To prevent diabetic foot ulcers, scientists at the University of Texas at Arlington have developed responsive footwear technology that relieves pressure on areas of the feet that experience high stress during walking and other activities.
Principal research scientist Muthu Wijesundara and his team have received a patent for a dual-layer insole apparatus for diabetic foot lesion prevention.
Due to numbness in their legs and feet, people with diabetes often are unable to detect and respond to stress-related pain by adjusting their foot loading. This can result in repeated stress to high-pressure foot regions such as the heel or toes and can worsen blisters, sores and ulcers to the point of severe tissue loss or life-threatening infection. For many, foot ulcers can lead to amputation of a toe, foot or leg.
“Diabetes is a leading cause of amputation worldwide, and there is a major role that technology can play to prevent its devastating effects,” Wijesundara said. “We are now one step closer to finding a solution to reduce risk of complications related to diabetic foot ulcers.”
The removable shoe insole relieves stress by periodically regulating and redistributing pressure across all areas of the foot. Using fluid-filled cells, the dual-layer apparatus provides variability in a person’s foot-loading patterns to reduce prolonged pressure to any given area. The insole can automatically adjust and is designed to accommodate people of various weights.
Additionally, the insole can be substituted for a total contact cast during the healing of a foot ulcer, and it can provide gait and ground force analysis.
Researchers have revealed biological reasons for how disease progression happens and why a certain population of asthma patients are less susceptible to severe COVID.
This research, published in PNAS, shows the importance of the well-known cytokine interleukin-13 (IL-13) in protecting cells against SARS-CoV-2, something which helps explain why people with allergic asthma fare better than the general population despite having a chronic lung condition. However, the same cannot be said for individuals with other diseases, such as chronic obstructive pulmonary disease (COPD) or emphysema, who are at very high risk of severe COVID.
“We knew there had to be a bio-mechanistic reason why people with allergic asthma seemed more protected from severe disease,” said Assistant Professor Camille Ehre, PhD, senior author of the paper. “Our research team discovered a number of significant cellular changes, particularly due to IL-13, leading us to conclude that IL-13 plays a unique role in defence against SARS-CoV-2 infection in certain patient populations.”
Although cytokines like IL-13 cannot be used as therapies because they trigger inflammation, it is important to understand natural molecular pathways that cells use to protect themselves from pathogen invasion, as these studies have the potential to reveal new therapeutic targets.
Many health factors increase a person’s risk of severe COVID, but during the pandemic, epidemiologists found that people with allergic asthma were less susceptible to severe disease.
“These are patients with asthma caused by allergens, such as mould, pollen, and dander,” said A/Prof Ehre. “To find out why they are less susceptible, we investigated specific cellular mechanisms in primary human airway epithelial cell cultures.”
Genetic analysis human airway cell cultures infected with SARS-CoV-2 revealed that the expression of ACE2 governed which cell types were infected and their viral load.
Electron microscopy (EM) identified an intense exodus of virus from infected ciliated cells, which move mucus along the airway surface. EM also revealed severe cytopathogenesis – changes inside human cells due to viral infection. And these changes culminating in ciliated cells (packed with virions) shedding away from the airway surface.
“This shedding is what provides a large viral reservoir for spread and transmission of SARS-CoV-2,” A/Prof Ehre said. “It also seems to increase the potential for infected cells to relocate to deeper lung tissue.”
Further experiments on infected airway cells revealed that a major mucus protein called MUC5AC was depleted inside cells, likely because the proteins were secreted to try to trap invading viruses. But the virus load kept increasing because the cells tasked with producing MUC5AC were overwhelmed in the face of a rampant viral infection.
The researchers knew from epidemiological studies that allergic asthma patients—known to overproduce MUC5AC—were less susceptible to severe COVID. A/Prof Ehre and colleagues also knew the cytokine IL-13 increased MUC5AC secretion in the lungs when asthma patients faced an allergen.
The scientists decided to mimic asthmatic airways by treating human airway cells with IL-13. They then measured viral titres, viral mRNA, the rate of infected cell shedding, and the overall number of infected cells. Each one was significantly decreased. They found this remained true even when mucus was removed from the cultures, suggesting other factors were involved in the protective effects of IL-13 against SARS-CoV-2.
Bulk RNA-sequencing analyses revealed that IL-13 upregulated genes that control glycoprotein synthesis, ion transport, and antiviral processes – all of which are important in airway immune defence. They also showed that IL-13 reduced the expression of the viral receptor, ACE2, as well as reducing the amount of virus inside cells and cell-to-cell viral transmission.
Taken together, these findings indicate that IL-13 significantly affected viral entry into cells, replication inside cells, and spread of virus, thus limiting the virus’s ability to find its way deeper into the airways to trigger severe disease.
“We think this research further shows how important it is to treat SARS-CoV-2 infection as early as possible,” A/Prof Ehre said. “And it shows just how important specific mechanisms involving ACE2 and IL-13 are, as we try our best to protect patients from developing severe infections.”
The prospect of an exodus of doctors and other key healthcare personnel from South Africa ahead of the planned introduction of the National Health Insurance (NHI) scheme has prompted concern among healthcare stakeholders.
In addition to the loss of skilled healthcare professionals, there is also a growing concern that the country could lose valuable training skills as professionals look to leave.
Thirteen years on from its inception, the NHI continues to suffer from the same criticisms. A May 2021 research paper [PDF} found that South Africa’s per capita spending on public healthcare was higher than even wealthier developing countries, yet it ranked near the bottom for measures of healthcare outcomes.
An informal poll on the QuickNews website in March showed that 81% of respondents had at least considered emigrating due to the planned introduction of NHI.
Professional associations are also warning of an exodus with the start of NHI. The South African Medical Association (SAMA) has said that its members cannot support the NHI in its current form.
This stems from a deep-rooted lack of confidence in the capacity of government and its financial ability to ensure the service is successful, the association said. Other concerns that members have raised include only providing emergency treatment to refugees and illegal immigrants, as well as their children.
SAMA conducted a survey which showed that up to 38% of its members plan to emigrate from South Africa due to the planned introduction of the NHI.
6% of members said that they plan to emigrate for other reasons, while 17% of doctors said that they were unsure about leaving the country. Many doctors have said that the aim should rather be to get the public sector to a state where it can appeal to private sector patients.
They added that there should be engagement with private doctors to provide additional services funded by the state. The group also called for a proper pilot of the proposed systems and payment mechanisms.
The Department of Health noted these concerns in a parliamentary briefing this week, noting that skilled personnel will be needed for the NHI to work. It added that this was not limited to healthcare professionals, but that general skilled human resources will be central to the health system going forward.
It added that the complex interactions between training, registration compliance and employment can all be greatly improved.
“This is a big ship that will need to be turned, but the framework is in place,” said acting director-general of health Dr Nicholas Crisp. “We have heard the threats that there will be an exodus of personnel if the NHI is implemented and a brain drain.”
The department is actively responding to this, he said, with a framework in place to ensure the country retains the necessary skills. A ‘Human Resources for Health strategy’ before was already under development before the start of the COVID pandemic, he added.
This framework sets out a multi-work implementation plan, but it requires money and investment in the health workforce to ensure the country is ready for universal health coverage, Dr Crisp said.
“Every health professional has a place in the National Health Insurance – whether you choose to work in the public portion of the delivery system or the private portion of that delivery system.
“We do not think there needs to be a threat on anybody, or their viability, or their role to be played.”
Using a rice-grain sized wireless implant to stimulate peripheral nerves from within blood vessels could potentially treat drug-resistant neuropathic pain, according to a study published in Nature Biomedical Engineering.
After receiving a grant, a team set out to create implantable, wirelessly powered nerve stimulators that can be used in place of opioids for pain management. The 1-millimetre large implants are small enough to be placed on stents and delivered within blood vessels adjacent to specific areas of the central and peripheral nervous system.
Co-principal investigator of the study, Sunil A. Sheth, MD, explained: “We’re getting more and more data showing that neuromodulation, or technology that acts directly upon nerves, is effective for a huge range of disorders—depression, migraine, Parkinson’s disease, epilepsy, dementia, etc. – but there’s a barrier to using these techniques because of the risks associated with doing surgery to implant the device, such as the risk of infection. If you can lower that bar and dramatically reduce those risks by using a wireless, endovascular method, there are a lot of people who could benefit from neuromodulation.”
Neuropathic pain can be a disabling disorder that accounts for nearly 40% of chronic pain sufferers, often leading to anxiety, depression, and opioid addiction. Previous studies showed that electrical stimulation is an effective treatment for reducing pain when doctors target the spinal cord and dorsal root ganglia (DRG), a bundle of nerves that carry sensory information to the spinal cord. However, existing DRG stimulators require invasive surgery to implant a battery pack and pulse generator.
According to the researchers, this new type of technology offers a way to perform minimally invasive bioelectronic therapy that helps with more precise placement of the implant and more predictable outcomes. The team are hoping to move forward with regulatory approval, which Dr Sheth estimates may take a few years.
Long-term brain damage resulting from neonatal hypoglycaemia can be warded off with proper treatment such as later education and dextrose gel after birth, new studies have found.
The study is the first of its kind to show that stabilising blood sugar levels in neonatal hypoglycaemia prevents brain damage.
Hypoglycaemia is very common, affecting more than one in six babies. Since glucose is the main energy source for the brain and the body, untreated low blood sugar can cause adverse effects on a child’s neurodevelopment up to the age of 4.5 years old.
While hypoglycaemia is known to alter early development, there has been a significant gap in our understanding of how hypoglycaemia can alter a child’s development after early childhood. A study in JAMA investigated the long-term impact on brain development in mid-childhood – ages 9 to 10 – and found that, compared to peers, there was no significant difference in academic outcomes for children exposed to hypoglycaemia as newborns.
“Rich pre-school and school experiences may help a child’s brain to re-organise and improve their academic abilities up to the developmental milestones of their peers,” said Professor Ben Thompson, who is part of the research team.
Following 480 children born at risk of neonatal hypoglycaemia, researchers assessed each child at aged nine to 10 in five key areas: academic achievement, executive function, visual-motor function, psychosocial adaptation, and general health. All child participants were involved in previous studies, providing researchers with information on their neuro-development outcomes at two and 4.5 years old.
This ability to catch-up in neuro-cognitive function could be because of the brain’s plasticity, the researchers suggest.
“It’s a big relief to know that babies who are born with and treated for a condition as common as hypoglycaemia are not likely to suffer long-term brain damage,” Prof Thompson said.
The researchers have also continued studying the efficacy of dextrose gel to treat low blood sugar in the first 48-hours of a newborn’s life, avoiding the need for babies to go to newborn intensive care units immediately after delivery.
In an additional study published in JAMA, the team assessed the later risks of dextrose gel as a treatment for hypoglycaemia in infancy, and found change to the risk of neuro-sensory impairment at age two. This treatment continues to be widely used in a growing number of countries, including Canada, Australia, the United Kingdom and the United States.
A recent study published in JAMA Surgery has demonstrated the viability of living-donor liver transplant for patients who have systemically controlled colorectal cancer and liver tumours that cannot be surgically removed.
“This study proves that transplant is an effective treatment to improve quality of life and survival for patients with colorectal cancer that metastasised to the liver,” said senior study author Dr Gonzalo Sapisochin.
The study focused on colorectal cancer partly for its tendency to spread to the liver. Nearly half of all patients with colorectal cancer develop liver metastases within a few years of diagnosis and 70% of liver tumours in these patients cannot be removed without removing the entire liver.
Unfortunately, most of these patients cannot get deceased-donor liver transplants because their liver function is fairly normal in spite of their tumours. This puts them near the bottom of the national organ transplant waiting list.
Thanks to recent advances in cancer treatments, many of these patients are able to get their cancer under systemic control, which means only their liver tumours prevent them getting a ‘cancer free’ label. It also increases the odds that these patients – and their new livers – will remain cancer free, which is crucial when balancing the benefit to the patient with the risk to a living donor.
“I’ve seen so many cancer patients, whose cancers were not spreading, but we couldn’t remove the tumours from their livers and we knew they would die,” said first study author Dr Roberto Hernandez-Alejandro. “We hoped living-donor liver transplant could give them another chance.”
Because it offered a last resort, the study attracted patients from near and far. All patients and donors went through a rigorous screening process to ensure they were good candidates for the procedure, and they were educated about the risks of the surgery and the possibility of cancer recurrence.
Patients and donors underwent staggered surgeries to fully remove patients’ diseased livers and replace them with half of their donors’ livers. Over time, both patients’ and donors’ livers regenerated and regain normal function.
Patient imaging and blood analysis was closely monitored for any signs of cancer recurrence and will continue to be followed for up to five years after their surgery. At the time of study publication, two patients had follow-up of two or more years and both remained alive and well, cancer-free.
“We have seen very good outcomes with this protocol, with 100 percent survival and 62 percent of patients remaining cancer free one year and a half after surgery,” said study author Dr Mark Cattral. “It is very strong data to support that we can offer this treatment safely and make appropriate use of scarce life-saving organs.”
