Type 2 diabetes alters the behaviour of discs in the vertebral column, making them stiffer, and also causes the discs to change shape earlier than normal. As a result, the disc’s ability to withstand pressure is compromised. This is one of the findings of a new rodent-based study published in PNAS Nexus.
Low back pain is a major cause of disability, often associated with intervertebral disc degeneration. People with type 2 diabetes face a higher risk of low back pain and disc-related issues. Yet the precise mechanisms of disc degeneration remain unclear.
Investigating the biomechanical properties of the intervertebral disc is crucial for understanding the disease and developing effective strategies for managing low back pain.
“These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition,” the research team wrote. The team consisted of engineers and physicians from the University of California San Diego, UC Davis, UCSF and the University of Utah.
The study emphasises that nanoscale deformation mechanisms of collagen fibrils accommodate compressive loading of the intervertebral disc.
In the context of type 2 diabetes, these mechanisms are compromised, resulting in collagen embrittlement.
These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition.
Researchers employed synchrotron small-angle x-ray scattering (SAXS), an experimental technique that looks at collagen fibril deformation and orientation at the nanoscale.
They wanted to explore how alterations in collagen behaviour contribute to changes in the disc’s ability to withstand compression.
They compared discs from healthy rats to those from rats with type 2 diabetes (UC Davis rat model). The healthy rats showed that collagen fibrils rotate and stretch when discs are compressed, allowing the disc to dissipate energy effectively.
“In diabetic rats, the way vertebral discs dissipate energy under compression is significantly impaired: diabetes reduces the rotation and stretching of collagen fibrils, indicating a compromised ability to handle pressure,” the researchers write.
Further analysis showed that the discs from diabetic rats exhibited a stiffening of collagen fibrils, with a higher concentration of non-enzymatic cross-links.
This increase in collagen cross-linking, induced by hyperglycaemia, limited plastic deformations via fibrillar sliding.
These findings highlight that fibril reorientation, straightening, stretching, and sliding are crucial mechanisms facilitating whole-disc compression.
Type 2 diabetes disrupts these efficient deformation mechanisms, leading to altered whole-disc biomechanics and a more brittle (low-energy) behaviour.
Scores of unemployed doctors, nurses and other health workers marched to the Union Buildings in Pretoria on Monday, calling for the Presidency to intervene in the ongoing financial problems facing the health sector.
One of their main demands is for the health budget to be increased to absorb about 800 medical professionals.
Joining the march, Mandla Matshabe, said he never imagined being unemployed when he completed his community service at Sefako Makgatho University in December last year after studying in Cuba.
“Now I’m sitting at home with a medical qualification when there is a dire need. It’s appalling to think there are medical professionals at home,” he said.
Matshabe, who lives in Hazyview in Mpumalanga, said many unemployed health workers were becoming depressed at home. He said hiring qualified doctors could help alleviate some of the burnout among doctors in the public sector.
“Doctors in communities are overburdened because we don’t have enough medical professionals, including physiotherapists and dieticians or everyone in the hospital,” he said.
University of Cape Town graduate Lerato Jaca said it was discouraging to be an unemployed doctor. “I come from KwaNzimakwe in Port Shepstone where there were literally no doctors when I was growing up.”
Jaca was raised by an unemployed single mother who relied on the money she made during Jaca’s three-year community service employment at Ermelo Hospital.
She said they now rely on her brother’s disability grant and his children’s child support grants to buy food.
Deputy President of the South African Medical Association, Dr Nkateko Minisi, said: “Other health professionals in the allied sectors, including pharmacy, are here with us to hand over a memorandum to build up the health system. But to do so, we feel that human capital must be optimised by hiring all these unemployed professionals. Not tomorrow, not next week but now!” she said.
Mnisi said more than 80% of the population depends on public health services. “Healthcare is not a privilege that should be enjoyed by some; it is a basic human right that every single person deserves.”
Communications Manager at The Presidency, Phil Mahlangu accepted the group’s memorandum.
He said that the presidency was “immensely worried as the presidency about the negative issues affecting the medical industry”. He promised the protestors a response within a week.
A discovery by researchers in Switzerland reveals that the sleeping body also reacts to the external world during sleep, explaining how some information from the sensory environment can affect sleep quality.
A collaboration between University of Liège and University of Fribourg has investigated whether the body is truly disconnected from the external world during sleep.
To do so, they focused on how heartbeat changes when we hear different words during sleep.
They found that relaxing words slowed down cardiac activity as a reflection of deeper sleep and in comparison to neutral words that did not have such a slowing effect.
This discovery, published in the Journal of Sleep Research, sheds new light on brain-heart interactions during sleep.
Matthieu Koroma (postdoctoral researcher), Christina Schmidt and Athena Demertzi (rsesearch) from the GIGA Cyclotron Research Center at ULiège teamed up with colleagues from University of Fribourg led a previous study analysing brain data (electroencephalogram) showing that relaxing words increased deep sleep duration and sleep quality, showing that we can positively influence sleep using meaningful words.
By that time, the authors hypothesised that the brain also remains able to interpret sensory information in a way that makes our body more relaxed after hearing relaxing words during sleep.
In this new study, the authors had the opportunity to analyse cardiac activity to test this hypothesis and found that the heart slows down its activity only after the presentation of relaxing, but not control words.
Markers of both cardiac and brain activity were then compared to disentangle how much they contributed to the modulation of sleep by auditory information.
Cardiac activity has been indeed proposed to directly contribute to the way we perceive the world, but such evidence was so far obtained in wakefulness.
With these results, the ULiège researchers showed that it was also true in sleep, offering a new perspective on the essential role of bodily reactions beyond brain data for our understanding of sleep.
“Most of sleep research focuses on the brain and rarely investigates bodily activity,” says Dr Schmidt.
“We nevertheless hypothesise that the brain and the body are connected even when we cannot fully communicate, including sleep. Both brain and body information need then to be taken into account for a full understanding of how we think and react to our environment,” explains Dr Demertzi.
“We shared freely our methodology following the principles of Open Science hoping that the tools that helped to make this discovery will inspire other researchers to study the role played by the heart in other sleep functions,” Dr Koroma advocates.
This work offers a more comprehensive approach about the modulation of sleep functions by sensory information. By looking into the cardiac responses to sounds, we may, for example, study in the future the role of the body in the way sounds influence emotional processing of memories during sleep.
Can technological advances enable a new era of patient-centric healthcare that goes beyond the boundaries of healthcare providers and extends to patients’ homes?
This dynamic is already unfolding in the global healthcare sector, says Nazia Pillay, Partner Head at SAP Africa – and Africa isn’t far behind.
“The emergence of patient-centric healthcare holds immense promise for better patient experiences, greater accessibility, and improved healthcare outcomes,” says Pillay. “Supported by rapid advances in a range of complementary technologies and driven by a growing need to expand healthcare access, the adoption of patient-centric healthcare models represents the next step in the evolution of healthcare provision.”
Flipping the healthcare model
Until now, healthcare service models have required that patients navigate through often-complex systems to receive diagnoses, treatment and medical advice. Patient-centric healthcare reimagines this dynamic, building systems around the needs and preferences of the patient and prioritising the quality of their experience.
A 2021 report by KPMG found that 79% of healthcare CEOs believed the sector needed to take a more patient-centric approach in order to better respond to patient needs and preferences. However, only 31% rated their organisation’s ability to do so as ‘excellent’.
“A patient-centric healthcare approach prioritises elements such as patient experience and multi-dimensional team engagement, leading to a more holistic patient engagement, explains Johann Joubert, CEO at Converge Solutions. “This approach also makes healthcare more accessible and affordable as the patient can receive expert services in the comfort of their homes. Home-based patient-centric healthcare also benefits the whole ecosystem as the hospital bed becomes available to patients who require more intensive care, while the overall cost of healthcare delivery can be driven downward.”
He adds that, to achieve this, healthcare providers must consider what might be viewed as non-conventional investments in technology to drive innovation across patient-centric operations. “The healthcare system, for valid reasons, is slow to innovate, but we cannot stagnate. The future of healthcare must be different, if we want better patient outcomes and more affordable and accessible healthcare services.”
Healthcare access reaches patients’ homes
Global healthcare providers are increasingly shifting to home-based care models that provide primary, acute and palliative care at the patient’s home. “Home-based care represents a golden opportunity to improve the quality of care while also lowering healthcare costs,” says Joubert. “The world is not as it was twelve months ago. Rapid advances in a range of enabling technologies such as AI, connectivity and device mobility have already set new thresholds of digital possibilities. What was science fiction two years ago, will be mainstream in the next twenty-four months.”
Joubert adds that, in his view, connected intelligence and microservices is the way of the future. “To try and do everything yourself would put you at a disadvantage. Instead, we hand-pick our partners and then combine the expertise of each partner to ensure rapid, relevant, affordable healthcare solutions with tangible value.”
Pillay adds: “Healthcare providers are increasingly adopting powerful new technologies ranging from advanced analytics to cloud capabilities, as well as a range of tools to improve planning, human capital management, financial processes and CRM-based technologies to enable the delivery of personalised healthcare. Over the next few years, the focus is likely to shift slightly to include emerging technologies that enable home-based care and diagnosis, such as AI and machine vision.”
Technology building blocks for improved healthcare
A McKinsey study noted the growing impact of several technologies on healthcare systems and services, including Generative AI to boost productivity and content development
However, to achieve this, healthcare providers will need to lay the technological foundation that will enable the integration of new healthcare innovations.
“The digital transformation of the healthcare industry at a global level is being enabled across a range of patient-centric technologies, spanning from improved healthcare data and analytics to smart healthcare operations and greater empowerment of healthcare workers,” says Pillay. “The outcomes of this transformation can be felt across patient engagement, patient diagnosis and the broader patient experience, as well as providers’ ability to convert health data into health insights to drive improved patient outcomes. And considering the acute skills shortage throughout the continent’s health sector, the use of technology to drive better employee experiences and improve talent retention is immensely valuable.”
Growing evidence for patient-centric model
According to Joubert, the evidence for a more patient-centric healthcare model is clear. “We survey more than fifty thousand patients every month and their feedback confirms that patients want more curated information, more medical worker engagement and rapid responses to questions. It is not only about the patient though. Healthcare is a collective effort and as much as our focus is on patient outcomes, this means we need to take the nursing community on the journey with us. Informed and knowledgeable collaboration is critical.”
Joubert points to the rapid recent advances in AI as an opportunity for the healthcare sector, with Generative AI becoming ‘mainstream’ just more than a year ago. “At the moment there are multiple schools of thought. Some argue that we are entering a ‘trough of disillusionment’, where we will realise AI is not the answer to every problem. Others argue that we are only now at very advent of the exponential AI explosion that will erupt over the next twelve to twenty-four months. I believe both views hold merit. AI is certainly not the answer to every problem. As in the case of IoT over the last couple of years, we will get smarter in how we apply the technology and, most importantly, how we do so in an ethical manner.”
He adds that the healthcare sector must embrace digital capabilities or risk becoming irrelevant in the next five years. “The healthcare industry, by virtue of erring on the side of caution and being highly regulated, typically steers away from disruption or transformation. But unless the healthcare providers embrace digital capabilities and explore the best applications of technology to improve healthcare outcomes, they won’t survive the years ahead.”
An existing biologic drug, omalizumab, can make life safer for children with food allergies by preventing dangerous allergic responses to small quantities of allergy-triggering foods, according to a new study led by scientists at the Stanford School of Medicine.
The findings, published in the New England Journal of Medicine, suggest that regular use of omalizumab could protect people from severe allergic responses, such as difficulty breathing, if they accidentally eat a small amount of a food they are allergic to.
“I’m excited that we have a promising new treatment for multifood allergic patients. This new approach showed really great responses for many of the foods that trigger their allergies,” said the study’s senior author, Sharon Chinthrajah, MD, associate professor of medicine and of pediatrics, and the acting director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford Medicine.
“Patients impacted by food allergies face a daily threat of life-threatening reactions due to accidental exposures,” said the study’s lead author, Robert Wood, MD, professor of pediatrics at Johns Hopkins University School of Medicine. “The study showed that omalizumab can be a layer of protection against small, accidental exposures.”
Omalizumab, which the Food and Drug Administration originally approved to treat diseases such as allergic asthma and chronic hives, binds to and inactivates the antibodies that cause many kinds of allergic disease. Based on the data collected in the new study, the FDA approved omalizumab for reducing risk of allergic reactions to foods on Feb. 16.
All study participants were severely allergic to peanuts and at least two other foods. After four months of monthly or bimonthly omalizumab injections, two-thirds of the 118 participants receiving the drug safely ate small amounts of their allergy-triggering foods. Notably, 38.4% of the study participants were younger than 6 years, an age group at high risk from accidental ingestions of allergy-triggering foods.
Allergies are common
Food allergies affect about 8% of children and 10% of adults in the United States. People with severe allergies are advised to fully avoid foods containing their allergy triggers, but common allergens such as peanuts, milk, eggs and wheat can be hidden in so many places that everyday activities such as attending parties and eating in restaurants can be challenging.
“Food allergies have significant social and psychological impacts, including the threat of allergic reactions upon accidental exposures, some of which can be life-threatening,” Chinthrajah said. Families also face economic impacts from purchasing more expensive foods to avoid allergens, she added.
In the best available treatment for food allergies, called oral immunotherapy, patients ingest tiny, gradually increasing doses of allergy-triggering foods under a doctor’s supervision to build tolerance. But oral immunotherapy itself can trigger allergic responses, desensitization to allergens can take months or years, and the process is especially lengthy for people with several food allergies, as they are usually treated for one allergy at a time. Once they are desensitised to an allergen, patients also must continue to eat the food regularly to maintain their tolerance to it – but people often dislike foods they were long required to avoid.
“There is a real need for treatment that goes beyond vigilance and offers choices for our food allergic patients,” Chinthrajah said.
Omalizumab is an injected antibody that binds and deactivates all types of immunoglobin E, or IgE, the allergy-causing molecule in the blood and on the body’s immune cells. So far, omalizumab appears able to provide relief from multiple food allergens at once.
“We think it should have the same impact regardless of what food it is,” Chinthrajah said.
Injections stave off severe reactions
The study included 177 children with at least three food allergies each, of whom 38% were 1 to 5 years old, 37% were 6 to 11 years old, and 24% were 12 or older. Participants’ severe food allergies were verified by skin-prick testing and food challenges; they reacted to less than 100 milligrams of peanut protein and less than 300 milligrams of each other food.
Two-thirds of the participants were randomly assigned to receive omalizumab injections, and one-third received an injected placebo; the injections took place over 16 weeks. Medication doses were set based on each participant’s body weight and IgE levels, with injections given once every two or four weeks, depending on the dose needed. The participants were re-tested between weeks 16 and 20 to see how much of each allergy-triggering food they could safely tolerate.
Upon re-testing, 79 patients (66.9%) who had taken omalizumab could tolerate at least 600 mg of peanut protein, the amount in two or three peanuts, compared with only four patients (6.8%) who had the placebo. Similar proportions of patients showed improvement in their reactions to the other foods in the study.
About 80% of patients taking omalizumab were able to consume small amounts of at least one allergy-triggering food without inducing an allergenic reaction, 69% of patients could consume small amounts of two allergenic foods and 47% could eat small amounts of all three allergenic foods.
Omalizumab was safe and did not cause side effects, other than some instances of minor reactions at the site of injection. This study marks the first time its safety has been assessed in children as young as 1.
More questions
More research is needed to further understand how omalizumab could help people with food allergies, the researchers said.
“We have a lot of unanswered questions: How long do patients need to take this drug? Have we permanently changed the immune system? What factors predict which people will have the strongest response?” Chinthrajah said. “We don’t know yet.”
The team is planning studies to answer these questions and others, such as finding what type of monitoring would be needed to determine when a patient gains meaningful tolerance to an allergy-triggering food.
Many patients who have food allergies also experience other allergic conditions treated by omalizumab, Chinthrajah noted, such as asthma, allergic rhinitis (hay fever and allergies to environmental triggers such as mold, dogs or cats, or dust mites) or eczema. “One drug that could improve all of their allergic conditions is exactly what we’re hoping for,” she said.
The drug could be especially helpful for young children with severe food allergies, she added, because they tend to put things in their mouths and may not understand the dangers their allergies pose, she added.
The drug could also make it safer for community physicians to treat food allergy patients, since it cannot trigger dangerous allergic reactions, as oral immunotherapy sometimes does. “This is something that our food allergy community has been waiting a long time for,” Chinthrajah said. “It’s an easy drug regimen to implement in a medical practice, and many allergists are already using this for other allergic conditions.”
The Third Biennial Rare Diseases Conference, Rare X 2024, took place at the Indaba Hotel in Johannesburg from 14 to 17 February, bringing together patients, healthcare professionals, and stakeholders in the rare disease community in a collaborative space to engage on rare diseases and their treatments. As a hub for South African, African, and international participants, the conference provided a platform for the exchange of ideas, offering academic and scientific insights while emphasising the importance of patient, caregiver, and support group experiences.
“The scarcity of genetic specialists, high costs, and limited access to advanced treatments make it challenging to manage rare diseases and congenital disorders in South Africa and on the continent,” said Kelly du Plessis, CEO & Founder of patient support group, Rare Diseases South Africa. “Rare X plays a pivotal role in advocating for the 4.1 million South Africans affected by these conditions, so that they can experience greater recognition, support, improved health services and better overall quality of life.”
Addressing the critical need for medical education programs in low- and middle-income countries, Prof Christian Hendriksz, extra ordinary Professor of Paediatrics and Child Health at the Steve Biko Academic Unit, University of Pretoria, and extra ordinary Professor of Human Metabolomics, North-West University, Potchefstroom, spoke about the significant step forward in healthcare equity and the provision of patient support in Africa.
Prof Hendriksz and his team have taken an inclusive and collaborative approach to addressing rare diseases on the continent. Meeting on virtual platforms, he has brought together people from 19 African countries, including clinicians, laboratory staff, and patient organisations. They found that there’s a noticeable lack of understanding about rare diseases among African political leaders, along with many misconceptions. A common belief is that rare diseases either don’t exist or are less important compared to major health issues like TB and HIV. This mindset hinders progress because without proper diagnosis, patients cannot be identified and treated. To change these views, there’s a need for education and awareness campaigns, along with the adoption of strategies that focus on the patients’ needs.
One of the major challenges Prof Hendriksz highlighted is the logistics of sample transportation and the urgent need for diagnostic services that are practical and sustainable. Through specialised training sessions at North-West University and the creation of a comprehensive network, significant advancements are being made in disease awareness, patient support, and diagnostic capabilities.
Looking ahead, Prof Hendriksz aims to enhance diagnostic and support pathways further, prioritising the development of local capacities.
Head Of Research at the Board of Healthcare Funders (BHF), Charlton Murove, explained that the BHF aims to ensure affordable access to healthcare services for all citizens. This is part of a broader initiative to improve the overall health system by establishing key relationships with various stakeholders and focusing on medical screenings and solutions for high-risk populations. The challenge lies in the complexity of conditions and the high costs associated with treatments, particularly for rare diseases. The BHF is exploring innovative solutions to mitigate these challenges, such as the creation of a pooled funding mechanism to smooth out the financial impact of high-cost treatments across participants. This approach aims to enhance efficiency, maintain funds within medical schemes, and ensure equitable access to necessary treatments.
According to Murove, the proposed system would allow for collective bargaining, potentially leading to negotiated price reductions and improved access to care. However, implementing such a system requires navigating legal, financial, and regulatory frameworks and a more cooperative attitude among medical schemes and stakeholders would be needed. The ultimate goal is to ease the financial burden on schemes and patients alike, ensuring sustainable access to critical treatments while promoting fairness and transparency in healthcare funding.
Meliska Volschenk, Head of Payer Solutions and National Accounts at global pharmaceutical company, Sanofi, and a participant in the Rare Diseases Access Initiative (RDAI) which aims to enhance equitable access to care for patients with rare diseases in South Africa, spoke of the need for collaboration across the healthcare spectrum to address the unique challenges faced by rare disease patients, such as life-threatening conditions, the need for specialised care, and often the lack of curative treatments.
“Recognising the significant impact of rare diseases on individuals, families, and the healthcare system, there is an urgent need for a national policy to ensure a coordinated approach to rare diseases,” said Volschenk. “South Africa, like many countries, lacks a comprehensive strategy to address these challenges effectively.”
To tackle the issues head-on, Volschenk said the Rare Disease Initiative (RDAI) has outlined six strategic priorities within a proposed national framework and strategy for rare diseases. These priorities include ensuring early and accurate diagnosis, improving access to treatments, enhancing data collection, providing coordinated care, improving access to services, and boosting collaborative research.
“The RDAI is working to improve healthcare for rare disease patients in South Africa by gradually introducing changes and involving different groups, including health organisations and government departments, in their efforts,” said Volschenk. “We are organising meetings and discussions with these groups to come up with practical changes and new policies aimed at better support and care for patients with rare diseases. This shows RDAI’s dedication to making the healthcare system fairer and more effective for people with rare conditions, ensuring they get the help and treatment they need.”
Overcoming the hurdles of rare disease care requires a united front, comprising healthcare professionals, policymakers, patient advocacy groups, and the pharmaceutical industry, said Prudence Selani, Head of Communications at Sanofi South Africa. The call to action is clear: to embrace a multifaceted approach that includes enhancing medical education, establishing a national policy for rare diseases, and developing a healthcare ecosystem that prioritises patient-centred strategies, affordability, and access to cutting-edge treatments. “That is how we can best contribute to a sustainable and equitable healthcare system for one of the most vulnerable patient groups,” said Selani.
The gut microbiome interacts with the loss of female sex hormones to exacerbate metabolic disease, including weight gain, fat in the liver and the expression of genes linked with inflammation, researchers report in the journal Gut Microbes.
The findings, using rodent models, may shed light on why women are at significantly greater risk of metabolic diseases such as obesity and Type 2 diabetes after menopause, when ovarian production of female sex hormones diminishes.
“Collectively, the findings demonstrate that removal of the ovaries and female hormones led to increased permeability and inflammation of the gut and metabolic organs, and the high-fat diet exacerbated these conditions,” said Kelly S. Swanson, the director of the Division of Nutritional Sciences and a professor in nutrition at the University of Illinois Urbana-Champaign who is a corresponding author of the paper. “The results indicated that the gut microbiome responds to changes in female hormones and worsens metabolic dysfunction.”
“This is the first time it has been shown that the response of microbiome to the loss of ovarian hormone production can increase metabolic dysfunction,” said first author Tzu-Wen L. Cross, a professor of nutrition science and the director of the Gnotobiotic Animal Facility at Purdue University. Cross was a doctoral student at the U. of I. when she began the research.
“The gut microbiome is sensitive to sex hormone changes and can further impact the risk of disease development.”
Cross said early microbiome research, beginning around 2005, looked at how the microbiome contributes to obesity development, but most of those studies focused on males.
“Metabolic dysfunction that is driven by the loss of ovarian-function in menopausal women – and how much the gut microbiome contributes to that – has not been studied. The aetiology is clearly very complex, but those gut-microbiome related factors are certainly components that we speculated play a role,” she said.
The scientists created diet-induced obesity in female mice and simulated the loss of female sex hormones by removing the ovaries in half of the population to examine any metabolic and inflammatory changes, including those to enzymes in the gut. The diets for both groups of mice were identical except for the proportion of fat, which constituted 60% or 10% of calories for those in the high-fat and low-fat groups, respectively.
In the second leg of the study, faecal samples were harvested from mice with or without ovaries and implanted in germ-free mice to study the impact on weight gain and metabolic and inflammatory activity in the gut, liver and fat tissue.
“The mice that were recipients of the gut microbiome of ovariectomized mice gained more weight and fat mass, and they had greater expression of genes in the liver associated with inflammation, obesity, Type 2 diabetes, fatty liver disease and atherosclerosis compared with those in the control group,” Swanson said.
Assessing the severity of fatty tissue and triglyceride concentrations in the liver, the scientists found that the triglyceride levels were significantly higher and fatty deposits in the liver and groin were greater in the mice that consumed the high-fat diet compared with all other treatment groups.
Those on the high-fat diet and those without ovaries had significantly larger fat cells, which are associated with cell death and the infiltration of macrophages. Along with elevated expression of the genes associated with inflammation and macrophage markers, these mice had lower expression of genes that are involved with glucose and lipid metabolism.
In the donor mice without ovaries that consumed the low-fat diet, the scientists found increased levels of beta-glucuronidase, an enzyme produced by the colon and some intestinal bacteria that breaks down and recycles steroidal metabolites such as oestrogen and various toxins, including carcinogens.
The scientists also examined the expression of genes coding for tight-junction proteins, which affect cell membranes’ permeability. They found that the mice without ovaries and those fed the high-fat diet had lower levels of these proteins in the liver and colon, which suggested their gut barriers were more permeable, compromised by either their diet or the absence of female hormones.
In the livers of the recipient mice that received transplants from donors without ovaries, the scientists found elevated expression levels of the gene for arginase-1, which plays a critical role in the elimination of nitrogenous waste. High levels of this protein have been associated with cardiovascular problems such as hypertension and atherosclerosis.
Spinal neuron. Image by Scientific Animations CC4.0
For the first time, researchers from The University of Queensland (UQ) have mapped out the proteins implicated in the early stages of motor neurone disease (MND). This paper was published in Nature Communications.
Dr Rebecca San Gil, the study’s first author, has developed a longitudinal map of the proteins involved in MND across the trajectory of the disease, identifying potential therapeutic pathways for further investigation. This includes one protein, TDP-43, implicated in a number of MNDs.
“The map is a springboard for many more projects exploring the proteins activated and repressed during the onset, early and late stages of MND,” Dr San Gil said. “These proteins are biological factors that drive disease onset and progress its development over time.
“We measured differences in protein levels in the brain across the trajectory of the disease and collated this information into a longitudinal map.”
The map is now available for scientists worldwide and will accelerate investigations into MND.
Dr San Gil, in the lab of Associate Professor Adam Walker, has been working in mouse models of MND to understand the mechanisms driving TDP-43 pathology in the brain, which accounts for 95% of amyotrophic lateral sclerosis (ALS) cases and 50% of frontotemporal lobar degeneration (FTLD).
Building on the mapping project, Dr San Gil chose to focus on a protein-folding factor called DNAJB5.
“Before the onset of MND in mouse models, we observed a marked increase in protein groups responsible for physically assisting in the protein folding process. “One of these ‘chaperone’ proteins, DNAJB5, was particularly abundant early on, sparking our curiosity about its role in disease progression.
“In human brain tissue, we found DNAJB5 enriched in areas where TDP-43 aggregates. The short-term elevation of DNAJB5 is likely a protective mechanism by neurons in an attempt to control TDP-43 as it begins to dysfunction.
“This protective response to TDP-43 needs further investigation because it may help us identify preventative and therapeutic approaches to MND.”
A/ Prof Walker envisions that the lab will continue to follow other identified protein pathways, using gene therapy and repurposing medicine, to see if they can alter or prevent the disease.
Compiling the TDP map was a collaborative project with researchers from Macquarie University, the University of Auckland, and the Children’s Medical Research Institute.
A new approach to blood tests could potentially be used to estimate a patient’s risk of type 2 diabetes, according to a new study appearing in BMC’s Journal of Translational Medicine. Currently, the most commonly used inflammatory biomarker currently used to predict the risk of type 2 diabetes is high-sensitivity C-reactive protein (CRP). But new research has suggested that jointly assessing of biomarkers, rather than assessing each individually, would improve the chances of predicting diabetes risk and diabetic complications.
A study by Edith Cowan University (ECU) researcher Dan Wu investigated the connection between systematic inflammation, assessed by joint cumulative high-sensitivity CRP and another biomarker called monocyte to high-density lipoprotein ratio (MHR), and incident type 2 diabetes.
The study followed more than 40 800 non-diabetic participants over a near ten-year period, with more than 4800 of the participants developing diabetes over this period.
Wu said that of those patients presenting with type 2 diabetes, significant interaction between MHR and CRP was observed.
“Specifically, increases in the MHR in each CRP stratum increased the risk of type 2 diabetes; concomitant increases in MHR and CRP presented significantly higher incidence rates and risks of diabetes.
“Furthermore, the association between chronic inflammation (reflected by the joint cumulative MHR and CRP exposure) and incident diabetes was highly age- and sex-specific and influenced by hypertension, high cholesterol, or prediabetes. The addition of the MHR and CRP to the clinical risk model significantly improved the prediction of incident diabetes,” said Wu.
Biological sex a risk factor
The study found that females had a greater risk of type 2 diabetes conferred by joint increases in CRP and MHR, with Wu stating that sex hormones could account for these differences.
Wu said that the research findings corroborated the involvement of chronic inflammation in causing early-onset diabetes and merited specific attention.
“Epidemiological evidence indicates a consistent increase in early-onset diabetes, especially in developing countries. Leveraging this age-specific association between chronic inflammation and type 2 diabetes may be a promising method for achieving early identification of at-risk young adults and developing personalised interventions,” she added.
Wu noted that the chronic progressive nature of diabetes and the enormous burden of subsequent comorbidities further highlighted the urgent need to address this critical health issue.
Although aging and genetics are non-modifiable risk factors, other risk factors could be modified through lifestyle changes.
Inflammation is strongly influenced by life activities and metabolic conditions such as diet, sleep disruptions, chronic stress, and glucose and cholesterol dysregulation, thereby indicating the potential benefits of monitoring risk-related metabolic conditions.
Wu said that the dual advantages of cost effectiveness and the wide availability of cumulative MHR and CRP in current clinical settings, potentiated the widespread use of these measures as a convenient tool for predicting the risk of diabetes.
3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute
Researchers have developed a revolutionary biosensor using terahertz (THz) waves that can detect skin cancer with exceptional sensitivity, potentially paving the way for earlier and easier diagnoses. Published in the journalIEEE Transactions on Biomedical Engineering, the study presents a significant advancement in early cancer detection, thanks to a multidisciplinary collaboration of teams from Queen Mary University of London and the University of Glasgow.
“Traditional methods for detecting skin cancer often involve expensive, time-consuming, CT, PET scans and invasive higher frequencies technologies,” explains Dr Shohreh Nourinovin, Postdoctoral Research Associate at Queen Mary’s School of Electronic Engineering and Computer Science, and the study’s first author.
“Our biosensor offers a non-invasive and highly efficient solution, leveraging the unique properties of THz waves – a type of radiation with lower energy than X-rays, thus safe for humans – to detect subtle changes in cell characteristics.”
The key innovation lies in the biosensor’s design. Featuring tiny, asymmetric resonators on a flexible substrate, it can detect subtle changes in the properties of cells.
Unlike traditional methods that rely solely on refractive index, this device analyses a combination of parameters, including resonance frequency, transmission magnitude, and a value called “Full Width at Half Maximum” (FWHM). This comprehensive approach provides a richer picture of the tissue, allowing for more accurate differentiation between healthy and cancerous cells and to measure malignancy degree of the tissue.
In tests, the biosensor successfully differentiated between normal skin cells and basal cell carcinoma (BCC) cells, even at different concentrations. This ability to detect early-stage cancer holds immense potential for improving patient outcomes.
“The implications of this study extend far beyond skin cancer detection,” says Dr Nourinovin.
“This technology could be used for early detection of various cancers and other diseases, like Alzheimer’s, with potential applications in resource-limited settings due to its portability and affordability.”
Dr Nourinovin’s research journey wasn’t without its challenges.
Initially focusing on THz spectroscopy for cancer analysis, her project was temporarily halted due to the COVID pandemic. However, this setback led her to explore the potential of THz metasurfaces, a novel approach that sparked a new chapter in her research.
