The Real Heroes of Universities

by Sharief Hendricks

The real heroes (or heroines if you like) of our tertiary institutions are the administrators and support staff. And like true heroes, their superpower often goes unnoticed, unrecognised.

No doubt, a University will not function without the work of the administrative and support staff. Our research, travel, teaching, and every day would not be possible.

The superpower though, is the care, kindness and generosity in their work. Work that is aimed to help us achieve our goals.

This time of the year, as we process postgraduate applications for the upcoming year, I always remember the kindness and generosity of our Faculty’s Postgraduate Office when I was a student applying to the Honours programme (back in 2007). The Postgraduate Office frequently shares this fond memory with me, a memory that serves our current working relationship well.

I always needed help with my student administration, and visited the Postgraduate Office more than usual, which I think provided me with the opportunity to experience their superpower. I can’t help wonder though, in today’s age, where everything is online and most communication takes place via email, are students and staff missing out on similar opportunities?

I have many stories similar to the above, where the care regularly goes beyond the call of duty. A more recent example is my trip to a conference in Monaco. On the Saturday, the last day of the conference, South Africa was issued a travel ban and my flight home got cancelled. True to form, my heroes emerged, and what could have been a complete nightmare without their kind and generous support, finding my way back home turned out to be somewhat of an adventure instead.

Have you experienced the superpower of your administrators and support staff? Please share.

As thanks for their work, I wanted to end off with naming all the administrators and support staff that have used their superpower to help me achieve my goals, like an author list on a paper. I decided against this though, in fear of missing a hero (and there are many heroes to mention). Also, like many of our favourite fictional superheroes in suits, anonymity is not a bad thing. So I’ll simply end with thank you.

In my own bubble

by Kaylene Baron

What makes the university experience more valuable is time spent with classmates and other students outside the lecture theatre. Due to COVID-19, that was minimal as all our lectures were online. With only a select few that were in person. Whenever we have a contact lecture or contact meeting, we have to wear masks. Needless to say, it is very uncomfortable for me. The reason is, if I do not know the people, then it leaves a very unsettling feeling inside me.

This year has just been eating, sleeping, work repeat with time for nothing else in-between. Even when we started with lab work, it was still very isolating as we are all trying to avoid contact with people.

For me, I am extra dependent on my peers for emotional support as I am a first-generation student. Meaning that I am the first person in my family to attend university, much less to obtain a postgraduate degree. Hence why getting emotional support, encouragement and motivation were very challenging. Yes, there is social media but in-person interactions for me at least, are much better. The ever-changing lockdown levels also aggravated it as it affects how much time I have in the lab, and how quickly I need to commute home when necessary. Nonetheless, even if it was virtual for the most part, I know that all my classmates and friends were supporting me in spirit

The New Genetics of Intelligence (Robert Plomin and Sophie von Stumm)

by Saleha Suleman

For centuries, humans have been defined by how intelligent they are. Although the definition of intelligence has changed with evolving times and the differences in lifestyles, the importance of intelligence has not. It is a predictor for occupational, health and overall quality of life outcomes, more than any other trait. This is because a higher intelligence involves the ability to adapt to quickly changing circumstances and undertakings that one would face in their work.

Worldwide, the most standard and widely accepted measurement for intelligence has been IQ (intelligence quotient). An IQ test is able to quantify a person’s reasoning and problem-solving abilities through various tests that the person goes through, and so should be able to account for creativity, thinking outside the box as well as skills needed in schooling subjects such as mathematics. The genetics of intelligence, however, has eluded humans for the longest time. Judging from simple logic, it can be said that there is a certain component of intelligence that is hereditary. But how much it is, and whether it outweighs other factors such as family support, schooling, socioeconomic status and others has not been determined yet. Simply put, intelligence is one of the facets of the ‘nature versus nurture’ debate.

In this paper, the authors performed a meta-analysis to accumulate the findings thus far of the effect of genetics on intelligence. They did this by reviewing results from initial genome wide association studies (GWAS) and showed how genome-wide polygenic scores (GPSs) are a better predictor of intelligence due to it’s accuracy and ability to measure the effects of thousands of DNA variants that are associated with intelligence.

The main findings of the paper are presented in the infographic bellow. Since this is a review, the authors confirmed that there have been multiple attempts to gauge the effect of genetics on intelligence, but the most recent success has come from the use of GPSs. At the time this paper was published, there was also a much larger scale GWAS study being performed that would allow identification of up to 10% of variance. Such studies would allow a clearer definition of the relationship of intelligence with socioeconomic environment, family support, educational attainment of parents and other environmental factors that have so far been attributed to nature in the nature versus nurture debate.

It is important to remember that such studies, and even any tests that would be available to take at a clinic for example, would still be probabilistic and not determinate. Because of that, despite the potential to understand the human mind more, as well as the fact that understanding measurable outcome differences in people of different genetic intelligence would be revolutionary, there have been major ethical concerns for these studies. These include four; biological determination and potential for stigmatization and discrimination, both which can see people being afforded opportunities such as in careers or social circles because of their genetic intelligence, ownership of information, and finally the emotional impact of knowing one’s own personal genetic intelligence levels. As results from current studies become available, it will be of utmost value to distinguish the benefits and shortcomings for them.

References:

Plomin, R. and Von Stumm, S., 2018. The new genetics of intelligence. Nature Reviews Genetics, 19(3), pp.148-159.

Running and Patellofemoral Pain Syndrome: What makes you weak at the knees? — Rugby Science

Patellofemoral Pain Syndrome (PFPS) is a knee condition associated with anterior knee pain when loading the knee in movements like squatting, stair climbing, running and jumping (Ferber et al., 2015). Due to its high prevalence and running becoming an increasingly common form of exercise, it is important that high quality evidence regarding treatment and preventative […]

Running and Patellofemoral Pain Syndrome: What makes you weak at the knees? — Rugby Science

DOCTRINE OF SIGNATURES (You are what you eat)

by Sedzani Mbedzi

The doctrine of signature is an ancient pharmacological theory which states that the way plants look, taste, react or shaped offers strong clues to their medical implications. Major category of doctrine of signature are the similarity between shape of the plant and ailing human organ, and the similarity of plant colour to disease syndrome. Indigenous people coined the concept “you are what you eat and so is the brain” which suggest that what you eat is valuable to your health and heart. They had a well versed and in-depth understanding of nature, and knowledge about how some plants work and what they are used for. Physical characteristics of plants reveal their therapeutic value, for instance the reddish color of beetroot (blood root) indicates the plant’s efficacy in treating blood disorders.

Pomegranates resembles the human heart and known to have rich antioxidant polyphenols, which includes tannis, anthocyanin and flavonoids. Study by Dos Santos and co-workers reveled that having pomegranates at least once a day can be significant in attenuating hypertension, stress level and making your skin glow (Dos Santos et al., 2016). Using pomegranate dried peels, extracts for dietary purposes attenuates stress and coronary angiotensin converting enzyme (ACE) activity. ACE is a zinc metallopeptidase comprised of two homologous domains, the N and C domain. These domains are the main targets of ACE inhibitors that act by binding to the zinc. Polyphenols have chemical structures that favor chelation of redox active metals which favor ACE inhibition. This fruit lowers cholesterol, blood pressure and melts away heart blockages.

Figure 1: Infographic presentation of pomegranate resembling a human heart with chambers inside and the seeds encased like blood vessels. Pomegranates contain punicalagins that benefit the heart and blood vessels. The fruit lowers cholesterol, blood pressure, and melts away heart blockages.

“You are what you eat” concept plays a crucial role in managing chronic diseases. Therefore, it is important to know what you eat and how that impacts your body. It is quite difficult to eat healthy under stressful situations. For instance, during examinations a lot of university students tend to eat more fast food and snacks. The doctrine of signature indicates that having healthy snacks such as walnuts regularly may improve brain health and reduces risks of heart disease and cancer. Figure two below just shows some of healthy food and organs that they resemble.

Figure 2: info graphic representation of certain medicinal plants (fruits and vegetables) and resemble organs that they are good for.

Studies suggest that doctrine of signature could be the future for development of effective drugs and reducing chronic illnesses. For instance, beneficial effects of pomegranate peels extracts may be considered in development of therapies for hypertension.

REFERENCE

Dos Santos, R.L., Dellacqua, L.O., Delgado, N.T., Rouver, W.N., Podratz, P.L., Lima, L.C., Piccin, M.P., Meyrelles, S.S., Mauad, H., Graceli, J.B. and Moyses, M.R., 2016. Pomegranate peel extract attenuates oxidative stress by decreasing coronary angiotensin-converting enzyme (ACE) activity in hypertensive female rats. Journal of Toxicology and Environmental Health, Part A79(21), pp.998-1007.

2021 Dissections

by Astrid Kühn

The first part of my year was spent in the pam lab, a small dissection hall, a temporary home to six bodies. My initial feeling upon entry to the lab was that this was a sacred space, housing those who had made a huge and noble sacrifice in their death, to teach someone like me a lesson in anatomy.

In the weeks to come, I would learn that my idea of the dissection hall was naïve and romanticised, some of the bodies are actually unclaimed- unknowing of their fate during their lifetime. It was advised by one of my lecturers that due to certain characteristics of the body assigned to my study, he was most likely one of these unclaimed people.

I began to feel that every mark I made on his body was a mark I did not actually have permission to make. It is common for students to name their bodies due to the amount of time spent with them and the strange intimacy foundered. But who was I to name someone who already had a name, to superimpose my own narrative onto a body whose soul I already felt unhappy, restless and turning? The more I dissected, the more I became cognisant of the fact that I had no clue what he had been through, what these hands had held, lost, hurt, cared for, perhaps prayed to. My familiarity with him was always marked with a respect, he was a stranger, a reluctant participant in my well-intentioned butchery. He will be cremated at the end of October 2021, his ashes scattered in a barren garden, unbeknownst to his loved ones- if he had any. I still feel a profound sadness and guilt for my part in the violation of his body, the vessel that carried him for a lifetime. However, through his circumstance I am reminded of my privilege, not only to learn anatomy in this deeply intimate way but for the support of my loved ones- a blessing I still, somehow, wished for him.

A LETTER FROM THE FUTURE YOU

by Lwanda Ndwandwe

To whom it may concern

It took me a while to figure out what I could say my honours year has been like, I’ve had so many mixed emotions and I haven’t taken the time to process everything. So instead, I thought to write a letter, a letter to myself 6 months ago, and to those who’ll soon find themselves on this incredible journey.

“Honours will be honours”, I am sure you are probably tired of hearing this line but trust me when I say you will grow to understand it. The honours programme itself needs you to be fully prepared not only to work hard but smart, it comes with a lot of exciting and different content that you will be engage in which will challenge your thinking while shaping you for the field ahead. The year will be a different experience for everyone, it may be difficult to adjust both to the environment and the work but keep in mind that this is all part of the process. While trying to be productive and on track with everything I had to learn these 4 lessons below, that may seem silly but really helped to keep me calm and enjoy the year thus far:

Lesson 1: It is okay to not be okay, please read that again. This year is meant to be challenging bringing you out of your comfort zone, but with that comes growth.

Lesson 2: Set a timetable and stick to it, this will help you stay ahead while being productive with your time. There will be activities, lab work, a project, individual and group assignments that will be expected from you, multitasking comes into play and this will be highly effective if there is a schedule/ timetable to work with.

Lesson 3: Give yourself a break, add it to your timetable, whether it’s a walk or going out for lunch it’s easy to forget to take a moment off your laptop or cellphone, so go outside and breath.

Lesson 4: Enjoy the process and the pressure it comes with; the year goes by so quickly and before you know it, you’re sitting in your room wondering where the time has gone.

Overall, this year is going to be an adventure filled with excitement, tears, disappointments, procrastination, self-doubt, great achievements, and most importantly new skills and greater knowledge; and through all this don’t forget to take care of yourself.

Warm Regards,

A Proud honours student

Genetic data and Global populations: Do we have enough data to do a genetic study on the correlation between mental illness and drug use in a South African population?

by Mellie Msipa

Studies into Crystal Meth and its association with Schizophrenia

We all know that drug abuse is “bad”. Cocaine, Benzodiazepines and Methamphetamine (Crystal Meth) are just some of the drugs that people abuse, and if you were like me and grew up around people that weren’t always politically correct, then you probably heard the saying that ‘drugs kill your brain cells, and make you mentally ill’. Although phrases like this are often thrown at children and adolescence as a scare tactic to deter them from experimenting with opioids, some researchers in South Africa, Germany and the United States may have taken it quite literally, when they investigated and later published their paper on, “Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in a South African Population” (Passchier, et al., 2020).

How was the investigation conducted?

Saliva samples were collected for various cases and controls. The cases included patients that had Methamphetamine-associated psychosis (MAP) and patients who had a methamphetamine dependence (MD) and no psychosis. Healthy controls (HC) were also investigated for comparative purposes (Passchier, et al., 2020). The samples were genotyped, and quality control was performed on the data. Principal component analysis was performed to account for stratification, Structural brain imaging was performed to investigate the brain regions that have been linked to MAP and schizophrenia (Passchier, et al., 2020). Polygenic risk scoring was performed to determine the effect of the risk variants on the phenotype/ disease. Statistical analysis was then performed using tests, one of which included a t-test that tested the differences between the two case groups and the healthy group.

The results found the following:

The aim of the study was to determine how the polygenic risk scoring data from a European ethnicity based GWAS study on MAP compared with the brain measurement volumes tested in the South African MAP patients (Passchier, et al., 2020). The results of the investigation showed no significant association between Schizophrenia-derived risk scoring and the MAP disease diagnosis in patients.

The researchers also found that there was no correlation between the polygenic risk scoring and the volume measures from the different parts of the brain in the patients. The paper explains that that the negative result could be since Schizophrenia polygenic risk scores have no relation to the brain volume measurements seen in the case samples (Passchier, et al., 2020).

Due to the lack of GWAS data available for patients of African descent, the researchers found that people of African descent had the lowest polygenic score performance, and they concluded that the Polygenic risk score data from European population based studies were not applicable for the South African patients studied in this paper (Passchier, et al., 2020).

Ultimately the results for the study were inconclusive due to the limitations due to sample size, stratification bias and the risk of misclassification from the diagnostic interviews.

Impact of this research:

African health care systems like South Africa saw that mental and substance used disorders like schizophrenia increased by over 50% in the different populations just between the years 2000 and 2015 (Sankoh, et al., 2018). Diseases like Schizophrenia have led to over 14% of deaths globally and previous studies have found 145 genome wide significant loci for Schizophrenia ( Stevenson, et al., 2019). Mental health is a global problem, however very little genetic data is available/ recorded for mental health diseases that plague non-white populations. While the results of the study could not show any strong correlation between Schizophrenia and Crystal Meth use, the design of the study highlighted the need for more studies into non-European populations, like African populations that could uncover new risk variants.

References:

Stevenson, A. et al., 2019. Populations-Psychosis (NeuroGAP- Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda. BMJ, Volume 9, pp. 1- 9.

Passchier, R. V. et al., 2020. Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in South African Population. Fronteirs in Genetics, Volume 11, pp. 1- 7.

Sankoh, O., Sevalie, S. & Weston, M., 2018. Mental health in Africa. The Lancet Global Health, Volume 6, pp. 954- 955.

Burn wounds and P-fibrin

by Alexander Geragotellis

Background:

Burns are a global public health challenge and claim the lives of ±180 000 people each year [1]. The vast majority (±90-95%) of these deaths occur in LMICs and disproportionately afflict African children under the age of 5 years, who carry double the incidence of burn deaths compared to children under the age of 5 years worldwide [1]. Despite the extensive catalogue of burn wound coverage options, skin repair could still be defective owing to the complexity of the healing process. Cell-mediated treatment achieved through bioengineered constructs may provide alternative and more effective avenues to resolve burn wounds. Hydrogels are valuable tools in tissue engineering and regenerative medicine for stabilising tissue, and for delivering growth factors, bioactive ingredients and stem cells. The polymers used to make hydrogels can be natural [2], synthetic [3] or hybridised using both polymer types to infuse the desirable properties into one construct. The group who published the current research paper have previously reported on the advantageous properties of the poly(ethylene-glycol)-fibrin hybrid hydrogels [4]. Figure 1 offers a resource with further clarity on relevant tissue engineering terminology.

Aim:

The current study [5] aimed to evaluate the burn-wound healing potential of a bio-engineered 3D PEGylated-fibrin (P-fibrin) hybrid hydrogel as a scaffold to deliver adipocyte derived stem-cell (ASCs) using a rat model. The synthesis scheme has been summarised in Figure 2.

Figure 1 – Glossary of useful terminology to guide interpretation of the paper and results.

Figure 2 – Synthesis scheme for the ASC-embedded P-fibrin hybrid hydrogels used in the study [5]. ASCs were embedded within the hydrogels to try further augment the pro-regenerative activity of the P-fibrin hydrogels.

Objectives:

Methods used to achieve objectives have been summarised in Figure 3. By comparing burns wounds (i) untreated, or treated with either (ii) P-fibrin or (iii) P-fibrin with embedded ASCs between 7-21 days post- burn injury, authors set out to determine:

  1. Whether or not the application of the gels negatively affected burn wound closure.
  2. Characterise wound coverage and wound integration of the hydrogels using light and fluorescent microscopy.
  3. Explore angiogenic potential via immunohistochemical analysis of burn wounds to quantify blood vessels.
  4. Evaluate macrophage activation status of regenerating wounds, and how it is impacted by hydrogel application using immunohistochemistry.
  5. Assess collagen deposition and organisation 21 days post-injury to understand longer-term recovery phenotype.

Figure 3 – Rat burn model, adapted from Chung et. al [5], and accompanying methodologies used to achieve the objectives of the study.

Take home messages:

  • The major value of using a P-fibrin hydrogel appears to be with the increased cellularity of the granulation tissue at one week post-burn, suggesting an increase in tissue regeneration capability. The increased cellularity was similar to that observed when the P-fibrin was embedded with ASCs, indicating that the scaffold itself was the responsible factor and that the ASCs had little effect.
  • Angiogenesis is central process in tissue regeneration. The major value of embedding ASCs within the P-fibrin scaffolds was the bolstered neovascularisation observed at 7 days post-burn, which was significantly superior to the small increase observed with the P-fibrin only group. This would support the authors’ supplementary findings that suggest a role of the ASC secretome upregulating pro-angiogenic genes [5]. Although not fully studied, it is likely that the ASCs influence the population diversity of regenerative cells recruited to the burn wound to influence this superior angiogenic response.
  • To this end, there is some evidence in the present study to suggest that embedded ASCs can inflict a local tolerising pro-regenerative phenotype. Specifically, wounds treated with P-Fibrin embedded with ASCs showed a drastically greater coverage of the M2 immunosuppressive, pro-regenerative macrophages than when the wounds were treated with P-Fibrin gel alone.
  • It is encouraging that the wound thickness, collagen deposition and organisation between the studied hydrogel groups did not vary significantly, because this suggests that the hydrogels only accelerate but do not change the orchestrated sequence of the in-vivo regenerative response to full-thickness burns.
  • P-fibrin hydrogels hold great promise for burn wound healing applications, especially when conjugated with biological agents. Infection control is a crucial consideration in the burn wound healing process, and was not explored in the present study [5]. Interestingly, a recent study found that both infection control and neovascularisation post-burn can be enhanced through sequential delivery of P-fibrin embedded silver sulfadiazine loaded chitosan microspheres followed by P-fibrin embedded ASCs [6]. Future studies will likely focus on further characterising similar functional hydrogel constructs prior to progressing to more advanced trials.

References:

  1. World Health Organisation. 2018. Burns. Online: https://www.who.int/news-room/fact-sheets/detail/burns
  2. Janmey PA, Winer JP, Weisel JW. Fibrin gels and their clinical and bioengineering applications. J R Soc Interface. 2009;6(30):1-10.
  3. Overby RJ, Feldman DS. Influence of Poly (Ethylene Glycol) End Groups on Poly (Ethylene Glycol)-Albumin System Properties as a Potential Degradable Tissue Scaffold. Journal of Functional Biomaterials. 2019;10:1.
  4. Nam SY, Chung E, Suggs LJ, Emelianov SY. Combined ultrasound and photoacoustic imaging to noninvasively assess burn injury and selectively monitor a regenerative tissue-engineered construct. Tissue Eng Part C Methods. 2015;21(6):557-566.
  5. Chung E, Rybalko VY, Hsieh PL, Leal SL, Samano MA, Willauer AN, et al. Fibrin-based stem cell containing scaffold improves the dynamics of burn wound healing. Wound Repair Regen 2016;24:810–9.
  6. Banerjee J, Seetharaman S, Wrice NL, Christy RJ, Natesan S. Delivery of silver sulfadiazine and adipose derived stem cells using fibrin hydrogel improves infected burn wound regeneration. PLoS One. 2019;14(6):e0217965.

The Science of Human Sexuality

by Sesethu Mbunge

What better time, than the time of the release of the ever so controversial Lil Nas X’s music video for his single titled “Industry Baby”, to write about the neurobiology that underpins human sexuality? This masterpiece features an iconic shower scene, with a group of male bodies dancing in the nude, that had naysayers claiming that Lil Nas X is “turning people gay”. Contrary to popular belief, the nuance subject matter of gender identity and sexual orientation is not as simple as deciding to be gay. Although there is a huge gap in the understanding of the biological underpinnings of human sexuality, many studies have suggested that the prenatal environment, including the maternal immune environment as well as exposure to certain sex hormones, may play a role in gender identity and sexual orientation of the developing foetus. Further studies hypothesize that there is a genetic determinant of human sexuality, although these studies have been difficult to reproduce. It is believed that this resultant maternal, and potentially genetic, environment results in the organizational differentiation of the developing foetal brain. In simple terms, this means that these factors contribute to the structural differences in certain regions of the brain, and that these differences are what is attributed to the difference in the human sexual identity. The assumption with many of these studies was that sexuality is categorizable and binary. For the sake of cohesiveness, this summary will also be written under this assumption, although it is understood that sexuality is a spectrum.

Human sexual identity is categorized as gender identity and sexual orientation. Gender identity refers to one’s perception of oneself as male, female, or non-binary and this can be the same, or different from one’s biological sex. Sexual orientation refers to the pattern of emotional and/or sexual and romantic attractions to males, females, or both. To understand the effects of different factors on sexuality, let’s look at these factors individually.

Pre- and Perinatal Hormone Environment:

Animal studies have demonstrated that prenatal exposure to testosterone resulted in masculinization (male-type development) and that in the absence of testosterone feminization (female-type development) occurred. Masculinization results in permanent neural structural differentiation and occurs within the period when the brain is most sensitive to testosterone. Brain areas that are affected by testosterone levels are thought to be important for sexual differences in various adult behaviours including sexual behaviour, aggression, and cognition as well as gender identity and sexual orientation. Clinical studies have shown that in XY (typical male genotype) children that were born with ambiguous genitals developed into males when exposed to testosterone prenatally, but that if they had an androgen receptor (receptor for testosterone) mutation, they were phenotypically female and identified as female.

Studies in several animal models have shown that perinatal exposure to testosterone resulted in female partner preferences, whereas testosterone deprivation resulted in male partner preferences. In humans, it has been observed that women that were born with congenital adrenal hyperplasia (were exposed to an elevated amount of testosterone) developed masculinized genitals and behaviours and were less likely to be exclusively heterosexual in comparison to unaffected women.

Genetic Factors:

It is difficult to analyse the biological basis of gender identity in animal models, thus this is best studied in individuals that identify with a gender that is different from their biological sex. Although there is very limited evidence, it has been observed that in female-to-male transsexual individuals, there was a higher incidence of the A2 allele polymorphism for the gene that codes for a testosterone-synthesis catalysing enzyme, CYP17A1, compared to male-to-female transsexual individuals.

Familial and twin studies have shown that sexual orientation is moderately accounted for by a genetic component. A recent study approximated that about 40% and 20% of the variance in sexual orientation in men and women respectively was due to a genetic component. In a linkage study performed by Hamer in 1993, it was hypothesised that a locus, namely Xq28, on the X chromosome contained a gene that was loosely associated with homosexuality in men. This was then also confirmed in a larger genome-wide study, and it was also found that there were associations with chromosome 7 and 8. No specific genetic locus has been identified as associated with sexuality yet.

Neuroanatomy:

Studies have found that transgender individuals had structural and functional brain features that are more similar with individuals of the same gender identity, rather than with individuals with the same biological sex.

Rodent models have identified the sexually dimorphic preoptic nucleus (SDN) of the brain as the region associated with sexual partner preferences. In male rodents it was found that the larger the SDN was, the greater its attraction to female rats. It was also subsequently found that destruction of the SDN in male rats and ferrets either resulted in neutral or male preferences. This finding was also confirmed in sheep models, where they found that larger the ovine sexually dimorphic nuclei (oSDN) were associated with more female-oriented rams, whereas male-oriented rams had smaller oSDN. It was found that oSDN due to prenatal exposure to testosterone. Exposure of female lamb foetuses at the proper time was shown to alter oSDN size independently of genetic and phenotypic sex.

In humans, the third interstitial nucleus of the anterior hypothalamus (INAH3) has been implicated in sexuality. Based on its localization and the structure of its cytoskeleton, this nucleus resembles the oSDN of sheep. Studies have shown the INAH3 is smaller in homosexual men in comparison to heterosexual men, and the INAH3 in homosexual men is similar in size to that of women.

Maternal Immune Environment:

One interesting observation that has been made is the effect that the maternal immune environment has been shown to affect the sexual orientation of the developing foetus. It has been observed that homosexual men have, on average, more older brothers that heterosexual men. This is referred to as the fraternal birth order, and incidence of homosexuality increase by about 33% with each older brother. This is hypothesised to be due to the mother developing antibodies against a gene on the Y-chromosome that is a key factor in male brain development, and this immune response increases with each male pregnancy. This is subsequently thought to alter the neural structures that affect sexual orientation in boys that are conceived later. It was found that the mothers of homosexual sons that had many brothers, had a concentration of antibodies against neurolignin 4 (NLGN4Y), a gene that codes for a protein that is assumed to play a role in foetal brain development.

These factors are an indication that the events and environments that occur during early foetal development play a crucial role in determining the sexual identity of the developing foetus. Animal models have been found to display the causality of the effects of prenatal hormones on sexual orientation, but this however has not translated to gender identity. There are so many more biological processes that are implicated in sexual development that are yet to be understood or discovered. As such, it is biologically incorrect to reduce sexuality and sexual identity to a mere choice!

Reference:

Roselli, C., 2018. Neurobiology of gender identity and sexual orientation. Journal of Neuroendocrinology, 30(7).

Facts, some realistic heartbreak story, and an outrageous ending paragraph

by Sagel Kundieko 


At first, I thought it was a new virus that was practically wiping out the Chinese population. It was unrealistic that it would actually spread to the entire continent and cover all the many kilometres that there is to cover. Then we heard of Italy and the consequences of their stubbornness. Then finally it hit us too, in waves and lockdowns. It is really scary to think about how the economy has plummeted in this very short period of time. Also, how easily a virus from one corner of the world was easily able to cross barriers at such an overwhelming rate. On the other hand, the global pandemic aspect of it brings a sense of “we are all on this earth together” at the end of the day.  

The recent lootings and taxi violence is an offspring of the (increased) poverty, depression, and frustration from the lockdowns. It is clear that those most affected are from the black community because they have to commute to work and do not (literally) have pantries full of food or big companies that can make them money while they lockdown at home. This is not even considering that some do not have “homes” conducive for a lockdown or quarantine. Acknowledging that the lockdown was necessary, the inadequacy of the government in providing the necessary food to those who needed it, was problematic. 

On my immediate hand (usually written as on the other hand), the lockdown meant that I could not pursue my driver’s license because our documents needed to be renewed by the Home Affairs. In the grander scheme of things, that seems like a minimal issue, but the sense of unfulfillment still lingers, getting behind on an imaginary timeline I had set for myself. 

Furthermore, last year started off on a left foot (in the heat of the rising cases and lockdowns). I always felt that a problem is only a problem in relation to the other problems at hand. I imagined that something worse than my heartbreak would happen and I would forget about the man that broke my heart and move on, and it did. The idea of the possible end of the world or how insignificant and fragile our bodies are and how my life is worth nothing more than a statistic if I and those around me were to die, cured me of my heartbreak. A terrible parallel to draw between actual real world problems to a common heartbreak, it is unforgivable really. It is not even a parallel if you think of it, it is more of a mountain and me realising that because I am a pebble, then my problems must be a grain of sand, thus nothing to ponder ever so deeply on. I am more motivated now to do better, study harder, work harder, love God more, help those in need, go after my dreams and goals, and as I find true love, I experience it to the fullest of its capacities, because we do not know when another virus will head our way and who it will want to claim. I pray we survive through this as a world and do better for the future (do better in reference to the social class structures that have governed our countries, now we should realise that we are more the same than different and more together than apart).  

I also realise that the virus is the main topic at hand, but everything else that was wrong with the world before still exists. Even more so, humans are the deadliest virus this planet has ever been invaded by. That is an undeniable and uncontained fact.

A Whole New World

by Jesmika Singh

Am I really writing a piece about being in HONOURS? I still feel like I was just yesterday sending in applications for my first year of university. When they say university is over before you know it, they really weren’t joking. Regardless, it has been an exciting ride (even though parts of it have been stressful).

Throughout my schooling career and general social life, I have been someone that gets stressed very easily. I put a lot of pressure on myself to achieve my academic goals. Particularly in the third year of my undergraduate degree in 2020, I felt an even stronger need to push myself and put all my time and effort into my studies since everything was done through remote learning. As a result, the stress I felt during that year was unexplainable. Directly following that, I came into honours with the expectation that my stress would be even worse- I was moving to Cape Town from Durban; gaining more independence; being isolated from the majority of my loved ones and having to begin what I was told would be the hardest year of my university career. Granted, these things have been as challenging as expected, yet, I’m surprised to say that this has been one of the least stressful academic years I have had- perhaps I have gotten used to the stress or lost my ability to stress my usual amounts.

Honours is a year that I was told would push me to my breaking point- granted the year is far from over and there is still plenty of time left for that, somehow I have enjoyed the academic aspect of this year much more than any previous academic year. To be fair, if it were not for online learning, recorded lectures (I don’t know where I would be without these), teamwork and the lecturers, I doubt I would have been able to cope.

Something I have admired greatly about how this course has been run and kept my morale up- is how we are assessed. Unlike previous years, we were allowed (in some cases) to indicate the type of assessment we felt would best showcase our understanding of work and the way we were marked has been one of my favourite parts of the year. From the time I started school if your answer was not exactly what was in the memo, you didn’t get the mark- that was not the case this year. The lecturers took their time with each individual script/assignment to determine whether someone understood the work or not. If we didn’t get the correct answer but showed understanding, we could still do well. This kind of teaching and learning has helped me better understand my work, but more than that, it has helped me grow my confidence. If I had been marked like this for my entire schooling career, perhaps I wouldn’t have been so stressed and I may have been able to retain my work better. Being able to chase knowledge and understanding over answers from an unseen memo, has made a big difference in the way I take in knowledge.

I was also very fortunate to get a very helpful supervisor and co-supervisor this year. Without the constant guidance, kindness and willingness to assist from my co-supervisor, I don’t think I would have managed half of the challenges phased by my project and even the modules. By allowing me to ask questions at any time of the day and equipping me with the ability to solve problems I had myself, she has also assisted in helping me deal with the stress of Honours.

I am very grateful for being given this opportunity to do this incredible degree this year. I have made great friends, met highly accomplished academics, and opened doors for my career goals that I didn’t think possible.

If there was anything I would change about the way I handled this year, I would go into every assessment to aiming show my full understanding of topics rather than just putting down answers I thought were wanted.

To every individual that has helped me along my way through this Whole New World of Honours at UCT- Thank you!

CANCER RISK ESTIMATION USING COLONOSCOPIC SURVELLANCE AND MMR GENE MUTATIONS

by Kelly-Robyn Singh

Lynch syndrome is an autosomal dominantly inherited cancer syndrome which predisposes individuals to a wide range of cancers, most commonly, cancer of the colon and/or rectum (colorectal cancer- CRC). It presents as colonic adenomas (benign epithelial tissue tumor) at an early age of onset that is averagely seen in other cancers. Lynch syndrome is the most common type of hereditary colon cancer, and it is estimated that approximately 1 in every 300 people carry mutations which are associated with Lynch syndrome. These associated mutations are found in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 or PMS2. Consider the following analogy: the MMR genes encode the MMR machinery, which we can think of as the police-force of the genetic code, in the sense that they recognize inconsistencies in the genetic code which may have arisen during DNA synthesis, and they repair it to restore genetic stability, much like a policeman/woman would in the instance of crime. In a society without the police to maintain law and order, there would be chaos, much like there is when the mutated MMR genes cause non-functional MMR and subsequently, deleterious mutations are allowed to accumulate in the genetic code, uninterrupted.

The question is, could mutations in some of these mismatch repair genes have a more severe effect than others? Is colonic surveillance and removal of pre-cancerous adenomas an effective strategy to manage CRC risk and incidence? The paper by Møller et al. aims to investigate the effects of surveillance in individuals carrying Lynch Syndrome associated mutations and their risk of cancer in more effective and accurate estimates than the usual risk estimation approaches which mainly involve retrospective studies.

To accomplish this, a cohort of patients carrying mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2 were studied and monitored on an Oracle regional database, with the aim to correlate data across categories like age, sex and mutated gene as the data develops to identify significant trends.

The findings were that 314 patients had developed cancer out of 1942 mutation carriers with no prior history of cancer. The cancers were found were mostly CRC, followed by endometrial and ovarian. Interestingly, carriers with mutations in the MLH1 and MSH2 had an earlier age of onset (25 years) as compared to that of MSH6 and PMS2 carriers (40 years). The cumulative cancer incidence rates at 70 years (patient age)for each gene as well as ten-year crude survival can be found below.

Table 1: Cumulative cancer incidences for each MMR gene and ten-year crude survivals for their respective cancers

Figure 1: Cumulative incidences by age and mutated MMR gene for any cancer

These findings conclude that there are varied penetrance and expression patterns of each of the mismatch repair genes, with that of MLH1 and MSH2 being higher and therefore causing an earlier age of onset as well as incidence. The results of this paper conclude that colonoscopic surveillance did not significantly decrease the incidence of CRC, but it did result in a lower mortality rate. The early detection of pre-cancerous adenomas is therefore imperative to prevention and the prolonging of life.

References:

Møller P, Seppälä T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons R, Jeffries J, Vasen H, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen J, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Frayling IM, Plazzer JP, Pylvanainen K, Sampson JR, Capella G, Mecklin JP, Möslein G; Mallorca Group (http://mallorca-group.eu). Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017 Mar;66(3):464-472. doi: 10.1136/gutjnl-2015-309675. Epub 2015 Dec 9. PMID: 26657901; PMCID: PMC5534760.

Are human personalities preprogrammed?

by Muhammad Adeeb Fakier

“The apple does not fall far from the tree”, is a common saying relating to offspring having a similar characteristic or quality to the parent. The advancement in genetic studies has allowed for the identification of genes associated with specific phenotypic observable characteristics, but what is the relationship between genetics and personalities?

Research from family, twin and adoption studies have indicated strong evidence for heritability of human personalities. However, the phenotypic architecture of the human personality is complex, and therefore includes uncertainty as either the same genetic networks may lead to different phenotypic outcomes; or different genetic networks in complex systems may lead to the same outcome. Past genome-wide association studies (GWAS) had very little success, where heritability of complex traits have been called “missing” or “hidden”.

The Temperament and Character Inventory (TCI) is a system that evaluates specific dimensions of personalities. TCI character traits have been identified to be associated with brain networks for metacognitive processes such as self-reflection and purposefulness; whereas temperament traits (innate traits) generate and condition automatic behaviors, such as stress reactions. Therefore focusing on self-regulatory character traits such as self-directedness, cooperativeness and self-transcendence can be used determine the health state of an individual’s adaptive functioning.

The study utilized a machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions. A discovery sample of 2149 individuals were used, and sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals were identified. Thereafter five cluster of individuals with distinct profiles were identified. Lastly the association significance of the SNP sets with one or more character profiles (resourceful, organized, creative, dependent and apathetic) were identified.

The GWAS analysis of the genotypic and phenotypic architecture of personality measured by the TCI, illustrated each SNP set maps to one or more genes, identifying its association to each of the five general character profiles (Figure 1). This was followed by categorizing the variation in health status of SNP sets as: well, ill and intermediate (Figure 2). It was found that 42 SNP sets identified to 727 gene loci were significantly associated with one or more of the character profiles. Interestingly the SNPs sets often had similar character profiles associated with particular molecular processes such as involved in regulation of inositol-calcium signaling for obtaining food (G_8_8) and for neuroprotection against injury (G_12_8).

In conclusion genetics have an influence on human personalities, and this study has illustrated that it is possible to characterize the complexity of genotypic and phenotypic architecture of self-regulatory character traits. The study highlighted that self-regulatory personality traits are strongly influenced by organized interactions among more than 700 genes, despite variable individual cultures and environments.

Reference

Zwir, I., Arnedo, J., Del-Val, C. et al. Uncovering the complex genetics of human character. Mol Psychiatry 25, 2295–2312 (2020). https://doi.org/10.1038/s41380-018-0263-6

Zwir, I., Mishra, P., Del-Val, C. et al. Uncovering the complex genetics of human personality: response from authors on the PGMRA Model. Mol Psychiatry 25, 2210–2213 (2020). https://doi.org/10.1038/s41380-019-0399-z

Into the Thick of it: Can Cannabinoids be used to treat COVID-19?

by Robyn Lesch

Weeding through fact and fiction in search of the truth

The therapeutic effects of cannabis have long been known because of the presence of cannabinoids like THC and CBD commonly used to treat various symptoms and side effects related to cancer – but what effect does cannabis have on COVID-19?

In recent years, with more research into its usefulness, cannabis has evolved from that substance your parents warned you about as a “gateway drug” into the shining flame at the end of a dark seemingly endless tunnel of research. As this research into the therapeutic properties of cannabis has developed, so has the mainstream use of cannabis products. These properties are mainly due to the presence of cannabinoids which refers to every chemical substance, regardless of structure or origin, that joins the cannabinoid receptors of the body and brain and that have similar effects to those produced by the Cannabis Sativa (C. Sativa) plant. With its remarkable healing potential, you may be wondering if cannabis could help fight the virus currently taking the world by storm – COVID-19. COVID-19 has resulted in millions of deaths, closed international borders, and has brought global economies to their knees. This contagious respiratory disease can leave one with a fever, feeling fatigued, and struggling to breathe and can very quickly become fatal. So, can cannabis help in the fight against COVID-19?

A January 2021 study published in the journal Aging has found that cannabis may offer some help for patients with COVID-19.

Cannabis and the cytokine storm

One of the main biological events that occur in patients with severe acute respiratory distress caused by COVID-19 is a “cytokine storm.” This is where the body experiences an extreme increase in proinflammatory cytokines. Cytokines are a category of proteins which are involved in the cytokine storm that leads to increased inflammation.

COVID-19 patients tend suffer from lung fibrosis, a dangerous and untreatable condition that leaves lung tissue scarred and making it difficult to breathe. If a substance could stop the cytokine storm, it would be able to suppress inflammation, prevent lung fibrosis, and possibly even put COVID-19 patients in remission.

The Experiment

Researchers used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model and exposed the tissues to UV in order to induce inflammation. The tissues were then treated with extracts of seven new cannabis cultivars. It was noted that out of seven studied extracts of novel C. sativa cultivars, three were the most effective, causing profound and concerted down-regulation of COX2, TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. This data was further confirmed in the WI-38 lung fibroblast cell line model.

The Conclusion

In this study, C. Sativa, a type of cannabis, was found to reduce multiple cytokines and pathways related to inflammation and fibrosis. Two of these cytokines of note that were reduced were TNFα and IL-6, which are thought to be the main targets when trying to block a COVID-19 cytokine storm and acute respiratory distress syndrome.

Closing Thoughts

Cannabis has shown great potential in fighting against COVID-19, thanks largely to its anti-inflammatory properties. The study shows that cannabis could significantly improve the condition of COVID-19 patients by reducing a cytokine storm and protecting lung tissue from inflammatory damage. Novel anti-TNFα and anti-IL-6 cannabis extracts can be useful additions to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions.

Although this research is exciting and shows the potential power of cannabis in the fight against COVID-19, always remember to follow your doctor’s advice when managing COVID-19.

References

Kovalchuk, A., Wang, B., Li, D., Rodriguez-Juarez, R., Ilnytskyy, S., Kovalchuk, I. and Kovalchuk, O., 2021. Fighting the storm: could novel anti-TNFα and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19?. Aging, 13(2), pp.1571-1590.

The Shot Heard Around the World: Achilles Tendon Injuries — Rugby Science

by Ashleigh Thomas If you’ve heard or experienced an achilles tendon rupture, you’ll know exactly what the title is alluding to. If you don’t know, an achilles tendon rupturing sounds like a gunshot, and it’s as painful as it sounds. Researcher Gregory Hess, in his 2010 review of “Achilles Tendon Rupture” in the Foot and […]

The Shot Heard Around the World: Achilles Tendon Injuries — Rugby Science

FIFA 11+: An effective way to reduce injuries in amateur soccer players? — Rugby Science

by Aminah Emeran Soccer is arguably the most popular sport globally, with an estimated 200 million players worldwide (1). There are many health benefits of playing soccer, including reducing the risk of type 2 diabetes and hypertension (2). Despite its health benefits, soccer also poses a significant risk of injury (3), particularly to areas such […]

FIFA 11+: An effective way to reduce injuries in amateur soccer players? — Rugby Science

Wimbledon – it’s not all just strawberries and cream — Rugby Science

by Jenna Bloom When you’re watching Wimbledon, have you ever wondered how busy the doctors and physiotherapists are behind the scenes? Well, McCirde et. al. (2016) wanted to determine the rate of injuries that occurred during Wimbledon, which could assist scientists to eventually develop measures to prevent injuries. (3) They study found that there were […]

Wimbledon – it’s not all just strawberries and cream — Rugby Science

Overuse injuries in basketball: A dribble of sprains and pains — Rugby Science

by Tumelo Lethule  Basketball has become one of the most popular sports in the world and has given us the pleasure of gushing over NBA stars such as O’neal, James, Curry and of course, the legendary Jordan. As a non-contact sport, basketball remained one of the safest sports ever played. However, as the sport seems […]

Overuse injuries in basketball: A dribble of sprains and pains — Rugby Science

Reflective piece.

by Nkosazana Shange

As time goes by, I think to myself, when is the end coming, I need a Holiday. I had already imagined in my mind what I will do to relax my body; sleep all day, watching TV with my family or going out to eat at a fancy restaurant with my friends. Meanwhile I have assignments to finish and tests to prepare for. Well, the progress has been excellent, and all due dates are met. What then is missing? a long break.

Many might agree with me when I say nothing ever comes easy in life, it all requires hard work and determination. As students, we have worked probably for more than 12years, and it’s no joke. In the end the wages of hard work are good. This is encouragement for those time where you feel down and drained. However, a break is still needed. It is no crime that want you to take a day off and do something nothing related to your work. There is no condemnation in relaxing amongst busy days. We all do need time some time to alleviate stress and burdens. Therefore, take a break and keep calm. The world will not end when you ease up. That has been my experience this year as a student. Yes, the work is plentiful and when one might feel burnt out that is the opportunity to take a break. Mental health is very important. If we take very good care of our mental health, then we can easily overcome a lot of challenges we face every day.

We do get tired and its okay, we have overcome so much to reach where we are, and we can persist. Thus, even though you have a busy schedule, take some time off and reward yourself for your hard work. Fill your day with sunshine and go to the beach. Remember you are important and awesome, be good to yourself and persevere.

ADHD, Honours and Me

by Robyn Lesch

I’m tired. I’m lonely. I’m bored. I’m happy. I’m excited. I’m torn. Honours has been a wild ride – the best year of my life and simultaneously the most emotionally, academically and mentally taxing year of my life. I knew it would be crazy from start to finish, but I wasn’t prepared for this. Studying in a pandemic – where university is basically a subscription streaming service? Madness.

I can be the smartest and dumbest person in the room, the hardest working lazy person, the most introverted extrovert, the most distracted person who can tear a concept apart into a million tiny details and then reassemble it into total clarity in a second, all at the same time. One of the odd things about ADHD is that if I’m unmotivated, walking through glue, and I try to push myself harder, the glue actually becomes deeper. So the harder I work, the harder it becomes. And either I manage to get there through supreme, superhuman effort, or I just get bogged down in the glue. Too exhausted to go on. Motivation happens in short bursts. No one is motivated all the time, what separates me from most is discipline.

That being said, in honours, I’m tired and overwhelmed. If it’s not one thing, it’s another. Sometimes I feel like there’s so much work to be done and not enough of me to get it done. I’m lonely. With all these feelings and the loss of the social element of university due to online learning, we’ve lost the connection as students that bonds us. We don’t get to talk to one another as we would in person and as such you don’t form proper, authentic connections with people. You don’t know where to turn when you’re stuck without feeling like you’re bothering someone because all you have is text. On the other hand, I’m happy because I finally get to focus on my area of interest completely and excited because the realm of possibilities seems infinite. This is what keeps me disciplined. I have a goal and I will achieve it.

However, I think more provision should be made for mental health related issues – there should be more support for students, particularly non neurotypicals. I think educators should be more empathetic towards their students, especially in a pandemic and lastly, because of the lack of social interaction due to COVID-19, I think universities should put more emphasis on teambuilding activities to boost morale and develop and nurture interactions among students.

In closing, if you take nothing from this reflection but this, may it be that the devil works hard, some people work harder, but no one is working harder than non-neurotypicals striving to reach their goals competing in a world with odds stacked against them. May setbacks never stop us. 

Does dissection of the human cadaver cause anxiety?

by Courteney Collins

As an anatomy student, I am often asked “how do you handle dissections, isn’t it scary?”. Students are taught that dissections provide a good foundation for a doctor-patient relationship (Bastos and Proenca, 2000). However, people begin to view doctors as insensitive, lacking human emotion. Recently there has been much research done on the emotional state medical students face when experiencing dissections.

Figure 1: Dissection Hall, Institute of Anatomy, University of Greifswald 2002.  

Fox (1979) described that students are naturally distraught when dissecting a human cadaver and in order to cope with it they develop a “scientific attitude”. The most common reactions to the experience are physical and psychological and have shown to reduce after the first few weeks of dissections (Penney,1985). Despite all the different views, this study proved that anxiety was the most common emotional reaction.

The aim of this research was to study students’ anxiety response to dissection and determine the factors involved in this response.

Three studies were carried out in the dissection room at the department of Human Anatomy and Embryology II at the Complutense University, Madrid, during the 3 academic years 2000–2003.The participants of the study were first time matriculants in the anatomy department. In the three studies, the student’s anxiety level was measured at different times and the student’s anxiety trait.

The first study showed that students anxiety levels decreased the more they experienced dissections. It makes sense that most students experience anxiety because they don’t know what to expect.

The second study demonstrated that the once students became comfortable with dissections, their anxiety reaction was a result of personal traits. This means that those who found it “scarier” had higher anxiety levels.

The third study found that by showing students videos or pictures from the dissection room, it reduces their anxiety levels when completing their first dissection.

Although students experience different emotions when they begin human dissections, anxiety is the most important. Anxiety was even one of the reasons for removing cadaver dissections from teaching practices (Aziz et al.,2002). So, to answer the question, yes, it is scary, and it can be challenging at times. But without this experience, how will it help future doctors when anatomy is so important?

This study proved that most effective solution is gradual exposure before dissecting a cadaver for the first time. Students should also be taught to have an ethical and humanistic approach to the cadaver. We should remember that “The human body is the most complex system ever created. The more we learn about it, the more appreciation we have about what a rich system it is.”- Bill Gates.

References:

Arráez‐Aybar, L.A., Casado‐Morales, M.I. and Castaño‐Collado, G., 2004. Anxiety and dissection of the human cadaver: an unsolvable relationship?. The Anatomical Record Part B: The New Anatomist: An Official Publication of the American Association of Anatomists, 279(1), pp.16-23.

Aziz MA, McKenzie JC, Wilson, JS, Cowie RJ, Ayeni SA, Dunn BK. 2002. The human cadaver in the age of biomedical informatics. Anat Rec (New Anat) 269:20–32.

Bastos LAM, Proenc¸a MA. 2000. A pra´ tica anato´mica e a formac¸a˜o me´dica. Pan Am J Public Health 7:395–402.

Fox RC. 1979. Essays in medical sociology: journeys into the field. New York: John Wiley and Sons.

Penney JC. 1985. Reactions of medical students to dissection. J Med Educ 60:58–60.

The Prevalence of Diabetes on Polycystic Ovarian Syndrome Patients

by Kaylene Baron

Polycystic Ovarian Syndrome (PCOS) is a disease that results in enlarged ovaries due to the ovaries being covered with cysts [2]. These cysts cause hormonal imbalances. The symptoms of PCOS will vary in degree from one person to another. But, for the most part, these are symptoms: being overweight or obese, few or no periods, irregular menstrual cycle, prone to acne, hirutism (excess body hair) on the face, breasts, insides of the legs as well as mood swings. What makes PCOS such a devasting disease, is that a woman’s fertility is questionable. (Obviously seeing that it is the ovaries we are talking about here). This is due to her irregular menstrual cycle and also no ovulation. This makes conception (falling pregnant) as well as pregnancy (being able to carry the baby to term-in other words, for the full 9 months) difficult [2]. But for me, what makes PCOS devasting is the fact that these hormonal imbalances also have an impact on your metabolism. This increases a woman’s chance of developing diabetes and heart disease [2]. This will be the focus of this blog post.  

To put this situation in a South African context, let me give you some statistics. According to an article in the South African Journal of Obstetrics and Gynaecology, [3]. the condition affects 15–20% of women in their childbearing years and is also linked to 40% of female infertility cases in South Africa. To date, there is no set cause for PCOS much less a cure. I am going to discuss an article with you that investigated the risk of PCOS patients having diabetes [1].

They performed this study by doing the following: Subjects were recruited from the diabetes clinic population (2500 patients) of The Middlesex Hospital. Various criteria were used to determine who is eligible for this study, this total later came down to 38. In subjects with regular menstrual cycles, studies were carried out during the follicular phase (i.e., the stage where menstruation takes place followed by the maturing of the egg until ovulation). Investigations were performed at random in those with marked oligomenorrhoea or amenorrhoea. Body mass index was calculated as weight/height2 (kg/m2). The waist circumference was taken at the level of the umbilicus, the hip circumference was taken at the level of the pubis symphysis to determine the waist/hip ratio. The pelvic ultrasounds were performed to confirm if a woman has polycystic ovaries or not. Fasting blood samples were drawn to test the levels of the various reproductive hormones as well as insulin levels [1].

From the results obtained, eighty-two per cent (31 out of 38) of the women studied had ultrasonographic evidence of polycystic ovaries. The influence of insulin on ovarian function in the group of women with PCO was further analysed using correlations between metabolic parameters and serum androgen concentrations. Body mass index was positively correlated with leptin and total testosterone. Ovarian volume was positively correlated with fasting insulin, androstenedione, total testosterone, body mass index, waist: hip ratio and negatively associated with SHBG [1].

From this study, we can conclude that women with PCOS have higher androgens (male hormones) than women with no PCOS. The impact of this results in a higher BMI and a higher waist: hip ratio. A woman who has uncontrolled weight gain ends up having heart disease and insulin resistance which later gives rise to diabetes.

References:

  1. Conn, JJ., Jacobs, HS., and Conway, GS. 2000. The prevalence of polycystic ovaries in women with type 2 diabetes mellitus. Clinical endocrinology, 52(1):81-86
  2. Glenville, M. 2001. The Natural Health Handbook for Women: The complete guide to women’s health problems and how to treat them naturally. London: Piatkus  
  3. Page, S. 2019. Life healthcare: Get informed about Polycystic Ovary Syndrome.

It’s been a while since the first batch of Covid-19 vaccination was distributed throughout the United Kingdom (UK)

by Koketso Ramotsila

In the United Kingdom, BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been swiftly carried out. In their healthcare worker (HCW) cohort study of staff receiving regular asymptomatic testing, they identified some variables related with vaccination coverage for both vaccines and demonstrated the immunization efficacy of the BNT162b2 mRNA vaccine.

This SIREN study arose back in December 2020 when infections were flooding at the UK. The SIREN project is basically a prospective cohort study including publicly financed hospitals and their employees.

At two-week intervals, baseline risk factors, vaccination status (from 8-Dec-2020 to 2-Feb-2021), and symptoms were documented, as well as all SARS-CoV-2 polymerase chain reaction (PCR) and antibody test findings.

A Poisson distribution was used in a mixed effect model. To an extent they evaluated the effects of the BNT162b2 vaccination on all infections, a mixed effect proportional hazards frailty model with a Poisson distribution which was used to compute hazard ratios to compare time to infection in unprotected and vaccinated patients. We understand that a Poisson distribution is a probability distribution that can be used to show how many times an event is likely to occur within a specified period of time.

On May 2, 2021, vaccine coverage was 89 percent. Prior infection, being under 35 years old, being from a minority ethnic group, porters/security guards, or a midwife were all linked to much poorer coverage. The BNT162b2 vaccination successfully protects both symptomatic and asymptomatic illness, according to a research. This group was vaccinated while B1.1.7 was the prevalent variation in circulation, demonstrating efficacy against it. Even fans are able occupy football matches in the UK. Did the available vaccines in South Africa produce similar successful results?

References:

Hall V, Foulkes S, Saei A, et al. Effectiveness of BNT162b2 mRNA vaccine against infection and COVID401 19 vaccine coverage in healthcare workers in England, multicentre prospective cohort study (the SIREN 402 study).

Antifungal Cross-Resistance and the need for an antifungal resistance database

by Oscar Megan

Triazole resistance in Aspergillus fumigatus is an emerging health problem. This fungus is a major cause of invasive fungal infections in immunocompromised individuals, and has spread significantly in the last decades (Zhang et al., 2017). There are two main classes of antifungals used to treat this fungal infection: (1) Medical triazoles, used for cases of human infection (For example, Itraconazole and posaconazole). (2) Sterol-Biosynthesis Inhibitors used as agricultural fungicides (Used in the treatment of wood fences, or decaying plant matter). There are two presumed paths to medical triazole resistance: (1) Through selection pressure of triazole use
when treating patients. (2) Through selection pressure of non-medical SIs used in the environment. Put simply, Aspergillus fumigatus is also presumed to develop medical triazole resistance when only exposed to the non-medical sterol-biosynthesis inhibitors (SIs).

In a 2017 study (Zhang et al., 2017), researchers sought out to determine the level, and speed at which this cross-resistance is developed in Aspergillus fumigatus. Evolved Aspergillus fumigatus samples were used from a previous study which tested for SI resistance for five different agricultural fungicides. In the 2017 study, these evolved lineages were then exposed to three medical Triazoles (1)itraconazole (2)posaconazole (3) voriconazole over seven weeks
at varying concentrations to determine the minimal inhibitory concentration (MIC) for the evolved lineages.

These figures show the change in relative MIC over time. Plot (a) shows the results of the previous study, plots (b), (c) and (d) show the changes when exposed to the three medical Triazoles.

The observable trend from these figures is that, over seven weeks the SI resistant strains develop medical triazole resistance (because of the increasing minimal inhibitory concentration). After whole-genome sequencing the now medical triazole resistant lineages, it was found that there were no structural changes needed to develop this resistance. Put simply, by developing SI resistance Aspergillus fumigatus also developed resistance to medical triazoles.

This finding is of major concern. If sterol-biosynthesis inhibitors are overused in agriculture or elsewhere, Aspergillus fumigatus could develop medical triazole resistance through selection pressures.

A similar phenomenon in antibiotics resistance has been observed in recent decades. To combat this, the antibiotic resistance database Comprehensive Antibiotic Resistance Database or CARD, was funded. CARD was made so that findings relevant to resistance could be made publicly available. Currently, there are no large-scale, well funded antifungal resistance databases, and the findings of this 2017 study highlight the growing need to fund such a database.

References:

Zhang, J., van den Heuvel, J., J. M. Debets, A., E. Verweij, P., J. G. Melchers, W., J. Zwaan, B. and E. Schoustra, S., 2017. Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides.

A year of challenges

by Muhammad Adeeb Fakier

Before starting the Honours Programme, my expectation was that it would be just another extra year of sacrifice and that it would be relatively straight forward. This idea was especially brought on since lockdown regulations prevents student from going to campus and therefore everything is online. I was basically picturing the ideal life of sitting by a computer with a cup of coffee and working through the courses materials, stress free. This was definitely not the case.

This year has presented itself as waves of deadly deadlines, with the durations getting shorter and workload getting more intense. For example; completing a module within a month that entails different content including assignments, project proposals, presentations, and worse… Exams. I have always felt that I coped well under pressure and that my organisational skills have allowed me to adapt to uncomfortable situations at a reasonable rate. However, having done my undergraduate three years ago, I completely forgot the feeling of exams and was genuinely reminded of its horror.

Despite my misjudgement of the process for furthering my education to Honours level, I found the challenges to be truly fulfilling as I have learned a lot within this year. The content within each of the modules are extremely interesting, with some of them also being super intensive that completing the module just immediately leaves a sense of satisfaction.

During this year, I have become especially appreciative of the contribution that articles have on the science community. A specific moment that comes to light was where in one of my modules, I was required to prepare a presentation of any choice relating to a high throughput biology article. The people in the module all presented incredibly interesting articles and could present the article as if it was written by them. At that point I realized how embedded science has become with us.

Level up

by Sahar Jamal

It is hard to wrap my head around the fact that I have just completed one of the last major exams of my life. I am both excited and daunted by the future. It feels like a ‘coming of age’ experience, to be focusing on research as opposed to studying. I am grateful to have made it this far, to be surrounded by such accomplished people. To be amidst individuals with similar interests and goals is illuminating. I am delighted to be apart of a community and to share my passion with others.

During my undergraduate degree I preferred self-studying from textbooks rather than attending lectures. When my class size jumped from 300 to 4-10 in the first half of this year it was energising. Attending classes became an engaging experience. I feel incredibly privileged to be attending seminars and participating in journal clubs and I look forward to working together with my peers on the pioneering projects that await.

The humanity of the health sciences is especially consoling. The focus is on wellbeing and there is no disconnect from people. Being able to express myself in a reflection like this and actively sharing knowledge with the community, for the community, is wholesome.

The periods of practical engagement were especially enlightening. I am particularly appreciative of my supervisor, Dorit Hockman, for introducing us to the foldscope in the last week of term. This was a great way to end off. I have subsequently started an Instagram page, scopes_and_quotes, where I post photographs I’ve taken of the world around me at 140x magnification. Each image I reflect on and assign a quote to. It is a combination of literature, art and science. This holistic energy is what resonates within the health sciences. I am thankful to be apart of it.

The Role of Kisspeptin in Immune Tolerance Formation During Pregnancy

by Katleho Matlatse

Have you ever wondered why pregnancy loss is an experience many women are and have been facing for centuries? But the more persistent question is why women experience recurrent pregnancy loss? and why, after the development of new technologies and novel knowledge, the incidence of it occurring is not reducing?

1-2% of women will experience recurrent pregnancy loss (Ford & Schust, 2009). Pregnancy loss, also known as loss of clinical pregnancy or miscarriage, is defined as the loss of fetus before the 20 completed weeks of gestational age. Recurrent pregnancy loss (RPL) occurs when women experience three or more consecutive miscarriages. When the etiology is often unknown or spontaneous, this is classified as idiopathic recurrent miscarriage (IRM). An imbalance in placental hormones and or immune dysregulation may give rise to implantation failure and eventually lead to pregnancy loss. The tumour metastasis suppressor decapeptide, kisspeptin, and its receptor, GPR54, are expressed in the placenta and are thought to play an important role in
embryo implantation, early placentation, and trophoblast invasion. Furthermore, kisspeptin regulates the behavior of regulatory lymphocytes thereby altering concentrations of IL-10 and IL-17A, events key for maternal immune tolerance.

If Kisspeptin increases the formation of aTreg (adaptive T regulatory) cells, would an increase occur in pro-inflammatory ( IL-17A) and anti-inflammatory (IL-10)? What would the mode of mechanism look like?

The study hypothesizes that in pregnancy, the expression of kisspeptin influences that of anti-inflammatory and pro-inflammatory cytokines which are key in setting maternal immune tolerance. To achieve this, the authors collected blood samples from nonpregnant women of reproductive age (from 23-37 years of age) but compared that data with peripheral blood samples of women in trimester I, II and II. The authors performed extraction of peripheral blood mononuclear cells (PBMCs) from blood samples, followed by immunomagnetic separation methods to extract CD4+ T cells. The cells
were induced with different concentrations of Kisspeptin, IDO and Lipopolysaccharide and incubated. To induce aTreg cells, the authors introduced cytokine specific monoclonal antibodies along with kisspeptin, IDO and liposaccharide (LPS) stimulation followed by ELISA tests (which detect protein expression) and Flow cytometry to evaluate lymphocyte phenotype.

Research done before this study suggested that increasing the production of aTreg cells, by increasing the production of anti-inflammatory cytokine IL-10 and reducing the production of IL-17A, a pro-inflammatory cytokine enhances immune tolerance. This ultimately reduces the immune response. Inducing aTreg cells with Kisspeptin, significantly increases the formation of increased CD4+ T cells at different concentrations during trimester I, II and III. This study discovered that aTreg cells, when induced with the hormone kisspeptin, enhanced the production of IL-10, and significantly reduces the production of IL-17A (prevents differentiation of Th17 lymphocytes) by CD4+ T lymphocytes of peripheral blood of women. An increase in anti-inflammatory cytokines, reduces immune response. Therefore, kisspeptin has shown to increase immune tolerance between the maternal-fetal interface (from the maternal body to the fetus) antigens, which ultimately determines the outcome of
pregnancy. What is interesting in this paper is that it stimulates the idea that pregnancy loss is not just a result of environmental factors, genetics, but rather hormone dysregulation can play a part. I believe more studies need to be done on hormone regulation between the maternal-fetal interface and how we can significantly reduce pregnancy loss.

References
Ford, H. B. & Schust, D. J., 2009. Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy. Obstetrics and Gynecology, 2(2), pp. 76-83.
Gorbunova, O. L. & Shirshev, S. V., 2014. The role of Kisspeptin in Immune Tolerane Formation during Pregnancy. Volume 457.

Gaba Regulates Synaptic Integration of Newly Generated Neurons in the Adult Brain

by Zamazimba Madi

Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult, it is a form of structural neuroplasticity and emphasizes regenerative ability of the adult mammalian brain​. It is known that neuronal activity regulates adult neurogenesis and, new neurons contribute to specific brain functions​. It is unknown how the integration of these new neurons into the existing functional neuronal circuits is regulated​. Expect to see that newborn granule cells are tonically activated by ambient GABA (γ-aminobutyric acid, an inhibitory neurotransmitter in the central nervous system) before sequential innervation by GABA- and glutamate-mediated synaptic inputs​. GABA initially depolarizes newborn neurons owing to their high cytoplasmic chloride content​. In vivo, GABA-induced depolarization converted into hyperpolarization in newborn neurons results in marked defects in synapse formation and dendritic development​. The purpose of this study was to establish the role of GABA in the synaptic integration and proposes a mechanism for the regulation of adult neurogenesis​.

DEVELOPMENT OF NEWBORN CELLS IN THE ADULT MICE

Thus, new-born cells are tonically activated by ambient GABA before any detectable phasic or synaptic activation, and we can conclude that new-born cells in the adult brain, as in neonates, first receive tonic GABA activation, then GABA-mediated synaptic inputs and finally glutamate-mediated synaptic inputs.

NATURE OF GABA-INDUCED ACTIVATION IN NEWBORN CELLS IN THE ADULT BRAIN​

GABA initially depolarizes new-born cells in the adult brain.  Tonic GABA activation led to hyperpolarization of NKCC1- shRNA [sodium (Na), potassium (K), chloride (Cl) co-transporter 1- short/small hairpin RNA (an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference its expression in these cells is usually achieved through the delivery of plasmids or viral or bacterial vectors. See image (Sliva & Schnierle, 2010)) expressing cells in contrast to depolarization on the control new-born cells. GABA depolarizes new-born cells during initial development due to their high chloride ion concentration from the expression of NKCC1. Therefore, tonic GABA activation not only depolarizes new-born cells but is also the bulk of GABA-induced activation during initial integration when phasic or synaptic GABA activation is weaker than tonic activation or does not exist.

SYNAPTIC INTEGRATION OF NEWBORN CELLS IN THE ADULT BRAIN

There are defects in the formation of GABA-mediated synapses by NKCC1-shRNA-expressing cells. Results show that postsynaptic currents and spontaneous synaptic currents were detected in NKCC1-shRNA-expressing cells halfway through the experiment, and the percentage of cells recorded with postsynaptic currents was largely reduced two weeks later.  Therefore, there were no general defects in receptor expression at the synapses.

DENDRITIC DEVELOPMENT OF NEWBORN CELLS IN THE ADULT BRAIN

NKCC1-shRNA expressing cells had marked defects in dendritic arborization i.e., total dendritic length, branch number and complexity were reduced.  Therefore, GABA-induced depolarization regulates the dendritic development of new-born neurons in the adult brain.

In conclusion, the integration of newborn neurons into existing functional circuitry involves tonic GABA activation to GABA-mediated synaptic innervation, then glutamate-mediated synaptic innervation​. GABA initially depolarizes newborn neurons, as it would neonatal neurons because of their high cytoplasmic chloride ion content from NKCC1 expression​. Converting GABA-induced excitation into inhibition leads to marked defects in the development of GABA- and glutamate-mediated synapses and dendritic development in newborn neurons​. Tonic GABA activation depolarizes newborn neurons and phasic activation non-existent or weaker​. A possible mechanism was proposed for activity-dependent regulation of adult neurogenesis i.e., through new neurons that sense neuronal network activities through local ambient GABA levels before receiving synaptic innervations​. The results from this experiment can be applied stem cell cell-replacement therapy for neurodegenerative diseases​.

REFERENCES

Ge, S., Goh, E.L., Sailor, K.A., Kitabatake, Y., Ming, G.L. and Song, H., 2006. GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature439(7076), pp.589-593.

Sliva, K. and Schnierle, B.S., 2010. Selective gene silencing by viral delivery of short hairpin RNA. Virology journal7(1), pp.1-11.

The Effects of Music intervention on Functional Connectivity Strength of the Brain in Schizophrenia

by Luxolo Mdolo

Schizophrenia is the 6th leading cause of years of life lost to disability in men and it ranks 6th in women. A reflection of the detrimental impact schizophrenia has on the quality of life of the world population. A Swiss Psychiatrist, Eugen Bleuler described this condition as a “divided mind” where there is a disconnection between brain functions while the patient oscillates between normal and abnormal states.

Schizophrenia is often treated with combinations of medicinal, psychosocial and individualized therapies. However, Yang et al. recently explored the effectiveness of music therapy in the treatment of schizophrenia. This study follows up from epilepsy research that has proven the effect of Mozart Sonata K.488 on improving brain function in the diseased state. In this study, the researchers were investigating the effects of music intervention on the functional connectivity strength of the brain in schizophrenia.

Subjects of the study were grouped into (1) healthy controls, (2) participants suffering from schizophrenia who would receive the music therapy and (3) participants suffering from schizophrenia who would continue receiving medicinal treatment for a month. Functional connectivity strength was tested using resting-state fMRI and schizophrenia symptoms using multiple psychiatric tests. The fMRI would show any brain functional activity improvement from baseline and the psychiatric symptom tests would correlate the improvements in brain function to improvement in schizophrenia symptoms.

The results below showed that music therapy improved functional connectivity of the middle temporal gyrus that is responsible for language and semantic memory processing, visual perception, and multimodal sensory integration. It is interesting that after 1 month of music therapy treatment, it is only the treated group that showed such improvements, and the controls show similar results to baseline.

In the graph below, the treated individuals were followed up for 5 months after they stopped the treatment at 1 month, and the results showed that their improvement declined back to baseline. This showed us that music therapy does not offer long lasting effects. However, this calls for further research to investigate how the effects of music therapy can be prolonged and how the improvements can be maintained.  

The results below also showed a positive correlation between functional connectivity improvement and symptom improvement in the schizophrenic patients treated with music therapy.

Reference

WebMD. 2020. Mental Health and Schizophrenia. Available at: https://www.webmd.com/schizophrenia/mental-health-schizophrenia

Yang, M., He, H., Duan, M., Chen, X., Chang, X., Lai, Y., Li, J., Liu, T., Luo, C. and Yao, D., 2018. The Effects of Music Intervention on Functional Connectivity Strength of the Brain in Schizophrenia. Neural Plasticity, 2018, pp.1-10.

From a Game Design undergrad to BMedSc in Bioinformatics

by Oscar Megan

Since I was a toddler I have always loved computers. Fixing, building, optimising; you name it! I’d never pictured myself in a lab with a white coat, working with my hands. I’ve always aspired to be the gremlin in the computer lab learning to shave minutes off the time it took to complete a task instead of shaving his face.

Naturally, I’ve taken any and every subject/course that helps me achieve this goal. Physics, mathematics, IT were crucial for my early development in computer science, but I chose one wild-card subject in high school, life sciences. Seeing animals and plants and viruses at a systems level brought me to the understanding that we are all just highly complex machines. I found myself just as fascinated in the silicone-based machines I had grown up with, and the fleshy, squishy machines I was now learning all about.

Regardless of my new found fascination, when the time came around I chose to pursue Game Design. What I considered to be the culmination of all that is cutting-edge; learning to push hardware as far as goes to build fantastic new worlds.

That was until the world as we knew it, had been put on hold. In 2020, all of a sudden, we were forced out of the world where we spent our free time, and left only to the digital worlds my peers and I were learning to create. Be it your Zoom meetings, the MSTeams collaborations, even the World of Warcraft! All of us were forced out of the real world and into the worlds others had made for us. As an avid video-gamer, at first I thought, “Well this can’t be too bad”! I had never been so wrong… The year 2020 came with the realization that the worlds I had been learning to create could never be the world I want to live in, the world where families spend time together, friends go on adventures together, where one can explore until one’s feet become sore. That’s the world I want to optimize, that’s the world worth building, and importantly, the world worth fixing.

So I jumped ship and applied to medical science, and I got accepted! Since day one of this course I haven’t looked back, to re-acquaint myself with flesh-machines has been a dream. Learning to avoid viruses in silicone is nothing like the hurdle of creating treatments for viruses in humans. Learning genetics and medical science is forcing me to confront what computer scientists understand least; people, and what makes them who they are.

I cannot lie and say that it has been easy, or a piece of cake. It’s been the most
head-ache-inducing year of my life. Learning three years worth of theory in a couple months was never going to be easy, and with no live lectures, I had a lot on my plate. But, now the halfway mark has been reached, exams written, modules done and for the first time, I feel like I’m learning how to fix, build and optimise the world I truly care for; the real world.

My journey through Honours

by Imaan Amien

Upon finishing my third year of medicine and a year of molecular medicine I was excited to be able to take a break away from the stress and anxiety that comes with being a full-time medical student (although I am sure this sentiment is common amongst all undergraduate programs).  I had heard from older students that there was a certain level of freedom associated with being termed a ‘postgraduate’ student, and that the Honours program would be like no other, although I was never really sure what I was getting myself into.

After the longest holiday period of my life, I couldn’t believe I was actually looking forward to class starting, and to hopefully meeting new people.  As the year progressed, I feel that I was able to build good relationships with my classmates, particularly those in the IDI stream, and I am looking forward to hopefully meeting them in person sometime in the near future.    

When comparing the honours program to the MBChB program that I came from, I can’t believe what a different experience it is.  One aspect that myself and fellow intercalated students found interesting and unique is that we now have time to digest the work that we are being taught.  The relaxed schedule gives us the time to enjoy what we are learning and take everything in, without constantly getting as much work done as possible before the next deadline arrives. 

Writing this post I cannot believe more than half the year has gone.  The thing I was most fearful of – exams, is now over, and the idea of starting fulltime lab work excites me.  I’m looking forward to seeing how the rest of the year pans out. 

Efficacy of commercial mouth‑rinses on SARS‑CoV‑2 viral load in saliva: randomized control trial in Singapore

by Imaan Amien

Can mouthwash stop the spread of COVID?

Introduction

They say that a warm smile is the universal language of kindness.  Thankfully there are dentists, oral hygienists and prosthodontists that can help us to improve our smiles, however according to the World Economic Forum analysis, these professions are listed amongst occupations that carry the highest risk of contracting COVID-19 (1). 

As of June 2021, over 181 million people have contracted the SARS-CoV-2 virus, and nearly 4 million people have lost their lives as a result.  South Africa is still very much behind on vaccine rollout compared to developed nations; therefore we rely on public health measures such as hand hygiene, mask wearing and social distancing to mitigate the spread.  Studies have shown that the SARS-CoV-2 virus is present in the saliva of 91.7% of COVID-19 patients, therefore people can contract the virus directly through aerosol droplets or indirectly by coming into contact with contaminated surfaces.  Therefore reducing salivary viral titers could be a key approach in preventing transmission. 

It has been suggested that anti-septic mouth-rinsing could be performed as a pre-procedural infection control measure when people undergo dental procedures to inhibit aerosol spread via saliva, however as of yet no clinical trials have been performed to measure the efficacy of mouth rinses to reduce SARS-CoV-2 salivary viral titers.  Therefore the researchers aimed to investigate the efficacy of three commercially-available mouth rinses containing either Cetylpyridinium chloride (CPC), povidone–iodine (PI) or chlorohexidine (CHX) on salivary SARS-CoV-2 viral load in COVID-19 positive patients. 

Methods

To do so a randomized clinical study was performed whereby researchers randomly separated patients into four groups to receive the three different mouthwashes and one group with water as a control.  Their saliva was collected & PCR was done to assess salivary viral load. 

Results & discussion

The results showed that CPC & PI mouth-rinses have a sustained effect in reducing the viral load compared to the control group.  This is due to the fact that both CPC & PI disrupt the lipid membrane of SARS-CoV-2 and therefore interfere with the ability of the spike protein to bind to the ACE2 receptor of oral mucosal cells. CHX-based mouthwash did not show a significant reduction in viral load (Figure 1). 

Conclusion

The data therefore proves that commercially available mouth-rinses that contain CPC (Colgate Plax) or PI (Betadine) can be used to effectively reduce salivary viral load.  This is useful not only for dental procedures, but also as an effective public health strategy, as it may help to minimize SARS-CoV-2 transmission in asymptomatic individuals via the oral route.  

Reference

1.         Seneviratne CJ, Balan P, Ko KKK, Udawatte NS, Lai D, Ng DHL, et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection. 2021;49(2):305-11.

The link between alcohol consumption and breast cancer progression

by Mbalentle Madolo

It is not a novel concept that the consumption of alcohol is linked to negative side effects- and not just trivial ones like a bad hangover. It carries other significant issues such as how alcohol consumption has been shown to be linked to the progression of breast cancer. In South Africa, it has been estimated that female drinkers consume around 16% of pure alcohol per year which is 80% above the world average (8.9 litres) (1). And with 19,4 million women over the age of 15 being at risk of being diagnosed with breast cancer- what do these statistics mean for South African women? (2) Does the devil really live in a bottle? Alcohol is not only a risk factor for breast cancer and other diseases, but with recent studies showing that alcohol might enhance the progression of breast cancer in breast cancer patients- South African women need to be wary of the detrimental effects alcohol has.

In a recent study, Yongchao Wang and colleagues investigated the cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer (3). Using a MMTV-neu mouse model, the researchers of this study were able to gather multiple potential mechanisms that are involved in alcohol-stimulated breast cancer progression.

Alcohol is said to induce the mobility of cancer cells through the degradation and re-structuring of the extracellular matrix leading to further cancer cell invasion. Using Boyden chamber, wound healing assays and a 3-dimension (3-D) Matrigel system, it was shown that alcohol induces the spread of breast cancer cells to the lungs and colon and even more shockingly, chronic exposure to alcohol lead to less aggressive cancer cells transforming into a more aggressive form. Additional evidence show that Matrix metalloproteinases (MMPs) have a crucial role in the degradation of ECM, and it has been demonstrated that alcohol induces the actions of certain MMPs on ECM therefore increasing mammary tumour malignancy. The disruption of endothelial integrity is also a possible mechanism of alcohol induced cancer metastasis through damaged adherens junctions by decreasing the electric resistance across the endothelial layer and which facilitates intercellular gaps between the endothelial cells. This study highlighted how mammary epithelial cells as well as breast cancer cells, have the capacity to metabolize alcohol through the presence of various alcohol-metabolizing enzymes.

The accumulation of reactive oxygen species is said to play a crucial role in mammary carcinogenesis and aggressiveness by inducing oxidative stress. ROS is found to increase cancer metastasis and promote tumour angiogenesis. The researchers have hypothesised that alcohol induced ROS and oxidative stress is mediated by the metabolism of alcohol as well as other factors. With the aid of electron spin resonance, It is demonstrated that alcohol has the capacity to generate a variety of ROS in breast cancer cells and in epithelial cells of mammary tissue. Additionally, the study highlighted the positive correlation between ErbB2, an epidermal growth factor receptor part of the epidermal growth factor receptor family (EGFR) and the promotion of tumour growth and spread due to alcohol consumption. Breast cancer cells and mammary epithelial cells that over express EGFR/ErbB2 are more susceptible to alcohol-induced tumour growth through the phosphorylation of EGFR. Additionally, this study concluded that the chronic exposure to alcohol in mammary tumours of MMTV-neu mice increased levels of the population of cancer stem cells (CSC).

The results indicate that alcohol consumption could indeed play a role in promoting breast cancer aggressiveness when observing at a cellular and molecular perspective. Even though the mechanisms by which this happens seem to be vast and complex, the researchers were able to shed more light onto the subject and further propose potential therapeutic targets for breast cancer patients that still consume alcohol.

References

1.         Women & Cancer. CANSA – The Cancer Association of South Africa. 2016. Available from: https://cansa.org.za/womens-health/

2.         The Demand for Alcohol in South Africa during the National Lockdown. Available from: https://www.issup.net/knowledge-share/publications/2021-02/demand-alcohol-south-africa-during-national-lockdown

3.         Wang Y, Xu M, Ke Z, Luo J. Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer. Pharmacological Research. 2017 Jan 1;115:299–308.

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

by Marlu McLean

The recent surge in SARS-CoV2 which cause COVID-19 cases worldwide which was driven by the delta variant.  The effectiveness of the new emerging vaccines is still unknown and researchers in the United Kingdom decided to investigate the effectiveness of the vaccines (Gower et al., 2021).

Since November 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has infected nearly 197 000 000 people and caused the death of 4 200 000 people.  This has not only burdened our healthcare systems, but economies worldwide have been shaken.  Due to the mutagenic potential of the virus, it has been able to change and adapt to overcome barriers to spreading the infection.  The delta variant was first detected in December 2020 in India, where it caused the largest wave of infections yet seen after the discovery of SARS-CoV2.  Scientists has been working on vaccines worldwide, but the efficiency of these vaccines are still uncertain and causes a lot of hesitancy among people.

A group of scientists in the United Kingdom decided to look at the effectiveness of the vaccines currently approved in the United Kingdom on the delta variant.  They looked at the effectiveness of BNT162b2 (Phizer-BioNTech) and ChAdOx1 nCoV-19(Novavax) vaccines after one and two doses. They also compared the effectiveness of the vaccine to the alpha variant.  The scientists accounted for possible confounders by looking at health seeking behaviour of the vaccinated and unvaccinated groups and looked at the effect of any vaccine compared with these two.  They used data acquired in England and used PCR tests to test for SARS-CoV2 and whole genome sequencing to determine which variant according to the spike protein, nucleocapsid and open reading frame 1ab.  The data was analysed and they also compared the results with previous studies on the alpha and delta variant which confirmed that the alpha variant control group was accurate. 

They determined that in the any vaccine group, Phizer-BioNTech and Novavax groups the effectiveness of the vaccine was more after the second dose than the first.  People who received any vaccine had an 87,5% effectiveness with the alpha and 79,6% with the delta variant.  The Phizer-BioNTech vaccine had 93,7% with the alpha and 88,0% with the delta variant.  The Novavax vaccine had an effectiveness of 74,5% effectiveness against the alpha variant and 67,0% with the delta variant.  In all three groups was there a very small difference between the alpha and delta strains. 

Ultimately was the effectiveness against the delta strain better in the group who received the two doses of the Phizer-BioNTech than the Novavax vaccine.  These results are also consistent with other studies.  This paper shows that the two vaccines studied in England had high levels of effectiveness against symptomatic disease caused by the delta variant.  The emergence of effective vaccines is a light at the end of the dark COVID-tunnel and brings hope that we would be able to win the fight against this pandemic.

References

Gower, C., Phil, D., Gallagher, E., Ph, D., Simmons, R., Ph, D., Thelwall, S., Ph, D., Stowe, J., Ph, D., Tessier, E., Sc, M., Groves, N., Sc, M., Dabrera, G., Myers, R., Ph, D., Campbell, C. N. J., & Amirthalingam, G. (2021). Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. 1–10. https://doi.org/10.1056/NEJMoa2108891

TOUGH TIMES NEVER LAST!

by Mbalentle Madolo

If someone would have told 23-year-old Mbali, a young budding scientist that had just been accepted into the honours programme of her dreams, that her honours year would leave her feeling emotionally drained, she would have told you that you are lying, but sadly it is absolutely true. Now don’t get me wrong, Clinical Anatomy still remains my passion and the fact that I was selected amongst many who applied to be a part of this honours cohort is something I don’t take lightly, but it can’t be escaped that this year has been one of my toughest years to date.

The academic content covered so far has been extremely interesting but also difficult to grasp. The challenges that I have faced so far this year go beyond handling academic stress and delve into the emotional turmoil that this year induced. As a black woman, I can’t say that I have been able to look around and see a lot of people who look like me in this field, something that has always bothered me when looking at the sciences as a discipline overall (in my opinion of course). It was this year where my imposter syndrome truly kicked in, and this left me feeling as though I was not fit to do this honors programme, like I was not intellectual enough, like I was too old etc. Granted, these feelings were fueled by academic stress and the fact that we are still living through a world-wide pandemic, but they were mostly exacerbated by how I felt that I could not speak to anyone about how I was struggling to adjust or ask for assistance as I felt that no one would understand.

On the bright side, the support that I have received from my mother and classmates has been absolutely amazing, hence why I find myself happier. I find myself going back to that 23-year-old Mbali who was ready to take on the world and, as cliché as it sounds, cement myself in the science community as a force to be reckoned with! This change came about because I decided to reach out to those around me, that included calling my family whenever I was overwhelmed instead of bottling up my emotions. It also included talking to my classmates about my anxiety, or even asking for assistance with understanding course material if needed. Because of that I will be eternally grateful to the Clinical Anatomy Honours Class of 2021. The friendship and support they have given me is unmatched, I discovered that I was not the only one feeling emotionally drained and overwhelmed, I discovered that I was not the only one having difficulty adjusting…. I discovered that I was not alone.

The first 6 months of my honours degree were extremely challenging for me, but I still recognize how much I have grown not only as a student, but as a person. It’s because of this growth that I am so excited for the next 6 months of this year. The rest of this year will be filled with academic success, further growth and blessings…I can feel it in my bones!

Reflection

by Luxolo Mdolo

This year has been long. Students have literally seen flames. Many times, I find myself trying to exist in isolation from the world we live in because the show must go on. There have been wars raging in the streets on which I walk. Severe taxi violence incidents have left us fearing for our parents who commute to put food on the table. Strikes and looting have turned the country upside down to reveal a side that we have all been trying so hard to hide in the name of freedom. The COVID 19 pandemic just keeps coming at us in waves – meanwhile the people are so fatigued from trying to keep afloat. I personally do not know how other students do this thing of living each day as though these things do not concern them. I even pay attention to my colleagues in MBChB as they continuously talk about the lives lost to COVID in the wards they work in. I reflect at times and just wonder what form of normality is left to go back to when we have finally overcome this pandemic? How do we mourn the lives lost when we could not even attend their burials or night vigils? It has stripped so much from our understanding of what is important to society. Schools were closed and education of children did not mean anything to anyone. The churches were closed, and religion became an afterthought. Businesses were closed and the economy did what it does best. My grandmother said that the last time she saw so many restrictions was during apartheid. It is interesting how this life never ceases to amaze us.

Anyway, on a lighter note, this year in Honours has given me the greatest gift that medicine (MBChB) continuously failed to offer. Time. I have had time to sit, think and reflect. It gave me the time to do things that I always thought I would do immediately when I got to university. I joined the gym. I found some work to make extra income. I do spur waffle Mondays with my friends. I play soccer with other friends at 4pm twice a week. I go on double dates and baecations. I do educational talks. I run a YouTube channel of 500 subscribers. I love it here. The most amazing thing about this year though is doing an amazing research project with a Supervisor who cares.

One of the biggest fears among the people who are in the intercalated programme like me is the fear of detachment from your classmates in the MBChB class and having to integrate with a new group of students. It is more like a fear of the unknown really because you can easily assume the worst of what could possibly happen. However, I have met the most amazing, easy and outgoing people that just fill up your day with smiles and laughter. I never even thought I would be doing study sessions in coffee shops and building solid friendships with my Honours colleagues. This has been such a holistic experience. The hardship and the joy in my life are at such a wonderful reversible potential. I was even going to make a joke about allostatic load, but I realized that it was too soon. Thank you for reading though.

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