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New glue sticks easily, holds strongly, and is a gas to pull apart

Research expands number of temporary adhesivesCredit: Photo courtesy of Nicholas Blelloch. HANOVER, N.H. – December 2, 2020 – Temporary glues

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Credit: Photo courtesy of Nicholas Blelloch.

HANOVER, N.H. – December 2, 2020 – Temporary glues may not steal headlines, but they can make everyday life easier.

Sticky office notes, bandage strips and painter’s tape are all examples of products that adhere to surfaces but can be removed with relative ease.

There’s only one drawback. To remove any of those adhesives, the glued surfaces need to be pulled apart from each other.

Dartmouth research has discovered a class of molecular materials that can be used to make temporary adhesives that don’t require force for removal. These non-permanent glues won’t be available as home or office supplies, but they can lead to new manufacturing techniques and pharmaceutical design.

“This temporary adhesive works in an entirely different way than other adhesives,” said Katherine Mirica, an assistant professor of chemistry at Dartmouth. “This innovation will unlock new manufacturing strategies where on-demand release from adhesion is required.”

The Dartmouth research focuses on molecular solids, a special class of adhesive materials that exist as crystals. The molecules in the structures are sublimable, meaning that they shift directly from a solid to a gas without passing through a liquid phase.

The ability to bypass the liquid phase is the key to the new type of temporary adhesives. The adhesive sticks as a solid but then turns to a vapor and releases once it is heated in a vacuum environment.

“The use of sublimation–the direct transition from solid to vapor–is valuable because it offers gentle release from adhesion without the use of solvent or mechanical force,” said Mirica.

Previous Dartmouth research was the first to identify how molecular solids can act as temporary adhesives. According to new research, published in the academic journal Chemistry of Materials, the class of molecules that can be used to make these new-generation materials is wider than previously thought.

“We’ve expanded the list of molecules that can be used as temporary adhesives,” said Nicholas Blelloch, a PhD candidate at Dartmouth and first author of the paper. “Identifying more materials to work with is important because it offers expanded design strategies for bonding surfaces together.”

The research team says the new temporary adhesives can be useful in technical applications such as semiconductor manufacturing and drug development.

When making computer chips, silicon components need to be temporarily bonded. The use of a strong adhesive that releases through sublimation can allow for the development of smaller, more powerful chips since tapes requiring forceful pulling would no longer be required.

In pharmaceuticals, the design principles highlighted through this work can help the development of smaller, faster-acting pills. The adhesives can also be helpful in the design of nano- and micromechanical devices where the use of tape is not possible.

The finding also gives researchers more flexibility in developing temporary adhesives.

“Identifying more molecules with adhesives properties refines our fundamental understating of the multi-scale and multi-faceted factors that contribute to the adhesive properties of the system,” said Blelloch

Most common temporary adhesives that are used in the home or office are polymers, long chemical chains that create strong bonds, but can be difficult to be pulled from surfaces.

If polymers can be described as long chemical strands that easily tangle, molecular solids are more like individual chemical beads that sit atop each other. Both can be made to adhere, but there are tradeoffs.

Polymers used to make super glues tangle so well that they form exceedingly strong bonds that are difficult to pull apart. Sticky office notes and painter’s tape are also polymers, but with much less holding strength. They also require a peeling or ripping action to remove the bond.

Molecular solids being studied by the Dartmouth team can be as strong as temporary, polymer-based adhesives. The advantage of the new glues is that they not only adhere easily, they can be released without force, and without disturbing the bonded surfaces.

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About Dartmouth

Founded in 1769, Dartmouth is a member of the Ivy League and offers the world’s premier liberal arts education, combining its deep commitment to outstanding undergraduate and graduate teaching with distinguished research and scholarship in the arts and sciences and its leading professional schools: the Geisel School of Medicine, the Guarini School of Graduate and Advanced Studies, Thayer School of Engineering and Tuck School of Business.

https://www.dartmouth.edu/press-releases/new-glue-sticks-easily-holds-strongly-gas-pull-apart.html

Dartmouth research has discovered a class of molecular materials that can be used to make temporary adhesives that don’t require force for removal. These non-permanent glues won’t be available as home or office supplies, but they can lead to new manufacturing techniques and pharmaceutical design.

Source: https://bioengineer.org/new-glue-sticks-easily-holds-strongly-and-is-a-gas-to-pull-apart/

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Bioengineer

Physical activity reduces cardiovascular risk in rheumatic patients

People with diseases such as rheumatoid arthritis and lupus are more likely to have heart attacks, angina, and strokes. A

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People with diseases such as rheumatoid arthritis and lupus are more likely to have heart attacks, angina, and strokes. A review of the scientific literature on the subject shows that regular exercise improves vascular function in these patients

The risk of developing atherosclerosis – a narrowing of the arteries as cholesterol plaque builds up, leading to obstruction of blood flow – is higher for people with autoimmune rheumatic diseases than for the general population. As a result, they are more likely to have heart attacks and other cardiovascular disorders.

The good news, according to a new study published in Rheumatology, is that regular exercise is a powerful weapon against vascular dysfunction in these patients.

In the article, researchers working in Brazil and the United Kingdom report the results of a systematic review of the scientific literature on the subject. The review, which was supported by FAPESP, covered ten studies involving 355 volunteers with various diseases, such as rheumatoid arthritis, lupus, and spondyloarthritis (inflammation of the spine). The subjects took exercise programs such as walking in a park or on a treadmill, stationary cycling, high-intensity interval training, and muscle building. Most of the programs lasted 12 weeks.

“Our analysis of the results showed that exercise improved small and large vessel endothelial function to a clinically significant extent. Accordingly, we suggested that exercise can be considered ‘medication’ for these patients because of its potential to reduce the incidence of cardiovascular events,” said Tiago Peçanha, first author of the article. Peçanha is a postdoctoral fellow at the University of São Paulo’s Medical School (FM-USP) in Brazil.

These rheumatic diseases, he explained, are the result of an imbalance in the immune system that leads to the production of antibodies against the subject’s own organism, especially joints, muscles, ligaments and tendons. While there is no definitive cure for these diseases, they can be controlled by treatment with anti-inflammatory drugs, immunosuppressants, and biologics (drugs from living sources).

“Treatment doesn’t prevent patients from developing certain co-morbidities. Cardiovascular disease is the most worrisome,” Peçanha said. “The risk of heart attack is twice as high for people with rheumatoid arthritis as for healthy people. For people with lupus or psoriatic arthritis, the incidence of ischemic events [heart attack, angina and stroke] is between twice and five times as high.”

Atherosclerosis develops rapidly in these patients owing to the chronic inflammation associated with rheumatic disease and continuous use of anti-inflammatory drugs. “It all begins with changes in blood vessel structure and function,” Peçanha said. “The arteries gradually harden and stop being able to dilate when necessary. Changes occur above all in the endothelium [the layer of cells lining the interior surface of blood vessels]. Alterations in vascular function, especially endothelial function, are considered initial markers of atherosclerosis for this reason.”

The systematic review showed that exercise improved small and large vessel vascular function in patients with autoimmune rheumatic diseases. However, the authors note that given the small number of studies reviewed the evidence is not sufficient to state categorically that exercise also promotes a structural recovery of damaged arteries.

“This area [physical activity in rheumatology] is still new, so more research is needed to identify the best exercise protocols and investigate such aspects as safety and adherence,” Peçanha said. “In any event, the data in our study underlines the importance of regular exercise to prevent and treat cardiovascular disease in these patients.”

For people with rheumatic disease, as indeed for everyone else, Peçanha recommends at least 150 minutes of moderate to vigorous exercise per week. Aerobic exercise should predominate and be complemented by activities that foster strength and balance.

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

In the article, researchers working in Brazil and the United Kingdom report the results of a systematic review of the scientific literature on the subject. The review, which was supported by FAPESP, covered ten studies involving 355 volunteers with various diseases, such as rheumatoid arthritis, lupus, and spondyloarthritis (inflammation of the spine). The subjects took exercise programs such as walking in a park or on a treadmill, stationary cycling, high-intensity interval training, and muscle building. Most of the programs lasted 12 weeks.

Source: https://bioengineer.org/physical-activity-reduces-cardiovascular-risk-in-rheumatic-patients/

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An atlas of HIV’s favorite targets in the blood of infected individuals

Gladstone researchers have identified the blood cells most likely to be targeted by HIV during a real-life infectionCredit: Photo: Gladstone

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Gladstone researchers have identified the blood cells most likely to be targeted by HIV during a real-life infection

SAN FRANCISCO, CA–April 27, 2021–In the 40-some years since the beginning of the HIV/AIDS epidemic, scientists have learned a lot about the virus, the disease, and ways to treat it. But one thing they still don’t completely understand is which exact cells are most susceptible to HIV infection.

Without this knowledge, it is difficult to envision targeting these cells to protect the millions of people who encounter the virus for the first time every year, or the infected people in which infection will likely rebound if they go off therapy.

Scientists have known for a long time that the virus homes in on so-called memory CD4+ T cells, a type of cell that helps the human body build lasting immunity against pathogens. But that is still too broad a category to target for therapy.

“CD4+ T cells orchestrate the immune response against all kinds of pathogens, so you can’t just eliminate them to prevent HIV infections,” says Gladstone Associate Investigator Nadia Roan, PhD. “But if you can find the more specific subsets of CD4+ T cells that are highly susceptible to HIV infection, you may be able to specifically target those cells without detrimental side effects.”

Much knowledge about HIV infection comes from in vitro experiments (in a petri dish), where scientists expose CD4+ T cells cultured in the lab to the virus. These cell cultures are not a perfect model for the human body’s complex ecosystems in which infection normally takes place. Might in vitro infection yield a skewed view of the virus’s preference?

To answer this question, Roan and her team compared CD4+ T cells infected in vitro to the CD4+ T cells circulating in the blood of 11 individuals at various stages of infection. Some blood samples were taken before the donors had started treatment with antiretroviral therapy, some after. Yet others came from individuals who had stopped their treatment and were experiencing new rounds of infection.

Using technology they have honed over the years, the researchers established a detailed atlas of the CD4+ T cells in individuals not on antiretroviral treatment, which they have now published in the scientific journal Cell Reports.

“Our work affords novel insight into the basics of how HIV behaves in the human body, rather than just in a lab dish,” says Roan, who is also an associate professor of urology at UC San Francisco. “It informs our understanding of what really happens during an active infection, which is interesting in its own right. Moreover, we know that some infected cells become reservoirs of latent virus, so our work could help us better understand how the reservoir forms during an infection.”

The technology Roan and her team deployed, called CyTOF/PP-SLIDE, distinguishes cells with exquisite precision based on the proteins they contain or carry on their surface. With this information, the scientists can classify CD4+ T cells into myriad subsets, and then determine whether some subsets are more susceptible to infection than others.

A crucial perk of this technology is that it can trace infected cells back to their original state prior to infection.

“That’s important,” says Guorui Xie, PhD, a postdoctoral researcher in Roan’s lab and the first author of the study. “We know that when HIV infects cells, it remodels the cells such that they no longer contain the exact same levels of proteins as they did before infection. With CyTOF/PP-SLIDE, we can identify the uninfected cells that most closely match the infected ones in the same patient. These uninfected cells can give us important information about what the cells targeted by HIV resembled before the virus remodeled them.”

Roan’s team found that remodeling was indeed extensive in blood CD4+ T cells infected in vivo (in people) as well as in vitro. In the process, they made a surprising finding about one of HIV’s preferred targets. Prior studies have suggested that HIV prefers to infect a subtype of CD4+ T cells, called Tfh, and Roan’s team confirmed these cells to be susceptible to HIV. However, they also discovered that the virus can infect non-Tfh cells and remodel them such that they adopt features of Tfh cells.

“This result strikes a cautionary note in our field,” says Roan. “You really can’t tell which cells HIV prefers to target simply by looking at infected cells. You need to know what the cells looked like before remodeling.”

The scientists also found that remodeling causes infected blood cells to alter their surface in ways that may change how they move through the body. Roan prudently speculates that this might help the virus steer infected cells toward sites where it can infect even more cells.

“Whatever its exact purpose, remodeling is probably not just a chance event,” adds Roan. “A virus as small as HIV depends crucially on the resources provided by its host to grow and spread. It’s likely that nothing the virus does to its host cell is an accident.”

The profile of HIV’s favorite cells differed somewhat between in vitro and in vivo infections. Nevertheless, the researchers found one subset of cells that was preferentially infected in both cases, and could become a useful model for further lab studies.

The team also confirmed that not all CD4+ T cells are equally susceptible to HIV infection in vivo, which gives them hope that the most susceptible cells could eventually become targets of preventive interventions.

Xie and Roan are now planning to obtain blood samples from more donors to see whether HIV’s targets differ between a first infection and the return of the virus after a lapse in therapy, or between men and women. Ultimately, they would also like to look at in vivo-infected cells from mucosal tissues such as the gut and genital tract, where most HIV infections begin. But these samples are much harder to procure.

In the meantime, the researchers are making public the atlas of all the cells they have analyzed, along with the dozens of proteins they found to be affected in these cells after HIV infection, which they hope will be a valuable resource for the HIV research community.

“There is still much to discover in this atlas that may help uncover new insights into HIV infection and how it develops, and perhaps lead to the identification of new approaches for HIV/AIDS prevention,” says Roan.

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About the Study

The paper “Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4+ T cell subsets in vivo” was published in Cell Reports on April 27, 2021: https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00354-5.

Other authors include Xiaoyu Luo, Tongcui Ma, Julie Frouard, Jason Neidleman, and Warner C. Greene from Gladstone Institutes; and Rebecca Hoh and Steven G. Deeks from UC San Francisco.

This work was supported by the National Institutes of Health (R01AI127219, R01AI147777, P01AI131374, and S10-RR028962), the amfAR Institute for HIV Cure Research (109301), the UCSF-Gladstone Center for AIDS Research (P30AI027763), and the James B. Pendleton Charitable Trust.

About Gladstone Institutes

To ensure our work does the greatest good, Gladstone Institutes (https://gladstone.org) focuses on conditions with profound medical, economic, and social impact–unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.

https://gladstone.org/news/atlas-hivs-favorite-targets-blood-infected-individuals

Source: https://bioengineer.org/an-atlas-of-hivs-favorite-targets-in-the-blood-of-infected-individuals/

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Trial of existing antibiotic for treating Staphylococcus aureus Bacteremia begins

NIH-supported trial will test Dalbavancin in hospitalized adultsCredit: NIAID A clinical trial to test the antibiotic dalbavancin for safety and

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A clinical trial to test the antibiotic dalbavancin for safety and efficacy in treating complicated Staphylococcus aureus (S. aureus) bacteremia has begun. The trial will enroll 200 adults hospitalized with complicated S. aureus infection at approximately 20 trial sites around the United States. The trial is being sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

S. aureus is a leading cause of antibiotic-resistant infection. S. aureus infections led to nearly 20,000 deaths in 2017 in the United States, according to the U.S. Centers for Disease Control and Prevention (CDC). This bacterium is of particular concern in healthcare-associated infections. S. aureus bacteremia–an infection of the blood–often requires inserting a central intravenous (IV) catheter to deliver long courses of antibiotics, an invasive procedure that can involve long-term care in healthcare facilities.

“As antibiotic-resistant infections become more widespread, better and easier treatment regimens are needed to ease the burden on both healthcare providers and patients,” said NIAID Director Anthony S. Fauci, M.D. “By investigating existing antibiotics for their action on a broader array of bacterial infections, we may be able to generate new treatment regimens more efficiently.”

The antibiotic dalbavancin has strong activity against gram-positive bacteria, including methicillin-resistant S. aureus, which suggests it could be an effective treatment for S. aureus bacteremia. Dalbavancin is currently FDA-approved in the United States for treating acute bacterial skin and skin structure infections, including those caused by S. aureus. If the two-dose regimen being tested in this trial proves effective, it could lead to a shorter, less invasive treatment for S. aureus bacteremia that does not require an indwelling IV access for daily therapy.

The Phase 2b trial is being conducted by the NIAID-funded Antibacterial Resistance Leadership Group (ARLG) under the leadership of Thomas Holland, M.D., of Duke University (Durham, North Carolina.) It is called the “Dalbavancin as an Option for Treatment of S. aureus Bacteremia (DOTS)” trial. Patients who have stabilized after initial treatment of their bacteremia will be eligible for enrollment in this study.

“Dalbavancin is appealing as a potential option for treatment of these serious S. aureus infections, and we need high quality data to find out if it works,” said Dr. Holland, “This trial will provide clinicians and patients with that data.”

One hundred participants will be randomized to receive the standard of care for complicated infections, including appropriate antibiotics, and 100 participants will receive two doses of dalbavancin intravenously. The doses will be given one week apart. Most participants receiving dalbavancin will be given 1500 milligrams (mg) per dose. Participants with signs of kidney dysfunction will be given 1125 mg per dose. All participants will be followed for approximately 70 days after enrollment, and up to six months if they have vertebral osteomyelitis, an infection of the vertebrae.

At the end of the trial, multiple patient outcomes will be assessed: survival; additional complications (such as relapse) or clinical failures; drug-related adverse events; and overall quality of life. The therapeutic regimen will have met the primary endpoint of the trial if participants who received dalbavancin fare better on these metrics than those who received the current standard of care. This trial could validate a dalbavancin regimen of only one dose a week for two weeks, compared to daily doses administered intravenously for four to six weeks with the current standard of care.

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The ARLG is a clinical research consortium working to reduce the impact of antimicrobial resistance. It is funded through NIH grant UM1AI104681. For more information about this trial, visit ClinicalTrials.gov and search identifiers NCT04775953.

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NIAID conducts and supports research–at NIH, throughout the United States, and worldwide–to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH…Turning Discovery Into Health®

Source: https://bioengineer.org/trial-of-existing-antibiotic-for-treating-staphylococcus-aureus-bacteremia-begins/

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Physical activity reduces cardiovascular risk in rheumatic patients

People with diseases such as rheumatoid arthritis and lupus are more likely to have heart attacks, angina, and strokes. A

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