We all focused on one topic throughout 2020: Covid-19. No single day passed without news on the pandemic as we counted numbers of positive cases and the death toll while anticipating for a vaccine. In the meantime, we got more familiar with some of the medical processes, like phases, clinical trials, mutations, etc. for all this had to deal with the most precious gift we are given: life.

In our last issue, we touched upon the history of pharmacology and how modern-day drugs are made in an article titled “Pharmacology: The Journey of a Chemical Compound into a Drug.” Now, we will explore the multiple, lengthy phases of clinical trials that drugs must undergo and why they are imperative in order for new medicines to get approved for the marketplace.

Clinical trials are a way to test new methods of diagnosing, treating, or preventing health conditions. The goal is to determine whether a substance is both safe and effective. A clinical trial is only done when there is strong reason to believe that a new test or treatment may improve the care of patients.

A variety of treatment methods such as medications, medication combinations, new uses for existing medications, and medical devices are evaluated through clinical trials. In the United States, all new treatments must go through these trials before being approved for public sale by the Food and Drug Administration (FDA).

At the discovery and development stages, thousands of compounds may be potential candidates for development into a “drug”. After early testing, however, only a small number of compounds look promising and call for further study. The entire process of developing a drug from its pre-clinical research stage to its final marketing phase can take approximately 12 to 18 years and often costs well over $1 billion [3, 4].

Clinical trials show us what works and what does not in the realm of healthcare and are designed to answer some important questions such as:

• Does the new treatment work in people? If it does, how effective is it?
• Is it better than currently used treatments?
• If it is not better, is it just as good and cause fewer side effects?
• Does it work in some people who do not benefit from current treatments?
• Is the new treatment relatively safe? There is virtually no treatment or procedure that is without risk, but do the benefits of the new treatment outweigh the risks?

Answering these questions, while giving as few people as possible an unknown treatment, often requires several clinical trials in different phases. Each phase is designed to answer certain questions while keeping trial participants as safe as possible.

Preclinical phase

Before clinical trials can begin in humans, tests and treatments are assessed in pre-clinical research, which can involve extensive laboratory research over several years of testing on animals and human cells. This research may aim to learn the chemical compound of a drug [1]. If the initial laboratory research is successful, researchers send the data to health authorities for approval in order to begin research and testing on humans.

Once pre-clinical research results are approved, human testing of experimental drugs can begin and is typically conducted in four phases that are denoted by Roman numerals (Phase I, II, III and IV). Each phase is considered a separate trial and, after completion of a phase over many years, researchers are required to submit their data to, and then wait for approval from their local health agency (the FDA in the US) before continuing onto the next phase. If the drug successfully passes through Phases I, II, and III then it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are “post-marketing” or “surveillance” studies that are conducted to monitor how safe the product is over several years [2].

Phase I

This is the first clinical phase that involves humans. Phase I trials most often include healthy volunteers, however there are some circumstances when clinical patients are used, such as patients who have terminal cancer or HIV. These treatments possess a much higher risk for healthy individuals and could cause to become ill and contract serious adverse side effects.

In a Phase I clinical trial, doctors collect information on:

• The dose or treatment
• When it should be taken, and how often
• Any side effects or complications
• How the treatment affects patients and their preexisting conditions

One of the primary goals of Phase I studies is to find the highest dose of a new treatment that can be given safely without causing severe side effects. Although the treatment has been tested in laboratory and most likely been used in animal studies, the side effects in people cannot be known for sure. During Phase I of a clinical trial, researchers spend several months to evaluate safety, side effects, optimal dosage amounts, and formulation method for the drug on about 20 to 80 people who have no underlying health conditions.

In addition to evaluating safety and ideal dosage, specialists also look at the best way to administer the drug such as orally, intravenously, or topically. These trials are often conducted in a clinical trial clinic where the subject can be observed by full-time staff. Safety always remains the foremost concern in Phase I. The research team keeps a close eye on the people and watches for any severe side effects.

Researchers start by giving very low doses of the drug to a few patients while higher doses are given to other patients until side effects become too severe or desired effects are seen. The drug may help patients, but Phase I trials are to test a drug’s safety. If a drug is found to be safe enough, it can be tested in a Phase II clinical trial. According to the FDA, approximately 70 percent of medications move on to Phase II.

Phase 2

Phase II of a clinical trial usually involves anywhere from 50 to several hundred who are living with the condition that the new medication is meant to treat. They are usually given the same dose that was found to be safe in the previous phase. Investigators monitor participants for several months, or years, to see how effective the medication is and to gather more information about any side effects it might cause.

Most phase II studies are randomized trials where one group of patients receives the experimental drug, while a second “control” group receives a standard treatment or placebo. These studies are mostly “blinded” which means that neither the patients nor the researchers know who has received the experimental drug in order to avoid from bias. Doctors use a computer program to randomly sort volunteers into these two separate groups. Each volunteer has an equal chance of ending up in any of the groups and are randomly put in any group.

This allows investigators to provide the pharmaceutical company and the health authority with comparative information about the relative safety and effectiveness of the new drug. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered to not to work as planned or to have toxic effects. The FDA estimates that roughly one-third of experimental drugs successfully complete both Phase I and Phase II studies.

Phase II clinical programs historically have experienced the lowest success rate of the four development phases. In 2010, the percentage of Phase II trials that proceeded to Phase III was 18% [5] and only 31% of developmental candidates advanced from Phase II to Phase III in a large study of clinical trials conducted during the period of 2006 – 2015 [6].

Phase III

Phase III of a clinical trial usually involves up to 3,000 participants who have the condition that the new medication is meant to treat. These participants must include men, women, and people of different ages and ethnic groups in many places across the country (or even around the world) at the same time. This helps doctors learn how treatment works in different people with different genetic backgrounds, races, and ethnicity. These studies tend to last longer – up to several years – than Phase I and II studies.

One of the additional purposes of Phase III is to evaluate how the new medication works in comparison to existing medications for the same condition. To move forward with the trial, investigators need to demonstrate that the medication is at least as safe and effective as existing treatment options. Due to the larger number of participants and longer duration of Phase III, rare and long-term side effects are more likely to show up during this phase.

There can be more than two treatment groups in Phase III trials. The control group may receive the current standard-of-care treatment for their illness while other groups receive the new treatment on trial. Phase III trials are usually double blinded to eliminate bias when interpreting results.

Placebos may be used in some Phase III studies, but they are never used alone if there is a treatment available that works. Sometimes, a patient who is randomly assigned to the placebo for part of the study will at some point be offered the standard treatment as well. As with other trials, patients in Phase III clinical trials are watched closely for side effects, and treatment is stopped if they become too hard to manage.

Every patient in a Phase III study is watched closely, and the study will be stopped early if the side effects of the new drug are too severe or if one group has significantly better results. Phase III clinical trials are often needed before the FDA will approve the use of a new drug for the general public. If researchers demonstrate that the medication is at least as safe and effective as others already on the market, then the FDA will usually approve the medication.

In the United States, when Phase III clinical trials (or sometimes Phase II trials) show a new drug is more effective or safer than the current treatment, a new drug application (NDA) is submitted to the FDA for approval. The FDA reviews the results from the clinical trials and other relevant information.

Based upon the review, the FDA then decides whether to approve the treatment for use in patients with the illness the drug was tested on. If approved, the new treatment often becomes a standard of care and newer drugs may be tested against it before they can be approved. If the FDA feels that more evidence is needed to show that the new treatment’s benefits outweigh its risks, it may ask for more information or even require that more studies be done. Once Phase III is complete, a pharmaceutical company can request FDA approval to begin marketing the drug. Roughly 25 to 30 percent of medications move on to Phase IV.

Phase IV

Phase IV trials test new drugs that are approved by health authorities and often are called Post Marketing Surveillance Trials. The drugs are available for doctors to prescribe to patients, but Phase IV studies might still be needed to answer important questions. In previous clinical phases the drug may not have been tested for interactions with other drugs, or on certain population groups, such as pregnant women, who are unlikely to subject themselves to trials. This phase involves thousands of participants and can last for many years. Investigators use this phase to get more information about the medication’s long-term safety, effectiveness, and any other benefits.

This is often the safest type of clinical trial because the treatment has already been studied a lot and has likely been given to many people. Phase IV studies look at safety over time. These studies may also look at other aspects of the treatment, such as quality of life or cost effectiveness.

Phase IV studies can result in a drug or device being taken off the market or restricted depending on the findings in the study. Unless an adverse effect of the approved drug is shown or the drug is accepted as safe, it will stay on the market and also in Phase IV forever.

This clinical trial algorithm has come out after many scientific studies. Every point of the clinical trials, and possible problems, have been clarified by policies which may differ from country to country. At the end, clinical trials are a very safe and cautious method of finding out the safest and most effective treatment, or diagnostic method, for people. During clinical trials, scientists are very careful about ethical issues and try not to harm any living organisms, be them animals or humans. There is an ongoing public debate over pharmaceutical companies. While some think they play a major role in the emergence of many methods and scientific developments to benefit human health, others doubt their motivations and questions their contribution to the public good. This debate will surely continue for a long time, but under the current circumstances, pharmaceutical companies are found in the center of all these clinical trials described in this article. Regardless of the truth behind these doubts, it is important to be always aware of the priceless value of life, that it has been given to us and all living things as an inalienable right and a precious gift, and that it is a major responsibility take care of it well and seek healing when needed.

• https://www.nccn.org/patients/resources/clinical_trials/phases.aspx
• “The drug development process”. US Food and Drug Administration. 4 January 2018. Retrieved 17 August 2020
• Holland J (2013). “Fixing a broken drug development process”. Journal of Commercial Biotechnology. 19. doi:10.5912/jcb588.
• Adams CP, Brantner VV (2006). “Estimating the cost of new drug development: is it really 802 million dollars?”. Health Affairs. 25 (2): 420–8. doi:10.1377/hlthaff.25.2.420. PMID 16522582.
• “New drugs failing Phase II and III clinical trials”. MedCity News. 2011-06-02.
• “Clinical Development Success Rates 2006-2015” (PDF). bio.org. Retrieved 2018-02-11.

Our hands are vital for performing tasks throughout our daily lives and must be taken care of and cleaned regularly. They can easily spread germs, bacteria, or viruses such as Covid-19 (Coronavirus). Coronavirus has spread rapidly throughout the entire world in the past few months and health officials are very adamant that hand hygiene can help prevent further escalation of the virus. The reason is simple; viruses can spread from our hands to other objects that we touch, to which other people can touch those same objects and possibly contract the virus by putting their hands on their face. According to the World Health Organization, proper hand sanitation that uses alcohol-based rub or hot water and soap can kill Coronavirus and other viruses [1].

For some people, such as healthcare professionals, there are actually major consequences for neglecting hand hygiene. For example, the dirty hands of these professionals have a negative impact of 40% in the transport and spread of resistant microorganisms among patients. Hospital infections are actually among one of the main catalysts for increased disability and death rates in hospitals, along with additional healthcare costs [2]. In the United States, 1.7 million patients develop health-related infections every year, and 100,000 of them die. This increases the length of hospital stay by 20 times and the cost of treatment by 5 times [3].

It was not until the 19^th century that we began to understand that infectious diseases can be prevented by washing our hands. In the middle of the same century, the pioneer of antiseptic processes, known as the “savior of mothers,” Hungarian physician Ignaz Semmelweis, showed that microorganisms could be transmitted to patients via the hands of medical staff. This discovery began a new era of hygiene and healthcare. It is now well known that microbes reproduce rapidly, and that it is possible to prevent the spread of disease by keeping the hands and body, which is possible by following personal hygiene rules.

Hand hygiene is maintained in different ways in modern medicine. In daily life, washing hands with soap and water to remove dirt is called “social hand washing.” Common examples include washing after a meal and when visiting the toilet. For this purpose, it is sufficient to rub the hands and fingers for 15 seconds with a non-antimicrobial feature soap, rinse, dry with a disposable towel, and turn off the tap with a towel. Cloth towels used by many people in public places are not considered suitable for hygiene.

The more serious and professional form of hand washing is “hygienic hand washing,” where antimicrobial soaps are used in the washing process before and after contact with patients and bodily fluids. Other hand hygiene methods during surgical operations cover applications where alcohol-based 3-5 ml hand-disinfectant is rubbed until dry along with hand disinfection and surgical hand antisepsis, which includes washing the hands, including the forearms, with chemical solutions such as soaps, isopropanol, chlorhexidine specifically produced for this purpose for 2-3 minutes, and later wearing sterile gloves until the end of any procedures.

The World Health Organization published a guide on proper hand hygienics and explained when, how often, and how healthcare providers should wash their hands [4]. Despite the development of various programs and policies, especially hand hygiene, and increasing material expenditures in the fight against infections observed in health services, the control of infections remains well below the desired level.

Today, research also looks at the effects of hand washing on individual psychology. An experiment carried out by two psychologists from the University of Michigan, Spike W.S. Lee and Norbert Schwarz, shows that hand-washing reduces this classic post-decisional dissonance effect:

In individual sessions, 40 undergraduates browsed 30 CD covers as part of an alleged consumer survey as if they were in a music store. They selected 10 CDs they would like to own and ranked them by preference. Later, the experimenter offered them a choice between their 5th and 6th ranked CDs as a token of appreciation from the sponsor. Following the choice, participants completed an ostensibly unrelated product survey that asked for evaluations of a liquid soap; half merely examined the bottle before answering, whereas others tested the soap by washing their hands. After a filler task, participants ranked the 10 CDs again, allegedly because the sponsor wanted to know what people think about the CDs after leaving the store.

For those who merely examined the soap, the preference for the chosen over the rejected alternative increased from before choice to after choice by an average of 1.9 ranks, replicating the standard dissonance effect. In contrast, for those who washed their hands, preferences were unaffected by their decision. Thus, handwashing significantly reduced the need to justify one’s choice by increasing the perceived difference between alternatives. “Washing one’s hands after making a choice eliminates post-decisional dissonance effects, suggesting that hand-washing psychologically removes traces of the past, including concerns about past decisions” [5].

In another study conducted in 2008, Schnall, et. Al. “hypothesized that physical cleanliness reduces the severity of moral judgments. In support of this idea, they found that individuals make less severe judgments when they are primed with the concept of cleanliness and when they wash their hands after experiencing disgust” [6]. This effect of hand washing, which relieves conscience, is called the “Macbeth Effect.”

Washing hands is one of those simple but compulsory practices we tend to take for granted and lose interest in as we progress in science and education. Simple practices like using each of our hands for different purposes and frequent hand-washing will surely contribute to the fight against healthcare infections and infectious diseases that threaten public health.

There are several traditions of Prophet Muhammad, peace be upon him, in which washing hands is strongly emphasized.

“The blessings of food lie in washing hands before and after eating.”

“Wash your hands after you wake up; you do not know where your hands have moved while you were sleeping.”

The Prophet advised using each hand for different tasks. It is narrated that his wife Aisha said: “The right hand of the Messenger of God (peace be upon him) was for his purification and food, and his left hand was for using the restroom and anything that was dirty.”

Notes

1. “Advice for Public.” World Health Organization, World Health Organization, www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public.
2. Pittet D, Allegranzi B, Storr J, Donaldson L. Clean care is safer care: the global patient safety challenge 2005-2006. Int J Infect Dis. 2006; 10(6): 419–24.
3. Allegranzi B, Storr J, Dziekan G, Leotsakos A, Donaldson L, Pittet D. The first global patient safety challenge “Clean care is safer care”: from launch to current progress and achievements. J Hosp Infect. 2007; 65(Suppl. 2): 115–23.
4. WHO Guidelines on Hand Hygiene in Health Care, www.who.int/gpsc/5may/tools/9789241597906/en/
5. Lee SW, Schwarz N. Washing away postdecisional dissonance. Science. 2010 May 7;328(5979):709. doi: 10.1126/science.1186799.
6. Schnall S, Benton J, Harvey S. With a clean conscience: cleanliness reduces the severity of moral judgments. Psychol Sci. 2008 Dec;19(12):1219-22. doi: 10.1111/j.1467-9280.2008.02227.x. Also see https://psycnet.apa.org/fulltext/2014-20922-011.html in which Johnson, D. J. et. al. suggest that “researchers investigating the connections between cleanliness and morality should therefore use large sample sizes to have the necessary power to detect subtle effects.”

Tears and touching are some of the most profound forms of connection among people. They soften hearts and open doors to each other’s hearts that were otherwise closed. Spiritual care in a hospital environment brings people together in the best way possible under the worst of conditions. I regularly meet strangers and confront situations that require patience and acceptance so I can do the best for others.

What does a multi-faith hospital chaplain do? First and foremost, a chaplain is always there to be a listening ear in a compassionate and caring manner. A hospital chaplain cares about spiritual and emotional well-being of patients, their families or loved ones, as well as the staff at the hospital. As chaplains, we are in the service of everyone, religious or non-religious, faithful, agnostic, or atheist, during both good times and bad times to share joy and sorrow. We visit the patients that need comfort and support, and listens to their worries, concerns or happiness. We are with the patient in their last moments to offer blessings and stay with the families when their loved ones are going through this transition. We are together the broken-hearted who need to be heard, patients who request prayers before their surgeries, and babies who are newly born or die young. We touch hearts, wipe tears, listen to life stories, open spiritual gates, and help people reflect on their own lives to find out where they are on their journey. Lastly, we encourage and empower the ones who are in their recoveries. Sometimes patients are the teachers who allow chaplains journey with them.

I had an interesting encounter with a 67-year-old Catholic lady who came to the hospital for spinal surgery. She did not ask for a chaplain visit but her name was on my unit list. I met her post-procedure during my regular rounds. She was frustrated and upset because the doctors told her that she had cancer; however, what type of cancer she had was still unknown ten days into her stay. She was emotionally overwhelmed with worry about her physical condition because the doctors were still testing the results, and she felt they were not giving her clear answers. She was not alone, because her daughters lived close to her however she could not help but cry when she started to speak about being away from her home and family for a long time, along with the uncertainty she faced which was obviously hindering her ability to cope. I was very concerned with her psychological and emotional state. She was not ready for a longer conversation with me. She dismissed me after a few more minutes and said, “I rather want to be alone at this moment”. I replied, “I understand, it is okay with me.” Upon leaving, I reflected on not being able to help her at all. I felt badly of the situation, and felt that I had missed an opportunity to provide care that I was not able to reach through to her.

The next day, the patient’s nurse telephoned the Spiritual Care Office and requested that I return. The phone call meant a lot for me because I anticipated that there was something significant happening. I immediately went to the patient’s floor and saw her nurse. She told me that the patient wanted to see me before she was transferred to another unit. Upon entering the room, the lady told me that she did not want me to know her as a rude person. She apologized for her attitude the other day and said, “We are both believers and we should not be like that towards each other.” I confirmed this sentiment, and she continued, “I don’t know as much about your faith as I should know, and I felt that I need to know more of it.” She asked me if I could talk about the main principles of Islam, and I accepted her request. I stayed with her explaining, shortly, the basics of Islam, how God sent prophets to all human beings throughout history, and how the Qur’an was revealed and compiled. We had a good discussion which relaxed her and as our conversation ended our relationship between each other was more important than her illness. Her embarrassment replaced with peace at the end. “I am so glad that I was able to call you back,” she said with contentment. “I am so glad that you took the opportunity to invite me again to your room” I responded with a smile. This time, I left her room with a great sense of relief and satisfaction.

“Can you hold my hand?”

Another thought-provoking visit was with a 69-year-old lady who came to the Emergency Department (ED) on a night when I was on overnight duty. It was 4:40 am when I was paged by the ED nurse as the patient asked for a Catholic priest, who was not available. She indicated that the multi-faith chaplain was okay to visit with her. She looked youthful and pretty in her bed but, as I asked her about her concern, she responded, “I am scared of dying.” Doctors had told her that she had an obstruction which was resulting in a removal of one of her kidneys. She was also experiencing blood pressure and diabetic issues.

She was alone at the hospital and her emotions were in a whirl with many thoughts on her mind as the surgery was imminent. We continued the conversation in a manner to address the frustration and fear she was feeling. She responded positively to my empathy and reassurance. She told me about her financial difficulties and that she would lose her home soon. Then she asked me, “Can you do me a favor?” I said, “Sure, what is it?” She asked, “Can you hold my hand?” I took her hand gently and prayed to God, asking Him to provide her with comfort, peace, relief from her worries and for a successful surgery. It was a moment that we both appreciated. After prayer, she asked me about myself and we spoke of our families. I reminded her that the Spiritual Care would be happy to be with her and that I would like to follow up with her during her stay. She seemed relieved and less anxious by the time I departed. I can only imagine how stressful it was for a lonely lady who was dealing with many issues in a strange place in the middle of the night.

From a personal point of view, conversations on faith or religion always remain behind the feelings or emotions of the patients during my visits. I focus on their current spiritual or emotional crisis within the hospital. My goal in my interactions with patients is to provide a safe and non-judgmental space built upon trust and a genuine human connection. After assessing their needs, sometimes I explore if they have a religious background or community, any spiritual practices such as reading holy texts, prayers, rituals, or meditations which might be helpful support for them. I also try to understand if any of their practices help them cope with their difficulties in any way. On the other hand, each patient is unique and each visit is different than the last. One common point is that when words cease to be enough, a warm touch on the hand or the shoulder, or a silent tear shed, become powerful enough to build the connection between the chaplain and the patient. The goal is to always share a genuine moment between two strangers, one of which may literally be on their death bed. It helps to remind us that our faith and appreciation of the Divine can unite us, and that we will all return to God someday.

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

Fear of obesity may sometimes lead people to an extreme diet, and this may cause a deadly disease: anorexia nervosa. The sufferer initially tries to lose weight by going on a diet, but the illness soon reaches the point of no return as the result of extreme dieting. At this point, weight loss cannot be stopped; the person can no longer eat, even if he or she may want to. If they do manage to eat a little food, they throw it up. This disease and many other health conditions are connected with how our bodily functions like appetite are regulated with the secretions in our brain.

Discovered in 1998, orexin is a neuropeptide, or protein-like substance secreted by the brain. It is responsible for regulating states like wakefulness, appetite, and arousal. There are tens of thousands of neurons in the lateral hypothalamus of the human brain that secrete orexin. It was first discovered to increase appetite, but later other functions – especially in relation internal organs – were identified, including regulating the body’s energy use.

Orexins play very important roles in the development and maturation of the brown adipose tissue, which is especially important for infants. The fats in this tissue are directly converted into heat. It is the duty of the adipose tissue to protect the body from illnesses in cold weather. Experiments on lab rats have revealed that body temperature decreases in animals without orexin in their body, and they fail to consume fats. The conclusion is that orexins help boost energy consumption, protect the body from cold-related illnesses by raising the body temperature, and prevent obesity.

Orexins also help regulate metabolic activity and its speed. They are also responsible for regulating the circadian rhythm, or the daily sleep-wake cycle, especially by helping us stay awake. Orexins help increase the secretion of dopamine, norepinephrin, histamine, and acetylcholine hormones, which are in charge of the proper functioning of the daily sleep-wake cycle. All these hormones are substances that increase wakefulness.

The destruction of neurons responsible for producing orexin leads to a severe illness called narcolepsy, which is a serious sleep disorder. Patients suffer from sudden fits of involuntary and extreme sleepiness, irregular nighttime sleep, sleep apnea, various hallucinations, and muscular paralysis called cataplexy. They may suddenly fall into REM asleep while driving and watching television. The muscular paralysis accompanied by REM sleep makes sufferers collapse wherever they may be. They sometimes cannot move and remain motionless, even when they wake up. The fits of sleep strike with or without forewarning and make the need for sleep impossible to fight off. Since frequent uncontrollable collapses may cause injury, narcoleptics know they have to take precautions when they perform daily tasks. Generally appearing in a person’s twenties, the disorder may result from organic factors such as inflammation or a tumor in the brain or other underlying hostile causes.

Narcolepsy is untreatable. It can sever patients from real life and incapacitate them, leaving them unable to perform routine daily tasks. Treatments that are available can only make patients’ lives bearable.

Cataplexy is a condition in which muscles become dysfunctional, speech becomes incomprehensible, and the body collapses due to loss of strength in the neck or knees. Fits may also appear in the form of emotional responses such as excessive laughter, anger, or fear. The duration of cataplexy may last from a few seconds to a few minutes. Patients do not become unconscious during the attack; they just lose control of their physical functions. More often than not, people who have a cataplexy attack in public places seem to be under the influence of alcohol or drugs. They can see and hear others, but they cannot respond.

Sleep paralysis is a temporary state of inability to speak or move during sleep. Although it may look frightening, it is in fact not dangerous. Hypnotic hallucinations, on the other hand, are extremely vivid and frightening dream-like states experienced when falling asleep or waking. An extreme tendency for daytime sleep and hypnotic hallucinations are consequences suffered by people who have not had enough sleep, whereas cataplexy is unique to narcoleptic patients.

Orexins are also responsible for increasing the amount of nutrition a body consumes. This duty is not about meeting the body’s daily diet. Orexins tend to increase appetite, even when the body does not need feeding. They suppress the feeling of satiety, causing the person to continue eating. The willpower should kick in at this point, and the person should use it to stop eating.

The secretion of orexin is influenced by two opposite hormones. The first is leptin, secreted in obese people. Leptin’s duty is to prevent the person from overeating by reducing orexin secretion. The second is ghrelin, a digestive hormone secreted when the stomach is empty. Ghrelin increases orexin secretion, causing an increase in appetite.

It has also been discovered that orexins are connected with smoking and drug addiction. Medicines that reduce orexin secretion are used in addiction treatment. Orexins stimulate the neurons of pleasure in the brain, the reward centers, and impact a person’s happiness or sadness. A reduction in orexin secretion leads to unhappiness and sadness.

References

• Herring W. J. et al. “Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications”, J Sleep Res., 2018; e12782. doi.org/10.1111/jsr.12782.
• Kaushik, M. K. et al. “Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy”, PNAS, June 5, 2018 115 (23) 6046–605.
• Zhou, W. et al. “Activation of orexin system facilitates anesthesia emergence and pain control”, PNAS, November 6, 2018 115 (45) E10740–E10747.

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/

Biggest extinction in Earth’s history caused by global warming—and how it could happen again

Penn JL et al. Temperature-dependent hypoxia explains biogeography and severity of end-Permian marine mass extinction. Science, December 2018.

Some 252 million years ago, long before dinosaurs, the vast majority of species on Earth were wiped out in the “Great Dying,” the worst mass extinction in our planet’s history. Up to 96% of all marine species and 70% of land animals were killed off during this event. Scientists have been trying to find the cause for this catastrophic event, which marked the end of the Permian period. One study suggested that a type of microbe spouted large amounts of methane into the atmosphere. Other studies suggested the event was triggered by a series of volcanic eruptions that released deadly amount of carbon dioxide into the air and led to cataclysmic ocean acidification. A new research study now claims that the Great Dying was primarily as a result of rapidly increasing temperatures. The researchers examined the marine fossil records and simulated the climate conditions to observe the effects of rising temperatures 252 million years ago. Researchers first ran a climate model with Earth’s configuration during the Permian period, when the tropical ocean temperatures at the surface had reached some 10 degrees Celsius (50 degrees Fahrenheit) higher. The model then reproduced dramatic changes in the oceans; oceans lost about 80 percent of their oxygen and about half the oceans’ seafloor became completely oxygen-free. To investigate the effects of these paleoclimate changes on marine species, the researchers then analyzed the varying oxygen and temperature sensitivities of 61 modern marine species including crustaceans, fish, shellfish, corals and sharks. Their calculations predicted that many marine organisms went extinct under these conditions, especially the organisms that lived far from the tropics were most sensitive to oxygen levels and they were nearly completely wiped out. To test this prediction, researchers analyzed late-Permian fossil distributions from the Paleoceanography Database and confirmed that species far from the equator suffered most during the event. The agreement between the simulations and fossils strongly suggests that climate warming and oxygen loss was a primary cause of the extinction. By 2100, warming in the upper ocean is projected to approach 20 percent of warming in the late Permian, and by the year 2300 it will reach between 35 and 50 percent. This study highlights the potential for a mass extinction arising from a similar mechanism under anthropogenic climate change. It is also a clear warning that Earth is on the path to another devastating mass extinction. According to experts, Earth could already be undergoing a sixth mass extinction that would kill off most animal and plant species. The International Union for the Conservation of Nature predicts that 99.9% of critically endangered species and 67% of endangered species will be lost within the next 100 years.

New target for therapeutic brain stimulation to treat depression found

Rao VR et al. Direct Electrical Stimulation of Lateral Orbitofrontal Cortex Acutely Improves Mood in Individuals with Symptoms of Depression. Current Biology, November 2018.

Researchers have finally found an effective target in the brain for electrical stimulation to improve mood in people suffering from depression. Stimulation of a brain region called the lateral orbitofrontal cortex (OFC) reliably produced acute improvement in mood in patients who suffered from depression. In a recent study, researchers studied 25 patients with epilepsy who had electrodes placed in the brain for medical reasons to locate the origin of their seizures. Many of those patients also suffered from depression, which is often comorbid with epilepsy. With the patients’ consent, researchers took advantage of those electrodes to deliver small electrical pulses to areas of the brain thought to be involved in regulating mood. The researchers focused their attention and the electrical stimulation on the OFC, which is a key hub for mood-related circuitry. Moreover, they specifically induced a pattern of activity in brain regions connected to OFC that was similar to patterns seen when patients naturally experienced positive mood states. The researchers applied these stimulation regimes while collecting verbal mood reports and questionnaire scores. Analyses of these reports revealed that unilateral stimulation of the lateral OFC produced acute, dose-dependent mood-state improvement in subjects with moderate-to-severe baseline depression. There is still substantial work remains to be completed before the deep brain stimulation (DBS) treatments could enter routine clinical practice. One major challenge in this study is to see whether stimulation of OFC produces durable improvement in mood over longer periods of time. Biomedical engineers hope to develop a medical device for patients with treatment-resistant mood disorders that can monitor brain activity in OFC and stimulate only when needed to keep that activity within a healthy range. Ultimately, it would be ideal if activity in mood-related brain circuits could be normalized indefinitely without patients needing to do anything.

How screen time can disrupt sleep

Mure LS et al. Sustained Melanopsin Photoresponse Is Supported by Specific Roles of β-Arrestin 1 and 2 in Deactivation and Regeneration of Photopigment. Cell Reports, 2018

For most of us, the time spent staring at screens on computers, phones and tablets adds up to many hours in a day and can often disrupt sleep. In a recent work, researchers now have pinpointed how certain cells in the eye process ambient light and reset our internal clocks, the daily cycles of physiological processes known as the circadian rhythm. When these cells are exposed to artificial light late into the night, our internal clocks can get confused, resulting in a host of health issues. A protein called melanopsin in these light-sensitive cells helps them process ambient light. Prolonged exposure to light causes melanopsin to regenerate and continuous regeneration of melanopsin triggers signals to the brain that inform it about ambient light conditions. The brain then uses this information to regulate sleep, alertness, and consciousness. In this study, the researchers turned on the production of melanopsin in retinal cells in mice and found that some of these cells are able to sustain light responses, but others lose sensitivity. Further investigations found that proteins called beta arrestin-1 and beta arrestin-2 help keep the melanopsin sensitive when exposed to light. One arrestin does its conventional job of arresting the response, and the other helps the melanopsin protein reload its retinal light-sensing co-factor. When these two steps are done in quick succession, the cell appears to respond continuously to light. This research uncovers the mechanisms behind how cells being exposed to artificial light confuses the internal body clock, and the ability to regulate sleep. It is hoped that this discovery could lead to new targets that could counter the impact of artificial light, for example by finding ways to influence melanopsin to reset the internal clock. This could lead to new treatments for insomnia, jet lag, and migraines.

Various studies exist about these compartments – which controls the expression of the soul through the body, which is responsible for memory, intelligence, belief, hatred and love. The brain’s two hemispheres have different functions and specialize in different areas. For example, linguistic abilities and tongue functions are usually controlled by the left hemisphere, while musical abilities and the ability to comment and analyze complex images are controlled by the right hemisphere. However, it is not possible to state that the forebrain functions independently from the hemispheres of the brain. The Wernicke’s area, located on the upper tail of the temporal lobe, is responsible for language comprehension, and the Angular Gyrus that is a mediator between sound and vision, is responsible for linguistic and mathematical operations. For this reason, the Angular Gyrus is accepted to be related with superior consciousness and intelligence. Scientists have proven that intelligence and consciousness decrease more dramatically upon the destruction of these areas when compared to the destruction of the forebrain. Therefore, for the spiritual functions to be able to operate in the body, it’s essential that these areas of the brain function.

The more accepted view, at least today, is that spiritual characteristics and personality function independent of the brain. A convincing proof disregarding this view is that during many tumor surgeries, even though the body’s vital activities remain intact, after removing tissue from the brain, spiritual characteristics sometimes degrade. Another proof is the surgery performed to remove the forebrain of depressed patients (a prefrontal lobotomy). The patients vital activities were not disrupted upon surgery and their mood improved for a while. For a short amount of time, patients stopped suffering from serious neurological and psychiatric disturbances. However, when the patients were observed several years after the surgery, it was concluded that the patients lacked the functions of the forebrain and these surgeries were abandoned. The most prevalent side effects related to the removal of the forebrain were:

• Loss of the ability to solve complex social problems,
• Loss of the ability to take sequential steps in order to resolve a complex problem,
• Loss of the ability to multitask,
• Loss of determination, effort and desire to do activities,
• Loss of the ability for a community response when faced with a problem,
• Loss of ethical values and the feeling of shame,
• Loss of coherent thought even though the ability to speak and understand what is said is not lost,
• Instant emotional changes: from kindness to frustration, passion, violence and insanity,
• Inability to use artistic or naturally existing talents for the sake of a purpose.

These dysfunctions made it apparent that there was a correlation between the forebrain and spiritual characteristics.

Single neurons, not from the human brain, were inoculated in the lab and an experiment was carried out.. Studies showed that these neurons were not a means to highly intellectual capabilities, such as intelligence; whereas when neurons taken from the forebrain were inoculated and experimented on, it was found that they were a means to uniquely human capabilities like intelligence. Complex problem solving and the capacity to make discoveries were found to be correlated with the forebrain. It is not possible to explain such a fact without taking the soul into consideration. Spiritual characteristics such as sadness, happiness, joy, peace, patience, compassion, and love are all the results of complex interactions within the brain. However, it is not convincing to say that they are only results of electrical or chemical interactions within the brain.

The prefrontal area is where all thoughts coming from lower brain areas (such as sight, hearing, and feeling cortex areas, and the thalamus and hypothalamus) are gathered and processed to be enriched. Many information and memories gathered from different parts of the brain come together in the prefrontal area to be synthesized into deeper thoughts. Active memory is when different pieces of information are synthesized together and form a thought; and this thought is later acted upon. This allows to accurately surmise future events, and to plan for them.

It also allows for a rapid, appropriate response to the signals gathered by the five sensory channels. It allows for predicting the consequences of actions before performing them and for resolving problems of a complex medical, mathematical, ethical, moral, or philosophical basis. It can also postpone emotional responses for an appropriate time, measure the consequences of verbal and physical communications, use will power to measure the ethical and moral consequences of actions, and use information gathered from all channels to diagnose a problem. People who have damaged prefrontal cortexes, have serious difficulty synthesizing information and processing it to form coherent thoughts (active memory). This situation shows us that the prefrontal cortex enables consciousness and highly intellectual actions.

Another function of the prefrontal cortex is to enable focus about a specific topic. Taking this into consideration, the prefrontal cortex is semi related to attention. An existing proof for this is that people with damaged prefrontal cortexes are unable to concentrate and their focus is easily disturbed. Individuals whose prefrontal cortex has been removed or damaged can acquire a spiritual consciousness; however due to their handicap, they are unable to express their thoughts in a serial and sensible fashion for more than a minute. They can be easily distracted from the original subject. The prefrontal cortex allows an individual to accomplish a process of thought despite distractions, and allows for communication between the soul and the mind.

To sum it up, the prefrontal cortex is correlated with intellectual characteristics such as consciousness, intelligence, and self control, and also relates to how well we perform our moral values. For example, if the prefrontal cortex is unable to function, the individual does not feel shame anymore. This makes people believe shame is related only to the prefrontal cortex. However, the brain is merely a bridge between the body and the soul. Our brain is a bridge and curtain for our soul, which is the source of our spiritual characteristics. When we physically have a problem with our brain, the soul carries on its existence as before, however it is unable to express its consciousness, intellect, and will power in this material world.

It’s not just modern medicine that utilizes bees and their products for healing. A clay tablet that dates back to 2000-2100 BC describes the healing properties of bee venom. In 1935, Forapin, which was isolated from bee venom, was introduced into the market. It’s still being used. Bee venom is collected by placing a small panel, which looks like a grill, in front of the bee hive. The panel is composed of metal wires in which low voltage electric currents flow. The entrance to the hive is through these wires. The bees that are entering or exiting the hive are subjected to a mild electric shock, and sting the panel with their needle as self defense. Meanwhile, the bee venom flows into the glass plate underneath the panel. Bee venom is collected and turned into a powder form without harming the bee.

The chemical composition and effects of bee venom

Bee venom is a colorless, odorless, clear, and water soluble liquid that is resistant to cold and hot temperatures. In normal seasonal temperatures, this venom dries up in 20 minutes and loses 65-70% of its weight. It takes a yellowish brown color after it is dry. 10,000 bee needles are needed for one gram of bee venom.

18 different bioactive molecules were found in the composition of bee venom. Some of these are: Melittin, adolapin, apamin, mast cell degranulation, histamine, phospholipase A, peptide, dopamine and hyaluronidase. These molecules show the characteristics of amino acid, protein, fat, sugar, and enzyme. Melittin and adolapin protein are anti-inflammatory; apamin increases nerve transmission; and mast cell degranulation is equipped with characteristics to help reduce allergies. Mellition, which is composed of 26 amino acids, is the main toxin molecule of the bee venom. Melittin triggers the synthesis of the cortisol hormone that suppresses inflammation and increases the resistance of cell walls. Melittin also triggers the immune system cells that prevent the formation of free radicals, which normally damage cells and tissue. As well as being antipyretic (fever decreasing), adolapin is also a pain reliever and also plays a role in the prevention of cyclooxygenase that are a cause of infection. Apaminin, which consists of 10 peptides, is thought to play a role in healing a damaged nervous system.

Low concentrations of mast cell degranulation proteins cause the synthesis of histamine, which triggers an allergic reaction; whereas high concentrations of it play a role in preventing these reactions. Although these molecules are called venom, they are provided with remarkable healing characteristics.

Treatment with bee venom

The fact that treatments for rheumatism are not completely effective has persuaded patients and healers to look into complimentary treatment techniques. Bee venom has gained acceptance as a complementary healing technique in China, the US, and Europe. Apitherapy centers have been popping up in these places – and the best method to apply apitherapy is by using bee venom.

The bee sting is mimicked by injecting bee venom into or underneath the skin, though creams or capsules of bee venom also exist. The injections function in a way similar to an actual sting, or to acupuncture. Acupuncture prevents pain by blocking the brain and spine paths (opioid and alpha 2 adrenergic receptors) that cause pain. Similarly, a bee sting stimulates the secretion of endorphins, which are a pain relief molecule. Therefore, in Chinese medicine, it is more common to apply the bee venom through acupuncture. In some cases, api-acupuncture is practiced by combining both treatments.

The treatment is started by injecting a small amount of bee venom underneath the skin to see if the patient will respond with an allergic reaction. If no allergic reaction occurs, the treatment is continued with one or two bee stings or injections. The treatment is carried out three times a week, by increasing the number of bee stings and injections each time. The treatment may cause allergic reactions in the patient that result in pain, swelling, itching, redness, or – very rarely – death. Therefore, as with every practice, treatment with bee venom should only be practiced by experts, and should not be tried by inexperienced healers.

As well as rheumatic complaints, bee venom is used for the treatment of arthritis (rheumatoid arthritis), joint calcification (osteoarthritis), bone weakening after climacteric, muscular rheumatism (fibromyalgia), and chronic pain.

In a study conducted with 80 inflamed articular rheumatism patients, 40 of them were treated with bee venom twice a week for two months. The rest of the patients were injected with physiological serum. The first group showed significant improvements on sensitive and inflamed joints, morning stiffness, and pain.

In a similar study, patients with inflamed joint rheumatism were injected with bee venom three times a week for three months, and there was a significant decrease in patient complaints. This study also proved that bee venom can be used for the treatment of inflamed joint rheumatism.

The healing quality of bees has long been noted. If we ruminate on this gift, it’s hard not to admire its wise design.