Publisher Health

Americans greeted the lifting of mask mandates on planes, trains, buses, and public transit with a mixture of joy, relief and alarm on Tuesday, marking an abrupt end to a directive that had been widely in place in various forms for nearly two years.The Transportation Security Administration, airlines, public transit officials and transportation providers started announcing the end of enforcement of the mask mandate after a federal judge ruled against the requirement on Monday. However, some transit agencies, including the M.T.A. in New York, said they would continue to require masks for now.Some airline passengers received the news in airports or in flight, sharing celebratory photos and videos on social media. That elation was accompanied by nervousness and dread from other people who are fearful that the end of the mandate would increasingly expose them and their loved ones to the coronavirus as a new variant is driving up case counts around the United States.On Monday afternoon, Peter Shankman, 49, took a United Airlines flight from Denver to Newark. Soon after boarding, the pilot announced that masks weren’t mandatory, but that those who took them off should be respectful to those who chose to keep them on. Most people around him continued wearing masks, even after that announcement, but only a few put their coverings back on after eating.“I kept mine on the entire plane,” he said.Mr. Shankman travels frequently for his job as a corporate keynote speaker and has been finding that since he began wearing a mask, he has been getting sick far less frequently. “I might continue it,” he said, adding, “It’s a little piece of fabric; it’s not that inconvenient.”He’s not alone. Support for the mask mandate has been declining, but most Americans still support it, a pair of recent surveys found. At least 60 percent of adults supported keeping the mandate in place, according to a Harris Poll survey conducted earlier this month. The Morning Consult reported this month that a similar share of adults in its poll supported a mask requirement, with those traveling over the next few months being most likely to back the mandate.For many flight attendants, the lifting of the mandate was a relief. Flight crews have faced a surge in threats and violence from passengers over the past two years. In many cases, the rage is sparked by belligerent resistance to complying with the mask mandate, which is enforced by flight crews on planes.“I’ve got nothing but extremely positive feedback,” said John Samuelsen, the international president of the Transport Workers Union, which represents thousands of flight attendants and other airline, railroad, and transit workers. “There was and remains a tension in the air.”David Neeleman, the founder of JetBlue Airways who is now chief executive of a new company, Breeze Airways, said that he and many of his crew members welcomed the news.“They don’t like being policemen on airplanes,” he said. “It’s not something that they signed up for and I think it creates more agitation with customers.”Unions representing flight attendants and pilots have long called for stronger action to address the increase in violence, with many welcoming a recent proposed bill in Congress that would impose tougher penalties for those convicted of assaulting flight crews and place those individuals on a no-fly list.Jonathan Russell Biehl, a pilot for Delta, was mid-way between Tampa and Minneapolis on Tuesday evening when he got a message that the T.S.A. was no longer enforcing the mask rule.“I would say this is the day I’ve been waiting for for a long time,” said Mr. Biehl, who was working as a first officer on Tuesday. “It’s really exciting not to have to be forced to wear a mask against my will.”A video he shared shows passengers cheering as the captain announced that masks were optional. When he got off the plane in Minneapolis around 8:30 p.m, he did not wear a mask.

Non-alcoholic fatty liver disease (NAFLD), commonly known as fatty liver disease, is a prevalent disease frequently seen in obese people. Having high fat content in the liver is detrimental as it is strongly associated with severe health problems like diabetes, high blood pressure, and liver cancer. A research team led by Dr Chi Bun CHAN, Assistant Professor from the School of Biological Sciences, Faculty of Science, the University of Hong Kong (HKU), uncovers a new protective mechanism against this disorder. The research findings have recently been published in the scientific journal Hepatology.
The liver is the vital organ that orchestrates the overall glucose and fat metabolisms in the human body. Disruption of the fat metabolism in the liver will eventually result in hyperglycemia and hyperlipidemia, which are strong risk factors for developing diabetes, hyperlipidemia, and liver cancer. It is predicted that the number of NAFLD patient will increase from 80 million in 2015 to 100 million in 2030. While the outcomes of fat accumulation in the liver have been well established, it remains unclear if the liver possesses any defensive mechanism to work against the damage.
To answer this question, Dr Chan’s team examined the expression of genes in the liver of high fat diet-induced obese mouse and found a protein, SH3 domain binding kinase (SBK1), was exclusively elevated in the obese mouse liver. SBK1 is a protein kinase first discovered in 2001, but no follow-up study has been performed to determine its functions in mammals. Hence, the functions of this novel protein remain unknown.
For the first time, Dr Chan’s team found that fatty acid accumulation is an inducer of SBK1 in the mouse liver. They also observed that the mice without the SBK1 gene in their liver, called ‘LSKO (liver-specific SBK1 knockout)’ mice, have higher lipid accumulation and fibrosis in this tissue. Moreover, the LSKO mice displayed uncontrolled hepatic glucose output and higher blood glucose level, and are less sensitive to insulin stimulation than their control cohort, which are strong indicators of diabetes development.
In addition to the animal studies, Dr Chan’s team also utilised cultured cell models to answer how SBK1 gene controlled the lipid metabolism in the liver. They found that SBK1 phosphorylated and enhanced the activity of Nur77, a well-established transcriptional factor, in liver cells to control fatty acid uptake and lipid synthesis. When the SBK1 protein activity was abolished in the liver cells, they took up more fatty acids and developed excessive lipid accumulation that interfered the insulin signaling. Surprisingly, another metabolic hormone in the liver cells, fibroblast growth factor 21 (FGF21), was also reduced when the SBK1 protein was abolished in the cultured liver cells and the LSKO mice. Since FGF21 is an important hormone from the liver to communicate with other peripheral organs like white adipose tissues, the reduced FGF21 hormone production in the LSKO liver thus impairs the communication between the liver and other organs, leading to the development of insulin resistance in other tissues.
To extend their findings to therapeutic application, the research team further tested if manipulating the SBK1 protein activity in the liver could rescue the damaging effect of obesity. Using adenovirus-mediated gene delivery, they transiently increased the amount of SBK1 protein in the mouse’s liver with fructose diet-induced fatty liver disease and found pathological symptoms like liver steatosis, inflammation, etc. hyperlipidemia, and hyperglycemia were all alleviated.

A scientific team supported by the National Institutes of Health has created a tiny, bioengineered 3-D model that mimics the biology of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy, a pair of rare, devastating neuromuscular diseases. The researchers used the organ-on-a-chip, or “tissue chip,” model to show how a drug could potentially treat the diseases. They provided key preclinical data for a drug company to submit to the U.S. Food and Drug Administration to get authorization for testing in a clinical trial.
This work provides one of the first examples of scientists using primarily tissue chip data for an FDA Investigational New Drug application to test the efficacy of a candidate drug in people with rare diseases. The drug company Sanofi started recruiting participants into a Phase 2 clinical trial in April 2021. The drug was tested for safety previously and approved by the FDA for a different indication.
The tissue chip research was led by Hesperos, Inc., an Orlando-based company partially funded by a Small Business Innovation Research grant from NIH’s National Center for Advancing Translational Sciences (NCATS). This study could open the door to studying and developing new therapies for other rare diseases by establishing a new avenue for repurposing existing drugs for rare diseases. Most of the known 7,000 rare diseases do not have effective treatments. Researchers often lack animal models for studying rare disease biology and testing potential drugs.
“This marks an important milestone in the evolution of the use of tissue chips,” said Lucie Low, Ph.D., scientific program manager for the NCATS Tissue Chip for Drug Screening initiative. “We know that pharmaceutical companies are using tissue chips internally. Submitting data to regulatory agencies generated from tissue chip platforms is a powerful indicator of their growing promise.”
James Hickman, Ph.D., chief scientist at Hesperos, and his colleagues described the development of the model and their research results in Advanced Therapeutics. In these diseases, the immune system makes proteins called antibodies that damage nerve cells and slow down messages moving from the brain to the muscles. This can make it hard for people to move their arms, hands and legs. Current treatments can help, but often are inconsistent.
The researchers developed a tissue chip model consisting of two cell types: motoneurons and Schwann cells. Motoneurons transmit messages from the brain to muscles. Schwann cells help the signals move more quickly. The model could mimic functional characteristics of the diseases, allowing the scientists to see how a drug was working by determining whether the brain’s messages to muscles were slowing down or not.
The researchers showed that exposing the cells to blood serum from people with these rare diseases caused a shower of immune system antibodies against the cells. This made the motoneuron signals move more slowly. After treatment with TNT005, a drug that blocks the immune system reaction, the cells and the message speed returned to normal.
“We’re confident that our system can reproduce what happens to a patient, including the disease symptoms and disease progression,” said Hickman. “It’s important to create functionally relevant patient models that will mimic what is seen in clinical trials.”
Approximately 90% of promising therapies fail in clinical trials because animal models used in preclinical testing are not good at predicting how people will respond. To improve that success rate and help get more treatments to people who have few options, scientists are exploring the uses of tissue chips. Designed to support living human tissues and cells, tissue chips mimic the structure and function of human organs and systems, such as the lungs, heart and liver. Researchers are studying their uses in many areas, including for testing the safety and effectiveness of candidate drugs and modeling diseases.
The potential clinical uses of tissue chip data are growing. Recently, an NIH-supported research team at Harvard University’s Wyss Institute reported using a tissue chip model to generate data on the effectiveness of a repurposed drug for treating lung damage from COVID-19 infection. In the NCATS-funded Clinical Trials on a Chip program, several projects examine how tissue chip data can help researchers design more useful clinical trials. This might include using such data to predict which patients in a trial are most likely to respond to a therapy.
“Creating a platform that can predict human responses to a drug in a rare disease could lead to exciting new opportunities in research,” said Low. “If tissue chip data can be generated that inform the decisions made before early human trials, this could reduce the risks to vulnerable populations.”
Funding for this research was provided by True North Therapeutics (now Sanofi), NCATS (SBIR 2R44TR001326-03) and internal Hesperos development funds.

Before being accidentally introduced to the New World by the 16th century slave trade, the yellow fever mosquito was a species native only to Africa. Highly adaptable, it has since become an invasive species in North America, but researchers at The Ohio State University may have found a way to squash the pesky population in its juvenile stages.
Recently published in the journal Insects, a new paper describes how mosquitoes have evolved a natural resistance to some chemical insecticides, and offers an alternative called carbon black, a type of carbon-based nanoparticles, or CNPs.
Study co-author and an associate professor of entomology at Ohio State, Peter Piermarini described CNPs as “microscopic” materials made out of organic elements. The study used a modified version of carbon black called Emperor 1800, which is often used to coat automobiles black. While CNPs are a relatively new scientific development, they have been considered as new tools to control various insect and pest infestations, he said.
“If we can learn more about how carbon black works and how to use it safely, we could design a commercially available nanoparticle that is highly effective against insecticide-resistant mosquitoes,” Piermarini said.
The yellow fever mosquito, or Aedes aegypti, is a species of mosquito known for spreading not just yellow fever, but also diseases like the Zika virus, dengue fever and chikungunya fever. Adults rarely fly more than a few hundred meters from where they emerge, but their abundance leads to steady transmission of diseases — enough to claim tens of thousands of lives every year and hospitalize hundreds of thousands more people.
Because of this, the mosquito is considered to be one of the deadliest animals on the planet. For this study, the researchers’ goal was to figure out how toxic these nanomaterials could be to mosquito larvae, or the immature form of the insect.

Carbohydrates, proteins and fats are essential nutrients to all animals. Yet dietary variation between species, populations and individuals can vary dramatically.
In an international collaborative study, researchers from Australia, Denmark and Finland investigated how individuals of a same population differ in their ability to survive on various diets.
The researchers utilised a genetic reference panel consisting of roughly 200 closely related fruit fly strains (Drosophila melanogaster). The flies were fed six different diets containing high concentrations respectively of protein, sugar, starch, coconut oil or lard, or a combination of sugar and lard. The strains used in the study have had their genomes fully mapped, which made it possible to link the differences seen in the experiments to specific genetic variation.
The study found that small genetic differences affected the flies’ ability to use the energy of various nutrients.
“Unexpectedly we found that the fruit fly strains differed considerably, for example, in their ability to survive on a high-sugar diet. What makes this particularly surprising is the fact that the food consumed by fruit flies in nature contains a lot of sugars,” says Essi Havula, now a postdoctoral researcher at the University of Helsinki and the lead author of the study.
“The genes that regulate metabolism have been conserved well in evolution, which is why we can learn a lot about human metabolism through studies carried out with fruit flies,” Havula adds.

In the fight against cancer, the development of efficacious drugs is only half the battle; equally important is how drugs may be delivered efficiently and safely to the diseased sites in the body.The challenge of drug delivery is especially pertinent for RNA therapeutics which target an important immuno-modulatory receptor, RIG-I. When activated by certain types of RNAs, the receptor can initiate immune responses to kill cancer cells. As RNAs are unstable and fragile by nature, RNA-based drugs must be packaged in suitable carriers to prevent degradation, and promote efficient uptake by target cancer tissues.
A study led by researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) — in collaboration with the Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore (LKCMedicine, NTU Singapore) and A*STAR’s Genome Institute of Singapore (GIS) — demonstrated that nano-sized vesicles released by red blood cells are a viable platform for delivering immunotherapeutic RNA molecules to suppress breast cancer growth and metastasis. Published in the Journal of Extracellular Vesicles, the study successfully delivered RIG-I-activating RNAs using small, lipid membrane-bound particles released by red blood cells, called red blood cell extracellular vesicles (RBCEVs), to suppress cancer progression. The team had also discovered in earlier studies that these vesicles are ideal therapeutic carriers with a natural ability to deliver bioactive molecules to many cell types.
Assistant Professor Minh Le from the Institute for Digital Medicine (WisDM) and Department of Pharmacology at NUS Medicine, who led the study, explained, “With the discovery of these vesicles’ ability to deliver therapeutics effectively to targeted receptors, we hope that our research can lead to better treatment outcomes for cancer patients. The correct homing of the therapeutics to diseased cells is also critical in minimising off-target effects that can result in toxicity.”
For the study, two novel RNA molecules were developed at LKCMedicine, and packaged into RBCEVs to activate the RIG-I pathway, induce cell death in breast cancer cell cultures, and suppress tumour growth in laboratory models with breast cancer. The team also engineered RBCEVs to improve their specificity of homing towards metastatic cells that took hold in the lungs. Associate Professor Luo Dahai, Associate Professor of Infection and Immunity at LKCMedicine, said, “Asst Prof Le’s RBCEV technology can overcome several hurdles related to therapeutic RNA delivery and unleash the anticancer potential of our immunomodulatory RNA (immRNA). I am thrilled to see the success of our collaboration.”
Dr Tam Wai Leong, Group Leader and Associate Director at GIS, one of the collaborators of the study, added, “The promising results highlight two key strengths of this innovative platform — the capacity for efficient delivery of different therapeutic cargoes, as well as the possibility for genetic modifications to enhance targeting to more cancer types.”
To further examine the function of RBCEVs in carrying a broader range of therapeutics to more cancer cell types, the team plans to conduct further research in collaboration with the National University Cancer Institute and Cancer Science Institute of Singapore. Concurrently, RBCEV technologies are under intensive research at Carmine Therapeutics, an EVX Ventures company which aims to develop the next generation of gene therapy based on RBCEVs for treatments of rare diseases and cancer. “We hope to expand the therapeutic value of the RBCEV platform to more cancer types and increase the reach of such novel forms of therapy to benefit more cancer patients,” said Asst Prof Minh Le, who is also one of the co-founders of the company.
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The various manifestations of head and neck carcinomas rank sixth in frequency worldwide and are fatal for about half a million people every year. In a quarter of cases, head and neck squamous cell carcinoma (HNSCC) is caused by human papillomavirus (HPV) and, currently, is not always treatable. A research team led by Lorenz Kadletz-Wanke from MedUni Vienna’s Department of Otorhinolaryngology and Head and Neck Surgery has now discovered a new therapeutic option in the context of a study.
In the course of their investigations, the researchers were able to identify a protein that can be used to predict above-average survival of patients with HPV-positive head and neck carcinoma and to achieve progress in treatment. Specifically, this involves the Creb-binding protein (CBP), which controls various cellular programs and plays a role in carcinogenesis, among other things. As the study shows, CBP is much more active in HPV-induced head and neck tumours.
Prognostic marker
The most common triggers of head and neck tumours continue to be alcohol consumption and smoking. That said, human papillomavirus infections have increasingly been identified as the cause of HNSCC in recent years. Patients with HPV-positive head and neck tumours have so far been treated with chemotherapy and radiotherapy. This standard method acts systemically, i.e. on the whole body, is often accompanied by serious side effects such as hair loss, nausea and anemia, and not all patients respond to it. In the search for targeted treatments, the interdisciplinary research group studied the tissue of patients with HPV-positive HNSCC tumours histologically and in preclinical models. In the process, they not only discovered the protein CBP as a prognostic marker for above-average patient survival but also found that HPV-positive HNSCC cell models in particular can be effectively treated with a CBP inhibitor.
Targeted therapy
CBP inhibitors are drugs currently in development and may be available within the next few years. “For patients with HPV-positive head and neck carcinoma, treatment with CBP inhibitors has the advantage that it can be targeted, rather than affecting the whole body. It is also better tolerated than conventional chemotherapy or radiotherapy and this would significantly improve the quality of life of those affected,” says study leader Lorenz Kadletz-Wanke, summarising the key finding of the research, which was conducted at MedUni Vienna’s Department of Otorhinolaryngology and Head and Neck Surgery in collaboration with Lukas Kenner (MedUni Vienna’s Department of Pathology, Department of Laboratory Animal Pathology at Vetmeduni Vienna) and Stefan Stoiber (MedUni Vienna’s Department of Biomedical Imaging and Image-guided Therapy).
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Researchers at Karolinska Institutet in Sweden have identified key signalling pathways that when blocked by existing drug candidates limit reproduction of the Crimean-Congo haemorrhagic fever (CCHF) virus. The findings, published in the journal eLife, offer hope for patients affected by this potentially deadly disease.
“The spread of the CCHF virus poses an increased threat to public health due to its high mortality rate in humans, which varies between 3 to as much as 40 per cent in some regions,” says the study’s senior author Ali Mirazimi, adjunct professor at the Department of Laboratory Medicine, Karolinska Institutet. “Unfortunately, there are currently no vaccines or effective treatments available, which is why it is of utmost urgency to identify promising drug candidates that could lead to better treatments and reduce the high mortality rate.”
The CCHF virus is primarily transmitted to people from tick bites or through contact with infected animals, although human-to-human transmission can also occur. The virus causes the disease Crimean-Congo haemorrhagic fever, which typically manifests itself with symptoms such as fever, muscle aches, joint pain, vomiting and bleeding, and can progress to organ failure and death.
The disease is endemic with fairly stable infection levels in 30 countries in Central Asia, the Middle East, southeast Europe and parts of Africa. However, with global warming, the ticks carrying the virus are spreading to other parts of the world, with more cases seen in other parts of Europe in recent years. The disease is classified as hazardous to society according to the Communicable Diseases Act.
Pathways identified
All viruses are parasites that are completely dependent on their hosts for reproduction. A virus that infects a cell reprograms the cell to create more virus. The cells’ energy supply and functions are controlled via signalling pathways, and viruses take advantage of these pathways to spread within the body.
In the study, the research group investigated how the CCHF virus infects cells and what types of changes take place. Using blood samples from patients with both acute infection and one year after recovery and cell culture experiments, the researchers found that the CCHF virus prefers pathways involving energy metabolism to reproduce.
Drug candidates reduce viral spread
By blocking two key metabolic pathways, glycolysis and glutaminolysis, with previously identified drug candidates, the researchers were able to significantly reduce viral reproduction in a laboratory setting. The findings build on earlier research from the same research groups at Karolinska Institutet, including a study that found similar mechanisms involved in the proliferation of SARS-CoV-2, which causes the disease COVID-19.
“We hope that our findings can lead to new antiviral treatments against Crimean-Congo haemorrhagic fever,” says the study’s first author Ujjwal Neogi, researcher at the Department of Laboratory Medicine at Karolinska Institutet. “Based on our discovery, we will soon begin in vivo studies in animals and hopefully translate these findings into clinical trials in the near future.”
The study was supported by grants from the Swedish Research Council, the Public Health England Grant In Aid, Karolinska Institutet and the European Union Horizon 2020 CCHF Vaccine Grant.
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In addition to memory problems and other cognitive symptoms, most people with Alzheimer’s disease also suffer from mental health issues. It has long been unclear whether these occur because of tissue changes in the brain, or whether they represent psychological reactions to cognitive symptoms. A study from Lund University in Sweden has provided new insight, and is published in Biological Psychiatry.
Cognitive symptoms combined with elevated levels of certain proteins form the basis for diagnosis of Alzheimer’s disease. At the same time, researchers and physician alike have, over the past decade, recognised that changes in mood and behaviour are often very early signs of the disease. Yet, these symptoms have not received as much scientific attention as cognitive ones.
Now, researchers from Lund University have investigated the complex relationships between psychological symptoms, Alzheimer’s proteins and cognitive symptoms. This was done within the framework of the internationally renowned BioFINDER study, led by Professor Oskar Hansson.
The study examined 356 people over the age of 65 with no cognitive symptoms at the start of the research. In addition to analysing the levels of the Alzheimer’s proteins amyloid beta and phosphorylated tau in their cerebrospinal fluid, participants’ levels of anxiety, apathy and overall cognitive function were also assessed on a biannual basis. Participants were followed for a total of eight years.
When data was analyzed, the researchers found a clear link between elevated levels of amyloid beta at the start of the study and future development of anxiety and apathy.
Maurits Johansson, physician and lead author of the study, explains: “Alzheimer’s disease affects large parts of the brain, including the regions that control our emotional life. Our study shows that psychiatric symptoms, just like cognitive symptoms, occur mainly as a direct consequence of the underlying changes to the brain, due to increased levels of amyloid beta.”
The researchers further demonstrated that amyloid beta drives the development of apathy predominately through direct effects, and that apathy only to a limited extent evolves secondary to cognitive decline. Anxiety was not linked to cognitive change.
“The findings thus argue against the idea that these early changes in emotion and motivation in Alzheimer’s disease are primarily psychological reactions to cognitive decline. Instead, the results suggest that for apathy and anxiety at least, these occur due to the pathological accumulation of amyloid beta,” clarifies Professor Oskar Hansson.
“Our findings imply that psychiatric symptoms in Alzheimer’s disease could be used as alternative outcome measures in treatment trials. Ultimately, this could lead to more effective study design,” he continues.
“A previous BioFINDER study suggested that the presence of anxiety or apathy among elderly people who continued to show no signs of dementia may point to an increased risk of future cognitive impairment. As a next step, studies are needed to clarify how these symptoms may contribute to the established clinical diagnosis in the early stages of disease, possibly even before cognition has been affected,” they conclude.
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A first-of-its-kind national study has found that a special program adopted in many states to help some families at risk of child maltreatment has been surprisingly successful.
The study found that states with what is called “differential response” (DR) programs had about 19% fewer substantiated reports of child maltreatment, 25% fewer substantiated reports of neglect and a 17% reduction in using foster care services when compared to states without DR programs.
The success of DR in reducing the number of children sent to foster care is especially important, said Michelle Johnson-Motoyama, lead author of the study and associate professor of social work at The Ohio State University.
“In certain situations, foster care is necessary to protect children from harm. However, it is also costly from human and societal perspectives and some states have been creative in finding ways to keep families together,” Johnson-Motoyama said.
“We found differential response programs may be getting families the resources they need to prevent foster care entry.”
The study was published recently in the journal Child Maltreatment.