Paracetamol may help protect against kidney damage in patients with malaria, according to a study recently published in Clinical Infectious Diseases.
The study found that for patients with severe malaria caused by the malaria parasite Plasmodium knowlesi (the most common cause of malaria in Malaysia), taking paracetamol regularly for 3 days led to improvements in kidney function when tested one week later.
The findings are important because they will help provide the best possible treatment to patients with severe malaria, said study leader Dr Daniel Cooper.
“Even minor kidney injury can have long-term effects, so anything we can do to minimise kidney injury from malaria will be beneficial for these patients’ long-term outcomes,” Dr Cooper said.
In collaboration with international partners, the study involved 396 people with knowlesi malaria in Sabah, Malaysia.
Assistant Professor Bridget Barber said that in severe malaria, red blood cells can rupture, releasing haemoglobin which can have a toxic impact on kidneys, and it is now believed that paracetamol can help to mitigate these toxic effects.
“These results are consistent with other studies conducted in patients with other forms of malaria, including in adults in Bangladesh, and in children in Africa. Importantly, these findings also suggest that paracetamol may help to protect the kidneys in other conditions that are also associated with rupture of red blood cells,” A/Prof Barber said.
Sleep bruxism, nocturnal teeth grinding and clenching of the upper and lower jaw, can have a number of health impacts. A new study published in the Journal of Advanced Research found that certain tooth shapes and tooth locations could well lead to temporomandibular joint problems as a result of bruxism.
About 15% of the population grind their teeth while they are asleep, a condition which is more common among younger people. The\ pressure exerted on tooth surfaces and on the jaws can be immense and is thought to cause various dental health problems. It can also result in pain in the jaw muscles and headaches. Specific combinations of tooth shape and tooth location during grinding are theorised to have an influence on the mechanical load on the temporomandibular joint and can thus be considered a risk factor for temporomandibular joint (TMJ) disorders.
To investigate whether sleep bruxism has a negative impact on the TMJ structures, researchers used a state-of-the-art computer model of the masticatory region, which includes bone, cartilage and muscular structures. Such computer models can be used to investigate research questions when direct studies on patients are not feasible on ethical grounds.
The study investigated two factors thought to be involved: tooth shape and location, The study simulated the effects of lateral grinding on the first molar and on the canine with six different wear facet inclinations, resulting in a total of twelve simulated scenarios.
“Our results show that both the inclination and location of the wear facets have an influence on the strength of the mechanical load on the temporomandibular joint,” explained study leader Benedikt Sagl. “However, it would appear that the decisive factor is the steepness of the grinding facet. The flatter the tooth, the higher the loading on the joint and therefore the higher the risk of a TMJ disorder.” Conversely, if the dental cusps involved in bruxism have a steeper angle of inclination, the calculated joint loading was lower, even with the same “grinding force” (bruxing force). Further research, coupled with clinical investigations, will seek to establish whether this finding can be incorporated into the development of therapeutic interventions for sleep bruxism.
A project sequencing the Candida glabrata genome has revealed insights into the pathogenic fungus’s virulence and resistance, which researchers found to have been enhanced by transmission through humans as they travel between continents. The project’s findings appear in Genetics.
C. glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system. It most commonly affects the urinary tract, genitals, mouth, and the bloodstream. If it is not caught, these infections can become deadly. It is also very resistant to certain antifungal drugs, so understanding why resistance occurs is key to knowing how to treat it effectively.
Using samples from eight hospitals in Scotland to sequence the genome of C. glabrata, new insights on the species were made. This includes information on how it reproduces and its genetic diversity. Genes increasing its infectivity also confer an advantage for survival, and the drug-resistance genes often evolve within patients.
These findings provide scientists with an advantage in treating fungus, allowing research to focus in ways that were not possible before. It also helps aid understanding on how the pathogen spreads, which is important to identifying infections.
Dr Rhys Farrer, one of the Principal Investigators at the MRC Centre for Medical Mycology at the University of Exeter, said: “Our study sheds new light on the genetic diversity of Candida glabrata. We have demonstrated that this deadly human fungal pathogen is being spread between continents, probably by humans, and recombining to form new populations, which is likely contributing to its high virulence and increasing drug resistance.”
By using a bioreactor aboard a flight that simulated zero gravity, researchers have found that the reason why women have a greater risk of developing knee osteoarthritis is down to genetic differences in knee meniscus tissue.
Better tests, prevention and treatments could be developed for knee osteoarthritis in women here on Earth, based on this research.
Though knee osteoarthritis is more common in females than in males, the difference cannot be explained solely by hormones. The researchers have pinpointed a genetic difference in the meniscus that makes about 50% of females more vulnerable to developing osteoarthritis than males or other females. Exposure to zero gravity is known to mimic the ageing process, as muscles atrophy and bones lose density. The zero gravity environment of space has greatly contributed to medical research.
Researchers ran the experiment aboard an aircraft flying in parabolic arcs to specially simulate zero gravity conditions, to mimic the damage that can happen to the meniscus due to lack of exercise.
“Some of the genes that were found in the females that responded more to simulated space microgravity were also associated with the development of knee osteoarthritis,” said principal investigator Adetola Adesida, professor of surgery in the Faculty of Medicine & Dentistry.
The results suggest that a blood test could screen for the high-risk gene, allowing for early interventions such as physiotherapy, and eventually even drug therapy. It might also allow women to stay in space longer.
“We’ve uncovered the mechanisms that lead to this higher response, and we are hoping to develop drugs to target those pathways and block those responses,” Adesida said.
Previously thought to be rather unimportant, meniscus acts as a load distributor for the body’s full weight. However, it is now known that just a small tear in the meniscus, often from a sports injury, increases the risk of later osteoarthritis, even if the damaged tissue has been removed. On the other hand, lack of use can also lead to deconditioning of the meniscus and increase arthritis risk.
Knee osteoarthritis is the most common joint problem, affecting an estimated 250 million people worldwide, including 14% of females older than 60 and 10% of males in the same age group.
Prof Adesida’s team has developed bioengineered meniscus tissue grown from cells that have been removed from the damaged menisci of otherwise healthy individuals. The hope is one day to be able to replace damaged tissue through transplant, preventing the development of knee osteoarthritis.
For their experiment on sex differences, the team studied how the bioengineered tissue functioned while at rest and under mechanical loading and unloading conditions. For the loading, they used a device that exerted hydrostatic pressure on the cells. For the unloading, they put the cells into a bioreactor designed by NASA to fly aboard the zero-gravity aircraft.
“Our loading and unloading experiment mimics what we actually see in a clinical situation where the development of spaceflight microgravity-induced knee osteoarthritic changes is possible,” he said.
“This will help us to have human relevant models to study knee osteoarthritis in the future. And our research has both Earth benefits and space benefits.”
Analysis of a large representative database shows that e-cigarette use is associated with an increased risk of prediabetes, posing a new concern for public health.
“Our study demonstrated a clear association of prediabetes risk with the use of e-cigarettes,” explained lead researcher Shyam Biswal, PhD, at Johns Hopkins Bloomberg School of Public Health. “With both e-cigarette use and prevalence of prediabetes dramatically on the rise in the past decade, our discovery that e-cigarettes carry a similar risk to traditional cigarettes with respect to diabetes is important for understanding and treating vulnerable individuals.”
According to the Centers for Disease Control and Prevention (CDC), traditional cigarette smokers are 30% to 40% more likely than non-smokers to develop type 2 diabetes, which increases their risk for cardiovascular diseases. e-cigarettes are sometimes promoted as a healthier option for cigarette smokers, and e-cigarettes use is rising among younger demographics.
The study analysed 2016–2018 data from the Behavioral Risk Factor Surveillance System (BRFSS), the largest annual nationally representative health survey of US adults. Among the 600 046 respondents, 9% were current e-cigarette users who self-reported prediabetes diagnoses. The data also showed that e-cigarette users have a higher prevalence of high-risk lifestyle factors and worse self-related mental and physical health status than non-smokers.
In this representative sample of US adults, e-cigarette use was associated with greater odds of prediabetes compared to those who did not use e-cigarettes or traditional cigarettes – a worrying link from a public health standpoint.
“We were surprised by the findings associating prediabetes with e-cigarettes because they are touted as a safer alternative, which we now know is not the case,” commented Dr Biswal. “In the case of cigarette smoking, nicotine has a detrimental effect on insulin action, and it appears that e-cigarettes may also have the same effect.”
Prediabetes is fortunately a reversible condition, given appropriate lifestyle management. The authors make a compelling recommendation for targeting the reduction in e-cigarette use and education of young adults to reduce diabetes risk.
“Our effort for smoking cessation has led to a decrease in smoking traditional cigarettes. With this information, it is time for us to ramp up our public health efforts to promote the cessation of e-cigarettes,” cautioned Dr Biswal.
The World Health Organization (WHO) defines prediabetes as a state of intermediate hyperglycaemia using impaired fasting glucose, defined as fasting plasma glucose of 6.1–6.9 mmol/L (110 to 125 mg/dL) and impaired glucose tolerance defined as 2h plasma glucose of 7.8–11.0mmol/L (140–200 mg/dL) after ingestion of 75g of oral glucose or a combination of the two based on a 2h oral glucose tolerance test. It is estimated that by 2030, more than 470 million people worldwide will be diagnosed with prediabetes.
The biologic tezepelumab provided year-round relief for patients with severe, uncontrolled asthma, according to findings from the year-long phase III NAVIGATOR study.
Tezepelumab was shown to significantly reduce the annualised asthma exacerbation rate by 56% in the overall study population, and by 41% in those with baseline blood eosinophil counts below 300 cells/µL, according to Andrew Lindsley, MD, PhD, medical director at Amgen in Thousand Oaks, California, presenting at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.
When stratified by season, the annualised asthma exacerbation rate was consistently reduced with tezepelumab:
Winter: 2.62 with placebo versus 0.96 with tezepelumab (63% reduction)
Spring: 1.71 versus 0.92 (46% reduction)
Summer: 1.93 versus 0.73 (62% reduction)
Autumn: 2.28 versus 1.05 (54% reduction)
Tezepelumab, recently approved for severe asthma by the FDA in 2021, inhibits thymic stromal lymphopoietin. It is a key component of airway inflammation and is thought to be released in response to airborne asthma triggers, such as pollen and viruses. Tezepelumab has been shown to reduce exacerbations when compared with placebo.
Dupilumab was shown to have similar results in the 52-week QUEST study, which established the effectiveness of dupilumab as an add-on treatment for asthma. This was also true of the 96-week TRAVERSE open-label extension trial, in which researchers found that asthma exacerbations were reduced to below 7% all year long, and staying mostly under 5%.
The seasonal studies were performed during NAVIGATOR because asthma exacerbation has a number of environmental, seasonal factors.
“We know that allergies are seasonal, but depend on the trigger for asthma – early spring is the tree pollen season, late spring is grass pollen, in the fall it is ragweed” Roxana Siles, MD, co-director of the asthma centre at the Cleveland Clinic, told MedPage Today. Dust mites and animal dander are year-round, but may affect people more in the winter when they spend more time indoors, she added.
There was a question of how biologics were affected by the seasons, she said, and as it turned out, they work on all types of asthma, year round.
Tezepelumab decreased the proportion of patients with at least one exacerbation during all seasons, from 33.4% to 18.3% in winter, 23.7% to 15.7% in spring, 26.9% to 13.2% in summer, and 33.4% to 20.6% in autumn.
Additionally, the average number of days with an exacerbation per patient in each season fell between:
A new study has found that vitamin D2 and D3 have significant differences in effect, with vitamin D2 having a questionable impact on human health. However, the study found that vitamin D3 (the ‘sunshine vitamin’) could balance people’s immune systems and help strengthen defences against viral infections.
In a study published in Frontiers in Immunology, researchers investigated the impact of vitamin D supplements, D2 and D3, taken daily over a 12-week period on the activity of genes in people’s blood.
Contrary to widely held views, the research team discovered that both types of vitamin D did not have the same effect, rather they found evidence that vitamin D3 influences the immune system in a way that could fortify the body against viral and bacterial diseases.
Professor Colin Smith, lead-author of the study from the University of Surrey, who began this work while at the University of Brighton, said: “We have shown that vitamin D3 appears to stimulate the type I interferon signalling system in the body – a key part of the immune system that provides a first line of defence against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body.
“Our study suggests that it is important that people take a vitamin D3 supplement, or suitably fortified foods, especially in the winter months.”
Few natural foods contain Vitamin D, although some such as bread and yoghurt may be fortified with it. Vitamin D3 is produced naturally in the skin from exposure to sunlight or artificial ultraviolet UVB light, while some plants and fungi produce vitamin D2.
Many people have insufficient levels of vitamin D3 because they live in locations where sunlight is limited in the winter, like the UK. Sunlight exposure has also been limited by the COVID pandemic as people spend more time in their homes.
Professor Susan Lanham-New, co-author of the study and Head of the Department of Nutritional Sciences at the University of Surrey, said: “While we found that vitamin D2 and vitamin D3 do not have the same effect on gene activity within humans, the lack of impact we found when looking at vitamin D2 means that a larger study is urgently required to clarify the differences in the effects. However, these results show that vitamin D3 should be the favoured form for fortified foods and supplements.”
A study using real-world data has shown that multiple sclerosis (MS) sufferers taking cladribine were less likely to experience disease relapse than those who took other oral disease-modifying therapies.
Relapse and discontinuation outcomes favoured cladribine tablets over oral fingolimod, dimethyl fumarate, and teriflunomide. The findings were reported Helmut Butzkueven, PhD, of Monash University at ACTRIMS Forum 2022, the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
For the study, researchers drew on data from the MSBase registry of more than 79 000 people with MS worldwide. Few clinical trials or real-world studies are available that compare the effectiveness of cladribine tablets to other oral disease-modifying therapies, the researchers noted.
“Many treatment choices that patients and their care teams have to make are not or not yet examined in classical randomised trials,” Dr Butzkueven told MedPage Today. “Sophisticated analysis of data gathered systematically and prospectively in clinical care is proving a valuable alternative to examine and compare the outcomes of different treatment choices in all kinds of scenarios.”
“Oral agents for use in relapsing MS are very convenient and effective treatment choices,” he added. “This work directly compares outcomes for people with MS who chose cladribine tablets versus other oral drugs.”
The chemotherapy drug cladribine, was recently approved by the FDA for active secondary progressive disease and relapsing MS. This was based on results from trial data showing that cladribine significantly decreased the number of MS relapses and reduced the progression of disability compared with placebo.
GLIMPSE was a longitudinal study that included data for 3475 MS patients on either cladribine, fingolimod, dimethyl fumarate or teriflunomide.
The 633 patients taking cladribine were propensity-score matched with those taking oral comparators on various factors such as age, sex and country.
In pairwise comparisons, cladribine versus fingolimod had 520 matched participants per group: the annualised relapse rate (ARR) was 0.09 compared with 0.15, respectively, the hazard ratio (HR) for time to first relapse was 0.60, and the HR for time to discontinuation was 0.22.
For cladribine versus dimethyl fumarate (450 people per group), the ARR was 0.10 compared with 0.15 the HR for time to first relapse was 0.58, and the HR for time to discontinuation was 0.10.
The cladribine versus teriflunomide (458 people per group) comparisons showed that the ARR was 0.09 compared with 0.17, the HR for time to first relapse was 0.33, and the HR for time to discontinuation was 0.10.
The reason why multiple sclerosis (MS) sufferers often complain of more severe disease symptoms after consuming dairy products may be down to the milk protein casein, which can trigger inflammation targeting the myelin sheath, according to a study published in the journal PNAS.
This link was demonstrated in mice, but there was evidence of a similar mechanism in humans. The researchers therefore recommend that certain groups of MS sufferers avoid dairy products.
“We hear again and again from sufferers that they feel worse when they consume milk, cottage cheese or yoghurt,” explained Professor Stefanie Kürten from the Institute of Anatomy at University Hospital Bonn. “We are interested in the cause of this correlation.”
The professor of neuroanatomy is considered a renowned expert on multiple sclerosis. “We injected mice with different proteins from cow’s milk,” she said. “We wanted to find out if there was a constituent that they were responding to with symptoms of disease.”
When they administered the cow’s milk constituent casein together with an effect enhancer to the animals, the mice went on to develop neurological disorders. Electron microscopy showed damage to the insulating myelin sheath, which normally prevents short circuits and significantly accelerates stimulus conduction.
In multiple sclerosis, the body’s immune system destroys the myelin sheath. Consequences range from paresthaesia and vision problems to movement disorders. With patients ending up in a wheelchair. In mice, the myelin sheath was also massively perforated, apparently triggered by casein administration. “We suspected that the reason was a misdirected immune response, similar to that seen in MS patients,” explained Rittika Chunder, a postdoctoral fellow in Prof. Kürten’s research group. “The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin.”
Such cross-reactivity can occur when two molecules share some similar parts, causing the immune system to mistake them for each other. “We compared casein to different molecules that are important for myelin production,” Dr Chunder said. “In the process, we came across a protein called MAG. It looks markedly similar to casein in some respects – so much so that antibodies to casein were also active against MAG in the lab animals.”
This means that in the casein-treated mice, the body’s own defences were also directed against MAG, destabilising the myelin. But to what extent can the results be transferred to people with MS? To answer this question, the researchers added casein antibodies from mice to human brain tissue. These did indeed accumulate in the cells responsible for myelin production in the brain.
The study found that the antibody-producing B cells in the blood of people with MS respond particularly strongly to casein. It is possible that at some point while consuming milk, the affected individuals developed an allergy to casein. Now, on consuming dairy products, the immune system produces masses of casein antibodies, which due to cross-reactivity with MAG, also damage the myelin sheath.
However, this only affects MS patients who are allergic to cow’s milk casein. “We are currently developing a self-test with which affected individuals can check whether they carry corresponding antibodies,” said Prof Kürten. “At least this subgroup should refrain from consuming milk, yogurt, or cottage cheese.”
It is possible that cow’s milk also increases the risk of developing MS in healthy individuals. Because casein can also trigger allergies in them – which is probably not even that rare. Once such an immune response exists, cross-reactivity with myelin can in theory occur. However, this does not mean that hypersensitivity to casein necessarily leads to the development of multiple sclerosis, Prof Kürten stressed. This would presumably require other risk factors. This connection is concerning worrying, said Prof Kürten, as “Studies indicate that MS rates are elevated in populations where a lot of cow’s milk is consumed.”
Melanoma cells. Source: National Cancer Institute.
By screening various drugs to inhibit a cancer-driving gene, researchers have hit upon a familiar drug – statins.
Cancer patients rarely die from the primary tumour, but rather from the metastases – even after successful tumour surgery. This is because cancer cells sometimes metastasise when the tumour is still very small and may not have even been discovered yet. To do this, they must break away from the extracellular matrix and migrate into neighbouring lymphatic vessels or blood vessels that transport them to new tissue, where they settle and proliferate.
Understanding the molecular mechanisms of metastasis is therefore a key piece of the puzzle in the fight against cancer. More than a decade ago, Professor Ulrike Stein and her lab discovered an important driver of this process in human colorectal cancer: the metastasis-associated in colon cancer 1 (MACC1) gene.
When cancer cells express MACC1, their ability to proliferate, move around the body, and invade other tissues is enhanced. “Many types of cancers spread only in patients with high MACC1 expression,” Prof Stein explained. MACC1’s role as a key factor and biomarker of tumour growth and metastasis – in many solid tumours beside colorectal cancer – has since been studied by many other researchers worldwide and confirmed in more than 300 publications. Now together with Dr Robert Preißner of Charité, Stein has discovered what could disrupt metastatic progression in such cases: statins, normally prescribed for lowering cholesterol, can inhibit MACC1 expression in tumour cells. The scientists are presenting their findings in the journal Clinical and Translational Medicine.
In their search for MACC1 inhibitors, the researchers conducted high-throughput drug screening, and independently arrived at statins. Tests on various tumour cell lines were favourable: All seven drugs tested reduced MACC1 expression in the cells, but to varying degrees. The scientists then administered the cholesterol inhibitors to genetically modified mice with increased MACC1 expression. This almost completely suppressed the formation of tumours and metastases in the animals. “What is particularly remarkable is that the benefits continued in the animals even after we reduced the animal dose to a human equivalent dose,” Stein said.
Dr Preißner and collaborators also examined data from a total of 300 000 patients who had been prescribed statins. This analysis found a correlation: “Patients taking statins had only half the incidence of cancer compared to the general population,” Preißner explains.
Prof Stein warned against taking statins as a preventive measure without consulting a doctor and having their lipid levels checked.
“We are still at the very beginning,” Dr Stein cautioned. “Cell lines and mice are not human beings, so we cannot directly transfer the results.” The experimental studies and retrospective data analysis will now be followed up by a clinical trial, she said. Only after that will it be possible to say with certainty whether statins actually prevent or reduce metastasis in patients with high MACC1 expression.
