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Early intervention with rituximab, a drug used in the treatment of rheumatoid arthritis (RA), can reduce the risk of deterioration in myasthenia gravis, an autoimmune disease that causes loss of muscle control. This is according to a randomised clinical study led by researchers at Karolinska Institutet in Sweden and published in the journal JAMA Neurology.
“Patients with new onset myasthenia who received rituximab as a complement to standard of care showed greater improvement compared with patients who were given a placebo,” says Fredrik Piehl, professor at the Department of Clinical Neuroscience, Karolinska Institutet, and the study’s principal investigator. “They also needed fewer adjuvant treatments and lower doses of cortisone than the placebo group. These are encouraging results that give hope for a more effective strategy for controlling new onset myasthenia more quickly, even if larger studies will be needed to assess the long-term effects of the treatment.”
In myasthenia gravis, the immune system attacks the receptors between nerves and muscles, causing abnormal muscle weakness and fatigue. It often starts around the eye muscles but usually spread to other muscles in the body. The disease tends to progress in flare-ups and since there is no curative treatment, intervention is primarily aimed at dampening the immune system and treating the symptoms. Around 25 per 100,000 people live with the disease in Sweden, the majority of whom are women.
There is only one approved drug for myasthenia, Soliris, but the treatment is costly, which means that very few patients — none to date in Sweden — have benefited from it. Instead, many patients are treated with cortisone, which can cause side effects, and older tablet treatments that tend to lack scientific support.
The current study included 47 adult patients who had been diagnosed with myasthenia over the past year. Twenty-five of them were randomly assigned to a one-off treatment with 500 mg rituximab, a tried and tested drug used to treat rheumatoid arthritis, and 22 to a placebo group. The study was conducted at seven clinics in Sweden and the patients were followed for up to 48 weeks.
After four months, 71 percent of the rituximab group had attained good control of their disease according to a well-established 13-item rating scale, compared with 29 percent of the placebo group. Later follow-ups at six, nine and twelve months produced similar results.
The rituximab group also received on average lower doses of cortisone, and needed fewer adjuvant treatments. However, they also reported more adverse reactions, most of which were mild. One patient with previously diagnosed heart disease in the group died from a myocardial infarction with cardiac arrest. Three patients in the placebo group needed hospital care during the study period, two for life-threatening conditions related to a deterioration of their myasthenia.
The researchers note that the study is relatively small with an imbalance in some of the baseline characteristics between the two groups, which is a limitation. At the same time, the results are promising and motivate further studies.
“The use of rituximab for myasthenia in Sweden increased even before the study results were finalized,” says Fredrik Piehl. “It is also a treatment that neurologists in Sweden are very familiar with thanks to the widespread and somewhat debated off-label prescribing for multiple sclerosis (MS). We’ll now, in a way similar to that with MS, analyse the long-term benefit-risk balance of the treatment with the help of national data collected via the Swedish myasthenia registry and national health registries. We also need to find markers that can predict the course of the disease at an early stage.”
The study was financed by the Swedish Research Council. Some of the researchers have received grants and fees from various pharmaceutical companies, including some that market rituximab, outside the scope of this study.
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Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.

If you’re already taking one blood thinner, mounting research suggests you might not need to take a second one.
In fact, when patients who are on a commonly prescribed blood thinner stop taking aspirin, their risk of bleeding complications drops significantly, a Michigan Medicine study finds.
Researchers analyzed over 6,700 people treated at anticoagulation clinics across Michigan for venous thromboembolism, or blood clots, as well as atrial fibrillation, an irregular heart rhythm that can cause stroke. Patients were treated with the common blood thinner warfarin but also took aspirin despite not having history of heart disease.
“We know that aspirin is not a panacea drug as it was once thought to be and can in fact lead to more bleeding events in some of these patients, so we worked with the clinics to reduce aspirin use among patients for whom it might not be necessary,” said Geoffrey Barnes, M.D., senior author of the study and a cardiologist at the University of Michigan Health Frankel Cardiovascular Center.
Over the course of the study intervention, aspirin use among patients decreased by 46.6%. With aspirin used less commonly, the risk of a bleeding complication dropped by 32.3% — amounting to one major bleeding event prevented per every 1,000 patients who stop taking aspirin. Results are published in JAMA Network Open.
“When we started this study, there was already an effort by doctors to reduce aspirin use, and our findings show that accelerating that reduction prevents serious bleeding complications which, in turn, can be lifesaving for patients,” said Barnes, who is also an associate professor of internal medicine at U-M Medical School. “It’s really important for physicians and health systems to be more cognizant about when patients on a blood thinner should and should not be using aspirin.”
This de-escalation of aspirin use is based off several studies that found concerning links between concurrent use of aspirin and different blood thinners.

Thank the rare crested ibis for a clue that could someday help our bodies make better drugs.
The species of bird is the only one known to naturally produce an enzyme able to generate a noncanonical amino acid; that is, one not among the 20 necessary to encode most proteins.
That it exists — a discovery made through computational comparison of genome databases — proves it’s possible for that enzyme to work within the context of living cells, even if scientists don’t know what it does for the bird.
But they have a pretty good idea of what it could do for us.
A new study by Rice University chemist Han Xiao, theoretical physicist Peter Wolynes and their colleagues shows that amino acid, sulfotyrosine (sTyr), a mutant of the standard amino acid tyrosine, is a key building block to program living cells that express therapeutic proteins. It could potentially allow cells to serve as sensors that monitor their environments and respond with the necessary treatment.
Mimicking the ibis’ ability to synthesize sTyr and incorporate it into proteins requires modifying a cell’s DNA with a mutant codon that, in turn, makes the transferase enzyme, sulfotransferase 1C1, found in the bird. This catalyzes the generation of sTyr, an essential recognition moiety in a variety of biomolecular interactions.

Thalamic atrophy needs to be considered in clinical studies of the functional abilities of individuals with multiple sclerosis, according to findings reported by a team of experts. The article, “Thalamic atrophy moderates associations among aerobic fitness, cognitive processing speed, and walking endurance,” was published in the Journal of Neurology on June 19, 2022.
The authors are Brian Sandroff, PhD, Cristina A.F. Román, PhD, Glenn R. Wylie, DPhil, and John DeLuca, PhD, of Kessler Foundation, Robert W. Motl, PhD, of the University of Illinois Chicago, Gary R. Cutter, MS, PhD, of the University of Alabama at Birmingham, and Ralph H.B. Benedict, PhD, Michael G. Dwyer III, PhD, and Robert Zivadinov, MD, PhD, of the University of Buffalo.
MS-related thalamic atrophy is a major biomarker for neurodegeneration and associated physical and cognitive decline, highlighting the importance of exploring ways to restore and maintain function in individuals who present with this consequence of the disease. Aerobic exercise training is one promising approach, but little is known about its potential effects in individuals who present with thalamic atrophy.
The team conducted a cross-sectional study to examine the associations among aerobic fitness, cognitive processing speed, and walking endurance in individuals with and without thalamic atrophy. Subjects comprised 44 fully ambulatory individuals with MS from three randomized controlled trials. Outcomes included aerobic fitness (peak oxygen consumption during graded treadmill exercise), processing speed (Symbol Digit Modalities Test), walking endurance (6-min walk test), and thalamic neuroimaging.
Results provided initial evidence for strong and selective associations among aerobic fitness, cognitive processing speed, and walking endurance in individuals with thalamic atrophy, according to lead author Dr. Sandroff. “This study suggests that aerobic exercise training has the potential to restore function in individuals with thalamic atrophy, who are clearly at risk for progressive physical and cognitive decline,” he stated. “To explore the impact on outcomes, we need to develop randomized controlled trials of aerobic exercise training in the subgroup presenting with thalamic atrophy.”
Supported by EMD Serono, Inc., Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under Award Number R01HD091155.
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Materials provided by Kessler Foundation. Note: Content may be edited for style and length.

Spinal cerebellar ataxia 6 (SCA6) is an inherited neurological condition which has a debilitating impact on motor coordination. Affecting around 1 in 100,000 people, the rarity of SCA6 has seen it attract only limited attention from medical researchers. To date, there is no known cure and only limited treatment options exist.
Now, a team of McGill University researchers specializing in SCA6 and other forms of ataxia, have published findings that not only offer hope for SCA6 sufferers but may also open the way to developing treatments for other movement disorders.
Exercise in a pill
In mice affected by SCA6, the McGill team, led by biology professor Alanna Watt, found that exercise restored the health of cells in the cerebellum, the part of the brain implicated in SCA6 and other ataxias. The reason for the improvement, the researchers found, was that exercise increased levels of brain-derived neurotrophic factor (BDNF), a naturally occurring substance in the brain which supports the growth and development of nerve cells. Importantly for patients with a movement disorder, for whom exercise may not always be feasible, the team demonstrated that a drug that mimicked the action of BDNF could work just as well as exercise, if not better.
Early intervention crucial
The researchers also discovered that BDNF levels in SCA6 mice declined well before movement difficulties began to appear. The drug, they found, worked to arrest the decline only if it was given before the onset of outwardly visible symptoms.
“That’s not something we really knew about SCA6,” said lead author Anna Cook, a Ph.D. candidate in Professor Watt’s lab. “If there are these early changes in the brain that people don’t even know about, it tends to advocate for more genetic screening and early intervention for these rare diseases.”
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Materials provided by McGill University. Note: Content may be edited for style and length.

There was once a time, not so long ago, when scientists like Casey Holliday needed scalpels, scissors and even their own hands to conduct anatomical research. But now, with recent advances in technology, Holliday and his colleagues at the University of Missouri are using artificial intelligence (AI) to see inside an animal or a person — down to a single muscle fiber — without ever making a cut.
Holliday, an associate professor of pathology and anatomical sciences, said his lab in the MU School of Medicine is one of only a handful of labs in the world currently using this high-tech approach.
AI can teach computer programs to identify a muscle fiber in an image, such as a CAT scan. Then, researchers can use that data to develop detailed 3D computer models of muscles to better understand how they work together in the body for motor control, Holliday said.
Holliday, along with some of his current and former students, did that recently when they began to study the bite force of a crocodile.
“The unique thing about crocodile heads is that they are flat, and most animals that have evolved to bite really hard, like hyenas, lions, T. rexes and even humans have really tall skulls, because all those jaw muscles are oriented vertically,” Holliday said. “They’re designed that way so they put a big vertical bite force into whatever they’re eating. But a crocodile’s muscles are oriented more horizontally.”
The 3D models of muscle architecture could help the team determine how muscles are oriented in crocodile heads to help increase their bite force. Helping to lead this effort is one of Holliday’s former students, Kaleb Sellers, who is now a postdoctoral researcher at the University of Chicago.

Native Hawaiians/Pacific Islanders, or NH/PIs, comprising more than 20 ethnic groups hailing from Polynesia, Micronesia, and Melanesia, are understudied despite being the third fastest growing racial group in the United States. Two studies now report that NH/PIs have been deeply affected by the COVID-19 pandemic.
Andrew Subica at the University of California, Riverside, led research groups that surveyed more than 300 NH/PIs from April-November 2021 in Washington, Utah, Oregon, California, and Arkansas — states with large NH/PI populations. Their findings are published in two journals.
Described in the first paper, published in Public Health Reports, the researchers found 30% of the NH/PI participants reported being diagnosed with COVID-19 and approximately 50% of the participants reported having a close family member with COVID-19.
Further, nearly 1 out of 5 NH/PIs reported the death of a close family member due to COVID-19 infection; the overall U.S. COVID-19 mortality rate was 1 death per 400 persons at the end of 2021.
“NH/PIs may carry the highest rates of COVID-19 infections and deaths of any U.S. racial/ethnic minority group during the pandemic,” said Subica, an associate professor in the School of Medicine’s Department of Social Medicine, Population, and Public Health. “For example, an earlier report found NH/PIs possessed the highest per capita death rate in 90% of states reporting NH/PI COVID-19 deaths.”
According to Subica, several factors increase NH/PIs’ risk for exposure to SARS-CoV-2, the virus that spreads COVID-19. These factors include employment in essential frontline positions, dwelling in dense households and neighborhoods, and traditional sociocultural practices and obligations that result in large in-person group contact.

Over the last decade, immune checkpoint blockers, or ICBs, have revolutionized treatment for various advanced cancers, including melanoma, the most aggressive skin cancer that was considered largely incurable not long ago. However, three-fourths of advanced-melanoma patients are resistant to ICBs.
Now, in a report published in Nature Communications, researchers reveal a potential target — using the clinically approved drug ruxolitinib — to suppress ICB-resistant melanomas.
“Since ruxolitinib is clinically approved and being tested in patients with advanced solid tumors, non-small-cell lung cancer and triple-negative breast cancer, our study justifies further testing of ruxolitinib in patients with advanced melanoma that are resistant to ICBs,” said Lewis Zhichang Shi, M.D., Ph.D., an associate professor in the University of Alabama at Birmingham Department of Radiation Oncology.
Shi notes that ruxolitinib will likely need to be combined with other therapeutic modalities to achieve a long-term cure.
For half a dozen years, it was known that tumor loss of interferon-gamma signaling was a major mechanism of resistance against two ICB drugs, anti-CTLA-4 and anti-PD-1. However, ways to overcome this resistance remained elusive.
This loss of interferon-gamma signaling in human melanomas is caused by dysregulation of genes in the interferon-gamma signaling pathway. However, in mouse models the knockdown mutations failed to show how a loss of interferon-gamma signaling in tumor cells modulated the activity of tumor-infiltrating T cells, or TILs, because those models still contain some interferon-gamma signaling. TIL immune cells are vital for cancer control because they are able to detect and destroy tumors. However, in a countermove, cancers learn to evade this destruction by upping immune checkpoint proteins on the surface of their cells, and these surface proteins send an “off” signal to TILs.
So researchers led by Shi and UAB Department of Radiation Oncology Chair James A. Bonner, M.D., created a cleaner mouse melanoma model by knocking out the receptor gene for interferon-gamma signaling. They used this improved knockout model — called IFNγR1KO — to probe the mechanisms of ICB resistance and how the IFNγR1KO melanomas alter the response of TILs to ICBs.
Compared to non-knockout melanomas, the mouse IFNγR1KO melanomas showed reduced infiltration of TILs such as CD8 killer T cells, and the TILs had reduced immune activity against the tumors. This revealed that normal interferon-gamma signaling in the melanoma plays an important role in shaping TILs. To corroborate these preclinical findings, the researchers, in collaboration with Zechen Chong, Ph.D., an assistant professor in the UAB Department of Genetics and Informatics Institute, also did bioinformatics analysis of human melanoma data from The Cancer Genome Atlas. They found that melanomas with attenuated interferon-gamma signaling also had decreased expression of T cell signature genes, indicating reduced T cell infiltration and function.
Mechanistically, the IFNγR1KO mouse melanomas had a network of continuously active protein tyrosine kinases that centered on activated JAK1/2 kinases, and this intracellular signaling pathway was mediated by activated mTOR signaling.
Ruxolitinib is an inhibitor of JAK1/2. The researchers found that ruxolitinib suppressed the cancerous growth of IFNγR1KO melanomas, but not control melanomas. Experimental depletion of T cells or host tumor necrosis factor signaling completely abrogated ruxolitinib efficacy, leading researchers to conclude that ruxolitinib suppression of the IFNγR1KO melanomas depends on T cells and the host cytokine tumor necrosis factor. Researchers also found that ruxolitinib mediates its therapeutic effect by reprogramming the TILs, not through direct killing of tumor cells.
Shi and Bonner say they now are actively soliciting clinical interest in exploring JAK1/2 inhibition as a strategy to bypass ICB resistance in melanoma patients, a pressing unmet medical need.
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Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

Like all living beings, human physiological processes are influenced by circadian rhythms. The disruption of our internal clocks due to an increasingly unbalanced lifestyle is directly linked to the explosion in cases of type 2 diabetes. By what mechanism? A team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG), in Switzerland, is lifting part of the veil: this disturbance disrupts the metabolism of lipids in the cells that secrete glucose-regulating hormones. Sphingolipids and phospholipids, lipids located on the cell membrane, seem to be particularly affected. This change in lipid profiles then leads to a rigidity of the membrane of these cells. These results, to be read in the journal PLOS Biology, provide further evidence of the importance of circadian rhythms in metabolic disorders.
Lipids have a variety of cellular functions. As one of the main components of cell membranes, they are involved in the signalling pathways through which cells communicate with each other and with their environment. “We have known for some time that the disruption of circadian clocks was closely linked to metabolic diseases, such as type 2 diabetes, where the body is no longer able to regulate blood sugar levels effectively,” explains Charna Dibner, a professor in the Departments of Surgery and of Cellular Physiology and Metabolism, as well as in the Diabetes Centre of the UNIGE Faculty of Medicine and the HUG, who led this research. “It is also established that lipids play a significant role in metabolic disorders. But the impact of circadian rhythms on lipid functions remained unknown.”
A complex in vitro model of human molecular clocks
Islets of Langerhans are clusters of different types of endocrine cells located in the pancreas, notably responsible for the secretion of insulin and glucagon, the hormones that regulate blood glucose. To understand how lipids are influenced by circadian rhythms, the scientists analysed the oscillation profiles of more than 1,000 lipids in human islets from people with type 2 diabetes and from healthy individuals. “The experimental design we used is particularly complex,” explains Volodymyr Petrenko, a researcher in Charna Dibner’s laboratory and first author of this study. “When we study a muscle, for example, we can take a biopsy every hour. But when it comes to internal organs such as the heart, liver or pancreas, as in this case, this is of course impossible. We therefore had to develop a model of disrupted molecular clocks in vitro with human pancreatic islets.”
In a living organism, a central clock in the brain orchestrates the peripheral clocks in the cells of all organs according to external stimuli. In the lab, scientists have therefore artificially replaced this central clock to resynchronise the cells. “In fact, in vitro, each cell retains its own rhythmicity but without overall coordination. However, our work is aimed precisely at understanding how rhythms, formed in a multicellular population that are necessary for the functioning of the endocrine pancreas as an entity, control intracellular lipids metabolism,” adds Volodymyr Petrenko.
A stiffening of the membrane
Comparing islets from people with type 2 diabetes and from healthy people showed that lipid profiles oscillate during the day much more than previously thought. “And not only are the islet lipid profiles in diabetics and non-diabetics different, but the way they oscillate over the course of the day also differs.”
In addition, the scientists observed a particularly large change in the temporal profile of phospholipids and sphingolipids, two classes of lipids that are the main components of the cell membrane. “Recent studies have shown a link between these phospho- and sphingolipids and the loss of insulin production capacity typical of type 2 diabetes,” explains Charna Dibner. “Our study goes in the same direction: we observed that islets with disrupted clocks had an accumulation of phospho- and sphingolipids that stiffened the membrane. This may affect the cell’s ability to detect environmental signals and therefore to secrete insulin when needed.” Moreover, the scientists were able to reproduce phenomenon with healthy pancreatic cells by artificially disturbing their circadian clocks. Studies will continue to understand the exact cause and mechanism of this phenomenon.
Promoting lifestyle changes?
This work establishes for the first time a direct link between the disruption of circadian clocks and the lipid changes typical of diabetics. These basic research data lay the foundation for research with patients. Charna Dibner’s research team is currently conducting two applied studies: the first, in collaboration with nutrition specialists at the University Hospitals of Geneva, is exploring the potential benefits of intermittent fasting from the perspective of personalised medicine, taking into account the precise circadian profile of each individual. The second, in collaboration with the University of Maastricht in the Netherlands, aims to resynchronise patients with the help of sun lamps.
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Materials provided by Université de Genève. Note: Content may be edited for style and length.

First, pause and take a deep breath.
When we breathe in, our lungs fill with oxygen, which is distributed to our red blood cells for transportation throughout our bodies. Our bodies need a lot of oxygen to function, and healthy people have at least 95% oxygen saturation all the time.
Conditions like asthma or COVID-19 make it harder for bodies to absorb oxygen from the lungs. This leads to oxygen saturation percentages that drop to 90% or below, an indication that medical attention is needed.
In a clinic, doctors monitor oxygen saturation using pulse oximeters — those clips you put over your fingertip or ear. But monitoring oxygen saturation at home multiple times a day could help patients keep an eye on COVID symptoms, for example.
In a proof-of-principle study, University of Washington and University of California San Diego researchers have shown that smartphones are capable of detecting blood oxygen saturation levels down to 70%. This is the lowest value that pulse oximeters should be able to measure, as recommended by the U.S. Food and Drug Administration.
The technique involves participants placing their finger over the camera and flash of a smartphone, which uses a deep-learning algorithm to decipher the blood oxygen levels. When the team delivered a controlled mixture of nitrogen and oxygen to six subjects to artificially bring their blood oxygen levels down, the smartphone correctly predicted whether the subject had low blood oxygen levels 80% of the time.