Culture

New research from the University of Arizona Health Sciences found that people who suffer from migraine may benefit from green light therapy, which was shown to reduce the frequency and intensity of headaches and improve patient quality of life.

According to the Migraine Research Foundation, migraine is the third most prevalent illness in the world, affecting 39 million people in the United States and 1 billion worldwide.

"This is the first clinical study to evaluate green light exposure as a potential preventive therapy for patients with migraine, " said Mohab Ibrahim, MD, PhD, lead author of the study, an associate professor in the UArizona College of Medicine - Tucson's Department of Anesthesiology, Pharmacology, and Neurosurgery and director of the Chronic Pain Management Clinic. "As a physician, this is really exciting. Now I have another tool in my toolbox to treat one of the most difficult neurological conditions - migraine."

Overall, green light exposure reduced the number of headache days per month by an average of about 60%. A majority of study participants - 86% of episodic migraine patients and 63% of chronic migraine patients - reported a more than 50% reduction in headache days per month. Episodic migraine is characterized by up to 14 headache days per month, while chronic migraine is 15 or more headache days per month.

"The overall average benefit was statistically significant. Most of the people were extremely happy," Dr. Ibrahim said of the participants, who were given light strips and instructions to follow while completing the study at home. "One of the ways we measured participant satisfaction was, when we enrolled people, we told them they would have to return the light at the end of the study. But when it came to the end of the study, we offered them the option to keep the light, and 28 out of the 29 decided to keep the light."

Dr. Ibrahim and co-author Amol Patwardhan, MD, PhD, who are affiliated with the UArizona Health Sciences Comprehensive Pain and Addiction Center, have been studying the effects of green light exposure for several years. This initial clinical study included 29 people, all of whom experience episodic or chronic migraine and failed multiple traditional therapies, such as oral medications and Botox injections.

"Despite recent advances, the treatment of migraine headaches is still a challenge," said Dr. Patwardhan, an associate professor and the vice chair of research in the Department of Anesthesiology. "The use of a nonpharmacological therapy such as green light can be of tremendous help to a variety of patients that either do not want to be on medications or do not respond to them. The beauty of this approach is the lack of associated side effects. If at all, it appears to improve sleep and other quality of life measures."

During the study, patients were exposed to white light for one to two hours a day for 10 weeks. After a two-week break, they were exposed to green light for 10 weeks. They completed regular surveys and questionnaires to track the number of headaches they experienced and the intensity of those headaches, as well as quality of life measurements such as the ability to fall and stay asleep or to perform work.

Using a numeric pain scale of 0 to 10, participants noted that green light exposure resulted in a 60% reduction in pain, from 8 to 3.2. Green light therapy also shortened the duration of headaches, and it improved participants' ability to fall and stay asleep, perform chores, exercise, and work.

None of the study participants reported any side effects of green light exposure.

"In this trial, we treated green light as a drug," Dr. Ibrahim said. "It's not any green light. It has to be the right intensity, the right frequency, the right exposure time and the right exposure methods. Just like with medications, there is a sweet spot with light."

Dr. Ibrahim has been contacted by physicians from as far away as Europe, Africa and Asia, all asking for the green light parameters and schematic design for their own patients.

"As you can imagine, LED light is cheap," he said. "Especially in places where resources are not that available and people have to think twice before they spend their money, when you offer something affordable, it's a good option to try."

The paper, "Evaluation of green light exposure on headache frequency and quality of life in migraine patients: A preliminary one-way cross-over clinical trial," was published online by Cephalalgia, the journal of the International Headache Society.

"These are great findings, but this is where the story begins," Dr. Ibrahim said. "As a scientist, I am really interested in how this works because if I understand the mechanism, then I can utilize it for other conditions. I can use it as a tool to manipulate the biological systems to achieve as much as we can."

Rushing to stock up on toilet paper before it vanished from the supermarket isle, stashing cash under the mattress, purchasing a puppy or perhaps planting a vegetable patch - the COVID-19 pandemic has triggered some interesting and unusual changes in our behavior.

Understanding the psychology behind economic decision-making, and how and why a pandemic might trigger responses such as hoarding, is the focus of a new paper published in the Journal of Behavioral Economics for Policy.

'Hoarding in the age of COVID-19' by behavioral economist Professor Michelle Baddeley, Deputy Dean of Research at the University of Technology Sydney (UTS) Business School, examines a range of cross-disciplinary explanations for hoarding and other behavior changes observed during the pandemic.

"Understanding these economic, social and psychological responses to COVID-19 can help governments and policymakers adapt their policies to limit negative impacts, and nudge us towards better health and economic outcomes," says Professor Baddeley.

Governments around the world have implemented behavioral insights units to help guide public policy, and influence public decision-making and compliance.

Hoarding behavior, where people collect or accumulate things such as money or food in excess of their immediate needs, can lead to shortages, or in the case of hoarding cash, have negative impacts on the economy.

"In economics, hoarding is often explored in the context of savings. When consumer confidence is down, spending drops and households increase their savings if they can, because they expect bad times ahead," explains Professor Baddeley.

"Fear and anxiety also have an impact on financial markets. The VIX 'fear' index of financial market volatility saw a dramatic 564% increase between November 2019 and March 2020, as investors rushed to move their money into 'safe haven' investments such as bonds."

While shifts in savings and investments in the face of a pandemic might make economic sense, the hoarding of toilet paper, which also occurred across the globe, is more difficult to explain in traditional economic terms, says Professor Baddeley.

Behavioural economics reveals that our decisions are not always rational or in our long term interest, and can be influenced by a wide range of psychological factors and unconscious biases, particularly in times of uncertainty.

"Evolved instincts dominate in stressful situations, as a response to panic and anxiety. During times of stress and deprivation, not only people but also many animals show a propensity to hoard."

Another instinct that can come to the fore, particularly in times of stress, is the desire to follow the herd, says Professor Baddeley, whose book 'Copycats and Contrarians' explores the concept of herding in greater detail.

"Our propensity to follow others is complex. Some of our reasons for herding are well-reasoned. Herding can be a type of heuristic: a decision-making short-cut that saves us time and cognitive effort," she says.

"When other people's choices might be a useful source of information, we use a herding heuristic and follow them because we believe they have good reasons for their actions. We might choose to eat at a busy restaurant because we assume the other diners know it is a good place to eat.

"However numerous experiments from social psychology also show that we can be blindly susceptible to the influence of others. So when we see others rushing to the shops to buy toilet paper, we fear of missing out and follow the herd. It then becomes a self-fulfilling prophesy."

Behavioral economics also highlights the importance of social conventions and norms in our decision-making processes, and this is where rules can serve an important purpose, says Professor Baddeley.

"Most people are generally law abiding but they might not wear a mask if they think it makes them look like a bit of a nerd, or overanxious. If there is a rule saying you have to wear a mask, this gives people guidance and clarity, and it stops them worrying about what others think.

"So the normative power of rules is very important. Behavioral insights and nudges can then support these rules and policies, to help governments and business prepare for second waves, future pandemics or other global crises."

A new publication by scientists from Children's Medical Research Institute has challenged one of the foundations of the gene therapy field and will help to improve strategies for treating serious genetic disorders of the liver.

The paper titled, Restoring the natural tropism of AAV2 vectors for human liver, was published in Science Translational Medicine today.

Adeno-associated virus 2 (AAV2) is a viral vector that is used to deliver gene therapy to the liver. It works as a delivery vehicle to carry therapeutic DNA to the target cells in the body. The way it does this is by binding a 'receptor' on the target cell, a molecule that tells the vector it is in the right place and helps to deliver its cargo into cells. However, clinical trials targeting diseases of the liver have had an unexpectedly low success rate using this vector and now the researchers from CMRI appear to have discovered the reason.

The teams of Dr. Leszek Lisowski, Head of the Translational Vectorology Research Unit, and Prof Ian Alexander, Head of the Gene Therapy Research Unit, have found that the original AAV2, which is commonly used in preclinical and clinical studies, binds tightly to its attachment receptor, heparan sulfate proteoglycans (HSPGs), but too tightly. Because HSPGs are found in many places in the body, not just on liver cells, the vector gets "trapped" before it reaches its intended destination. Therefore, very few vectors manage to deliver their therapeutic cargo to the liver, which greatly diminishes the therapeutic efficacy.

This led the CMRI teams to study naturally occurring adeno-associated viruses which they found were much more successful at delivering the therapy into the liver. These viruses use another receptor that's yet to be discovered. CMRI researchers are now able to make vectors in the lab that use this better receptor, instead of HSPGs, potentially making the next generation of gene therapy targeting the liver vastly more successful.

"This really challenges a basic concept in our field that binding strongly to HSPG was essential for AAV's entry into human cells and suggests that vectors targeting the other receptor used by natural AAVs, of human liver origin, are likely to be more effective for clinical gene therapy applications'' Dr. Lisowski said. "The prototypical AAV2, discovered over 50yrs ago, is the serotype on which the entire field of AAV vectorology and gene therapy is based. Our discovery will shake the foundations of the field of AAV-based gene therapeutics and will mark the beginning of a new era not only for biomedical research, but most importantly, for millions of patients affected by genetic disorders"

"It sheds new light and challenges our previous understanding and corrects misconceptions about how the vector binds to the cells,'' he added.

Lead author on the publication, Dr. Marti Cabanes-Creus, said they could now move forward to improve on the use of vectors to help children with liver conditions. "It will help us understand previous clinical data and how to improve on these" he said.

"By having a better vector, we can increase the safety and improve the efficiency. Because a lower dose will be needed to achieve therapeutic efficacy, the cost of those therapies will be decreased, which is an additional benefit to the patients, their families, and the healthcare system."

Dr. Cabanes-Creus added that "The lessons learned can potentially be extended to other tissues, beyond the liver, making this a very impactful study which will change the trajectory of AAV-based gene therapies."

Qubits--the carriers of quantum information--are prone to errors induced by undesired environmental interactions. These errors accumulate during a quantum computation and correcting them is thus a key requirement for a reliable use of quantum computers.

It is by now well known that quantum computers can withstand a certain amount of computational errors, such as bit flip or phase flip errors. However, in addition to computational errors, qubits might get lost altogether. Depending on the type of quantum computer, this can be due to actual loss of particles, such as atoms or ions, or due to quantum particles transitioning for instance to unwanted energy states, so that they are no longer recognized as a qubit. When a qubit gets lost, the information in the remaining qubits becomes scrambled and unprotected, rendering this process a potentially fatal type of error.

Detect and correct loss in real time

A team of physicists led by Rainer Blatt from the Department of Experimental Physics at the University of Innsbruck, in collaboration with theoretical physicists from Germany and Italy, has now developed and implemented advanced techniques that allow their trapped-ion quantum computer to adapt in real-time to loss of qubits and to maintain protection of the fragile stored quantum information. "In our trapped-ion quantum computer, ions hosting the qubits can be trapped for very long times, even days", says Innsbruck physicist Roman Stricker. "However, our ions are much more complex than a simplified description as a two-level qubit captures. This offers great potential and additional flexibility in controlling our quantum computer, but unfortunately it also provides a possibility for quantum information to leak out of the qubit space due to imperfect operations or radiative decay." Using an approach developed by the Markus Müller's theoretical quantum technology group at RWTH Aachen University and Forschungszentrum Jülich, in collaboration with Davide Vodola from the University of Bologna, the Innsbruck team has demonstrated that such leakage can be detected and corrected in real-time. Müller emphasizes that "combining quantum error correction with correction of qubit loss and leakage is a necessary next step towards large-scale and robust quantum computing."

Widely applicable techniques

The researchers had to develop two key techniques to protect their quantum computer from the loss of qubits. The first challenge was to detect the loss of a qubit in the first place: "Measuring the qubit directly was not an option as this would destroy the quantum information that is stored in it", explains Philipp Schindler from the University of Innsbruck. "We managed to overcome this problem by developing a technique where we used an additional ion to probe whether the qubit in question was still there or not, without disturbing it", explains Martin Ringbauer. The second challenge was to adapt the rest of the computation in real-time in case the qubit was indeed lost. This adaptation is crucial to unscramble the quantum information after a loss and maintain protection of the remaining qubits. Thomas Monz, who lead the Innsbruck team, emphasizes that "all the building blocks developed in this work are readily applicable to other quantum computer architectures and other leading quantum error correction protocols."

Feline leukaemia virus (FeLV) is a gammaretrovirus that occurs worldwide in domestic cats, as well as small wild cats. It is associated with various serious, and sometimes fatal, diseases including anaemia, immunosuppression and certain cancers. First described over 55 years ago, FeLV has been the subject of intense research interest, which has led to increasingly robust diagnostic assays and efficacious vaccines. While the prevalence of this infection in domestic cats has reduced in many geographic regions, the disease is still something of an enigma and can spread quickly, particularly within naïve 'multi-cat' populations such as shelters and breeding catteries, as well as within pet homes with multiple cats. An important goal in order to reduce the prevalence further is understanding the FeLV status of every cat at risk of infection.

A state-of-the-art Premier Review published in the Journal of Feline Medicine and Surgery this month aims to contribute diagnostic expertise to veterinarians in practice by reviewing recent insights into infection pathogenesis, gained using molecular techniques.1 Writing for an international audience of veterinary practitioners and feline researchers, Professors Regina Hofmann-Lehmann, of the University of Zurich, Switzerland, and Katrin Hartmann, of LMU Munich, Germany, explain that not only are there several different outcomes of FeLV infection, but that these can vary over time. Newly classified as 'progressive', 'regressive', 'focal' and 'abortive' infection, the authors describe how it can be helpful to think of these outcomes in terms of a set of balance scales, with the cat's immune response on one side and the virus on the other.

From an epidemiological point of view, it is the progressively infected cat that is most significant. In these infections, the virus has the upper hand - these cats shed high numbers of FeLV particles and pose an infection risk to other cats. Regardless of their health status, progressively infected cats need to be kept apart from FeLV-naïve companions. From a clinical point of view, progressively infected cats are a priority too: they are at high risk of succumbing to potentially fatal disease; though, if well cared for, many can continue to live a healthy and happy life, sometimes for years.

Of the other possible outcomes, abortive infection is the most favourable for the cat - these cats have strong anti-FeLV immunity. Regressively infected cats will have developed a partially effective antiviral immune response that can keep the virus in check; however, they probably never clear the infection completely, and can shed virus, and thus pose an infection risk, in the early phase of infection or if reactivation occurs. In focal infection, which is comparatively rare, the cat's immune system keeps viral replication sequestered in certain tissues.

When it comes to FeLV testing, seemingly perplexing or 'discordant' test results are not uncommon, particularly in the early phase of infection, and can pose considerable challenges for the practitioner needing to establish the FeLV status and implement appropriate therapeutic and epidemiological measures. The authors discuss the most frequently used methods for FeLV detection, including free FeLV p27 antigen testing, viral RNA testing and FeLV provirus testing, focusing on when to test and how to interpret a positive or a negative result. The detection of anti-FeLV antibodies, including a point-of-care test for FeLV p15E introduced recently onto the European market, is also discussed. A diagnostic algorithm produced by the European Advisory Board on Cat Diseases (ABCD) that provides guidance on which test to choose in which scenario is incorporated within the review article.

As well as being expert members of the ABCD, both authors were members of an expert panel for recently published consensus guidelines from the American Association of Feline Practitioners (AAFP) on feline retrovirus testing and management,2 and together the guidelines and review article present the current state of knowledge about this potentially deadly virus. Discussing their ambition for their article, Professors Hofmann-Lehmann and Hartmann comment: 'We hope that this review will not only increase awareness of this fatal but preventable disease, but also help veterinarians in clinical practice when diagnosing this remarkable but tricky infection'.

A newly published study looking at cats in Wuhan, where the first known outbreak of COVID-19 began, shows more cats might be contracting the disease than first believed.

Researchers from Huazhong Agricultural University, in the Chinese city, took blood samples from 102 cats between January and March 2020, following the first outbreak. Nasal and anal swabs were also collected.

Reporting their findings in peer-reviewed journal Emerging Microbes & Infections, they show COVID-19 antibodies present in 15 of the blood samples taken from the cats. Of these, 11 cats had neutralizing antibodies - proteins that bind so successfully to a virus they block the infection.

None of the cats actually tested positive for COVID-19 or displayed obvious symptoms and, according to the results of return visits, none of these felines have died.

The sample of cats looked at included 46 abandoned from 3 animal shelters, 41 from 5 pet hospitals, and 15 cats were from COVID-19 patient families.

The three cats with the highest levels of antibodies were all owned by patients who had been diagnosed with COVID-19, whilst there were also signs of cats being infected with the virus by other cats from those that were abandoned (4) or based in the pet hospitals (4).

Commenting on the findings, lead author Meilin Jin states that whilst there is currently no evidence for cat-to-human transmission, precautions should be considered.

"Although the infection in stray cats could not be fully understood, it is reasonable to speculate that these infections are probably due to the contact with SARS-CoV-2 polluted environment, or COVID-19 patients who fed the cats.

"Therefore measures should be considered to maintain a suitable distance between COVID-19 patients and companion animals such as cats and dogs, and hygiene and quarantine measures should also be established for those high-risk animals."

The team assessed the type of antibody reactions in thorough detail and were able to describe the dynamic characteristics of the antibodies found.

Amongst many discoveries within the antibodies, they saw that the type of reaction produced by the cats resembles those observed in seasonal coronavirus infections, implying that the cats who have had SARS-CoV-2 infection "remain at risk of re-infection".

The authors state that this is a similar transient antibody response to also be observed in humans, and that their study should be used going forwards as a "reference for the clinical treatment and prevention of COVID-19".

"We suggest that cats have a great potential as an animal model for assessing the characteristic of antibody against SARS-CoV-2 in humans," they add.

From here, the team state that more research is needed to establish the route of Covid-19 from humans to cats.

"Retrospective investigation confirmed that all of antibody positive samples were taken after the outbreak, suggesting that the infection of cats could be due to the virus transmission from humans to cats. Certainly, it is still needed to be verified via investigating the SARS-CoV-2 infections before this outbreak in a wide range of sampling," Jin states.

Gut microbes affect human health, but there is still much to learn, in part because they're not easy to collect. But researchers now report in ACS Nano that they have developed an ingestible capsule that in rat studies captured bacteria and other biological samples while passing through the gastrointestinal (GI) tract.

Currently, researchers obtain gut microbes by collecting stool samples or using techniques such as colonoscopy or endoscopy. However, stool samples can't capture all the microorganisms in the upper GI tract, and they can't keep microbes from different parts of the tract separate. Colonoscopy and endoscopy are invasive procedures, which deters some patients. Sarvesh Kumar Srivastava and colleagues wanted to avoid these drawbacks by designing a device that could be swallowed and then eliminated.  

The researchers developed a self-polymerizing reaction system of poly(ethylene glycol) diacrylate monomer, iron chloride and ascorbic acid -- all loaded into tiny hollow cylinders. The cylindrical microdevices were packaged in miniature gelatin capsules, which were coated with a protective layer to prevent digestion in the stomach's acidic environment. After they were fed to rats, the capsules remained protected in the stomach but disintegrated in the small intestine's more-neutral pH, releasing the microdevices. Exposure to intestinal fluid caused the cylinders' chemical cargo to polymerize, forming a hydrogel that trapped microbes and protein biomarkers in its surroundings, much like an instant snapshot of the intestine. The devices, which didn't cause inflammation or toxicity, were then surgically removed -- a step that the researchers say will be replaced by natural elimination in future. High-throughput sequencing studies showed that the bacterial population the devices captured closely resembled that of the gut. The researchers also demonstrated that these tiny cylinders could be triggered over a range of pH to deliver biologics, like insulin, to cells in a petri dish in the presence of intestinal mucus. This technology could advance understanding of host-microbiome interactions, providing insight into associated GI disease progression and paving the way for personalized gut therapies, the team says.

CHAMPAIGN, Ill. -- Every human cell harbors its own defenses against microbial invaders, relying on strategies that date back to some of the earliest events in the history of life, researchers report. Because this "cell-autonomous immunity" is so ancient and persistent, understanding it is essential to understanding human evolution and human medicine, the researchers said.

Like amoebae, most human cells can transform themselves to engulf and degrade foreign agents in a process known as phagocytosis, said Jessica Brinkworth, a professor of anthropology at the University of Illinois, Urbana-Champaign who wrote the new report with former undergraduate student Alexander Alvarado. And the methods that human cells use to detect, pierce or hack up invading microbes are inherited from - and shared by - bacteria and viruses, she said.

"Every cell has these things and they have this deep evolutionary history," Brinkworth said. "This means that if you're going to study humans, you need to accept that immunity is always going to be part of what you're looking at. And you're going to have to go deep into evolutionary time."

The authors reject the notion that the immune system is distinct from other bodily systems.

"Immunity is literally everywhere," Brinkworth said. "The whole of the organism, from the skin down to the level of the last enzyme floating anywhere in the body, almost all of it is engaged in protection in one form or another."

For that reason, she suggests that medical approaches to fighting infection that try to tamp down evolutionarily conserved immune responses such as pro-inflammatory pathways are misguided. While it can be useful or necessary to use immune-suppressing drugs against autoimmune conditions or in the case of organ transplants, such drugs do not appear to work against severe microbial infections.

"In the context of severe infections, there have been many attempts to come up with ways of reducing the immune response by throwing a bunch of steroids at it or blocking the body's ability to detect the pathogen," Brinkworth said. "But targeting these immune mechanisms that have been around for millions of years is potentially counterproductive."

In the case of sepsis, which Brinkworth studies, this approach has not been fruitful.

"More than 100 trials of immunomodulatory approaches to sepsis have failed," she said. "And the one drug that made it to market then failed. Most of these drugs tried to block highly evolutionarily conserved defenses, like mechanisms of cell-autonomous immunity."

Many immunomodulatory drugs now being tested against the new coronavirus are failed sepsis drugs, she said.

Similarly, anthropologists often fail to consider how millions of years of battle against infections at the cellular level have shaped human genetics, physiology and even behavior, Brinkworth said.

"If you're talking about human evolution, if you're in any physiological system, you're going to have to address at some point how pathogens have shaped it," she said.

The manuscript on which this press release is based has an associated correction, which can be found here: https://pubs.acs.org/doi/10.1021/acs.jproteome.1c00273

SARS-CoV-2, the virus responsible for COVID-19, can cause a wide range of symptoms, from none at all to severe respiratory stress, multi-organ failure and death. The virus notably targets the lungs, but many patients also experience non-respiratory symptoms. Now, researchers reporting in ACS' Journal of Proteome Research compared lipoproteins and metabolites in the blood of COVID-19 patients and healthy subjects, revealing signs of multi-organ damage in patients that could someday help diagnose and treat COVID-19.

Current diagnostic tests for COVID-19 rely on the detection of viral RNA or antibodies against the virus. Both types of tests are prone to false-negative results, as well as having other limitations. Another possible way of detecting SARS-CoV-2 infection could involve analyzing metabolic changes the virus causes in an infected person. Jeremy Nicholson, Elaine Holmes and colleagues wanted to analyze the systemic effects of the disease and determine whether there is a general metabolic signature of COVID-19.

The researchers collected blood samples from 17 patients who tested positive for COVID-19 with current assays and from 25 healthy age-, sex- and body mass index-matched controls who were proven negative for current or prior SARS-CoV-2 infection with an antibody test. Then, the team analyzed the plasma lipoprotein, metabolite and amino acid levels in blood plasma with nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. Through multivariate statistical analyses that detected differences between patients and controls, the researchers revealed a metabolic signature of SARS-CoV-2 infection involving signs of acute inflammation, liver dysfunction, diabetes and cardiovascular disease risk. The team is now validating the data in a much larger group of patients.  In addition to possibly being used to develop a metabolite-based diagnostic test, these results suggest that recovered COVID-19 patients should be evaluated for increased risks for other conditions, the researchers say.

Allergy is one of the most common diseases in Europe, it is estimated that more than 150 million Europeans suffer from recurring allergies and by 2025 this could have increased to half of the entire European population.1 Allergic patients initially undergo a process of "sensitization", meaning that their immune system develops a specific class of antibodies, so called Immunoglobulin E antibodies (IgE), which can recognize external proteins, referred to as allergens. IgEs bind and interact with cells that express a specific receptor called FcεR1. There are only a few cell types in the body that express the FcεR1 receptor and probably the most important ones are mast cells, a type of immune cell found in most tissues throughout the body.

When re-exposed to the allergen, mast cells (with IgE bound to their FcεR1 receptors) immediately react by rapidly releasing different mediators (e.g. histamine, proteases or cytokines) that cause the classic allergic symptoms. These symptoms depend on the tissue where the contact with the allergen happens and can range from sneezing/wheezing (respiratory tract) to diarrhea and abdominal pain (gastrointestinal tract) or itching (skin). Systemic exposure to allergens can activate a large number of mast cells from different organs at the same time, causing anaphylaxis, a serious and life-threatening allergic reaction.

Despite decades of research and detailed knowledge of the critical role of IgEs and mast cells in allergies, the physiological, beneficial function of this "allergy module" is still not completely understood. In 2006, Stephen J. Galli, senior co-author of this study, and his laboratory at Stanford University revealed the importance of mast cells for innate resistance against venoms of certain snakes and the honeybee (Science. 2006 Jul 28;313(5786):526-30. DOI: 10.1126/science.1128877). Subsequent work from the Galli laboratory showed the critical role of the "allergy module" in acquired host defense against high doses of venom (Immunity. 2013 Nov 14;39(5):963-75. doi: 10.1016/j.immuni.2013.10.005): this finding (to which Philipp Starkl, first author of the current study, contributed importantly) represented the first clear experimental evidence supporting the "Toxin Hypothesis" postulated by Margie Profet in 1991. This hypothesis proposed a beneficial function for allergic reactions against noxious substances (Q Rev Biol. 1991 Mar;66(1):23-62. doi: 10.1086/417049).

Following up on this discovery, Philipp Starkl, Senior Postdoctoral fellow at the Medical University of Vienna and CeMM, together with Sylvia Knapp, Professor at the Medical University of Vienna and CeMM PI, and Stephen J. Galli, Professor at Stanford University School of Medicine, and colleagues, set out to investigate whether this phenomenon could be relevant in defense against other toxin-producing organisms, in particular, pathogenic bacteria. The authors selected the bacterium Staphylococcus aureus as pathogen model due to its enormous clinical relevance and broad repertoire of toxins. This bacterium is a prototypic antibiotics-resistant pathogen and is also associated with the development of allergic immune responses in diseases such as asthma and atopic dermatitis. For their research, they used different experimental S. aureus infection models in combination with genetic approaches and in vitro mast cell models to reveal the functions of selected components of IgE effector mechanisms.

The scientists found that mice with a mild S. aureus skin infection develop an adaptive immune response and specific IgEs antibodies against bacterial components. This immune response grants these mice an increased resistance when they are confronted with a severe secondary lung or skin and soft tissue infection. However, mice that are lacking functional IgE effector mechanisms or mast cells are unable to build such protection. These findings indicate that the "allergic" immune response against bacteria is not pathological, but instead protective. Hence, defense against toxin-producing pathogenic bacteria might be an important biological function of the "allergy module".

This study is an important collaboration initiated by Philipp Starkl at the laboratory of Stephen J. Galli at Stanford University together with other colleagues and then continued at the laboratory of Sylvia Knapp at CeMM and the Medical University of Vienna. This exciting discovery not only advances the general understanding of the immune system and most notably allergic immune responses, but it could also explain why the body has maintained the "allergy module" throughout evolution. Despite their dangerous contributions to allergic diseases, IgEs and mast cells can exert beneficial functions that the immune system can capitalize on to protect the body against venoms and infections with toxin-producing bacteria, such as S. aureus.

Maternal overweight and obesity increase the risk of gestational diabetes mellitus. Gut microbiota composition has recently been associated with both overweight and a range of metabolic diseases. However, it has thus far been unclear whether gut microbiota is involved in the incidence of gestational diabetes.

A clinical study with the purpose to investigate the impact of two food supplements, fish oil and probiotics (containing Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420), on maternal and child health was conducted at the University of Turku and Turku University Hospital in Finland. The microbiota was analysed from fecal samples of 270 overweight and obese women using the state of the art analytical and bioinformatics methods based on deep sequencing metagenomics analysis.

"Metagenomics is a next-generation sequencing tool that provides species level resolution of the gut microbiota composition. Metagenomics also provides information on the bacterial genes and gives clues about the possible function of the gut microbiota," says Senior Researcher Kati Mokkala from the Institute of Biomedicine of the University of Turku, Finland.

"Our study shows that gut microbiota composition and function is not involved in the onset of gestational diabetes in overweight and obese women. Also, no difference were found in women with gestational diabetes when compared to women remaining free from the condition," explains Associate Professor Kirsi Laitinen from the Early Nutrition and Health research group.

Probiotics have been shown to influence gut microbiota composition, but the impact of the combination of probiotics and fish oil is less well characterized. The women were randomised into four groups to consume two food supplements either as a combination or separately: fish oil + placebo, probiotics + placebo, fish oil + probiotics, or placebo + placebo. The women consumed the supplements from early pregnancy onwards until after the pregnancy.

"Interestingly, our study revealed that the combination of fish oil and probiotics modulated the composition of gut microbiota particularly in women who did not develop gestational diabetes," Mokkala explains.

Whether the gut microbiota of women with gestational diabetes is less amenable for modification by food supplements needs to be confirmed in further studies.

A tick species associated with bats has been reported for the first time in New Jersey and could pose health risks to people, pets and livestock, according to a Rutgers-led study in the Journal of Medical Entomology.This species (Carios kelleyi) is a “soft” tick. Deer ticks, which carry Lyme disease, are an example of “hard” ticks.
“All ticks feed on blood and may transmit pathogens (disease-causing microbes) during feeding,” said lead author James L. Occi, a doctoral student in the Rutgers Center for Vector Biology at Rutgers University–New Brunswick. “We need to be aware that if you remove bats from your belfry, attic or elsewhere indoors, ticks that fed on those bats may stay behind and come looking for a new source of blood. There are records of C. kelleyi biting humans.”
This soft tick species, a parasite of bats, is known to be in 29 of the 48 contiguous U.S. states, and was confirmed in New Jersey as larvae collected from big brown bats (Eptesicus fuscus) in Mercer and Sussex counties. This is a new addition to the list of New Jersey ticks.
While the public health risk remains unknown, “finding them on New Jersey bats was an unusual event that prompted bat specialists to contact us. Maybe these ticks are becoming more common,” said senior author Dina M. Fonseca, a professor and director of the Center for Vector Biology in the Department of Entomology in the School of Environmental and Biological Sciences.In other states, C. kelleyi has been found infected with microbes that are harmful to people, pets and livestock. There have been reports of this soft tick feeding on humans, and the bat that hosts them regularly roosts in structures such as attics and barns, underscoring the need to learn more about them, the study says.

“This tick belongs to the family Argasidae, known as 'soft ticks' because their body looks leathery and soft,” Fonseca said. That is in contrast to the "hard ticks" (family Ixodidae) that New Jerseyans are more familiar with.Scientists in the Endangered and Nongame Species Program of the Division of Fish and Wildlife in the New Jersey Department of Environmental Protection found the tick larvae on bats last year. Technically, this is not the first time a soft tick has been reported in New Jersey. In 2001, a related tick species – Carios jersey – was found in amber in Middlesex County. That specimen was 90 million to 94 million years old.

“The next steps are to collect more soft tick specimens and test them for disease-causing microbes,” Occi said.
Rutgers coauthors include Andrea M. Egizi, a visiting professor in the Department of Entomology and a research scientist with the Monmouth County Tick-borne Diseases Laboratory hosted by the Rutgers Center for Vector Biology. Scientists at the New Jersey Division of Fish and Wildlife, Smithsonian Institution and Walter Reed Army Institute of Research contributed to the study.

Journal

Journal of Medical Entomology

DOI

10.1093/jme/tjaa189

Boston, MA -- As COVID-19 began to surge in the Boston area earlier this year, new infection control measures were put in place at Brigham and Women's Hospital to protect patients and staff. Over the ensuing weeks, infection control policies continued to evolve, eventually encompassing:

Universal masking of all patients, staff and visitors

Dedicated COVID-19 units with airborne infection isolation rooms

Personal protective equipment in accordance with CDC recommendations

A restricted visitor policy

Daily symptom screening for employees and patients

Testing of all patients being admitted to the hospital

A new study addresses a critical question: Were these infection control measures successful in preventing transmission of COVID-19 to patients in the hospital? In a paper published in JAMA Network Open, a team of investigators from the Brigham report on an analysis of all cases in which a patient tested positive for COVID-19 three days or later after coming to the hospital and up to 14 days after discharge during the first 12 weeks of the surge in Massachusetts. They found that although the Brigham cared for over 9,000 inpatients during this timeframe -- including nearly 700 with COVID-19 -- only two patients likely acquired the disease within the hospital, including one who likely acquired it from his visiting spouse prior to universal masking and restriction of visitors, and one with no clear exposures within or outside the hospital.

"Our data show that in a hospital with robust, rigorous infection control measures, it is very much possible to prevent the spread of COVID-19 to patients," said corresponding author Chanu Rhee, MD, MPH, an infectious disease and critical care physician and associate hospital epidemiologist at the Brigham. "This is an important finding as we know that many patients are avoiding essential care due to fear of contracting COVID-19 in health care settings. Our study shows that the hospital is in fact very safe, and if people need to go the hospital for care, they should go."

Rhee and colleagues conducted their study on data from all patients seen at the Brigham beginning March 7 (when the first patient with COVID-19 was admitted) through May 30, 2020. During that 12-week period, 9,149 patients were admitted to the hospital. More than 7,300 diagnostic COVID-19 tests were performed, with 697 people testing positive. Twenty-three patients were diagnosed with COVID-19 after the third day of hospitalization or within two weeks after discharge. All cases were reviewed in detail by Rhee and hospital epidemiologist and co-author Michael Klompas, MD, MPH, to assess the most likely source of each patient's infection. Of these 23 patients, 14 had symptoms on admission and were deemed to have been infected prior to admission, while seven were diagnosed following high-risk, post-discharge exposures. Of the remaining two patients who may have acquired their infection in the hospital, one likely acquired his, prior to visitor restrictions and universal masking, from a visiting spouse who was found to have COVID-19. There was only one other patient without a clear exposure who may have been infected in the hospital.

Rhee characterized the team's findings as "an exceedingly low rate of infection" and a "near-zero incidence" of COVID-19 acquisition among patients seeking care at the hospital during the surge.

The authors note that their study cannot determine which infection control measures in place at the hospital were most critical. In addition, while the researchers comprehensively analyzed and reviewed each case, they could not definitively determine the source of infection in every case. Results were also limited to the Brigham and may not be applicable to hospitals that have adopted other infection control measures. The study did not examine infection among health care workers, and the authors believe that this important topic warrants a separate, detailed analysis.

"Overall, our results should provide confidence to clinicians and patients around the country that currently recommended infection-control measures -- if carefully implemented and followed -- can prevent the spread of COVID-19 within the hospital," said Rhee.

PHILADELPHIA -- Penn Medicine researchers have solved a decades old mystery around a key molecule fueling the power plant of cells that could be exploited to find new ways to treat diseases, from neurodegenerative disorders to cancer.

Reporting in a new study published today in Nature, researchers from the Department of Physiology in the Perelman School of Medicine at the University of Pennsylvania and other institutions found that the SLC25A51 gene dictates the transport of nicotinamide adenine dinucleotide (NAD+), a fundamental coenzyme in cellular metabolism, to the mitochondria, where energy from nutrients is converted into chemical energy for the cell. A low level of NAD+ is a hallmark of aging and has been associated with diseases including muscular dystrophy and heart failure.

"We have long known that NAD+ plays a critical role in the mitochondria, but the question of how it gets there had been left unanswered," said co-senior author Joseph A. Baur, PhD, an associate professor of Physiology and member of Penn's Institute for Diabetes, Obesity, and Metabolism. "This discovery opens up a whole new area of research where we can actually manipulate--selectively deplete or add--NAD+ at a subcellular level, now that we know how it's transported."

Xiaolu Ang Cambronne, PhD, an assistant professor in the department of Molecular Biosciences in The University of Texas at Austin, served as co-senior author.

The finding closes out a longstanding unknown around how NAD+ finds its way into the mitochondrial matrix. Several hypotheses had been circulating, including the idea that mammalian mitochondria were incapable of NAD+ transport, instead relying entirely on synthesis of NAD+ within the organelle, but in 2018, Baur's lab put that idea to rest when it reported in an eLife study that a transporter was in fact responsible.

From there, the team began its search for the genetic identity of the mammalian mitochondrial NAD+ transporter, homing in on several genes, including SLC25A51, that were predicted to be transporters, but for which the function remained unknown. SLC25A family members encode mitochondrially-localized proteins that carry materials across mitochondrial membranes.

"In our approach, we focused in on genes that were determined to be essential for cellular viability. NAD+ is a fundamental molecule required for maintaining the mitochondrial-mediated energy production. We predicted that loss-of mitochondrial NAD+ transport would disrupt oxidative phosphorylation and possibly reduce cell survival," said lead author Timothy S. Luongo, PhD, a postdoctoral fellow in the Baur lab.

In laboratory experiments, the researchers isolated the mitochondria from human cells and measured the levels of NAD+ after knocking out SLC25A51 or overexpressing it. Using mitochondrially-targeted NAD+ "biosensors," they showed that a change in the gene expression level controls mitochondria NAD+ levels specifically.

"We observed that loss of SLC25A51 expression dramatically altered the mitochondria's ability to consume oxygen and generate ATP as well as transport NAD+ into the matrix. Also, in collaboration with the Cambronne lab, we were able to demonstrate that expression of SLC25A51 in yeast lacking their endogenous mitochondrial NAD+ transporters restored NAD+ mitochondrial transport," said Luongo.

NAD+ levels can be targeted in various disease treatments; however, it has been more of a catch-all approach, where levels are increased or reduced in all parts of the cell, which runs the risk of unintended alterations of gene expression or other types of metabolism. This study is the first published case where researchers identified a specific target and reduced the levels solely in the mitochondria and no other parts of the cell.

Controlling the levels of NAD+ and thus metabolic processes in the mitochondria could have major implications for the study and development of new treatments for diseases. Activating the transport mechanism could potentially make cells favor a state of respiration to make energy, instead of glycolysis. Different cancer types, for example, rely heavily on glycolysis, so creating an unfavorable environment without that metabolism could be one strategy. Or, conversely, it might be possible to deny highly respiratory cancer cells mitochondrial NAD+, so they're forced to rely on glycolysis. The heart requires abundant quantities of mitochondrial-produced energy to continually supply blood to peripheral tissue. A major contributor to heart failure is mitochondrial dysfunction, so targeting the mitochondria's capacity to transport NAD+ may improve cardiac function of the failing heart. With respect to exercise, shifting towards a more oxidative metabolism could boost endurance.

The work is in its early days, but a door has been opened for new investigations centered on mitochondrial NAD+ and this gene. Next, the researchers will study the physiological function of NAD+ transport and how this mechanism is regulated, as well as ways to turn the transport on and off outside of reducing or increasing gene expression.

"An approach to specifically alter the mitochondrial NAD+ pool is something many researchers have been looking for, so I would expect that we will see this gene targeted in a multitude of systems," Baur said. "I think this is going to be a really valuable tool to help us better understand the function of mitochondrial NAD+ and its therapeutic potential."

PHILADELPHIA (September 9, 2020) - Confronting the uncomfortable reality of systemic racism - the system that creates and maintains racial inequality in every facet of life for people of color - is having a national heyday. But calling out this injustice and doing something about it are two different things.

Throughout its history, nursing has been on the forefront of advocacy addressing public policies, institutional practices, and other norms that perpetuate racial group inequities. Yet structural racism still remains in the teaching, research, scholarship, and practice of nursing.

In an editorial for the journal Nursing Outlook, two nurse leaders propose a framework to guide thinking and action to effectively address racial inequities and injustices throughout nursing.

"There remain too many examples of structural racism throughout nursing and we must be open to continuing to examine, identify, and change these within our own profession," writes Antonia M. Villarruel, PhD, RN, FAAN, Professor and Margaret Bond Simon Dean of Nursing at the University of Pennsylvania School of Nursing (Penn Nursing). Villarruel wrote the editorial titled "Beyond the naming: institutional racism in nursing," along with Marion E. Broome, PhD, RN, FAAN, Dean of the School of Nursing at Duke University.

The framework the authors outline identifies ways that nurses can lead in their organizations and change policies, practices, and traditions that disadvantage and diminish people of color in schools of nursing, nursing professional organizations, and health systems. The authors challenge nurses to use the framework to dismantle structural racism in practice.

"If it is to be different, it is time to act. Actions, if inclusive and well thought out, can be the medium to bring people together to make a real difference--especially the younger students and faculty who we so often 'protect' from that work," the authors add.