Tag: 20/4/21

Categories : CancerTags :

Glioblastoma Induces ‘Stockholm Syndrome’ to Subvert Body’s Defences

On By ModernMedia

Glioblastoma, an aggressive form of brain cancer, has been found to corrupt immune cells and make the tumour harder to treat.

Most people diagnosed with glioblastoma die in a short period of time after their diagnosis, but some glioblastoma patients see great benefits from chemotherapy and survive beyond expectations. Researchers at the University of Minnesota have revealed the reason for this in a new study published in the Proceedings of the National Academy of Sciences.

“Deciphering the molecular underpinning of these exceptional responses may hold the key to transforming the hope for miracles into the reality of an expected cure for glioblastoma patients,” said lead author Clark C Chen, MD, PhD, Lyle French Chair in Neurosurgery and head of the Department of Neurosurgery at the University of Minnesota Medical School.

Examining the gene expression profiles of glioblastoma samples from approximately 900 glioblastoma patients, the researchers sought to identify unique features associated with exceptional responders, defined as glioblastoma patients who survive more than two years after treatment.

“We utilized different state-of-the-art analytics to study these samples, including methods innovated by Dr. Aaron Sarver, a member of the University of Minnesota Institute of Health Informatics. Impressively, these analytics converged on a single observation, a paucity of microglia and macrophages,” Dr Chen said.

Specialised immune cells, microglia and macrophages act as scavengers, spotting and removing out-of-place cells in healthy brains. They travel to abnormal cancer cell sites to mount a defence, and can form over half the cells in a glioblastoma sample.

“If microglia and macrophages normally fend off cancer cells, more of them should allow the body to better fend off the tumor. So, we expected to see more of them in the exceptional responders; however, we found the contrary,” said Jun Ma, a researcher in the Department of Neurosurgery at the U of M Medical School and a co-first author of this study.

In order to resolve this paradox, the research team then demonstrated that glioblastoma cells can recondition the surrounding microglia and macrophages, corrupting their normal anticancer functions. Where they once fought off cancer growths, these immune cells are now re-programmed by glioblastoma cells to promote tumour growth.

“It is frightening to consider the possibility that cancer cells can ‘brainwash’ our own immune cells and convert them from cells that fight cancer to cells that promote cancer,” said Judith Varner, a co-senior author of the study and professor of pathology at the University of California, San Diego. “Fortunately, we have figured out how glioblastoma cells subvert our immune system and can now reverse this cellular version of the ‘Stockholm syndrome.'”

Stockholm syndrome is characterised as when a captive begins to identify closely with their captors, as well as with their agenda and demands, however there is little evidence for it being a true psychological phenomenon.

A protein known as phosphoinositide-3-kinase gamma isoform (PI3Kγ) could hold the key to cure this cellular “Stockholm syndrome” and possibly glioblastoma. This protein, when activated, is the switch that corrupts their anti-cancer role. Having studied this process for many years, Varner has pioneered drugs that restore the anti-tumour activities of microglia and macrophages.

“In our animal glioblastoma models, treatment with drugs targeting PI3Kγ consistently resulted in impressively durable responses to chemotherapy,” Chen said. “We are eager to translate these findings into a human trial, with the hope of transforming every glioblastoma patient into an exceptional responder.”

Source: Medical Xpress

Journal information: Jie Li et al, PI3Kγ inhibition suppresses microglia/TAM accumulation in glioblastoma microenvironment to promote exceptional temozolomide response, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2009290118

Categories : Mental HealthTags :

Dietary Supplement Treats Schizophrenia in Mouse Model

On By ModernMedia

A study has found that a simple dietary supplement reduces behavioral symptoms in mice with a genetic mutation that causes schizophrenia. 

Schizophrenia is estimated to affect about 1 in 100 people globally and is one of the top 15 leading causes of disability worldwide.

The study examined the role of betaine in schizophrenia, as it is known to be reduced in the brains of schizophrenia patients. Betaine, often associated with sweetness or umami flavours, was first isolated from sugar beets and is acquired through the diet and also produced in the body. Betaine supplements are already used clinically to treat the metabolic disease homocystinuria.

“I don’t encourage anyone to take betaine for no reason, if a doctor has not recommended it. But, we know this drug is already used clinically, so repurposing it to treat schizophrenia should be safe,” said study leader Professor Nobutaka Hirokawa, MD, PhD, from the University of Tokyo Graduate School of Medicine.
“There are treatments for schizophrenia, but they have side effects and unfortunately there is still no effective drug for patients to take that we can explain biochemically why it works,” Prof Hirokawa added.

Genetic studies have found possible links between schizophrenia and variations in the kinesin family 3b (kif3b) gene as well as another gene involved in the body’s production of betaine. The researchers categorised all 45 members of the kinesin superfamily of genes in mammals, most of which encode motor proteins that move materials throughout the cell. Together with another protein kinesin superfamily, the KIF3B protein transports cargo throughout a neuron, travelling up and down the cell’s skeleton.

The researchers mice used to model schizophrenia which had only one functional copy of the kif3b gene. These mice have different behaviours to normal mice such as avoiding social interactions and being less startled by a sound test. The Kif3b mutant mice that were raised on a diet with triple the normal amount of betaine had normal behaviour.

To work out why betaine had this effect on mice, researchers grew nerve cells with the kif3b mutation in the laboratory and added fluorescent labels so they could watch the development of cellular skeleton.

Kif3b mutant neurons grown in the lab have an unusual, overly branched structure with too many dendrites, unlike the normal tree-like shape of healthy neurons. Similar overly branched neurons are also seen in brain samples donated by people with schizophrenia, regardless of any treatments or medications they took while alive.

During healthy neuron development, the cell’s main body fills with a skeleton component called tubulin. Meanwhile, the cell’s front growth cone builds outwards in a spiky, erratic dance due to the movements of another skeleton component known as filamentous actin. In kif3b mutants, this dancing movement, which experts refer to as lamellipodial dynamics, is reduced and the distinction between tubulin and actin is blurred.

Chemical analyses of the brains of kif3b mutant mice and human schizophrenia patients reveal significant chemical damage to CRMP2, a protein which helps assemble actin. This damage causes the proteins to clump together. However, betaine is known to prevent the kind of chemical damage, carbonyl stress, responsible for CRMP2 dysfunction.

“In postmortem brains of schizophrenia patients, CRMP2 is the protein in the brain with the most carbonyl stress. Betaine likely eliminates the carbonyl stress portion of the schizophrenia equation,” said Hirokawa.

It appears that by shielding CRMP2 from damage, betaine treatment allows kif3b mutant neurons to build normal structures, allowing the remaining functional KIF3B protein can shuttle cargo around the cell. Other in vitro experiments showed that KIF3B and CRMP2 can bind together, but their exact relationship remains unclear.

“We know that the amount of betaine decreases in schizophrenia patients’ brains, so this study strongly suggests betaine could be therapeutic for at least some kinds of schizophrenia,” said Hirokawa.

Source: Medical Xpress

Journal information: Shogo Yoshihara et al. Betaine ameliorates schizophrenic traits by functionally compensating for KIF3-based CRMP2 transport, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.108971

Categories : COVIDTags :

SA’s Phase 2 Vaccination Rollout to Commence Soon

On By ModernMedia

South Africa’s Health Department said that it was preparing to vaccinate 5.5 million people over the age of 60 by October.

Phase two will commence from mid-May to the end of October, and Health Minister Zweli Mkhize visited hospitals in Mitchells Plain to assess its readiness for the expanded rollout. The Health Department is aiming to vaccinate as many people before a possible third wave.

Dr Mkhize said that plans to inoculate 16 million people during phase two remained on track.

“After that, after October of course everybody else who has not been vaccinated will have to come in, starting with those who will be in congregate settings and risk and so on.”

Dr Mkhize said that all the paperwork and contracts with Johnson & Johnson and Pfizer had been concluded. However, the use of the J&J vaccine is still waiting on an ethics committee’s signoff for the South African Health Products Regulatory Authority’s (Sahpra) recommendation to allow resumption of that vaccine’s trial.

Last week, the SA trial was temporarily stopped after regulators in the US paused the J&J vaccine rollout in that country after six women developed a rare blood clot. Sahpra has now recommended a conditional lifting of the suspension, although its US counterpart is expected to take two weeks to assess the clot problem.

Dr Boitumelo Semete-Makokotlela at Saphra said that the protocol would now have to be altered and safety regulations tightened.

“The screening and monitoring of the participants, particularly those with high risks of blood clotting,” Dr Semete-Makokotlela said. “Secondly, the safe management and immediate management of any participants who may present with any vaccine-induced thrombosis.”

Source: Eyewitness News

Categories : CancerTags :

Wrapping up Tumours With Micromesh Nets

On By ModernMedia

An innovative new nanomedicine has been developed that wraps up tumours in a micromesh net, conforming to the surface of tumor masses and efficiently delivering drugs.

The scientists at the IIT (Istituto Italiano di Tecnologia (Italian Institute of Technology) who developed the mesh described it in the journal Nature Nanotechnology.

Brain tumors are rare but they are some of the most aggressive and difficult to treat. In particular, glioblastoma multiforme (GBM), which is a grade 4 glioblastoma has the most severe prognosis: the average survival is just over 12 months and only 5% of the patients survive beyond 5 years.

GBM typically affects men and women between 45 and 75 years of age. Furthermore, unlike other malignancies, there has been no significant diagnostic and therapeutic improvements for this malignancy over the past 30 years. In fact, both the incidence of new cases and the number of deaths has remained practically unchanged. The only therapeutic strategy currently used is based on surgery, which consists of removing a part of the tumor mass and reducing intracranial pressure, followed by radiotherapy and/or chemotherapy.

The biomedical system developed by IIT and its collaborators can play a very important role in the fight against the disease, representing a possible effective alternative to the few pharmacological treatments used to date.

The microMESH is a micrometric-scale polymeric net, made from biodegradable materials and wraps around the tumour mass, enclosing it. In fact, the micrometric thick polymeric fibers are very flexible and are arranged to form regular openings, which are also on the same scale as cancer cells. This unique feature allows the microMESH to achieve a closer interaction with the tumor mass, increasing the therapeutic efficacy.

Its structure consists of two separate compartments in which different drugs can be loaded which are released towards the tumor mass in an independent, precise, and prolonged fashion. Combining different therapies: chemotherapy, nanomedicine, and immunotherapy enables the microMESH to ‘attack’ glioblastoma.

This work has been carried out by a team led by Prof Paolo Decuzzi, head of the IIT Laboratory of Nanotechnology for Precision Medicine, in collaboration with the Neural Stem Cell Biology Laboratory of Dr Rossella Galli at the San Raffaele Hospital in Milan and a team led by Prof Gerald Grant at the Lucile Packard Children’s Hospital of Stanford University.

The group will continue to develop the microMESH by integrating different types of drugs and therapies to tackle other types of tumors. In the short term, their major objective will be to validate the technology on glioblastoma patients.

Source: News-Medical.Net

Journal information: Mascolo, D. D., et al. (2021) Conformable hierarchically engineered polymeric micromeshes enabling combinatorial therapies in brain tumours. Nature Nanotechnology. doi.org/10.1038/s41565-021-00879-3.

Categories : Medical Research & TechnologyTags :

Spacesuit Tech Leads to Improved Patient Outcomes

On By ModernMedia

A tech startup is pioneering wearable health technology derived from spacesuit technology.

Maarten Sierhuis, a NASA alum, commented to Rachna Dhamija, a tech veteran and his future cofounder saying, “If your dad would just wear a space suit, I could monitor him”. Both had ageing parents with health issues.

Having worked for 12 years as a senior research scientist at NASA, Sierhuis used sensors and artificial intelligence (AI) to monitor astronauts in space. When astronauts go on spacewalks, their spacesuits contain various sensors that monitor their vitals, with the data being sent to NASA and distributed to the flight surgeon, biomedical engineers, and others. The ground-based crew uses that information to guide its support efforts—perhaps a reminder to drink some water and avert dehydration, or to take a short break to lower heart rate. This technology—called the Brahms Intelligent Agent platform—was licensed to Ejenta from NASA. Now, hospitals and health systems are using it to help better their patient care.

“When we started the company, we just had a very strong conviction that our parents deserve the same level of care NASA provides its astronauts,” Dhamija said.

Ejenta integrates wearable and home sensors that gather data from patients with AI-driven virtual assistants. Using a chat function, patients can use the platform to exchange messages with these assistants, called “intelligent agents” by Ejenta, right from their homes. Clinicians can securely access patient information from the Ejenta platform to better inform their care decisions.

Advances in cloud computing enabled the technology to be adapted from space to the Earth. Ejenta’s founders use a cloud infrastructure to securely collect, store and analyse health data.

Ejenta—whose name is a Bengali slang term for “agents”— is one of them. The company, which was founded in 2012, originally focused on government-related work, including projects for NASA. However, in the last four years, Ejenta evolved into a digital health company. Dhamija said the company’s AI-driven technology is what makes Ejenta unique from other digital health startups.

“There are a lot of healthcare devices available to consumers, but what’s missing is AI and the automation that can turn this data into insights a doctor can use—actionable data to make care more preventative and more proactive,” she said.

Ejenta uses its NASA technology to take data from wearable Internet of Things (IoT) devices and at-home sensors to monitor a patient’s health. Patients can interact with their assistant via text or voice and ask questions like, “What medication do I need to take with breakfast?”and receive an appropriate answer.

A clinical trial with Ejenta by one of the country’s largest healthcare providers, saw heart failure readmissions dropped by 56%. Readmissions come are costly for both patients and the healthcare system, so this application can save considerable amounts of money as well as improving the patient’s quality of life. Ejenta, in separate clinical trials, also contributed to improved outcomes for women who had high-risk pregnancies, reducing risk for gestational diabetes, preterm birth and cesarean sections. These successes were made possible by years of difficult development.

“We had a big challenge adapting our solution, which was originally designed to monitor 12 astronauts in space, to scale up to support thousands of patients across a number of different customer types and a number of different health conditions while still being HIPAA compliant,” Dhamija said.

However, by leveraging Amazon Webs Servers (AWS) as its cloud provider, Ejenta was able to scale up. Dhamija said her team chose AWS because it offers both flexibility and scalability in a secure cloud environment, which is critical when dealing with healthcare data. Ejenta wanted a “cloud provider that had a reputation for providing HIPAA-compliant services our customers would trust,” she said.

Ejenta was part of the Alexa Accelerator, an Amazon programme to help companies incorporate voice technology into their innovations. Before entering the programme, Ejenta had used Alexa to support improved diabetes care management for patients. It continued this work during the accelerator.

“Alexa is one of the only voice-based solutions that gave us the ability to engage customers, whether it’s patients or their family, with voice and do it in a HIPAA-compliant way,” Dhamija said.

Ejenta’s participation in the accelerator led to its involvement in AWS Connections, a program that introduces startups to large organisations that have specific technological or business needs. Through this programme, Ejenta is developing a health and communication management system for astronauts in deep space to relay health informationa and communicate with their families.

“It’s translational, meaning it can be applied for both Earth and space,” Dhamija said. “If you look at some of the problems we face on Earth or space, they do inform each other, so the goal is to have our Earth-based work inform space, and vice versa.”

Source: Forbes

Categories : AgeingTags :

Leg Motion Can Protect Against Leg Swelling in the Elderly

On By ModernMedia

A study from Kanazawa University in Japan has shown that leg swelling can be reduced in the elderly as the muscle pumping action of the leg is as effective in people of all ages.

Chronic lower-limb oedema (CLO) — the permanent accumulation of fluid in the leg — often occurs in elderly people. The condition leads to various physical and mental problems, including difficulty in walking or moving, fatigue and anxiety. Lack of physical activity, associated with a decrease in muscle pump action is one of the causes of CLO.

Leg muscles can act as a blood pump: when contracted, the muscle squeezes veins together, forcing blood to flow. But it was not known whether muscle pump action changes as people age had not been thoroughly investigated. Now, Junko Sugama from Kanazawa University and colleagues have addressed this issue. In addition, they studied the effect of leg posture on the muscle pump action.

For their study, the researchers recruited 76 healthy volunteers, categorised into young, middle-aged and old, with average ages of 24, 47 and 72 years, respectively. To investigate blood flow and visualise the morphology of muscles and veins at a given position along the leg, the researchers used MRI cross-section images at 21 positions in the calf region.

To assess the effect of leg motion, subjects were asked to perform plantar flexion (pointing the foot downwards) every 2 seconds for a minute, and MRI images were taken before and after the exercise. This procedure was repeated over three different body positions: supine, sitting and standing.

The scientists found that for all postures, blood flow increased after the exercise, implying that the latter promotes muscle pump action. The blood flow velocity was observed to increase most for the standing posture (90-135%), followed by the supine (55-90%) and sitting (30-40%) postures. No age difference was seen in the flow changes, however the elderly patients had exercise habits, the researchers pointed out.

The researchers suggested that nurse measurement of muscle pump action is useful for deciding whether intervention exercise is necessary to prevent CLO but an easier measurement tool than MRI is needed.

Additional studies are needed, such as adapting the measurement equipment so that it can be applied to elderly people with reduced mobility. The scientists nevertheless concluded that for their set of subjects, “no difference was found in the changes in muscle pump action with age”, and that “elderly people may be able to maintain their muscle pump action when they have exercise habits”.

Source: News-Medical.Net

Journal reference: Fujii, T., et al. (2021) Gravity magnetic resonance imaging measurement of muscle pump change accompanied by aging and posture. Japan Journal of Nursing Science. doi.org/10.1111/jjns.12407.