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Single brain scan can diagnose Alzheimer’s, UK study finds

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The MRI brain scans are used to check for protein deposits in the brain and shrinkage of the hippocampus

A single MRI scan of the brain could be enough to diagnose Alzheimer’s disease, according to new research by Imperial College London.

The research uses machine learning technology to look at structural features within the brain, including in regions not previously associated with Alzheimer’s.

The advantage of the technique is its simplicity and the fact that it can identify the disease at an early stage when it can be very difficult to diagnose.

Although there is no cure for Alzheimer’s disease, getting a diagnosis quickly at an early stage helps patients.

It allows them to access help and support, get treatment to manage their symptoms and plan for the future.

Being able to accurately identify patients at an early stage of the disease will also help researchers to understand the brain changes that trigger the disease, and support development and trials of new treatments.

The research was published in the Nature portfolio journal, Communications Medicine, and funded through the National Institute for Health and Care Research (NIHR) Imperial Biomedical Research Centre and the Medical Research Council.

Common form of dementia

Alzheimer’s disease is the most common form of dementia, affecting over half a million people in the UK.

Although most people with Alzheimer’s disease develop it after the age of 65, people under this age can develop it too.

The most frequent symptoms of dementia are memory loss and difficulties with thinking, problem solving and language.

Doctors currently use a raft of tests to diagnose Alzheimer’s disease, including memory and cognitive tests and brain scans.

The scans are used to check for protein deposits in the brain and shrinkage of the hippocampus, the area of the brain linked to memory. All of these tests can take several weeks, both to arrange and to process.

The new approach requires just one of these – a magnetic resonance imaging (MRI) brain scan taken on a standard 1.5 Tesla machine, which is commonly found in most hospitals.

Algorithm

The researchers adapted an algorithm developed for use in classifying cancer tumours, and applied it to the brain.

They divided the brain into 115 regions and allocated 660 different features, such as size, shape and texture, to assess each region.

They then trained the algorithm to identify where changes to these features could accurately predict the existence of Alzheimer’s disease.

Using data from the Alzheimer’s Disease Neuroimaging Initiative, the team tested their approach on brain scans from over 400 patients with early and later stage Alzheimer’s, healthy controls and patients with other neurological conditions, including frontotemporal dementia and Parkinson’s disease.

They also tested it with data from over 80 patients undergoing diagnostic tests for Alzheimer’s at Imperial College Healthcare NHS Trust.

The team found that in 98 per cent of cases, the MRI-based machine learning system alone could accurately predict whether the patient had Alzheimer’s disease or not.

It was also able to distinguish between early and late-stage Alzheimer’s with fairly high accuracy, in 79 per cent of patients.

‘An important step forward’

Professor Eric Aboagye, from Imperial’s Department of Surgery and Cancer, who led the research, said: “Currently no other simple and widely available methods can predict Alzheimer’s disease with this level of accuracy, so our research is an important step forward.

“Many patients who present with Alzheimer’s at memory clinics do also have other neurological conditions, but even within this group our system could pick out those patients who had Alzheimer’s from those who did not.

“Waiting for a diagnosis can be a horrible experience for patients and their families.

“If we could cut down the amount of time they have to wait, make diagnosis a simpler process, and reduce some of the uncertainty, that would help a great deal.

“Our new approach could also identify early-stage patients for clinical trials of new drug treatments or lifestyle changes, which is currently very hard to do.”

Future uses

The new system spotted changes in areas of the brain not previously associated with Alzheimer’s disease, including the cerebellum (the part of the brain that coordinates and regulates physical activity) and the ventral diencephalon (linked to the senses, sight and hearing).

This opens up potential new avenues for research into these areas and their links to Alzheimer’s disease.

Dr Paresh Malhotra, who is a consultant neurologist at Imperial College Healthcare NHS Trust and a researcher in Imperial’s Department of Brain Sciences, said: “Although neuroradiologists already interpret MRI scans to help diagnose Alzheimer’s, there are likely to be features of the scans that aren’t visible, even to specialists.

“Using an algorithm able to select texture and subtle structural features in the brain that are affected by Alzheimer’s could really enhance the information we can gain from standard imaging techniques.”

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Evening exercise benefits elderly hypertensives

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Evening exercise benefits elderly hypertensives

A study conducted at the University of São Paulo with 23 volunteers found that aerobic exercise performed in the evening benefits elderly hypertensives more than morning exercise.

Aerobic training is known to regulate blood pressure more effectively when practiced in the evening than in the morning.

Researchers who conducted a study of elderly patients at the University of São Paulo’s School of Physical Education and Sports (EEFE-USP) in Brazil concluded that evening exercise is better for blood pressure regulation thanks to improved cardiovascular control by the autonomic nervous system via a mechanism known as baroreflex sensitivity.

Leandro Campos de Brito, first author of the article, commented: “There are multiple mechanisms to regulate blood pressure, and although morning training was beneficial, only evening training improved short-term control of blood pressure by enhancing baroreflex sensitivity.

“This is important because baroreflex control has a positive effect on blood pressure regulation, and there aren’t any medications to modulate the mechanism.”

In the study, 23 elderly patients diagnosed and treated for hypertension were randomly allocated into two groups: morning training and evening training. Both groups trained for ten weeks on a stationary bicycle at moderate intensity, with three 45-minute sessions per week.

Key cardiovascular parameters were analysed, such as systolic and diastolic blood pressure, and heart rate after ten minutes’ rest. The data was collected before and at least three days after the volunteers completed the ten weeks of training.

The researchers also monitored mechanisms pertaining to the autonomic nervous system, which controls breathing, heart rate, blood pressure, digestion, and other involuntary bodily functions, such as muscle sympathetic nerve activity, which regulates peripheral blood flow via contraction and relaxation of blood vessels in muscle tissue, and sympathetic baroreflex sensitivity, assessing control of blood pressure via alterations to muscle sympathetic nerve activity.

In the evening training group, all four parameters analysed were found to improve: systolic and diastolic blood pressure, sympathetic baroreflex sensitivity, and muscle sympathetic nerve activity. In the morning training group, no improvements were detected in muscle sympathetic nerve activity, systolic blood pressure or sympathetic baroreflex sensitivity.

“Evening training was more effective in terms of improving cardiovascular autonomic regulation and lowering blood pressure. This can be partly explained as due to an improvement in baroreflex sensitivity and a reduction of muscle sympathetic nerve activity, which increased in the evening. For now, all we know is that baroreflex control is the decisive factor, from the cardiovascular standpoint at least, to make evening training more beneficial than morning training, since it induces the other benefits analysed. However, much remains to be done in this regard in order to obtain a better understanding of the mechanisms involved,” said Brito, who is currently a professor at Oregon Health & Science University’s Oregon Institute of Occupational Health Sciences in the United States, and continues to investigate the topic via circadian rhythm studies.

Baroreflex sensitivity regulates each heartbeat interval and controls autonomic activity throughout the organism.

“It’s a mechanism that involves sensitive fibres and deformations in the walls of arteries in specific places, such as the aortic arch and carotid body. When blood pressure falls, this region warns the brain region that controls the autonomic nervous system, which in turn signals the heart to beat faster and tells the arteries to contract more strongly. If blood pressure rises, it warns the heart to beat more slowly and tells the arteries to contract less. In other words, it modulates arterial pressure beat by beat,” Brito explained.

In previous studies, the EEFE-USP research group showed that evening aerobic training reduced blood pressure more effectively than morning training in hypertensive men (read more at: agencia.fapesp.br/34194), and that the more effective response to evening training in terms of blood pressure control was accompanied by a greater reduction in systemic vascular resistance and systolic pressure variability (read more at: agencia.fapesp.br/37432).

“Replication of the results obtained in previous studies and in different groups of hypertensive patients, associated with the use of more precise techniques to evaluate the main outcomes, has strengthened our conclusion that aerobic exercise performed in the evening is more beneficial to the autonomic nervous system in patients with hypertension. This can be especially important for those with resistance to treatment with medication,” Brito said.

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Revolutionising cancer treatment: intracellular protein delivery using hybrid nanotubes

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Revolutionising cancer treatment: intracellular protein delivery using hybrid nanotubes

A new hybrid nanotube stamp system has been developed which revolutionises precision medicine with high efficiency and cell viability rates for cancer treatment.

Precision medicine and targeted therapies are gaining traction for their ability to tailor treatments to individual patients while minimising adverse effects. Conventional methods, such as gene transfer techniques, show promise in delivering therapeutic genes directly to cells to address various diseases.

However, these methods face significant drawbacks, hindering their efficacy and safety. Intracellular protein delivery offers a promising approach for developing safer, more targeted, and effective therapies. By directly transferring proteins into target cells, this method circumvents issues such as silencing during transcription and translation and the risk of undesirable mutations from DNA insertion. Additionally, intracellular protein delivery allows for precise distribution of therapeutic proteins within target cells without causing toxicity.

A group of researchers led by Professor Takeo Miyake at Waseda University, Japan in collaboration with the Mikawa Group at the RIKEN Institute have now developed a hybrid nanotube stamp system for intracellular delivery of proteins. This innovative technique enables the simultaneous delivery of diverse cargoes, including calcein dye, lactate oxidase (LOx) enzyme, and ubiquitin (UQ) protein, directly into adhesive cells for cancer treatment.

The researchers explored the therapeutic potential of delivering LOx enzyme for cancer treatment. “Through our innovative stamp system, we successfully delivered LOx into both healthy mesenchymal stem cells (MSC) and cancerous HeLa cells. While MSC cells remained unaffected, we observed significant cell death in HeLa cancer cells following LOx treatment with viabilities decreasing over time. Our findings highlight the promising efficacy of intracellularly delivered LOx in selectively targeting and killing cancer cells, while sparing healthy cells, offering a targeted therapeutic strategy for cancer treatment,” explains Miyake.

Finally, the team successfully delivered 15N isotope-labeled UQ proteins into HeLa cells using the HyNT stamp system. This delivery allowed for the analysis of complex protein structures and interactions within the cells. In addition, optical and fluorescence imaging confirmed the presence of delivered UQ in HeLa cells, and nuclear magnetic resonance spectroscopy matched the intracellular UQ protein concentration with that of a solution containing 15N-labeled UQ. These results demonstrate the effectiveness of the stamp system in delivering target proteins for subsequent analysis.

The results demonstrate the remarkable capability of the HyNT stamp system in delivering LOx and UQ into a substantial number of adhesive cells, as required for regenerative medicine applications. The system achieved a notably high delivery efficiency of 89.9%, indicating its effectiveness in transporting therapeutic proteins into the target cells with precision. Moreover, the cell viability rate of 97.1% highlights the system’s ability to maintain the health and integrity of the treated cells throughout the delivery process.

The HyNT stamp system offers transformative potential in intracellular protein delivery, with applications spanning from cancer treatment to molecular analysis. Beyond medicine, its versatility extends to agriculture and food industries, promising advancements in crop production and food product development. With precise cell manipulation and efficient delivery, the HyNT stamp system is poised to revolutionize biomedical research, clinical practice, and diverse industries, paving the way for personalized interventions and shaping the future of modern medicine.

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Heat waves damage humans’ vital organs, shows new study

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Researchers from the University of California, Irvine have found evidence of the molecular causes of the damaging impact heat stress causes on the gut, liver and brain in the elderly.

The researchers suggest these findings point to the potential of developing precise prognostic and therapeutic interventions.

These organs have a complex and multidirectional communication system that touches everything from our gastrointestinal tract to the nervous system. Whether it is our brain affecting hunger or the liver influencing mental health, understanding the gut-liver-brain communication or “axis” is crucial to protecting human health.

Their study, which was conducted on mouse models, is published in the journal Scientific Reports, a Nature Portfolio journal. It is one of the first to fill the knowledge gap on the effects of heat stress on a molecular level of this crucial biological conversation.

“Inflammation in the brain and spine contributes to cognitive decline, compromises the ability to form new neurons and exacerbates age-related diseases,” said corresponding author, Saurabh Chatterjee, a professor of environmental & occupational health at the UC Irvine Program in Public Health. “By investigating the effects of heat stress on the gut-liver-brain crosstalk, we can better protect our increasingly vulnerable aging population.”

Using RNA analysis and bioinformatics to analyse elderly, heat-stressed mice, Chatterjee and his team found evidence of heat stress-affected genes in the brain and liver. A significant increase in the production of ORM2, a liver-produced protein, was observed in the heat-stressed mice. The control group of unstressed mice did not show a change, providing proof of organ dysfunction in the heat-stressed mice.

Researchers believe that increased secretion of ORM2 is a coping mechanism that may be due to gut inflammation and imbalance. In addition, ORM2 may impact the brain through a leaky blood-brain barrier, emphasizing intricate multi-organ crosstalk.

Additionally, the study shows the potential to use ORM2 for targeted biomarker interventions to prevent liver disease in heat exposure. This observation advances molecular insights into the pathophysiology of adverse heat events and will serve as a foundation for future research.

“Our findings have the potential to be used for the development of prognostic and therapeutic markers for precise interventions,” said Chatterjee. “In a dynamically changing global landscape, the imminent threat of climate change is evident in rising temperatures, raising concerns about intermittent heat waves. Our heating planet is undoubtedly leading to acute and chronic heat stress that harms the health of our aging population.”

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