Month: July 2023

Gravity-powered Biomedical Devices Pull Droplets Through a Maze

Source: Unsplash CC0

Biomedical engineers at Duke University have developed an entirely new approach to building point-of-care diagnostic devices that only use gravity to transport, mix and otherwise manipulate the liquid droplets involved. The demonstration, in the journal Device, requires only commercially available materials and very little power to read results, making it a potentially attractive option for applications in low-resource settings.

“The elegance in this approach is all in its simplicity – you can use whatever tools you happen to have to make it work,” said Hamed Vahabi, a former postdoctoral researcher at Duke. “You could theoretically even just use a handsaw and cut the channels needed for the test into a piece of wood.”

The study was conducted in the laboratory of Ashutosh Chilkoti, the Alan L. Kaganov Distinguished Professor of Biomedical Engineering at Duke.

There is no shortage of need for simple, easy-to-use, point-of-care devices. Many demonstrations and commercial devices seek to make diagnoses or measure important biomarkers using only a few drops of liquid with as little power and expertise required as possible. Their goal is to improve health care for the billions of people living in low-resource settings far from traditional hospitals and trained clinicians.

All of these tests have the same basic requirements; they must move, mix and measure small droplets containing biological samples and the active ingredients that make measuring specific biomarkers possible. More expensive examples use tiny electrical pumps to drive these reactions. Others use the physics of liquids within microchannels (microfluidics) that create a sort of suction effect.

This is the first demonstration that only uses gravity. Each approach offers uniquely useful abilities as well as drawbacks.

“Most microfluidic devices need more than just capillary forces to operate,” Chilkoti said. “This approach is much simpler and also allows very complex fluid paths to be deigned and operated, which is not easy or cheap to do with microfluidics.”

The new gravity-driven approach relies on a set of nine commercially available surface coatings that can tweak the wettability and slipperiness at any given point on the device. That is, they can adjust how much droplets flatten down into pancakes or remain spherical while making it easier or harder for them to slide down an incline.

Used together in clever combinations, these surface coatings can create all the microfluidic elements needed in a point-of-care test. For example, if a given location is extremely slippery and a droplet is placed at an intersection where one side pulls liquid flat and the other pushes it into a ball, it will act like a pump and accelerate the droplet toward the former.

“We came up with many different elements to control the motion, interaction, timing and sequence of multiple droplets in the device,” Vahabi said. “All of these phenomena are well-known in the field, but nobody thought of using them to control the motion of droplets in a systematic way before.”

By combining these elements, the researchers created a prototype test to measure the levels of lactate dehydrogenase (LDH) in a sample of human serum. They carved channels within the test platform to create specific pathways for droplets to travel, each coated with a substance that stops the droplets from sticking along their journey. They also primed specific locations with dried reagents needed for the test, which are soaked up by droplets of simple buffer solution as they travel through.

The whole maze-like test is then capped with a lid containing a couple of holes where the sample and buffer solution are dripped in. Once loaded, the test is placed inside a box-like device with a handle that turns the test 90° to allow gravity to do its work. This device is also equipped with a simple LED and light detector that can quickly and easily detect the amount of blue, red, or green in the test results. This means that the researchers can tag three different biomarkers with different colours for various tests to measure.

In the case of this prototype LDH test, the biomarker is tagged with a blue molecule. A simple microcontroller measures how deep of a blue hue the test results become and how quickly it changes colour, which indicates the amount and concentration of LDH in the sample, to generate results.

“We could eventually also use a smart phone down the line to measure results, but that’s not something we explored in this specific paper,” said Jason Liu, a PhD candidate in the Chilkoti lab.

The demonstration provides a new approach for consideration when engineering inexpensive, low-power, point-of-care diagnostic devices. While the group plans to continue developing their idea, they also hope others will take notice and work on similar tests.

“While a well-designed microfluidic system can be fully automated and easy-to-use by passive means, the timing of discrete steps is usually programmed into the design of the device itself, making modifications to protocol more difficult,” added David Kinnamon, a PhD candidate in the Chilkoti group. “In this work, the user retains more control of the timing of steps while only modestly sacrificing ease-of-operation. Again, this is an advantage for more complex protocols.”

Source: Duke University

You’re Not Getting Sleepy: Six Myths and Misconceptions about Hypnosis

Photo by Bruce Christianson on Unsplash

A strange mystic swings a pocket watch back and forth, repeating the phrase “You’re getting sleepy, very sleepy,” giving them absolute command over their subject. That’s not how hypnotism really works, but it’s the way it’s often depicted in pop culture. Even some clinicians and hypnosis educators propagate harmful myths about hypnosis.

Steven Jay Lynn, a professor of psychology at Binghamton University, State University of New York, is an expert on hypnosis who has made major contributions to the judicial system for his insight on the practice. Lynn believes that hypnosis has many useful clinical applications, but that myths keep it from being utilised to its full potential.

In a recent paper published in BJPsych Advances, he and his colleagues, Madeline Stein and Devin Terhune from the Institute of Psychiatry, Psychology & Neuroscience at King’s College, addressed a number of errors and misconceptions regarding the characteristics and practice of hypnosis. These are a few of the common myths that are widely believed and commonly circulated in popular culture.

Hypnotised people can’t resist suggestions

A deeply hypnotised person is believed to display “blind obedience,” going along automatically with whatever the hypnotist suggests. Yet individuals do not lose control over their actions during hypnosis – contrary to the notion the media reinforces that hypnosis is something done to you and that hypnosis can be used to control someone. In fact, people can resist and even oppose hypnotic suggestions. Their experience of control during hypnosis depends on their intentions and expectations regarding whether or not they retain voluntary control.

Hypnosis is a “special state”

Hypnosis is often mischaracterised as a “special state” where defence mechanisms are reduced and a “unique state of physical relaxation and conscious unconsciousness’ allows us to ‘enter our subconscious depths through hypnosis. However, people can respond to hypnotic suggestions even while they are alert and on an exercise bicycle. Aside from being a contradiction in terms, ‘conscious unconsciousness’ is an inaccurate depiction, because during hypnosis even the most highly suggestible individuals remain fully conscious and cognisant of their surroundings. It is more accurate to consider hypnosis as a set of procedures in which verbal suggestions are used to modulate awareness, perception and cognition, rather than to unnecessarily invoke ‘special states.’

People are either hypnotisable or they are not

People’s responsiveness to hypnosis can be relatively stable over time. Yet it is inaccurate to assume that people are either hypnotisable or not. People vary greatly in their responsiveness and often respond to some suggestions but not others. Still, most people are sufficiently hypnotisable to reap substantial benefits from therapeutic suggestions.

Responsiveness to suggestions reflects nothing more than compliance or faking

Suggested behaviours during hypnosis can seem so much a departure from the mundane that questions inevitably arise regarding whether hypnotic responses are genuine. However, neuroimaging studies reveal that the effects of hypnotic suggestions activate brain regions (eg, visual processing) consistent with suggested events (eg, hallucinating an object).These findings provide convincing evidence that hypnotic effects are represented at the neurophysiological level consistent with what people report.

Hypnotic methods require great skill to administer

One popular misconception is that of the mesmerist, or magician-like hypnotist with special powers of influence who can “hypnotise” anyone. This widespread idea is pure myth; in actuality, administering a hypnotic induction and specific suggestions do not require any special skills or abilities beyond those required for basic social interactions and administration of experimental or clinical procedures, such as the ability to establish rapport. However, hypnosis should be practiced only by professionals trained in the use of hypnosis.

Hypnotic age regression can retrieve accurate memories from the distant past

TV shows and movies often feature people being able to recall extremely accurate memories from a distant past life under hypnosis. But research suggests a contrary view. When researchers check the accuracy of memories of people who are “age regressed” to an earlier time (e.g., 10th century) against factual information from the suggested period, they find that the information is almost invariably incorrect. What people report is mostly consistent with information experimenters provide regarding their supposed past life experiences and identities (eg, different race, culture, sex). These findings imply that “recall” reflects participants’ expectancies, fantasies, and beliefs regarding personal characteristics and events during a given historical period.

Source: Binghamton University

High Court Ruling Paves the Way for Affordable Medical Scheme Benefits in South Africa

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The recent judgement by the Pretoria High Court in favour of the Board of Health Funders (BHF) carries substantial implications for medical schemes in South Africa. This follows BHF’s court application, which sought to compel the Council for Medical Schemes (CMS) to give a complete record, providing light on the LCBO’s decision-making process thus far.

The Court ordered the Minister of Health and the CMS to provide all of the papers listed in Rule 30A within 10 days of receiving the applicant’s notice of motion. The completion of this crucial milestone hinges on the provision of several documents, which we eagerly await.

This significant victory brings us closer to the ultimate goal of granting Medical Schemes exemptions to offer Low-Cost Benefit Options (LCBOs), which aim to provide greater access to affordable medical scheme benefits for low-income earners. The BHF’s success aligns with the mission of improving
healthcare accessibility and advancing progress towards universal healthcare coverage (UHC) in the country.

In the main application lodged on 8 August, the BHF requested the High Court to:

  • Lift the moratorium that prevents medical schemes from offering LCBOs when the Council for Medical Schemes (CMS) refuses to grant applications for exemptions to medical schemes, pending the finalisation of LCBO guidelines.
  • Declare the failure by the respondents to develop and implement LCBO guidelines as irrational, unreasonable, and unlawful, as per Section 6 of the Promotion of Administrative Justice Act and Section 1(c) of the Constitution.

The BHF represents the majority of the country’s medical schemes and healthcare funders, encompassing schemes and administrators serving nearly 4.5 million individuals.

According to Charlton Murove, the protracted process of crafting a framework for Low-Cost Benefit Options has taken over seven years and is yet to be finalised. Many policymakers have criticised medical schemes for their lack of affordability. The proposed solution aims to address these concerns and move closer to the principles of UHC, ensuring that the healthcare system grants everyone access to quality and affordable healthcare.

Murove stated, “This application seeks to drive a progressive agenda for the public and private healthcare sectors, fostering collaboration to alleviate the current challenges in our healthcare system. The Council for Medical Schemes and the Minister have pivotal roles in implementing policies that enhance access to healthcare. However, progress with LCBOs has been hindered by the CMS’s failure to take the necessary steps for reform, despite the publication of demarcation regulations in 2016.”

The BHF’s victory in the High Court represents a significant step forward in the pursuit of affordable and accessible medical scheme benefits. By addressing the current burdens faced by the state and ensuring that medical scheme premiums remain affordable, we can strive towards a healthcare system that benefits all South Africans.

Mast Cells Instruct the Brain to Avoid Allergens

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Mast cells functions are still something of a mystery, but scientists have now shown in mice that mast cells act as a sensor that signals the animals to avoid antigens, including harmful allergens, and thereby protect themselves from health-threatening inflammatory reactions. The findings were published in the journal Nature.

Mast cells are found primarily in tissues that separate the outside and inside worlds of the body, such as the epithelia of the gastrointestinal tract and lungs. Within the tissues, mast cells often reside near nerve endings. Mast cells are well known to persons suffering from allergies because they secrete messenger substances such as histamine, which cause annoying to health-threatening allergic symptoms. These symptoms occur when mast cells are activated by IgE class antibodies during repeated antigen contact.

“Why mast cells and IgE exist at all has not yet been conclusively explained,” says immunologist Hans-Reimer Rodewald at the at the German Cancer Research Center (DKFZ). The researcher his team have now been able to show for the first time in mice, in a combination of behavioural experiments and immunological studies, that mast cells act like a sensor that helps to avoid contact with allergens

Mast cells and IgE needed for antigen avoidance

The DKFZ researchers immunised mice with the allergen ovalbumin, a protein component of chicken egg white. They then gave the animals the free choice of preferring either normal or egg white-containing drinking water. Immunised animals avoided the egg white-enriched water, while their non-immunised conspecifics clearly preferred it. A large proportion of the immunised animals avoided the egg white-containing water already one day after immunisation, some mice even after the first sip.

However, when the scientists performed this behavioural test with mice that genetically lack mast cells, both immunised and non-immunised animals preferred the egg white-containing water. Mice genetically unable to produce IgE also showed no avoidance behaviour. Thus, both mast cells and IgE are responsible for antigen avoidance.

When the immunised mice had no choice because the egg white solution was instilled in them, the animals developed inflammation in the stomach and small intestine. “The avoidance behaviour mediated by mast cells apparently protects the animals from harmful immune reactions,” explains Thomas Plum, one of the first authors.

How do mast cells “talk” to the brain?

An important open question for the scientists was now: How can mast cells, as a component of the immune system, influence behaviour? In what ways do immune cells “talk” to the brain? The scientists examined a variety of biologically active substances released by mast cells. These include leukotrienes, pro-inflammatory messengers known to activate sensory nerves. If the researchers blocked leukotriene synthesis, the immunized mice no longer showed the same consequence in avoiding egg white. Leukotrienes therefore appear to be at least partly involved in avoidance behaviour. Further immunological and neurobiological experiments are needed in the future to identify the nerve connections through which the mast cell signal is reported to the brain.

“In the intestine, lungs or skin, immune reactions against non-infectious antigens can occur as a result of so-called barrier disorders, permeability of the tissues from the outside to the inside. In the case of allergy, we call such antigens allergens. Whether these substances are dangerous or not, it is important for the organism to avoid their further intake in order to prevent inflammatory diseases. This is an evolutionary advantage and finally a conclusive explanation of the physiological role of mast cells and IgE,” Rodewald summarizes the results.

Whether mast cells also contribute to the avoidance of harmful antigens in humans must be addressed in further studies.

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Is A Healthy Diet Using Ultra-processed Food Possible?

Photo by Julia M Cameron

Researchers constructed a healthy diet with 91% of the calories coming from foods classified as ultra-processed but still in line with the 2020–2025 Dietary Guidelines for Americans (DGA). The seven-day diet, which consists more of ultra-processed foods like dried fruit and canned beans instead of doughnuts and hot dogs, was published in The Journal of Nutrition.

“The study is a proof-of-concept that shows a more balanced view of healthy eating patterns, where using ultra-processed foods can be an option,” said Research Nutritionist Julie Hess at the USDA Agricultural Research Service (ARS). “According to current dietary recommendations, the nutrient content of a food and its place in a food group are more important than the extent to which a food was processed.”

In the study, scientists used the NOVA scale to determine which foods to classify as ultra-processed. The NOVA scale first appeared in literature in 2009 and is the most commonly used scale in nutrition science to classify foods by degree of processing.

According to the NOVA scale, foods can be classified into four groups depending on their degree of processing: (1) Unprocessed or minimally processed foods; (2) Processed culinary ingredients; (3) Processed foods; and (4) Ultra-processed foods.

To test if ultra-processed foods can be used to build a healthy diet, ARS scientists and collaborators created a menu with breakfast, lunch, dinner, and snacks using MyPyramid as a guide for a seven-day, 2000-calorie food pattern The menu consisted of foods categorised as ultra-processed by at least two NOVA graders. The foods included in the menu also aligned with 2020 DGA recommendations for servings of groups and subgroups of fruits, vegetables, grains, protein foods, and dairy. Scientists selected food products that have lower levels of saturated fats and added sugars while still containing enough micronutrients and macronutrients. Some of the ultra-processed foods used in this menu included canned beans, instant oatmeal, ultra-filtered milk, whole wheat bread, and dried fruit.

“We used the Healthy Eating Index to assess the quality of the diet as it aligns with key DGA recommendations,” said Hess. “The menu we developed scored 86 of 100 points on the Healthy Eating Index-2015, meeting most of the thresholds, except for sodium content [exceeded recommendations] and whole grains [below recommendations].”

Scientists will continue researching this concept, understanding that observational research indicates that ultra-processed products could be associated with adverse health outcomes. This research shows that there is a role for a variety of foods when building a healthy diet and that more research is needed in this field, especially intervention studies.

Source: US Department of Agriculture – Agricultural Research Service

An Existing Cancer Drug Could Have a New Target: Cancer Cells’ ‘Fountain of Youth’

A team of scientists has found that ponatinib, an existing cancer drug could be repurposed to target a subset of cancers that currently lack targeted treatment options and is often associated with poor outcomes. Their findings are published in Nature Communications.

Cancerous cells have a ‘fountain of youth’ by continually lengthening telomeres, but some use a different mechanism called the alternative lengthening of telomeres (ALT). This subset makes up 15% of all cancers and is especially prevalent in aggressive tumours such as osteosarcoma and glioblastoma. The team, led by Nanyang Technological University, Singapore (NTU Singapore), showed that ponatinib, a cancer drug approved by the US Food and Drug Administration, blocks key steps in the ALT mechanism that leads it to fail.

The scientists found that ponatinib helped to shrink bone tumours (a type of ALT cancer) without causing weight loss, a common side effect associated with cancer drugs. In mice with tumours treated with ponatinib, they found a reduction in a biomarker for ALT cancer as compared to untreated mice.

The researchers say that the findings move them a step closer to developing a targeted therapeutic option for ALT cancers, which lack clinically approved targeted treatments to date.

Dr Maya Jeitany and a team of researchers from the NTU School of Biological Sciences, together with collaborators are seeking to address this unmet need.

Dr Jeitany, study lead and senior research fellow at NTU’s School of Biological Sciences, said: “A prominent feature of cancer is its ability to evade cell death and acquire indefinite replication – to stay immortal, in other words – which it can do through the alternative lengthening of telomeres (ALT) mechanism. While a sizeable portion of cancer cells depend on this mechanism, there is no clinically approved targeted therapy available.

“Through our study, we identified a novel signalling pathway in the ALT mechanism and showed that the FDA-approved drug ponatinib inhibits this pathway and holds exceptional promise in stopping the growth of ALT cancer cells. Our findings may provide a new direction for the treatment of ALT cancers by repurposing an FDA-approved drug for these types of tumours.”

Commenting as an independent expert, Assistant Professor Valerie Yang, medical oncologist with the Department of Lymphoma and Sarcoma at the National Cancer Centre Singapore, said: “Sarcomas and glioblastomas are both highly complex cancers that are more prevalent in young people and currently have limited treatment options. The identification of a drug that is FDA-approved which can be repurposed to target ALT, an Achilles heel in these cancers, is very exciting.”

To date, there is no clinically approved targeted treatment for ALT cancers. Furthermore, many ALT cancers, such as osteosarcoma and glioblastoma, show resistance to chemotherapy, highlighting the need for a more targeted form of treatment.

Drug affects telomeres in ALT cancer cells

Through high-throughput drug screening and subsequent testing of shortlisted compounds, the scientists discovered that ponatinib, a drug approved by the FDA for a type of bone marrow cancer, can kill ALT cancer cells effectively.

When osteosarcoma and liposarcoma cells were treated with ponatinib, the scientists found that the drug led to DNA damage, dysfunctional telomeres, and triggered senescence. Importantly, the synthesis of telomeres in the cells also dropped after 18 to 20 hours of treatment with the drug.

Pre-clinical studies conducted on mice that had received transplants of human bone cancer cells further validated the potential of ponatinib. The drug reduced the tumour sizes without affecting the mice’s body weight, a common side effect associated with cancer treatments.

In mice with tumours treated with ponatinib, there was also a reduction in a biomarker for ALT cancer as compared to untreated mice – an indicator that the drug was effective in inhibiting ALT cancer growth.

The scientists ran further tests to identify ponatinib’s mode of action on telomeres in ALT cancer cells and identified a signalling pathway (a series of chemical reactions in which a group of molecules in a cell work together to control a cell function) that could be responsible for the drug’s effect on ALT.

The researchers are now studying further how ponatinib affects telomeres to understand in more detail the signalling pathway they have identified. They are also assessing potential ponatinib-based combinatorial drug treatments for ALT cancers.

Source: Nanyang Technological University

A Natural Repair Process for Damaged Auditory Hair Cells

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Auditory researchers have discovered how hair cells can repair themselves after being damaged, an important insight could benefit efforts to develop new and better ways to treat and prevent hearing loss. Their findings are published in the free online journal eLife.

Found in the inner ear, hair cells derive their name from the hair-like structures that cover them and serve as mechanical antennas for sound detection. The prevailing belief is that when auditory hair cells are killed, they are gone for good. But this new research from University of Virginia School of Medicine shows that these delicate cells have the ability to repair themselves from damage caused by loud noises or other forms of stress.

“For many years, auditory research has placed considerable emphasis on the regeneration of sensory hair cells. Although these efforts continue, it is equally important to enhance our comprehension of the intrinsic mechanisms that govern the repair and maintenance of these cells. By gaining a deeper understanding of these inherent repair processes, we can uncover strategies to fortify them effectively. One such approach in the future might involve the utilisation of drugs that stimulate repair programs,” said researcher Jung-Bum Shin, PhD, of UVA’s Department of Neuroscience. “In essence, when replacement of hair cells proves challenging, the focus shifts towards repairing them instead. This dual strategy of regeneration and repair holds strong potential in advancing treatments for hearing loss and associated conditions.”

Repairing the damaged cells

In order to sense sound, hair cells are naturally fragile, but they also must withstand the continuous mechanical stress inherent in their jobs.

Prolonged exposure to loud noise harms hair cells in a variety of ways, and one of those is by damaging the cores of the “hairs” themselves. These hair-like structures are known as stereocilia, and Shin’s new research shows a process they use to repair themselves.

The hair cells do this by deploying a protein called XIRP2, which has the ability to sense damage to the cores, which are made of a substance called actin. Shin and his team found that XIRP2 first senses damage, then migrates to the damage site and repairs the cores by filling in new actin.

“We are especially excited to have identified a novel mechanism by which XIRP2 can sense damage-associated distortions of the actin backbone,” Shin said. “This is of relevance not only for hair cell research, but the broader cell biology discipline.”

The pioneering work has netted a grant to fund additional research into how the cores are repaired. By understanding this, scientists will be better positioned to develop new ways to battle hearing loss – even the kind that comes from aging, the researchers say.

“Age-related hearing loss affects at least a third of all older adults,” Shin said. “Understanding and harnessing internal mechanisms by which hair cells counteract wear and tear will be crucial in identifying ways to prevent age-related hearing loss. Furthermore, this knowledge holds potential implications for associated conditions such as Alzheimer’s disease and other dementia conditions.”

Source: University of Virginia Health System

Mouse Study Highlights Potential Therapeutic for Metabolic Syndrome

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Mopping up free radicals with antioxidants was a major health fad in the 1970s. In an effort to supposedly blunt the effects of aging and stave off chronic disease, people took huge amounts of antioxidants in the form of minerals and vitamins. Not only was this ineffective, it sometimes caused harm because untargeted antioxidants also compromised beneficial cellular signalling pathways. As theories of mitochondrial causes of disease fell out of favour, this health fad disappeared along with bell bottoms and disco.

Now, research recently published in Free Radical Biology and Medicine suggests a new way of dealing with free radicals: rather than mop them up, take a pill that selectively keeps them from being produced in the first place. Building on this work, collaborative research between the Buck and Calico Labs shows that specifically inhibiting free radical production at a particular mitochondrial site prevents and treats metabolic syndrome in mice, by preventing and reversing insulin resistance.

“We think that mitochondrial radical production drives many chronic diseases of aging, and that blocking the production of free radicals is a viable disease-treating and anti-aging intervention,” said Martin Brand, PhD, Buck Professor Emeritus and senior investigator of the study. “We’ve found a way to selectively keep problematic free radicals in check without compromising normal energy production in the mitochondria. These compounds act like a cork in a wine bottle. They plug a specific site so that it doesn’t produce free radicals, without hindering the mitochondria’s critical function of energy metabolism. We look forward to continuing this groundbreaking area of research.”

The orally bioavailable compound that has been developed, S1QEL1.719 (a new “S1QEL” – Suppressor of site IQ Electron Leak), was given both prophylactically and therapeutically to mice fed a high-fat diet that causes metabolic syndrome. Treatment decreased fat accumulation, strongly protected against decreased glucose tolerance and prevented or reversed the increase in fasting insulin levels by protecting against the development of insulin resistance.

Acting on mitochondrial complex I highlights potential interventions for other conditions

S1QEL1s act on site IQin mitochondrial complex I. (The mitochondrial electron transport chain consists of four protein complexes integrated into the inner mitochondrial membrane. Together they carry out a multi-step process, oxidative phosphorylation, through which cells derive 90% of their energy.)

First author and Buck staff scientist Mark Watson, Ph.D., says current literature strongly implicates complex I in a number of different diseases, from metabolic syndrome to Alzheimer’s, fatty liver disease, and noise-induced hearing loss, as well as the underlying aging process itself.

“S1QELs don’t sequester oxidants or radicals. Rather, they specifically inhibit radical production at the IQ site on complex I without interfering with other sites,” Watson said. “So the normal redox signaling that we require in our cells will continue. S1QELs just modulate that one site. They are very clean, very specific, and do not disrupt mitochondrial functioning like inhibitors of mitochondria do.”

Brand says the data shows that free radical production from complex I is an essential driver of insulin resistance and metabolic syndrome, a major disease of poor lifestyle choices and of aging. He says this feature is a strong reason to revisit the mitochondrial theory of aging. “These compounds fine-tune mitochondrial production of free radicals,” he said. “And it’s really interesting; just inhibiting this specific site improves the whole redox environment and prevents metabolic disease, and that is amazing.”

Source: Buck Institute for Research on Aging

Faecal Microbiota Transplants Could Boost Melanoma Immunotherapy

3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

In a world-first clinical trial published in the journal Nature Medicine, a multi-centre study has found faecal microbiota transplants (FMT) from healthy donors are safe and show promise in improving response to immunotherapy in patients with advanced melanoma.

While immunotherapy drugs can significantly improve survival outcomes in those with melanoma, they are only effective in 40–50% of patients. Preliminary research has suggested that the human microbiome may play a role in whether or not a patient responds.

“In this study, we aimed to improve melanoma patients’ response to immunotherapy by improving the health of their microbiome through faecal transplants,” says Dr John Lenehan, Medical Oncologist at London Health Sciences Centre’s (LHSC).

A faecal transplant involves collecting stool from a healthy donor, screening and preparing it in a lab, and transplanting it to the patient. The goal is to transplant the donor’s microbiome so that healthy bacteria will prosper in the patient’s gut.

“The connection between the microbiome, the immune system and cancer treatment is a growing field in science,” explains Dr Saman Maleki, senior investigator on the study. “This study aimed to harness microbes to improve outcomes for patients with melanoma.”

The phase I trial included 20 melanoma patients recruited from LHSC, CHUM and Jewish General Hospital. Patients were administered approximately 40 faecal transplant capsules orally during a single session, one week before they started immunotherapy treatment.

The trial found that combining faecal transplants with immunotherapy is safe for patients. The study also found 65% of patients who retained the donors’ microbiome had a clinical response to the combination treatment. Five patients experienced adverse events sometimes associated with immunotherapy and had their treatment discontinued.

“We have reached a plateau in treating melanoma with immunotherapy, but the microbiome has the potential to be a paradigm shift,” says oncologist Dr Bertrand Routy.

The study is unique due to its administration of faecal transplants (from healthy donors) in capsule form to cancer patients – a technique pioneered in London by Dr Michael Silverman.

“Our group has been doing faecal transplants for 20 years, initially finding success treating C. difficile infections. This has enabled us to refine our methods and provide an exceptionally high rate of the donor microbes surviving in the recipient’s gut with just a single dose,” says Dr Silverman. “Our data suggests at least some of the success we are seeing in melanoma patients is related to the efficacy of the capsules.”

The team has already started a larger phase II trial involving centres in Ontario and Quebec.

Source: Lawson Health Research Institute

Would it be Ethical to Entrust Human Patients to Robotic Nurses?

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Advancements in AI have resulted in typically human characteristics like creativity, communication, critical thinking, and learning being replicated by machines for complex tasks like driving vehicles and creating art. With further development, these human-like attributes may develop enough to one day make it possible for robots and AI to be entrusted with nursing, a very ‘human’ practice. But… would it be ethical to entrust the care of humans to machines?

In a step toward answering this question, Japanese researchers recently explored the ethics of such a situation in the journal Nursing Ethics.

The study was conducted by Associate Professor Tomohide Ibuki from Tokyo University of Science, in collaboration with medical ethics researcher Dr Eisuke Nakazawa from The University of Tokyo and nursing researcher Dr Ai Ibuki from Kyoritsu Women’s University.

“This study in applied ethics examines whether robotics, human engineering, and human intelligence technologies can and should replace humans in nursing tasks,” says Dr Ibuki.

Nurses show empathy and establish meaningful connections with their patients, a human touch which is essential in fostering a sense of understanding, trust, and emotional support. The researchers examined whether the current advancements in robotics and AI can implement these human qualities by replicating the ethical concepts attributed to human nurses, including advocacy, accountability, cooperation, and caring.

Advocacy in nursing involves speaking on behalf of patients to ensure that they receive the best possible medical care. This encompasses safeguarding patients from medical errors, providing treatment information, acknowledging the preferences of a patient, and acting as mediators between the hospital and the patient. In this regard, the researchers noted that while AI can inform patients about medical errors and present treatment options, they questioned its ability to truly understand and empathise with patients’ values and to effectively navigate human relationships as mediators.

The researchers also expressed concerns about holding robots accountable for their actions. They suggested the development of explainable AI, which would provide insights into the decision-making process of AI systems, improving accountability.

The study further highlights that nurses are required to collaborate effectively with their colleagues and other healthcare professionals to ensure the best possible care for patients. As humans rely on visual cues to build trust and establish relationships, unfamiliarity with robots might lead to suboptimal interactions. Recognising this issue, the researchers emphasised the importance of conducting further investigations to determine the appropriate appearance of robots for facilitating efficient cooperation with human medical staff.

Lastly, while robots and AI have the potential to understand a patient’s emotions and provide appropriate care, the patient must also be willing to accept robots as care providers.

Having considered the above four ethical concepts in nursing, the researchers acknowledge that while robots may not fully replace human nurses anytime soon, they do not dismiss the possibility. While robots and AI can potentially reduce the shortage of nurses and improve treatment outcomes for patients, their deployment requires careful weighing of the ethical implications and impact on nursing practice.

“While the present analysis does not preclude the possibility of implementing the ethical concepts of nursing in robots and AI in the future, it points out that there are several ethical questions. Further research could not only help solve them but also lead to new discoveries in ethics,” concludes Dr Ibuki.

Source: Tokyo University of Science