University of Utah scientists have discovered a new type of neuron in the retina, which will help fill in our understanding of how sensory information is relayed.
In the central nervous system a complex network of neurons communicate with each other to relay sensory and motor information. In this chain of communication, a type of neuron called interneurons serve as intermediaries . A research team led by Ning Tian, PhD, identified a previously unknown type of interneuron in the mammalian retina. Their findings were published in the journal PNAS.
This discovery is a major step forward for the field as scientists strive to build a better understanding of the central nervous system by identifying all classes of neurons and their connections.
“Based on its morphology, physiology, and genetic properties, this cell doesn’t fit into the five classes of retinal neurons first identified more than 100 years ago,” said Dr Tian. “We propose they might belong to a new retinal neuron class by themselves.”
The research team called their discovery the Campana cell after its shape, which resembles a hand bell. Campana cells relay visual signals from both types of light-sensing rod and cone photoreceptors in the retina, however their exact purpose is the subject of ongoing research. Experiments revealed that Campana cells remain activated for an unusually long time – as long as 30 seconds – in response to a 10 millisecond light flash stimulation.
“In the brain, persistent firing cells are believed to be involved in memory and learning,” said Dr Tian. “Since Campana cells have a similar behaviour, we theorise they could play a role in prompting a temporal ‘memory’ of a recent stimulation.”
New research from the US has found that older adults who experienced social isolation had higher blood levels of interleukin-6 and C-reactive protein, two markers of inflammation that can have long-term negative impacts for the health of individuals as they age.
Social isolation is a risk factor for morbidity and mortality comparable to well-established risk factors including smoking, hypertension, and a sedentary lifestyle. The specific biological mechanisms that connect social isolation to morbidity and mortality remain unclear.
The study, published in the Journal of the American Geriatrics Society, used data from the National Health and Aging Trends Study (NHATS), which included a nationally representative sample of 4648 Medicare beneficiaries aged 65 years and older. The researchers defined social isolation with a multi-domained typology that considers living arrangement, core discussion network, religious attendance, and social participation The authors noted that clinical and social interventions that address social isolation among older adults may influence biological processes such as inflammation, as well as their potentially negative effects.
Credit: JAGS
“Our findings demonstrate an important association between social isolation and biological processes. This work is a step in the journey to disentangle the mechanisms by which social isolation leads to higher levels of morbidity and mortality,” said lead author Thomas K.M. Cudjoe, MD, MPH, of Johns Hopkins School of Medicine. “My hope is that investigators incorporate objective measures of social isolation and biological markers in future longitudinal studies so that we might continue to advance our understanding of these complex biopsychosocial interactions.”
In Scotland, about one in 20 people diagnosed with type 2 diabetes achieve remission from the disease, according to research appearing in PLOS Medicine. This suggests people are achieving remission outside of research trials and without bariatric surgery. Recognition of individuals in remission, following their progress, and understanding better the factors linked to remission could result in improved initiatives to help others.
In 2019 there were an estimated 463 million people with diabetes in the world, 90–95% of whom have type 2 diabetes. Ageing populations, growing obesity and sedentary lifestyles are increasing these numbers. The likelihood of achieving remission after 15% weight loss has been shown to be mainly determined by the duration of diabetes, with responders having better beta‐cell function at baseline.
Some people with type 2 diabetes have achieved remission after bariatric surgery, or after taking part in a research trial of a very low-calorie diet, but it is unknown how many people in the general population are in remission. Mireille Captieux at the University of Edinburgh and colleagues used a Scottish national register of people with type 2 diabetes to estimate the number of people in remission in 2019 and described the characteristics of those in remission and not in remission.
Of 162 316 patients aged > 30 who were eligible for the analysis, 7710 (5%) were in remission in 2019. Individuals in remission tend to have not previously taken glucose lowering medication; have lost weight since their diagnosis; be older; have lower blood sugar levels at diagnosis; or have had bariatric surgery. This finding helps to establish a baseline for future studies, and could also help clinicians identify patients with whom to discuss remission and weight loss.
Captieux added, “We have been able to show, for the first time, that 1 in 20 people in Scotland with type 2 diabetes achieve remission. This is higher than expected and indicates a need for updated guidelines to support clinicians in recognising and supporting these individuals.”
Despite high hopes, the first placebo controlled trial of inhaled steroids for COVID suggests that ciclesonide, an inhaled and nasal steroid drug commonly used for asthma and rhinitis, does not help young healthy people with COVID and respiratory symptoms improve earlier.
The study, published in the BMJ, was motivated by research showing that ciclesonide, which is safe, inexpensive and widely available, could decrease viral replication of SARS-Cov2 in mouse models of COVID. A randomised, double-blind, placebo-controlled trial of inhaled ciclesonide was designed to evaluate the resolution of symptoms in adults with COVID presenting with respiratory symptoms.
“Based on my experience treating asthma, I thought it made sense to see if it would decrease the lung inflammation in patients with COVID early in the disease, as lung disease has an important impact for patients and is a major effect of the virus,” explained Dr Nicole Ezer, the first and lead author of the study, who is a lung specialist and a researcher in the Translational Research in Respiratory Diseases Program at the RI-MUHC. “In addition, we felt it was important to study a drug for COVID that has a very good safety profile and could be used in high, middle and low-income countries safely to reduce respiratory symptoms. Access to affordable medications is very important to decrease disparities in health outcomes across the world.”
The importance of placebo control From Sept. 15, 2020 to June 8, 2021, the study recruited 215 symptomatic adults and randomly assigned them to either inhaled and intranasal ciclesonide or inhaled and intranasal placebo for 14 days. Participants were asked to complete a survey online on the day of enrollment and on six other occasions until day 14, with a follow-up survey at day 29.
Based on the assumption that treatment would be most effective if given early in the disease process, participants were recruited within five days of a positive PCR test result for SARS-CoV-2 and symptom onset and received the treatment at home by commercial courier. No vaccinated participants were included in the trial.
No significant difference was seen between the intervention and control group. After seven days of treatment, 40% taking ciclesonide had no more fever and respiratory symptoms, vs 35% taking placebo. At day 14, these figures amounted to 66% in the ciclesonide group compared with 58% in the placebo group.
Those results are disappointing, especially since two recent open label studies had raised hopes in the scientific community that inhaled steroids could alleviate respiratory symptoms associated with COVID, and one study demonstrated efficacy of dexamethasone in admitted patients with COVID.
“The previously published studies had a major limitation: they were open label with no placebo. Other studies have shown that inhalers have a strong placebo effect,” explained the study’s senior author, Dr Emily McDonald, associate professor of medicine at McGill University. “Here’s a strong reminder that any study of a medication, in particular of inhalers, needs to be controlled with a placebo before we rush to recommend them.”
In spite of the study’s outcome, researchers still believe there is potential for the treatment of COVID with inhaled steroids.
“It’s still possible that inhaled steroids might be beneficial for older at-risk populations,” said Dr Ezer, who is also an assistant professor of medicine at McGill University. “We need more research focused on older adults and people who are high-risk, but those studies must have a placebo arm to make sure they aren’t coming to a false conclusion of benefit.”
A trend of amalgamations is underway in the South African private healthcare industry, in the face of growing challenges and the impending introduction of National Health Insurance (NHI).
Escalating healthcare inflation and costs, a declining and ageing membership, the impact of the COVID pandemic and a growing burden of disease are all impacting the not-for-profit Medical Scheme industry, which is highly regulated.
Medical scheme consolidation is one of the prominent trends, particularly given the prospect of NHI on the horizon, where smaller schemes will not compete, said Lee Callakoppen, principal officer of Bonitas Medical Fund.
The Council for Medical Schemes (CMS) advises that schemes that cannot compete sustainably on price should consider amalgamation partners, Callakoppen said.
“The trend towards amalgamations is not only for the sustainability of the medical scheme but for the benefit of members who ‘own’ the fund’.
“It is not only the call from CMS for schemes to join forces but also strict regulations around minimum solvency ratios and reserves which are more difficult for smaller schemes to maintain.”
It is a requirement of the Medical Schemes Act that medical schemes shall at all times maintain their business in a financially sound condition. They need to have sufficient assets for conducting business, providing for liabilities and having the prescribed solvency requirements of 25%, said Callakoppen.
“It’s a big ask for small schemes in this volatile and uncertain healthcare market,” he said.
A trend of amalgamation for small schemesThe CMS provides regulatory supervision of more than 80 medical schemes registered in the country and oversees amalgamation prospects.
One proviso for amalgamation is that schemes should complement each other and provide a more comprehensive offering to members.
“One clear indicator of risk is the size of the pool of lives being covered,” said Callakoppen. “Schemes with smaller risk pools are struggling to survive and experience more volatile claims”.
“Amalgamation into a bigger scheme means cross-subsidisation of costs. It is a trend I believe will continue, if not accelerate. In fact, in the past decade, we have seen 28 amalgamations approved by the CMS and the Competition Commission.”
The NHI has been criticisedfor potentially stifling innovation in healthcare, as well as not actually being able to fix the country’s flawed and unequal healthcare system.
In a welcome finding, researchers have found that women who have had gestational diabetes can use the popular 5:2 dietfor weight loss to help prevent the onset of type 2 diabetes.
It can be a challenge to lose weight and keep it off, especially for mothers with a new baby. The study by the University of South Australia suggests that the popular 5:2 or intermittent fasting diet is as effective as a conventional energy-restricting diet, giving women greater choice and flexibility for weight loss.
The 5:2 diet allows five days of normal eating each week while substantially restricting calories over two days a week, as opposed to a typical diet that requires moderate energy restrictions daily.
A fifth of pregnancies are affected by gestational diabetes, which carries a ten-fold risk of developing type 2 diabetes later in life, exacerbated even further by being overweight.
A welcome finding for a growing problem The study’s lead researcher, Dr Kristy Gray, said women looking to lose weight will welcome the finding: “Gestational diabetes is the fastest growing type of diabetes in Australia, affecting 15% of pregnancies.
“Healthy eating and regular physical activity are recommended to manage gestational diabetes, with continuous energy restriction diets – or diets that cut calories by 25–30% being the most common strategy for weight loss and diabetes prevention.
“The trouble is, however, that new mums often put themselves last – they’re struggling with fatigue and juggling family responsibilities – so when it comes to weight loss, many find it hard to stick to a low-calorie diet.
“The 5:2 diet may provide a less overwhelming option. As it only cuts calories over two days, some women may find it easier to adopt and adhere to, as opposed to a consistently low-calorie diet requiring constant management.
“Our research shows that the 5:2 diet is just as effective at achieving weight loss as a continuous energy-restricted diet in women who have had gestational diabetes, which is great, because it provides women with greater choice and control,” she said, adding that women should seek advice from health professionals before starting the diet.
The research investigated the effects of both the 5:2 diet (five days eating normally and two days eating 500 calories) and a continuous energy-restricted diet (1500 calories per day) on weight loss and diabetes risk markers in women with a previous diagnosis of gestational diabetes. Both diets cut energy intake by about 25% a week.
Embedded within bone tissue are osteocytes, and the tree-like communication cells known as dendrites. Loss of dendrites to ageing contributes to bone fragility and osteoporosis.
A study published in Nature Communications has revealed how osteocytes form dendrites – a discovery that might yield strategies to maintain these projections and therefore help maintain people’s bone health throughout their lives.
In their study, the researchers found that deletion of Sp7, a gene linked to both rare and common skeletal diseases, in osteocytes causes severe defects in osteocyte dendrites. This gene codes for a protein called a transcription factor, which controls the expression of other genes. The team found that the Sp7 transcription factor targets a gene called osteocrin, which promotes osteocyte dendrite formation. In mice, activating the osteocrin gene made up for the absence of Sp7 and reversed defects in osteocyte dendrites.
“In this work, we demonstrate key roles for the transcription factor Sp7 and its target osteocrin in orchestrating a gene regulatory network needed to promote healthy connections between bone cells,” said senior author Marc Wein, MD, PhD, an investigator in the endocrine unit at MGH and an assistant professor of medicine at Harvard Medical School. “Understanding how osteocytes maintain this network of connections opens up exciting possibilities for new ways to treat osteoporosis and other diseases where bones are prone to fracture.”
Earlier this year, UCT professor Ambroise Wonkam published the Three Million African Genomes (3MAG) project in Nature, which he said started with a “crazy idea”. Now, it looks like his vision is starting to take shape.
The idea of creating a huge library of genetic information about the population of Africa emerged from his work on how genetic mutations among Africans contribute to conditions like sickle-cell disease and hearing impairments.
African genes contain great genetic variation, more than that seen outside of Africa. As he explained, “We are all African but only a small fraction of Africans moved out of Africa about 20–40 000 years ago and settled in Europe and in Asia.”
Another concern for Prof Wonkam is equity, saying: “Too little of the knowledge and applications from genomics have benefited the global south because of inequalities in health-care systems, a small local research workforce and lack of funding.”
Thus far only about 2% of genomes mapped are African, a good proportion of which are African American. This stes from a lack of prioritising funding, policies and training infrastructure, he says, but it also means the understanding of genetic medicine as a whole is lopsided. By studying African genomes, injustics can be corrected, such as finding that genetic risk profiles based on Europeans could be misleading for those of African descent.
To address these disparities, Prof Wonkam and other scientists are speaking to governments, companies and professional bodies across Africa and internationally, in order to build up capacity over the next decade to make the vision a reality.
He expects three million is the number needed to accurately map genetic variations across Africa. The project will take a decade, he says, costing around $450m per year, with industry already showing interest.
Biotech firms welcome prospects of new data The Centre for Proteomic and Genomic Research (CPGR) in Cape Town works with biotech firm Artisan Biomed on a variety of diagnostic tests. Gaps in the applicability of genetic data to the local population are a challenge for the firm, it said.
A genetic mutation in someone could be found but it would be uncertain if that variation is associated with a disease, especially as a marker for that particular population.
“The more information you have at that level, the better the diagnosis, treatment and eventually care can be for any individual, regardless of your ethnicity,” said Dr Lindsay Petersen, the company’s chief operations officer.
Artisan Biomed says the data it collects feeds back into CPGR’s research – allowing them to design a better diagnostic toolkit that is better suited to African populations, for instance.
Dr Judith Hornby Cuff said that the 3MAG project would help streamline processes and improve research, and one day could provide cheaper, more effective and more accessible health care, particularly in the strained South African system.
Prof Wonkam acknowledged that while the costs are huge, the project will “improve capacity in a whole range of biomedical disciplines that will equip Africa to tackle public-health challenges more equitably”.
“We have to be ambitious when we are in Africa. You have so many challenges you cannot see small, you have to see big – and really big,” he said.
The surprise discovery of a new type of cell explains how distress to the skin early in life may prime a person for inflammatory skin disease later, according to a new study in Nature. This finding will likely lead to treatments for autoimmune disorders like scleroderma, and inform understanding of inflammatory disease.
“The results reinforce the idea that what you’re exposed to initially may have lasting ramifications,” said lead researcher Michael Rosenblum, MD, PhD. “It appears that early exposure to inflammation can, through these cells we discovered, imprint an ability for tissues to develop inflammatory disease later in life.”
The team came across this new type of cell while investigating the effects of certain actions known to evoke immune response in mice. One of these actions involved knocking out a group of skin cells that suppress the immune system. Without that regulation, said Dr Rosenblum, a unique cell was observed that seemed to act as a shelter for pathogenic immune cells not typically seen in skin tissues.
“We had to knock out one cell population to see that they were controlling the growth and capacity of these other, unknown cells,” he said, noting that the new cells only became apparent in the tissue exposed to inflammatory triggers. “What normally would be a deserted island on the skin was now inhabited by all these strangers,” he said.
The team dubbed these strangers ‘TIFFs’ (Th2-interacting fascial fibroblasts) after the Th2 immune cells that they help to house. The location of TIFFs in the skin suggests that they belong to a group of cells that make up the fibrous connective tissue that is fascia, said lead author Ian Boothby, a graduate student in Dr Rosenblum’s lab.
“Because most organs have fascia of some sort, what we’re learning about TIFFs in skin may well be widely applicable to the rest of the body, meaning that these cells may play a role in a huge number of inflammatory diseases,” he said.
Boothby and Dr Rosenblum when skin without regulatory cells receives inflammatory triggers, the TIFFs spread like wildfire and become a sort of holding pen for the Th2 immune cells. Later in life, when there is even a small insult to the skin, Dr Rosenblum said, the TIFFs open their floodgates, unleashing the Th2 cells.
It seems that, through these cells, early exposure to inflammalation can leave a life-long imprint.
“All you need to do is push the immune system just a little bit, with a wound or with stress, to unleash all the pathogenic cells living in these TIFFs and create an exaggerated inflammatory response,” he said.
The researchers hypothesise that the exaggerated response may manifest as the creation of fibroses in the fascia, the driving force behind inflammatory skin diseases such as scleroderma.
To confirm the presence of TIFFs in human skin, the team obtained samples from volunteers with eosinophilic fasciitis (EF), a rare inflammatory disorder in which eosinophils build up in the skin fascia, the fibrous tissue between the skin and the muscles below it.
Comparing the EF samples to those of healthy skin, the researchers found TIFFs in both, but looked completely different. In healthy skin, the fascia forms a thin, spidery network between fat cells, while in the EF skin sample, the cells had expanded to form thick bands of fibrous tissue.
Revealing the mysteries of inflammation TIFFs appear to be present in every organ, said Dr Rosenblum, usually found in the fascia surrounding major organs and serve a role in maintaining structure. They’re also prone to interacting with immune cells. He postulates that TIFFs might have evolved as a sort of emergency brigade in case of injury, able to jump-start repair in the case of internal injury.
“In patients with scleroderma or other fibrosing diseases like EF, that repair program may be kind of co-opted, resulting in this chronic wound-healing response,” said Dr Rosenblum. “If we can understand the biology of these cells, we can come in with drugs that revert them back to what they’re supposed to be doing.”
Scientists in Japan have developed a plasma device that promotes bone regeneration in fractures.
Unlike blood plasma, plasma here refers to the fourth state of matter, effectively a highly ionised gas, which has been long investigated as an effective surgical scalpel which cauterises tissue as it cuts. Other recent applications of plasma technology include surface sterilisation.
Now, a new type of plasma device, termed non-thermal atmospheric pressure plasma (NTAPP), was successfully tested in healing of bone fractures in animal bone defect models. It is cooler than most plasmas that are typically used. In a study published in PLOS ONE, researchers from Osaka City University detailed their findings using the technology in this world-first application.
Acceleration of cell growth “NTAPP is considered a new therapeutic method,” said first author Akiyoshi Shimatani, “as it has been shown to accelerate cell growth when applied at low enough levels.” He explained that in an ambient atmosphere it can generate highly reactive oxygen and nitrogen species (RONS) which can be directly exposed to tissues.
Indirect treatments have shown the potential advantages of plasma in supporting the creation of stem cells that cause reactive oxygen species and in inducing osteogenic differentiation and bone formation, however, as the team points out there is no report on directly using NTAPP for bone fracture therapy. “Direct exposure of NTAPP is a key part of this study” states Jun-Seok Oh, professor at the OCU Graduate School of Engineering and advisor to the study, “It required a device specifically designed to generate and deliver RONS to areas of the bone defect ‘effectively’.”
The research group developed a pencil-like plasma device that can effectively generate and deliver RONS to an animal model with a well-established critical bone defect, allowing the team to search for the optimal exposure conditions. Comparing groups that were treated with NTAPP for 5, 10, and 15 minutes to control groups with no plasma administered, micro-CT images at eight weeks showed the 10-minute treatment time as the most successful bone regeneration with 1.51 times larger bone volume than the control group.
Since micro-CT images could not determine whether a bone defect has been filled with new bone, tissue or both, the team also ran a histological analysis and confirmed bone defects in the groups treated with plasma were in fact filled with new bone, and had no tissue or gaps like the control groups.
Precision therapy The biological effect of plasma, like other therapies, depends on the treatment dose delivered into the targets. Although future research will be needed to clarify why the study saw the most bone regeneration during the 10-minute treatment period, surface wettability is understood to promote greater cell spreading and adhesion to biomaterials and implants. Hiroaki Nakamura, professor at the Graduate School of Medicine explained: “We wondered if something similar was occurring where we saw a strong generation of new bone. And we found that compared to the control group, bone surface of the plasma-treated group as statistically and significantly more hydrophilic.”
The research team hopes the plasma device they developed can be applied for surgical use.
