Year: 2022

Categories : Medical Research & TechnologyTags :

New Coating Makes the Nanomedicine Go Down

On By ModernMedia
Upon injection into the blood, nanomedicines (blue spheres) are immediately attacked by proteins of the immune system called complement proteins (orange). Complement proteins cause rapid destruction of the nanomedicine, and also induce an anaphylaxis-like reaction. By attaching complement-degrading proteins (yellow ninjas made of protein) to the surface of nanomedicines, Penn researchers have largely solved this problem, potentially allowing more diseases to be safely treated by nanomedicine. Credit: University of Pennsylvania

In nanomedicine, immune reactions against the nanoparticles that contain the medicine or vaccine, reducing its effectiveness. Researchers have now come up with a new method to prevent the body from treating nanomedicines like foreign invaders, by covering those nanoparticles with a coating to suppress the immune response.

As soon as they are injected into the bloodstream, unmodified nanoparticles are swarmed by complement proteins, triggering an inflammatory response and preventing the nanoparticles from reaching their treatment targets. Penn Medicine researchers, whose findings are published in Advanced Materials, have devised a coating for nanoparticles that suppresses complement activation.

Nanoparticles are tiny capsules, typically made from proteins or fat-related molecules, that contain certain types of treatment or vaccine. The best-known examples of nanoparticle-delivered medicines are mRNA COVID vaccines.

“It turned out to be one of those technologies that just works right away and better than anticipated,” said study co-senior author Jacob Brenner, MD, PhD.

RNA- or DNA-based therapies generally need delivery systems to get them through the bloodstream into target organs. Harmless viruses often have been used as carriers or “vectors” of these therapies, but nanoparticles are increasingly considered safer alternatives. Nanoparticles also can be tagged with antibodies or other molecules that make them hone in precisely on targeted tissues.

The complement attack problem has been a serious impediment to nanomedicine. Circulating complement proteins treat nanoparticles as if they were bacteria, immediately coating nanoparticle surfaces and summoning macrophages to engulf them. Researchers have attempted to reduce the problem by pre-coating nanoparticles with camouflaging molecules, such as forming a watery, protective shell around nanoparticles using polyethylene glycol (PEG).

But nanoparticles camouflaged with substances like PEG still draw at least some complement attack. In general, nanoparticle-based medicines that move through the bloodstream (mRNA COVID vaccines are injected into muscle, not the bloodstream) have had a very low efficiency in getting to their target organs, usually under 1%.

In the study, the researchers came up with a new approach to protect nanoparticles, based on natural complement-inhibitor proteins that circulate in the blood, attaching to human cells to help protect them from complement attack.

In vitro tests using standard PEG-protected nanoparticles with one of these complement inhibitors, called Factor I, provided dramatically better protection from complement attack. In mice, the same strategy prolonged the half-life of standard nanoparticles in the bloodstream, allowing a much larger fraction of them to reach their targets.

“Many bacteria also coat themselves with these factors to protect against complement attack, so we decided to borrow that strategy for nanoparticles,” said co-senior author Jacob Myerson, PhD, a senior research scientist in the Department of Systems Pharmacology and Translational Therapeutics at Penn.

In a set of experiments in mouse models of severe inflammatory illness, the researchers also showed that attaching Factor I to nanoparticles prevents the hyper-allergic reaction that otherwise could be fatal.

Further testing will be needed before nanomedicines incorporating Factor I can be used in people, but in principle, the researchers said, attaching the complement-suppressing protein could make nanoparticles safer and more efficient as therapeutic delivery vehicles so that they could be used even in severely ill patients.

The researchers now plan other protective strategies for medical devices, such as catheters, stents and dialysis tubing, which are similarly susceptible to complement attack. They also plan to investigate other protective proteins.

“We’re recognising now that there’s a whole world of proteins that we can put on the surface of nanoparticles to defend them from immune attack,” Dr Brenner said.

Source: University of Pennsylvania School of Medicine

Categories : Ethics and Law Mental HealthTags :

‘No NGOs Were Ready’, Life Esidimeni Inquest Reveals

On By ModernMedia
Photo by Tingey Injury Law Firm on Unsplash

The former Gauteng deputy director-general for mental health services, Hannah Jacobus, has the process to move Life Esidimeni patients was rushed. She was being cross-examined by the State’s Advocate Willem Pienaar.

The much-delayed inquest meant to determine any criminal liability for the deaths of 144 mental health patients in the 2016 Life Esidimeni disaster continued virtually on Monday.

Jacobus’ role was in downscaling of patients at Life Esidimeni for cost savings, and says there was no indication of it closing at the time. When its closure was announced, these downscaling plans were not implemented and there was no timeframe given for when patients were to move out.

The former deputy DG admitted to writing false licences for NGOs, under pressure from then head of Gauteng mental health services, Dr Makgoba Manamelashe. However, Jacobus maintained that while she assessed their suitability, she ultimately did not issue any licences.

Dr Manamela signed licences authorising inexperienced‚ underfunded‚ poorly equipped NGOs to look after patients with profound mental illnesses.

After the Gauteng health department terminated the contract with Life Esidimeni, NGOs were used to care for the 1712 patients.

Dr Manamela admitted to Solidarity advocate Dirk Groenewald that the NGOs to which she gave authority did not comply with the legal requirements. In 2017,  it was found that patients were transferred to NGOs that had been issued “unlawful and knowingly fraudulent” licences.

Many NGOs were subsequently found to be entirely unprepared for the patients they received, some lacking sufficient food, water, medication, staff or blankets.  According to Jacobus, the process have only been completed by 2020 according to the downscaling schedule.

“From December 2015 to the end of March 2016 [is not] a sufficient period to determine and appoint suitable NGOs to receive mental healthcare [patients]. No NGOs were ready by the end of March. We needed more time,” she said.

Source: Times Live

Categories : Diseases, Syndromes and ConditionsTags :

Study Shows New Possibilities of Treating Rare Ossifying Disease

On By ModernMedia
Source: National Cancer Institute on Unsplash

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterised by anomalous bone growth at the site of even minor injuries. It results in what some term a “second skeleton,” which locks up joint movement and even making breathing difficult. However, new research shows that forming extra-skeletal bone might not be the only driver of the disease. Impaired muscle tissue regeneration allows unwanted bone to form instead of muscle regeneration after injury.

This study was published in NPJ Regenerative Medicine.

“While we have made great strides toward better understanding this disease, this work shows how basic biology can provide great insights into appropriate regenerative medicine therapies,” said the study’s lead author, Foteini Mourkioti, PhD. “From the lab, we’re now able to show that there is potential for a whole new realm of therapies for patients with this devastating condition.”

About 15 years ago, researchers discovered that a mutation in the ACVR1 gene was responsible for FOP. In that study, the team found that the mutation changed cells within muscles and connective tissues, causing them to behave like bone cells and create new, extraneus bone.

“However, while investigations of how the FOP mutation alters the regulation of cell fate decisions have been extensively pursued in recent years, little attention has been paid to the effects of the genetic mutation on muscle and its impact on the cells that repair muscle injuries,” Shore said. “We were convinced that pursuing research in this area could provide clues not only for preventing extra bone formation but also for improving muscle function and regeneration, bringing new clarity to FOP as a whole.”

The researchers studied muscle from mice with the same mutation in the ACVR1 gene that people with FOP have. They focused on two specific types of muscle tissue stem cells: fibro-adipogenetic progenitors (FAPs) and muscle stem cells (MuSCs). Typically, muscle injury repair requires a careful balance of these two cell types. Injured tissue responds by an expansion of FAP cells, which are assigned to recruit muscle stem cells that will regenerate the damaged muscle tissue. After about three days, FAPs die off, their job done. At the same time, MuSCs transition toward a more mature, differentiated state, called muscle fibre, essential to organised movement of our muscles.

In the mice with the ACVR1 mutation being studied, apoptosis – the process through which FAP cells die as a part of proper muscle regeneration – had slowed significantly, leading to a high presence of FAPs past their usual lifespan, altering their balance with the MuSCs. The injured tissue also showed a diminished capacity for muscle stem cell maturation and, as a result, muscle fibres were considerably smaller in mice carrying the ACVR1 mutation compared to muscle fibres in mice lacking the mutation.

“The prolonged persistence of diseased FAPs within the regenerating muscle contributes to the altered muscle environment in FOP, which reduces muscle regeneration and allows the over-abundant FAPs to contribute to the formation of extra-skeletal bone,” Mourkioti said. “This provides a completely new perspective on how excess extra-skeletal bone is formed – and how it could be prevented.”

The current targets for treating FOP focus on slowing extra-skeletal bone growth. This research may provide a pivotal new direction. “We propose that therapeutic interventions should consider promoting the regenerating potential of muscles together with the reduction of ectopic bone formation,” the authors wrote. “By addressing both stem cell populations and their roles in the origin of FOP, there is the possibility of greatly enhanced therapies.”

Source: University of Pennsylvania School of Medicine

Categories : Metabolic DisordersTags :

Newly Discovered Hormone Implicated in Development of Diabetes

On By ModernMedia
Image by Nataliya Vaitkevich on Pexels

A newly discovered hormone named fabkin helps regulate metabolism and may play an important role in the development of both type 1 and type 2 diabetes, according to a new study published in Nature.

Fabkin levels were abnormally high in mice and human patients with either type 1 or type 2 diabetes, and blocking the activity of fabkin prevented the development of both forms of diabetes in the animals. Fabkin likely plays a similar role in humans and the hormone complex could be a promising therapeutic target, according to the researchers.

“For many decades, we have been searching for the signal that communicates the status of energy reserves in adipocytes to generate appropriate endocrine responses, such as the insulin production from pancreatic beta cells,” said senior author Gökhan S. Hotamisligil. “We now have identified fabkin as a novel hormone that controls this critical function through a very unusual molecular mechanism.”

Many hormones are involved in the regulation of metabolism, such as insulin and leptin. Fabkin is different from traditional hormones in that it is not a single molecule with a single defined receptor. Instead, fabkin is composed of a functional protein complex consisting of multiple proteins, including fatty acid binding protein 4 (FABP4), adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK). Through a series of experiments, the researchers determined that fabkin regulates energy signals outside of cells. These signals then act through a family of receptors to control target cell function. In the case of diabetes, fabkin controls the function of beta cells in the pancreas that are responsible for insulin production.

Hotamisligil and colleagues previously discovered that a protein known as FABP4 is secreted from fat cells during lipolysis, the process in which lipids stored within fat cells are broken down, typically in response to starvation. Since then, many studies showed links between circulating FABP4 and metabolic diseases including obesity, diabetes, cardiovascular disease, and cancer. However, the mechanism of action was unknown.

In the new study, the researchers showed that when FABP4 is secreted from fat cells and enters the bloodstream, it binds with the enzymes NDPK and ADK to form the protein complex now identified as fabkin. In this protein complex, FABP4 modifies the activity of NDPK and ADK to regulate levels of molecules known as ATP and ADP, which are the essential units of energy in biology. The researchers discovered that surface receptors on nearby cells sense the changing ratio of ATP to ADP, triggering the cells to respond to the changing energy status. As such, fabkin is able to regulate the function of these target cells.

The pancreas’ beta cells are a target of fabkin and the hormone is a driving force behind the development of diabetes, the researchers showed. When fabkin in mice was neutralised with an antibody, the animals did not develop diabetes. When the antibody was given to obese, diabetic mice, they reverted to a healthy state.

“The discovery of fabkin required us to take a step back and reconsider our fundamental understanding of how hormones work.” said lead author Kacey Prentice. “I am extremely excited to find a new hormone, but even more so about seeing the long-term implications of this discovery.”

Source: Harvard University

Categories : COVIDTags :

Over 50s Have Greater Risk of Reduced Mobility after COVID

On By ModernMedia
Photo by Bennett Tobias on Unsplash

Adults over 50 with mild or moderate COVID have increased risk of worsening mobility and physical function, even if hospitalisation is not required to treat the virus, new research has found.

The study, published in JAMA Network Open, highlights the burden of COVID among middle-aged and older adults who are not hospitalised, and suggests that even those who experienced even mild COVID have lasting, troublesome symptoms.

Researchers surveyed more than 24 000 people over the age of 50 from across Canada during the initial phase of the lockdown in 2020 to determine the effect of a COVID diagnosis on their mobility. 

The team looked at mobility issues including difficulty getting up from sitting in a chair, ability to walk up and down stairs without assistance and walking two to three neighbourhood blocks, as well as changes in participants’ ability to move around the home, engage in housework and physical activity.

“We found that even those with mild and moderate illness due to COVID experienced adverse changes in mobility and physical function compared to individuals without COVID,” said co-author Professor Susan Kirkland.

“These findings are worth noting because they indicate that the negative effects of COVID are much broader and impact a wider range of older adults than those who are hospitalised for COVID.”

Participants with COVID had nearly double the odds of worsening mobility and physical function, although most had mild or moderate symptoms. Of the 2748 individuals with confirmed, probable or suspected COVID, 94% were not hospitalised.

Individuals with confirmed or probable COVID had double the odds of worsening ability to engage in household activities and participate in physical activity than those without COVID. Similar results were found for those with suspected COVID.

“Our results showed there was a higher risk for mobility problems in people who were older, had lower income, those with three or more chronic conditions, low physical activity and poorer nutrition,” said co-author, assistant professor Marla Beauchamp.

“However, those factors alone did not account for the mobility problems we observed among people with COVID. Rehabilitation strategies need to be developed for adults who avoid hospitalisation due to COVID but still need support to restore their mobility and physical function.”

The researchers concluded that there is a need to further understand the long-term impacts of COVID and consider “the development and implementation of effective intervention and management approaches to address any persistent deficits in mobility and functioning among those living in the community.”

Source: Dalhousie University

Categories : Neurodegenerative DiseasesTags :

MS Likely Caused by Epstein-Barr Virus

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Source: NCI on Unsplash

Multiple sclerosis (MS) is likely caused by infection with the Epstein-Barr virus (EBV), according to a new Harvard University study.

“The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality,” said senior author Professor Alberto Ascherio. “This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.” The findings were published in Science.

Currently incurable, MS is a chronic inflammatory disease of the central nervous system that attacks the myelin sheaths protecting neurons in the brain and spinal cord. One of the top suspects for its cause is EBV, a herpes virus that can cause infectious mononucleosis and establishes a latent, lifelong infection of the host. Establishing a causal relationship between the virus and the disease has been hard because EBV infects approximately 95% of adults, MS is relatively rare, and the onset of MS symptoms begins about ten years after EBV infection. To determine the connection between EBV and MS, the researchers conducted a study among over 10 million US military personnel, identifying 955 who were diagnosed with MS during their period of service.

The team analysed serum samples taken twice a year by the military and determined the soldiers’ EBV status at time of first sample and the relationship between EBV infection and MS onset during the period of active duty. In this cohort, the risk of MS increased 32-fold after infection with EBV but remained unchanged after infection with other viruses. Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection. The findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

The delay between EBV infection and the onset of MS may be partly a result of the disease’s symptoms being undetected early on and partly the evolving relationship between EBV and the host’s immune system, which is repeatedly stimulated whenever latent virus reactivates.

“Currently there is no way to effectively prevent or treat EBV infection, but an EBV vaccine or targeting the virus with EBV-specific antiviral drugs could ultimately prevent or cure MS,” Prof Ascherio said.

Source: Harvard University

Categories : Ageing Diet and NutritionTags :

Consumption of Olive Oil Reduces Risk of Premature Death

On By ModernMedia
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A new study has found that people who consume higher amounts of olive oil may lower their risk of premature death overall and from specific causes including cardiovascular disease, cancer, and neurodegenerative disease, compared to people who never or almost never consume olive oil. People who consumed olive oil instead of animal fat were also found to have a lower risk of total and cause-specific mortality.

“Olive oil consumption has been linked to lower cardiovascular disease risk, but its association with premature death was unclear,” said Marta Guasch-Ferré, a senior research scientist in the Department of Nutrition at Harvard Chan School. “Our findings confirm current dietary recommendations to replace animal fats with plant oils for the prevention of chronic diseases and premature death.”

The researchers used health data collected between 1990 and 2018 for 60 582 women participating in the Nurses’ Health Study and 31 801 men in the Health Professionals Follow-up Study. All participants were free of cardiovascular disease or cancer at the study start.

Participants were asked how often they used olive oil in salad dressings, added to food or bread, or in baking or frying. According to the findings, people in the highest category of olive oil consumption (> 7g/day) had 19% lower risk of total and cardiovascular disease mortality, 17% lower risk of cancer mortality, 29% lower risk of neurodegenerative mortality, and 18% lower risk of respiratory mortality, compared with those who never or rarely consumed olive oil. Compared to margarine, butter, mayonnaise, or dairy fat, olive oil usage was correlated with reduced risk of total and cause-specific mortality. However no significant risk reduction was seen compared to use of other vegetable oils.

“Clinicians should be counselling patients to replace certain fats, such as margarine and butter, with olive oil to improve their health,” advised Guasch-Ferré. “Our study helps make specific recommendations that will be easy for patients to understand and hopefully implement into their diets.”

The findings were published in the Journal of the American College of Cardiology.

Source: Harvard University

Categories : Environmental EffectsTags :

Ozone Linked to Cognitive Impairment with Age

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A robust link has been established between long-term ozone exposure and an increased risk of cognitive impairment in older adults, according to a large-scale study published in Environment International.

Air pollution has long been considered a major risk factor for an ageing society. Fine airborne particulate matter can lead to dementia and other cognitive disabilities. But beyond airborne particles, little is known about the way in which other pollutants can pose a similar danger.

The researchers chose to focus on ambient ozone, a highly reactive gas that exists in much of smog at ground level. They then observed health outcomes in nearly 10 000 older adults across China and analysed the extent to which long-term ozone exposure may have impacted their cognitive ability over time.

The results, they found, were startling. For every 10 microgram increase of yearly average ozone exposure, the risk for cognitive impairment grew by more than 10%. Through their analysis, the researchers also found that this association held even when they abstracted away individual risk factors such as smoking, drinking and education level. That is, older adults in China who were exposed to high levels of yearly ozone pollution were more likely to develop cognitive disabilities later in life, no matter what other activities they were involved in.

“Our findings suggest potential benefits in delaying the progression of cognitive decline among older adults if ozone levels are reduced below the new WHO Global Air Quality Guideline for ozone pollution,” said Kai Chen, Ph.D., assistant professor at the Yale School of Public Health and the study’s lead author.

The researchers acknowledged limitations such as observational data being unable to establish a causal link. More research is needed into ozone’s destructive mechanism. And since many older adults in China spend more time indoors, their ozone exposure may be different.

Nonetheless, the findings match what other researchers have found in areas across the globe: Over the past several years, studies have traced a similar link in adults in the United States and in Taiwan, and have also found an association between ozone exposure and other neurological diseases.

The study shows that ozone exposure needs to be curbed worldwide to prevent healthcare systems from being overwhelmed as populations age and pollution increases.

Study co-author Professor Robert Dubrow said what makes this issue more urgent is that “ozone pollution is projected to be worsening under climate change.” Reducing this threat could bring significant benefits to public health and improve quality of life.

Source: Yale University

Categories : Mental HealthTags :

Politics Makes People Sick – Literally

On By ModernMedia
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According to a new US study, all the political jockeying is harmful to our health, has been for some time, and even a change in party power didn’t help.

Political scientist Kevin Smith followed up a landmark 2017 survey study where he measured the effects of the political climate on Americans’ physical, social, mental and emotional health. Smith repeated the same 32-question survey twice in 2020 – two weeks prior to the election, and two weeks after. The 2020 findings mirrored the 2017 results, and again found that a large proportion of American adults blame politics for causing them stress, loss of sleep, fractured relationships and more.

Similar to the 2017 findings, the results of the 2020 surveys, published in PLOS One, showed that an estimated 40% of Americans identified politics as a significant source of stress. Between a fifth and a third of US adults also blamed politics for causing fatigue, feelings of anger, loss of temper and triggering compulsive behaviours. About a quarter of adults reported they’d given serious consideration to moving because of politics.

That the results remained mostly stable after nearly four years is cause for alarm, Smith said.

“This second round of surveys pretty conclusively demonstrates that the first survey was not out of left field – that what we found in that first survey really is indicative of what many Americans are experiencing,” Smith, chair and professor of political science, said. “It’s also unpleasant to think that in that span of time, nothing changed. A huge chunk of American adults genuinely perceive politics is exacting a serious toll on their social, their psychological and even their physical health.”

Smith repeated the survey with the same group of people both before and after the election to see if the election’s outcome would recast people’s perceptions.

“We wondered if a change in presidency, which indeed was the case, would shift attitudes, and the short answer is no,” Smith said. “If anything, the costs that people perceive politics is exacting on their health increased a little bit after the election.”

Smioth was most surprised at the repeated finding that 5% of Americans blame politics for having suicidal thoughts.

“One in 20 adults has contemplated suicide because of politics,” Smith said. “That showed up in the first survey in 2017, and we wondered if it was a statistical artifact. But in the two surveys since, we found exactly the same thing, so millions of American adults have contemplated suicide because of politics. That’s a serious health problem.”

Those most likely to be negatively affected by politics were younger, more often Democratic-leaning, more interested in politics and more politically engaged.

“If there’s a profile of a person who is more likely to experience these effects from politics, it’s people with those traits,” Smith said.

This could mean problems for democracy if this trend continued. Smith suggested investigating whether civic education had a positive effect, as those who were more knowledgeable about politics seemed to be less affected.

Source: University of Nebraska

Categories : COVIDTags :

Fourth Wave Ending as COVID Becomes Endemic

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Speaking to  the media on Friday, Dr Joe Phaahla said that vaccinations had “uncontestably” lowered the rate of hospitalisations as seen by reduced hospital admissions in the fourth wave. saying that there has been a decoupling between new infections and hospital admissions and deaths. An article awaiting peer review on the medRxiv preprint server shows evidence of this in Cape Town.

Vaccinations were still lower than expected, despite a renewed vaccination drive from 17 December, a situation he attributed to people focussing on their festivities. As of Thursday, 45.5% of all SA adults had received at least one dose, with just under 40% being fully vaccinated. However, only 31.6% of 18–34 year olds have been vaccinated. About one million doses have been administered to the newly opened 12–17 year age group.

In an interview with eNCA, Dr Phaahla said that he concurs with experts that COVID is heading towards becoming an endemic disease, emphasising that South Africa is prepared for this. A new dashboard is to be unveiled which will show the number of vaccinated and unvaccinated in hospitals.

Dr Phaahla has also said that the issue of mandatory vaccinations is currently being deliberated by the government and that an announcement will be made in due course. In the US, the Supreme Court blocked President Biden’s vaccine mandate for large companies, which is seen as a significant blow to his administration’s COVID response plan.

The NICD’s Dr Michelle Groome said that almost 99% of all COVID cases sequenced are caused by Omicron. Gauteng, has exited the fourth wave with a low rate of new cases (1.4 cases per 100 000) and slight (2.2%) increase, likely attributable to increased testing. All other provinces had observed a decrease in weekly incidence of new cases, save Northern Cape (21.9 per 100 000, 18.3% increase). A 14.3% positivity rate was seen as of 13 January, down from highs above 35% in mid-December.

Test positivity rate had fallen from 25–30% in the last week of 2022 to 14% on Thursday.