Categories
Biomedical Research

Osteo-odonto-keratoprosthesis: How Teeth Can Restore Your Vision

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 [1], 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:

  • Cicatricial trachoma
  • 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.

Stage one:

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.

Stage two:

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.
  • Glaucoma
  • Choroidal/retinal detachment
  • Vitreous hemorrhage
  • Endophthalmitis

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 [7].

Conclusion: 

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

References:

[1] 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.

[2] 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.

[3] Zarei-Ghanavati, M., Avadhanam, V., Perez, A. V., & Liu, C. (2017). The osteo-odonto-keratoprosthesis. Current opinion in ophthalmology, 28(4), 397-402.

[4] 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.

[5] 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.

[6] 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.[7] 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

Categories
Neuroscience

The Brains Behind Social Conformity and Change

By Nara Ito

Published 6:05 EST, Mon December 20th, 2021

Conformity: A change in a person’s behaviour or opinions as a result of real or imagined pressure from a person or group of people’ (Elliot Aronson 2011).

We all want to believe that we are in full control of our thoughts, make righteous judgments, and spot when others are trying to manipulate us.  However, psychology and neuroscience has shown that we are all influenced by social factors, and are influenced by peer pressure to adhere to others’ beliefs and behaviours. This article highlights how we as individuals shift our beliefs, mannerisms, and behaviour according to our environment, attachments and the situations we are in.

Conformity, according to an increasing number of neuroscientific studies, attracts brain signals that are comparable to those engaged in reinforcement learning. (Kim et al., 2012)

Reinforcement learning, or operant conditioning, is a core behavioural approach of psychology  that elucidates how we are able to learn behaviours.  Proposed by B.F. Skinner, operant conditioning is based on the idea that a behaviour can be learned of unlearned through constant reinforcement,  either positive or negative..

3  main types of conformity are:

Internalisation: when a person genuinely accepts the group norms, resulting in  private and public change of opinions, becoming part of the way the person thinks and acts.

Identification: conforming to the opinions of a group because there is something about that group we value thus publicly change our opinions to achieve approval.

Compliance :simply ‘going along with others’ in public, but privately not changing personal opinions.

Morton Deutsch and Harold Gerard (1955) developed a two-process theory, in order to explain the basis and reasons for conformity

Informational social influence (ISI) – The concept that one conforms with the opinion of the majority because we believe it is correct.  This may often lead to internalisation

Normative social influence (NSI) – When we agree with the opinion of the majority because we want to be accepted, gain social approval and be liked, possibly leading to compliance

So can social conformity and perception change brain physiology?

Potentially. In a study run by Campbell-Meiklejohn, Frith, and colleagues, found that the lateral orbitofrontal cortex is particularly sensitive to signs of social conflict or disagreement, which may influence changes of opinion.

Adorno et al. (1950) wanted to understand the anti-Semitism of the Holocaust, which their research they came to believe that a high level of obedience was basically a psychological disorder, and tried to locate the causes of it in the personality of the individual, in a study of more than 2000 middle-class, white Americans and their unconscious attitudes towards other racial groups. They developed the fascism scale (F-scale) which is still used to measure authoritarian personality. 

 Findings: Probably the most interesting discovery from this study was that there was a strong positive correlation between authoritarianism and prejudice. Authoritarian characteristics included a tendency to be especially obedient and conferment to authority. They have an extreme respect for authority and submissiveness to it.

For obvious reasons, there are no brain scans or images of the participants’ brains however, in a more recent study by Warner, Tranel and Asp, they concluded that clearly tendencies toward authoritarian attitudes and prejudicial beliefs are the result of environmental and genetic factors, but sufficient damage to the ventromedial prefrontal cortex can contribute to creating authoritarian individuals. Throughout both cognitive and psychometric tests, patients with lesions to this region exhibit consistent conformity and obedience to authoritarian commands as well as, patients with vmPFC damage. 

More modern neuroimaging studies complement these neuropsychological findings and provide evidence that the vmPFC and amygdala are critical structures involved in inhibiting and facilitating authoritarian attitudes.

In conclusion, this argument that we have free will, and control over who ‘we’ are is an extensive debate, but what is currently understood, is that humans conform, and have the potential to change aspects of themselves depending on the situation, whether it be consciously or unconsciously.

Nara Ito, Youth Medical Journal 2021

References:

Warner, K., Tranel, D., & Asp, E. (2016). The henchman’s brain: Neuropsychological implications of authoritarianism and prejudice. In J. R. Absher & J. Cloutier (Eds.), Neuroimaging personality, social cognition, and character (pp. 325–335). Elsevier Academic Press. https://doi.org/10.1016/B978-0-12-800935-2.00017-8

Deutsch, M., & Gerard, H. B. (1955). A study of normative and informational social influences upon individual judgment. The journal of abnormal and social psychology, 51(3), 629.

Aronson, E. (2011). The evolution of cognitive dissonance theory: a personal appraisal. In The Science of Social Influence (pp. 115-135). Psychology Press.

Kim, D., & Hommel, B. (2015). An event-based account of conformity. Psychological Science, 26(4), 484-489.

Campbell-Meiklejohn, D. K., Bach, D. R., Roepstorff, A., Dolan, R. J., & Frith, C. D. (2010). How the opinion of others affects our valuation of objects. Current Biology, 20(13), 1165-1170.

Campbell-Meiklejohn, D. K., Kanai, R., Bahrami, B., Bach, D. R., Dolan, R. J., Roepstorff, A., & Frith, C. D. (2012). Structure of orbitofrontal cortex predicts social influence. Current Biology, 22(4), R123-R124.

Snyder, M., & Ickes, W. (1985). Personality and social behavior. Handbook of social psychology, 2(3), 883-947.

Adorno, T., Frenkel-Brenswik, E., Levinson, D. J., & Sanford, R. N. (2019). The authoritarian personality. Verso Books.

Hollander, E. P. (1958). Conformity, status, and idiosyncrasy credit. Psychological review, 65(2), 117.

Categories
Health and Disease

What OCD Really Entails

By Nara Ito

Published 4:50 PM EST, Sat May 22, 2021

Introduction

The DSM system recognizes OCD, or Obsessive-compulsive disorder, and a range of related disorders as characterized by either obsessions (recurring thoughts and images), or compulsions (repetitive actions). Most with a diagnosis of OCD have both obsessions and compulsions.

Compulsions

A behavioural characteristic of OCD is compulsive behaviour.

Compulsions are repetitive

Sufferers of OCD feel compelled to repeat a certain behaviour. For example, excessive hand washing; what seems like a simple action that particularly amidst the current COVID-19 pandemic we’ve encouraged to do more, can affect sufferers of OCD by which they wash their hands to the extent it causes damage. Other common compulsive repetitions include counting, praying and tidying/ordering groups of objects.

Compulsions reduce anxiety

Around 10% of sufferers of OCD show compulsive behaviour alone – they have no obsessions, just a general sense of irrational anxiety. For the vast majority, however, compulsions are used to manage the anxiety produced by obsessions. For example, linking to the previous example compulsive hand washing is carried out as a response to an obsessive fear of germs.

Avoidance 

Another behavioural aspect of OCD is that sufferers of OCD tend to try to manage their OCD by avoiding situations that trigger anxiety. For example, sufferers who wash compulsively may avoid coming into contact with germs. However, this avoidance can lead people to avoid very ordinary situations, such as emptying their rubbish bins. These actions end up interfering with their lives and prevent them from leading a normal life. 

Obsessions

For around 90% of OCD sufferers, the major cognitive feature of their condition is obsessive thoughts. Though heavily varying between individuals, obsessive thoughts are intrusive and unpleasant. Some sufferers may respond by adopting cognitive coping strategies. For example, a religious person tormented by obsessive guilt may respond by praying or meditating.

Insight into excessive anxiety  

Sufferers of OCD are aware that their obsessions and compulsions are not rational. In fact this is necessary for a diagnosis of OCD. OCD sufferers experience catastrophic and intrusive thoughts about the worst scenarios and also tend to be hypervigilant, focusing on potential hazards. 

Anxiety

OCD causes severe emotional arousal swell as distress due to the anxiety that accompanies both obsessions and compulsions.  It is also often accompanied by depression, so anxiety can be accompanied by low mood and lack of enjoyment in activities and irrational guilt over minor issues

Genetic explanation of OCD

OCD is an example of a condition that is presently largely understood as biological in nature.

OCD has been found to be polygenic, whereby multiple genes are involved in vulnerability to OCD; Taylor (2013) suggested ~230 different genes can be linked to the onset of OCD. Lewis (1936) observed that of his OCD patients 37% had parents with OCD and 21% had siblings with OCD, suggesting that OCD can run in families, but rather provides genetic vulnerability to OCD rather than causality. The diathesis-stress model suggests that the presence of certain genes make people more likely and vulnerable to suffer a mental disorder. However, environmental stress is also necessary to trigger the condition. 

Certain genes, which create vulnerability for OCD, called candidate genes have been identified, including the gene 5HT1-D beta. This gene has been found to affect the efficiency of transport of serotonin across synapses. 

Neural explanation of OCD

The genes associated with OCD are likely to affect the levels of key neurotransmitters as well as structures of the brain are called neural explanations. 

Serotonin:

The neurotransmitter serotonin is known to regulate mood. Neurotransmitters are chemicals responsible for relaying information from one neuron to another. Some cases of OCD may be explained by a reduction in the functioning of the serotonin system in the brain, and some other  cases of OCD, and in particular hoarding disorder, seem to be associated with impaired decision making. 

Treating OCD with Drug Therapy

Selective serotonin reuptake inhibitors (SSRI) are the standard class of drugs used to treat OCD. They work on the serotonin system in the brain, by preventing the re-absorption and breakdown of serotonin, increasing its levels in the synapse and continuing to stimulate the postsynaptic neuron.

It takes three to four months of daily use for SSRIs to have much impact on symptoms. 

Drugs are often used alongside cognitive behaviour therapy (CBT) to treat OCD. The drugs reduce a patient’s emotional symptoms, such as feeling anxious or depressed. This means that patients can engage more effectively with the CBT. 

In practice some people respond best to CBT alone whilst others benefit more from drugs like Fluoxetine. Occasionally other drugs are prescribed alongside SSRIs. 

Whereby patients do not respond to SSRIs, a second line of defence can be other drugs such as:

  • Tricyclics (an older version of antidepressant) have the same effect on the serotonin system as SSRIs. Tricyclics like clomipramine have more severe side effects than SSRIs thus are generally kept in reserve.
  • SNRIs (serotonin-noradrenaline reuptake inhibitors) increase levels of serotonin as well as another different neurotransmitter – noradrenaline.

Nara Ito, Youth Medical Journal 2021

References

Tolin, D. F., Worhunsky, P., & Maltby, N. (2006). Are “obsessive” beliefs specific to OCD?: A comparison across anxiety disorders. Behaviour Research and Therapy, 44(4), 469-480.

Pertusa, A., Fullana, M. A., Singh, S., Alonso, P., Menchón, J. M., & Mataix-Cols, D. (2008). Compulsive hoarding: OCD symptom, distinct clinical syndrome, or both?. American Journal of Psychiatry, 165(10), 1289-1298.

Team, P. O. T. S. P. (2004). Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. Jama, 292(16), 1969-1976.

Masellis, M., Rector, N. A., & Richter, M. A. (2003). Quality of life in OCD: differential impact of obsessions, compulsions, and depression comorbidity. The Canadian Journal of Psychiatry, 48(2), 72-77.

Ivarsson, T., Melin, K., & Wallin, L. (2008). Categorical and dimensional aspects of co-morbidity in obsessive-compulsive disorder (OCD). European Child & Adolescent Psychiatry, 17(1), 20-31.

Renshaw, K. D., Steketee, G., & Chambless, D. L. (2005). Involving family members in the treatment of OCD. Cognitive Behaviour Therapy, 34(3), 164-175.

Billett, E. A., Richter, M. A., Sam, F., Swinson, R. P., Dai, X. Y., King, N., … & Kennedy, J. L. (1998). Investigation of dopamine system genes in obsessive–compulsive disorder. Psychiatric genetics.

Denys, D., Van Nieuwerburgh, F., Deforce, D., & Westenberg, H. G. (2006). Association between serotonergic candidate genes and specific phenotypes of obsessive compulsive disorder. Journal of affective disorders, 91(1), 39-44.

Sinopoli, V. M., Burton, C. L., Kronenberg, S., & Arnold, P. D. (2017). A review of the role of serotonin system genes in obsessive-compulsive disorder. Neuroscience & Biobehavioral Reviews, 80, 372-381.

Frisch, A., Michaelovsky, E., Rockah, R., Amir, I., Hermesh, H., Laor, N., … & Weizman, R. (2000). Association between obsessive-compulsive disorder and polymorphisms of genes encoding components of the serotonergic and dopaminergic pathways. European Neuropsychopharmacology, 10(3), 205-209.

Stewart, S. E., & Pauls, D. L. (2010). The genetics of obsessive-compulsive disorder. Focus, 8(3), 350-357.

Categories
Health and Disease

Phobias and How We Can Treat Them

By Nara Ito

Published 11:58 PM EST, Tues April 27, 2021

Introduction

All phobias are characterized by excessive fear and anxiety, initiated by a phobic stimulus. The extent of the fear is most typically blown out of proportion in contrast to the real threat the phobic stimulus actually poses.

The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders), published by the American Psychiatric Association, is a system that many researchers and clinicians use to identify and diagnose mental health problems. It recognizes the following categories of phobia and related anxiety disorder: 

  • Specific phobia: phobia of a particular object, such as an animal or body part, or a certain situation. 
  • Social anxiety (social phobia): phobia of a social situation such as public speaking. 
  • Agoraphobia: phobia of being outside or being in a public place.

Phobias can be diagnosed as clinical phobias and be disabling by causing tremendous suffering and the inability for a person to function adequately. In fact, a clinical phobia is only diagnosed if anxiety is considerable and it impacts the sufferer’s life. But regardless if the phobia is clinically mild or not, individuals exhibit certain characteristics when they have a phobia falling under three categories of behavioral, cognitive, and emotional.

Behavioral characteristics of phobias 

Evolutionarily, we have a fight or flight response when we feel like we are in the presence of a threat. We respond to things or situations we fear by behaving in particular ways. Phobias cause the individual to feel high levels of anxiety and try to escape, even if the level of fear is irrational, out of all proportion to the phobic stimulus. 

Panic: Someone with a phobia may panic in response to the phobic stimulus. This may be recognized by a range of behaviors including screaming, running away, or crying heavily. Amongst children, some may express panic by freezing, clinging to an object or person, or having a tantrum. 

Avoidance: Unless the phobic person requires to or makes a conscious effort to face their fear, most of the time they attempt to avoid coming into contact with the phobic stimulus. For many with phobias of specific objects that stay in particular areas and spaces, this may be easy to avoid, however, avoidance can easily affect the individual’s daily life. For example, someone with a fear of pigeons would have to heavily limit the time spent outside, as a pigeon can fly over or appear at any moment as they are a very common bird to see around.

Endurance: The alternative to avoidance is endurance, in which the individual remains in the presence of the phobic stimulus and somewhat tolerates it but only with very high levels of anxiety. In some situations, this may be unavoidable, for example for a person who has an extreme fear of flying having to sit through a flight.

Emotional characteristics of phobias 

Anxiety: In the DSM-5 phobias are classed as anxiety disorders. Anxiety being an unpleasant state of high arousal, phobias prevent the individual from relaxing and make it very difficult to experience any positive emotion as they are continually tense.

Emotional responses are unreasonable: Being heavily irrational fears, emotional responses we experience in relation to a phobic stimulus often exceed what is considered reasonable to most others.

Cognitive characteristics of phobias 

Cognitive characteristics affect the ways people process information and think. 

Selective attention to the phobic stimulus: When phobic people can see the phobic stimulus their attention remains constantly on it as they see the stimulus as a threat. When in actual danger, this ability to have selective attention is crucial so that we can react quickly to a threat,  however, this isn’t useful when the fear is irrational.

Irrational beliefs:Someone with a phobia may hold irrational beliefs in relation to phobic stimuli. This is particularly prevalent when it comes to social phobias as the individual starts to create irrational beliefs about the self that can foster toxic mindsets and increase the pressure on the sufferer to perform well in social situations. 

So how are phobias treated?

The two main methods of treatment when it comes to phobias are systematic desensitization and flooding.

Systematic desensitization (SD) is a behavioral therapy designed to reduce unwanted responses to the phobic stimulus, this may include emotional characteristics such as anxiety. SD involves drawing up a hierarchy of anxiety-provoking situations related to the phobic stimulus, teaching the patient to relax, and then slowly exposing them to phobic situations, working their way through the hierarchy whilst maintaining relaxation. As the patient gets more accustomed to the stimulus, a new response to the phobic stimulus is learned by which the phobic stimulus is paired with relaxation instead of anxiety. This learning of a different response is called counterconditioning. 

Flooding on the other hand is a behavioral therapy in which a phobic patient is exposed to an extreme form of high concentrations of the phobic stimulus in one go in order to reduce anxiety triggered by that stimulus. This takes place across a small number of long therapy sessions, but sometimes only one long session is needed to cure a phobia, making it quick and efficient.

Flooding stops phobic responses very quickly because without the option of avoidance behavior or escaping, the patient has to tolerate and withstand the stimulus, thus quickly learning that the phobic stimulus is harmless. In classical conditioning terms, this process is called extinction. In some cases, the patient may achieve relaxation in the presence of the phobic stimulus simply because they become exhausted by their own natural fight or flight response.

Nara Ito, Youth Medical Journal 2021

References

Regier, D. A., Kuhl, E. A., & Kupfer, D. J. (2013). The DSM‐5: Classification and criteria changes. World psychiatry, 12(2), 92-98.

Kilpatrick, D. G., Resnick, H. S., Milanak, M. E., Miller, M. W., Keyes, K. M., & Friedman, M. J. (2013). National estimates of exposure to traumatic events and PTSD prevalence using DSM‐IV and DSM‐5 criteria. Journal of traumatic stress, 26(5), 537-547.

Heimberg, R. G., Hofmann, S. G., Liebowitz, M. R., Schneier, F. R., Smits, J. A., Stein, M. B., … & Craske, M. G. (2014). Social anxiety disorder in DSM‐5. Depression and anxiety, 31(6), 472-479.

Marks, I. M. (2013). Fears and phobias. Academic Press.

Seligman, M. E. (1971). Phobias and preparedness. Behavior therapy, 2(3), 307-320.

Merckelbach, H., de Jong, P. J., Muris, P., & van Den Hout, M. A. (1996). The etiology of specific phobias: A review. Clinical Psychology Review, 16(4), 337-361.

Öst, L. G. (1989). One-session treatment for specific phobias. Behaviour research and Therapy, 27(1), 1-7.

Burstein, M., He, J. P., Kattan, G., Albano, A. M., Avenevoli, S., & Merikangas, K. R. (2011). Social phobia and subtypes in the National Comorbidity Survey–Adolescent Supplement: prevalence, correlates, and comorbidity. Journal of the American Academy of Child & Adolescent Psychiatry, 50(9), 870-880.

Emmelkamp, P. M., & Wittchen, H. U. (2009). Specific phobias.

Straube, T., Glauer, M., Dilger, S., Mentzel, H. J., & Miltner, W. H. (2006). Effects of cognitive-behavioral therapy on brain activation in specific phobia. Neuroimage, 29(1), 125-135.

Davis, T. E., & Ollendick, T. H. (2011). Specific phobias. In Handbook of child and adolescent anxiety disorders (pp. 231-244). Springer, New York, NY.

Categories
Health and Disease

A Review of Prion Diseases

By Nara Ito

Published 2:42 PM EST, Wed March 24, 2021

Introduction

As suggested by the name, prion disease is ultimately caused by prions. Prions are abnormal, pathogenic agents, that can cause the abnormal folding of normal cellular proteins, called prion proteins. Prion proteins are found most abundantly on the surface of cells in the brain thus when having become abnormal, and clump together, can easily lead to brain damage and rapidly progressive and fatal conditions. 

About Prion Disease

The individual can develop prion disease sporadically, which is by chance, which occurs the most often; genetically, where the patient inherits prion disease however, fewer than 15% of people with prion disease have a family history of the disease or test positive for a genetic mutation associated with prion disease; and by contamination, by which in few cases people have developed prion disease after being exposed to infected human tissue amidst medical procedures, such as during a cornea or skin transplant and a few people have developed prion disease after undergoing brain surgery with contaminated instruments. A small number of people have also developed prion disease from eating meat contaminated with mad cow disease. 

Some types of prion disease would include: 

CJD (Creutzfeldt-Jakob Disease)

  •  Most cases of CJD are sporadic and tend to occur in those around age 60. Symptoms of CJD quickly lead to severe disability and death. In most cases, death occurs within a year.  

Variant CJD

  •  First capturing major public attention in the 90s after people in the UK developed this after eating meat from diseased cattle, this is an infectious type of the disease that is related to “mad cow disease.” Eating diseased meat may cause the disease in humans. This type of the disease usually affects younger people. 

Variably protease-sensitive prionopathy (VPSPr)

  • Similar to CJD but the proteins involved in pathogenesis are less sensitive to digestion. It is more likely to occur in individuals over the age of 70 who have a family history of dementia.  

The most common form of prion disease that affects humans is Creutzfeldt-Jakob disease (CJD). 

  • Creutzfeldt-Jakob is a degenerative brain disorder that leads to dementia and, ultimately, death.  Symptoms are similar to those of other dementia inducing brain disorders, such as Alzheimer’s disease.  Worldwide, about one to two cases of CJD are diagnosed per million people each year. 

General symptoms of CJD include: 

  • Rapidly developing dementia 
  • Difficulty walking and changes in gait 
  • Hallucinations 
  • Muscle stiffness 
  • Confusion 
  • Fatigue 
  • Difficulty speaking 
  • This abnormal accumulation of protein in the brain can cause memory impairment, personality changes, and difficulties with movement. 

The pattern of symptoms can vary depending on the type of Creutzfeldt-Jakob disease (CJD). 

In sporadic CJD, the neurological symptoms, affecting the CNS develop rapidly and worsen in the space of a few months. 

Initial neurological symptoms of sporadic CJD can include: 

  • difficulty walking caused by balance and coordination problems  
  • slurred speech  
  • numbness or pins and needles in different parts of the body  
  • dizziness  
  • vision problems, such as double vision and hallucinations 

Advanced neurological symptoms of all forms of CJD can include: 

  • loss of physical coordination, which can affect a wide range of functions, such as walking, speaking and balance
  • muscle twitches and spasms  
  • loss of bladder control and bowel control 
  • blindness 
  • swallowing difficulties 
  • loss of speech  
  • loss of voluntary movement 

In variant CJD, behavioural and psychological will usually develop first.  

Initial psychological symptoms of variant CJD can include: 

  • severe depression 
  • intense feelings of despair  
  • withdrawal  
  • anxiety 
  • irritability  
  • insomnia 

Advanced psychological symptoms of all forms of CJD include: 

  • loss of memory, which is often severe  
  • problems concentrating  
  • confusion  
  • feeling agitated  
  • aggressive behaviour  
  • loss of appetite, which can lead to weight loss  
  • paranoia   
  • unusual and inappropriate emotional responses 

Familial CJD has the same sort of pattern as sporadic CJD, but it often takes longer for the symptoms to progress, usually 2 years, rather than a few months. 

The pattern of iatrogenic CJD is unpredictable, as it depends on how a person became exposed to the infectious prion that caused CJD. 

The vast majority of CJD patients usually die within 1 year of illness onset. In about 85% of patients, CJD occurs as a sporadic disease with no recognizable pattern of transmission. A smaller proportion of patients (5% to 15%) develop CJD because of inherited mutations of the prion protein gene. 

Physicians suspect a diagnosis of CJD on the basis of the typical signs and symptoms and progression of the disease, including the presence of 14-3-3 protein in the cerebrospinal fluid however, as CJD is always fatal this must be confirmed with other means. 

Prion diseases are confirmed by taking a sample of brain tissue during a biopsy or after death. Healthcare providers, however, can do a number of tests before to help diagnose prion diseases such as CJD, or rule out other diseases with similar symptoms. 

The tests include: 

  • MRI scans of the brain 
  • Samples of fluid from the spinal cord 
  • Blood tests 
  • Neurologic and visual exams to check for nerve damage and vision loss 
  • Electroencephalograms 

Prion diseases can’t be cured, but certain medicines may help slow their progress. Besides sporadic onset, this disease can be prevented by properly cleaning and sterilizing medical equipment and tougher regulations governing the handling and feeding of cows. 

Nara Ito, Youth Medical Journal 2021

References

Prusiner S. B. (1991). Molecular biology of prion diseases. Science (New York, N.Y.), 252(5012), 1515–1522. https://doi.org/10.1126/science.1675487 

Prusiner, S. B. (1996). Molecular biology and pathogenesis of prion diseases. Trends in biochemical sciences, 21(12), 482-487. 

Prusiner, S. B. (1996, January). Molecular biology and genetics of prion diseases. In Cold Spring Harbor symposia on quantitative biology (Vol. 61, pp. 473-493). Cold Spring Harbor Laboratory Press. 

Clarke, A. R., Jackson, G. S., & Collinge, J. (2001). The molecular biology of prion propagation. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 356(1406), 185-195. 

Weissmann, C. (1994). Molecular biology of prion diseases. Trends in cell biology, 4(1), 10-14. 

Sarnataro, D., Pepe, A., & Zurzolo, C. (2017). Cell biology of prion protein. Progress in molecular biology and translational science, 150, 57-82. 

Harris, D. A. (1999). Cellular biology of prion diseases. Clinical microbiology reviews, 12(3), 429-444. 

Collinge, J. (2005). Molecular neurology of prion disease. Journal of Neurology, Neurosurgery & Psychiatry, 76(7), 906-919. 

Wadsworth, J. D., & Collinge, J. (2011). Molecular pathology of human prion disease. Acta neuropathologica, 121(1), 69-77. 

Sigurdson, C. J., Bartz, J. C., & Glatzel, M. (2019). Cellular and molecular mechanisms of prion disease. Annual Review of Pathology: Mechanisms of Disease, 14, 497-516. 

Moore, R. A., Taubner, L. M., & Priola, S. A. (2009). Prion protein misfolding and disease. Current opinion in structural biology, 19(1), 14-22. 

Cohen, F. E. (1999). Protein misfolding and prion diseases. Journal of molecular biology, 293(2), 313-320. 

Nunziante, M., Gilch, S., & Schätzl, H. M. (2003). Prion diseases: from molecular biology to intervention strategies. Chembiochem, 4(12), 1268-1284. 

Horwich, A. L., & Weissman, J. S. (1997). Deadly conformations—protein misfolding in prion disease. Cell, 89(4), 499-510. 

Taraboulos, A., Raeber, A. J., Borchelt, D. R., Serban, D., & Prusiner, S. B. (1992). Synthesis and trafficking of prion proteins in cultured cells. Molecular biology of the cell, 3(8), 851-863. 

Categories
Health and Disease

What Hair Can Say About Your Health

Dry and Dull Hair

Dry and dull hair could indicate a lack of unsaturated fats in your diet. 

These are vital because they promote healthy skin and a healthy scalp, which revitalizes your strands. Contrary to popular belief, curlier and kinkier hair (types 3A-4C) are naturally more prone to being drier, as coils make it harder for hair’s natural oils to coat and moisturise each strand.

You can improve your hair by including avocado, olive oil, and salmon into your diet, as well as using argan, olive, or black castor oil on your hair.

Brittle Hair

Naturally curly hair tends to be more fragile than straight hair. Due to the uneven shape of the fibre, the hair shaft has spots where the internal structure becomes exposed, leaving the hair vulnerable to damage and dehydration. Although everyone’s locs need moisture, extremely brittle hair can actually be a sign of a zinc or an iron deficiency. Zinc and iron are important in the production of keratin, the main structural fibrous protein that hair is made up of, and having an insufficient amount can lead to changes in the structure of hair. To combat brittle hair, you could take zinc supplements, alone or with a mineral formula including iron, or you could eat foods that are high in zinc (e.g. beef, pumpkin seeds, and lentils). 

Having brittle hair could also be one of the many symptoms of Cushing’s syndrome, a rare condition caused by too much cortisol, the body’s primary stress hormone, alongside high blood pressure, fatigue, and back pain.

Thinning and Shedding Hair

Thinning hair could mean your diet lacks protein.

Hair is made of protein and needs adequate protein levels to be healthy. Made up of keratin, the aforementioned fibrous protein, hair can thin or deplete in overall health due to calorie cuts in your diet. It is not a perfect measure, but some experts estimate that we may shed up to 100 or more hairs a day. For adult males, balding is at a higher rate, but genes cause 90% of male hair loss

Sudden shocks and changes to your body’s system such as chemotherapy, giving birth, diets, severe stress, and thyroid problems can push hair into its resting, or telogen, state. Excessive shedding could indicate a more serious condition. Lack of iron (anemia), thyroid diseases, vitamin D deficiency, and low ferritin levels are a few things doctors may look into when severe hair loss is being reported out of ‘nowhere’.. A general rule of thumb is if you are experiencing hair loss and your ferritin is below 40 ng/mL, it’s a good idea to supplement. Too much or too little testosterone in women can also have negative effects for hair loss. In alopecia areata, your immune system mistakenly attacks hair follicles, causing hair to fall out. Most patients will have one or two bald patches, which can be treated easily with injections.

Premature Greying

Greying is part of the natural aging process, however, early and premature greying may not be. Genetics might play a part, but in some cases, the lack of pigment in hair at a young age can indicate a copper deficiency. We do not need too much copper in our diets however, it is suggested to add more mushrooms, sesame seeds, and seaweeds to combat the deficiency.

Stress is constantly labelled as the biggest killer, and a prevalent root of many health complications, including premature greying. Oxidative stress, in particular, may affect pigment-producing cells.

Hair For Drug Tests

Hair can be used in forensics to test for an extremely extensive range of substances: cannabis, cocaine, opiates, amphetamines, methamphetamines, benzodiazepines, methadone, mephedrone and ketamine. Drugs in the bloodstream can be recognised between 7 days and 6 months after their use. Test results also indicate the month someone ingested the substance and can be used to build an estimated timeline of substance use. In case the hair is unsuitable for testing, such as highly bleached or damaged, body hair or fingernails can also be used, as they are made of the same fibrous proteins.

Nara Ito, Youth Medical Journal 2021

References

  1. Nayak, B. S., Ann, C. Y., Azhar, A. B., Ling, E., Yen, W. H., & Aithal, P. A. (2017). A Study on Scalp Hair Health and Hair Care Practices among Malaysian Medical Students. International journal of trichology, 9(2), 58–62. https://doi.org/10.4103/ijt.ijt_76_16
  2. St Pierre SA, Vercellotti GM, Donovan JC, Hordinsky MK. Iron defi ciency and diffuse nonscarring scalp alopecia in women: more pieces to the puzzle. J Am Acad Dermatol. 2010;63:1070–6.
  3. Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron defi ciency and its potential relationship to hair loss. J Am Acad Dermatol. 2006;54:824–44.
  4. Rushton DH, Dover R, Norris MJ, Gilkes JJH. Iron and hair loss in women; what is deficiency? This is the real question! J Am Acad Dermatol. 2007;56:518–9; author reply 519.
  5. https://www.ncbi.nlm.nih.gov/pubmed/22364157
  6. Usman, M., Naseer, A., Baig, Y. et al. Forensic toxicological analysis of hair: a review. Egypt J Forensic Sci 9, 17 (2019). https://doi.org/10.1186/s41935-019-0119-5
  7. Marrinan, S., Roman‐Urrestarazu, A., Naughton, D., Levari, E., Collins, J., Chilcott, R., … & Corazza, O. (2017). Hair analysis for the detection of drug use—is there potential for evasion?. Human Psychopharmacology: Clinical and Experimental, 32(3), e2587.
  8. Hara, M., Kovacs, J., Whalen, E. et al. A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1. Nature 477, 349–353 (2011). https://doi.org/10.1038/nature10368
Categories
Neuroscience

An Overview of Memory and Amnesia

Introduction

Often described as simply the partial or total loss of memory, amnesia is one of those conditions we’ve all heard of, have seen in media and can somewhat grasp a hold of what it is.  But aside from just waking up with no recall in movie scenes, in reality, amnesia works in a much deeper and complex manner.

What is Amnesia?

There are two main classifications of amnesia: retrograde amnesia and anterograde amnesia. Retrograde amnesia is when the patient cannot process information and memories typically before the date of what has triggered the amnesia such as an accident or operation. Anterograde amnesia is when new information cannot be transferred from the short term memory store into the long term memory store.  In order to understand how amnesia is affected and affects the brain, you first need to understand how the brain should store memories.

How are Memories Stored in the Brain?

The way memories are processed is not clearly known however there have been several models made by psychologists and neuroscientists.  One of the most commonly referred to encompass the whole is the multi store model (MSM).  This model was curated by Richard Atkinson and Richard Shiffrin (1968, 1971) shows how information flows through the system through processing.

 A stimulus from the environment firstly will pass into what’s known as the sensory register.  Our sensory register has temporary stores for each of our five senses that has a high capacity of approximately one hundred million cells in each eye storing data and information, but it only lasts a period of half a second.  A couple of our biggest is our echoic store, which encompasses auditory information coded acoustically, and an iconic store, which encompasses visual information coded visually.  As our daily lives are full of billions of stimuli, the brain can only usually focus on a couple in order to process on to the short term memory store, hence the key to moving the information on is paying attention to particular stimuli.

Short term memory is a limited capacity store.  Many researchers have studied how large exactly the STM is.  One famous value being Miller’s magic number, 7±2; on average being able to store 5-9 pieces of information.  Information stored in the STM is coded acoustically, meaning that we remember it primarily by how we heard it or how it sounded.  In order for the information to eventually go to the long term memory (LTM) store, it needs to be maintenance rehearsed, otherwise it would last only about half a minute in our STM.

Long term memory store, also known as our permastore is for information that has been rehearsed constantly to the point the information can be remembered and recalled for many years and possibly decades.  The capacity for LTM is proposed to be unlimited.  According to the MSM, memories are ‘retrieved’ from the LTM back into the STM in order to recall it; none of the information is directly from the LTM.

This multi-store model is evaluated as somewhat insufficient as cases of patients with amnesia have proven there to be more stores within the STM and LTM than Atkinson and Shiffrin had proposed.

How Memories are Affected by Amnesia

Curated by Tulving (1985) in response to the MSM not elaborating further on the LTM, are a few different types of memory within long term memory.  They can be classified as declarative, broken down into episodic and semantic memories which you have to consciously think about to recall, and non-declarative as procedural memory, by which you can recall without conscious recognition. 

Episodic refers to our ability to recall from events that occur in ‘episodes’, or events in our daily lives.  These memories are associated to us by time stamps for example recalling something that happened to us last weekend, as well as certain people, places, and behaviours can also be associated to that episodic memory.

Semantic memories are our knowledge of the world, including facts and general knowledge.  These memories are clearly not as personal as episodic as they’re not time stamped, but rather just stockpile if rehearsed enough in your brain.

Procedural memory is also known as muscle memory.  It is our memory of how we physically do things like riding a bike.  Even if we do not ride a bike for an extended period of time, if we learned how to ride it as a child,  it should almost be instant picking it back up later on.  Procedural memories can proceed independently of the brain regions required for declarative memory.  According to fMRI studies, procedural memories activates the basal ganglia, the premotor cortex and the supplementary motor areas in the brain; regions that aren’t typically associated with the processing of declarative memories.

Famous cases of Henry Molaison (H.M.) and Clive Wearing prove that there’s multiple stores of LTM.  Both men were patients with amnesia; Clive had a viral infection in his brain, severely damaging the hippocampus, and Henry had a surgery to cure his epilepsy both resulting in amnesia that affected episodic memories.  They could not recall things they did or what happened to them shortly before, but their semantic and procedural memories were very much intact; Clive could play the piano pieces he knew by heart perfectly and they both knew how to tie shoelaces.  These two cases of amnesiacs had proven evidence the presence of different stores of LTM and they were in different regions of the brain, so if one was affected, the others aren’t  necessarily affected either.

Conclusion

Whilst amnesia detrimentally affects individuals and their loved ones roughly, having patches of memories disappear unbeknownst to the individual, amnesiacs have been one of the biggest contributions to neuroscience, psychology, and the general understanding of memory and how amnesia is initiated in individuals.

Nara Ito, Youth Medical Journal 2021

References

Atkinson, R. C., & Shiffrin, R. M. (1968). Human memory: A proposed system and its control processes. Psychology of learning and motivation, 2(4), 89-195.

Eichenbaum, H. (1993). Memory, amnesia, and the hippocampal system. MIT press.

Schacter, D. L. (1987). Memory, amnesia, and frontal lobe dysfunction. Psychobiology, 15(1), 21-36.

Aggleton, J. P., & Brown, M. W. (1999). Episodic memory, amnesia and the hippocampal-anterior thalamic axis. Behavioral and brain sciences, 22(3), 425-444.

Hoerl, C. (1999). Memory, amnesia and the past. Mind & Language, 14(2), 227-251.

Nadel, L., & Moscovitch, M. (1997). Memory consolidation, retrograde amnesia and the hippocampal complex. Current opinion in neurobiology, 7(2), 217-227.

Squire, L. R., & Zola, S. M. (1998). Episodic memory, semantic memory, and amnesia. Hippocampus, 8(3), 205-211.

Ryan, J. D., Althoff, R. R., Whitlow, S., & Cohen, N. J. (2000). Amnesia is a deficit in relational memory. Psychological science, 11(6), 454-461.

De Renzi, E., Liotti, M., & Nichelli, P. (1987). Semantic amnesia with preservation of autobiographic memory. A case report. Cortex, 23(4), 575-597.

Lewis, D. J., Misanin, J. R., & Miller, R. R. (1968). Recovery of memory following amnesia. Nature, 220(5168), 704-705.

Snodgrass, J. G., & Corwin, J. (1988). Pragmatics of measuring recognition memory: applications to dementia and amnesia. Journal of experimental psychology: General, 117(1), 34.

Tulving, E. (1985). How many memory systems are there?. American psychologist, 40(4), 385.

Shimamura, A. P. (1986). Priming effects in amnesia: Evidence for a dissociable memory function. The Quarterly Journal of Experimental Psychology Section A, 38(4), 619-644.

American Association for Research into Nervous and Mental Diseases, Squire, L. R., & Zola, S. M. (1997). Amnesia, memory and brain systems. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 352(1362), 1663-1673.

Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company.

Squire, L. R., & Alvarez, P. (1995). Retrograde amnesia and memory consolidation: a neurobiological perspective. Current opinion in neurobiology, 5(2), 169-177.

Squire, L. R., & Knowlton, B. J. (1995). Memory, hippocampus, and brain systems.

Scoville, W. B. (1968). Amnesia after bilateral medial temporal-lobe excision: Introduction to case HM. Neuropsychologia.

Wilson, B. A., & Wearing, D. (1995). Prisoner of consciousness: A state of just awakening following herpes simplex encephalitis.

Categories
Neuroscience

The Neuroscience Behind Hiccups

Abstract

The quick gaps of air, amid a barrage of hiccups, is something that almost all of us can relate to. Derived from the Latin word ‘singult’, that means ‘to catch one’s breath while sobbing’.  Hiccups are defined as the involuntary contractions of the diaphragm followed by the abrupt closure of the trachea, creating a ‘hic’ sound.  And while in evolution, hiccups haven’t been found to hold any significant value to survival, little is actually known about its pathophysiology, and what is its purpose. 

Background

Hiccups are clinically classified by duration, and can be divided into multiple categories:

  • Transient hiccups – A few minutes or seconds
  • Acute hiccups – Less than 48hrs
  • Persistent – Over 2 days
  • Intractable – Over a month
  • Idiopathic chronic hiccup (aka Diabolic hiccup) – recurring hiccup attacks over 1 month

While there haven’t been any big studies on the average duration of hiccups, most hiccups are transient and go unreported. The National Health Service in the United Kingdom says that hiccups should typically last a few minutes but it really varies from person to person.

Hiccups can be onset for a variety of reasons, laughter being one of the most common reasons. Other factors include extreme emotions (e.g. anxiety, stress and excitement), a sudden change in temperature,  eating and drinking too fast, spicy food,  drinking carbonated beverages or too much alcohol.  Hiccups may also be caused by brain tumours, vascular disorders or nerve damage. Sometimes hiccups can also be a symptom of an underlying medical disease such as -Parkinson’s Disease, strokes and ischemia.  

Causes

Whilst the mechanism behind hiccups isn’t fully understood, researchers have concluded that there is a neurological reflex arc associated with hiccups.  The reflex arc primarily consists of two parts: the vagus nerve, and the phrenic nerves sending signals from the brain to the diaphragm.  The vagus nerve extends from the medulla to the abdomen, and it conveys innate sensory signals that naturally fire in our CNS.  The phrenic nerves send these signals and electrical impulses from the brain to the diaphragm and intercostal muscles.  The neurological mechanisms behind hiccups are still very poorly understood thus for now is not concrete as it may not only be confined to the medulla but may also involve other parts of the central nervous system (CNS) located between the brainstem and spine.  Researchers assume that patients with chronic hiccuping are likely to have irritation involving this reflex arc such as signals being sent at the wrong times.  Neurotransmitters involved in the process of hiccup have so far been found to include dopamine) and gamma-aminobutyric acid (GABA).  This has been demonstrated as some psychiatric medications that are used to stabilise or modify levels of dopamine and GABA have been found to induce hiccuping.  An example would be Aripiprazole, which is used to stabilize dopamine and serotonin systems through dopamine receptors as well as baclofen, a GABA derivative, which is used to treat hiccup due to CNS tumours and chronic renal failure.

Newborns and infants are particularly prone to hiccups, as they spend roughly 15 minutes a day hiccuping.  Hiccups begin in the womb at around nine weeks.  Researchers found that contractions of the diaphragm from a hiccup triggers two large brain waves followed by a third.  Researchers suppose that as a baby hiccups, the brain may associate the sound of hiccups with the feel of the diaphragm contraction. Being one of the first processes for an infant to experience, a study by Whitehall et al. suggests that hiccuping is significant in the early development of multi-sensory brain connections and signalling.

Parkinson’s Disease

In one study twenty percent of parkinsonism (PD) patients had frequent hiccups. Even in some patients, PD was diagnosed after the occurrence of intractable hiccups. Replacement therapy with dopamine agonists in PD patients is considered to induce certain episodes of a hiccup, however, in others, hiccup may occur as the non-motor symptom of PD rather than a side effect of anti-PD treatment. The pathogenesis is believed to be related to the fact that dopamine agonists share a high affinity for dopamine receptors which may be involved in the hiccup reflex arc.  The drugs to block dopaminergic neurotransmission including chlorpromazine and metoclopramide may be employed in treating hiccup episodes

Treatments for Chronic Hiccuping

Many interventions and nonclinical “cures” for hiccuping have been passed down by word of mouth and experience such as breathing into a bag, holding breath, swallowing granulated sugar, drinking/gargling iced water, forceful traction of the tongue, biting lemon,, eyeball compression, fright etc.  While these remedies can be very convenient and less hazardous, their effectiveness to treat serious hiccups is highly questionable.

For example, gag reflex has long been used as an immediate remedy to treat hiccup.  A possible method of “curing” hiccups could include the regulation of rhythm at which the phrenic nerve operates.

Typically, in the clinical setting, hiccups are not usually the problem itself but is rather a symptom of an underlying problem, thus most cures targeting the root cause of hiccuping such as prokinetics being widely used to treat hiccups due to stomach distension.  Chlorpromazine is currently the only medication approved for hiccups by the US Food and Drug Administration, and for many years it was the primary drug used to treat hiccups.  It acts by targeting dopamine within the hypothalamus.  It has serious potential side effects, including that of- hypotension, urinary retention, glaucoma, and delirium. Initially used to control seizures in patients with epilepsy, vagus nerve stimulators are also the only piece of equipment approved by the FDA for treating hiccups. It sends rhythmic electrical impulses from the brain to the vagus nerve, which passes through the neck, within the reflex arc behind hiccups.  Even a left vagal blockade via nerve stimulation might be applied to stroke-related intractable hiccup after the failure of the phrenic nerve block.

Conclusion

Hiccups for the most part aren’t to be intimidated of, in fact are typically rather humorous.  But as with anything, too much of something can be indicative of much more going on behind the scenes, and this can be particularly applied with hiccups.  A lot of us will look past hiccuping for 5 minutes or so, and cure them with natural or remedies that we’ve tried and tested by past experiences, however,  for those that suffer from such a ‘comedic’ symptom and problem that is chronic hiccuping, there are, but still lacking, drugs and technologies out there that can hopefully help treat this issue.

Nara Ito, Youth Medical Journal 2020

References

Chang, F. Y., & Lu, C. L. (2012). Hiccup: mystery, nature and treatment. Journal of neurogastroenterology and motility, 18(2), 123–130. https://doi.org/10.5056/jnm.2012.18.2.123

Mayo Clinic. (2017, May 24). Hiccups – Symptoms and causes

https://www.mayoclinic.org/diseases-conditions/hiccups/symptoms-causes/syc-20352613

Genetic and Rare Diseases Information Center. (2020, 11 5). Chronic Hiccups.

https://rarediseases.info.nih.gov/diseases/6657/chronic-hiccups

Woelk C. J. (2011). Managing hiccups. Canadian family physician Medecin de famille canadien, 57(6), 672–e201.

Moretto, E. N., Wee, B., Wiffen, P. J., & Murchison, A. G. (2013). Interventions for treating persistent and intractable hiccups in adults. The Cochrane database of systematic reviews, 2013(1), CD008768. https://doi.org/10.1002/14651858.CD008768.pub2

Kohse, E. K., Hollmann, M. W., Bardenheuer, H. J., & Kessler, J. (2017). Chronic Hiccups: An Underestimated Problem. Anesthesia and analgesia, 125(4), 1169–1183. https://doi.org/10.1213/ANE.0000000000002289

Whitehead, K., Jones, L., Laudiano-Dray, M. P., Meek, J., & Fabrizi, L. (2019). Event-related potentials following contraction of respiratory muscles in pre-term and full-term infants. Clinical Neurophysiology, 130(12), 2216-2221.

Categories
Biomedical Research

Bromelain: The Enzymes in Pineapple

Introduction

Bromelain is an aqueous enzyme extract obtained from both the stem and fruit of the pineapple plant and it’s the cause of why your tongue may become irritated or hurt when eating pineapple. Bromelain contains a number of proteolytic enzymes, otherwise known as digestive proteins, and as many people often say, as you’re eating pineapple, it ‘eats’ you too.  Despite this, it has been proven to be quite functional within medicine, demonstrating, in vitro and in vivo, anti-edematous, anti-inflammatory, anti-thrombotic, and fibrinolytic activities.  This article will briefly explore bromelain’s uses within treating inflammatory diseases, specifically osteoarthritis.

Why Bromelain?

Although not a licensed medical product, having reviewed the mechanisms of action, bromelain has been shown to have a number of beneficial properties that include anti-inflammatory and analgesic actions, anti-oedematous, anti-thrombotic, and fibrinolytic effects [1].   

In Central and South America, pineapple has been used for centuries to treat indigestion and inflammation. And in the late 1800s, bromelain was first isolated from the pineapple and more recently, bromelain has been approved to treat swelling and inflammation after surgery, particularly sinus surgery in Germany.  Hence many scientists and physicians have pondered the efficacy and potential uses of bromelain within future therapeutics and treatments for other inflammatory conditions and diseases.  From an economic standpoint, bromelain being overtly found within pineapples can easily be accessed and extracted, minimizing any complex costs to produce any bromelain based products for the pharmaceutical market.

Bromelain for Inflammatory Disease

Bromelain, an extract from the pineapple plant, has been demonstrated to show anti-inflammatory and analgesic properties and was first reported to be of value to provide a safer alternative or adjunctive treatment for both rheumatoid arthritis and osteoarthritis patients in 1964 [2, 6].

Some studies suggest that bromelain as an anti-inflammatory agent works by increasing serum fibrinolytic activity which reduces plasma fibrinogen levels and decreases bradykinin levels which all result in reduced vascular permeability and thus reducing pain [2-4]. Thus is often used to reduce inflammation from tendonitis, sprains and strains, and other minor muscle injuries as well as reducing inflammation and pain after dental, nasal, and foot surgeries or trauma.  In addition, it controls prostaglandin levels and through modulation of certain immune cell surface adhesion molecules which play a role in the pathogenesis of arthritis [5]. However, further data is needed to clarify definitive mechanisms of its action.

Typically in modern-day medicine, knee pain from osteoarthritis is relieved through drugs like rutosid and trypsin as well as nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used pain relievers, including ibuprofen, naproxen and diclofenac.  However, bromelain is a food supplement that may provide an alternative treatment to NSAIDs for patients with osteoarthritis that is found to be just as effective [2, 7,8].

Conclusion:

The active factors involved can be biochemically characterized only in part.  However, due to its safety, efficacy and it is freely available to the general public in health food stores and pharmacies in the USA and Europe, and most obviously found in pineapples directly, bromelain is gaining acceptance among some as a phytotherapeutic drug.  The future for bromelain in medicine seems to be a promising one, but much more work is needed and many more clinical trials need to be done to administer it properly in an upscale setting, but bromelain, for now, will be easily accessible even without a prescription.

Nara Ito, Youth Medical Journal 2020

References

[1] Cooreman, W. M., Scharpé, S., Demeester, J., & Lauwers, A. (1976). Bromelain, biochemical and pharmacological properties. Pharmaceutica acta Helvetiae, 51(4), 73–97.

[2] Brien, S., Lewith, G., Walker, A., Hicks, S. M., & Middleton, D. (2004). Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evidence-based complementary and alternative medicine : eCAM, 1(3), 251–257. https://doi.org/10.1093/ecam/neh035

[3] Kumakura, S., Yamashita, M., & Tsurufuji, S. (1988). Effect of bromelain on kaolin-induced inflammation in rats. European journal of pharmacology, 150(3), 295–301. https://doi.org/10.1016/0014-2999(88)90010-6

[4] Maurer H. R. (2001). Bromelain: biochemistry, pharmacology and medical use. Cellular and molecular life sciences : CMLS, 58(9), 1234–1245. https://doi.org/10.1007/PL00000936

[5] Taussig, S. J., & Batkin, S. (1988). Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. Journal of ethnopharmacology, 22(2), 191–203. https://doi.org/10.1016/0378-8741(88)90127-4

[6] COHEN, A., & GOLDMAN, J. (1964). BROMELAINS THERAPY IN RHEUMATOID ARTHRITIS. Pennsylvania medical journal (1928), 67, 27–30.

[7]Cooreman, W. M., Scharpé, S., Demeester, J., & Lauwers, A. (1976). Bromelain, biochemical and pharmacological properties. Pharmaceutica acta Helvetiae, 51(4), 73–97.

[8]Walker, A. F., Bundy, R., Hicks, S. M., & Middleton, R. W. (2002). Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine : international journal of phytotherapy and phytopharmacology, 9(8), 681–686. https://doi.org/10.1078/094471102321621269

Categories
Biomedical Research

The Ketogenic Diet and Epilepsy

Introduction

The ketogenic diet, commonly referred to as ‘keto,’ is an increasingly popular recent trend in the dieting world. While there are a variety of ketogenic diets, including the Atkins and  South Beach diet,  the principle idea behind keto is that you use fats and ketones in your body to provide energy, rather than carbohydrates and glucose.  

However, keto isn’t just a new practice that started in the past couple of years.  With the first records of this practice dating back to the time of Hippocrates, ketogenic diets and fasting have been used for many medicinal reasons besides weight loss such as helping to treat or reduce the symptoms of various conditions such as acne, polycystic ovary syndrome to even genetic disorders. 

Ketogenic diets have been studied extensively in people with epilepsy. They are often recommended for those who either fail to respond to anti-seizure medications or can’t tolerate their side effects and have been proven quite effective.

How Does the Ketogenic Diet Work?

Typically in standard diets, some carbohydrates burn up quickly and are packed with intense fuel that yields large bursts of energy.  The human body’s main energy store is through fats [1].  Proteins and fats burn slowly thus results in a constant stable release of energy.  This is beneficial as you would not experience any peaks or crashes in energy in comparison to carbohydrates by which glucose is released instantaneously in the body and not stored [1,2].  This is how ketosis also regulates blood glucose levels without complications. Involving complex carbs into your diet causes your body to heighten your blood sugar and as a result, produce insulin.  As high glucose levels are perceived as toxic by the body, insulin is released by the pancreas as negative feedback to decrease and regulate this.  When your body starts struggling to keep up, excess glucose is converted into fat, and insulin stores it in cells. Your body is capable of regulating your blood sugar on its own without help when you aren’t mainlining so much sucrose. Ketogenic diets avoid such problems.

Fat is essentially satiety. Consuming fat keeps you full and combines with low carbohydrate intake, allows the body to produce ketones [2,3].  In Glucose 1 transporter (Glut 1) deficiency and pyruvate dehydrogenase (PDH) deficiency ketones provide an alternative energy source to glucose [3].

As with any alterations to the body, the Ketogenic diet too has side effects whilst adjusting to the low-carb lifestyle.  Though for many the intended goal is weight loss, in other cases where the ketogenic diet is prescribed, side effects can include feeling weary with symptoms of influenza, also known as the Keto-Flu, constipation, or diarrhea, and high cholesterol.

The Ketogenic Diet for Epilepsy

Most often lifelong, epilepsy is a common condition that affects the brain and causes frequent seizures. Seizures that are resistant to standard medications remain a major clinical problem.

In severe epileptic patients, after 2-3 days of fasting from food, and even in some cases, water, there was severe seizure control observed.  These observations have been around for millennia. 

We don’t completely understand how the ketogenic diet works but there is some evidence that the brain needs energy from glucose to create a seizure. The ketogenic diet makes the body think that it’s in a state of starvation or fast [3].

Though having years of insight and trials, clinically, doctors do not assign patients keto from initial diagnosis of epilepsy; it is usually reserved for drug-resistant epilepsy.  This is due to the balance of the diet needing to be carefully worked out for each individual and because vitamins and other special supplements are needed. It is not advisable as a treatment option for some with some metabolic disorders or other neurological disorders.

The ketogenic diet was initially for children and currently in the UK, medically still is; this treatment is offered for children between 3 months to 16 years suffering from any type of epilepsy [2,4,5].  During infancy, the brain is much more efficient at extracting and utilizing ketone bodies from the blood due to the higher levels of ketone metabolizing enzymes and monocarboxylic acid transporters produced during this period [6-8]. 

In a review by Mcgill et al., four studies with 385 participants reported that more children achieved seizure freedom with a ketogenic diet than with control. Two small underpowered studies reported no events in adults with 141 participants reported no adults achieved seizure freedom; the analysis was underpowered [9].

There is limited evidence for how effective or tolerable the ketogenic diet is for adults but it has been highly proven to be effective for pediatric epilepsy. Some particular studies show that keto can be effective on the adult brain as it increases its levels of monocarboxylic acid transporters and ketone metabolizing enzymes rapidly during periods of stress such as ischemia, trauma, or low glucose as in the case of keto [8,10].  A review of 16 studies in adults with uncontrolled epilepsy found that ketogenic diets were well-tolerated long term and typically resulted in significantly fewer seizures or, in a minority of cases, complete freedom from seizures [8].

A study by Rho et al. suggests that adults may produce ketones at different levels in response to a ketogenic diet, possibly explaining the inconsistencies in findings on the effect of keto on the adult brain.  In addition, they also demonstrated variations between the production of ketones in rats and humans, which is a crucial consideration when running animal trials before implementing techniques and diets clinically [11].

Conclusion

The ketogenic diet is not just a trend for health gurus to lose weight.  It lessens the burden and potentially frees many, if not, millions of those suffering from drug-resistant seizures from epilepsy.  Though not much is known about epilepsy as a condition in itself, and the ketogenic diet heavily varying in effect amongst people of different ages, for centuries, techniques like fasting and keto have been observed to be helpful.  Though not as commonly prescribed or allocated to adults, it is an extremely effective technique on children, potentially improving their trajectory and progress of the condition.

Nara Ito, Youth Medical Journal 2020

References

[1] Wasserman, D. H. (2009). Four grams of glucose. American Journal of Physiology-Endocrinology and Metabolism, 296(1), E11-E21.

[2] Great Ormond Street Hospital for Children. (2011). Ketogenic diet. https://www.gosh.nhs.uk/medical-information/procedures-and-treatments/ketogenic-diet

[3] Laffel, L. (1999). Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes/metabolism research and reviews, 15(6), 412-426.

[4] Lambrechts, D. A., de Kinderen, R. J., Vles, J. S., de Louw, A. J., Aldenkamp, A. P., & Majoie, H. J. (2017). A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy. Acta neurologica Scandinavica, 135(2), 231–239. https://doi.org/10.1111/ane.12592

[5] Sharma, S., Goel, S., Jain, P., Agarwala, A., & Aneja, S. (2016). Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial. Epilepsy research, 127, 152–159. https://doi.org/10.1016/j.eplepsyres.2016.09.002

[6] Sokoloff L. (1973). Metabolism of ketone bodies by the brain. Annual review of medicine, 24, 271–280. https://doi.org/10.1146/annurev.me.24.020173.001415

[7] Bilger, A., & Nehlig, A. (1992). Quantitative histochemical changes in enzymes involved in energy metabolism in the rat brain during postnatal development. II. Glucose-6-phosphate dehydrogenase and beta-hydroxybutyrate dehydrogenase. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 10(2), 143–152. https://doi.org/10.1016/0736-5748(92)90042-x

[8]McNally, M. A., & Hartman, A. L. (2012). Ketone bodies in epilepsy. Journal of neurochemistry, 121(1), 28–35. https://doi.org/10.1111/j.1471-4159.2012.07670.x

[9] Martin‐McGill, K. J., Jackson, C. F., Bresnahan, R., Levy, R. G., & Cooper, P. N. (2018). Ketogenic diets for drug‐resistant epilepsy. Cochrane Database of Systematic Reviews, (11). 

[10]Prins M. L. (2008). Cerebral metabolic adaptation and ketone metabolism after brain injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 28(1), 1–16. https://doi.org/10.1038/sj.jcbfm.9600543[11]Prins M. L. (2008). Cerebral metabolic adaptation and ketone metabolism after brain injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 28(1), 1–16. https://doi.org/10.1038/sj.jcbfm.9600543