RESSONÂNCIA Edição AIMS Meeting 2023

Dear colleague, Welcome to the AIMS Meeting 2023!

This year, once again, our Organizing Committee has worked tirelessly in order to deliver the AIMS Meeting experience to biomedical science students worldwide.

We’re thrilled to be back to a full on-site congress, without the need of masks or nasal swabs. Although new challenges emerged, such as the ongoing war or the energetic crisis, science goes on and we’re proud to keep spreading knowledge.

As a student congress which happens to be entirely organized by students, we have a particular proximity and insight to what are the specific interests, curiosities and needs of our peers in today's global world; and are motivated in going the extra mile to keep science appealing, exciting and interesting in the eyes of our participants.

During the four days of our congress, we hope to inspire our colleagues, bring them into close contact with the world of science and research, and create a platform for communication and knowledge sharing that is approachable and accessible to everyone. This year, we aimed higher and we’re proud to bring participants from more than 30 different countries, contributing to enrich the cultural differences in the way we live the AIMS Meeting. In person or at a distance, from anywhere around the globe, hundreds of participants will be encouraged to discuss science and healthcare.

As a team, we aim to create a stage of educational, cultural and recreational opportunities, contributing to the development of a generation that is more aware of its environment and current issues.

General Coordination of the AIMS Meeting 2023

Beatriz Figueiredo and Diogo Vianez Oliveira

KEYNOTE LECTURES

Joan Steitz: A Pioneer in Science and Women's Empowerment

Born in 1941 in Minneapolis, Minnesota, Joan Argetsinger Steitz is an influential figure in the world of science. Since college, she has dedicated her life to being a scientist and has made immeasurable contributions to current scientific knowledge. While pursuing her PhD, Joan Steitz was the only woman in her class. Ever since, she has continuously fought for women's empowerment in a world that, for most of her career, has been dominated by men.

When Joan started her journey she didn’t think she would ever become the head of a lab, let alone earn so many awards while competing against male colleagues. In fact, while she was an undergraduate, Joan decided to apply to medical

school because, until that point, she had never seen a woman as a science professor or heading a lab. Therefore, Steitz felt she should become a physician, following the path of every woman she had seen working in science. Everything changed the summer before heading to medical school, when Steitz worked in Joe Gall's lab, where she was able to conduct her project and discovered her passion for scientific research. As a result, although she had already been accepted into the medical school program, she asked to switch to the biochemistry and molecular biology PhD program. From there on, through hard work, dedication, and passion she ended up heading her own lab at Yale University, thriving in her field of study.

Joan Steitz, PhD

In the late 1970s and early 1980s, along with her student Michael Lerner, at Yale University, Joan developed the work for which she is best known: she discovered the RNA and protein components that make up snRNPs* (pronounced "snurps") and was able to characterize multiple key protein components required for their function. What are snRNPs? snRNPs (small ribonucleoproteins) are early products of DNA transcription that play a crucial role in the splicing process of excising the noncoding RNA regions (introns) of the messenger RNA. These findings about alternative splicing led to a better understanding of how a limited number of genes can produce a diverse range of complex protein products. For her important contributions to the field of molecular biology, Joan Steitz was awarded the Lasker-DeBakey Clinical Medical Research Award in 1986.

Steitz has dedicated a lot of her time to mentoring young female scientists, something she believes is essential to bolster them in the field of science. She is living proof of what women can achieve in current times and encourages them through her successes and accomplishments. To this day, she is an outspoken figure in the fight for equal opportunities in scientific research.

Scientist, mentor, and role model. Joan Steitz has earned multiple awards as recognition of her work in research and mentorship, including the L’Oréal–UNESCO Award for Women in Science in 2001 and the US President’s National Medal of Science in 1986. Formally recognized for the guidance she provided generations of postdoctoral scholars at Yale University, she is a pioneer in science and women’s empowerment and a main figure in society.

"I consider myself a scientist. It's my identity, and identity is important to everyone. It just happens to be mine."

Dean Burnett and the funny findings of the ‘flapping’ brain

Dean Burnett, PhD

‘If the human brain were so simple that we could understand it, we would be so simple that we couldn’t’, says Doctor Dean Burnett, in The Idiot Brain: A Neuroscientist Explains What Your Head is Really Up To. life to trying.

Burnett was born and raised in Wales, having developed a taste for performing and quite the sense of humour during his childhood and teenage years. He went on to graduate from Cardiff University with a Bachelor of Science degree in Neurosciences, and a PhD in the role of the hippocampus in configuration learning though this academic career wasn’t the sole foundation for his accomplishments.

The passion for comedy and writing, which he started to explore in between degrees, would eventually lead him to a regular blog on The Guardian (Brain Flapping) and, from there, to

many articles in several news outlets, interviews, conferences, and a growing list of published books.

As such, he has certainly earned his fair share of titles, as he likes to jest about ‘neuroscientist, lecturer, author, blogger, podcaster, pundit, science communicator, comedian and numerous other things, depending on who’s asking and what they need.’[1]

Even so, his work mostly revolves around science communication, which, put simply, is the act of conveying scientific knowledge and ideas to nonexpert audiences, thus making them accessible and understandable[2]. In a way, this embodies the words of Albert Einstein – ‘If you can't explain it simply, you don't understand it well enough’ - but Burnett takes it a step further, having both the insight and the skills to turn science communication into art.

References: [1] - Burnett D. About Dean. Dean Burnett. https://www.deanburnett.com/about-dean-burnett/. Published 2018. Accessed March 12, 2023. [2] - Cherry B. Libguides: Science Communication: Introduction to science communication. Introduction to science communication - Science Communication - LibGuides at. https://libguides.ncl.ac.uk/ sciencecommunication. Published February 21, 2023. Accessed March 13, 2023. [3] - Burnett D. The Idiot Brain: a Neuroscientist Explains What Your Head Is Really up To. London, London: Guardian books; 2017. [4] - Burnett D. The Happy Brain: The Science of Where Happiness Comes from, and Why. London, London: Guardian Faber; 2018. [5]Fox K. Dean Burnett: 'happiness shouldn't be the default state in the human brain'. The Guardian. https://www.theguardian.com/books/2018/apr/28/dean-burnett-happinessshould-not-default-state-human-brain-the-happy-brain. Published April 28, 2018. Accessed March 12, 2023.

He is amazingly capable of deconstructing complex processes and concepts into bite-sized pieces, and does so with a casual, humorous (and sometimes sarcastic) tone that brings the reader closer, through the doors of the vast and intimidating world of neuroscience. All things considered, it’s no surprise that since 2016 his books have been read by hundreds of thousands of people in over 20 different countries. [1]

In his debut book, The Idiot Brain: A Neuroscientist Explains What Your Head is Really Up To, Dr. Burnett takes the readers on a deep dive into the brain, the key that made humankind a species like no other. On the one hand, our conscience and cognitive functions are seen as the pinnacle of evolution. On the other hand, the brain sometimes falls into faulty behaviours – like when we worry too much to sleep at night, deal badly with emotions, or forget an important meeting. And so, Burnett explores questions about memory, self-confidence, and the general mess that is the human mind, as well as why sometimes its purpose seems to be sabotaging our own lives. [3]

A striking point of this book is that throughout the journey, the author speaks of the brain as if building a character - giving it traits, skills,

convictions, and making it sort of a separate entity. And so, it becomes quite easy to imagine the brain as a little person living inside one’s head, with all its quirks and peculiar habits to guide us through life (and, somehow, that explains a lot).

In his following works, Dr. Burnett addresses themes like the origins of happiness, the meaning of human life [4][5], and the neuroscience behind mental illness and its correlation to the ‘modern lifestyle’ [6][7]. There’s even a book that attempts to explain to teenagers their parents’ reasoning during the typical family arguments of those years [8]. His most recent book, Emotional Ignorance: Lost and Found in the Science of Emotion [9], was derived from Burnett’s own grief after his father’s death. It aims to explore feelings and emotions, delivering insight on how they work and their impact on relationships, routine, and well-being.

There’s no question that Dr. Dean Burnett has widely contributed to unveil the myths and mysteries of neuroscience amongst the general population, and that anyone can learn and benefit from reading his work. Therefore, it is with great excitement that we welcome him as a keynote speaker for AIMS Meeting 2023.

Guardian Faber Publishing; 2021. [7] - Rigby S. Dean Burnett on the Neuroscience of Mental Illness. BBC Science Focus Magazine. https://www.sciencefocus.com/the-human-body/dean-burnett-on-the-neuroscience-of-mental-illness/. Published June 28, 2022. Accessed March 14, 2023. [8] - Burnett D. Why Your Parents Are Driving You up the Wall and What to Do about It. London, London: Puffin; 2019. [9]Burnett D. Emotional Ignorance: Lost and Found in the Science of Emotion. London, London: Guardian Faber Publishing; 2023.

‘The brain apparently thinks logic is a precious resource to be used only sparingly.’

CATARINA RIBEIRO Rohin Francis, MD

Humor can move mountains. (It’s actually love, but I hope this little change makes sense.)

When we tell a story, we always like to add a point and tell it in our own way. And if there's anyone who can do it with humor and, I would say, idiosyncratic irony, it's Rohin Francis.

The stories this cardiologist brings us portray the past of medicine and how it has been that way here – from the first transplant in Jackson, Mississippi (insert Uptown Funk, Bruno Mars) to the importance the breasts had in the evolution of medicine.

Dr. Francis is a Consultant Cardiologist and a Doctoral Researcher at the University College London. His passion for science communication and medical education has crystallized in his YouTube channel Medlife Crisis.

But the forgotten chapters in medical history are not the only thing he is going to tell us about. With his sarcastic way along with what he defines as "bad jokes", Rohin Francis intends to explore current health sensitive themes and clichés, often considered as taboos, defending evidence based medicine, as well as showcasing the shortcomings of modern medicine.

There is no better or worse way to say things, there is only our way. We can touch people more, be more empathetic, use Star Wars characters to make our point. However, we know that the dayto-day communication of a health professional is the "philosopher's stone" for a good relationship with our patients and families.

Using humor can be a weapon (and one of the good ones) in this contact with the other, reducing the anxiety and fear that patients may be feeling.

Humor Can Move Mountains

And that's what Rohin teaches us, even though we don't think so. When he speaks, our attention is immediately caught by his sarcastic jokes, a communication strategy whose main goal is to make us think and question what is being presented to us.

But, moving on to the "necks" (well, next) level:

Talking about medicine on the internet is not always easy, much less when talking about what no one wants to hear about and in the way that pleases people the most. Rohin manages to be controversial while leaving us thinking, especially with his idea of "good death": "A good death should be doctors and patients' last life goal."

We all agree that the internet is an easy place where we can find the answers we are looking for and a place where we communicate. And we all do the same – "Siri, what is this one-sided headache that doesn't go away?" Siri gives the answer. The podcast we listen to while showering gives the answer. Deep down, we know that none of that can be true, but we all google the same.

Despite having his stage on the internet, Rohin is the first to state "please don't get your health info from podcasters". Although it's an easy way to quickly come up with a supposedly false diagnosis, we can't get from it the comfort a doctor would give us.

Yeast is Humankind’s oldest friend

Leland Hartwell, PhD

Throughoutits evolution, the Homo sapiens species has been closely linked to several other forms of life, which we have modified, but also depend on for our own survival. I could be referring to wild animals that have been domesticated, or plants that originated from agriculture. However, the species that shares the strongest connection with us is Saccharomyces cerevisiae. This type of fungus shaped the development of society and culture as we know it, and in recent years has even been the object of remarkable scientific works, as is the case with AIMS 2023’s Nobel Lecturer, Dr. Leland Hartwell.

You may know it as “baker’s yeast”, because its fermentation has allowed us to make bread for millenia. In fact, the first known records of humans using it for this purpose comes from 1300 B.C. in ancient Egypt, while its use for beer brewing and wine-making has been observed in archeological findings in Sumeria and Babylonia from around 6000 BCE. Yeast has been known and used worldwide since approximately 170 BCE. In 1857, Louis Pasteur discovered that this was

the agent responsible for alcoholic fermentation, turning carbohydrates into alcohol and carbon dioxide. Later, were described two forms of yeast cells, with sexual or asexual reproduction, either way undergoing a life cycle of mitosis and growth. Under conditions of stress, haploid asexual cells end up dying, while diploid cells can enter meiosis, a process that results in four haploid spores, each with one set of genes, which can subsequently mate.

According to Dr. Lee Hartwell, yeast “smells good”. But why has it remained so scientifically relevant? This single celled, easily cultured organism has a rapid generation time, doubling its population in 1,5 to 2 hours. Being an eukaryotic cell, the intracellular processes that occur are relatively similar to those that happen in humans, which means yeast could be used as a model organism. It has 16 chromosomes that comprise 6,000 genes, with roughly a third of them having survived with relatively little alteration over the one billion years of evolution that separate humans and yeast.

Lee Hartwell first studied at the California Institute of Technology, soon becoming interested in developing a research career. He then moved to Massachusetts, having received his Ph.D. from MIT in 1964. In 1968, he moved to the University of Washington where he developed a series of genetic and biochemical methods in order to study S. cerevisiae over the following four years. He discovered genes that encode for cyclin and cyclin-dependent kinase, molecules involved in the control of cell division Hartwell found that in response either to nutrients or to a cell that they are going to mate with, when yeast cells receive damage, they stop dividing and repair the damage. This point of arrest prior to DNA replication is what we know as G1, as in “gap”. Similarly, when human cells are not dividing, they may sit in this G1 for years before they get a signal to divide. This control mechanism recognizes damage and prevents it from transmitting it to daughter cells.

Hartwell recognizes he’s always been motivated to better understand certain aspects of cancer. In 1996, he joined the Fred Hutchinson Cancer Research Center in Seattle, Washington, having served as president and director. In 2009, he was a founding member and chief scientist of the Center for Sustainable Health at Arizona State University. Thanks to his breakthrough research, we now know that the genetic instability of cancer cells leads to mutations in the genes that control cell division and allow the transmission of damaged DNA. Tumor cells have small specific genetic mutations that have implications for cancer diagnosis. Targeted therapy for each patient has recently been a reality, improving overall outcomes of cancer therapy. Professor Hartwell’s work in the field of genetics has proven essential to understanding the promotion and regulation of the cell cycle. And to think all of this has been made possible with the same organism used for ancestral production of bread and alcoholic beverages…

A cyclist breaking the vicious cycle of climate change

Diarmid Campbell-Lendrum, PhD

Dr. Diarmid Campbell-Lendrum is a Scottish epidemiologist and public health expert who has worked extensively on the health impacts of climate change. He is currently the Head for the Climate Change and Health Unit at the World Health Organization (WHO), where he leads a team of experts in researching and advising on the health risks and opportunities associated with climate change.

For the past 20 years, he has contributed significantly to the field of Climate Change and Health, specifically focusing on the impacts of climate change on infectious diseases, food and water security, and also investigating the health impacts of extreme weather events such as

heatwaves, floods, and droughts. One of his goals is to try to make quantitative estimates about how much global health suffers from the impact of climate change. He has also attempted to tackle health inequalities and has been involved in researching the health benefits of low-carbon emissions and sustainable energy development strategies.

Dr. Campbell-Lendrum has worked on several global health initiatives and research projects, including the Global Burden of Disease project and the Intergovernmental Panel on Climate Change (IPCC). In addition, he worked at the London School of Hygiene and Tropical Medicine, where he led research projects on climate change

and health in low and middle-income countries. Moreover, he has worked for the UK Department of Health and the UK Health Protection Agency, and has advised a range of international organizations on climate change and health issues. He has also been involved in developing and implementing public health interventions to address climate change-related health risks.

Dr. Diarmid is the author of approximately 100 peer-reviewed journal papers, reports and book chapters on the topic of climate change and health, being a lead author not only on 3 IPCC reports, but also on the first health report to the United Nations Climate Negotiations. He is widely recognized as an expert in this field, having received awards for his work for the outstanding contributions in the field of public health.

Diarmid has been an agent of change playing a key role in raising awareness of the health risks and opportunities associated with climate change at the global level . By making use of his passion for cycling, he rode his bike from Geneva to Paris for WHO’s 2nd Global Conference on Health and Climate Change in 2016 and, 5 years later he rode from Geneva to London to hand over the “2021 COP26 Special Report – The Health Argument for Climate Action” to a group of pediatricians cycling to Glasgow.

His “stubborn optimism despite all evidence” is what always gives him the fuel to do what he does, and hopefully there will always be great people that can keep fighting, that can keep working to make others people see that the future is now, that there is no Planet B, and so we must can act to protect what we care the most about - our Home.

Living in Extremes – An Outlook on Human Adaptivity Living in Extremes – An Outlook on Human Adaptivity

Cara Ocobock, PhD

Despite her debut in the field of Cellular, Molecular, and Developmental Biology in the University of Michigan, Dr. Ocobock, Director of the Human Energetics Laboratory at the University of Notre Dame, Indiana, has since shifted her focus towards Life on a more macroscopic scale – and particularly, towards the human species.

Combining her background in Anthropology with her enthusiasm for powerlifting and outdoor sports [1], Ocobock has taken part in numerous studies exploring the physiological and behavioral mechanisms underlying biological adaptation to extreme climates and how these factors could affect physical activity. One of her current projects with collaborators at the University of Missouri and the University of North Texas seeks to gauge the physiological correlation between cold adaptations’ specific anatomical indicators and the advantages extinct cold- climate populations such as the Neanderthals may have had in comparison to modern humans [1].

Ocobock’s love for Humanity goes far beyond organic matter, biochemical reactions, and Darwinian evolution. Through her work, she has encountered many different people across the world, from runners in a cross-country race to reindeer herders in Northern Finland [2]. The latter are currently the protagonists of Ocobock’s work in collaboration with researchers from the University of Lapland and University of Oulu.

Reindeer herders in the Arctic Circle are a highly active population inhabiting extreme environments subject to a cold, rigorous climate. By studying their life ways, habits, and traditions through a multidisciplinary lens, Ocobock and her research team expect to gain anthropological and biological context regarding how these cold climate populations evolved to adapt to their harsh surroundings.

Chief among these adaptations could be the very expansion of the average lifespan in such individuals. Although reindeer commerce management has been linked to an increased risk of fatal occupational accidents [3], intrinsic factors related to health indicators in these populations have consistently shown a promising outlook on human health improvement.

One such factor is the prevalence of brown adipose tissue (BAT) in the body composition of reindeer herders. This uniquely mammalian tissue is particularly relevant for neonatal body temperature maintenance, favoring heat production by combusting triglycerides in mitochondria-rich brown adipocytes. This process occurs due to the presence of uncoupling protein 1 (UCP-1) in the inner mitochondrial membrane, which transports hydrogen ions across the membrane to dissipate the proton gradient generated during organic substrate oxidation [4].

IN EXTREMES – AN OUTLOOK ON HUMAN ADAPTIVITY

BAT ubiquity upon birth is progressively lessened throughout natural development as the human body adjusts to its surroundings by accumulating increasing amounts of white adipose tissue (WAT), which is critical for energy storage in the form of lipids, endocrine communication, and insulin sensitivity [5]. Nonetheless, overexpressed WAT in the body leads to serious health complications and harbors life-threatening risks, interfering with regular metabolism and promoting cardiovascular diseases, chronic inflammation, type 2 diabetes, and even some types of cancer. [6]

By understanding how evolution has favored the lifelong permanence of a considerable BAT percentage in reindeer herders’ bodies, we could be looking at a breakthrough in the management of the obesity crisis currently afflicting billions of people worldwide.

In fact, according to estimates in the fifth World Obesity Atlas published by the World Obesity Federation on March 2023, on current trends, overweight and obesity will cost the global economy over US$4 trillion of potential income in 2035, nearly 3% of current global gross domestic product (GDP) [7]. The enormous costs on global healthcare systems attributed to cardiovascular disease or type 2 diabetes have obesity jostling with armed conflict as one of

pact on the global economy [8]. Therefore, it’s no surprise that Ocobock’s work has earned the interest and funding of the National Science Foundation and the American-Scandinavian Foundation [1], among other entities invested in bringing human biology research closer to the heart of current global healthcare concerns.

This emergency proves especially dire following a period marked by extensive restrictions and lockdowns in most countries in the wake of the COVID-19 pandemic. Although well-rounded studies are still lacking given the recent nature of these issues, it is known that the curtailment of movements outside the home exacerbated dietary and sedentary behaviors linked to weight gain while concomitantly reducing access to primary healthcare. The consensus is that a side-effect of managing the COVID-19 pandemic has been the worsening of the obesity epidemic, especially among children [7].

Cara Ocobock’s research is widely recognized as one of the most promising anthropological outlooks on human adaptivity to extreme climates and how those adaptations could lead to more robust healthy lifestyles. We are pleased to welcome her to the AIMS Meeting 2023 and hear her thoughts on these matters – and many more –in her own words.

[3] Sjölander, P. (2011, October 14). What is known about the health and living conditions of the indigenous people of northern Scandinavia, the Sami? National Library of Medicine (US), National Center for Biotechnology Information. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195409/ [4] Brown Adipose Tissue - an overview. ScienceDirect Topics. Available from: https://www.sciencedirect.com/topics/neuroscience/brown-adipose-tissue [5] Richard, A.J.; White, U.; Elks, C.M.; Stephens, J.M. (2020, April 4). Adipose Tissue: Physiology to Metabolic Dysfunction. National Library of Medicine (US), National Center for Biotechnology Information. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555602/ [6] Chait A and den Hartigh LJ (2020) Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front. Cardiovasc. Med. 7:22. https://doi.org/10.3389/fcvm.2020.00022 [7] World Obesity Federation, World Obesity Atlas 2023. https://data.worldobesity.org/publications/?cat=19 [8] Dobbs, R, & Manyika; (2015, July

obesity

McKinsey Global Institute. Available from: https://www. mckinsey.com/mgi/overview/in-the-news/the-obesity-crisis

5). The

crisis.

“WE’RE ONLY HUMAN”: ODE TO IMPERFECTION

Nathan H. Lents, PhD

When studying the human body, one can only stand in amazement. Countless people spend their lives studying it, writing Odes to the constellations you see in wonder when gazing at the human eye; the whisper of a longing sea in the chest; the musical rhythm of a pounding heart; the delicate architecture of arteries; the art in the paradox of the arms, between strength and delicacy.

However, Nathan Lents didn’t write an Ode to the human body. Or maybe he did, since its shortcomings are, even though, as you’ll see, not “short” at all, what, in fact, makes us human. Every cell, protein, molecule, and little letter in the genome has its own story to tell. Professor Nathan Lents is a scientist and author, who sits beside them, listens to their stories, and writes about them, shedding new light over the human body as a whole and in its nuances

All of time and all of natural selection have shaped our bodies like an old and bearded craftsman molds a block of clay into a masterpiece. The human body is strong, resilient, and clever (sometimes, anyways). We are indeed the best Evolution could master. But we soundly lack perfection, and Professor Nathan challenges the naïve thought that we are perfect.

Every Biology teacher mentions Evolution in the past tense, as if we were done evolving because we reached our perfect present shape. However, this is senseless to the fact that we are very flawed, and that Evolution is an ongoing and never stopping process.

I find it funny that we use the expression “I’m only human” as an excuse to fail, since I don’t think we fail because we are human. Instead, I believe we are human because we fail.

You are probably reading this without thinking that you are doing so with a retina that is so imperfect that is facing backwards instead of the logical forwards. You are reading this while ignoring the fact that the feet you’re standing on have way too many little pointless bones. Without thinking that your Recurrent Laryngeal Nerve takes an unnecessary loop and is three times longer than it should. That we are not quite adapted to upright walking, even though we have done it for millions of years, making intervertebral disks prone to herniating; knee ligaments like the ACL prone to tearing; and mesenteries prone to rupturing if you stand for too long. That our immune system sometimes attacks our own body when mistaking a peanut for a very dangerous pathogen; and that autoimmune diseases

like Myasthenia Gravis, Lupus and Grave’s are a very cosa nostra, absent in any other species. That sinusitis and gastroenteritis are also a very human ailment, which aren’t (luckily for them) as common in any other species. That vegetarians get shortages of Vitamin B12 despite our gut bacteria producing it, because these bacteria are in the colon, while this Vitamin is absorbed in our small intestine.

Clearly, we are flawed creatures, since we are a product of an Evolution that works by the survival of the fittest, not of the perfect;

Natural Selection gave us so much, like our intricate brains capable of both creating String Theory and composing a masterpiece like Toxic, by Britney Spears. In turn, in a sense, we betrayed Evolution. We didn’t allow the Hourglass to correct the flaws in our Anatomy and Physiology: we corrected them ourselves. Or, rather, found ways to make those errors pointless, and save people with them regardless.

Was committing forever to this flawed design and creating drugs and surgeries to correct it a fair trade for our species? The

BEATING ALL ODDS

IMPOSSIBLE DISEASES

Rare but Real: Shining a light on rare diseases

Perhapsrarer than the diseases you will often see referred to in the footnotes of medical textbooks or the conclusion of lectures, is an understanding or proper discourse around these conditions. Such is what Dr. Lucy McKay - Bachelor of Medicine, and Science in Human Genetics - has dedicated her professional career to remedy. As CEO and founder of the non-profit Medics4RareDiseases (M4RD), she is dedicated to changing the attitude towards rare diseases amongst medical students and doctors in training to improve the patient odyssey.

For McKay, rare diseases were a topic of interest long before she attended any university lecture, having lost a brother to mucopolysaccharidoses (MPS) - a lysosomal storage disorder with a prevalence of roughly 1 in 25,000 [1] - before she had even been born. Through the subsequent MPS Society her mother founded, she had frequent contact with people afflicted with this disease, from early on seeing the humans behind the affliction.

While in medical school, she recalls being puzzled by the teaching of rare diseases, remembering knowing more than her lecturer when MPS was brought up. She believes the attitude towards the education of these

conditions to be outdated and based on fallacious grounds. Such pleonasms as “common things are common” or “if you hear hooves, think horse not zebra” might be true when thinking about the global population but grossly reductive when considering which portion will frequent the clinician. The medical professional will always see a higher number of sick people than the normal person, and if they see more diseases, they will see more rare diseases as well. On top of that, despite being seemingly counterintuitive, these conditions are cumulatively common, affecting nearly 4% of the population [2] with 70% of these being in children [3].

Lucy

McKay, MD

“WITH OVER 7000 UNIQUE RARE DISEASES, LEARNING EACH INDIVIDUALLY WOULD BE UNFEASIBLE“

With these numbers, it is troubling to think that most general practitioners feel inadequately trained to take care [4] of these patients and are actively interested in training to improve their care. To help supply this dearth in the medical formation, M4RD made the online course Rare Disease 101. Easily accessible and free on their website, this 8 lesson module covers what a rare disease is, how to suspect a rare disease, the challenges of the patients who suffer with these conditions and how to support them. McKay hopes this multiplatform collaborative effort will be a proof of concept so a more elaborate approach on rare diseases may be eventually integrated into medical curricula.

As a second-generation rare disease advocate and practising clinician, McKay sees the teaching of rare diseases as too selective of a few conditions and molecular mechanics and not enough on the patient’s point of view. The literature supports this sentiment, showing that not only is patient perspective and

cooperation key in bringing funding and meaning to the work of clinicians and researchers [5], but that databases such as the Undiagnosed Disease Network and the Rare Diseases Registry are extremely useful to an evidence-based personalised approach to these cases [6] .

Despite the many strides in rare diseases since the insurgence of M4RD and other rare disease organizations, much work is still left to be done. McKay says her organisation won’t be truly successful until it no longer needs to exist, and though that may be a ways away, we can commend the efforts that have brought us this far. Conversations which weren’t even considered a decade ago are now held on every level of our practice. For that, both doctors and patients alike can be grateful of her proposal to dare to think rare.

" However, there are vast commonalities between these conditions and the impacts they have on patients. Treating rare disease as an ‘umbrella term’, for education, highlights the similarities and shared factors that rare disease patients experience and helps address a current gap in medical education. ”

Dr. Ari Zimran is a specialist in Internal Medicine, as well as an Associate Professor at the Hadassah School of Medicine, Hebrew University of Jerusalem. Beside this, he works at Shaare Zedek Medical Center in Jerusalem.

It was there that he founded the Gaucher’s Disease Unit, which he directed himself from 1989 to 2018. He is now a senior physician in this unit, which is nothing less than the leading outpatient clinic for people with this rare disease in Israel, as well as the largest referral centre for Gaucher’s disease worldwide, having monitored around 900 patients in its 30 years of existence.

Professor Zimran has also been involved in clinical trials for treatments for this illness, published several hundreds of papers and edited three books on this subject. [1]

He has therefore dedicated his whole life to the treatment and studying of Gaucher’s disease. But what does this rare lysosomal storage disease consist of?

People with Gaucher’s disease have a genetic mutation which causes them to have lower activity levels of a lysosomal enzyme called glucocerebrosidase, which is responsible for breaking down glucocerebroside (a glycolipid present

Ari Zimran, MD

in our cell membranes) into glucose and ceramide. This means that glucocerebroside accumulates in these people’s cells, specifically in their macrophages (since these are heavily involved in phagocytosis and digestion of multiple cell types), causing them to increase in size and lipidic components – they become Gaucher cells. [2]

These bloated cells predominantly infiltrate the bone marrow, the spleen, and the liver. The accumulation of glucocerebroside has metabolic implications as well. All of this leads to symptoms such as: hepatosplenomegaly, bone pain and fragile bones, anaemia and fatigue and inefficient coagulation. Neurological impairment may also be present in more severe types of the disease. [2]

Gaucher’s disease is an autosomal recessive genetic disorder. [2] This means that, for someone to have this disease, that person must inherit two mutated copies (one from each parent) of the GBA1 gene, the gene which encodes glucocerebrosidase. More than 300 different mutations in this gene have been described, and generally they prevent the enzyme from folding properly, therefore preventing it from working adequately.

Dr. Ari Zimran - A lifetime dedicated to a single-molecule disease

There are two types of treatment for this condition [2]:

1) Enzyme Replacement Therapy (ERT), with administration of recombinant glucocerebrosidase (such as Cerezyme®, Vpriv® and Elelyso®, all of which Dr. Zimran helped test in clinical trials), which allows for the breakdown of glucocerebroside.

2) Substrate Reduction Therapy (SRT), that aims to reduce the amount of glucocerebroside in the cells through the administration of substances which inhibit enzymes necessary to the production of glucocerebroside (such as Zavesca® and Cerdelga®, also tested by Dr. Zimran).

More recently, Professor Zimran has been investigating the connection between GBA1 mutations and Parkinson’s disease: patients with Gaucher’s disease, as well as carriers of GBA1 mutations, have been found to be predisposed to developing Parkinson’s disease.

The loss of function of the enzyme glucocerebrosidase compromises lysosomal degradation of α-synuclein, a protein which regulates synaptic vesicle trafficking and, therefore, involved in the control of neurotransmitter release. The accumulation of aberrant, soluble forms of this protein creates a neurotoxic environment [3]; this is aggravated by Gaucher’s disease, since

glucocerebroside possesses the ability to stabilize these soluble oligomers, further potentiating the formation of amyloids and Lewy bodies and so, the progression of Parkinson’s disease. Moreover, these α-synuclein oligomers have the power to inhibit glucocerebrosidase, therefore creating a vicious cycle of progression of both Gaucher’s disease and Parkinson’s disease. [2]

Professor Zimran is also investigating the use of ambroxol (a drug which was initially used as a mucolytic) in patients with Gaucher’s disease. It is thought that it can be a pharmacological chaperone for this ailment (chaperone therapy consists of the administration of small molecule

compounds which can specifically bind to misfolded glucocerebrosidase and help it fold correctly, allowing it to function normally) [4]. In a paper from May 2021, Professor Zimran and the other authors present some rather promising results, with clinical improvement observed in 25 patients.[5]

Other of Dr. Zimran’s areas of interest are the development of oral enzyme replacement therapy and gene therapy for Gaucher’s Disease.

Professor Zimran has a truly outstanding career, filled with accomplishments, and therefore it will undoubtedly be a privilege to attend his lecture and be able to experience his knowledge first-hand.

AMANDA BROWN, THE COMPASSION DOCTOR

Amanda Brown, MD

“Icryalotandit’sembarrassing,butthedayIlose mycompassionisthedayIstopworking”[1]

That said, it is difficult and even unfair to write a summary paragraph about such a woman. Nevertheless, Amanda Brown is currently a general practitioner (GP) at the largest womenonly prison in Europe, His Majesty Prison Bronzefield (HMP Bronzefield) and the author of The Prison Doctor, the three-volumes book about her prison memoirs and her own journey as she morphs from a GP in a quiet, comfortable patch of England, her homeland, into a passionate advocate on behalf of prisoners.

Amanda’s father was also a GP. Having grown up watching her father’s devotion to his patients, the little girl always wanted to follow in his footsteps - and that became a reality. She was a regular National Health Service (NHS) GP for twenty years, until she gave up her practice because of a deep sense of dissatisfaction and disillusionment following a new GP contract that would force her to change her consultation style for bonus pay. Therefore she found no other option than to resign her job.

“Iwasnearly50,thatwasmypension,Ihadtwo kids and a mortgage, but it was my ‘sliding doors’ moment.” [1]

Amanda wrote a blistering piece for Pulse — the GP magazine – to show her displeasure with the erratic health policy-making at the time and it was as a result of the article that she was headhunted by a doctor looking to recruit for the prison service.

“I was intrigued because, as naive as it sounds, I never even considered that prisons had their own doctors.’” [2]

Amanda’s first step in her second career was in HMP Huntercombe, then a male prison for juveniles aged 15 to-18 – curiously her sons’ age at the time. Later, she worked at one of the oldest and most notorious prisons in the United Kingdom, HMP Wormwood Scrubs, as well as the already mentioned women’s prison, HMP Bronzefield, where she continues to work to this day.

Dr. Brown partook in the exhilaration and chaotic nature of prison life, while trying her utmost to make a positive difference and leave a lasting impact on the lives of those that society had turned its back on.

“They'vecommittedcrimesbuttheystillneedtobe caredfor”- so Amanda said in an interview with Sky News.

Dr. Brown recognises that these people with chaotic lives and too little experience of unconditional love, affection and recognition can also be brave, kind and funny. Amanda considers it part of her mission to bring such impressive stories to the light and that’s how she became the author of The Prison Doctor bestsellers.

These are books brimming with empathy, compassion and commitment. Books that might transport the reader into an unfamiliar yet deeply human world and reveal Dr. Brown’s audacity and strong-will, an unwavering drive to help others that sustained her through the transition

from a typical community GP to a violence-filled, adrenaline-pumping job.

Throughout the books the reader understands that compassion, solidarity and the capacity of being a good listener are imperative tools to live in society and, specifically, to be a better health agent.

With Amanda’s life and books we become aware of how much courage is needed to transform guilt, shame and self-doubt into pride, empathy and strength. As such, Dr. Brown’s generosity and kindness is what this years’ AIMS Meeting has the honour to host.

References:

[1] Available from: https://www.theguardian.com/lifeandstyle/2019/jun/08/prison-doctor-amandabrown-compassion-medicine

[2] Available from: https://www.dailymail.co.uk/femail/article-7172755/How-did-middle-class-

A different kind of medical professional

Christof Neuner, MD

Have you ever thought about what to do after finishing your degree? Do you want to be a doctor in a hospital and deal with the everyday life of all its surgeries and appointments? Do you know that there are different ways in which you can help people as a doctor without being in a hospital or clinic?

The truth is that, nowadays, people seek new challenges and opportunities in order to broaden their horizons and get away from the “normal life” everyone expects they will have. Just by watching the news, one can acknowledge how important and even essential it is to have medical professionals in the most diverse environments, whether it is in war zones or countries affected by natural disasters, among others.

However, to be able to give such specialized help to the ones in need, a doctor needs to acquire knowledge and experience in these specific scenarios, as they are very different from the reality one lives in a hospital. Therefore, it is important to not only be informed about the opportunities available but also to seek training in these specific areas.

All around the world, armed conflicts are constantly happening and lives are being taken away indiscriminately, at the same time that Human Rights and the International Humanitarian Law are being violated.

Whether it is in Ukraine, Afghanistan or Syria, people are going through hard times and need the help of others to overcome this difficult and rather unfair situation.

in a lab without any distractions, there are no emotional and motivational major factors going on and they perform similarly to adults: they take approximately the same number of risks. However, when they are given some motivational context, such as a couple of friends standing behind them, there is an increase in risk behaviors adopted by adolescents.

But why are adolescents particularly susceptible to peer influence? Studies suggest that they might be hypersensitive to being socially excluded. This, when considered in the context of decision making, sheds risk taking in a more rational light.

People in groups behave differently than on their own, so, having someone else overseeing them changes their behavior on cognitive tasks. Professor’s lab research suggests that, in adolescence, social influence is particularly heightened.

The question is: do wars have laws? Yes, they do. The 1949 Geneva Conventions established the main treaties of Humanitarian Law after the devastating Human Rights violation during the Second World War. Although these

Conventions exist, unfortunately, these violations are still taking place in most war zones and having Non-governmental Organizations as well as trained people to help the ones in danger is crucial. This matter is of such importance because lots of people are affected by it, as Amnesty International estimates that around 89.2 million people were forcibly displaced by the end of 2021 due to conflict, violence, persecution and human rights violation.

Beyond helping the wounded with our medical knowledge, we, as medical students and future healthcare workers, can also have a positive impact in these scenarios by trying to empathize with them, understanding their problems and reporting war crimes that we witness.

At the AIMS Meeting 2023, we will have the pleasure to have an amazing lecture regarding this theme led by Doctor Cristof Neuner who took his medical degree in Freie Universität Berlin and had clinical training in general and trauma surgery. Dr. Neuner is now a Senior Consultant General and Trauma Surgery and Commander (on Reserve) of the German Navy Maritime Special Forces. By listening to his talking about his personal experience in this area, you will have a broader view about this theme and be more informed about it. And who knows, maybe you’ll be joining the Navy in the future! It is certainly a lecture you don’t want to miss!

"Amnesty International estimates that around 89.2 million people were forcibly displaced by the end of 2021 due to conflict, violence, persecution and human rights violation."

The stealth education

Daniel Grant, MD

“How to be healthy without knowing it?

As students of health and science, we are taught to look at our patients from a very direct and objective standpoint, learning as much as we can in order to be able to fix the body, cure diseases and further manage patients and their families. But what about all the things we can do without even realizing that, at the same time, improve our health?

This is what Stealth Medicine is all about. It’s based on 6 fundamental concepts: light , not just in its physical sense, but in the way it affects our mood, cognition and wellbeing; sound , from the way it can both makes us fall asleep or drive us insane, to the way it molds our brains since long before

have the power to affect our overall health; and finally, the you and me , pertaining to the way we, as social creatures, affect the health of others, and also the way our own self-image influences our overall wellbeing.

As a means to spread the word on the Stealth Medicine approach to health, Dr. Daniel Grant created The Stealth Doctor output. He shares his word across multiple platforms, aiming to educate and enlighten everyone about all the ways that we could be healthy without explicitly working towards it, but at the same time doing things that perhaps we never imagined would have such a positive impact on ourselves.

(a talent that would later contribute to his success in becoming a NHS Clinical Entrepreneur). In medicine, though, he is an MD, having started his career as an Extreme Environment Physiologist and Advance Immunologist.

Daniel fell in love with space at a very young age, and he received the news that he could study it as a part of his degree with delight. His love and interest for the impact of extreme environments on the human body later led him into Space Medicine. Daniel’s increased involvement in Space Medicine led him to take a course in Principles of Aviation and Space Medicine at The University of Texas, where his knowledge in physiology expanded as he understood more about the way this environment influences our body.

Astronauts are a microcosm of preventative medicine - you have to make sure they’re healthy enough to travel, and then keep them healthy while they’re up there. You can do this by manipulating their environment to ensure they stay fit and well. Decades of working with astronauts has now informed our understanding of bone and muscle development, balance, blood pressure, circadian rhythms and so much more.

Through all these passions - across science and art, he now wants to focus on helping people stay well - especially through environment, culture, and also by using the growing medtech phenomenon to help people. Utilizing skills learned from all areas, he now talks about health through Stealth. Dan has been to NASA, shaken hands with astronauts and given lectures in Space Medicine. In fact, it was from his passion for space medicine that the initial idea for stealth health came to light. It’s fair to say that the ideas behind Stealth Health were born in Space.

It goes without saying that space exploration has allowed us to understand our solar system, our planet, energy, weather and the very roots of our existence more than ever before. But did you know we’ve also learnt loads about the human body and medicine?

He is The Stealth Doctor.

References:

1. http://www.case-medicine.co.uk/Dr-Daniel-Grant

2. https://thestealthdoctor.com

3. https://www.youtube.com/@TheStealthDoctor/videos

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APR. 2023