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.

Some medications are effective directly over the area they are applied to. Some however are transported to distant regions via blood flow and that is where they are most effective. Medication is either taken orally or through injection. When medicine passes into the blood stream from the place of administration, it is considered to be absorbed. A good example is the transportation of medicine into the blood stream of capillary vessels between the muscle cells when injected into muscle tissue. A drug taken orally however is absorbed through the blood vessels in the gastro-intestinal system.

For orally-taken medication to be absorbed, it should be able to dissolve in gastro-intestinal fluids. First, it is broken into smaller units due to the corroding effects of stomach acid and various enzymes are secreted, then chemicals in the drug composition pass into the gastro-intestinal fluid in a molecular form. This event resembles the dissolving of a sugar cube inside a glass of hot tea. First, the sugar cube gets broken into pieces and then dissolves. A mix with a tea spoon makes this event happen a little faster. In a similar fashion gastro-intestinal movements help with the absorption of medicine. Liquid drugs like syrups dissolve in the gastro-intestinal fluid faster since they are already in smaller units; therefore they get absorbed faster.

Drugs mostly get absorbed through the small intestine. The most important task of this organ is to enable the absorption of nutrients. It is approximately 10 meters long and 4 centimeters wide. The inner lining of the small intestine has finger-like projections called villus and even smaller projections that are located on these villi are called microvillus. One of the reasons, maybe the most important reason, why the our intestines are created in this way is that as a result, the inner surface area of intestines increases multifold. Such that the inner surface area of a human beings small intestine can increase up to 200 m2 and this greatly facilitates the absorption. These projections are made of intestinal cells.

The molecules carrying the medication reach the capillary vessels by passing through these cells and then join the blood stream by crossing through capillary vessel cells. Furthermore, intestinal cell membranes host a special protein that filters unwanted substances for the cell and returns them back to intestinal lumen. Thus these unwanted substances are excreted out of the body along with other unabsorbed matter. In the same way, some drugs are held by this protein and released back into the lumen thus decreasing absorption rate for drugs experiencing this reaction.

Liver: The organ responsible for eliminating the harmful effects of medication

As soon as medication joins the bloodstream after absorption, it is first transported to the liver. This is because pulmonary veins that collect blood from the intestines are connected primarily to the liver. One of the many functions of the liver is the elimination of harmful substances entering the body. For this reason, absorbed substances are directly sent to the liver. The liver is employed with the task of chemical conversion with these substances that are transported to it. One of the wisdoms behind liver metabolism is to reduce the effects of these harmful substances via these events and to convert them into an excretal material. In the same way, drugs are metabolized in the liver, lose their efficacy and prepare for excretion.

Many drugs interfere with each other’s metabolism. If one drug’s metabolism is inhibited, blood concentration of such chemicals increase and adverse effects of drugs become more frequent. Irresponsible drug use must be avoided for this reason. Drug interactions may lead to major damage in addition to the drug’s individual adverse effects. Moreover different nutrients also affect drug metabolism. For instance, grapefruit inhibits metabolism of certain medicines, as a result blood concentration of these medicines increase and adverse effects can be observed. On the other hand, some nutrients like broccoli, cabbage, and charcoal roasted meat speed up the metabolism of certain medicines. In this case, the blood concentration of the affected drug drops and may lead to reduced benefits from intended use. Because of this reason, patients on long-term medicine treatment should not consume these types of food.

The rest of the drug molecules that escape these metabolisms is directed towards blood vessels feeding other organs. Some drug metabolisms in the liver present individual differences as metabolic levels change from person to person. Thus, a drug with the same dosage develops desired blood concentrations for some people, fails to meet this level for others or can even cause high blood concentrations enough to generate adverse effects in other individuals. That is why a medicine that has benefited a patient should never be used by somebody else without consulting a doctor.

The function of bile

Bile secretion originating from the liver and gall bladder has critical importance in the digestion and absorption of fats. Bile breaks apart fats into small pieces so that digestive enzymes can affect them. As a result of this, absorption is provided for fats and vitamins like A, D, E, K that are soluble in fats. In a similar fashion bile improves solubility and absorption of some drugs that does not dissolve in gastro-intestinal fluid. Another task of bile secretion is the removal of certain substances from the body. Waste materials in the bile that is dumped into duodenum are excreted through the digestive track. Some drugs are excreted in this way.

Drug intake before or after meals

It is a well known practice that medications are advised either to be taken after or before meals. When medications are taken after a meal, they cause less of the possible unwanted disturbances such as stomach sickness, aches or indigestion.

On the other hand, nutrients may reduce intake of certain drugs, therefore they need to be taken before meals. However medications taken right before a meal does not apply in this case since the food will still mix with the medication in the stomach. When taking these medicines, it should at least be an hour before meals. Generally consumption of a medicine before or after a meal does not really change its absorption level. But medications taken before meals pass the stomach into the intestines without delay and therefore get absorbed faster. This practice is important in cases where an immediate effect is desired such as pain relief. Plentiful water intake also helps with faster and improved absorption of drugs.

Some medications are packed into capsules made of gelatin-like substances. Medicines with undesirable taste and smell can be offered in this form for consumption. Moreover, if a drug is harmful to the stomach or gets degraded in stomach acid, then this drug can be prepared in capsules that are durable to stomach acid but soluble in the intestines. That is why consumption of medication without its intended capsule should be avoided. In a similar fashion, some medicinal tablets are designed to deliver its molecular contents particularly to the intestines. These types of medication must be taken as a whole unit. Otherwise it can be ineffective or may lead to harmful reactions.

Delivery of drugs to targeted regions

The molecules carrying medication that join the blood via absorption get dispersed by blood circulation throughout the body. These molecules reach various parts of the system via blood vessels, and then diffuse into organs via capillary vessels. However, their entry to the brain is difficult because this vital organ of the body has a special protection to guard itself from possible harmful effects of various substances that enter the body from the outside. Capillary vessels in the brain are different from other capillary structures in the rest of the body as they are created without an intercellular space in between vessel cells. Furthermore, these cells are bound to each other with their tight connective regions.

These capillaries are surrounded by a thicker membrane compared to other capillary vessels. This membrane is also host to various cells that wrap around the vessel. Therefore, because of these factors and other similar ones, some medications can enter the brain in very limited amounts. Drug molecules can display their targeted effects when they bind to target proteins, called receptors, in the organs. These proteins, which are very unique to each drug, exist on the cell membrane or in the cell. In addition, drug molecules also bind to other receptors that are not specific for them, and this causes adverse effects as a result.

Excretion of drugs from the body

Drugs are excreted from the body via the liver and kidneys. One function of these organs is to filter the blood from foreign substances. It was previously mentioned that absorbed substances from intestines are transported to the liver first where some amount gets metabolized and the remaining amount rejoins blood circulation that feeds other organs. Drug molecules that pass through the liver return back to it repeatedly many times because of continual blood circulation. In each of these arrivals, some amount is again metabolized. Molecules of metabolized drugs are excreted out of the body via the kidneys and through the bile at a limited level.

Only some portion of drug molecules get excreted via the kidneys without being metabolized. This ratio is higher with some medications. These types of medications are considered to be removed only by the kidneys, whereas some other drug types cannot be excreted without getting metabolized through the liver. As previously mentioned, the purpose of drug metabolism is to convert drugs into easily removable forms. If these types of drugs are not metabolized, they are rejoined to the blood circulation after filtration by the kidneys without joining the urine. It is impossible for the liver to sense these happening within the kidneys if it was not that the liver and every cell in it were employed by one authority who created them in the first place. Drug molecules concentrate in the liver and kidneys since these organs are employed with drug removal. As a result harmful effects of drugs are often experienced in these organs. Therefore unnecessary drug use should be avoided, otherwise the health of these organs deteriorate and eventually fail to carry out their basic functions.

As noted above, events that are taking place within many of our organs, stomach and elsewhere like kidneys impact on the journey of drugs in our body, therefore changing its effect. The harmonious creation of our organs that are home to many miraculous events is the major component of the entire process in which causations have their due role only as much as they are allowed by their Creator. As a test for humankind, both illness and the cure is provided by God, the All-Healer. Therefore it is the duty of a patient to see a doctor, take the medication properly and never forget that cure is only provided by the Almighty, without obsessing over causational chains.

References

• Guyton, Arthur C., John E. Hall. 1991. Textbook of Medical Physiology, Saunders.
• Patton, Kevin T., Gary A. Thibodeau. 1993. Anatomy & Physiology, Mosby.
• Rang, Humphrey P., Maureen B. Dale, James M. Ritter. 1999. Pharmacology, Churchill Livingstone.
• Brunton, Laurence, John Lazo, Keith Parker. 2006. The Pharmacological Basis of Therapeutics. McGraw-Hill Professional

A wanted child brings happiness to a family; it is a gift from God. And, of course, every woman who wants to give birth wants to bring up a healthy and beautiful child. Unfortunately, the health index of the modern generation of women at child-bearing age is not very high (there are many chronic diseases, spiritual poverty, with a high vulnerability to different infections due to a variety of reasons). Due to this reason, medical interference in what is a natural process has become more frequent recently. Statistics show that more than 92% of women use different drugs at different stages of pregnancy. The question is to what extent this medication is safe for the future baby. This is a fundamentally important matter to investigate because a pregnant woman taking any chemicals is in essence applying a kind of experiment on her as well as the baby’s health which can have a variety of different consequences.

The problem of medical effects on the development of a fetus has recently become very acute. This is because there are many different medications that are common and easily available nowadays, and they are very often taken without a doctor’s prescription. Unfortunately, the consequences of this fact are not pleasant. Prenatal development is one of the most important and difficult stages in a person’s life. Just in 9 months an ovicell (an egg cell) and a sperm cell form an extremely complex living organism that consists of millions and billions of cells! Moreover, all these cells are combined into tissues, organs and systems that are always interacting. The fetus has a fascinating rate of growth to become a structure with an ever-increasing complexity. In addition, all these processes do not happen chaotically but in a strict order. This order is supplied by two factors: the first is a sound genetic program. It is obtained by the fetus from its parents and the decoding of the genome vividly denotes the existence of Divine Power. The second factor is the state of a maternal organism which supplies everything necessary for the realization of the genetic program and protects the fetus from the negative influence of the environment. In this way the failure of one of the mentioned factors can lead to different deviations and to the disturbance of the development, including the formation of congenital malformations of the fetus and even prenatal death.

The history of medicine shows that medications can be the most harmful etiological factor in relation to the fetus. Today, there are many examples proving this fact. One of the best-known is the thalidomide tragedy which happened in Europe in the 1950-60s. As a result of taking a poorly studied medicine (a light tranquilizer) the children of hundreds (!) of women were born with serious physical defects. Unfortunately, the list of drugs that causes fetal malformation is not short. Nowadays doctors are aware of syndromes caused by hydantoin, warfarin, aminopterin, and many other medications. Each of these has a specific effect on the fetus (mostly leading to serious abnormalities) when taken by a pregnant woman. In the past, people believed that such children were marked by Satan. But nowadays we say that it is the unpredictable effect of the medicine on the realization of the Creator’s program. Medical interference can lead to a disruption in the rate of development and affect the order of differentiation in the tissues and organs of fetus. Moreover, drugs can interrupt the blood circulation in the placenta, change the metabolic process between the fetus and the mother, causing a retardation of intrauterine growth or premature labor, or they can be the reason for a falloff in the health of the child in the first years of life.

The influence of drugs on the fetus depends on different factors, such as the term of gestation at which the drug is administered, the dosage, and the length of time that the medicine is taken, as well as the ways that the drug is excreted, the health of the mother and her inherited sensitivity to medicine, and, of course, the properties of the medicine itself. There are many drugs whose influence on the fetus have not yet been examined, as such research is very difficult, expensive, or in many cases simply impossible. If we understand this, we can see that the outlook for scientific interference in God’s creation of human beings is not good.

You may wonder why the wide-spread usage of medication by pregnant women throughout the whole world has not lead to a continuous increase in congenital malformations if it is really this dangerous. Thanks to a happy concourse of circumstances, this process has not become too wide-spread, as there are many factors that allow the fetus to “escape” medical danger. For example, there may be an inherited insensitivity on the part of the fetus to the influence of different medications, the placenta has its own inherent protective function, the medication may be taken in a small dosage, the developmental stage of the fetus may be at a “non-critical” period, plus many other factors. Doubtless, although this has not been proven, is the fact that the mother has a sincere faith in God and believes in God’s protection of her and her child, which has a positive influence on the development of the fetus.

The initial clustering of embryonic cells and the formation of all the fetus’ organs and systems occur in the first trimester of pregnancy. It is particularly in this period that the fetus is very sensitive to the influence of different factors, including different drugs.

It is quite common that the results of the use of some teratogens¹ by pregnant women, which can have fatal effects, can simply go unnoticed in some cases, resulting in the death of the fetus during the first two weeks of development. In this case, the woman does not even know that she is pregnant. Such cases are not rare (according to some researchers, up to 70% of all pregnancies finish in the early death of the fetus).

What should a pregnant woman do if she is ill or feeling unwell? How can she effectively help herself and minimize the risk of any medications on her baby at the same time? It is never a good idea to self-medicate if you are pregnant, particularly in the case of little-known or untested medications. In any case, it is better to consult an experienced doctor or pharmacist. If for some reason this is impossible, please read the prospectus which is to be found with the medicine carefully. Which dangers the medicine can cause are probably mentioned on the prospectus, and it may be written that the drug should not be used if pregnant. If a drug has been used while being unaware of pregnancy (for example, during the first 2 weeks) then immediately consult a specialist about any possible negative effects there might be for the fetus as soon as you found out that your are pregnant. Going to see your doctor early will allow you the necessary time to avoid any dangers and allow you to arrive at a decision about this pregnancy. If the medicine has been prescribed by a doctor then be sure to ask about possible unwanted side effects for the fetus. Don’t hesitate to ask such questions. If it seems to you that your doctor’s attitude to this question is not serious enough (unfortunately, this happens quite often) then consult a competent specialist (a geneticist or a clinical pharmacist).

If you are just planning your pregnancy, then try to predict all the negative factors beforehand. If you have some chronic diseases which may become acute during the pregnancy, or if you have an allergic predisposition or high sensitivity to acute respiratory diseases, then you should consult a doctor. Preventive methods which have been worked out especially for you minimize the risk of the illness and the risk of using drugs that are potentially harmful to the fetus.

During early stages of ontogenesis the fetus has almost no adaptation mechanisms or specific reactions in its response to the influence of pathogenic agents. Only with time will the fetus’ main organs and systems become mature and the functions of the placenta fully form the morphological and functional backgrounds of the response characteristics peculiar to a new-born baby. We usually say that everything happens according to God’s Will but He has created us for a full, vivid, and creative life. And He wants us to understand and be attentive to the miracle that happens during pregnancy.

Note

1. Agents such as drugs, chemicals and infections that can cause birth defects when a mother is exposed to them during pregnancy.