A brain to brain interface is a direct communication pathway between the brain of one animal and the brain of another animal. Brain to brain interfaces have been used to help rats collaborate with each other.
The ability to transmit information between brains sounds extraordinary, but how can we use this technology and can it be developed in the future to revolutionise neuroscience – and what will the effect of this be?
BBIs transfer data from a sender to a receiver through a computer, which allows the sender to, essentially “telepathically” communicate with the receiver. In addition to this a BBI can be used to manipulate a receiver’s actions. A brain to brain interface transfers data from a sender to a receiver through a computer, which allows the sender to, essentially, telepathically communicate with the receiver. In addition to this a brain to brain interface can be used to manipulate a receivers actions.
Can BBI’s be manipulated?
A study conducted by Rajesh Rao and Andrea Stocco, completed in 2013 , showed that, without any source of communication other than the brain to brain interfaces, a motor response could be created using an electroencephalogram – which extracts the information from the sender – and transcranial magnetic stimulation – which creates the response through sending a motor command to the brain. This study clearly shows that whilst this technology is in its infancy, there is substantial evidence of efficacy.
In conjunction with this discovery, brain to brain interfaces can be used to manipulate the actions of animals. A study conducted by Miguel Pais-Veira entitled Pais-Veira entitled “Human Mind Control of Rat Cyborgs Continuous Locomotion with Brain-to-Brain Interface” showed that it is possible to guide rats through a maze using brain to brain interfaces. This discovery not only implies that humans can increase their control over the animal kingdom, but that eventually, animals could also be used to access tighter spaces or areas that are unreachable, such as the deepest depths of the ocean.
Whilst the discoveries made in the development of this new technology are impressive, there are areas for development. Firstly, transcranial magnetic stimulation and electroencephalograms are non-invasive; meaning that no surgery is needed. Therefore, the amount of motion that can be stimulated is limited compared to invasive techniques, such as the technology used for the cyborg rats, which had technology implanted into their brain, thus the information transferred in these tests is simple. This not only means that there must be the development of non-invasive technology (for the cyborg-rats), but it also means that there is already a method to help improve the precision of brain to brain interface – even though these methods are prohibited due to the risks.
An additional reason for the development of these techniques to be prohibited, is the moral complications of having technology that can force actions onto the subject; due to the stimulation being mechanical and thus there is no need for consent. As a result, there is a lot of necessary precaution in the production of such technology, due to the risks being so high. Consequently, there is a lack of support for researchers meaning that the development is Invasive BCI Non Invasive stunted. This issue can only be fixed once laws that prevent exploitation using this technology are made.
What are the advantages and disadvantages of BBIs?
As to any form of technology there are pros and cons. Brain to brain interface is smart technology, for example it can help disabled people move their prosthetic limbs easily. It has an ability for telepresence – an example of this advantage would be that it can allow military personnel to keep an eye on any suspicious activities taking place through a distance. This technology if implemented correctly can go as far as prevented road accidents.
However, the research is still in its beginning stages meaning the current technology is crude. Ethical issues may arise from this form of invasive technology as the electrodes are placed inside the skill creating a scar tissue in the brain as the electrode outside of the skull can detect very few electric signals from the brain.
So, what should people hope for in the future? As the understanding of neurology improves, it is clear that brain to brain interfaces will become more and more precise, allowing the transmission of data between two subjects to become increasingly complex with Andrea Stocco expressing that, “The holy grail of BB1 would be sharing rich content that cannot be better expressed in words, such as emotions and feelings”.
The concept of blood groups is well-known, and there are a total of eight main blood group types (within the ABO group). The four main types are Type O, Type A, Type B and Type AB, and each type can be either positive or negative. The blood type an individual has is determined by the genes they inherit from their parents, and the gene for type O blood is recessive while the genes for types A and B are both dominant. Blood types are categorised based on the antibodies in the plasma and antigens on the cell surface membrane of the erythrocytes. The knowledge of the different blood types plays a vital role in medicine–and one significant reason for this is ensuring blood compatibility for blood transfusions–otherwise this could result in the death of the recipient.
However, beyond the ABO group, there are 34 other blood group systems, and within these systems there are over 300 variants. Examples of such lesser-known and rarer blood group systems are the MNS blood group system and the Duffy Blood Group.
Blood Group ABO
Blood transfusions were common before the discovery of human blood groups in the year 1900, but it was not understood why some were unsuccessful while others were fatal. It was in 1900 that Karl Landsteiner, who was working at the University of Vienna, discovered blood groups through his scientific experimentation1. Karl Landsteiner took blood samples from his staff members and mixed them together, finding in some cases that the erythrocytes would be agglutinated when combined with the blood serum from a separate person. The results of these initial experiments led Karl Landsteiner to conclude that there were three blood types: A, B, and C (which would later be renamed O) and this then became known as the ABO system. The blood group AB was discovered in 1901. In 1930, Karl Landsteiner was awarded the Nobel Prize in physiology and medicine2.
Classifying Blood Groups
Blood types are classified into distinct groups based on the presence and form of antibodies and antigens in the blood. Antigens are structures found on the cell surface membrane of cells, here it is the erythrocytes, and they trigger an immune response. As part of this immune response, antibodies are produced by lymphocytes, and they bind to specific antigens. Some forms of antibodies attack the antigens by disabling processes in the cells which they are attached to, while others cause the foreign cells to clump together – and so facilitate the eradication of them, for example, by phagocytosis.
A person with blood type A will have Anti-B antibodies in their blood plasma, and A antigens. A person with blood type B will have Anti-A antibodies in their blood plasma, and B antigens. A person with blood type AB will have both A and B antigens but will not have any antibodies in their blood plasma. On the other hand, a person with blood type O will have both Anti-A and Anti-B antibodies in their blood plasma, but no antigens on their erythrocytes. Due to the presence of these antibodies and antigens, not all blood types are compatible with one another. For instance, if a person with blood type B received a blood transfusion where the donor has blood type A, the Anti-B antibodies in the recipient’s plasma will attack the erythrocytes from the donor blood. This will cause the erythrocytes to clump together, leading to clots and ultimately culminating in the death of the recipient.
Blood type AB is considered to be the universal recipient due to the absence of antibodies in the plasma of individuals with this blood type. Thus, when donor blood enters the circulatory system, antibodies will not attack the erythrocytes. Inversely, blood type O is considered to be the universal donor, as there are no antigens to be recognised nor stimulate an immune response3.
However, the rules of blood compatibility also depend on whether the individual has a positive or negative blood type. Whether an individual has a positive or negative blood group type is determined by the presence of the rhesus protein – named after the rhesus monkey, which also carries genes to code for this specific protein4. The rhesus protein is otherwise known as the D antigen or the Rh factor, and an absence of Rh antigens means that a person is Rh negative while the presence of such antigens makes a person Rh positive. Just as blood ABO group is inherited from parents, the positive or negative Rh factors are also genetically inherited. For an individual to have a Rh-negative blood type, both of their parents must have at least one negative Rh factor each in their genetic material. Therefore, a Rh-negative blood group is less common than a Rh-positive blood group, as a person has to have at least one negative Rh factor to have Rh negative blood themselves4.
Rh Protein and Pregnancy
A Rh-positive individual is able to receive blood from an Rh positive or Rh-negative donor, but a Rh-negative person is only able to receive Rh negative blood. This presents a problem during pregnancy and delivery when the mother and the foetus may be opposing Rh groups. For example, the mother is Rh negative, but the foetus is Rh positive, and if the mother is exposed to the foetus’s blood during birthing (or at any point during the pregnancy) then this can have fatal consequences. The result of this would be that the mother’s body would be stimulated to produce antibodies to the Rh antigens. If the mother had subsequent pregnancies, these antibodies her body has produced would attack the erythrocytes of the foetus’s should they also have Rh positive blood. This can be done as the mother’s antibodies can cross the placenta and reach the foetus, where they attack its erythrocytes. This leads to a condition called ‘haemolytic disease of the new-born’ (HDN) and can cause anaemia, seizures, jaundice, brain damage or potentially even kill the foetus5.
The difficulties of Rh groups of the mother and foetus during pregnancy and delivery – as well as later pregnancies – are greatly reduced. This is done through injecting the (Rh negative) pregnant woman with Rh antibodies, which eliminates the immune response in the mother that the Rh antigens from the foetus’s blood could potentially trigger. These antibodies are injected into the pregnant woman as ‘RhoGam’, which was only approved by the FDA in 1968. RhoGam is only given if the pregnant mother is Rh negative, but her foetus is Rh positive, and this injection is typically given at an early stage in the third trimester of the pregnancy. The mother can also receive a second RhoGam injection within 72 hours of giving birth.
Before the development and use of RhoGam, HDN affected approximately 1% of all new-born infants and led to the death of 1 out of every 2200 births6, according to an article entitled ‘Management of pregnancies with RhD alloimmunisation”. Also, in this article is stated that “in England and Wales, about 500 foetuses develop haemolytic disease each year, and about 25-30 babies die from haemolytic disease of the new-born”.
MNS and Duffy Blood Groups:
The MNS blood group is categorised by the presence of MNS antigens, which are carried by glycophorin proteins and are located on the cell surface membrane of erythrocytes. MNS antigens are carried by the glycophorins A and B, which can also be receptors for pathogens such as plasmodium falciparum, one of the deadliest malarial parasites. The MSN blood group was discovered shortly after the ABO blood group, in 1927, and the M and N antigens were identified then. It took approximately 20 years for the S and s antigens to be detected. While the M, N, S, and s antigens are the most frequently occurring within the MSN blood group, there are more than 40 other antigens7.
Like the glycoproteins for the MSN antigens, the Duffy glycoprotein is also a receptor for Plasmodium vivax – another malarial parasite8. This means that individuals lacking the Duffy antigens could potentially be immune to this strain of malaria, as the Plasmodium vivax parasites would not be able to connect to the Duffy antigens if they are absent. As well, the Duffy glycoprotein is a receptor for chemicals which cells secrete as the result of inflammation. The Duffy blood group is a blood type classification determined by the presence of the Duffy glycoprotein, otherwise known as Fy antigens, on the cell surface membranes of erythrocytes. Fy antigens can also be located on endothelial cells, epithelial cells in the alveoli and in the collecting ducts in nephrons. The four possible Fy phenotypes are: Fya+b+, Fya+b-,Fya-b+,andFya-b-, and the first Duffy antigen discovered was Fya, in the year 19509.
While the general knowledge of blood groups is well known by most, there are many more blood types and variants within these groups that are newly discovered and less-commonly known about. Despite the fact that the ABO blood group system is at least 20 million years old, and has mutated and been inherited since its development, it remains a scientific mystery as to why exactly humans (and other primates) have distinct blood types in the first place. It is hypothesised that the frequency and distribution of blood types worldwide is linked to where diseases/infectious organisms are endemic. For instance, an article titled “Why do people have different blood types?”10 written by Harvey G. Klein (Chief of the Department of Transfusion Medicine for the National Institutes of Health) comments that people with blood type A are more susceptible to smallpox. Klein notes the correlation between this and the fact that there is a higher frequency of blood type B across China, India, and Russia – where there were prolific epidemics of smallpox in the past. The full extent of why a variety of blood groups exist remains unknown but linking it to evolution and global distribution of both people and pathogens seems an auspicious theory.
Multiple personality disorder is the term that was previously used to describe what is now known as dissociative identity disorder (DID). This is a psychological condition which the brain instigates as a method of self-preservation and is often the result of prolonged and habitual abuse. DID is, according to WebMD, “a severe form of dissociation”1 where an individual becomes mentally disconnected from their thoughts, memories, and even their self-identity. Although severe, this is one way that the human body tries to protect itself from traumatic and difficult situations – by shutting the primary consciousness away and creating other consciousnesses to deal with the present trauma. When each alteration is in control of the individual’s body, this is referred to as fronting. According to the American Psychiatric Association2, approximately 90% of those in Europe, Canada, and the United States suffering from DID have experienced abuse and neglect during childhood. Sufferers of DID have at least two separate and distinct personalities or consciousnesses, and the other personalities cannot remember what happened when they were not the fronting consciousness.
DID is an example of a dissociative disorder, and sufferers of such disorders perpetually feel disconnected from their reality. Approximately 2% of the US population have dissociative disorders3, and women are more likely to have such conditions than men. The three primary dissociative disorders are dissociative identity disorder (DID), derealisation disorder, and dissociative amnesia. Post-traumatic stress disorder (PTSD) and acute stress disorder share similar symptoms with dissociative disorders – including memory loss and depersonalization – but are not considered to fully be dissociative disorders in their own right.
An article published in the International Journal of Social Psychiatry4 entitled “Dissociative Disorders in a Psychiatric Institution in India – a Selected Review and Patterns over a Decade” discusses research into DID. The purpose of this study was to examine patterns of DID sufferers across ten years and included inpatients and outpatients who attended a psychiatric hospital between the years 1999 and 2008. The research discovered that between 1.5 and 15.0 per 1,000 outpatients were diagnosed with DID, while between 1.5 and 11.6 per 1,000 of the inpatients were diagnosed. This review concluded by stating that “dissociative motor disorder and dissociative convulsions are the most common disorders” and that DID is especially under-diagnosed outside of Western regions.
What Causes DID?
Although there is no single definitive cause of DID, the main factor for this condition is severe and repeated abuse – including physical, emotional, and sexual abuse. This abuse often will begin in childhood, and, compounded with the fact that the child often does not have a safe refuge from such abuse because it is typically, though not always, carried out by a family member, can cause the child to develop DID. In rarer cases, a person can develop DID due to experiencing a violent and traumatic event, such as living in a combat zone.
Signs and Symptoms
For a person to be categorized as having DID, they have to have at least two distinct personalities. The predominant identity of the individual is known as the ‘core’ identity, and the personalities created are the ‘alters’5. Someone with DID can have many alters, possibly over 100. These alters, if there are many, tend to vary in age, gender, ethnicities, and characters even within a single person – and for some people with DID their alters are able to interact with one another.
The main symptom of DID is sudden and involuntary transitions between these alters. As a result, this can mean that the core identity has many long-term gaps in their memory, as they can only remember details from when they are fronting. Self-harm and suicide attempts are unfortunately very prevalent amongst DID sufferers, and over 70% of outpatients with DID have attempted suicide at least once3.
6Some common symptoms of DID include sudden flashbacks, feeling detached from one’s own body/out-of-body experiences, hallucinations, and inability to be aware of one’s surroundings – for example, finding yourself in a place with no memory of how you got there. Long periods of memory loss are also typical for DID sufferers, and this is known as dissociative amnesia – which is a type of memory loss that is greater than forgetfulness. Dissociative fugue is an episode of amnesia that can cause the person to not remember personal information or to experience emotional detachment7. In addition to these symptoms of DID, sufferers of this condition may also endure mood swings, anxiety, panic attacks, unexplained phobias, insomnia, night terrors, migraines, severe pain anywhere on the body, sexual dysfunction, and the increased likelihood of developing eating disorders.
Not only does DID cause intense emotional and psychological difficulty for an individual with the condition, but also it can physically change the brain. A paper published in The American Journal of Psychiatry8 examined the results of a study involving 38 women. Fifteen (15) of these women had DID, while the other 23 did not have DID, nor any other psychiatric condition. Each woman underwent MRI scanning to measure the volumes of their hippocampus, which controls memory, and amygdala, which controls emotions. The results were compared between these two groups and showed that the volume of the hippocampus was 19.2% smaller for those with DID. The volume of the amygdala was 31.6% smaller in the DID patients too. Overall, this suggests that people with DID will generally have a lower hippocampal and amygdalar volume compared to people who do not have DID. This leads to impacts on memory and emotions, which is common for sufferers of DID – who typically have long periods of memory loss or significant gaps in their memory, in addition to frequent mood swings and swiftly changing emotions.
In a paper published in the National Library of Medicine9, a study was carried out to measure hippocampal volume in 21 women who had been severely sexually abused during childhood, as well as 21 women who had not previously been abused. Again, magnetic resonance imaging (MRI) was used to determine the hippocampal volume for each of the 42 women, and the results of this study showed that the left-sided hippocampal volume was, on average, 5% smaller in the women who were sexually abused compared to the women who had not been. While the same test was carried out on the right-sight hippocampus for each woman, the article states, “hippocampal volume was also smaller on the right side, but this failed to reach statistical significance.” The results of this study show how abuse – of any kind, but in this research, it was specifically sexual abuse – can physically damage the brain, as it tries to protect the individual by having extensive gaps in their memory. As discussed previously, sustained abuse can cause DID to manifest in the individual, as sufferers of this condition present with similar changes to the hippocampal volume.
Intervention and Treatment
Like other psychological conditions, there is no cure for DID, but there are several treatment methods that have proved effective. Treatment for DID can take several years, and the most common method is psychotherapy. Throughout this process, the aim is to work with the patient so that their individual alters can merge to form a single, cohesive identity5. This is an arduous process, as it involves the patient working through the trauma and/or abuse that caused them to develop DID in the first place. Family therapy can also be helpful for sufferers of DID, as it can educate friends and family members about the difficulties of living with DID and how best to support that person. Less frequently, clinical hypnosis can be used as a possible treatment method for DID, in which patients can access repressed memories that they experienced as one of their alters and so cannot remember when any other alter is fronting6. Furthermore, cognitive behavioral therapy is another commonly used method in an attempt to treat DID.
The American Psychiatric Association led a question-and-answer panel with an expert of psychiatry: Dr. David Spiegel, Professor and Associate Chair of Psychiatry & Behavioural Sciences at Stanford University School of Medicine10. When he was asked the question, “are people with dissociative identity disorder often misdiagnosed?” Dr. Spiegel said: “they are sometimes misdiagnosed as having schizophrenia. Another common misdiagnosis is borderline personality disorder.” Later in the article, Dr. Spiegel says, “typically those with dissociative identity disorder experience symptoms for six years or more before being correctly treated.” This shows not only how difficult it is to acquire treatment but, even when treatment is given it can frequently be based on a misdiagnosis. If a person with DID is misdiagnosed as having schizophrenia, they may be prescribed antipsychotic medications, and their emotions will be dulled when they take this. This will lead to further increases in this antipsychotic medication on the belief that it is an effective treatment for the individual. Dr. Spiegel remarks that “dissociation is a common coping mechanism,” saying that “many rape victims experience the crime as though they were floating above their bodies.” While dissociation is a natural human response to a traumatic event, it is when this trauma is sustained and repeated that this dissociation can develop into DID.
Jeni Haynes is a woman who has DID and has over 2500 distinct personalities/alters – though only six predominant ones. Jeni developed DID due to her intensely traumatic childhood, where she was subjected to horrific physical and sexual abuse from her father, Richard Haynes. In the trial against Richard Haynes for this abuse, Jeni testified through her multiple personalities, allowing each one to front her in turn. After the core personality of Jeni Haynes, there was Symphony, a four-year-old girl who endured much of the abuse – and described by Jeni to be her most significant alter. Jeni addressed the court, telling them: “Symphony intended to testify in court for the whole thing. When my father raped Jennifer Haynes, he raped Symphony.” Jeni’s other alters included an eleven-year-old boy called Judas and a 17-year-old boy called Muscles11. This trial was the first trial in Australia where an individual was allowed to provide evidence through their alters. While Richard Haynes was convicted, that does not mean that Jeni has a normal life now. Her DID causes her struggle every day, and in her victim impact statement, she said, speaking about her and all of her different alters: “we have to hide our multiplicity and strive for a consistency in behavior. Having 2,500 different voices, opinions and attitudes is extremely hard to manage”12.
Another example of an individual’s struggle with DID is that of a 25-year-old soldier. In an article written by the American Psychiatric Association13, she is referred to only as “Sandra”, which is a pseudonym to maintain confidentiality. Sandra was hospitalized due to her sudden behavioral changes and episodes of acute memory loss. As she underwent clinical hypnosis, it was discovered that she had a series of significantly large gaps in her memory, and she was also found to have swift and severe changes in her emotions. She then began to have psychotherapy, where she worked through the memories of sexual abuse she had endured since the age of 11. Sandra was diagnosed with DID, and now she continues to have psychotherapy as well as take anti-depressants. She reportedly rarely dissociates and has now been able to establish stable relationships.
To conclude, dissociative identity disorder (DID) is a psychiatric condition that can present immense difficulty to those with it, as they can feel completely disconnected from their surroundings – and it can be terrifying when individuals cannot remember what has happened to them and feel like they do not have autonomy over their own body. Furthermore, DID is hugely underdiagnosed or misdiagnosed and can mean that the treatment people need – which is already a lengthy process of many years at least – is delayed. There needs to be more information about DID, as some do not believe it is even an actual condition. Educating people about DID can mean that they can recognize if their friends or families show signs of this condition and can potentially aid them to attain treatment and support faster than if they waited to do so themselves.
Got an annoying cold or nasty virus? Your first instinct may be to reach for some Dayquil or Tylenol, medicines that are considered to be purely beneficial and a trick to feel-better instantly. However, doctors are just now realizing that these drugs might not be all that they seem.
Cold medicines are amongst the most commonly prescribed drugs by American doctors, however, healthcare professionals are beginning to acknowledge the many flaws with these types of medications. The first and most notable being increased transmission of infection, and the second being that medicated individuals may stay sick for longer. Despite these flaws, these drugs are effective at alleviating symptoms, so whether or not to go through with taking them is ultimately a personal choice.
What really is cold medicine?
Cold medicines, also referred to as fever reducers, are made up of 4 key parts: decongestants, antihistamines, cough suppressants, and pain relievers. The decongestants work to relieve sinus congestion by narrowing blood vessels within the nose, antihistamines boost the immune system by blocking histamine, cough suppressants clear away mucus within the lungs, and pain relievers work within your nervous system to stop pain signals from getting to the brain. In addition to these 4 parts, cold medicines hinder the production of prostaglandins, which controls a hypothetical thermostat within our brains.
Some of the most commonly used of these drugs include: acetaminophens such as tylenol, ibuprofens such as Advil and Motrin, and aspirins (Mui, 1).
What’s the catch?
Despite the obvious benefits of cold medicines, it is important to recognize their inherent drawbacks. Among the most notable of these downsides is that they treat symptoms, but not the actual disease. While this may seem beneficial, it can actually be extremely harmful in terms of containment of the disease because ill individuals who have taken one of these medications may feel well enough to participate in normal day-to-day activities such as work or school. And, because such activities often require close contact with peers, they are putting everyone around them at a higher risk for catching the disease. In fact, it was found that the use of antipyretics, a type of fever reducer, increases transmission of the flu virus by about 5% each year, which translates to about 1,000 more deaths (Earn, 1).
In addition to more people catching the given disease, cold medications will actually cause individuals to stay sick for longer. This is because fevers are crucial to fight infection. An increased body temperature creates an inhospitable environment for viruses or bacteria to grow and survive, therefore eliminating the illness. Therefore, while one might feel worse, they are actually at a better position to fight off whatever is making them sick (NIH, 1).
The bottom line
It is ultimately your choice whether or not to medicate for a cold or fever, but next time you consider it, be courteous of those around you by recognizing that just because you are feeling better, does not mean you are truly better. Plus, if you are continuously taking these medications throughout the course of an illness and do not seem to be getting any better, you might want to lay off the medicines and consider other forms of treatment such as hydration and sleep.
Lily Kangas, Youth Medical Journal 2022
“Fever.” MedlinePlus.Gov, medlineplus.gov/ency/article/003090.htm#:%7E:text=Fever%20is%20an%20important%20part,fevers%20with%20 mid%20viral%20illnesses. Accessed 26 July 2021.
This study examines the psychological and emotional effects of music listening interventions on stress and anxiety-related symptoms and emotional responses in adolescents 14-18 years of age. The study was done through a thorough preceding examination of similar studies and research papers over music medicine and therapeutic interventions. In addition, a survey that simulates music listening interventions found in music medicine was distributed on a virtual platform. The creation and structure of the survey is based on information according to the methodology, assessments, and findings of other research papers. The survey includes music samples and self-reported questionnaires that observe stress and anxiety (State Trait Anxiety Inventory, Perceived Stress Scale, and Healthy Unhealthy Music Scale). Results from the study revealed that there is a significant change in state anxiety level for participants with a jazz genre survey version (p = 0.038, α 0.05). There were also observed correlations between stress level v HUMS-Healthy scores, where a lower stress level results in a higher HUMS-Healthy score, and music genre preference v state anxiety level, where receiving a survey version of the most preferred genre of music results in a generally more positive and greater STAI change. These findings could encourage further studies into the field of music listening interventions as a therapeutic method and as a potential highly-accessible way of coping with stress and anxiety on a daily basis.
Understanding the impacts of music on the mental health of adolescents could bring benefits to the community. With the onset of the COVID-19 pandemic, many aspects of healthcare, including therapy involving music interventions, have moved to a virtual setting. Virtual therapy is also becoming more widely used with the increasing accessibility to technology and the internet. Using music as a way to achieve self-relaxation and other benefits is common and popular. At the same time, mental health—especially for adolescents—has called more attention to the development of interventions because of its significant impact on social functioning (Porter et al., 2016). The purpose of this study is to conduct a survey involving music listening interventions and observing the emotional responses of adolescents in order to potentially establish a relationship—possibly beneficial—between the music listening and resulting mental health.
Up to 20% of adolescents in the U.S. will experience a depressive episode by the time they are 18 years old. Adolescent depression and anxiety commonly co-occur depending on the physiological, psychological, and social changes they experience (Porter et al., 2016). Many of these changes are a result of similar environments that most adolescents share, such as a school setting or within a friend group. An individual’s experience of emotions is linked to their social environment, and many adolescents live in similar environments, thus resulting in similar impacts on emotional response. With the aspect of music, any significant effect of music on the emotional response of an individual requires consideration and observation of the person’s social surroundings (Sloboda et al., 2001). Music has also been shown to reduce negative emotions and feelings, including state anxiety, and increase positive emotions and feelings (de Witte et al., 2020).
The concept of music therapy overshadows the more specific music interventions and music medicine concepts. Music therapy involves the use of specific aspects of music with a music therapist. The defined relationship between the patient and therapist differentiates music therapy from other music interventions. Active music interventions involve the individual actively engaging with the music through means such as improvisation, music composition, or vocalizing and singing (de Witte et al., 2020). In receptive interventions, the patient responds to the music rather than actively making music; both active and receptive interventions consider specific musical components of the music, including tempo, rhythm, dynamics, and melody (de Witte et al., 2020). Most people who use music for purposes involving self-benefit or pleasure are not engaging in music therapy, but rather music medicine, and more likely receptive music interventions.
This present research studies the emotional effects of music listening interventions on adolescents using receptive music interventions. It contributes to the smaller number of studies that focus on adolescents by targeting individuals 14 to 18 years of age.
H0A: A participant who completes an experimental survey version(music stimulus) will not have a significant change in state anxiety level compared to a participant who receives a control survey version(non music stimulus).
H1A: A participant who completes an experimental survey version(music stimulus) will have a significant change in state anxiety level compared to a participant who receives a control survey version(non music stimulus).
H0B: Among the participants who completed experimental versions of the survey, there will not be a significant change in state anxiety levels between the categories of key, genre, and tempo.
H1B: Among the participants who completed experimental versions of the survey, there will be a significant change in state anxiety levels between the categories of key, genre, and tempo.
Materials & Methods
The purpose of the study was to mainly focus on observing the emotional responses in adolescents, so the age range was between 14 to 18 years of age in order to obtain results from individuals who are exposed to similar social changes and communities. The population of interest thus is mainly high school students. Most participants resided in the Dallas Fortworth area Participants were not compensated for their completion of the survey. Participants were told that their answers from their survey would be used for a research study, and that they would remain anonymous and confidential throughout the entire study.
The average age of the 40 participants was 15.8 years. 12.5% of participants were freshmen, 5% were sophomores, 65% were juniors, and 17.5% were seniors. 70% of participants were female, 27.5% were male, and 2.5% marked “other” for gender.
The survey was created and taken on the voice and video feedback platform Phonic (https://www.phonic.ai/), which allowed for the successful inclusion of audio files into questions. The online platform required participants to utilize an electronic device, most frequently a desktop or laptop, and the audio portion of the survey required a sound output device, most commonly speakers and headphones. Based on the research done prior to this study, the three following assessments were selected to measure the levels of stress and anxiety: State Anxiety version of the State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Healthy Unhealthy Music Scale (HUMS).
With restrictions to online distribution of the survey and limited access to advanced technology and research primarily due to the COVID-19 pandemic, the survey was determined to be online. This decision was made in order to achieve the most optimal method of obtaining responses. The survey remained anonymous and confidential for the respondents, and was sent online to each individual participant using participants’ emails provided through a Google form. Participants were instructed in the email to complete the survey within 48 hours and given the survey link.
The purpose of the study was to observe music and non-music related effects on adolescents, and thus the survey was composed of a control and experimental groups: the control is composed of white noise and pink noise, both of which are regularly used as music listening interventions for the purpose of obtaining therapeutic effects or self-relaxation (Lu et al., 2020). The experimental variable consists of music with three specific observable attributes.
In the experimental versions of the survey, three major music characteristics were taken into consideration and included during the process of developing the survey: key, genre, and tempo (measured in beats per minute).
The key of a musical composition denotes a scale that creates the foundation for the creation of the composition, and is present in all three genres that were included in the survey.
Three genres were selected based on popularity and use in past studies of the topic of music interventions (de Witte et al., 2020). Classical music was observed across several of the studies and papers used during the pre-research process. Jazz was included as one of the most-preferred genres rated by the general public. Hip hop was included to extend from a previous study that observed therapeutic effects of hip hop lyrics (Tyson, 2002).
Music at a slower tempo(with steady rhythm) was shown to potentially provide stress reduction (de Witte et al., 2020). Music with an identified tempo range was found to have larger effects on stress-related outcomes (de Witte et al., 2019). Thus, there were three designated categories for tempo: slow(60-76 bpm), moderate (76-120 bpm), and fast (> 120 bpm). The parameters of these three categories were based on the most frequently-used terms in classical music to denote tempo: adagio – slow, moderato – moderate, allegro – fast. Studies concerning music listening interventions also utilized specific tempo ranges to categorize the composition used (de Witte et al., 2019).
A within subjects design was used; 20 versions of the survey were created, each with three music compositions of the same key, tempo range, and genre from the categories described above.
Table 1: Individual survey versions’ music compositions(experimental)
The surveys were identified with letters to represent key, genre, and tempo; key was labeled with either a lowercase ‘m’ or uppercase ‘M’ (minor, major respectively); genre was labeled with a ‘c’, ‘j’, or ‘h’(classical, jazz, hip hop respectively); tempo was labeled with ‘s’, ‘mo’, or ‘f’(slow, moderate, fast respectively).
White noise and pink noise consist of random distributions of frequencies as opposed to intentionally spaced frequencies that compose music. The control variable consisted of white noise and pink noise in order to compare effects of musical and nonmusical acoustic stimulation on emotional response. Sounds that fall under the category of white noise and/or pink noise lack the typical components of music, such as rhythm and melody (Thoma et al., 2013), but are still acoustic stimuluses, and thus were used as the control in this study.
Table 2: Control variable audio sample descriptions
All twenty versions of the survey follow the same structural format. The first questions obtain general information from the respondent: age, gender, grade level, race and ethnicity, and musical experience. The participant was asked to complete STAI, PSS, and HUMS questionnaires respectively, before being asked to listen to the audio clips. Participants were then given instructions regarding the three following audio questions.
Phonic survey – instructions given to participants before providing audio stimuli
The same STAI-S questionnaire was given to the respondent to fill out after the three audio questions. The survey included a question regarding the individual’s preference for each of the three genres included in the study (classical, jazz, hip hop), and a final question about the sound output device used.
Phonic survey – Music Preference questionnaire (Likert scale 1-5)
The State Trait Anxiety Inventory is used to assess state anxiety and trait anxiety (STAI-S; Spielberg, 1989). The state version, STAI-S, of the questionnaire is used in studies measuring stress-related outcomes (de Witte et al., 2019). The 20-question State-Anxiety questionnaires were completed before and after providing the audio samples in the survey in order to measure for possible changes as a result of the acoustic stimulation, as seen used in the study by Thoma et al.. Each of the 20 statements are Likert-scale based with a range of 1 to 4(1 – not at all, 2 – a little, 3 – somewhat, 4 – very much so). Before and after results, measured on a scale of 20(low anxiety level) to 80(high anxiety level), were compared to analyze the impact of the acoustic stimulation on state-anxiety levels.
The self-report questionnaire, Perceived Stress Scale(PSS), was used to measure the level of stress of participants before listening to the audio samples (Cohen et al., 1983). The PSS score can range from 0 to 40; scores ranging from 0-13 would be considered low stress, 14-26 would be considered moderate stress, and 27-40 would be considered high perceived stress. The scale ranged from 0 to 4 on a Likert-scale(0 – never, 1 – rarely, 2 – sometimes, 3 – often, 4 always). The scores were calculated for each participant to compare their levels of stress.
The Healthy-Unhealthy Music Scale(HUMS) was developed to address the engagement of music as an indicator of proneness to adolescent depression (Saarikallio et al., 2015). The scale can be used to observe music-based emotion regulation and healthy and unhealthy music use (Silverman, M. J., 2019). The scale consists of 13 items divided into subscales of healthy and unhealthy on a Likert-scale of 5 items (never, rarely, sometimes, often, always), which were calculated for each participant in this study and compared to each other and the other participants.
The STAI-S questionnaire was provided first out of the three questionnaires(STAI-S, PSS, and HUMS) used in the survey prior to the audio questions. Scores were calculated by adding each number provided by the participant for all 20 questions. The number for questions regarding a positive emotion or description was recorded on a reversed 1-to-4 Likert scale. Scores for the before and after STAI-S questionnaires were compared by subtracting the after-score by the before-score. A positive difference signifies a positive impact of the audio stimulus on state-anxiety.
Figure 1: Average STAI-S score change per category
The Perceived Stress Scale (PSS) questionnaire was provided in the question following the STAI-S questionnaire. The number for questions pertaining to a positive description or idea was recorded on a reversed 0-to-4 Likert scale. Scores for the PSS were then calculated by the number provided by the participant per question. Scores from 0-13 are considered a low stress level, 14-26 are considered moderate stress, and 27-40 are considered high perceived stress. According to results from the PSS questionnaire, 15% of participants were found to have a high level of stress, 65% had a moderate level of stress, and 20% had a high level of stress.
Figure 2: Percent of participants per stress level (low stress: 0-13, moderate stress, 14-26, high stress: 27-40)
The Healthy-Unhealthy Music Scale questionnaire was asked after the PSS. The questions were divided into HUMS Healthy and HUMS Unhealthy based on their positive or negative description of music’s role in the participant’s life. The HUMS Healthy is expected to positively correlate with indicators of good mental health, and HUMS Unhealthy is expected to correlate negatively with indicators of good mental health (Saarikallio et al., 2015). Participants’ answers were scored on a Likert scale from 1 to 5 (1-never, 2-rarely, 3-sometimes, 4-often, 5-always). HUMS Healthy and Unhealthy scores were calculated for each individual. Comparisons between the scores for HUMS Healthy and HUMS Unhealthy showed that 85% of participants had a higher HUMS Healthy score than HUMS Unhealthy score, 7.5% of participants had the same HUMS Healthy and HUMS UNhealthy score, and 7.5% of participants had a lower HUMS Healthy score than HUMS Unhealthy score.
Figure 3: HUMS Healthy and Unhealthy scores for participants with classical genre category survey versions
Figure 4: HUMS Healthy and Unhealthy scores for participants with jazz genre category survey versions
Figure 5: HUMS Healthy and Unhealthy scores for participants with hip hop genre category survey versions
Figure 6: HUMS Healthy and Unhealthy scores for participants with control(white noise, pink noise) survey versions
The z-score was calculated for the experimental versions and control versions comparison, and t-scores were calculated for comparisons between control versions and major, minor, classical, jazz, hip hop, slow tempo, moderate tempo, fast tempo experimental versions. p-values were found for all nine categories.
Table 1: z-score and t-score statistics for comparisons of STAI change between music component category and control versions. Statistically significant p-values: **p ≤ 0.05
The experimental versions had a sample size of 36, and its significance compared to the control versions showed a z-score of -1.439, and p-value of 0.150. Eight other comparisons were made between each music component included in the study (key: major & minor, genre: classical, jazz, hip hop, tempo: slow, moderate, fast). The sample sizes for the experimental versions of each music component were below 30, so t-score was used and p-values were calculated for each one. A confidence level of 95% was used; jazz versions compared to the control was the only comparison out of the eight that had a p-value below 0.05. On the other hand, major, minor, classical, hip hop, slow, moderate, and fast versions did not have a significant impact on the change of STAI score (p = 0.232, p = 0.488, p = 0.313, p = 0.245, p = 0.899, p = 0.302, p = 0.295, respectively). The t-score for hip hop versus control was the only one out of the comparisons that was negative because of having a smaller sample mean than population mean(mean of control STAI-changes).
The purpose of this study was to find potential changes in stress and anxiety levels as a result of specific music components. We found a significant difference between jazz genre versions and the control versions (p = 0.038), therefore H0B can be rejected. The t-score for jazz versions versus control versions was the largest out of all the comparisons because the mean of STAI-change of the jazz versions was the greatest compared to the other categories. We did not find significant differences between the other experimental variables and the control. There was no significant STAI change in comparing all the experimental versions with the control, thus we fail to reject H0A.
The results from the Perceived Stress Scale questionnaire show that all of the individuals with a jazz version of the survey displayed either a moderate or low level of stress, while some individuals with classical or hip hop versions displayed a high level of stress. We also observed that individuals with low levels of stress had either a higher HUMS-Healthy score than HUMS-Unhealthy score, or the same score for both. Participants with the greatest positive difference between HUMS-Healthy and HUMS-Unhealthy scores also had low levels of stress (M-c-mo: PSS = low, H-Healthy = 25, H-Unhealthy = 8). This suggests that there is a correlation between lower levels of stress and a higher H-Healthy score than H-Unhealthy. There did not seem to be a correlation between HUMS scores and participants who displayed moderate or high levels of stress.
Out of the twenty participants who received survey versions not of their preferred genre out of the three tested genres, five participants displayed a negative STAI difference (25%). And out of the sixteen participants who received a survey version with their most preferred genre, two of them displayed a negative STAI difference (12.5%). This may signify a correlation between state anxiety levels and the selected genre of music based on an individual’s preference. The majority of participants (87.5%) indicated that they had musical experience with a musical instrument sometime in the past and/or present day. However, whether the participants had musical experience or not, both displayed negative and positive STAI differences, so there was no observable correlation between musical experience and state anxiety levels.
The research process has identifiable limitations that need to be considered. The sample size was limited to 40 individuals due to the reduction of face-to-face social interaction because of current restrictions from the COVID-19 pandemic, and individuals were given the survey online to take on their own time. Thus, the environment in which each participant took the survey likely varies and could potentially have affected responses. Because there were three experimental variables tested in this study, the number of control samples was very low, which can inaccurately represent the results of the control. This study ideally should have had thirty-six control responses in order to balance the number of experimental responses. Participants were also located primarily in the Dallas Fortworth area, so the findings from this study cannot be generalized for adolescents in other regions of the U.S. or beyond. The selection of music stimuli was based on previous studies involving the use of music listening interventions and also general lists of music therapy song repertoire (University of Kansas Music Therapy Song Repertoire Resource List), and was done based on the three components of music that were observed. As a result, the music selections are likely limited and are not able to fully encompass each music characteristic. It is suggested to take other music components into consideration in future studies and increase the amount and variation of music stimuli given to participants. This study was also limited to a total of three scales to analyze participants’ responses. Therefore, it is suggested that replication studies include other scales that can contribute to the observation of stress and anxiety levels in order to observe potentially more defined data.
A significant implication of this study is that the use of music listening interventions can affect changes in stress and anxiety levels in adolescents. The stress that the rigorous environment in which adolescents live in today could be lessened with the knowledge of basic effects of music interventions and potential benefits they could bring. The concept and findings from this study could encourage further research in the scope of music interventions and their possible benefits to the mental health of adolescents. Gaining more research in the field of music medicine and interventions can help make music a more established part of mental health care and increase its accessibility to cope with stress and anxiety levels.
Cohen, S., Kamarck, T., & Mermelstein, R. (1983). A global measure of perceived stress. Journal of Health and Social Behavior, 24, 385-396.
Hense, C., Silverman, M. J., & McFerran, K. S. (2018). Using the Healthy-Unhealthy Uses of Music Scale as a Single-Session Music Therapy Intervention on an Acute Youth Mental Health Inpatient Unit. Music Therapy Perspectives. Published. https://doi.org/10.1093/mtp/miy013
de Witte, M., Pinho, A. D. S., Stams, G. J., Moonen, X., Bos, A. E., & van Hooren, S. (2020). Music therapy for stress reduction: a systematic review and meta-analysis. Health Psychology Review, 1–26. https://doi.org/10.1080/17437199.2020.1846580
de Witte, M., Spruit, A., van Hooren, S., Moonen, X., & Stams, G. J. (2019). Effects of music interventions on stress-related outcomes: a systematic review and two meta-analyses. Health Psychology Review, 14(2), 294–324. https://doi.org/10.1080/17437199.2019.1627897
Liu Y, Liu G, Wei D, Li Q, Yuan G, Wu S, Wang G and Zhao X (2018) Effects of Musical Tempo on Musicians’ and Non-musicians’ Emotional Experience When Listening to Music. Front. Psychol. 9:2118. doi: 10.3389/fpsyg.2018.02118
Porter, S., McConnell, T., McLaughlin, K., Lynn, F., Cardwell, C., Braiden, H. J., Boylan, J., & Holmes, V. (2016). Music therapy for children and adolescents with behavioural and emotional problems: a randomised controlled trial. Journal of Child Psychology and Psychiatry, 58(5), 586–594. https://doi.org/10.1111/jcpp.12656
Saarikallio, S., Gold, C., & McFerran, K. (2015). Development and validation of the Healthy-Unhealthy Music Scale. Child and Adolescent Mental Health,20(4). https://doi.org/10.1111/camh.12109
Sharma, M. (2015). Expanding Horizons Of Academically Stressed Adolescents Through Music Therapy By Enhancing Perceived Social Support And Academic Resilience. Prestige International Journal of Management & IT – Sanchayan, 04(01), 1–12. https://doi.org/10.37922/pijmit.2015.v04i01.007
Silverman, M. J. (2019). Music-based emotion regulation and healthy and unhealthy music use predict coping strategies in adults with substance use disorder: A cross-sectional study. Psychology of Music, 49(3), 333–350. https://doi.org/10.1177/0305735619854529
Sloboda, J. A., & O’Neill, S. A. (2001). Emotions in everyday listening to music. In P. N. Juslin & J. A. Sloboda (Eds.), Music and emotion: Theory and research (pp. 415–429). Oxford University Press.
Spielberger, C. D. (1989). State-Trait Anxiety Inventory: Bibliography (2nd ed.). Palo Alto, CA: Consulting Psychologists Press.
Tyson, E. H. (2002). Hip Hop Therapy: An Exploratory Study of a Rap Music Intervention with At-Risk and Delinquent Youth. Journal of Poetry Therapy, 15(3).University of Kansas Music Therapy Song Repertoire Resource List [Music therapy song repertoire resource list acts as a reference for music therapy students as they work to develop a diverse repertoire of songs for use in their musical, pre-clinical, and clinical work.]. (2021). University of Kansas.
Osteo-odonto-keratoprosthesis (OOKP), or ‘tooth in eye surgery’, is a medical procedure involving removing a patient’s tooth to replace the cornea and inserting a tiny lens before being implanted into the eye.
As of the moment, the intersection between dentistry and medicine hasn’t been explored too much, however using teeth, a body part that most people have an excess of, is useful in being able to maximise the potential of the body’s own properties.
First described by Italian Professor Benedetto Strampelli in the early 1960s and modified by Falcinelli , creating the modified osteo-odonto-keratoprosthesis (MOOKP), the procedure is used in patients with bilateral end-stage ocular surface disease.
The procedure is still rarely practiced and as of the moment, only one surgeon, Professor Christopher Liu, can do the operations in the UK.
OOKP is usually reserved as a last resort for patients with severely rare types of corneal blindness and cases of bilateral end-stage ocular surface diseases whereby other methods of treatment and surgery have been ineffective.
Some severe autoimmune diseases can also be approached with OOKP:
End-stage autoimmune dry eye disease; Sjögren’s and graft-versus-host disease
Severe exposure keratopathy
Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
The MOOKP is carried out in two stages done 4–5 months apart, each lasting 6 to 8 hours.
Firstly the patient’s tooth with some jawbone is removed and cut into a block.
Half the root is removed, pulp is removed and the dentine of the tooth is polished to the desired thickness.
Through the root of the tooth remaining, a hole is drilled and a plastic lens or optic cylinder is placed and set with acrylic bone cement, or universal resin cement.
Then the tooth and lens are sutured in place, into a pocket of skin underneath the opposite eye to the one it will be implanted into.
A piece of skin from inside the patient’s cheek is cut and stitched over the eyeball being operated on, covering the cornea and sclera with the conjunctiva or with lid suturing; for the time being, this forms the front of the new eye.
For 4 to 5 months, the patient will have lived without being able to see anything due to the skin covering the eye. By then, the tooth will have grown its own soft tissue and the cheek skin over the patient’s eye will have developed circulation.
In the second stage of MOOKP procedure, the tooth is retrieved from the pocket of skin and excess tissue removed, ensuring that some is left for stitching.
The cheek skin that had been covering the eye is carefully peeled back, and then the entire front of the eyeball is removed; this part of the procedure can’t be reversed.
The tooth and lens are then implanted into the eye and the cheek skin stitched back leaving a small hole for the lens. The skin now forms the front of the patient’s eye.
If the procedure is successful, the patient will recover their sight as their eye would have developed circulation and the brain begins to recognise and process the images now reaching the retina.
If unsuccessful, any remaining sight they had before surgery would be lost.
MOOKP has produced good long-term functional success rates. The largest study so far, included 181 patients and showed a 93.9% success rate, and at 18 years of follow up, there was an 85% probability of retention of vision.
But as with any surgery, especially with one so high risk, and specialised as MOOKP is, there are several complications including:
Lamina-resorption } potentially leading to anatomical failure.
How feasible is making OOKP a more widespread procedure in medicine?
I find it unlikely that OOKP will become a more widely utilized procedure.
According to NHS England, only 5 patients annually are expected to undergo the procedure, with 60 patients being followed up on each year. Due to the high number of professionals required for each section of the surgery, and due to the lack of professionals specialized in this specific procedure and due to the costs, estimated to be around $55,150, as proposed in a paper by Dong et al, I can’t see OOKP becoming a popularized option for those wanting to regain vision. However, as a procedure that can highly improve the quality of life for some, and treat blindness and visual impairments highly effectively, it has much potential to grow .
Modified OOKP surgery for corneal blindness can provide longterm, anatomically stable vision retention as well as an effective, rehabilitating recovery of the cornea. I think that OOKP is an interesting intersection between medicine and dentistry, and as there’s not too much research, and cases of OOKP being carried out, due to its highly fragile nature, and lack of professionals that are trained to carry it out, it would be an exciting surgical process to see further developed. Despite the complications that OOKP can carry along with it, considering its long term benefits, and its ability to restore vision in patients, it can impact many more patients in future.
Nara Ito, Youth Medical Journal 2022
 Falcinelli, G., Falsini, B., Taloni, M., Colliardo, P., & Falcinelli, G. (2005). Modified osteo-odonto-keratoprosthesis for treatment of corneal blindness: long-term anatomical and functional outcomes in 181 cases. Archives of Ophthalmology, 123(10), 1319-1329.
 Basu, S., Pillai, V. S., & Sangwan, V. S. (2013). Mucosal complications of modified osteo-odonto keratoprosthesis in chronic Stevens-Johnson syndrome. American journal of ophthalmology, 156(5), 867-873.
 Zarei-Ghanavati, M., Avadhanam, V., Perez, A. V., & Liu, C. (2017). The osteo-odonto-keratoprosthesis. Current opinion in ophthalmology, 28(4), 397-402.
 Tan, A., Tan, D. T., Tan, X. W., & Mehta, J. S. (2012). Osteo-odonto keratoprosthesis: systematic review of surgical outcomes and complication rates. The ocular surface, 10(1), 15-25.
 Sawatari, Y., Perez, V. L., Parel, J. M., Alfonso, E., Falcinelli, G., Falcinelli, J., & Marx, R. E. (2011). Oral and maxillofacial surgeons’ role in the first successful modified osteo-odonto-keratoprosthesis performed in the United States. Journal of oral and maxillofacial surgery, 69(6), 1750-1756.
 Hille, K., Landau, H., & Ruprecht, K. W. (1999). Improvement of the osteo-odonto-keratoprosthesis according to Strampelli: influence of diameter of PMMA cylinder on visual field. Graefe’s archive for clinical and experimental ophthalmology, 237(4), 308-312. Dong, D., Tan, A., Mehta, J. S., Tan, D., & Finkelstein, E. A. (2014). Cost-effectiveness of osteo-odonto keratoprosthesis in Singapore. American journal of ophthalmology, 157(1), 78–84.e2. https://doi.org/10.1016/j.ajo.2013.08.004
The urinary tract infection (UTI) is considered the most common infection and causes around 8 million trips to the clinic and emergency department every year in the US. This infection is more common in women and is also known to affect many elders. A UTI is caused when bacteria from the skin or rectum enter the urinary tract. While the most common UTI is a bladder infection, kidney infections are a more severe form of UTI. The typical symptoms of a UTI consist of a burning sensation while urinating, pain in the groin or lower abdomen, and a fever.
CDC, “Urinary Tract Infection.”
After recurring UTIs, bacteria is infamous for growing resistant to antibiotics, which constantly pushes scientists to develop new forms of treatment. A research team at Baylor College of Medicine and Washington University School of Medicine found a new use of a familiar medicine to treat UTIs by analyzing how the body naturally fights back against E. coli, which causes more than 85% of UTIs. They noticed that a specific pathway greatly contributed to the elimination of E. coli as well as the protection of bladder tissue and wanted to see how they could use this to treat UTIs.
With around 5,600 lab-grown urothelial cells, cells inside the lining of the bladder, the team infected them using E. coli bacteria and allowed them to proliferate. These cells were also stained with a fluorescent dye to indicate the presence of active compounds known as reactive oxygen species (ROS). In response to the growing bacteria population, the urothelial cells produced ROS that killed the E. coli bacteria, which the researchers confirmed through immunofluorescence staining. However, this increase in ROS levels was dangerous as ROS damages urothelial cells alongside E. coli bacteria, causing significant issues with the bladder. Then, the Baylor researchers found that the high levels of ROS led to an anti-ROS response called the NRF2 pathway. Nuclear factor erythroid 2-related factor 2 (NRF2) is a protein in the cytoplasm that is bound to another protein called Kelch-like ECH-associated protein 1 (KEAP1). After a certain level of ROS accumulates, NRF2 separates from KEAP1 and enters the nucleus, where it activates a series of genes. Some of these genes reduce the inflammation in the bladder, and others reduce ROS levels. One activated gene, RAB27B, expels E. coli from the urothelial cells. The NRF2 pathway’s dual ability to protect the bladder tissue and fight off bacteria suggested a new treatment of UTIs. On the other hand, the scientists found that the loss of NRF2 resulted in an increase in ROS, bacteria levels, and inflammation.
With this new information, the team searched for an NRF2 pathway activator and found one FDA-approved drug called dimethyl fumarate (DMF). DMF is typically used to treat relapsing multiple sclerosis, but the scientists believed DMF would be effective in treating UTIs as well. A related study showed that a high concentration of DMF can directly kill bacteria, so the scientists treated their lab-grown cells with lower levels of DMF. Additionally, the team tested DMF on mice with UTI and observed the activation of NRF2 in both experiments, which in turn mitigated the damage from the ROS and increased RAB27B expression to eliminate the E. coli. The mice had fewer bacteria in their urine, reduced damage to their bladder tissue, and reduced inflammation.
Cell Reports, “Graphical abstract.”
Continued use of antibiotics not only develops resistant bacteria but also harms the “good bacteria,” or microbiome, of the body. However, the professor of molecular virology and microbiology at Baylor, Dr. Mysorekar, commented, “The most exciting part about this work was identifying a non-antibiotic-based therapy that contained the infection and reduced inflammation.” Since the DMF treatment does not utilize antibiotics, it eliminates the concern of the bacteria becoming resistant. The researchers at Baylor realized that the activation of NRF2 is critical for our body’s defense against UTIs. They recognize the long process before this treatment can be applied clinically and hope that this experiment will open up the possibility of DMF treatment to aid women who suffer from recurrent UTIs. The team also hopes that future efforts focus on identifying additional NRF2 modulators like DMF. It is imperative that we continue to search for more effective methods of treatment in order to continue revolutionizing the world of medicine.
Kyle Phong, Youth Medical Journal 2021
Cell Reports, “NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression”, 19 October 2021
Autism is a very complex disorder, as it cannot be categorized by one simple cause or one simple effect. The molecular basis of this disease is not a commonly explored topic, but this review will go over some parts of it. ASD is commonly caused by mutations, both in non-coding genes and through protein-coding sequences. This review will also outline some experiments performed in order to specify certain genes that lead to ASD. Brain structure will be explored and potential cures for ASD will be identified as well.
Autism spectrum disorder (ASD) is a disorder characterized by deficits in social communication and the presence of restricted interests along with repetitive behaviors . The first ever documentation of ASD was done in 1943 by Leo Kanner . Some causes for the disorder include genetic mutations, an overgrowth of the brain known as macrocephaly, and other lesser known causes. Overall, ASD is a pretty rare disease, affecting about 1% of all populations worldwide. Symptoms for diagnosis of ASD include social-communication deficits, and restricted and repetitive interests/behaviors. However, ASD is also linked with other abnormalities such as motor and sensory abnormalities . ASD is a wide-encompassing disorder as there is not a single locus where the disorder occurs. Instead, it is widespread and several regions throughout the body have been identified to cause autism. No widespread treatment exists for ASD yet, treatments such as gene therapy and protein replacement therapy are some potentially widespread therapies that will be discussed in this review.
Molecular Basis of ASD
Importance of GABA Signalling
Gamma-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. It is primarily used to calm down neural responses throughout the nervous system. GABA is synthesized from glutamate and catalyzed by the enzyme glutamic acid decarboxylase . GABA affected by autism has negative effects due to mutations that lead to an inverse effect of the inhibition originally caused. Rather than inhibiting neural signals, patients with autism have GABA receptors that are mutated, allowing for a sensory overload at times that can make them more susceptible to touch based responses. As shown in figure 1, interrupted GABA signalling will lead to less interrupted signals and may even overload the brain through an increased amount of neural connections sent from the hand to the brain.
Figure 1: A) A schematic showing proper tactile perception of a ball recognized from a hand. Arrows indicate information travelling from the hand to the brain. Red octagons represent inhibited signals within synapses and green lightning bolts represent excitatory signals within synapses. B) As in A, but, arrows show overload of information reaching the brain as a cause of too little inhibition within synapses illustrated by green lightning bolts and a lack of red octagons. Red splatter shows a brain with ASD getting overloaded with information due to mutations in GABRG1, GABRA2,GABRA4, and GABRB1.
Mutations Correlated with Autism
List of Potential Genes that are Correlated with Autism
Autism is a very complex disease that does not have only one cause to it. Since it has numerous factors, there are multiple genes that affect it as well. Some such genes include GABRG1, GABRA2,GABRA4, and GABRB1, which all are related to GABA signalling in some way or another. Mutations in these gene subunits will affect the inhibition of neural signals and may cause a sensory overload due to the sheer amount of neural signals being sent at once .
Proteins Affected by Genetic Mutations Associated with ASD
Since genes code for proteins, they also play an important role. One minor change in a codon can entirely change the proteins being synthesized. An example of a protein affected by asd is CPEB4, a protein involved in coordinating the expressions of hundreds of genes required for neural activity. In one study, rats were found to show signs of ASD linked with defects in the ability to express this protein . Another protein linked gene is CNOT1, which is a commonly mutated gene found in numerous autism patients. One study discovered that variations in this gene led to problems with learning and memory .
Details About Brain Structure
Sights of Interest in the Brain
The cortex is made up of 4 lobes: the temporal lobe, the parietal lobe, the occipital lobe, and the frontal lobe. The frontal lobe includes the frontal cortex and all other cortices, along with broci’s area. The temporal lobe contains white matter, part of the lateral ventricle, the tail of the caudate nucleus, and the hippocampal formation. The occipital lobe contains the primary and association visual cortex and is the smallest lobe of the brain . Lastly, the parietal lobe contains the postcentral gyrus, the superior parietal lobule, and the inferior parietal lobule. All the lobes are located in the cerebrum. Other parts of the brain include the brainstem, cerebellum, and amygdala. In terms of function, the frontal lobe controls emotions and regulates them in interpersonal relationships and social situations.
ASD in the Brain
Several different brain regions across the brain are listed to show causes of autism. For example, in this study, researchers found that in the cerebellum, a lack of RNF8 led to too many synapses forming in the brain. However, the extra synapses worked and did not cause too many problems for the mice. The mice that did not have the RNF8 gene showed signs of struggling to learn new motor skills, a prevalent factor of ASD .
ASD out of the Brain
Not just brain – sensory deficits also drive certain behaviors in ASD as well. Manipulating certain senses can lead to ASD, for example messing with the sense of touch to make someone more susceptible to pain may lead to ASD. Somatosensory touch can happen in a number of places on the skin, and thus can lead to more awkwardness in outside scenarios and potentially even a form of ASD. Impacts to the peripheral nervous system will also affect the central nervous system because they are interlinked. ASD affects the link between them by reducing the threshold for the peripheral nervous system to send signals to the central nervous system.
Potential Treatments for ASD
Treatments that might work
Currently, no existing treatment exists for ASD. However, there have been numerous studies theorizing some potential solutions to the disorder that may lead to some success. One study talks about using GABA A receptor agonists in order to treat tactile overreactivity . These agonists activate the GABA receptors, allowing them to inhibit receptors to counteract the overstimulation of neurons within the brain.
Gene therapy is a relatively newer method for curing potential autism along with other genetic disorders and diseases. Gene therapy is defined as the treatment of disease by transfer of genetic material into cells . An example of gene therapy would be if someone had a cancerous tumor forming from a genetic mutation. Gene therapy could be used to correct that mutation by rewriting it. Gene therapy works by doctors first delivering a copy of healthy cells with the correct genes into the patient’s system and allowing them to adjust to the body. However, some pitfalls to this method include the developmental nature of the disorder, causing genetic therapy to potentially become ineffective in some cases. Additionally, specific targeting may be difficult such as targeting specific types of neurons.
Protein Replacement Therapy is another potential treatment for ASD as well. As the name suggests, this treatment works by replacing non functioning proteins or proteins that are not working properly. Protein replacement therapy is a newer treatment method, but it may be the next innovative way to cure rare diseases in a much simpler way . Downfalls of this method include the lifespan of proteins, ranging from a few hours to a few weeks. However, future research of protein replacement therapy could lead to a more universal and lasting change in proteins.
ASD is a complex disorder, consisting of numerous causes and symptoms. Ever since Leo Kanner discovered the first case, the prevalence of the disorder has increased substantially. Various mutations, both genetic and protein based, can induce ASD in children and adults. The molecular basis of Autism is rooted in chemical changes within the brain, both with responses to stimuli and receptors not firing off correctly. Overall, the brain is the most affected part of the body by ASD, physically and psychologically. Some potential treatments are discussed in this review, and they have potential to work through further testing.
Tebartz van Elst, L., Pick, M., Biscaldi, M., Fangmeier, T., & Riedel, A. (2013). High-functioning autism spectrum disorder as a basic disorder in adult psychiatry and psychotherapy: Psychopathological presentation, clinical relevance and therapeutic concepts. European Archives of Psychiatry and Clinical Neuroscience, 263(S2), 189–196. https://doi.org/10.1007/s00406-013-0459-3
Won, H., Mah, W., & Kim, E. (2013). Autism spectrum disorder causes, mechanisms, and treatments: Focus on neuronal synapses. Frontiers in Molecular Neuroscience, 6. https://doi.org/10.3389/fnmol.2013.00019
Ma, D. Q., Whitehead, P. L., Menold, M. M., Martin, E. R., Ashley-Koch, A. E., Mei, H., Ritchie, M. D., DeLong, G. R., Abramson, R. K., Wright, H. H., Cuccaro, M. L., Hussman, J. P., Gilbert, J. R., & Pericak-Vance, M. A. (2005). Identification of Significant Association and Gene-Gene Interaction of GABA Receptor Subunit Genes in Autism. The American Journal of Human Genetics, 77(3), 377–388. https://doi.org/10.1086/433195
Parras, A., Anta, H., Santos-Galindo, M., Swarup, V., Elorza, A., Nieto-González, J. L., Picó, S., Hernández, I. H., Díaz-Hernández, J. I., Belloc, E., Rodolosse, A., Parikshak, N. N., Peñagarikano, O., Fernández-Chacón, R., Irimia, M., Navarro, P., Geschwind, D. H., Méndez, R., & Lucas, J. J. (2018). Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing. Nature, 560(7719), 441–446. https://doi.org/10.1038/s41586-018-0423-5
Vissers, L. E. L. M., Kalvakuri, S., de Boer, E., Geuer, S., Oud, M., van Outersterp, I., Kwint, M., Witmond, M., Kersten, S., Polla, D. L., Weijers, D., Begtrup, A., McWalter, K., Ruiz, A., Gabau, E., Morton, J. E. V., Griffith, C., Weiss, K., Gamble, C., … de Brouwer, A. P. M. (2020). De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay. The American Journal of Human Genetics, 107(1), 164–172. https://doi.org/10.1016/j.ajhg.2020.05.017
Valnegri, P., Huang, J., Yamada, T., Yang, Y., Mejia, L. A., Cho, H. Y., Oldenborg, A., & Bonni, A. (2017). RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain. Nature Communications, 8(1), 1271. https://doi.org/10.1038/s41467-017-01333-6
Orefice, L. L., Mosko, J. R., Morency, D. T., Wells, M. F., Tasnim, A., Mozeika, S. M., Ye, M., Chirila, A. M., Emanuel, A. J., Rankin, G., Fame, R. M., Lehtinen, M. K., Feng, G., & Ginty, D. D. (2019). Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models. Cell, 178(4), 867-886.e24. https://doi.org/10.1016/j.cell.2019.07.024
Gorzelany, J. A., & de Souza, M. P. (2013). Protein Replacement Therapies for Rare Diseases: A Breeze for Regulatory Approval? Science Translational Medicine, 5(178), 178fs10-178fs10. https://doi.org/10.1126/scitranslmed.3005007
Mitochondrial replacement therapy: a brief introduction
Three-parent IVF or mitochondrial replacement therapy is a unique form of in-vitro fertilization that produces an embryo possessing the nuclear DNA of two parents and the mitochondrial DNA (mt-DNA) from a female donor. Different types of this procedure include maternal spindle transfer, pronuclear transfer, and polar body genome transfer. The primary aim behind the development of this technique is to allow women with defective mitochondrial DNA to have biologically related healthy offspring without fatal mitochondrial dysfunction. It also increases the chances of pregnancy in older women.
WHAT ARE MITOCHONDRIAL DYSFUNCTIONS?
To understand mitochondrial dysfunctions, let’s go back to mitochondria. Mitochondria are intracellular organelles that are responsible for ATP production in eukaryotic organisms. Mitochondria contain their own genome consisting of approximately 37 genes. Mitochondrial disorders originate from the mutations of this genome. Organs with high energy demands such as the heart, central nervous system, and endocrine system are particularly affected by this. About 100 babies are born with severe mt-disorders in the UK, the majority of which die in the infant stage These conditions are exclusively inherited from the mother.
TYPES OF MRT
Pronuclear transfer Technique
In this technique, both the mother and donor eggs are fertilized by the father’s sperm. The pronucleus of the donor zygote (containing healthy mitochondria) is replaced by that of the biological parents’. The biological mother then carries the embryo to term.
Maternal Spindle Transfer (MST)
This technique extracts the maternal spindle complex in the metaphase of the mother’s egg and transplants it into the donor’s egg with healthy mitochondria. It is a form of preimplantation genetic diagnosis. This lowers the chances of mt-DNA carryover and mutations.
Polar body genome transfer (PBT)
In this technique, the polar body is removed from a zygote in the pronucleus stage and transferred to a zygote with the maternal nucleus and the polar body previously removed or the polar body is withdrawn from the oocyte in meiosis II and transferred to an oocyte in MII with the spindle previously removed, followed by fertilization of the reconstructed oocyte.
MRT AROUND THE WORLD
The United Kingdom
In February 2015, the United Kingdom became the first country in the world to legalize maternal spindle transfer and pronuclear transfer. In 2017, the UK fertility clinic was granted the first license to start its first clinical trial by HFEA.
On 6th April 2016, the world’s first baby was born in Mexico conceived via maternal spindle transfer to a 36-years old Jordanian woman who was a carrier of Leigh’s disorder. This was done with the consent of the Internal Review Board (IRB) of the Mexican clinic.
On 5th January 2017, the world’s second 3-parent baby was born in Ukraine conceived via pronuclear transfer. The procedure was approved by the Ukrainian Association of Reproductive Medicine.
United States of America
The mitochondrial replacement therapy remains illegal in the United States because of social and privilege stemming from social and economic peculiarities is the main cause. Mitochondrial disorders have an extremely low prevalence in the United States and according to 2017 data, only 12,423 American women were at the risk of passing on their defective mitochondrial DNA to their offspring. Hence, the country refrains from allocating large amounts of resources to MRT.
On 9 April 2019, using the maternal spindle transfer technique of MRT, a woman in her early 30s conceived a child in Athens. This is considered unique as it was termed as a “Global first” because the motive was not to avert a genetic disorder, it was to treat infertility.
MRT- A revolutionary technology?
Reproductive autonomy is a basic human right. Mitochondrial replacement therapy allows women to have biologically related children without passing on possible life-threatening disorders. Inability to have children has been shown to have profound psychological impact on women. MRT can be a solution to both these problems. The risks of mixing the mother and donor mt-DNA is negligible and such a case has not yet been reported.
No suitable alternatives
Egg donation cannot establish a genetic link between the child and the mother as the child will possess both the nuclear DNA and mt-DNA of the donor. It may also cause ovarian hyperstimulation. Surrogacy cannot also be a possible solution as the child will get the mt-DNA from the mother. Preimplantation genetic diagnosis is only appropriate for women with low amounts of defective mt-DNA.
Creation not Cure
Mitochondrial replacement therapy is meant to create healthy offspring free of a genetic mitochondrial disorder and not as a cure. It can indirectly reduce the prevalence of mitochondrial disorders in society.
Lesbian couples can particularly benefit from this novel technology as the nuclear and mitochondrial genomes can each come from one of the two partners. This will allow both women to establish a hereditary link to the child.
Treating infecundity in older women
Older women have fewer mitochondrial DNA in their oocytes compared to younger women.Defective mt-DNA can lower the stability of nuclear DNA of oocytes leading to embryo aneuploidy and subsequent infections. Using mitochondria from a younger woman can thus improve the quality and fertility of the older woman’s eggs.
The technique is extremely expensive. Mitochondrial diseases have a low occurrence. 1/40000 in the United States suffer from this. Critics question the feasibility of investing a massive sum of money and resources for a small segment of the population.
MRT does not cure mitochondrial disorders and does not guarantee prevention. A wide variety of heteroplasm may occur in the children. If the nuclear genome does not co-operate with mt-DNA may have terrible medical results. Due to ethical concerns of reproductive research on humans and lack of related data, there is a fear of unknown conditions developing in the future. This is also germline as a female offspring can pass on this genetic change to the next generations.
Mitochondrial replacement therapy alters the germline as the offspring inherits the genetic change. If the child is female, the new mt-DNA will be passed on to her offspring.
Effects on specific interest groups
There are an increasing number of people to trace their genetic ancestry using the Y-chromosome and mitochondrial DNA. This information can provide individuals a sense of identity. If MRT is applied, they might receive misleading information which can affect their personal perspectives of themselves.
“Nature or nurture” is a long standing question in the sciences; are people more influenced by biological or environmental factors when maturing? Twin studies attempt to answer that question, and although it has not been fully answered, these studies begin to provide an understanding of which aspects of human beings can be attributed to specific factors, whether those are genes or the environment in which people have grown up. Twin studies were first introduced to the scientific world in the 1870s by Sir Francis Galton. Galton attempted to answer this question of “nature or nurture” (Twin studies, 2007). In a number of published articles, he ultimately argued that nature was the more influential factor after studying the results of a questionnaire that focused on how similar or different twins turned out to be after aging, regardless of growing up together or separately. Although Galton’s conclusion was an early argument to a question that has still not been fully answered, it revealed the potential of studying twins in terms of gaining knowledge of the different genetic and environmental influences in human lives, and, eventually, how that knowledge relates to biomedical research relating to diseases.
Twins studies are valuable to biomedical research in that the unique cases of twins allow researchers to separate genetic and environmental influences. Twin cases are separated into two types: Dizygotic and Monozygotic. Dizygotic, or fraternal, twins are not genetically identical but are raised in the same settings from birth. These twins are conceived through two separate, fertilized eggs. They develop in the womb and are born at the same time, but they do not share the same genetics. Monozygotic, or identical, twins—on the other hand—do have the same genetic predispositions, as they have developed from the same fertilized egg. The single fertilized egg splits into two, allowing for two embryos to develop and explaining the identical genetic material (Brogan, 2020). Twin studies also offer the opportunity to control for the factors of age and gender, but the genetic similarity between identical twins is ultimately key to twin research.
When raised in separate environments, identical twins are not influenced by environmental factors, allowing for researchers to study only the biological influences. Similarities in behavior or predispositions to diseases that both twins possess would indicate a biological basis, as environmental influences have been controlled (Brogan, 2020). Conversely, studying identical twins raised in the same environments also have the potential to identify environmental triggers that are connected to diseases. When the genetics and environment of identical twins are the same, similar reactions or onsets to diseases after exposures from the environment can be identified, possibly linking environmental triggers to different conditions.
One twin study conducted by Chirag Lakhani that utilizes insurance claims data from the insurance company Aetna analyzed more than 56,000 twins. The insurance records allowed researchers to study the health of the twins while looking for a connection with some of the 560 diseases that the study focused on. Diseases that occur more often in identical twins in the study were believed to have a genetic influence, and the diseases that occurred in siblings regardless of their twin status were believed to have an environmental influence. Ultimately, the study found that of the 560 diseases that researchers focused on, 40% had a genetic component, while 25% had an environmental component (“Nature or nurture twins study”).
Twin registries are collections of data on twins that are used for future studies. Many countries have established their own twin registries, and they may be overseen by universities or other nongovernmental organizations. Twin registries allow researchers to analyze existing twin data that has been archived, study data related to the development of twins, and pursue twins overtime for longitudinal data for studies completed over longer time frames (Brogan, 2020).
Advantages and Disadvantages
The major advantage of twin studies is that the unique situation of twins allows researchers to begin to calculate and separate the genetic and environmental influences on characteristics of people. Factors, specifically genetics or environment as well as age and gender, can be controlled in order to focus on the impact of a specific factor (Brogan, 2020).
In addition, there are also disadvantages and limitations. Separated, identical twins can still have (and often do still have) similar living environments (although they will not be the same). Twins that become orphans are commonly raised by relatives that share similar socioeconomic situations, influencing housing, living conditions, and financial stability. Adopted twins may also be sent to similar families to avoid favoritism (Brogan, 2020). These situations lessen the ability to effectively separate genetic and environmental influences, which is what makes twin studies valuable.
Twin studies are valuable opportunities to study the genetic and environmental factors that influence a person’s characteristics. Looking through the scope of medicine, twin studies can be used to identify genetic and environmental components of diseases or conditions. While these components are still yet to be fully understood, twin studies have offered partial answers and have the potential to return more significant research that relates to disease onset or other areas of medicine.
Michelle Li, Youth Medical Journal 2021
Brogan, R. F. (2020). Twin studies. In Gale Science Online Collection. Gale. Retrieved September 20, 2021, fromhttps://link.gale.com/apps/doc/KEIGGJ810319895/SCIC?u=mlin_m_newtnsh&sid=bookmark-SCIC&xid=2c42af4e