Day: September 21, 2023

Categories : Paediatrics Skeletal SystemTags :

Newly Discovered Bone Stem Cell Drives Premature Skull Fusion

On By ModernMedia
Photo by Mathew Schwartz on Unsplash

Craniosynostosis, the premature fusion of the top of the skull in infants, is caused by an abnormal excess of a previously unknown type of bone-forming stem cell, according to a preclinical study published in Nature.

Occurring in one in 2500 babies, craniosynostosis arises from one of several possible gene mutations. By constricting brain growth, it can lead to abnormal brain development if not corrected surgically. In complex cases, multiple surgeries are needed.

Led by researchers at and led by researchers at Weill Cornell Medicine, the team focused on what happens in the skull of mice with one of the most common mutations found in human craniosynostosis. They found that the mutation drives premature skull fusion by inducing the abnormal proliferation of a type of bone-making stem cell, the DDR2+ stem cell, that had never been described before.

“We can now start to think about treating craniosynostosis not just with surgery but also by blocking this abnormal stem cell activity,” said study co-senior author Dr Matt Greenblatt, an associate professor of pathology and laboratory medicine at Weill Cornell Medicine and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Histology image with stem cells labeled in red and skull region in green

A new stem cell driving disorders of premature skull fusion was transplanted (red), showing that it makes the cartilage seen at sites of skull fusion (green). Credit: Greenblatt lab.

In a study published in Nature in 2018, Dr Greenblatt, study co-senior author Dr Shawon Debnath and their colleagues, described the discovery of a type of bone-forming stem cell they called the CTSK+ stem cell. Because this type of cell is present in the top of the skull, or “calvarium,” in mice, they suspected that it has a role in causing craniosynostosis.

For the new study, they knocked out genes associated with craniosynostosis in CSTK+ stem cells in mice. They expected that the gene deletion somehow would induce these calvarial stem cells to go into bone-making overdrive. This new bone would fuse the flexible, fibrous material called sutures in the skull that normally allow it to expand in infants.

“We were surprised to find that, instead of the mutation in CTSK+ stem cells leading to these stem cells being activated to fuse the bony plates in the skull as we expected, mutations in the CTSK+ stem cells instead led to the depletion of these stem cells at the sutures – and the greater the depletion, the more complete the fusion of the sutures,” Dr Debnath said.

The unexpected finding led the team to hypothesise that another type of bone-forming stem cell was driving the abnormal suture fusion. After further experiments, and a detailed analysis of the cells present at fusing sutures, they identified the culprit: the DDR2+ stem cell, whose daughter cells make bone using a different process than that utilised by CTSK+ cells.

The team found that CTSK+ stem cells normally suppress the production of the DDR2+ stem cells. But the craniosynostosis gene mutation causes the CTSK+ stem cells to die off, allowing the DDR2+ cells to proliferate abnormally.

Collaborating with other researchers, they found the human versions of DDR2+ stem cells and CTSK+ stem cells in calvarial samples from craniosynostosis surgeries—underscoring the likely clinical relevance of their findings in mice.

The findings suggest that inappropriate DDR2+ stem cell proliferation in the calvarium, in infants with craniosynostosis-linked gene mutations, could be treated by suppressing this stem cell population, through mimicking the methods that CTSK+ stem cells normally use to prevent expansion of DDR2+stem cells. The researchers found that the CTSK+ stem cells achieve this suppression by secreting a growth factor protein called IGF-1, and possibly other regulatory proteins.

“We observed that we could partly prevent calvarial fusion by injecting IGF-1 over the calvarium,” said study first author Dr Seoyeon Bok, a postdoctoral researcher in the Greenblatt laboratory.

“I can imagine DDR2+ stem cell-suppressing drug treatments being used along with surgical management, essentially to limit the number of surgeries needed or enhance outcomes,” Dr. Greenblatt said.

In addition to treatment-oriented research, he and his colleagues now are looking for other bone-forming stem cell populations in the skull.

“This work has uncovered much more complexity in the skull than we ever imagined, and we suspect the complexity doesn’t end with these two stem cell types,” Dr Greenblatt said.

Source: Weill Cornell Medicine

Categories : Diet and Nutrition Metabolic DisordersTags :

Almonds Help Weight Loss and Improve Cardiometabolic Health

On By ModernMedia
Photo by Pavel Kalenik on Unsplash

Diets often recommend avoiding nuts as they contain a large amount of fat even though they are high in protein and fibre. Now, a large study published in the journal Obesity demonstrated that including almonds in an energy restricted diet not only helped participants to lose weight, but also improved their cardiometabolic health.

Examining the effects of energy restricted diets supplemented with Californian almonds or with carbohydrate- rich snacks, researchers found that both diets successfully reduced body weight by about 7kg.

Globally, more than 1.9 billion adults are overweight (650 million with obesity). Two in three people (approximately 12.5 million adults) are overweight or have obesity, as do one in every two South Africans.

UniSA researcher Dr Sharayah Carter says the study demonstrates how nuts can support a healthy diet for weight management and cardiometabolic health.

“Nuts, like almonds, are a great snack. They’re high in protein, fibre, and packed with vitamins and minerals, but they also have a high fat content which people can associate with increased body weight,” Dr Carter says.

“Nuts contain unsaturated fats – or healthy fats – which can improve blood cholesterol levels, ease inflammation, and contribute to a healthy heart.

“In this study we examined the effects of an almond-supplemented diet with a nut-free diet to identify any influence on weight and cardiometabolic outcomes.

“Both the nut and nut free diets resulted in approximately 9.3% reduction in body weight over the trial.

“Yet the almond-supplemented diets also demonstrated statistically significant changes in some highly atherogenic lipoprotein subfractions, which may lead to improved cardiometabolic health in the longer term.

“Additionally, nuts have the added benefit of making you feel fuller for longer, which is always a pro when you’re trying to manage your weight.”

The study, funded by the Almond Board of California, had 106 participants complete a 9-month eating program (a three-month energy-restricted diet for weight loss in Phase 1, followed by Phase 2, a six-month energy-controlled diet for weight maintenance). In both phases, 15% of participants’ energy intake comprised unsalted whole almonds with skins (for the nut diet) or 15% carbohydrate-rich snacks – such as rice crackers or baked cereal bars (for the nut-free diet).

Reductions occurred in fasting glucose (−0.2mmol/L), insulin (−8.1pmol/L), blood pressure (−4.9 mmHg systolic, −5.0mmHg diastolic), total cholesterol (−0.3 mmol/L), low-density lipoprotein (LDL) (−0.2mmol/L), very low-density lipoprotein (−0.1mmol/L), and triglycerides (−0.3mmol/L), and high-density lipoprotein increased (0.1mmol/L) by the end of Phase 2 in both groups.

Source: University of South Australia

Categories : Ethics and Law Expert OpinionTags :

Medical Gaslighting: When Conditions Turn out not to be ‘All in the Mind’

On By ModernMedia

By Caitjan Gainty, Senior Lecturer in the History of Science, Technology and Medicine, King’s College London

Photo by cottonbro studio

Gaslight, a psychological thriller starring Ingrid Bergman, was a box-office hit when it was released in 1944, but its time in the limelight could have ended there. However, the ruse employed by its villain gave the work remarkable staying power.

Set in 1880s London, the story plays out in the upper-middle-class, gas-lit home of Gregory and Paula Anton. Gregory is intent on making Paula think she is going insane so that he can have her committed to a mental institution and claim her inheritance. He attempts to convince her that the gas lighting in their house, which the audience can see is flickering, is not really flickering. What her senses tell her is a lie – a sign of her steady descent into madness.

Today, the term “gaslighting” is widely used to describe psychological manipulation, where a person is made to doubt their perception of reality. Politicians are accused of it, as are celebrities. The term also used in discussions about health.

Medical gaslighting refers to cases in which a healthcare practitioner imposes a pattern of questions, testing or diagnosis that runs counter or tangential to the history or symptoms the patient is describing or experiencing.

There is usually a clear power imbalance at play. More often than not, gaslit patients are women, members of the LGBTQ community, people of colour and older adults.

It is a painful reminder that medicine does not occupy a rarefied space apart from society and history. Those who are socially, culturally, politically or economically marginalised don’t find that this experience suddenly changes when they walk through the clinic door.

In many ways, the term gaslighting is an apt fit for medical settings, especially when it comes to the common refrain: “It’s all in your head.”

One of the best-known examples relates to heart disease, where a woman’s symptoms are twice as likely as a man’s to be simply written off as mental illness. This missed diagnosis is often explained by the fact that women’s heart attack symptoms are “strange and unpredictable” (compared with a man’s “normal” symptoms). However, that excuse doesn’t hold water – there is a large overlap in heart attack symptoms between the sexes.

Elsewhere, social media and news reports are full of egregious examples of women being medically gaslit. There are those whose cancer reached an advanced stage before they could get a doctor to take them seriously. And those whose lives were imperilled by a doctor who dismissed their pain as anxiety, as postpartum depression, as not nearly as bad as they think it is.

Examples of medical gaslighting also accrue around chronic but poorly understood diseases. In recent years, there’s been the medical community’s slow and halting recognition of long COVID. Before that, it was long Lyme disease or chronic fatigue syndrome, as Jennifer Brea’s 2017 documentary Unrest movingly shows.

Algorithmically out of whack

Yet medical gaslighting is a far more complex creature than gaslighting in other contexts. While Gregory’s attempts to gaslight his wife were malicious and intentional, medical gaslighting quite often overlaps with a more basic problem in medicine: misdiagnosis.

In many cases, misdiagnosis occurs not because an individual doctor is being malicious or even intentionally – though perhaps unconsciously – prejudiced, but because the symptoms they observe in the patient before them are “algorithmically” out of whack with the standard set of symptoms and characteristics they have been taught to look for and associate with different diseases.

Since these algorithms were explicitly built around heterosexual white men, it makes sense that the vast majority of those who have experienced medical gaslighting or misdiagnosis hail from beyond this extremely narrow band of the population. But even at a more basic level, individuals are simply not standard. Human bodies don’t conform as closely to the algorithms as medicine would ideally like them to.

“The bottom line,” as one doctor put it, “is that diagnosis is hard.” It does not help that research into diagnosis is never as well-funded as research into treatment.

That’s not to say there aren’t any covert (or overt) Gregory Antons out there in medical practice, of course. But it does mean that if we want to address medical gaslighting, the answer is probably not as simple as training medical professionals to be more sensitive to their patient’s descriptions of their symptoms.

Indeed, the very foundation of modern medicine agitates against this kind of attention to individual symptoms, asking medical professionals instead to measure patients against a set of standards – to think statistically as they make their diagnostic decisions.

Until a much greater part of society is included in that statistical reckoning, we can expect medical gaslighting to remain a part of our medical experiences. And even if or when that happens, our system will still be one that grapples with the difficult task of matching the emphatically square holes of symptom and diagnostic categories with the differently shaped realities of individual symptoms and illness experiences.

The Conversation

Republished from The Conversation under a Creative Commons License. Read the original article.

Categories : General InterestTags :

Med Student’s Stellar Academic Record Paves Way for Elective Abroad

On By ModernMedia

By NIÉMAH DAVIDS

Photo: Supplied

Fifth-year Bachelor of Medicine and Surgery (MBChB) student Moses Malebana’s stellar academic record has paved the way for a special international elective at the University of Graz – making him the maiden recipient of this golden opportunity – and galvanising ties between the University of Cape Town’s (UCT) Department of Medicine and the Medical University of Graz (Med Uni Graz) in Austria.

Malebana will depart in November and return to UCT’s Faculty of Health Sciences in January 2024. And with just a few short weeks before he boards his flight, he said he is excited for what awaits, and plans to absorb every detail of the experience.

“I plan on becoming a giant sponge while there. I am excited and feel privileged that I’ve been selected for this opportunity. I look forward to learning all there is to learn and flying UCT’s and the Department of Medicine’s flag[s] high at Med Uni Graz,” he said.

Tough grind

But this opportunity didn’t just fall into his lap. To be considered for the elective abroad, the application and selection criteria was clear – the candidate needed to prove an unmatched academic record. Each applicant was also tasked with supplying a motivational letter that highlighted why they felt they deserved the opportunity. It’s safe to say that Malebana passed the test with flying colours.

He said he used the motivational letter to reflect and relay personal anecdotes that focused on the sacrifices that led him to study medicine at UCT, and he enjoyed documenting his story.

“I remember seeing the email and thinking that this is my opportunity to reflect on my journey and to just tell my story. It was interesting because I don’t often reflect on things. But when I started, I realised that my whole life up to this point was about making the most of the opportunities that have come my way,” he said.

First-class motivation

In his motivation, Malebana touched on the events in his life that moulded him into the man he is today. And the list is endless – walking for more than an hour to and from school every day in rural Limpopo, contending with a lack of in-school resources, and a shortage of skilled teachers were just some of the challenges he experienced. These hurdles, he added, provided the impetus he needed to give his high school education and his medical studies his all.

“All of this taught me resilience; it motivated me to work even harder to reap the rewards later in life. I worked very hard to get to UCT, and now that I’m here, I’m working even harder to attain success in my degree,” he said. “I don’t take any opportunities for granted. I’m humbled that I’ve been chosen to represent the faculty and the university in Austria,” he said.

As he prepares for his big trip, Malebana said he’s looking forward to understanding the Austrian health system and gaining some valuable insight into how medical doctors practice medicine in that country and how it compares to South Africa.

A whole new world

The elective will consist of several rotations in different areas of internal medicine and Malebana will be based at a teaching hospital affiliated to Med Uni Graz. He said he is most excited about his oncology rotations after developing a keen interest in this area of medicine.

“I have always enjoyed studying and learning more about the management of different cancers. So, I really look forward to seeing how things are done in Austria. I know each day will be filled with something new to learn, whether it’s in oncology or a different area of medicine. I’m eager to get going,” he said.

But over and above the work, Malebana said he is thrilled to have the opportunity to travel outside of South Africa’s borders for the first time, to experience diverse cultures and cuisines, gain insight into a new way of life, and build new, lasting friendships.

“It’s going to be an adventure, that’s for sure – one that I’ve already embraced with my arms wide open. I’m grateful that it has come my way,” he said.

Republished from the University of Cape Town under a Creative Commons Attribution-NoDerivatives 4.0 International Licence.

Source: University of Cape Town

Categories : Gastrointestinal Immune SystemTags :

Atopic Dermatitis Increases Risk of New-onset IBD

On By ModernMedia
Source: CC0

Adults with atopic dermatitis (AD) have a 34% increased risk of developing new-onset inflammatory bowel disease (IBD) compared to those without the skin condition, according to a new recently published in JAMA Dermatology. The study also shows for children, the risk increase is 44%. Additionally, as the severity of AD increased, the risk of developing IBD rose.

These findings clear up ambiguity from previous research, especially among populations of children and between the different types of IBD: ulcerative colitis and Crohn’s disease. While IBD is located in the gut and AD affects the skin, both diseases are driven by the immune system and are categorised by severe inflammation. Insight offered from this study from the Perelman School of Medicine at the University of Pennsylvania could lead to new treatments for both IBD and AD.

“It is imperative for clinicians to understand atopic dermatitis and the trajectory of our patients with it in order to provide the best standard of care,” said senior author Joel M Gelfand, MD, dermatology professor at Penn. “There are new and better treatments for AD today, and there will likely continue to be more. But providers have to understand how those treatments could impact other autoimmune diseases. For patients with AD and another autoimmune disease, some currently available medications can exacerbate symptoms of their other disease or can help treat two immune diseases at the same time.”

While this is not the first study to explore AD and IBD, its size, with one million adult and child participants with AD drawn from a UK medical database, and its separation between ulcerative colitis and Crohn’s disease advances previous research.

When looking at ulcerative colitis and Crohn’s disease separately, AD was not linked to higher ulcerative colitis in children unless the kids had severe AD. Children with AD, however, had a 54–97% increased relative risk of Crohn’s disease, and among children with severe AD, their risk was roughly five times higher. Results among adults were more straightforward. Adults with AD had a 32% increased relative risk of ulcerative colitis and a 36% increased relative risk of Crohn’s disease. Gelfand notes that the absolute extra risk of developing IBD in individuals with AD is still quite small, but the association is meaningful in better understanding health outcomes in AD. Moreover, since millions of people have AD, this small increase in risk spread among many people is likely important from a public health perspective.

Although Penn researchers did not look at the root cause of IBD linked to AD, they have strong hypotheses about the links.

“AD and IBD can cause changes in the microbiome, chronic inflammation, and the dysfunction in the skin and gut barrier respectively,” said Gelfand, who is also the director of the Center for Clinical Sciences in Dermatology at Penn. “There are also specific cytokines, certain kinds of proteins, that play a role in immune system activity and that seem to be related to AD and IBD. For example, we think dysfunction of types of T cells common to both AD and IBD, could be the culprits. Those need to be explored further to uncover both what’s happening at a microscopic level and what proteins or structures could be targeted to treat one or both conditions.”

As a leading expert on psoriasis, a disease known to be tied to IBD genetically, Gelfand is well aware of how closely skin health can affect other parts of the body. He and his colleagues are also studying AD’s relationship to infections, neurologic and psychiatric disorders, and cardiovascular disease.

“Investigating the relationship between skin diseases and other diseases doesn’t just offer new insight into how these diseases can affect a patient with both, but these studies are especially powerful because they also highlight unique characteristics of each disease and how they behave individually,” Gelfand shared.

Source: University of Pennsylvania School of Medicine