Society of America, 2017, Vol. 110, No. 1.
11. El-Naggar, Zaghloul, (2010). Housefly Falls into One’s Drink! 09 September 2010. www.quranandscience.com/quran-science/sunnah-science/204-housefly-falls-into-ones-drink-274
12. Aydogan, D.Y., Hadimli, H.H. (2016). Bakteriyofaj Tedavisi (Bacteriophage Treatment), Etlik Vet. Mikrobiyol. Derg.; 27 (1): 38–47.
13. Stanford University Medical Center, 2007. Fruit Fly Insight Could Lead to New Vaccines. Science Daily. www.sciencedaily.com/releases/2007/03/070308220904.htm
14. Atta, R. M. (2014): Microbiological Studies on Fly Wings (Musca domestica) Where Disease and Treat. World Journal of Medical Sciences 11 (4): 486–489.
15. Aj-Taili, S.I., A.A.R. Al-Misnid and K.D. Al-Uteybi, (2002). Wing One and the Other Disease Carrying the Cure. Qassim University. Danny Kingsley.
16. Abduldaem al-Kaheel, 1995. New facts: fly have a cure, www.kaheel7.com/eng.

In 1981, scientists discovered ways to derive embryonic stem cells from early mouse embryos. Since then, they have been the subject of intense scrutiny, controversy, and advocacy.

They are unique cells, which can be derived from human embryos and can be differentiated into virtually any kind of different cells. In humans, there are about 200 different types of cells including bone, muscle, and nerve cells, and within these cells there are about 20 different types of structures or organelles. Essentially, stem cells can be derived from human embryos, and with the right enzymes, can be stimulated. For instance, bone cells can originate from osteocyte cells, or liver tissues can come from hepatocytes.

Stem cell types and research

There are three types of stem cells:

• Embryonic stem cells
• Adult stem cells
• Induced Pluripotent Stem Cells (iPSC)

Embryonic stem cells are derived from human embryos. Adult stem cells are undifferentiated cells (meaning “clean slates” with the potential to change into another cell variant) found throughout the body after development; they multiply via cell division to replenish dying cells and regenerate damaged tissues. Induced Pluripotent Stem Cells (iPSC), which were discovered in 2006, are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. While these types of cells are interesting and certainly worthy of research, this article will focus on embryonic stem cells as they are consistently the most well-known and discussed type by the general public.

Embryonic stem cells are potent and often sought after due to their abilities to proliferate without limit and contribute to any cell type. However, with great power comes great responsibility and stem cells are no exception. Poorly processed cells have been documented to mutate into cancerous tumors that can wreak havoc upon people’s bodies. Bearing this in mind, scientists also do not believe that this should derail stem cell therapies considering that there are DNA tests to check if stem cells will turn out to be problematic or not.

The stem cell project is regularly a subject of ethical debate in both the academic and public sectors. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro—in an in vitro fertilization clinic—and then donated for research purposes with the informed consent of the donors. People willingly donate their eggs for this research, and this process does not constitute child-killing since the eggs are near their zygote phase, not a whole mature embryo. Scientists obtain those types of cells from an embryo which has not yet completed its formation to develop into a human being. Researchers then use these cells for various treatment and research purposes. It is important to stress that they are not derived from eggs fertilized in a woman’s body and that they are produced in a plastic laboratory culture via clinics in vitro.

Some examples of embryonic stem cells being used in research include the following:

1. UCLA stem cell gene therapy cures bubble baby disease

Researchers at UCLA (University of California, Los Angeles) have developed a cure for babies born with Bubble Baby Disease, a rare and life-threatening condition that can be fatal within the first year of life, by using stem cells from multiple patients and gene therapy to correct the genetic mutation of these patients.

2. Asterias biotherapeutics restores some independence to those suffering from paralysis caused by spinal cord injuries

Asterias Biotherapeutics spent much of 2016-2017 developing a stem cell therapy to restore upper body motor function to quadriplegic spinal cord injury victims. Through lengthy and rigorous testing in human clinical trials, the therapy was found to be safe for use in people with all patients treated reporting at least some improvements. Asterias is now expanding its clinical trials to include patients with sub-acute injuries.

3. UC Irvine scientists engineer stem cells to destroy cancer

In a study conducted by University of California, Irvine researchers, a stem cell-based technique was devised to find and destroy breast cancer cells that had already metastasized. The cells “feel” the stiffness of the surrounding tissues and destroy the cancer-causing cells.

Embryonic stem cells can remain undifferentiated when they are grown in a well taken care of culture that is under stable conditions. Problems primarily begin to arise if cells are allowed to clump together to form embryoid bodies in which they begin to differentiate, or change into more specific cell variants, spontaneously. Although spontaneous differentiation is a good indication that shows which cultures of embryonic stem cells are healthy, the process is uncontrolled and, therefore, an inefficient strategy to produce cultures of specific cell types.

The ability of stem cells being able to differentiate into hundreds of other types of cells continues to amaze scientists as this is no small discovery. Researchers believe that the possibilities with stem cells are near endless, especially in regard to “regenerative medicine,” the process of “replacing, engineering, or regenerating human cells, tissues, or organs to restore or establish a new function.” It is even believed that even whole organs could be synthetically grown by using them.” Additionally, stem cells have the potential to rebuild healthy tissues, help people with heart disease, diabetes, ALS, Alzheimer’s disease, liver disease, Parkinson’s disease, cancer, and many more illnesses.

In a stem cell transplant, embryonic stem cells are first specialized into the necessary adult cell type. Then, those mature cells replace tissue that is damaged by a disease or injury. This type of treatment could be used to:

• Replace neurons damaged by spinal cord injury, a stroke, Alzheimer’s disease, Parkinson’s disease, or other neurological problems.
• Produce insulin that could treat people with diabetes and heart muscle cells that could repair damage after a heart attack
• Replace virtually any tissue or organ that is injured or diseased.

Sometimes scientists use stem cells as a drug. For example, it is possible to inject a stem cell into joints to reduce swelling and pain, or in order to promote the healing processes of soft tissues. Stem cell therapy is performed by injecting the patient’s own stem cells to stimulate the body to repair and replace damaged tissue in any joint or soft tissue structures – such as knees, shoulders, hips, wrists, ankles, elbows, tendons, ligaments and non-healing bone fractures. Cellular Dynamics, a large biotechnical company, sells human heart cells called cardiomyocytes that are derived from induced pluripotent stem (IPS) cells. Pharmaceutical companies are adapting to this new and innovative trend on a day-to-day basis. Stem cells can also be used to test the quality and safety of investigational drugs by testing them on stem cells that have been transformed into tissue-specific cells. Researchers are able to monitor the side effects before exposing the drug to a patient and thus have a greater expectancy of how their body may respond to the drug. This allows us to test for cures for potentially fatal diseases in ways that would otherwise be risky or unethical.

With all of the aforementioned advantages, stem cells are a fairly new, but exceptionally promising, research area. For some people, it may seem unethical to use stem cells on the grounds that extracting stem cells damages the blastocyst, which is a structure formed in the early development of mammals, more specifically the sixth or the eighth day of the development of an embryo. In 2006, President Bush vetoed the Stem Cell Research Enhancement Act stating that the federal government should not support “the taking of innocent human life.” Although stem cells are very promising for science and can open new doors to many new treatments in the medical field, it looks like there are still differences of opinion on their ethical use. This is perhaps because there is need for more convincing evidence or people are not informed accurately on the details of this research area.

References

• https://stemcells.nih.gov/info/Regenerative_Medicine/2006Chapter1.htm
• https://www.healthline.com/health/stem-cell-research
• https://www.statnews.com/2017/04/26/stem-cells-cancer-mutations/
• https://plato.stanford.edu/entries/stem-cells/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398703/
• https://www.mayoclinic.org/documents/the-amazing-stem-cell/doc-20249792
• https://www.unmc.edu/stemcells/educational-resources/history.html
• https://www.cirm.ca.gov/patients/power-stem-cells
• https://www.nature.com/news/stem-cells-take-root-in-drug-development-1.10713
• https://hsci.harvard.edu/examining-ethics-embryonic-stem-cell-research#:~:text=Opponents%20argue%20that%20the%20research,taking%20of%20innocent%20human%20life.%E2%80%9D

Most of us have taken, or at least interacted with, medicine at some point or another in our lives. This can range from more “simple” over-the-counter drugs to more complex medicines specifically designed for exact illnesses. Considering the Covid-19 era we are going through and as search for a vaccine is at the highest possible speed, it is important to have at least a general idea on how medicines are developed for our use. This article aims to explore how a complicated mix of chemical compounds in a laboratory end up as pills on a shelf in your local pharmacy. We will also explore a brief history of pharmacology, where drugs get their names, how drugs come into fruition, the various affects that drugs can have on our bodies, along with the discrepancies that exist between them in regard to when, how, and why they should be taken.

Pharmacology is the study of the interactions that occur between a living organism and the chemicals that affect normal or abnormal biochemical functions. It includes the study of how a drugs can affect our biological systems, such as individual organs or an entire part of the body, and how the body overall responds to the drug. The discipline encompasses the sources, chemical properties, biological effects and, therapeutic uses of drugs. Substances with medicinal properties are considered pharmaceuticals, whereas drugs given for therapeutic purposes are usually called medications. Drug therapy, which is also called pharmacotherapy, is the use of drugs to prevent, diagnose, and treat signs, symptoms, and disease processes. When prevention or cure is not a reasonable goal, relief of symptoms can greatly improve quality of life and the ability to function properly on a day-to-day basis. Developing an understanding of this craft can allow us to better appreciate how molecules interact to form the drugs and medicines that can change our lives, and perhaps even allow us to contemplate their complex creation and existence.

In its most simplistic definition, a medication is a substance that is ingested or placed onto the body in order to cure a disease or condition (antibiotics are given to cure an infection), treat a medical condition (anti-depressants are given to treat depression), relieve symptoms of an illness (pain relievers are given to reduce pain), given to prevent diseases (flu vaccine helps to prevent the person from complications of having the flu).

Source of drugs

Historically, drugs were mainly derived from plants, animals, and minerals. Morphine, insulin, and iron are all commonly used examples of their respective sources. Belief in the curative powers of plants and certain substances rested exclusively upon traditional knowledge. But empirical information was not subjected to critical examination. Until the end of the 19th century, medicines were made by natural organic or inorganic products including mostly dried or fresh plants and their parts. These compounds might contain substances that possess healing properties or reactions that exert a toxic effect. It is important to remember that many fruits, vegetables, and plants still possess great power despite not having a “modern” origin.

Most drugs used nowadays are synthetic chemical compounds manufactured in laboratories which are synthesized by altering the chemical structure of an existing drug. The first drug of a particular group of drugs are called prototypes. For example, morphine is the prototype of opioid analgesics, and penicillin is the prototype of antibacterial drugs. Drug classifications and prototypes are defined and most new drugs can be assigned to a group. We must be hopeful and continue to search far and wide for cures for all  diseases, whether they be organic or synthetic, since our world is full of an infinite amount of possibilities and discoveries.

Drug names

The systematic naming of pharmaceutical drugs is called “drug nomenclature.” Drugs primarily have three types of names: chemical names, generic names, and trade names. The chemical names are the scientific names that often sound complex and are based upon the molecular structure of a drug. During development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, such as the U.S. Food and Drug Administration (FDA), and will be granted a generic name for it. Generic names usually indicate, via their stems, what drug class the drug belongs to. For example, oseltamivir is an antiviral drug because its name ends in the -vir suffix.

After development, testing, and regulatory acceptance of a drug, the pharmaceutical company gives the drug a trade name, which is a standard term in the pharmaceutical industry for a brand name or trademark name. Many drugs have multiple trade names which can reflect separate marketing strategies in different countries, manufactured by different companies, or both.

Drug investigation

A new drug investigation is the beginning of the journey of a chemical compound to a drug that will be used in clinics. The testing process of a chemical compound begins with animal studies to determine potential beneficial uses and also potential toxic side effects of the candidate compound.  The results from these animal studies are reviewed, and if the results are satisfactory, the compound then undergoes clinical trials in humans that people can voluntarily sign up for. Most clinical trials use a randomized, controlled experimental design that involves selection of subjects according to established criteria, random assignment of subjects to experimental groups, and administration of the test drug to one group and a control substance to another group.

Patent protection

New drugs that are developed by pharmaceutical companies will be covered under patent protection. This means that only the pharmaceutical company that holds the patent is allowed to manufacture, market, and eventually profit from the drug. This is seen as a return on the company’s investment that it took to develop the drug, which may require years of work and millions of dollars, along with an incentive for developing other drugs. Other pharmaceutical companies cannot manufacture and market the drug during the patent period.

Usually, the drug patent is awarded for around twenty years in the United States, however the number of years varies across countries and drugs. Pharmaceutical companies apply for a patent long before the clinical trial period even begins. The effective patent period after the drug has finally received approval is often around seven to twelve years. After the patented period expires the drug can be manufactured and sold by other companies. The drug is referred to as a generic drug at this point, and they are required to be therapeutically equivalent and much less expensive than trade name drugs.

Pharmacoeconomics

Pharmacoeconomics involves all of the costs that are accrued due to drug therapy and experimentation including those related to purchasing supplies, dispensing the drug, storing it, administrative fees, laboratory and other tests that are used to monitor patient responses, and losses from expiration. The length of a patient’s illness or hospitalization is also considered. While the most important factor is the health of the patient the costs for treatment are increasingly being considered as a major factor when choosing medications, and research projects that compare costs have greatly increased in recent years. The goal is to make it easier for patients to choose the most cost-effective drugs that combine high quality treatment at an affordable price. For drugs or regimens of similar efficacy and toxicity, there is considerable pressure upon doctors and pharmacies to prescribe less costly drugs for shorter duration.

Prescription and non-prescription drugs

In many countries, consumers have two legal routes of access to therapeutic drugs. One route involves a prescription or order from a licensed health care provider, such as a physician, dentist, or nurse practitioner. The other route is by over-the-counter (OTC) purchase of drugs that do not require a prescription. Both of these routes are regulated by various drug laws that change from country to country. Acquiring and using prescription drugs for non-therapeutic purposes, by persons who are not authorized to have the drugs or for whom they are not prescribed, is illegal.

The rejection of drugs in modern society

Nowadays, there are some people who deny various kinds of treatments because of their religious beliefs. This category of people is only a minority, as the majority of religions advocate for people to be healthy and to take care of their health as much as they can. In almost all belief traditions, the human body is believed to be a trust, and in case of any disease, the most appropriate and fastest treatment methods should be used. Even substances that are not normally permitted are allowed by scholars to be used if the person’s safety is concerned. For believers, the most important goal in life is to worship God, and for this to be possible the body must be healthy.

One day, people asked Prophet Muhammad, peace be upon him:

“Should we make use of medical treatment?”

He replied: “Make use of medical treatment, for God has not made a disease without appointing a remedy for it, with the exception of one disease, namely old age.”

People are encouraged to seek out those remedies and to use them with skill and kindness. Let us also remember that Jesus, peace be upon him, too, was very active in his ministry of healing. He showed by God’s permission miracles like curing the blind and the deaf, and bringing the dead back to life. Thus, religions do not refuse treatment with any available methods, and they even strongly encourage treatment and prevention of diseases.

Religions are also well known to treat stress, which wreaks havoc on the mind and body. It is still not known exactly how stress harms our health, but researchers have found that chronic psychological stress is associated with body’s losing its ability to regulate the inflammatory response. It has been shown that the effects of psychological stress on the body’s ability to regulate inflammation can promote the development and progression of disease. We know that religions and beliefs give people hope and significantly decrease the stress.

Human beings are the most precious creation, and health is necessary for us to achieve the purpose of our existence. Using scientific medicine together with faith and religion can help people to protect their health. Being the science of drugs and by investigating new drug therapies, pharmacology helps us exactly with that.

History of Pharmacology

Claudius Galen (129–200 A.D.) was the first person who attempted to consider the theoretical background of pharmacology.

Ali al-Tabari (838 A.D.) Medieval Islamic physicians used natural substances such as Papaver somniferum Linnaeus, poppy, and Cannabis sativa Linnaeus, hemp as a source of medicinal drugs. Although poppy had medicinal benefits, Ali al-Tabari explained that the extract of poppy leaves was lethal, and the extracts and opium should be considered poisons (4).

Theophrastus von Hohenheim (1493–1541), also known as “Paracelsus”, began to question doctrines from antiquity. He prescribed chemically defined substances with such success that professional enemies had him prosecuted as a poisoner. Against such accusations, he defended himself with the thesis that has become an axiom of pharmacology:

“If you want to explain any poison properly, what then isn‘t a poison? All things are poison, nothing is without poison; the dose alone causes a thing not to be poison.”

Johann Jakob Wepfer (1620–1695) was the first to use animal experimentation for pharmacological or toxicological actions.

Rudolf Buchheim (1820–1879) founded the first institute of pharmacology at the University of Dorpat (Tartu, Estonia) in 1847, which firstly made pharmacology as an independent scientific discipline. In addition to a description of effects, he strove to explain the chemical properties of drugs.

Oswald Schmiedeberg (1838–1921), together with his many disciples, helped to establish the high  reputation of pharmacology. He partnered with pathologist Bernhard Naunyn (1839–1925) to found the first journal of pharmacology, which has since been published without interruption.

After 1920, the pharmacological industry had their own pharmacology laboratories outside established university institutes. After 1960, departments of clinical pharmacology were set up at many universities and in industry.

References

1. Clinical Drug Therapy: Rationales for Nursing Practice – Seventh 7th Edition, Lippincott Williams &Wilkins.
2. Basic&Clinical Pharmacology, 12^th Edition, McGrawHill Lange.
3. Modern Pharmacology with Clinical Applications, Sixth Edition, Charles R. Craig and Robert E. Stitzel, Lippincott Williams &Wilkins.

The Coronavirus pandemic has swept the world in recent months and with it came a wave of panic, unease, and a need for courage. Humanity is collectively fighting for its health, a treasure that we sometimes take for granted. It is imperative that we constantly look to maintain our health through reviewing potentially harmful practices and working to discover new methods of cleanliness and purity. Many of our articles in this issue will explore the theme of health across the spectrum including bodily, psychological, spiritual, and moral health. We also discuss Coronavirus in detail in this issue’s Science Square and dispel some conspiracy theories that the virus is man-made.

Washing our hands regularly is actually one of the most simple and effective ways to help prevent the spread of viruses, including Covid-19. Such a simple procedure seems like common sense nowadays, but this process was actually a breakthrough in the nineteenth century. Consistent hand washing and sterilization is especially important for hospital staff as they can easily transmit new diseases and germs into patients with weakened immune systems. Taking responsibility for our individual health will contribute to the overall health of our society by at least not spreading disease.

Diabetes is another disease that threatens the well-being of millions across the globe. It is complicated, and we explore in this issue the differences that excessive fat and sugar consumption can have in regards to causing and accelerating diabetes. We can best preserve our health with reasonably sized diets that are rich in nutrients, and routines that physical exercise.  

The effects of selfishness versus selflessness on the mind are also explored. It is no secret that many current societies promote selfishness over the well-being of others whether through subliminal advertisement messaging or the consistent emphasis placed upon trampling over others for career success. The way that we view and treat others, whether positively or negatively, has a rippling effect throughout society and works to either bolster or deteriorate our collective mental health and happiness.

We must especially work hard to preserve the health of our children, from the food that they eat to the media and technology that they use. Cell phone usage among infants and toddlers is becoming more and more widespread, however studies have shown that excessive usage can stunt their growth or even permanently alter their very fragile and rapidly developing brains.

Our world is rapidly changing, as it seems that every year produces new innovations and challenges to keep up with. It is up to us to stay informed and aware, lest we fall behind and fail to preserve the very things that we hold most dear.

If you heard that a very destructive creature was in your village, what would you expect this creature to look like? Perhaps a ferocious cat, or a colossal beast that was capable of leveling whole buildings? Such a creature does exist in Africa, except it is a single celled bacterium by the genus Trypanosome, a microscopic creature with the capacity to strike fear into the heart of virtually an entire continent. Living a segment of its life as a parasite in the bloodstream of humans and other mammals, Trypanosome can trigger a lethal neurological disorder in the circulatory system. It has also been found that it is the cause of a serious sleep disorder in humans. The disease can ruin a person’s circadian cycle, cause fevers, and changes in personality. Unfortunately, about 60 million people in 36 of the 52 countries in Africa are at constant risk.

Another significant role in the lifecycle of trypanosomiasis is the tsetse fly, the bacteria’s most common intermediate host, which transports the Trypanosome from one mammalian host to another. Trypanosomiasis is endemic in a large area of approximately 3.8 million sq. mi. in Africa, where both the parasitic disease and the tsetse fly coexist. Moreover, the danger is not limited to humans because it also affects many other mammal species, most notably livestock and horses. Malnutrition often follows as a direct consequence when large swaths of animals are killed by trypanosomiasis, as there will be less meat and dairy to consume.

The trypanosome parasite invites disease for the host mammal by collapsing or neutralizing its immune system. Let us first remember how the immune system works:

The immune system

Every living thing is provided with two things: food and protective systems. Immune system is one of these vital systems. Most immune systems across mammals function in similar ways; Antibodies are produced to destroy toxic substances and antigens on foreign bacteria, fungal cells, or the virus sheath invading the body. These antigens can be found on the infected foreign cells and have a unique shape and structure according to the organism that causes each disease. The immune system binds to the antigens of the foreign organism in the same manner as a key-lock system with its antibodies produced while fighting against the disease, thus neutralizes the invading organism.

Most of the antigens, which reveal the identity of a foreign being, are structures created of proteins, polysaccharides, or protein-based fats. Our immune system has the sensitivity and the capacity to produce an infinitely diverse variety that can discern even quite identical but foreign substances bearing antigenic properties for our body. To draw an analogy, a specific antibody can be produced for each speck of dust on Jupiter. Our immune system is blessed with the ability to synthesize appropriate antibodies by selecting proteins that differ in type or location of one amino acid.

The mechanism of binding of the antibody to the antigen is carried out with effective economy, because each type of antibody is produced specifically against a particular antigen. This mechanism works like a key-lock system, so the body recognizes its own cells and does not attack them. Each antibody produced in the immune system is created in a three-dimensional, one-to-one compatible structure with the antigen that causes it to be produced, and easily recognizes and locates it, binds as the key fits into the lock, and thus renders it harmless by disrupting the chemical structure of the antigen.

Trypanosome and the immune system

The case of trypanosome vs. the immune system is somewhat exceptional. The abovementioned almost universal immunity principle does not work against trypanosome. Even though parasites are constantly exposed to the mammalian immune system in the blood, they constantly change the antigen that forms the surface sheath. They thwart the host’s defense, as if rapidly changing their password so that it can never be guessed. Until the immune system produces new antibodies to bind to new antigens, some of the trypanosomes discard their sheaths and drape themselves in another one. If this condition persists, the immune system of the host cannot cope with the infection and may succumb to it.

This extraordinary phenomenon astonishes the scientific community and many scientists are investigating the molecular structure of antigen diversity extensively in African, European, and US laboratories. These parasites are only 0.015–0.030 mm in size, and its two most notorious species are Trypanosoma rhodesiense and Trypanosoma gambiense, which inflict serious damage on the human body.

Like many other parasitic species, the life cycle of trypanosomes is very complex. In each phase of this life journey, the parasite takes different forms and exhibits different characteristics in such an unusual way that generates curiosity. The life cycle can be summarized as follows: when the tsetse fly bites a disease-bearing mammal, the trypanosomes in the mammal’s blood are sucked up and settle in the middle intestine of the fly. They undergo a series of complex processes including several structural and biochemical changes. After about three weeks, the trypanosomes appear in the fly’s salivary glands in a disease-bearing form. Meanwhile, they are also draped in new surface sheaths.

When the secondary host fly bites a healthy person, the disease-causing trypanosomes enter the blood of the new host. In this new stopover, parasites are transformed into a form in which they can rapidly multiply. First, they wreak havoc in blood vessels and on lymph nodes, causing fever, marks and swelling in the body. At this stage, a constant struggle with the host’s immune system ensues. A likely invasion the patient’s central nervous system by the trypanosomes can cause intense drowsiness, coma, and eventually death.

In years of research on the trypanosomes, the thick surface sheath covering the cell membrane of the parasite was first described in 1965 by Keith Vickerman of the University of Glasgow. Shortly thereafter, different surface sheaths were discovered in different trypanosome clones. In 1968, Richard W. F. Page from the Molteno Parasitic Research Institute in Cambridge analyzed and decoded the isolated antigenic surface proteins from several clones, revealing that each clone had a biochemically different protein. The clarity of these differences suggests that each antigen is expressed by a different gene. In the 1970s, George Cross and his colleagues found evidence supporting Le Page’s proposal. These antigens are now called Variable Surface Glycoproteins (VSG). As a result of subsequent research, the picture became even more clear.

Once the infection has begun, antibodies are formed in the host’s immune system that bind to the variable surface glycoproteins that appear on the surface sheath of the invading parasites. These antibodies kill most of the initial trypanosomes. Yet interestingly, on a few remaining trypanosomes a new sheath to which antibodies cannot bind is built, and the trypanosomes evade the immune system’s grasp. The survivors induce a new population producing new variable surface glycoproteins. This time, the immune system produces new antibodies against these freshly constructed antigens. Meanwhile, the parasitic population grows. Newly produced antibodies are able to kill 99% of new parasites again. However, until that time, the parasitic group constituted by about 1% of the survivors has already changed its sheath. Hence, another population begins to multiply. This process of life being a struggle unfortunately continues until the host mammal dies.

The mechanisms of antigen diversity in trypanosomes are very complex and variable, and the total capacity to produce varieties is not clearly known. Recombinant DNA technology is used to investigate the structure of the genes for producing variable surface glycoproteins, the mechanism of cell membrane binding, and the selection and expression of one of the codes. In addition to the four licensed medicines produced for the treatment of parasitic diseases, new drugs are being developed.

It is astonishing that this tiny window of invisible dimensions has such a huge potential opening to different branches of science. Many such exceptional and precise situations exist in the universe that may showcase contradicting mechanisms with general principles and procedures. Sometimes we may wonder why God creates such harmful parasites. Since we do not know the performance at every point of an entire ecosystem with our insufficient scientific knowledge, limited sensory organs and temporary observation, we tend to see any seemingly harmful being as futile and devoid of wisdom and immediately raise our voices in protest. However, with new discoveries in science, thousands of wise meanings may be extracted from a creature we generally take for granted.

References

Lori Peacock, Simon Cook, Vanessa Ferris, Mick Bailey, Wendy Gibson (2012): The life cycle of Trypanosoma (Nannomonas) congolense in the tsetse fly, Parasites & Vectors, 5:109 www.parasitesandvectors.com/content/5/1/109.

Michael P Barrett, Richard J S Burchmore, August Stich, Julio O Lazzari, Alberto Carlos Frasch, Juan José Cazzulo, Sanjeev Krishna, (2003): The Trypanosomiases, The Lancet, Vol 362, November 1, Pages 1469-1475, www.thelancet.com.

www.cdc.gov/dpdx/trypanosomiasisafrican/index.html

Life is in the center of existence, and food is in the center of life. All living things are in pursuit of their sustenance to continue their lives. Failing this pursuit means the end of it all. Yet, it is not only the lack or scarcity of food, but also its abuse that is a major cause for disorders. Consuming food without any criteria of lawfulness, or with no heed to virtues like contentedness or gratitude, but with greed and wastefulness, leads to many health problems – mental and physical – at both individual and societal levels. Among these problems are many notorious eating disorders such as obesity, anorexia, and bulimia nervosa. Illnesses that relate to overeating, such as obesity, are now beginning to be considered as food addictions, even as a type of substance abuse, in some medical literature [1].

One serious consequence of eating and food addictions is a clinical condition that is called “metabolic syndrome” (MetS). Characterized by multiple cardiovascular disease risk factors such as obesity and high blood pressure, this syndrome has been recognized as a crucial public health problem worldwide. Characteristics such as geography, race, age and gender are influential in the frequency of the disease, which spreads daily as a pandemic that affects approximately 20-30% of the global adult population [2]. Among US adults aged 18 years or older, the prevalence of metabolic syndrome rose by more than 35% from 1988–1994 to 2007–2012, increasing from 25.3% to 34.2% [3].

First described by Dr. Gerald Reaven, MD, in 1988, metabolic syndrome is also referred to as “insulin resistance syndrome,” “deadly quartet,” and “civilization syndrome” [4]. In 2001, the Adult Treatment Panel (NCEP-ATP III) defined metabolic syndrome in adults as the combination of central obesity (waist circumference >102 cm in men, >88 cm in women), hypertriglyceridemia (>150 mg/dl), low HDL (<40 mg/dl in men, <50 mg/dl in women), hypertension (blood pressure> 130-85 mm-Hg), and hyperglycemia (fasting blood sugar >110 mg/dl). In 2005, the International Diabetes Federation (IDF) published a global guideline describing different thresholds for different ethnic groups. According to this guideline, the diagnosis of metabolic syndrome should be based upon central obesity and high triglyceride, low HDL, high blood pressure, and high fasting glucose. The IDF also reported that the presence of at least two factors sufficed for diagnosing anyone as a patient of metabolic syndrome.

as one of the likely pathological findings in metabolic syndrome, central obesity is observed in one in three adults. Hypertension, another crucial factor, is generally acknowledged to be originating from insulin resistance in metabolic syndrome, but the actual features of its development mechanism still remains controversial. Global awareness about hypertension, its treatment, and how to control it is low, and there are significant differences in between people worldwide. A National Health Examination Survey (NHANES) spanning 2011-2014 revealed that 34% of US adults aged 20 years and older are hypertensive and NHANES 2013-2014 data showed that 15.9% of these hypertensive adults are unaware they are hypertensive [5].

Dyslipidemia, which increases as a result of central obesity and insulin resistance in patients with metabolic syndrome, is characterized by low HDL cholesterol and high triglycerides, the most crucial factors that increase the risk of cardiovascular disease. In one study done in 2008, the average total cholesterol levels for American men and women were found to be 197 mg/dl [6].

The presence of overt diabetes or impaired glucose tolerance (fasting blood sugar above 110 mg/dl) indicates the first step of the diagnostic criteria of the metabolic syndrome, and insulin resistance is not sought for further. People diagnosed with metabolic syndrome are 2.34 times more likely to contract diabetes [7]. A 2011 study conducted in America reported that roughly half of all adults have impaired glucose metabolism as a result of type 1 diabetes, type 2 diabetes, and prediabetes. Diabetes has been a prevalent global ailment similar to asthma, autoimmune diseases, and cancer [6].

Insulin resistance, which can be observed in metabolic syndrome, increases the risk of cardiovascular disease by 2.35 times, deaths by cardiovascular disease by 2.40 times, risk of myocardial infarction by 1.99 times, and stroke by 2.27 times, as independent of other risk factors. However, the presence of metabolic syndrome, not obesity, increases the risk of cardiovascular disease [7]. Another significant result is that women with metabolic syndrome have a higher risk of cardiovascular disease than men. Women are more likely to have central obesity than men, have a different cholesterol profile, and higher triglyceride levels that cause more coronary artery disease, while polycystic ovary syndrome, hormone support therapies, and pregnancy diabetes pose additional risk for women [8]. Fatty liver disease, cirrhosis, chronic kidney disease, polycystic ovary syndrome, gout, dementia, and decreased cognitive functions are more common in individuals with metabolic syndrome than the normal population [7].

Treatment of Metabolic Syndrome

Since metabolic syndrome is caused by environmental and genetic factors, and is appearing in people with increasing frequency, the best treatment approaches involve a well-regulated lifestyle, with the main objective being to prevent diabetes and cardiovascular diseases that cause fatal or disabling conditions. Weight loss that results from an appropriate nutrition and exercise program has a corrective effect on almost all disorders observed in metabolic syndrome.

In the treatment of metabolic syndrome, prevention of central obesity seems to be a priority solution. This can be achieved by a lifestyle planning that provides and maintains a 7-10% reduction in total body weight by limiting caloric intake and increasing physical activity. Even methods that increase weekly physical activity by 150-300 minutes and provide only a 5-7% reduction in body weight are considered sufficient to correct the metabolic syndrome. This has especially been reported to have a positive effect on lipid disorders, glucose intolerance, and hypertension, with a 58% reduction in the risk of diabetes with additional lifestyle changes [9].

Since a well-regulated diet is one of the focal points of life style change for people with metabolic syndrome, dietary models that are limited to saturated fats and cholesterol, rich in complex carbohydrates, based upon an abundant consumption of fruits and vegetables, and a restricted use of salt (for those with hypertension) are strongly recommended.

Even though the traditional Mediterranean diet is lauded as one of the vibrant treatment options in the prevention of coronary heart disease and metabolic syndrome, it is not sufficient to correct the metabolic syndrome unless the diet is in tandem with significant weight loss [10]. According to numerous studies, increasing the consumption of nutrients such as fish, vegetables, fruits, dried legumes, and unrefined grains that are rich in olive oil, omega-3 fatty acids, and antioxidants reduce the risk of coronary diseases and death. It goes without saying, that smoking and alcohol use may increase cardiovascular, metabolic and hepatic complications in patients with metabolic syndrome.

Patients with metabolic syndrome should have their blood lipids checked annually, and should be determined to keep low-density lipoprotein (LDL) cholesterol lower than 100 mg/dL, high density lipoprotein (HDL) cholesterol higher than 40 mg/dL, and triglyceride levels lower than 150 mg/dL. Diabetic patients should set their blood pressure target as lower than 130/80 mm-Hg. Changes in lifestyle such as regular exercise and a controlled diet are extremely vital. The use of low-dose aspirin to prevent complications in patients with coronary artery disease is also among treatment recommendations.

The basic sustenance that is provided to us in the form of fruits, animals, grains, and other bounties is such a precious, rich and full-fledged treasure, for which we should be grateful for. However, gluttony and wastefulness pave the way for thanklessness, disease, and even conflicts with the wisdom in the universe.

Almost all living beings are engaged in the pursuit of sustenance and revolve around this goal. We humans have been equipped with the ability to taste and appreciate all kinds of food, and can draw an appreciation for the Divine through these gifts. Just as everything revolves around sustenance, thankfulness has been placed in the center of sustenance. That is, gratitude should be at the center of all sustenance. Through gratitude, we live healthier physical, spiritual, and mental lives.

Notes

1. Meule A, Rezori V, Blechert J. Food addiction and bulimia nervosa. Eur Eat Disord Rev. 2014;22:331–337.
2. Grundy SM. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 2008; 28: 629-36.
3. Moore JX, Chaudhary N, Akinyemiju T. Metabolic Syndrome Prevalence by Race/Ethnicity and Sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Prev Chronic Dis 2017;14:160287
4. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539-53.
5. Alexander, Matthew R.; Eric H. Yang. “What is the prevalence of hypertension (high blood pressure) awareness of in the US?” https://emedicine.medscape.com/article/241381-overview#a2
6. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States, 2011. Atlanta, GA, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
7. Balcı M.K, Metabolik Sendrom, Türkiye Klinikleri J Med Sci 2008;28:102-106.
8. Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010; 56: 1113-32
9. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403
10. Carbonneau É1, Royer MM2, Richard C3, Couture P4, Desroches S5, Lemieux S6, Lamarche B7. Effects of the Mediterranean Diet before and after Weight Loss on Eating Behavioral Traits in Men with Metabolic Syndrome. Nutrients. 2017 Mar 19;9(3).

Gastro-esophageal reflux disease (GERD) is among the most common chronic diseases in the Western world, affecting up to 30% of the general population in Europe and the US. It is a condition which develops when the acidic contents of the stomach flow backwards into the esophagus and cause what’s known as heartburn. While most patients respond well to the standard therapy of proton pump inhibitors which block acid-secreting cells in the stomach, we are still trying to understand the molecular reasons why 30-40% of reflux patients do not respond adequately to acid-suppressant therapy. Not only does GERD have a significant negative impact on health-related quality of life, but the over-subscription of ineffective drugs causes a significant economic burden on healthcare.

Heartburn is the most noticeable and troublesome symptom of GERD. From what we currently understand about the pathophysiology of the disease, we know that the reflux of acid evokes different types of pain, but the basic mechanisms and pathways by which this pain is generated is incompletely understood. The junction between the esophagus and stomach is structurally and functionally designed in a way to ensure that any acid secreted in the gastrointestinal tract flows towards the stomach, and not up onto the lining of the esophagus. This function is served by the muscle structure sitting at this junction, called the lower esophageal sphincter (LES), which ensures that the ingested food following a meal does not reflux. However, there are several factors which can make the LES’s job more difficult. One of the most obvious factors includes the excessive consumption of food, particularly during the later hours of the day. There is convincing evidence that 90% of reflux episodes occur post-prandially, due to minor elevations of intragastric pressure which causes the LES to relax and therefore allow the reflux of acid. In more advanced cases of reflux disease, acid pockets form at the gastroesophageal junction where unbuffered acid collects into a reservoir. When the LES fails in this setting, there is reflux of a higher volume of acid.

Focusing on the microscopic structure of the esophagus and stomach, we can see a minute yet essential difference between the linings of these two gastrointestinal organs. The esophagus has a stratified squamous epithelial lining, which acts as a tight protective barrier against food but is readily damaged when exposed to a chemical environment. On the other hand, the stomach is lined by tall columnar epithelium, which is designed to withstand very low pH and high levels of proteolytic activity. Our gastrointestinal tract (and the human body in its entirety) is perfectly designed to carry out the specific role of transporting food from the oral cavity from the esophagus to the stomach, where it is digested for our nourishment. It is oftentimes our greediness and overindulgence which disrupt the perfect order of our anatomy at a molecular level, resulting in the macroscopic changes we see at endoscopy and the symptomatic discomfort we feel from the painful circumstances of reflux. 

The stomach is our center of nourishment. Given that every food particle has the purpose of nourishing the cells of our body, why do we so commonly make the mistake of eating excessively, nocturnally, and quickly? Fatty foods influence the relaxation of the lower esophageal sphincter, along with alcohol, coffee, and acidic drinks. Large meals and rapid food intake distend the stomach, increase intragastric pressure and facilitating the reflux of acid from the stomach. Given these, it is plain to see that, in most cases, simple lifestyle changes can prevent the development of such chronic and discomforting diseases. The following verse in the Holy Qur’an offers a short but very effective prescription: “Eat and drink, but do not be wasteful” (7:31).

The philosopher and physician Ibn Sina (Avicenna) summarized the science of medicine as follows: “Eat little when you eat, and after eating do not eat again for a certain period of time; health lies in digestion. There is nothing heavier for the body to tolerate than putting food after food in the stomach.” Frugality in eating is also echoed in the teachings of Prophet Muhammad, peace be upon him, who famously said “There is no vessel which the son of Adam can fill more evil than his stomach, for it is sufficient for him to take a few mouthfuls in order to straighten his back; but if he must, then fill one-third with food, one-third with drink, and one-third with air” (Tirmidhi).

The lifestyle factors that are strongly associated with GERD are obesity and smoking. In the 30-40% of GERD patients who do not respond to acid-suppressant therapy, simple lifestyle changes such as cutting out acidic drinks and eating more slowly, and not after 7 pm have been effective alternative treatments. While our understanding of molecular pain mechanisms of the esophagus need further improvement, the simple act of making minor changes in our eating habits can ensure that the anatomy and function of our gastrointestinal tract remains optimal.

Amyotrophic Lateral Sclerosis (ALS) is a terminal illness of the nervous system, resulting in the degeneration of neurons. When the motor neurons in the lateral spinal cord degenerate, the muscle cannot be stimulated and gradually atrophies. As the disease progresses, the brain cannot initiate and control muscle movement, so voluntary muscle actions, such as reaching for your phone or typing on a keyboard, are lost. Currently there are no treatments or cures to reverse the effects of ALS and the disease process is still widely unknown. Some noteworthy individuals diagnosed with this disease have included Lou Gehrig, Stephen Hawking, Jon Stone, George Yardley, Henry A. Wallace, and Steve Gleason. These are the facts, but I could have never realized what living with ALS was like until I listened to a retired senior, a teacher, and a musician tell me their stories.

The older couple told us of their past year as the husband wrote on an electronic note pad to fill in the gaps of his spouse’s version of their story. They had first noticed his symptoms when he began choking on his food, and they had to adapt as the disease progression got more and more severe. His wife comically said that she doesn’t know where to look when he’s trying to talk to her – “Should I look at his eyes, his mouth, this pad?” Every day, they had to face a new challenge and overcome it together, as a family.

Another patient was a mother, a teacher, now wheelchair bound and with a respirator to help her breathe. Because of her age, none of her physicians expected ALS and thought she was struggling from carpal tunnel syndrome or an ulnar nerve injury. She told us her husband was her biggest caregiver and supporter; her husband joked, “She makes the list and I carry it out.” He talked about his struggles, working full time as well as being a full-time caregiver for his wife and their 3-year-old daughter, as well as still finding time for self-care. Even with all this juggling, he felt guilty. This guilt was expressed by many of the caregivers: some because they didn’t even notice the symptoms and others because they felt like they couldn’t help their spouses. Guilt was felt by the patients too. The mother was upset because her daughter would only remember her in a wheelchair. Despite the difficulties, family was a major support system for each patient.

When asked about how she felt after getting her diagnosis, the musician said, “I felt like a deer in headlights… I never pictured I was going to go out that way… with a terminal illness… Last year I had no trouble walking, singing, cooking, gardening, and this year…” Despite all of this, she said she felt relieved. Her struggle to find a neurologist who respected her was heartbreaking. She had gone to a physician because she felt helpless; she was having trouble playing guitar, she was losing her identity as a musician. However, the physician assumed from her past medical history of anxiety that she was having mental issues with memory, anxiety, and depression. As she continued to receive hostile treatment, she found a second doctor who listened to her. Unfortunately, even though he took her seriously, he didn’t have the courage to diagnose her with ALS, telling her instead that she had a motor neuron disease and referring her to a specialist. When she finally received the diagnosis of ALS, she was relieved. She no longer felt crazy. She was able to be heard. She was able to communicate with someone who wanted to help her. ALS is already a hard disease to diagnose; not having someone on her side only made her situation more difficult. She says now, as each symptom appears, she isn’t afraid anymore, because she knows it’s ALS. This relief of having a concrete diagnosis, of having a diagnosable disease, even one that is untreatable, was reiterated by several of the other panelists.

Although a diagnosis was a relief for many of the patients, they all saw the importance of taking part in clinical trials. They recognized that ALS affects everyone at different times in different ways and hoped that one day they could explain why this illness is so hard to detect and track. Participating in various studies and trials made them feel like they were helping future patients and physicians to be able to better understand why this terminal disease can strike at any time, with no discernable warning signs, affecting each individual uniquely in initial symptoms and progression.

Getting a concrete diagnosis gave these patients the freedom to seize the day and live in the moment. For the musician, as her ability to play guitar diminished chord by chord, and she started slurring her words, preserving her voice and her identity became very important to her. She is using a message banking app to preserve her voice. The software requires her to read thousands of words and sentences. Although she had to accept the things she could no longer do, she realized that she did not have to give up her identity or love of music because of ALS. Overflowing with her love of music, she told us about how when choirs sings together, their hearts become synchronized; and how music lowers blood pressure and stimulates all areas of the brain. As she interwove details about her symptoms with her favorite song, Fire on the Mountain by the Grateful Dead, the two had become part of the same spiritual transformation. Smiling peacefully, she explained, “Maybe nobody else hears it the way I do. I see death as the final healing, finally being released from your body.” She viewed her diagnosis as graduating early and the symptoms that came attached with it as her disappearing slowly, rather than all at once. The unavoidable indignities were just something she had to accept. What mattered most to her was keeping her individual personality in the face of intense daily struggles.

By the end of our discussion, I felt the weight of my white coat as I never had before and recognized that this would be the first of many times that I would have to carry this symbol of patient advocacy. As these patients spilled all their vulnerabilities to a group of 50 students, I realized the most important thing I will learn in medical school is opening my heart without getting crushed under negativity. I learned that, as doctors, we have the tendency to think the ultimate solution is life, when in truth, mortality is the reality. What matters is being present when there is a fire, realizing that “a pail of water” may not be enough to put it out, but continuing to carry that water for your patient.

Long distance runner, what you standin there for?
Get up, get out, get out of the door

There’s a dragon with matches that’s loose on the town
Takes a whole pail of water just to cool him down
-The Grateful Dead

Alzheimer’s disease is “an irreversible, progressive brain disease that slowly destroys memory and thinking skills, eventually even the ability to carry out the simplest tasks” according to the Alzheimer’s Association. Alzheimer’s affects mostly senior citizens, and symptoms first appear in most people between 60 and 70. The first signs of Alzheimer’s, though, can be noticed between the ages of 30 and 65. However, it is very rare for younger people to exhibit symptoms. Most cases of dementia are caused by Alzheimer’s disease [1]. It is known that all Alzheimer’s patients have dementia; however, one cannot say that all dementia patients have Alzheimer’s disease. Alzheimer’s is a deadly disease, finishing predictably in death [2].

Alzheimer’s disease is named after Dr. Alois Alzheimer. In the early twentieth century (1906), Dr. Alzheimer observed alterations in the brain tissue of a woman who had expired of an uncommon mental disease. Her signs involved loss of memory, language difficulties, and erratic conduct. After her death, Dr. Alzheimer inspected her brain and discovered many uncharacteristic clusters (now called amyloid plaques) and scrambled packets of filaments (now called neurofibrillary, or tau, tangles) [1].

Based on his findings, he correctly theorized that these anomalous buildups were accountable for the patient’s loss of memory and other mental complications.

The plaques and tangles in the brain are some of the foremost characteristics of Alzheimer’s disease. Another characteristic is the damage of contacts between nerve cells (neurons) in the brain. Neurons conduct communications between different segments of the brain – for example, they conduct communications from the brain to muscles and organs in the body. Many other multifaceted brain alterations are thought to play a function in Alzheimer’s disease.

In the beginning, this impairment seems to take place in the hippocampus of the brain. The hippocampus is the part of the brain that is indispensable in forming memories. When neurons perish, further parts of the brain are distressed. In the last stage of Alzheimer’s, destruction is extensive, and brain tissue has shortened substantially.

How many Americans have Alzheimer’s disease?

It is estimated   that more than 5 million Americans may have Alzheimer’s disease. If existing population developments continue, the number of people with AD will increase significantly. However, this trend can be stopped if the disease can be effectively treated or prevented.

The reasons people develop Alzheimer’s are still not fully understood. One known reason is aging.   Age is the most significant accepted risk factor for Alzheimer’s disease. In 2010, in the United States, close to 5 million people 65 years and older were living with Alzheimer’s illness. A 2013 report from the Alzheimer’s Association suggests that 1/10^th of all Americans over 65 are suffering from Alzheimer’s. The proportion goes up to about a third of the population for those who are over 85. According to the Alzheimer’s Association, AD incidence is between 60% and 80% of all incidents of dementia [3].

Incidence of Alzheimer’s disease in South Asia

Globally, at least 44 million individuals live with dementia, making the disease a worldwide health catastrophe that must be tackled. In excess of 4 million individuals have some appearance of dementia in India [4].

In the Southern Indian state of Kerala, 1066 qualified members who were cognitively regular at reference, 104 of them acquired dementia (98 of them were found to have AD) over a continuation time of 8.1 years. The occurrence rates per 1000 person-years for AD was 11.67 for persons aged ≥55 years and greater for those aged ≥65 years (15.54). Individuals who were aged ≥65 years, the global age consistent occurrence rate, was 9.19 per 1000 person-years, prevalence rate of AD raised substantially and proportionally with growing age. These are the initial AD occurrence rates to be conveyed from southern India. When compared to reports from rural North India these occurrence rates appear to be much greater. But they are comparable with those reported from China, and slightly lesser than that reported from the western world [5].

Signs of Alzheimer’s disease

Memory difficulties are characteristically one of the first signs of Alzheimer’s; nonetheless, early indications may differ from individual to individual. A decrease in other facets of thinking, for example forgetting words, sight/three-dimensional problems, and diminished thinking or decision making, may additionally indicate the precise initial periods of Alzheimer’s disease. Mild cognitive impairment (MCI) is a disorder that can be an initial mark of Alzheimer’s. However, not everyone with MCI will develop Alzheimer’s.

Patients with Alzheimer’s have difficulty performing routine things like paying bills, driving a car, or cooking food. They repeatedly ask the same questions, go astray without difficulty, misplace things or put them in unusual places, and find even easy things puzzling. As the disease advances, some patients become anxious, wrathful, or furious.

Longevity of a person with Alzheimer’s disease?

At the time of diagnosis, if the person is older than 80, they are only likely to live another three or four years. If the person is younger then 80, they could live for as many as ten years or more.

Currently Alzheimer’s disease is graded as the sixth greatest cause of death in the United States. But fresh evaluations show that the illness may be listed as third, after heart disease and cancer, as a source of death for elderly people.

At the present time, there is no cure for Alzheimer’s. However, treatment can help patients cope with symptoms [1].

In the 21^st century, Alzheimer’s can only be diagnosed with 100 percent precision through a postmortem examination that discloses the occurrence of the distinctive plaques and tangles. However, a complete examination and suitable checkup can afford a dependable diagnosis with better than 90 percent certainty.

Malformed accumulations of particular proteins inside the brain interrupt normal brain performance and produce the reasoning and efficient difficulties characteristically connected with Alzheimer’s Disease. Ultimately, as the sediments expand all over the brain, brain material begins to die. This results in additional intellectual damage. CT scans and MRI scans show the subsequent brain contraction. CT scan shows enlargement of the ventricles in the brain and loss of brain tissue in a patient with Alzheimer’s disease. Recent research is endeavoring to ascertain what produces these accumulations and is watching for techniques to avoid or change them before they cause lasting brain destruction [2].

Alzheimer’s is not curable.
Alzheimer’s is not contagious.
Alzheimer’s is not a natural part of the aging process.
Alzheimer’s is not something you get from using deodorant or cooking in aluminum pans.
Alzheimer’s is not inevitable if you live long enough.

In some families, Alzheimer’s disease is hereditary. But these appearances are very rare, and they account for fewer than five percent of all incidents. If a family member like a mother or a brother has Alzheimer’s disease, it doesn’t inevitably mean that you’re prone to contract it as well.

There is no test that can foretell whether you’ll get Alzheimer’s disease, save tests for the very rare hereditary Alzheimer’s. A blood test can tell whether you have a certain form of cholesterol-carrying protein connected with an elevated occurrence of the disease. This examination can’t convey whether you’ll actually contract the condition; at least 50 percent of people who have an elevated risk factor never get Alzheimer’s.

Taking into consideration medical ethics, healthcare authorities counsel against taking this blood test or undertaking other genetic testing because they want to save their patients from unwarranted fear about something that will perhaps never happen. There are others reasons for which they also advise against testing. If a person has the inherited gene or elevated risk factor, it might negatively affect their ability to acquire health insurance or long-term care.

Causes of AD

All types of dementia are a result of brain cell death. As such, Alzheimer’s Disease is also caused by brain cell death. When there is an ongoing brain cell death occurring over a period of time, then it is called a neurodegenerative disease. When the brain tissue has an increasingly smaller number of nerve cells and connections, then the total brain size shrinks due to Alzheimer’s.

Plaques in the brain are a result of the build-up of a protein called beta-amyloid (also known as “amyloid plaques”). These plaques cannot be seen or tested for in the living brain affected by Alzheimer’s Disease. A postmortem or autopsy will show these plaques and masses. Plaques are found between the dying cells in the brain.

These unusual protein clusters in the brain tissue are always present with Alzheimer’s disease. Scientists are not yet sure if there could be an additional primary activity that is really causing Alzheimer’s Disease. This sort of alteration in brain nerves is also observed in other illnesses. Researchers want to find out how these protein abnormalities progress so that a cure or treatment might be discovered. Researchers have not completely comprehended why the alterations that lead to Alzheimer’s disease befall a patient. It is known that several dissimilar factors are believed to be implicated, aging and a family history of Alzheimer’s, chief among them.

Diagnosis

Alzheimer’s disease is not straightforward to diagnose, as there is no single test for it. The first step physicians take is to rule out other complications before validating whether mental indications and signs are stark enough to be a type of dementia or something else.

Signs and symptoms [6]

Phases of Alzheimer’s Disease:

Aging has effects on memory but not AD.

• Occasionally forgetting things.
• Sometimes items are misplaced.
• Slight temporary memory loss.
• Not recalling precise particulars.

Early phase

• Not recollecting incidences of deprived memory.
• Forgetting names of family or friends.
• Only close friends or relatives may notice the changes.
• Some perplexity in conditions outside the acquainted.

Middle-phase

• Enormous effort recollecting newly acquired knowledge
• Increasing misperception in numerous situations
• Difficulties with slumber or sleep
• Difficulty in recognizing where they are

Late-phase

• Low capability to reason
• Difficulties in talking
• Retelling same dialogues
• Extra rude, nervous, or suspicious

Treatment

For Alzheimer’s there is no recognized treatment. The loss of brain cells cannot be stopped or overturned.

Drug therapy

There are no disease-altering medicines obtainable for Alzheimer’s, but some choices may decrease its symptoms and help recover quality of life. Four drugs are available. They’re called cholinesterase inhibitors. They include Donepezil (brand name Aricept), Rivastigmine (Exelon), and Tacrine (Cognex). Another type of drug, called memantine (Namenda), which is an NMDA receptor antagonist, may also be used. This drug may be used alone or with a cholinesterase inhibitor.

Other therapies

As with other kinds of dementia and neurodegenerative illness, a chief part of therapy for patients with Alzheimer’s comes from the patronage given by healthcare personnel. Quality-of-life care becomes more imperative as needs increase with diminishing freedom [3].

There are other treatments outside the US. In India, Alzheimer’s disease is treated with Ayurveda [7]. Ashwaganda, an ancient Herb used in Ayurveda, is confirmed to be a possible cure for Alzheimer’s [8]. It has also been found that Curcumin (in India it is called Haldi) is more efficient at hindering the formation of the protein fragments than many other potential Alzheimer’s treatments. Optimizing vitamin D and vitamin B12 intake, as well as a nutritious diet rich in folate and coconut oil, have also been tested as to their efficacy at treating Alzheimer’s Disease [9].

Daily mental challenges

Mental stimulation, particularly acquiring something novel, such as learning to play an instrument or a new language, is linked with a reduced risk of Alzheimer’s. Researchers theorize that mental tasks assist in developing the brain, making it less prone to the lesions connected with Alzheimer’s Disease [8].

References

1. What Is Alzheimer’s Disease? National Institute on Aging, U.S. Department of Health and Human Services. https://www.nia.nih.gov/health/what-alzheimers-disease
2. Alzheimer’s for Dummies, Patricia B. Smith, Mary M. Kenan, Mark Edwin Kunik, Leeza Gibbons. October 2003. http://www.dummies.com/health/knowing-what-alzheimers-is-and-is-not/

3. What’s to know about Alzheimer’s disease? Medical News Today. Newsletter. 13 February 2018. https://www.medicalnewstoday.com/articles/159442.php
4. About Alzheimer’s and Dementia. org. India, Alzheimer’s association. https://www.alz.org/in/dementia-alzheimers-en.asp
5. Incidence of Alzheimer’s disease in India: a 10-years follow-up study. Mathuranath PS1, George A, Ranjith N, Justus S, Kumar MS, Menon R, Sarma PS, Verghese J. Neurol India. 2012 Nov-Dec;60(6):625-30 https://www.ncbi.nlm.nih.gov/pubmed/23287326

6. Alzheimer’s disease. From Wikipedia, the free encyclopedia. https://en.wikipedia.org/wiki/Alzheimer%27s_disease
7. Treating Alzheimer’s disease with the help of Ayurveda by Hunila. November 1, 2012 org. http://www.alzheimerindia.org/treating-alzheimers-disease-with-the-help-of-ayurveda/

8. Ashwaganda: Ancient Herb Proven to be a Potential Cure for Alzheimer’s by Dr. Mercola April 07, 2012 https://articles.mercola.com/sites/articles/archive/2012/04/07/ashwaganda-effect-on-alzheimers-disease.aspx

9. Coconut Oil and Alzheimer’s Disease By anh-usa (Alliance for Natural Health) on October 5, 2010. http://www.anh-usa.org/coconut-oil-and-alzheimers-disease/