Category: 8. Health

Involving parents in therapy helps children with anxiety and depression feel safer, communicate better, and recover more quickly, a new study shows.

Levels of anxiety and depression in children have soared globally since the COVID-19 pandemic, leaving many parents grappling with feelings of helplessness. But fresh research from Murdoch University offers renewed hope: when therapy includes parents and caregivers, it can make a profound difference.

The study, led by Dr Kim Lee Kho, tested the efficacy of Behaviour Exchange and Systems Therapy – Foundations (BEST-F) in the treatment plans of children aged 3-11. This involved a family-based approach where the parent-child relationship was a primary focus. 

BEST-F was developed in Melbourne and Perth by a team of researchers including Dr Kho’s primary supervisor Professor Andrew Lewis. 

Dr Kho said results of her study showed this approach had a large influence on reducing how often a child internalised symptoms of depression and anxiety. 

Supervisor and co-author Dr Renita Almeida said the psychological distress experienced by both children and caregivers globally supported the need for the research.

“We know that children are embedded within many systems, and the family system is of prime importance,” Dr Almeida said.

“There is substantial evidence that caregiving and family environmental factors have an impact on the transmission of depression and anxiety – what this also means is that the family base is full of potential to enable change, and that families can have a significant role in supporting a child’s affect regulation.” 

A critical element of the study was the safety and trust that parental participants felt within the therapy setting – fostered by empathy, care, and understanding for their unique situations. 

One parent who was quoted in the study said BEST-F therapy transformed the way they communicated with their family and the world around them, which also impacted the way their child communicated.

“I felt heard and seen by you [therapist] when we talked about what I’ve experienced in the past. I felt safe and that changed everything for me, and my family could tell the difference too.”  

In turn, the participant’s child mirrored that sense of safety and felt encouraged to open up about their own feelings.

“I feel it’s safe talking about it here… now I can tell mum when I am upset if something happens at school or with dad.” 

Dr Almeida said the key finding was that as improvements occurred across various parts of the family system, the changes continued to unfold into further improvements, as observed at follow-ups.

“Evaluation studies of Behaviour Exchange and Systems Therapy demonstrate that when you engage the whole family system in the therapeutic intervention, improvements are seen not only in the child’s mental health, but also in the parent’s mental health and family functioning,” she said.

Dr Kho said these results could influence the future of the treatment of childhood depression and anxiety.

“We are hoping that the results of this study motivate a larger clinical trial in the near future with the vision of potentially being offered as an intervention option in the community,” she said. 

The original version of this story first appeared in a media release from Murdoch University.

With the help of artificial intelligence, daily continuous glucose monitor (CGM) insights resulted in significant improvements in glycemic control, according to an abstract presented at the American Diabetes Association 85th Scientific Sessions, held in Chicago, Illinois, from June 20-23, 2025.¹

“A shortage of diabetes specialists, uneven distribution of medical resources, low adherence to medications, and improper self-management contribute to poor glycemic control in patients with diabetes,” wrote authors of a study published in Cell Reports Medicine.² “Recent advancements in digital health technologies, especially artificial intelligence (AI), provide a significant opportunity to achieve better efficiency in diabetes care, which may diminish the increase in diabetes-related health care expenditures.”

Among all of the advancements in health care, one of the more notable developments has been AI’s integration within CGMs. With previous evidence showing a significant opportunity to combine AI with CGM technology, researchers and providers alike are trying to better understand how the 2 technologies can be leveraged in diabetes management.

READ MORE: Pharmacist Integration in Health Care Team Improves Patient Access, Outcomes | ADA 2025

With AI on the cusp of advancing health care to places it has never been before, researchers of the current study wanted to better understand the effectiveness of AI within the diabetes and CGM spaces.

“AI-powered diabetes management platforms integrating CGM technology represent a promising advancement in health care,” wrote authors of the abstract.¹ “This study evaluates the effectiveness of AI-integrated SDRMP platform in improving glycemic control.”

By including AI-driven solutions and insights within each patients’ diabetes care regimen, researchers also provided interventions for all participants through the SDRMP platform, or the SugarFit Diabetes Reversal and Management Program. The platform “integrates dietary changes, physical activity, and continuous support, evaluating its effectiveness in improving health outcomes,” according to authors of a study published in the International Journal of Diabetes and Technology.³

Using this program, researchers of the current study aimed to understand AI’s capabilities in meshing with CGM technology and improving patients’ diabetes outcomes.¹

To understand the effectiveness of an AI-powered CGM, researchers conducted a 100-day retrospective study assessing the impact of personalized interventions for glycemic control. They recorded patients’ time in range (TIR), time below range (TBR), and time above range (TAR) using the CGM. Researchers also recorded patients’ HbA1c, fasting blood sugar (FBS), and weight.

The final analysis included a total of 1752 patients (77.5% men; mean age, 50.22 years). Finally, all participants gave their measurements at the start of the study period and were re-evaluated after an average of 100 days.

The most significant changes in glycemic control were identified in patients’ TBR, TAR, and TIR. Indeed, TBR decreased from 7.46 to 5.34, while TAR decreased from 49.89 to 45.33. TIR increased from 45.74 to 49.31. Finally, researchers uncovered reductions in weight, HbA1c, and FBS.

“Previous studies have shown that applying AI in diabetes management involves all aspects of disease control, including prediction, prevention, screening, diagnosis, and treatment,” continued authors of the Cell Reports Medicine study.² “Integrating AI into clinical practice care could shift diabetes care toward precision, penetration, prediction, and personalization.”

AI within health care, and society as a whole, may be at its beginning stages. However, studies have gradually shown progress and integration of AI-powered technology within approaches to optimizing diabetes care. As diabetes becomes more prevalent worldwide, researchers continue to find better ways to adapt technology and streamline valued care for patients.

“Daily CGM trend-associated insights with intervention led to significant improvements in glycemic control, evident in substantial improvements in TIR, TBR, TAR, HbA1c, FBS, and weight, highlighting its effectiveness in optimizing metabolic outcomes and diabetes management,” concluded authors of the abstract.¹

Read more from our coverage of the ADA’s 85th Scientific Sessions.

Ready to impress your pharmacy colleagues with the latest drug information, industry trends, and patient care tips? Sign up today for our free Drug Topics newsletter.

References

1. Kumar S, Raymond AM, Sequeira A, et al. Real-world impact of AI-driven CGM platform on glycemic status in type 2 diabetes—a retrospective study. Presented at: American Diabetes Association 85th Scientific Sessions; June 20-23, 2025; Chicago, IL.

2. Guan Z, Li H, Liu R, et al. Artificial intelligence in diabetes management: advancements, opportunities, and challenges. Cell Rep Med. 2023 Oct 17;4(10):101213. doi: 10.1016/j.xcrm.2023.101213. Epub 2023 Oct 2.

3. DTechCon abstracts 2025. Int J Diabetes Technol. 4(Suppl 2):p S8-S22, June 2025. doi: 10.4103/ijdt.ijdt_20_25

In the fight against cancer, immunotherapy – which aims to boost the body’s natural defences against cancer – is experiencing remarkable growth. Most of these treatments are based on CD8 T lymphocytes, ”killer cells” able to eliminate diseased cells. A team from the University of Geneva (UNIGE) has explored an alternative approach involving CD4 T lymphocytes. Long considered mere auxiliary cells, their therapeutic potential has been considered of secondary importance. But the scientists have discovered that they also have strong killing capacity, while continuing to support other immune cells. Using cell engineering technologies, the team reprogrammed the cells to target a tumour marker found in many cancers, both in adults and children. These results, published in the journal Science Advances, offer hope for a faster therapeutic strategy that could benefit a greater number of patients.

Traditionally considered as auxiliary cells, CD4 T cells produce molecules to support the action of other immune cells by facilitating their functions, migration or proliferation in the organism. Recent work by Camilla Jandus, Assistant Professor in the Department of Pathology and Immunology, in the Centre for Inflammation Research and in the Translational Research Centre in Onco-haematology at the UNIGE Faculty of Medicine, shows that they have been vastly underestimated.

In collaboration with the CHUV-UNIL Oncology Department and the Lausanne Branch of the Ludwig Institute for Cancer Research, UNIGE scientists studied the molecular characteristics of CD4 T lymphocytes isolated from melanoma patients (a skin cancer). They identified that a unique subset of these cells bears a T cell receptor (TCR) capable of efficiently recognising an antigen specific to tumour cells: NY-ESO-1. This TCR was then isolated and artificially expressed in other CD4 T cells.

We then evaluated the effectiveness of these engineered cells against cancer cells, both in vitro and in animal models. The results are impressive: they effectively target not only melanoma, but also lung, ovarian, sarcoma and brain cancers, while sparing healthy cells. This demonstrates that TCR-modified CD4 T cells can attack tumours directly, in addition to their auxiliary role”.

Camilla Jandus, Assistant Professor in the Department of Pathology and Immunology, UNIGE Faculty of Medicine

The major advantage of a widespread allele

The HLA system is a set of genes responsible for immune recognition. Everyone inherits different versions of these genes, known as alleles. ”They code for cell surface proteins, HLA molecules, which enable the T cells to distinguish healthy cells from pathogen infected or malignant cells,” explains Camilla Jandus. ”The effectiveness of T cell-based therapies depends on whether the patient carries the specific HLA allele that presents the tumour antigen. The NY-ESO-1 antigen, recognised by our TCR, is presented by a widespread allele, found in about half the Caucasian population, compared to only 10 to 15% for other HLA alleles. This dramatically expands the pool of patients who could benefit, especially since the targeted antigen is expressed in many types of cancer”.

Hope for adults and children with cancers

Camilla Jandus’ team is currently preparing a clinical trial of TCR-engineered CD4-based cell therapy. The trial will include different types of cancer expressing NY-ESO-1. First, a HLA test will verify the presence of the appropriate HLA allele, and then tumours will be analysed to confirm expression of NY-ESO-1. The CD4 T cells will then be harvested, modified in the laboratory to express the TCR, multiplied and reinjected into the patient.

But Camilla Jandus envisages a further step: the creation of a bank of ready-to-use TCR engineered immune cells from healthy donors, matched to avoid rejection, which would save precious time, especially in the case of aggressive cancers. This strategy could also pave the way for treatments for cancers that are currently incurable, particularly in children. The first in vitro tests on paediatric neuroblastomas are indeed promising.

This research was supported by the ISREC Foundation, as part of the ISREC Tandem programme and the Fondazione San Salvatore.

Today, a new ESC Clinical Consensus Statement published in the European Heart Journal discusses the key role of vaccination in preventing cardiovascular events following various viral and bacterial infections.

We have known for many years that influenza can increase the risk of major adverse cardiovascular events such as heart attacks and can exacerbate heart failure. More recently, evidence suggests that other respiratory infections are also associated with increased cardiovascular morbidity and mortality. The new publication describes how vaccinations not only prevent infections but also reduce the risk of cardiovascular events, particularly in susceptible individuals.”

 Professor Thomas F. Lüscher, ESC President and senior author of the ESC Clinical Consensus Statement

The ESC Clinical Consensus Statement describes data on the risk of cardiovascular complications following infections such as pneumococcal pneumonia, influenza, SARS-CoV-2 and respiratory syncytial virus, among others, and describes the inflammatory mechanisms that may be responsible. Evidence is then summarised for the beneficial effects of vaccines in reducing cardiovascular events following various viral and bacterial infections, particularly in at-risk patient groups. Clinical practice guidelines from the ESC and from the American College of Cardiology (ACC)/American Heart Association (AHA) are presented, which advocate for vaccination against influenza and other widespread infections in patients with chronic coronary syndromes (including coronary artery disease) and in those with heart failure.

Serious adverse reactions to vaccinations are very rare. The consensus statement also discusses the risks of cardiovascular adverse events after vaccination, such as myocarditis, and describes appropriate management strategies. Then follows advice on which vaccines should be given to patients with cardiovascular diseases and how often. Vaccination of pregnant women and other vulnerable patient groups, such as those with congenital heart disease and heart transplantation, is considered.

Professor Lüscher concluded: “Prevention is crucial for reducing the considerable burden of cardiovascular disease. The totality of the evidence indicates that vaccinations should become a foundational pillar of preventive strategies alongside other established measures.”

Real-world study demonstrates next-gen EpiSwitch PSE blood test safely reduces unnecessary biopsies by up to 79% while accurately detecting prostate cancer.

---

A real-world study published high-impact journal Cancers demonstrates the transformative potential of a next-generation prostate cancer blood test developed in the UK to accurately detect more cases of early prostate cancer, while potentially drastically reducing the cost needed to implement a UK-wide screening program.

Prostate cancer is the most common cancer among men in the UK, yet there is no national screening program due to traditional testing relying on an initial prostate-specific antigen (PSA) test, which is not an accurate indicator of prostate cancer by itself.

Approximately 3 in 4 men with a high PSA level do not have cancer, according to Prostate Cancer Research. As a result, many healthy men undergo unnecessary medical scans, invasive procedures, and, in some cases, even overtreatment, leading to  significant anxiety and burden for patients, while also straining healthcare resources.

Dr. Garrett Pohlman, MD, Urologist at Kearney Urology Center and lead author of the study said: “The results we have seen by integrating EpiSwitch PSE have been transformative. These findings show that a routine blood test can enable us to safely avoid biopsies in up to a staggering 79% of patients with an elevated PSA without compromising diagnosis. This is a major advancement that helps our patients benefit from reduced anxiety and the avoidance of unnecessary, costly medical procedures.”

By integrating EpiSwitch PSE into clinical practice, the healthcare system could achieve significant savings. The study found that among 187 patients, the PSE test potentially avoided 97 unnecessary prostate biopsies and 95 MRIs in this group alone.

This translates into an estimated cost saving of over 170,000 GBP (230,000 USD), or almost 1,000 GBP per patient, accounting for reduced subsequent procedures, MRI scans, and occasional downstream complications due to risks from prostate biopsies. Fewer MRI scans also reduce the need for substantial government investment in additional imaging infrastructure.

When expanded to the national level, the health-economic impact of incorporating PSE into a screening workflow could be substantial according to the study. In the US, the authors estimates that PSE has the potential to conservatively help avoid up to 593,000 prostate biopsies per year, with the economic benefit approaching 2 billion USD annually.

Oliver Kemp, MBE, Chief Executive Officer of UK charity Prostate Cancer Research, said: “This study shows how smarter testing can save millions while improving care for patients. Reducing unnecessary biopsies and scans means less stress for men and more capacity in the system.”

The innovation behind EpiSwitch PSE originates from a British company, Oxford BioDynamics (OBD), in collaboration with leading researchers and clinicians at the Imperial NHS Trust, Imperial College London, and the University of East Anglia.

Dr. Alexandre Akoulitchev, MA, PhD, FRSM, Chief Scientific Officer at Oxford BioDynamics, said: “This study builds on our earlier robust clinical validation work which demonstrated the application of EpiSwitch PSE as a precise, minimally invasive test that empowers clinicians and patients with clarity, reduced patient risk, and improved outcomes, while easing the pressure on the diagnostic pathway.”

Given these health and economic outcomes, Oxford BioDynamics says that EpiSwitch PSE is poised to ‘set a new standard’ and streamline prostate cancer diagnosis and management strategies in the US, where it is routinely reimbursed by Medicare, and the UK, where it is currently widely available to private patients and reimbursed by Bupa Health Insurance.

Related

Washington State University researchers have discovered how the bacteria that cause anaplasmosis and Lyme disease hijack cellular processes in ticks to ensure their survival and spread to new hosts, including humans.

Based in the College of Veterinary Medicine, the team found that the bacteria can manipulate a protein known as ATF6, which helps cells detect and respond to infection, to support its own growth and survival inside the tick. The findings, published in the journal Proceedings of the National Academy of Sciences, could serve as a launching point for developing methods to eliminate the bacteria in ticks before they are transmitted to humans and other animals.

Most research has looked at how these bacteria interact with humans and animals and not how they survive and spread in ticks. What we have found could open the door to targeting these pathogens in ticks, before they are ever a threat to people.”

Kaylee Vosbigian, doctoral student and lead author on the study

Vosbigian and her advisor, Dana Shaw, the corresponding author of the study and an associate professor in the Department of Veterinary Microbiology and Pathology, focused their research on Ixodes scapularis, also known as the blacklegged tick, which is responsible for spreading both Anaplasma phagocytophilum and Borrelia burgdorferi, the causative agents of anaplasmosis and Lyme disease. Both diseases are becoming increasingly common and can cause serious illness in humans and animals.

The team discovered that when ATF6 is activated in tick cells, it triggers the production of stomatin, a protein that helps move cholesterol through cells as part of a normal cellular processes. The bacteria exploit this process against their tick hosts, using the cholesterol –which they need to grow and build their own cell membranes but cannot produce themselves – to support their own survival and success.

“Stomatin plays a variety of roles in the cell, but one of its key functions is helping shuttle cholesterol to different areas,” Vosbigian said. “The bacteria take advantage of this, essentially stealing the cholesterol they need to survive.”

When the researchers blocked the production of stomatin, restricting the availability of cholesterol, bacterial growth is significantly reduced. The researchers believe this shows targeting the ATF6-stomatin pathway could lead to new methods for interrupting the disease cycle in ticks before transmission occurs.

As part of the study, Vosbigian also developed a new research tool called ArthroQuest, a free, web-based platform hosted by WSU that allows scientists to search the genomes of ticks, mosquitoes, lice, sand flies, mites, fleas and other arthropod vectors for transcription factor binding sites – genetic switches like ATF6 that control gene activity.

“There aren’t many tools out there for studying gene regulation in arthropods,” Vosbigian said. “Most are built for humans or model species like fruit flies, which are genetically very different from ticks.”

Using ArthroQuest, the team found that ATF6-regulated control of stomatin appears to be prevalent in blood-feeding arthropods. Since the hijacking of cholesterol and other lipids is common among arthropod-borne pathogens, the researchers suspect many may also exploit ATF6.

“We know many other vector-borne pathogens, like Borrelia burgdorferi and the malaria-causing parasite Plasmodium, rely on cholesterol and other lipids from their hosts,” Shaw said. “So, the fact that this ATF6-stomatin pathway exists in other arthropods could be relevant to a wide range of disease systems.”

The research was supported in part by a National Institutes of Health R01 grant and a College of Veterinary Medicine intramural seed grant.

When ocrelizumab became the first FDA-approved treatment for early forms of multiple sclerosis (MS) in 2017, it offered patients immense hope. The long-awaited drug is a monoclonal antibody that depletes B cells—the immune cells that drive MS progression. Exactly how ocrelizumab does this, however, remains unclear.

In a new study published in The Journal of Clinical Investigation, Yale scientists begin to answer this question. By using single-cell RNA sequencing—a technique that provides a window into the gene expression in individual cells—the researchers laid out a detailed view of how ocrelizumab achieves its therapeutic effects.

“The surprise was that the drug doesn’t work at all the way we thought it was working,” says David A. Hafler, MD, William S. and Lois Stiles Edgerly Professor of Neurology at Yale School of Medicine, who led the study. “We knew what the end result was and that the drug was enormously effective in patients. But what’s driving the drug’s action is a type of white blood cell in the central nervous system. No one would ever hypothesize that.”

The roles of T cells and B cells in multiple sclerosis

B and T cells have closely intertwined roles in the immune system. B cells are critical cells that recognize foreign objects, bind them, and present them to T cells, which then signal other immune cells to take action. But this relationship goes awry in disease.

In MS, abnormally active B cells trigger T cells to attack the myelin sheath, the protective layer of nerve fibers, leading to neurological symptoms, such as loss of vision, muscle weakness, and cognitive impairment. More than two decades ago, Hafler and his team discovered this was due to defects in regulatory T cells, which normally put the brake on immune responses, but when defective, unleash immune cells that mistakenly target the body’s own tissues.

In the early stages of MS, both B and T cells are deemed to be the drivers of the disease. Once the disease progresses to a neurodegenerative stage, other inflammatory processes become more prominent.

“Once you enter the neurodegenerative phase of the disease, it is much more difficult to stop the process,” Hafler says. “What we’ve learned is that the earlier you treat the disease, the better the outcome.”

Ocrelizumab binds to the surface of B cells, leading to their destruction. And especially for people in the early stages of MS, it can be quite effective. “The drug works incredibly well,” Hafler says. But Hafler and his team found that ocrelizumab was doing far more than just controlling B cells.

What we’ve learned is that the earlier you treat the disease, the better the outcome.

In the new study, the researchers analyzed the blood and cerebrospinal fluid of 18 patients, all of whom had an early-onset form of multiple sclerosis in which patients cycle between periods of disease remission and relapse. The scientists measured the cell type-specific changes in protein expression before and after the patients received six months of ocrelizumab, in an effort to identify immune molecules that might change in response to the drug.

They discovered that the reduction in B cells driven by ocrelizumab led to an increase in the pro-inflammatory molecule TNF-α. This was unexpected because TNF-α has been shown to trigger the immune system and exacerbate inflammation in certain diseases. In fact, medications that block the activity of TNF-α are typically used for treating various autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease.

As they looked further, the researchers found that by inducing TNF-α, ocrelizumab led to an increase in a specific type of regulatory T cell. This, in turn, curbed the circulation of T cells that attack the myelin.

“This unpredicted increase in TNF-α shows that ocrelizumab works in a paradoxical way,” says Hafler.

Understanding the cause of multiple sclerosis

One of the current working models of MS suggests that the disease originates from the Epstein-Barr virus. “How the Epstein-Barr virus triggers the disease is a point that we don’t yet understand,” Hafler says. However, there is a strong body of evidence to show that the virus infects B cells. Therefore, understanding how a B cell-depleting drug affects T cell activity may lead to further explanations.

The current finding also explains why a fifth of the genes linked to MS risk involve the TNF pathway and why many of those genetic changes are protective in other diseases, such as inflammatory bowel diseases.

“This shows that biology has a richness to it,” Hafler says. “When these molecules are made, where they’re made, and what cell they’re working on have very different effects.”

Hafler suspects that ocrelizumab might be acting through other mechanisms as well, an inkling that motivates his lab to continue their investigation. “For something to work that well, there must be other things going on,” he says.

The team is now beginning to study the pathogenesis of MS in a large cohort of women who have at least one parent with the disease. By following the genetic evolution of the disease, the scientists are hoping to better understand how B cells change the immune landscape in real time.

“This study is only one piece of the puzzle,” Hafler says. “We’ll continue to look for other pieces.”

The research reported in this news article was supported by the National Institutes of Health (awards P01AI073748, U19AI089992, U24AI11867, R01AI22220, UM1HG009390, P01AI039671, P50CA121974, and R01CA227473) and Yale University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by Race to Erase MS, the National MS Society, Genentech, and F. Hoffmann-La Roche.

Dementia poses a major health challenge with no safe, affordable treatments to slow its progression.

Researchers at Lawson Research Institute (Lawson), the research arm of St. Joseph’s Health Care London, are investigating whether Ambroxol – a cough medicine used safely for decades in Europe – can slow dementia in people with Parkinson’s disease.

Published today in the prestigious JAMA Neurology, this 12-month clinical trial involving 55 participants with Parkinson’s disease dementia (PDD) monitored memory, psychiatric symptoms and GFAP, a blood marker linked to brain damage. Parkinson’s disease dementia causes memory loss, confusion, hallucinations and mood changes. About half of those diagnosed with Parkinson’s develop dementia within 10 years, profoundly affecting patients, families and the health care system.

Led by Cognitive Neurologist Dr. Stephen Pasternak, the study gave one group daily Ambroxol while the other group received a placebo. “Our goal was to change the course of Parkinson’s dementia,” says Pasternak. “This early trial offers hope and provides a strong foundation for larger studies.”

Key findings from the clinical trial include:

• Ambroxol was safe, well-tolerated and reached therapeutic levels in the brain

• Psychiatric symptoms worsened in the placebo group but remained stable in those taking Ambroxol.

• Participants with high-risk GBA1 gene variants showed improved cognitive performance on Ambroxol

 • A marker of brain cell damage (GFAP) increased in the placebo group but stayed stable with Ambroxol, suggesting potential brain protection.

Although Ambroxol is approved in Europe for treating respiratory conditions and has a long-standing safety record – including use at high doses and during pregnancy – it is not approved for any use in Canada or the U.S.

Current therapies for Parkinson’s disease and dementia address symptoms but do not stop the underlying disease. These findings suggest Ambroxol may protect brain function, especially in those genetically at risk. It offers a promising new treatment avenue where few currently exist.”

Dr. Stephen Pasternak, Cognitive Neurologist 

Ambroxol supports a key enzyme called glucocerebrosidase (GCase), which is produced by the GBA1 gene. In people with Parkinson’s disease, GCase levels are often low. When this enzyme doesn’t work properly, waste builds up in brain cells, leading to damage. Pasternak learned about Ambroxol during a fellowship at The Hospital for Sick Children (SickKids) in Toronto, where it was identified as a treatment for Gaucher disease – a rare genetic disorder in children caused by a deficiency of GCase.

He is now applying that research to explore whether boosting GCase with Ambroxol could help protect the brain in Parkinson’s-related diseases. “This research is vital because Parkinson’s dementia profoundly affects patients and families,” says Pasternak. “If a drug like Ambroxol can help, it could offer real hope and improve lives.”

Funded by the Weston Foundation, this study is an important step toward developing new treatments for Parkinson’s disease and other cognitive disorders, including dementia with Lewy bodies. Pasternak and his team plan to start a follow-up clinical trial focused specifically on cognition later this year.

Odors from earwax may help distinguish individuals with Parkinson’s disease (PD) from those without the condition, a new study suggests.

Researchers found that four volatile organic compounds (VOCs) in ear canal secretions significantly differed between participants with and without PD.

The compounds — ethylbenzene, 4-ethyltoluene, pentanal, and 2-pentadecyl-1,3-dioxolane — may represent potential biomarkers. An artificial intelligence olfactory (AIO)-based screening model used in the study identified those with PD with 94% accuracy.

“The accuracy of the model really surprised us,” study investigator Hao Dong, Research Center for Frontier Fundamental Studies, Zhejiang Lab, Hangzhou, China, MD, told Medscape Medical News.

However, the study was a “small-scale, single-center experiment,” he noted in a press release.

“The next step is to conduct further research at different stages of the disease, in multiple research centers, and among multiple ethnic groups in order to determine whether this method has greater practical application value,” Dong said.

The findings were published online recently in Analytical Chemistry.

Unique Odor Profile

“Our team has long been engaged in the detection of [VOCs] secreted by the human body. By chance, we came across reports on the detection of sebum VOCs for Parkinson’s,” Dong said.

Sebum, the oily substance secreted by the skin, may carry a distinct scent in individuals with PD. In a 2019 study cited by Dong, researchers noninvasively collected sebum samples from the upper backs of 64 participants. The findings suggested that samples from those with PD contained compounds associated with a unique odor profile.

Dong and his team began with a confirmatory experiment using sebum samples collected from the upper back, as in the original study. However, they found that earwax was easier to collect and had a more stable chemical composition. These findings led them to focus on earwax in the current study.

Ear wax also contains sebum. But unlike sebum on the surface of the skin, which is exposed to various factors that can degrade it. In contrast, sebum on skin inside the ear canal is protected.

Dong’s study included 209 participants, 108 of whom had a diagnosis of PD. Ear canal secretions were collected from all participants using swabs and analyzed using gas chromatography-mass spectrometry.

Results showed that ear canal secretions from participants with PD contained 196 distinct VOCs compared with 168 VOCs in those without PD. Interestingly, no two participants had identical VOC profiles.

A Disease ‘Fingerprint’?

“In this case, VOC components could be used as a ‘fingerprint’ for disease identification,” the researchers wrote.

Adjusted analyses identified four VOCs that significantly differed between participants with and without PD: ethylbenzene, 4-ethyltoluene, pentanal, and 2-pentadecyl-1,3-dioxolane.

The investigators trained the AIO system using VOC data. By combining gas chromatography-surface acoustic wave sensors with a convolutional neural network (CNN) model, the AIO system achieved up to 94.4% accuracy in distinguishing participants with PD from those without.

In addition, the CNN model demonstrated a high level of performance with an area under the curve of 0.98, well above the 0.8 threshold considered strong by the researchers.

“Further enhancements to the diagnostic model could pave the way for a promising new PD diagnostic solution and the clinical use of a bedside PD diagnostic device,” the investigators wrote.

For now, Dong said the study’s takeaway message for clinicians is that “the potential of volatile organic compounds secreted by the skin as biomarkers for Parkinson’s disease has been further verified.”

The study was funded by the National Natural Science Foundation of China, “Pioneer” and “Leading Goose” R&D Program of Zhejiang Province, and the Fundamental Research Funds for the Central Universities. The investigators reported having no relevant financial relationships.

Our findings have contributed to a better understanding of the pathophysiology of this condition. We identified abnormalities in rectal sensitivity, anorectal pressure dynamics, and defecation-related anorectal dyscoordination in FARP. Additionally, We explored the psychological characteristics of patients with FARP and found that comorbid mood disorders are common in patients with FARP. Our findings provide a basis for the diagnosis and treatment of FARP.

Changes in the properties of the rectal wall and abnormalities in neural afferent pathways and central processing may all cause changes in rectal sensation. In terms of rectal sensory function, we found that when compared with controls, patients with FARP had significantly reduced sensation thresholds for desire to defecate, urgency to defecate and maximum tolerable sensation, indicating rectal hypersensitivity. Visceral hypersensitivity is a hallmark of IBS and manifests as reduced pain thresholds as a result of rectal distension and enhanced perception of bowel lumen distension, and studies have demonstrated a correlation between pain thresholds and the severity and frequency of pain symptoms [23]. FARP and irritable bowel syndrome are both centrally mediated FGIDs, and the mechanisms via pain that occur in these conditions may be similar. Several studies have shown that patients with IBS have lower initial sensation and initial pain thresholds and that visceral hypersensitivity to intestinal dilatation correlates with symptom severity [24,25,26]. Our findings suggest that visceral hypersensitivity is an important pathophysiological mechanism of FARP. Although the findings regarding first sensation were not statistically significant, patients with FARP showed an overall trend toward reduced sensation threshold, which might be related to the material in the expanded balloon used in our examination to assess rectal sensation. Rectal sensory thresholds are influenced by the stiffness of the rectal balloon. This balloon was mounted on a manometry catheter, and its tension might directly affect rectal compliance [27]. In future studies, we plan to investigate rectal sensory thresholds in patients with FARP further by using non-compliant polyethylene balloons and constant pressure or by means of electrical stimulation.

In this study, resting anal pressure and maximum anal squeeze pressure were significantly lower in the patients with FARP than in the controls, and the pelvic floor muscles were predominantly flaccid, which is consistent with previous findings [28]. Some investigators have focused on FARP associated with abnormal anorectal pressure. The correlation between abnormal anorectal pressure and anal pain is controversial, with few relevant reports in the literature. However, it is generally believed that anal levator ani syndrome is mostly caused by spasm of the pelvic floor muscles and elevated annal resting pressure and that an overactive anal sphincter muscle causes chronic pain. Grimaud et al. have suggested that chronic idiopathic anal pain may be caused by persistent abnormal contraction of the external anal sphincter and that this pain can be relieved by biofeedback treatment to relax the external anal sphincter and reduce muscle spasm and neuropsychological stress [23, 29]. We found that the anal resting pressure was lower in patients with FARP, which was the opposite of previous findings and might reflect the epidemiological characteristics of FARP. In our study, 72.14% of FARP patients were female, mainly perimenopausal patients, which is consistent with the characteristics of FARP patients in the study of Atkin GK et al. [30]. Most of these women had a history of pregnancy and childbirth, with obstetric damage to the anal sphincter and pubic nerves, damage to the tissues supporting the pelvic floor muscles, decreased muscle function, decreased hormone levels, and loss of elastin, manifesting as reduced pelvic floor muscle strength and decreased muscle tone [31, 32]. Weakness or spasm of the pelvic floor muscles is thought to be one of the pathophysiological bases for chronic pelvic pain [33].

During testing, we identified paroxysmal, transient, periodic sphincter spasms with elevated pressure in some patients with FARP, which might explain the spasm-related pain that occurs in these patients. Proctalgia fugax is short and episodic and is usually considered to be pain caused by abnormal smooth muscle contractions [34, 35, 36]. Some studies have shown that botulinum toxin injections relax the anal sphincter or levator ani muscle, but their therapeutic effect is inconsistent. The mechanism underlying anal sphincter or levator ani muscle tension in FARP remains unclear.

Some studies reported that the majority of patients with functional defecation disorders had anal levator muscle pressure pain and that their defecation disorders were improved with biofeedback treatment, suggesting that rectoanal incoordination of defecation is the pathophysiology of levator ani syndrome [37]. Interestingly, this hypothesis was consistent with our finding of paradoxical contraction of the anal sphincter during defecation in 76.92% of men with FARP. Defecation coordination disorders are manifested by insufficient rectal impulsion or abnormal anal canal relaxation during defecation. Chronic pain over time may cause the patient to fear defecation, which further increases pelvic floor muscle coordination disorders. Therefore, pelvic floor muscle dysfunction may be one of the causes of FARP.

Our findings indicate that anal resting pressure is positively correlated with sensory thresholds. The anal resting pressure mainly reflects the pressure of the internal anal sphincter (smooth muscle), so it is inferred that there may be a correlation between rectal sensitivity and smooth muscle pressure, but the mechanism of action needs to be investigated further. In contrast, the pathogenesis of FARP in patients with high anal resting pressure may be pain caused by smooth muscle spasms.

In our study, most patients with FARP exhibited symptoms of anxiety and depression. Although no significant gender differences were observed in anxiety and depression scores, female patients tended to report higher levels of these symptoms than males. Currently, Gut-brain interaction disorder is the most widely accepted theory regarding the pathogenesis of FGIDs. These disorders are often associated with psychiatric comorbidities, such as depression and anxiety, and these mood disorders cause gastrointestinal symptoms [38]. Anxiety states are widespread in patients with irritable bowel syndrome, and psychological factors may influence the persistence and perceived severity of these symptoms, which are significantly associated with pain levels and physical symptoms. Women’s anxiety, depression, and somatization are more obvious [39, 40]. Pain intensity is closely related to emotional symptoms. Pain has been shown to cause emotional disorders, and emotional disorders can exacerbate pain [41]. Whether pain is a somatic manifestation of psychological disorders and whether chronic pain is the main cause of emotional problems requires further research. Although our study did not find a correlation between mood and pain, it provides a basis for guidelines for the management of mood disorders in patients with FARP, which may include central neuromodulators, such as antidepressants, antipsychotics, and other central nervous system-targeted agents.

There were several imitations in our study. First, as a retrospective study, we were unable to obtain complete data on VAS scores, HAM-A scores, and HAM-D scores. A prospective study is needed to further investigate the anorectal physiological characteristics of FARP. Second, we did not assess the structure and function of the pelvic floor muscles in patients with FARP using a combination of pelvic floor ultrasound and defecography. Although HARM can aid in understanding the physiological features of the anus and rectum, it is better to be combined with other examinations to improve the diagnostic system for FARP, clarify its etiology and pathogenesis.