Tag: 6/9/24

Meet Kamogelo – The Teen with the Can-do Attitude

Spinal cord injury survivor is a capable and helpful big brother

Kamogelo Sodi, who was injured in a car crash when he was just six years old, says he learned valuable skills on how to regain his independence at the Netcare Rehabilitation Hospital. The teenager enjoys cooking for himself, taking care of his three younger brothers, and playing basketball when he’s not studying hard to achieve his dream of being a medical practitioner one day.

5 September 2024: At 14 years old, Kamogelo Sodi of Alberton enjoys listening to music, chatting with his friends on social media and working hard at school towards his dream of becoming a neurosurgeon one day. He cooks for himself when he’s hungry and loves looking after his three little brothers. He also likes playing basketball. The difference between him and most other teenagers is that he does all this from his wheelchair.

“Since I’ve been in a wheelchair, I’ve become more confident,” says the vivacious teenager. “I was extremely shy, and I didn’t have a lot of friends, but now I have loads of friends.”

In 2016, when he was just six years old, Kamogelo’s life changed forever. He was in a devastating car crash, which left him with fractures in the lumbar region of his spine, resulting in complete paraplegia.

Once discharged from the hospital, where he had emergency surgery, Kamogelo was sent to the Netcare Rehabilitation Hospital to learn how to cope with, as his mother Reshoketswe Sodi calls it, his new normal. He was to stay there for almost six months.

Mrs Sodi, a radiation therapist, says the enduring care of the doctors, occupational therapists and physiotherapists there helped support Kamogelo and their family on their journey towards accepting and learning to cope with this difficult transition in his life. “It was important for me that he continued his schoolwork while there. When the social worker asked me what I wanted to happen, the first thing I said was that I didn’t want to break the routine of what he had been doing and that I wanted him to continue with school.

“It’s been a struggle, but with the help of the occupational therapists and physiotherapists, it has been an easier journey. We saw real progress when they taught Kamogelo something, and he grasped it, putting all his energy into it by thinking positively about it. It’s been hard, but with the support of the team from Netcare Rehabilitation Hospital, we managed it,” she says.

“After he was discharged, initially, we lived in a flat on the seventh floor. When the lifts weren’t working, like during load shedding, I’d have to carry him upstairs on my back – there was no other way to take him up. I’m so fortunate that I had a lot of support from my family and friends who’ve been pillars of strength for us.”

Kamogelo remembers his first visit to the Netcare Rehabilitation Hospital in Auckland Park. “When I first got to the hospital, I was lost. I didn’t know how to use a wheelchair. I was still so young. But they were so kind and taught me everything I needed to know. 

“At first, I struggled to move around. I battled to transfer myself from place to place, but they showed me what to do, and over time, I started getting used to it. I managed to start moving myself around, and I began to enjoy it. From that day forward, I didn’t like people pushing me around. The staff also taught me how to transfer myself from my wheelchair to the car. It was a bit difficult at first, but I learned to push myself up properly so my bottom wouldn’t scrape on the wheelchair.

“It does help you become more independent, but you must be consistent. You don’t need to complain about things,  you just need to listen to the people who want to help you learn to be independent.”

Later, in 2022, when he was 12 years old, Kamogelo returned to the Netcare Rehabilitation Hospital after he developed a severe pressure sore.

Dr Anrie Carstens, a doctor at the Netcare Rehabilitation Hospital, said Kamogelo was operated on at Netcare Milpark Hospital under the care of a plastic surgeon who did a flap to close the wound. “When the doctor was happy with his progress, Kamogelo came to us to help him because you get weak after surgery. The wound had healed, but the skin was delicate, so we had a graded seating approach for him to build up his strength and so that the areas of the skin didn’t break down. Another area of focus for Kamogelo was spasticity at the ankles. We worked on relaxing the ankles to get to a ninety-degree angle so he could sit better in his chair with his feet positioned well in the footrest.”

When homesickness inevitably struck, the staff comforted Kamogelo. “I began to miss home, and I cried and said I wanted to go home. They spoke nicely to me and said they first had to help me so I could go back home with no problems so my parents wouldn’t have to worry about me because of the pressure sore.”

Kamogelo said the staff also taught him valuable techniques to help him empty his bladder and bowels and assisted him in his journey to independence. “I was worried it would be painful and was a bit hesitant to try them out. But, doing it daily helped my routine and helped me become independent.”

Charne Cox, a physiotherapist at Netcare Rehabilitation Hospital, describes Kamogelo as bubbly, intelligent and with lovely manners. “He’s so motivated and tried so hard in therapy. He manages to go to school each day, not because of us, but because of his character.”

She says as children grow, their needs change. “The pressure sore developed because his seating in his wheelchair was not adequate because he had grown so much. We collaborated with the wheelchair manufacturer to re-evaluate and reassess the wheelchair seating, and they made him a new wheelchair. He was getting heavier, and his feet weren’t in alignment, so it was trickier for him to safely transfer from the wheelchair to the bed, for instance. It was good to re-educate him on pressure relief and pressure sores. It’s vital that adolescents are taught to take responsibility for themselves.”

Cox also helped Kamogelo work towards getting his feet in a better position.

“Children are so good about learning to use a wheelchair. Kamogelo was so motivated to move and be independent. He absorbed the information we gave him to enable him to go up ramps, turn and even do wheelies because he liked to explore.

“Children want to learn and have fun. They want to be independent. It’s amazing to help give them the tools to be the best new person they can be. Unfortunately, sometimes we can’t fix the injury, but we can give them the best opportunity to be as independent as possible. It’s so satisfying to know that Kamogelo is going to school and playing basketball.”

Kamogelo is determined to pursue a career as a neurosurgeon. “As long as I follow the path that I want to do and enjoy it, I will continue pursuing that path.  Academically, I was the top achiever from grade four to grade six at my school.”

When he’s not at school, he loves going around the estate he lives in, getting fresh air, and being a good big brother to his three younger brothers. “They’re a handful, but what can I say – they’re my brothers, and I love them,” he says with a laugh.

Asked who his hero is, Kamogelo is quick to say his mother and father are both his heroes. His mom clearly thinks he’s a hero too. She’s smiling as she speaks about her son. “He’s playful and has a great sense of humour. He’s helpful in the house. Instead of wanting us to help him, thanks to the skills he learned at Netcare Rehabilitation Hospital, Kamogelo always says, ‘Let me give you a hand. Let me help you.’”

Older Women more Vulnerable to Heat than Men, Researchers Find

Photo by Loren Joseph on Unsplash

As global climate change causes extreme heat waves to become more common around the world, epidemiological studies have shown that heat kills more women than men. Now, a new study by researchers at Penn State has found that older women are physiologically more vulnerable to high heat and humidity than older men, and that women between the ages of 40 and 64 are as vulnerable as men 65 years of age or older. This is the first study to determine this disparity exists due to physiological differences rather than from a preponderance of women at old age due to greater longevity.

Led by Olivia Leach, doctoral candidate in kinesiology at Penn State, and her adviser, W. Larry Kenney, professor of physiology and kinesiology at Penn State, the researchers demonstrated that middle-aged and older women were affected by heat at lower temperature/humidity combinations than middle-aged and older men. The results, published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, were somewhat unexpected, according to Leach, because there are no differences in heat vulnerability based on biological sex in adults younger than 30.

While the researchers did not directly compare middle-aged men to middle-aged women, the physiological responses of middle-aged women were similar to the responses of older men in the study, which demonstrated that middle-aged women are more vulnerable to heat than men of the same age.

“In addition to demonstrating that middle-aged and older women are at greater risk from extreme heat, we also identified what levels of heat and humidity are safe for women as they age,” Leach said. “This information is presented as a temperature/humidity curve based on a person’s age, and it can be useful for setting policies designed to keep people safe during a heat wave.”

The researchers tested the heat thresholds of 72 participants between 40 and 92 years of age in a specialized environmental chamber in Kenney’s laboratory. Before the experiment, participants swallowed a tiny device encased in a capsule that measured their core temperature throughout the experiment.

During the study, participants entered the specialised environmental chamber where they performed light physical activity to simulate the effort of minimal day-to-day tasks – the types of things people would need to do even during a heat wave. The researchers then gradually increased the temperature and/or humidity in the chamber until the participant’s body could no longer adequately cool itself, and their core temperature began to rise.

The study is part of the PSU HEAT, or Human Environmental Age Thresholds, project, led by Kenney. For five years, researchers in the PSU HEAT project have examined the levels of combined heat and humidity that humans can tolerate before their core temperatures begin to rise. When core temperatures rise, people become vulnerable to heat-related illnesses including heat exhaustion, heat stroke and even death.

“We’re not saying that people who experience a certain temperature will necessarily become sick or die,” Kenney said. “We are identifying the limits of livability – the thresholds where people can no longer continue their daily life unimpeded. Once people reach these temperatures, they need to take actions like seeking air conditioning to cool their bodies.”

Previous research by Kenney and others demonstrated that people become increasingly vulnerable to heat as they age, because their ability to efficiently sweat and pump blood to the skin – two primary cooling mechanisms – decreases. Sweat evaporation carries heat away from the body, while extra blood pumped to the skin dissipates heat to the environment and supports sweating.

To date, the PSU HEAT project has conducted more than 600 experiments on nearly 200 participants between ages 18 and 92, but the results of this experiment still yielded surprises, according to Leach.

“Among young adults, there is no difference in heat vulnerability between men and women,” Leach said. “Young people tend to be healthier, so any measurable health metric – from blood pressure to cholesterol – is more homogeneous among young people than it is among older people.”

As with other health measures, older adults have a wide range in their vulnerability to heat, Leach explained.

“We have examined many factors that might explain who faces the most risk in a heat wave,” Leach said. “We found that age and biological sex are the two most important factors that can predict whether a healthy adult would be at risk from high heat and humidity.”

While cardiovascular health and certain medications can affect a person’s sensitivity to heat, biological sex and age appear to be the two primary drivers of heat vulnerability among healthy people, the researchers said.

“Other factors – for example someone’s cardiovascular fitness or their body mass – have little impact on how vulnerable a person is to heat at rest or during light activity,” Leach continued. “Older women really are at greater risk from heat than other people. As governments and other social leaders prepare for extreme heat to become more common, the vulnerability of older women needs to factor into their planning.”

Source: Penn State

Scientists Figure out Paradoxical Effect of Testosterone in Prostate Cancer

Ball and stick 3D model of testosterone. Source: Wikimedia CC0

A treatment paradox has recently come to light in prostate cancer: Blocking testosterone production halts tumour growth in early disease, while elevating the hormone can delay disease progression in patients whose disease has advanced.

The inability to understand how different levels of the same hormone can drive different effects in prostate tumours has been an impediment to the development of new therapeutics that exploit this biology.

Now, a Duke Cancer Institute-led study appearing in Nature Communications, provides the needed answers to this puzzle.

The researchers found that prostate cancer cells are hardwired with a system that allows them to proliferate when the levels of testosterone are very low. But when hormone levels are elevated to resemble those present in the normal prostate, the cancer cells differentiate.

“For decades, the goal of endocrine therapy in prostate cancer has been to achieve absolute inhibition of androgen receptor function, the protein that senses testosterone levels,” said lead investigator Rachid Safi, PhD, research assistant professor in the Department of Pharmacology and Cancer Biology, at Duke University School of Medicine.

“It’s been a highly effective strategy, leading to substantial improvements in overall survival,” he said. “Unfortunately, most patients with advanced, metastatic disease who are treated with drugs to inhibit androgen signaling will progress to an aggressive form of the disease for which there are limited therapeutic options.”

Using a combination of genetic, biochemical, and chemical approaches, the research team defined the mechanisms that enable prostate cancer cells to recognise and respond differently to varying levels of testosterone, the most common androgenic hormone.

It turned out to be rather simple. When androgen levels are low, the androgen receptor is encouraged to “go solo” in the cell. In doing so, it activates the pathways that cause cancer cells to grow and spread. However, as androgens rise, the androgen receptors are forced to “hang out as a couple,” creating a form of the receptor that halts tumour growth.

“Nature has designed a system where low doses of hormones stimulate cancer cell proliferation and high doses cause differentiation and suppress growth, enabling the same hormone to perform diverse functions,” McDonnell said.

In recent years, clinicians have begun treating patients with late-stage, therapy resistant prostate cancers using a monthly, high-dose injection of testosterone in a technique called bi-polar androgen therapy, or BAT. The inability to understand how this intervention works has hindered its widespread adoption as a mainstream therapeutic approach for prostate cancer patients.

“Our study describes how BAT and like approaches work and could help physicians select patients who are most likely to respond to this intervention,” McDonnell said. “We have already developed new drugs that exploit this new mechanism and are bringing these to the clinic for evaluation as prostate cancer therapeutics.”

Source: Duke University

Macrophages are Involved in the Aggravation of Rheumatoid Arthritis by Oral Bacteria

Photo by Caroline Lm on Unsplash

Researchers from Japan have discovered a certain oral bacteria associated with rheumatoid arthritis causes inflammation, through macrophages and an inflammatory enzyme, caspase-11. Their results appear in the International Journal of Oral Science.

Periodontal disease, which affects the gums and tissues that surround the teeth, is one of the most prevalent dental conditions worldwide, and besides tooth loss is associated with other health effects. Over the past few decades, clinical studies have revealed that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is closely related to the onset and worsening of rheumatoid arthritis (RA), a serious autoimmune disease that affects joints. However, what goes down at the molecular level remains largely unexplored and unclear. 

In this study, a research team from Tokyo Medical and Dental University (TMDU) in Japan sought to fill this knowledge gap through detailed mechanistic studies in an animal model. 

First, the researchers conducted preliminary experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis in mice. To this end, they used the collagen antibody-induced arthritis mouse model, which is a well-established experimental model that mimics several aspects of RA in humans. They found that infection with this specific bacterium led to increased limb swelling, cellular infiltration into the lining of the joints, and higher levels of the inflammatory cytokine interleukin-1β (IL-1β) within the limbs. 

Notably, these symptoms of worsening RA could be suppressed by administering a chemical agent called clodronate that depletes macrophages. This demonstrated that macrophages were somehow involved in aggravating RA caused by A. actinomycetemcomitans infection.

Further investigation using macrophages derived from mouse bone marrow revealed that A. actinomycetemcomitans infection increased the production of IL-1β. In turn, this triggered the activation of a multiprotein complex known as the inflammasome, which plays a key role in initiating and modulating the body’s inflammatory response to infections. 

The researchers added yet one more piece to this puzzle using caspase-11-deficient mice. In these animals, inflammasome activation due to A. actinomycetemcomitans was suppressed. Most importantly, caspase-11-deficient mice exhibited less deterioration of arthritis symptoms, hinting at the important role that caspase-11 plays in this context. “Our research findings provide new insights into the link between periodontal pathogenic bacteria and the exacerbation of arthritis through inflammasome activation, offering important information on the long-debated relationship between periodontal disease and systemic diseases,” highlights Professor Toshihiko Suzuki, one of the lead authors of the study. 

With any luck, these efforts will contribute to the development of novel therapeutic strategies to manage RA. “The findings of this research may pave the way for advances in clinical treatments for RA induced by infection with A. actinomycetemcomitans. Our suggestion to inhibit inflammasome activation could attenuate the expansion of inflammation to joints, resulting in a recovery from arthritis symptoms,” says lead author Dr Tokuju Okano. “Moreover, the outcome of our work could contribute to the development of treatment strategies for not only arthritis but also other systemic diseases, such as Alzheimer’s disease, which is also related to periodontal pathogenic bacteria,” he predicts. 

Source: Tokyo Medical and Dental University

New Research Explains Differences in Men’s and Women’s Immune Systems

Photo by Daniil Onischenko on Unsplash

By analysing the immune system of female-to-male transgender individuals, Swedish researchers demonstrate the role of sex hormones in regulating the immune system. This newfound knowledge, published in Nature, explains differences between men and women, particularly in terms of immune signalling, and can be used to develop new immunological medications according to researchers.

Sex differences in the immune system are regulated both by genetics and by sex hormones. However, immunological comparisons between men and women can never fully distinguish the significance of genetic versus hormonal variations.

Now, three Swedish research groups led by Karolinska Institutet and Uppsala University has conducted a unique study analysing the regulation and adaptation of the immune system over time in 23 trans men who have undergone gender-affirming testosterone treatment, starting at the age of 18–37 years.

“We have followed individuals who were assigned female sex at birth and later received testosterone treatment in adulthood. Their genetic profile remains unchanged, while their hormone profile shifts entirely from typically female to male hormone levels,” says Petter Brodin, paediatrician and professor of paediatric immunology at the Department of Women’s and Children’s Health, Karolinska Institutet, who led the study together with Nils Landegren, assistant professor at Uppsala University, and Olle Kämpe, Professor at the Department of Medicine, Solna, Karolinska Institutet. “This unique change allows us, for the first time, to identify which parts of a person’s immune system are directly regulated by sex hormones rather than genetic sex differences.” 

The researchers can now demonstrate that increased testosterone levels and the accompanying reduction in oestrogen particularly affect the balance between two crucial immune signalling systems: antiviral interferon type 1 (IFN-1) and proinflammatory signals such as tumour necrosis factor alpha (TNFα).  

Specifically, they found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. 

The immune system changes throughout life

They also have a hypothesis about why the immune system needs to be dynamically regulated by hormones throughout life. 

“All individuals must be able to adjust their immune systems over the course of their lives to be optimally regulated for the conditions and challenges we face. During puberty and sexual maturation, new demands arise, and the immune system must be regulated differently to enable pregnancy in women and muscle growth in men,” says Petter Brodin. 

By regulating these key functions via sex hormones, this can be achieved, and in women, it is dynamically controlled even during a menstrual cycle,” he adds. 

The results of the study open an entirely new field of research, according to Nils Landegren. 

“The newfound knowledge will help us better influence people’s immune systems even without using sex hormones. For example, new drugs can be developed to impact these regulatory mechanisms and thus rebalance the immune response, especially for women with the autoimmune rheumatic disease SLE,” he explains. 

However, the results also have a more direct implications for transgender individuals. 

“This research is also of crucial for transgender individuals undergoing gender-affirming hormone therapy, and I believe that this group deserves significantly more scientific attention and follow-up to ensure their long-term health,” says Petter Brodin. 

Source: Karolinska Institutet