Tag: Research

Investigating the efficacy and safety of existing drugs in patients with rare immune diseases
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This month the first study within the DRIMID consortium (DRIMID stands for Drug Rediscovery for Rare Immune Mediated Inflammatory Diseases) has started. This study will investigate the efficacy and safety of the drug filgotinib (approved for treatment of rheumatoid arthritis and ulcerative colitis) in three rare immune diseases (Behçet’s disease, idiopathic inflammatory myositis, IgG4-related disease). DRIMID aims to investigate whether this drug – despite the absence of formal drug approval – can also be used to treat these rare immune diseases.

New drugs are usually developed (and therefore faster accessible) for conditions involving large patient groups. However, for rare diseases, drug development is more difficult. With the establishment of the DRIMID partnership, major steps have now been taken to make new drugs available to such patient groups. The project is a collaboration between ARCH foundation, ReumaNederland, drug company AlfaSigma and a number of Dutch hospitals with the aim of (re)developing drugs for rare disorders.

Rare immune diseases

Rare immune-mediated inflammatory diseases usually have an unknown cause, and are often associated with the formation of autoantibodies (the immune system attacks its own body). Examples of such diseases include granulomatosis with polyangiitis, inflammatory myositis, vasculitis of the great vessels, IgG4-related disease, Behçet’s disease, Sjögren’s disease and systemic sclerosis. A major problem in clinical practice is that many patients do not respond adequately to common anti-inflammatory drugs over time. Thus, there is an unmet medical need for adequate treatment options for this group.

The study

The aim of the study is to investigate if filgotinib is efficacious when used by patients with rare immune diseases and whether the drug is well tolerated. Now that the first study within the DRIMID framework has been approved by the medical ethics review committee, patients are being sought with one of the following rare immune diseases:
- Behçet’s disease
- idiopathic inflammatory myositis
- IgG4-related disease
It is important that participants have active symptoms of the disease at the start of the study. In addition, it is important that they have first tried regular treatment methods, such as prednisone and at least one other anti-inflammatory agent. If the disease did not or insufficiently respond to these drugs, or if the patient was hypersensitive to these drugs, the patient may be eligible for this new study.

The study will follow up patients for 26 weeks. At several points during the study, the effect of the drug on symptoms will be measured by a physician via physical examination, blood tests and questionnaires. If the drug appears to be working well for the patient at the end of the study, the patient will be allowed to continue taking it. Participation in the study is free of charge.

Participating hospitals

The study, coordinated by rheumatologist Prof. Jaap van Laar MD PhD (Department of Rheumatology & Clinical Immunology, UMC Utrecht), will start in six Dutch hospitals. Patients can be approached by their physician to participate, but they can also inquire about eligibility themselves. They can do so by sending an e-mail to [email protected]. The research nurse at UMC Utrecht will then contact the hospital most suitable for the patient. The study will be conducted at the following locations:

– UMC Utrecht

– Amsterdam UMC

– Erasmus MC (Rotterdam)

– Radboudumc (Nijmegen)

– Haga Hospital (The Hague)

– Zuyderland Medical Center (Heerlen)

DRIMID consortium

DRIMID is an acronym and stands for ‘Drug Rediscovery for Rare Immune Mediated Inflammatory Diseases’. ARCH (Arthritis Research and Collaboration Hub, a Dutch medical expertise platform for rare autoimmune diseases), ReumaNederland and UMC Utrecht (the first academic partner within DRIMID) established the public-private DRIMID consortium in 2021. The consortium is funded by ReumaNederland and Health Holland. In time, the investigators within the consortium intend to expand the project to other immune diseases and also to other drug companies and drugs.

Source:

University Medical Center Utrecht
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April 23, 2024
Variability shown across patient characteristics

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In a recent study published in the BMC Medicine, a group of researchers identified the factors influencing the variability in depression prevalence among chronic pain sufferers and developed clinical prediction models for estimating depression likelihood in this group.

Study: Variability in the prevalence of depression among adults with chronic pain: UK Biobank analysis through clinical prediction models. Image Credit: fizkes/Shutterstock.com

Background

Chronic pain is a major global disability cause, affecting over 30% of the population and often coexisting with depression, which disables roughly 5% of adults worldwide. The relationship between chronic pain and depression is well-established; each condition has the potential to worsen the other.

Despite this, the prevalence of depression among those with chronic pain is variable, with estimates ranging from 15% to 85%, influenced by differences in depression definitions, pain severity, and demographic factors such as gender, additional health conditions, and socioeconomic status.

Further research is needed to refine the understanding of the complex relationship between chronic pain and depression and to enhance the accuracy and applicability of clinical prediction models across diverse populations.

About the study

The present study utilized data from the United Kingdom (UK) Biobank. It focused on participants who completed the “online mental health self-assessment” between 2016 and 2017 and the “experience of pain” questionnaire from 2019 to 2020.

The UK Biobank’s large dataset, combined with detailed surveys on pain and mental health, provided a unique platform for exploring chronic pain and its association with depression.

The “experience of pain” questionnaire was selected over the baseline data due to its more extensive array of pain types and additional variables related to pain characteristics.

Chronic pain was defined using criteria from the International Classification of Diseases 11th Revision, categorizing it as either widespread or regional based on participant responses. This distinction was important because the nature and location of pain are significant factors in the prevalence of depression among those affected.

Additionally, the study considered multisite pain and its impact on mood disorders, integrating questions about the most bothersome pain areas and the nature of the pain (neuropathic or not).

Depression was defined using a dual approach: a professional diagnosis linked from healthcare records and self-reported symptoms through a validated short form of the Composite International Diagnostic Interview.

This method aimed to capture a comprehensive view of participants’ lifetime mental health history, which is crucial for understanding fluctuating conditions like depression.

The study also used the Patient Health Questionnaire to assess current depression among participants, adding another layer to the analysis. Statistical analyses included logistic regression models developed to estimate depression probability among chronic pain sufferers.

The models integrated a range of predictors, including demographic details, pain characteristics, and lifestyle factors, highlighting the complexity of chronic pain’s impact on mental health.

Study results

The present comprehensive analysis involved 24,405 UK Biobank participants with chronic pain. Among these individuals, 3.7% reported present depression, 32.6% had a lifetime history of depression, 21.8% exhibited subthreshold depressive symptoms throughout their lives, and 45.6% had no lifetime history of depression.

The cohort predominantly comprised white individuals (97.1%) with an average age of 64.1 years, highlighting the need to consider a variety of demographic factors in understanding depression among those with chronic pain.

For those experiencing chronic widespread pain, 45.7% reported a lifetime history of depression, with prevalence rates varying significantly from 25.0% to 66.7% based on individual characteristics.

A prediction model incorporating variables such as age, body mass index (BMI), smoking status, physical activity, and medical history showed moderate discrimination and good calibration, suggesting its utility in clinical settings. Notably, age, gender, and BMI emerged as significant predictors of a lifetime history of depression.

Similarly, among those with chronic regional pain, 30.2% had a lifetime history of depression. The model for this group included predictors like the nature of pain and regular opioid use, and it demonstrated similar levels of discrimination and calibration.

Key predictors again included age, gender, and the specific characteristics of pain, which significantly influenced depression outcomes.

The study also assessed present depression, finding that 10.5% of individuals with chronic widespread pain and 2.5% of those with chronic regional pain were currently depressed.

Different predictors were relevant for these outcomes, with smoking status, physical activity, and comorbid conditions like chronic kidney disease playing significant roles. Models developed for current depression demonstrated moderate to high levels of discrimination and good calibration, indicating their potential reliability.

Additional analyses confirmed that the prediction models were generally robust across different types of regional pain, although some categories, like stomach and chest pain, showed slightly lower predictive accuracy.

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April 23, 2024
Replacing dinner calcium with breakfast intake could reduce heart disease risk, study finds

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In a recent study published in BMC Public Health, researchers investigated whether the quantity of calcium consumed at breakfast and dinner was associated with cardiovascular disease (CVD) in the general population.

Study: Association of dietary calcium intake at dinner versus breakfast with cardiovascular disease in U.S. adults: the national health and nutrition examination survey, 2003–2018. Image Credit: Goskova Tatiana/Shutterstock.com

Background

Cardiovascular disease is the primary cause of mortality globally and the most prevalent chronic illness among individuals living in the United States.

Calcium, a crucial dietary element, helps prevent and manage CVD by regulating blood vessels, muscular contraction, nerve transmission, hormone production, fat mass, blood pressure, and blood lipids. Circadian clocks in animals govern circadian rhythms, which are biological rhythmic patterns that last 24 hours.

Diet is a significant external element that influences the synchronization of circadian clocks. Recent research indicates that calcium intake can influence physiological variations in circadian pacemaker-type neuronal cells and alter the expression of the biological clock genes.

However, the relationship between calcium consumption at various times of the day and cardiovascular disease is unclear.

About the study

The present study examined the relationship between dietary calcium consumption at dinner and breakfast and CVD.

The study comprised 36,164 United States individuals (17,456 males, 18,708 females, and 4,040 cardiovascular disease patients) from the 2013–2018 National Health and Nutrition Examination Surveys. They stratified the participants into five groups based on their calcium intakes from night and early morning meals.

The study focused on the fraction of calcium consumption in night and morning meals (Δ=calcium intake from dinner /calcium intake from breakfast).

The study’s endpoint was cardiovascular disease, based on a self-reported history of angina, heart failure, stroke, coronary artery disease, or heart attack.

Potential confounders included age, sex, educational attainment, smoking status, physical activity, marital status, annual income, alcohol consumption, body mass index (BMI), high-density lipoprotein (HDL), uric acid (UA), total cholesterol (TC), hypertension, and type 2 diabetes (T2DM).

Following confounder adjustment, the researchers used logistic regression to calculate the odds ratios (OR) for the relationship between the calcium intake percentage at night and morning and cardiovascular disease.

They used dietary replacement models to investigate changes in cardiovascular disease risk by replacing 5.0% calcium from dinner with calcium consumption in the morning.

The team conducted home interviews with individuals and collected data at a mobile testing facility. They excluded individuals under 20 years, pregnant women, those with incomplete data, those consuming more than 4,500 kcal per day, and those using calcium supplements.

They assessed dietary consumption using a 24-hour diet recall completed on two non-consecutive days. They assessed nutrient intake using the Food and Nutrient Database for Dietary Studies recommendations by the United States Department of Agriculture. They performed sensitivity studies to investigate the validity of the study findings.

Results and discussion

Individuals in the uppermost quartile showed a higher likelihood of having cardiovascular disease than those in the lowermost quintile, with adjusted OR values of cardiovascular disease of 1.2.

While keeping total calcium consumption constant, substituting a 5.0% calcium consumption from dinner meals with calcium consumption at breakfast reduced CVD risk by 6.0%.

Breakfast meals with morning snacks or dinner meals with evening snacks reduced CVD risk by 6% (OR, 0.9). Compared to the lowermost quintile, having breakfast and morning snacks as breakfast or dinner and evening snacks as dinner in the uppermost Δ quintile significantly reduced CVD risk, with adjusted ORs of 1.1 and 1.1, respectively.

Consuming dinner with evening snacks and breakfast with morning snacks yielded an adjusted OR of 1.1. Among overweight and obese individuals, the adjusted odds ratio of cardiovascular disease in the uppermost Δ quintile was 1.2 after adjusting for various confounding variables.

The circadian clock governs several cardiovascular processes, including endothelial function, thrombus development, blood pressure, and heart rate. Basic helix-loop-helix ARNT-like protein 1 (Bmal1), a primary clock gene, regulates calcium absorption and metabolism.

Sleep periods improve calcium retention capability. Circadian rhythm influences the inflammatory nuclear factor kappa B (NFκB) pathway, metabolism, and immune system adaptability.

The study found that those in the top percentile of calcium consumption at dinner and breakfast are more likely to develop cardiovascular disease. The findings imply that allocating calcium intake to both meals is critical.

The study demonstrated a positive correlation between the Δ value and cardiovascular disease risk. Replacing 5.0% of calcium consumption from dinner meals with the same amount at breakfast reduced CVD risk by 6.0%. However, further research is required to corroborate these findings across races and nations.

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April 23, 2024
US study links extended sitting and lack of coffee to higher death rates

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The researchers of a recent study published in BMC Public Health examined the independent and combined effects of daily sedentary times and coffee consumption on cardiovascular disease (CVD)-related and any-cause mortality in the United States.

Study: Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults. Image Credit: ViDI Studio/Shutterstock.com

Background

Sedentary behavior and coffee drinking are associated with chronic illnesses, but their combined links with mortality are poorly understood.

Prolonged sitting raises the risk of all-cause and heart disease-related mortality, particularly in individuals who do not meet the recommended physical activity levels. According to studies, death rates are increasing for all causes, including cancer.

Coffee consumption varies depending on lifestyle and demographics, with age playing a primary role. Its antioxidant qualities can lower chronic disease morbidity and mortality.

However, further study is required to discover the best coffee intake technique and dose. The growing incidence of sedentary behavior and coffee drinking raises concerns about their relationship.

About the study

In the present prospective cohort study, researchers investigated the combination effects of daily sedentary times and coffee consumption on death from all causes and CVDs.

The researchers examined data from the National Health and Nutrition Examination Surveys (NHANES) conducted between 2007 and 2018, including 10,639 participants.

They excluded individuals with missing data on exposure factors, outcome variables, and covariates and those with inconsistent daily energy intake. They gathered mortality data from interviews and physical examinations until 31 December 2019 and assessed self-reported daily sedentary time data.

All participants had offline interviews, physical examinations, and laboratory investigations at testing sites. They collected coffee beverage data from one-day food recall questionnaires and used the Global Physical Activity Questionnaire (GPAQ) to assess sedentary time.

The primary study outcomes were cardiovascular disease and all-cause death, established using ICD-10 numbers.

The team used Cox proportional hazard regressions to calculate hazard ratios (HR) values adjusted for sociodemographic variables, lifestyle factors, and medical history covariates. Sociodemographic variables included sex, ethnicity, race, educational attainment, marital status, poverty income ratio, body mass index (BMI), and waist circumference].

Lifestyle factors included smoking habits, alcohol intake, the Healthy Eating Index (HEI) 2015 values, and physical activity. Medical history included hypertension, diabetes, hypercholesterolemia, cancer, and medications.

Results

Individuals being sedentary for six hours or more daily showed a higher likelihood of being white, non-Hispanic, and educated beyond high school. They also exhibited a larger waist circumference, abdominal obesity, and a higher BMI.

Coffee users showed higher odds of being non-Hispanic, Caucasian, older, and educated beyond high school. Only 52% of US people drink coffee, and over half report sitting for at least six hours daily. Twenty-three percent of Americans stated they sat for six hours or more daily and did not drink coffee.

Over a 13-year follow-up, 945 fatalities occurred among research participants, with 284 of these being due to CVD.

Sedentary times of >8.0 hours daily were linked to increased death rates from all causes (HR, 1.5) and CVD-related (HR, 1.8) compared to sitting times of <4.0 hours daily, according to multivariate analysis. Individuals in the uppermost quartile for coffee consumption had decreased odds of any-cause deaths (HR, 0.7) and CVD-related fatalities (HR, 0.5) compared to non-coffee users.

Joint analyses revealed that coffee non-drinkers sitting for at least six hours per day had a 1.6-fold higher likelihood of any-cause mortalities than coffee consumers who sat for <6.0 hours daily.

The findings indicate that the relationship between sitting time and increased death risk was exclusive for adult non-consumers of coffee, not among coffee drinkers.

Any-cause death risk was considerably greater in those aged >65 years inactive for >8.0 hours daily (HR, 1.7). Individuals aged >65 years, females, those with truncal obesity, former alcohol consumers, former cigarette smokers, and insufficient physical activity had higher HR values for all-cause death risk as their daily sedentary time increased, and the trend showed statistical significance.

Subgroup analyses stratified by coffee intake showed that the relationship between coffee drinking and all-cause death risk was considerably more robust among black and non-Hispanic individuals consuming coffee (HR 0.6).

Conclusions

The study showed sedentary behavior associated with increased any-cause and heart disease-related mortality. However, any-cause fatalities were lower in the highest percentile of coffee consumption, and the lower risk was strongly associated with any amount of coffee consumed.

The relationship was exclusively to individuals who did not drink coffee. Over a 13-year follow-up, the researchers found a statistically significant link between individuals sitting for more than eight hours per day and an elevated risk of any cause and cardiovascular death.

Prolonged and unbroken sitting tends to decrease glucose metabolism and exacerbate inflammation. Coffee consumption reduces the risk of metabolic syndrome, which promotes inflammation.

Prospective cohort studies are needed to analyze the influence of coffee intake on health benefits in sedentary populations, and further research, especially multicenter studies, is required to investigate the effects of individual coffee types on mortality and causal linkages.

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April 23, 2024
The hidden struggle of lateropulsion in stroke survivors

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Lateropulsion, a clinical condition which results in the body leaning to one side, affects about half of all stroke survivors.

Edith Cowan University (ECU) PhD graduate Dr Jessica Nolan said while the problem is common, lateropulsion is still severely under recognized and under assessed around the world.

A person with lateropulsion uses the limbs on their stronger side, to push themselves over toward their weaker side. Often those with lateropulsion resist correction back towards their stronger side or the mid-line, and this can cause problems with sitting, standing, walking and looking after themselves. It is also associated with a higher risk of falling, reduced recovery and a reduced likelihood of discharge after in-patient rehabilitation.”

Dr Jessica Nolan, Edith Cowan University

“The treatment of lateropulsion in stroke survivors is a critical aspect of rehabilitation, however the issue requires better understanding and more research.”

It is estimated that in 2020, there were some 39 500 stroke events in Australia, averaging more than 100 a day. In that same year, it was estimated that more than 445 087 Australians were living with the side effects of stroke. Stroke is one of Australia’s biggest killers, with the event killing more women than breast cancer and more men than prostate cancer.

Despite the prevalence of lateropulsion following a stroke event, a lack of agreement on terminology and the defining features of the condition present obstacles to understanding its prevalence, accurately comparing research results, and agreeing on a consistent approach to rehabilitation.

“People affected after a stroke may be at a disadvantage, because of the inconsistent approaches to rehabilitation and the failure of health policy to accommodate their rehabilitation needs,” Dr Nolan said.

“Improved understanding of the condition could lead to improved management, which will enhance patient outcomes after stroke and increase efficiency of healthcare resource use.”

Dr Nolan has previously led a Delphi consensus process, partnering with 21 international experts to reach a consensus on the terminology used to describe the condition and on the rehabilitation requirements for people living with severe lateropulsion, as well as recommendations for rehabilitation.

While a consensus regarding terminology was not reached, the panel achieved some agreement that lateropulsion was the preferred term to describe the phenomenon. More than 100 consensus-based recommendations were also provided to guide rehabilitation of lateropulsion.

In her latest research, Dr Nolan found that lateropulsion could continue to resolve up to one-year post-stroke, far beyond the period of in-patient rehabilitation. Average in-patient length of stay following a stroke varies, but for those patients presenting with lateropulsion, in-patient stay was about three to four weeks longer compared to those without.

“This study was the first to investigate functional recovery up to 12 months post-stroke, and to compare outcomes among people with and without lateropulsion. This study supports findings from previous work that lateropulsion severity was a predictor of long-term functional outcomes.”

“Lateropulsion after stroke can resolve, but it is dependent on access to ongoing rehabilitation.

“People who do not have access to long-term rehabilitation following a stroke did not show the same extent of lateropulsion resolution or functional recovery.”

A copy of the research, as it appears in Topics in Stroke Rehabilitation, can be found here.

Source:

Journal reference:

Nolan, J., et al. (2024). Lateropulsion resolution and outcomes up to one year post-stroke: a prospective, longitudinal cohort study. Topics in Stroke Rehabilitation. doi.org/10.1080/10749357.2024.2333186.

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April 23, 2024
The vital role of therapeutic alliances in psychedelic treatment

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Drug effects have dominated the national conversation about psychedelics for medical treatment, but a new study suggests that when it comes to reducing depression with psychedelic-assisted therapy, what matters most is a strong relationship between the therapist and study participant.

Researchers analyzed data from a 2021 clinical trial that found psilocybin (magic mushrooms) combined with psychotherapy in adults was effective at treating major depressive disorder.

Data included depression outcomes and participant reports about their experiences with the drugs and their connection with therapists. Results showed that the stronger the relationship between a participant and clinician – called a therapeutic alliance – the lower the depression scores were one year later.

What persisted the most was the connection between the therapeutic alliance and long-term outcomes, which indicates the importance of a strong relationship.”

Adam Levin, Study Lead Author and Psychiatry and Behavioral Health Resident, College of Medicine, The Ohio State University

Past research has consistently found that as mental health treatments changed, a trusting relationship between clients and clinicians has remained key to better outcomes, said senior author Alan Davis, associate professor and director of the Center for Psychedelic Drug Research and Education in The Ohio State University College of Social Work.

“This concept is not novel. What is novel is that very few people have explored this concept as part of psychedelic-assisted therapy,” Davis said. “This data suggests that psychedelic-assisted therapy relies heavily on the therapeutic alliance, just like any other treatment.”

The study was published recently in the journal PLOS ONE.

Twenty-four adults who participated in the trial received two doses of psilocybin and 11 hours of psychotherapy. Participants completed the therapeutic alliance questionnaire, assessing the strength of the therapist-participant relationship, three times: after eight hours of preparation therapy and one week after each psilocybin treatment.

Participants also completed questionnaires about any mystical and psychologically insightful experiences they had during the drug treatment sessions. Their depression symptoms were assessed one week, four weeks, and up to one year after the trial’s end.

The analysis showed that the overall alliance score increased over time and revealed a correlation between a higher alliance score and more acute mystical and/or psychologically insightful experiences from the drug treatment. Acute effects were linked to lower depression at the four-week point after treatment, but were not associated with better depression outcomes a year after the trial.

“The mystical experience, which is something that is most often reported as related to outcome, was not related to the depression scores at 12 months,” Davis said. “We’re not saying this means acute effects aren’t important – psychological insight was still predictive of improvement in the long term. But this does start to situate the importance and meaning of the therapeutic alliance alongside these more well-established effects that people talk about.”

That said, the analysis showed that a stronger relationship during the final therapy preparation session predicted a more mystical and psychologically insightful experience – which in turn was linked to further strengthening the therapeutic alliance.

“That’s why I think the relationship has been shown to be impactful in this analysis – because, really, the whole intervention is designed for us to establish the trust and rapport that’s needed for someone to go into an alternative consciousness safely,” Davis said.

Considering that psychedelics carry a stigma as Schedule I drugs under the Controlled Substances Act, efforts to minimize negative experiences in future studies of their therapeutic potential should be paramount – and therapy is critical to creating a supportive environment for patients, the authors said.

This study ideally will help clearly position psychedelics treatment as a psychotherapeutic intervention moving forward – rather than its primary purpose being administration of a drug, Levin said.

“This isn’t a case where we should try to fit psychedelics into the existing psychiatric paradigm – I think the paradigm should expand to include what we’re learning from psychedelics,” Levin said. “Our concern is that any effort to minimize therapeutic support could lead to safety concerns or adverse events. And what we showed in this study is evidence for the importance of the alliance in not just preventing those types of events, but also in optimizing therapeutic outcomes.”

This work was supported by the Center for Psychedelic and Consciousness Research, funded by the Steven & Alexandra Cohen Foundation, the RiverStyx Foundation and private donors. It was also supported by the Center for Psychedelic Drug Research and Education (CPDRE), funded by anonymous donors.

Additional co-authors are Rafaelle Lancelotta, Nathan Sepeda and Theodore Wagener of Ohio State, and Natalie Gukasyan, Sandeep Nayak, Frederick Barrett and Roland Griffiths of the Center for Psychedelic and Consciousness Research at Johns Hopkins University, where Davis is an affiliate.

Source:

Journal reference:

Levin, A. W., et al. (2024) The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder. PLOS ONE. doi.org/10.1371/journal.pone.0300501.

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April 23, 2024
Womb pressure shapes facial features, UCL study reveals

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Physical cues in the womb, and not just genetics, influence the normal development of neural crest cells, the embryonic stem cells that form facial features, finds a new study led by UCL researchers.

The study published in Nature Cell Biology found that an increase in hydrostatic pressure sensed by the embryo can hinder the healthy development of facial features in mouse and frog embryos and in human embryoids (cell structures grown in the lab from human stem cells), suggesting that differences in pressure might affect the risk of facial malformations.

The researchers found that when neural crest cells are exposed to higher-than-usual levels of pressure, key cell signaling pathways are impeded, and the risk of craniofacial malformations significantly increases.

Lead author Professor Roberto Mayor (UCL Cell & Developmental Biology) said: “Our findings suggest that facial malformations could be influenced not only by genetics but by physical cues in the womb such as pressure.

“When an organism is experiencing a change in pressure, all the cells – including the embryo inside the mother – are able to sense it.

Our work shows that embryos are sensitive to pressure, but we do not know how sensitive they are; for instance, will a change in the pressure inside the uterus be able to affect the embryo? This will require further research to understand how changes inside the body as well as in environmental pressure might influence human embryo development.”

Roberto Mayor, Professor, Cell & Developmental Biology, University College London

The researchers say their findings could also have implications for stem cell research, as the study indicates that the development and differentiation (the process of stem cells becoming specialized cells) of stem cells are under the influence of pressure. Understanding this connection could transform how scientists manipulate stem cells for various therapeutic purposes.

The findings add to work by Professor Mayor and colleagues at UCL into how mechanical cues in the womb can influence the development of facial features, as they have previously found that cells in the developing embryo sense the stiffness of other cells around them, which is key to them moving together to form the face and skull.

Source:

University College London

Journal reference:

Alasaadi, D. N., et al. (2024). Competence for neural crest induction is controlled by hydrostatic pressure through Yap. Nature Cell Biology. doi.org/10.1038/s41556-024-01378-y.

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April 23, 2024
Higher zinc intake linked to lower asthma risk in overweight kids

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In a recent study published in the World Allergy Organization Journal, researchers examined the relationship between asthma occurrence and intake of dietary zinc among children and adolescents overweight and obesity, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2020.

The study suggests that higher dietary zinc intake is associated with a reduced risk of asthma in this population, highlighting the potential role of zinc in mitigating asthma risk among children and adolescents.

Study: Association between dietary zinc intake and asthma in overweight or obese children and adolescents: A cross-sectional analysis of NHANES. Image Credit: Danijela Maksimovic / Shutterstock

Background

Childhood asthma, a prevalent respiratory condition, poses a growing global concern, with increasing rates among children and adolescents. This trend is compounded by the rising prevalence of obesity in this demographic, which exacerbates asthma symptoms and reduces treatment effectiveness.

Recent research has focused on the role of nutrients, particularly zinc, in asthma management due to its involvement in inflammation and oxidative stress regulation. Prior studies yielded inconsistent results regarding the association between asthma and zinc intake.

To address this gap, a study utilizing NHANES data examined the relationship between dietary zinc intake and asthma among overweight or obese children and adolescents, hypothesizing that asthmatic individuals in this group would have lower zinc intake than their healthy counterparts.

About the study

The study utilized data from NHANES, covering four survey cycles from 2011 to 2020, to investigate the relationship between asthma and dietary zinc intake among overweight or obese adolescents and children in the United States.

Participants under 20 years old were included, with those having incomplete data or falling under the categories of underweight or normal weight being excluded.

Asthma status was determined based on participants’ self-reported history of diagnosis and recent asthma attacks. Dietary zinc intake was assessed through 24-hour dietary recall interviews and categorized into quartiles.

In multivariate logistic regression models, various potential covariates, including demographic factors, family history of asthma, and dietary factors, were considered and adjusted for.

Restricted cubic splines were used to analyze the relationship between zinc intake and asthma while controlling for these covariates.

Additionally, multivariate logistic regression analysis was performed to evaluate potential interactions between dietary zinc and other factors such as sex, age, and family history of asthma.

Sensitivity analyses were conducted to validate the robustness of the findings.

Findings

The final sample included 4,597 individuals, 20, with 963 reporting asthma. Participants with incomplete asthma questionnaires, incomplete dietary zinc intake data, or normal weight were excluded.

The median age was 11 years, and 20.9% of the participants were diagnosed with asthma; 49.6% reported their gender as male. Higher zinc intake was correlated with male gender, non-Hispanic white ethnicity, lower household income, absence of familial asthma history, and no dietary supplement use.

After controlling for various factors, including demographics and dietary intake, a significant inverse relationship was found between dietary zinc intake and asthma.

The adjusted odds ratios for asthma in the second, third, and fourth quartiles were 0.78, 0.76, and 0.71, respectively, compared to the lowest zinc intake quartile.

Stratified analyses showed no significant interactions, and sensitivity analyses confirmed the robustness of the findings. Furthermore, dietary zinc intake was inversely associated with recent asthma attacks and remained so after adjusting for asthma treatment.

These results suggest a consistent negative linear trend between the intake of dietary zinc and the risk of developing asthma in children and adolescents who are overweight or obese.

Conclusions

Researchers found a significant inverse association between dietary zinc intake and asthma risk, even after controlling for various factors such as demographics and dietary intake. This association remained robust across stratified and sensitivity analyses, indicating its reliability.

Previous research has shown inconsistent conclusions regarding the relationship between zinc levels and asthma, with most focusing on body fluid zinc levels rather than dietary intake.

However, the current study, focusing on dietary zinc intake in a large population of overweight or obese children and adolescents, demonstrated a clear inverse correlation with asthma risk.

The study highlighted potential pathways through which zinc may influence asthma, including its antioxidant properties, immunomodulatory effects, and anti-inflammatory effects. These mechanisms suggest that zinc could be a potential therapeutic target for alleviating asthma symptoms among people with overweight or obesity.

The study’s strengths include its large sample size, focus on overweight or obese children and adolescents, and use of diverse statistical methods. However, limitations such as potential residual confounding effects, reliance on self-reported asthma diagnosis, and the cross-sectional design prevent causal inferences.

These results emphasize the importance of considering nutritional factors in asthma management and warrant further research into the therapeutic potential of zinc supplementation.

Future studies using prospective cohort designs and randomized controlled trials may shed further light on the causal effect of dietary zinc intake on alleviating asthma in this population.

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April 23, 2024
Ophthalmological method can be used to monitor neurodegeneration in Parkinson’s patients

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A study by the University of the Basque Country (UPV/EHU) and Biobizkaia proposes using an available, simple, non-invasive tool to monitor this neurodegeneration.

Although there are still some aspects pending confirmation for its use in the clinical setting, and its resolution needs to be improved slightly, a study by the UPV/EHU and Biobizkaia has shown that a method routinely used to carry out ophthalmological tests can also be used to monitor the neurodegeneration that occurs in Parkinson’s patients. In the course of the research it was found that the neurodegeneration of the retina probably precedes cognitive impairment.

When Parkinson’s or another neurodegenerative disease is diagnosed, patients always ask: “And now what? What will happen? What can be expected from the disease?” For neurologists, however, it is not possible to answer these questions precisely, as “the evolution of patients tends to be very varied: some experience no change over the years, while others end up with dementia or in a wheelchair”, explained Ane Murueta-Goyena, researcher in the UPV/EHU’s department of Neurosciences.

Today, identifying Parkinson’s patients at risk of cognitive impairment poses a major challenge, yet this is necessary when it comes to providing more effective clinical treatments and stepping up clinical trials. In fact, Dr. Ane Murueta-Goyena, in collaboration with Biobizkaia’s research staff, wanted to see “whether the visual system can enable this deterioration to be predicted, in other words, what future the patient can expect within a few years”. The thickness of the retina was used for this purpose.

The retina is a membrane located at the back of the eyeball, it is related to the nervous system and comprises several layers. During the study, a cohort of Parkinson’s patients had the thickness of the innermost layer of their retinas measured using optical coherence tomography. This type of tomography is a routinely used instrument in ophthalmological tests, as it allows high-resolution, repeatable and accurate measurements to be made. So the evolution of this retinal layer was analysed and compared in people with and without Parkinson’s disease over the 2015-2021 period. The results of the analysis of the images of the retinal layers of Parkinson’s patients were also confirmed in a UK hospital.

The results showed that the retinal layer is noticeably thinner in Parkinson’s patients. It was also observed that “during the initial phases of the disease it is in the retina where the greatest neurodegeneration is detected, and, from a given moment onwards, when the layer is already very thin, a kind of stabilising of the neurodegeneration process takes place. Retinal thinning and cognitive impairment do not occur simultaneously. The initial changes in the retina are more evident and then, over the years, patients are observed to worsen clinically in both cognitive and motor terms”, explained Murueta-Goya. In other words, the slower retinal layer thickness loss is associated with faster cognitive decline; this slowness is linked to greater severity of the disease”.

The researcher has attached great importance to the results: “We have obtained information on the progression of the disease, and the tool we are proposing is non-invasive and available at all hospitals.” The results need to be validated internationally and “by slightly improving the resolution of the technology, we will be closer to validating the method for monitoring the neurodegeneration that takes place in Parkinson’s disease”. The researcher also revealed that they are continuing the research on another cohort of patients and that funding is the key.

Source:

University of the Basque Country

Journal reference:

Murueta-Goyena, A., et al. (2024). Association of retinal neurodegeneration with the progression of cognitive decline in Parkinson’s disease. Npj Parkinson’s Disease. doi.org/10.1038/s41531-024-00637-x.

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April 22, 2024
ChatGPT shows promise in automating data transfer for stroke treatment

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In an ischemic stroke, an artery in the brain is blocked by blood clots and the brain cells can no longer be supplied with blood as a result. Doctors must therefore act quickly and unblock the artery with the help of catheters. During the so-called mechanical thrombectomy, a lot of data has to be recorded and then transferred to various registers. Dr Nils Lehnen, senior physician at the Clinic for Diagnostic and Interventional Neuroradiology and Paediatric Neuroradiology at the University Hospital Bonn (UKB), has now discovered in a study that ChatGPT could be a great help in this data transfer. The results have now been published in the specialist journal “RADIOLOGY”.

When did the patient arrive, when was a CT scan performed, when was the first puncture, when could the blood flow be restored,… During mechanical thrombectomy, a range of data must be recorded in the patient report and then manually transferred to various registers for the clinical outcome and for prospective studies.

“This is a labor-intensive task that is also prone to transcription errors,” says Dr Nils Lehnen, who also conducts research at the University of Bonn. “We therefore asked ourselves whether an AI such as ChatGPT could perform this transfer faster and possibly even more reliably.”

In radiology, ChatGPT is already being tested in various procedures – for example, in the simplification of reports or in answering patient questions on breast cancer screening. However, whether ChatGPT can correctly extract data from free-text reports of a mechanical thrombectomy for a database and simultaneously generate clinical data was previously unexplored and was the research objective of this new study.

Dr Lehnen’s research group first created a German prompt for ChatGPT and tested it on 20 reports in order to identify errors and subsequently adapt the prompt. After the correction, the data extraction using ChatGPT was tested on 100 internal reports from the UKB. For optimal comparison, an experienced neuroradiologist also compiled the results without seeing the ChatGPT evaluation. The researchers then compared the results and found that ChatGPT had correctly extracted 94 per cent of data entries and no post-processing was required. The researchers only considered the ChatGPT data entries that exactly matched that of the expert to be correct. Any deviations, such as additional symbols, punctuation marks or synonyms, were categorized as incorrect.

To validate these results, the researchers tested a further 30 external reports with the same prompt. ChatGPT achieved 90 per cent correct data entries.

This suggests that ChatGPT could be an alternative to manually retrieving this data. However, the reports and the prompt were only created by us in German, so the results of our study may need to be confirmed for other languages. In addition, we still observed poor results for certain data points, which shows that human supervision is still needed. However, we expect that further optimization of the prompt will further improve the results and that ChatGPT can make work easier in this area in the future.”

Dr. Nils Lehnen, senior physician at the Clinic for Diagnostic and Interventional Neuroradiology and Paediatric Neuroradiology at the University Hospital Bonn (UKB)

Source:

University Hospital of Bonn (UKB)

Journal reference:

Lehnen, N. C., et al. (2024). Data Extraction from Free-Text Reports on Mechanical Thrombectomy in Acute Ischemic Stroke Using ChatGPT: A Retrospective Analysis. Radiology. doi.org/10.1148/radiol.232741.

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April 22, 2024