Exoskeletons have a problem: They can strain the brain

Exoskeletons — wearable devices used by workers on assembly lines or in warehouses to alleviate stress on their lower backs — may compete with valuable resources in the brain while people work, canceling out the physical benefits of wearing them, a new study suggests.
The study, published recently in the journal Applied Ergonomics, found that when people wore exoskeletons while performing tasks that required them to think about their actions, their brains worked overtime and their bodies competed with the exoskeletons rather than working in harmony with them. The study indicates that exoskeletons may place enough burden on the brain that potential benefits to the body are negated.
“It’s almost like dancing with a really bad partner,” said William Marras, senior author of the study, professor of integrated systems engineering and director of The Ohio State University Spine Research Institute.
“The exoskeleton is trying to anticipate your moves, but it’s not going well, so you fight with the exoskeleton, and that causes this change in your brain which changes the muscle recruitment — and could cause higher forces on your lower back, potentially leading to pain and possible injuries.”
For the study, researchers asked 12 people — six men and six women — to repeatedly lift a medicine ball in two 30-minutes sessions. For one of the sessions, the participants wore an exoskeleton. For the other, they did not.
The exoskeleton, which is attached to the user’s chest and legs, is designed to help control posture and motion during lifting to protect the lower back and reduce the possibility of injury.

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Lifting advice doesn't stand up for everyone, study finds

Commonly accepted advice to keep a straight back and squat while lifting in order to avoid back pain has been challenged by new Curtin University research.
The research examined people who had regularly performed manual lifting through their occupation for more than five years and found those who experienced low back pain as a result were more likely to use the recommended technique of squatting and keeping a straight back, while those without back pain tended not to adhere to the recommended lifting advice.
Lead researcher PhD candidate Nic Saraceni from the Curtin School of Allied Health said the study required participants to each perform 100 lifts using two differently weighted boxes, with researchers observing and measuring their action.
“We found those with low back pain were more likely to lift with a slower, less flexed low back and a more squat-like technique,” Mr Saraceni said.
“While both groups lifted using a more comparable technique at the end of the 100 lifts, the low back pain group still demonstrated a tendency to perform a slower and more squat-like lift throughout the task.
“These findings are the opposite of what is expected to occur according to existing advice on correct lifting techniques.”
Research supervisor John Curtin Distinguished Professor Peter O’Sullivan, also from the Curtin School of Allied Health, said although the study did not reveal why people with low back pain lift with a more squat-like action, the findings were in line with previous research showing people with low back pain lift in a manner that society perceives to be correct or ‘protective’ of them.
“It is likely ‘a one size fits all’ approach to preventing and managing lifting-related low back pain does not exist, rather a more individualised approach may be required, which may be the subject of future research,” Professor O’Sullivan said.
“Common assumptions that people who experience low back pain during lifting do so in a way that is ‘incorrect’ were not supported by our research and this raises questions about current advice regarding ‘safe lifting’.
The paper, “Exploring lumbar and lower limb kinematics and kinetics for evidence that lifting technique is associated with LBP,” was published in journal PLOS ONE.
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Ibrutinib effective treatment for difficult-to-treat forms of hairy cell leukemia, study finds

The oral targeted therapy drug ibrutinib is an effective treatment option for high-risk hairy cell leukemia, according to a new study conducted by researchers at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC — James).
Hairy cell leukemia is a rare form of B-cell blood cancer that is diagnosed in 600 to 800 people annually in the United States. Researchers note that while the disease generally has a good prognosis for the majority of people affected, a small group of patients with variants of the disease do not respond well to existing U.S. Food and Drug Administration (FDA) approved therapies or cannot tolerate the side effects of established therapies.
“There is a critical unmet need for therapy options in this subset of patients to achieve long-term cancer control,” said Dr. Kerry Rogers, principal investigator of the clinical trial and a hematologist/scientist at the OSUCCC — James. “Our study shows that ibrutinib (pronounced eye-broo-ti-nib) is a safe, effective and well-tolerated option for patients with relapsed or variant forms of hairy cell leukemia. It is a very important discovery for patients facing this diagnosis.”
For this phase 2 clinical trial, a multi-institutional team led by the OSUCCC — James recruited 44 patients with high-risk hairy cell leukemia to test the effectiveness of the drug ibrutinib, 15 of whom were treated in Columbus, Ohio, at the OSUCCC — James.
All study participants had either classic hairy cell leukemia and had received other treatments previously or the variant form of the disease where it is not likely that the standard therapies — the chemotherapy drugs cladribine (pronounced KLAD-rih-been) and pentostatin (pronounced PEN-toh-STA-tin) — would be effective.
Researchers reported their findings in the June 24 issue of Blood.
Ibrutinib is an oral therapy in a class of drugs known as Bruton’s tyrosine kinase (BTK) inhibitors. These drugs block specific chemical reactions in the body that are involved in cellular processes. Use of the drug for this study was considered experimental; however, ibrutinib is FDA approved for the treatment of certain cancers, including mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma and others.
“The underlying cellular biology of these diseases is similar, so we wanted to determine if this FDA-approved drug that is used to treat other forms of blood cancer could also serve as an effective treatment for this small segment of hairy cell leukemia patients who did not respond to traditional therapies,” said Rogers, who is an assistant professor in Ohio State’s College of Medicine.
“Even though hairy cell leukemia is a disease with a generally good prognosis, there is a small group of patients for whom current therapies are inadequate for cancer control,” Rogers added. “This is an effective, well-tolerated new treatment option for patients impacted by the highest-risk forms of hairy cell leukemia. It’s a very exciting development that could transform survivorship for this subset of patients from months and years, to years and decades.”
This study was sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute and grants from the National Cancer Institute/National Institutes of Health and conducted at the OSUCCC — James; the NCI clinical trials center, Karmanos; Mayo Clinic and MD Anderson Cancer Center. The study began in 2013 and is closed to patient accrual.
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Study links vaccine immune response to age

Older people appear to have fewer antibodies against the novel coronavirus, a new laboratory study from Oregon Health & Science University suggests.
Antibodies are blood proteins that are made by the immune system to protect against infection. They are known to be key players in protection against SARS-CoV-2 infection.
The study published today in the Journal of the American Medical Association.
“Our older populations are potentially more susceptible to the variants even if they are vaccinated,” said senior author Fikadu Tafesse, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine.
Tafesse and colleagues emphasized that even though they measured diminished antibody response in older people, the vaccine still appeared to be effective enough to prevent infection and severe illness in most people of all ages.
“The good news is that our vaccines are really strong,” Tafesse said.

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Chromosomes separation under focus

During cell division, chromosomes are duplicated and separated so that one copy of each chromosome is inherited by each of the two emerging daughter cells. Correct distribution of chromosomes requires high accuracy and defects in this process can cause aberrant distribution of chromosomes and facilitate cancer development. By analyzing the structure of the protein responsible for chromosome separation, an international team, led by scientists from the University of Geneva (UNIGE), has shed light on the mechanisms controlling this essential player in cell division. This work is published in the journal Nature.
Before dividing, the cell duplicates its DNA and goes from single chromosomes with one arm to double chromosomes with two identical arms linked together by a ring-shaped protein complex: cohesin. The two arms are then separated by the action of a molecular scissor — separase — which cuts a subunit of the cohesin complex to open up the ring. Once the chromosomes are separated, the cell divides and gives birth to two identical daughter cells. The cleavage of cohesin by separase is highly regulated and must occur only at a very specific time during the cell cycle. To achieve this, several inhibitory proteins independently block the activity of separase until the chromosomes have to be separated. However, up until now, the molecular mechanisms by which inhibitors control separase activity have remained elusive.
High resolution electron microscopy used to reveal regulatory mechanisms
In this study led by the team of Andreas Boland, professor in the Department of Molecular Biology at the UNIGE Faculty of Science, the scientists used cryogenic electron microscopy (cryoEM). “This technique allows us to observe biological samples at very high resolution, while maintaining them in their natural state,” explains Jun Yu, researcher in the Department of Molecular Biology and first author of this study.
Using this method, they were able to determine several structures of human separase in complex with one of its inhibitors, revealing new regulatory mechanisms for the enzyme. “It turns out that these inhibitors occupy sites that also recognize the cohesin substrate, blocking the cleavage activity of the molecular scissors,” explains Andreas Boland.
Inhibiting a protein by changing its conformation
While one of the inhibitors, securin, binds directly to the molecular scissors to block its active site, another inhibitor — the CCC complex — acts through a more sophisticated mechanism. By binding to the periphery of separase, the CCC complex induces a conformational change in separase itself. As a result, loops in separase — usually flexible and disordered — are reorganized into a fixed position, leading to an auto-inhibition of the enzyme.
“Our work significantly contributes to the understanding of the mechanisms that regulate separase activation and could help design novel anti-cancer therapies,” concludes Andreas Boland.
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Thumb-sized device quickly 'sniffs out' bad breath

No one wants bad breath — not when visiting friends and family, at a job interview, and especially not on a first date. Smelly breath can make things awkward, but it also is a natural warning sign, indicating that serious dental issues are occurring. Now, researchers reporting in ACS Nano have constructed a portable, thumb-sized device that diagnoses bad breath by quickly “sniffing” exhalations for the gas that makes it stinky — hydrogen sulfide.
Because most people can’t smell their own breath, they need to ask someone else, which can be embarrassing and awkward. Some devices measure small amounts of stinky hydrogen sulfide, but they require exhaled air to be collected and tested on expensive instruments in a lab, which is not feasible for consumers. Previous studies have shown that when some metal oxides react with sulfur-containing gases, their electrical conductivity changes. And when metal oxides are paired with noble metal catalysts, they can become more sensitive and selective. So, to develop a small, real-time bad-breath analyzer, Kak Namkoong, Il-Doo Kim and colleagues wanted to find the right combination of substances that would elicit the fastest and strongest response to hydrogen sulfide in air blown directly onto it.
The researchers mixed sodium chloride (an alkali metal salt) and platinum (a noble metal catalyst) nanoparticles with tungsten, and electrospun the solution into nanofibers that they heated, converting the tungsten into its metal oxide form. In preliminary tests, the composite made from equal parts of each metal had the largest reactivity to hydrogen sulfide, which the team measured as a large decrease in electrical resistance in less than 30 seconds. Although this nanofiber reacted with a few sulfur-containing gases, it was most sensitive to hydrogen sulfide, creating a response 9.5 and 2.7 times greater than with dimethyl sulfide or methyl mercaptan, respectively. Finally, the team coated interdigitated gold electrodes with the nanofibers and combined the gas sensor with humidity, temperature and pressure sensors into a small prototype device that was about the size of a human thumb. The device correctly identified bad breath 86% of the time when real breaths from people were exhaled directly onto it. The researchers say that their sensor could be incorporated into very small devices for quick and easy self-diagnosis of bad breath.
The authors acknowledge funding from the National Research Foundation of Korea and the Nano Convergence Foundation.
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Toward one drug to treat all coronaviruses

Safe and effective vaccines offer hope for an end to the COVID-19 pandemic. However, the possible emergence of vaccine-resistant SARS-CoV-2 variants, as well as novel coronaviruses, make finding treatments that work against all coronaviruses as important as ever. Now, researchers reporting in ACS’ Journal of Proteome Research have analyzed viral proteins across 27 coronavirus species and thousands of samples from COVID-19 patients, identifying highly conserved sequences that could make the best drug targets.
Drugs often bind inside “pockets” on proteins that hold the drug snugly, causing it to interfere with the protein’s function. Scientists can identify potential drug-binding pockets from the 3D structures of viral proteins. Over time, however, viruses can mutate their protein pockets so that drugs no longer fit. But some drug-binding pockets are so essential to the protein’s function that they can’t be mutated, and these sequences are generally conserved over time in the same and related viruses. Matthieu Schapira and colleagues wanted to find the most highly conserved drug-binding pockets in viral proteins from COVID-19 patient samples and from other coronaviruses, revealing the most promising targets for pan-coronavirus drugs.
The team used a computer algorithm to identify drug-binding pockets in the 3D structures of 15 SARS-CoV-2 proteins. The researchers then found corresponding proteins in 27 coronavirus species and compared their sequences in the drug-binding pockets. The two most conserved druggable sites were a pocket overlapping the RNA binding site of the helicase nsp13, and a binding pocket containing the catalytic site of the RNA-dependent RNA polymerase nsp12. Both of these proteins are involved in viral RNA replication and transcription. The drug-binding pocket on nsp13 was also the most highly conserved across thousands of SARS-CoV-2 samples taken from COVID-19 patients, with not a single mutation. The researchers say that novel antiviral drugs targeting the catalytic site of nsp12 are currently in phase II and III clinical trials for COVID-19, and that the RNA binding site of nsp13 is a previously underexplored target that should be a high priority for drug development.
The authors acknowledge funding from the Natural Sciences and Engineering Research Council of Canada, the European Molecular Biology Laboratory and the Structural Genomics Consortium.
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Breakthrough in detection of SARS-CoV-2 variant in wastewater

Researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, alongside collaborators from Biobot Analytics, Nanyang Technological University (NTU) and Massachusetts Institute of Technology (MIT), have successfully developed an innovative, open-source molecular detection method that is able to detect and quantify the B.1.1.7 (Alpha) variant of SARS-CoV-2. The breakthrough paves the way for rapid, inexpensive surveillance of other SARS-CoV-2 variants in wastewater.
As the world continues to battle and contain COVID-19, the recent identification of SARS-CoV-2 variants with higher transmissibility and increased severity has made the development of convenient variant tracking methods essential. Currently, identified variants include the B.1.17 (Alpha) variant first identified in the United Kingdom and the B.1.617.2 (Delta) variant first detected in India.
Wastewater surveillance has emerged as a critical public health tool to safely and efficiently track the SARS-CoV-2 epidemic in a non-intrusive manner, providing complementary information that enables health authorities to acquire actionable community-level information. Most recently, viral fragments of SARS-CoV-2 were detected in housing estates in Singapore through a proactive wastewater surveillance programme. This information, alongside surveillance testing, allowed Singapore’s Ministry of Health (MOH) to swiftly respond, isolate and conduct swab tests as part of precautionary measures.
However, detecting variants through wastewater surveillance is less commonplace due to challenges in existing technology. Next-generation sequencing (NGS) for wastewater surveillance is time-consuming and expensive. They also lack the sensitivity required to detect low variant abundances in dilute and mixed wastewater samples due to inconsistent and/or low sequencing coverage.
The method developed by the researchers is uniquely tailored to address these challenges and expands the utility of wastewater surveillance beyond testing for SARS-CoV-2, towards tracking the spread of SARS-CoV-2 variants of concern. Dr Wei Lin Lee, Research Scientist at SMART AMR and first author on the paper added, “This is especially important in countries battling SARS-CoV-2 variants. Wastewater surveillance will help find out the true proportion and spread of the variants in the local communities. Our method is sensitive enough to detect variants in highly diluted SARS-CoV-2 concentrations typically seen in wastewater samples, and produces reliable results even for samples which contain multiple SARS-CoV-2 lineages.”
Led by Associate Professor Janelle Thompson of NTU, and MIT Professor and SMART AMR Principal Investigator Eric Alm, the team’s research “Quantitative SARS-CoV-2 Alpha variant B.1.1.7 Tracking in Wastewater by Allele-Specific RT-qPCR” has been published in Environmental Science & Technology Letters. The research explains the innovative, open-source molecular detection method based on allele-specific RT-qPCR that detects and quantifies the B.1.1.7 (Alpha) variant. The developed assay, tested and validated in wastewater samples across 19 communities in the US, is able to reliably detect and quantify low levels of the B.1.1.7 (Alpha) variant with low cross-reactivity, and at variant proportions down to 1% in a background of mixed SARS-CoV-2 viruses.
Targeting spike protein mutations that are highly predictive of the B.1.1.7 (Alpha) variant, the method can be implemented using commercially available RT-qPCR protocols. Unlike commercially available products that use proprietary primers and probes for wastewater surveillance, the paper details the open-source method and its development that can be freely used by other organisations and research institutes for their work on wastewater surveillance of SARS-CoV-2 and its variants.
The breakthrough by the research team in Singapore is currently utilised by Biobot Analytics, a global leader in wastewater epidemiology headquartered in Cambridge, Massachusetts, in the US, serving states and localities throughout the country. Using the method, Biobot Analytics is able to accept and analyse wastewater samples for the B.1.1.7 (Alpha) variant and plans to add additional variants to its analysis as methods are developed.
“Using the team’s innovative method, we have been able to monitor the B.1.1.7 (Alpha) variant in local populations in the US — empowering leaders with information about COVID-19 trends in their communities and allowing them to make considered recommendations and changes to control measures,” said Dr Mariana Matus, Biobot Analytics CEO and Cofounder.
The SMART AMR team is also currently developing specific assays that will be able to detect and quantify the B.1.617.2 (Delta) variant, which has recently been identified as a variant of concern by the World Health Organisation.
“This method can be rapidly adapted to detect new variants of concern beyond B.1.1.7,” said co-corresponding author Professor Eric Alm of MIT and Principal Investigator at SMART AMR. “Our partnership with Biobot Analytics has translated our research into real-world impact beyond the shores of Singapore and aid in the detection of COVID-19 and its variants, serving as an early warning system and guidance for policymakers as they trace infection clusters and consider suitable public health measures.”
The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) programme.

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Wearable brain-machine interface turns intentions into actions

A new wearable brain-machine interface (BMI) system could improve the quality of life for people with motor dysfunction or paralysis, even those struggling with locked-in syndrome — when a person is fully conscious but unable to move or communicate.
A multi-institutional, international team of researchers led by the lab of Woon-Hong Yeo at the Georgia Institute of Technology combined wireless soft scalp electronics and virtual reality in a BMI system that allows the user to imagine an action and wirelessly control a wheelchair or robotic arm.
The team, which included researchers from the University of Kent (United Kingdom) and Yonsei University (Republic of Korea), describes the new motor imagery-based BMI system this month in the journal Advanced Science.
“The major advantage of this system to the user, compared to what currently exists, is that it is soft and comfortable to wear, and doesn’t have any wires,” said Yeo, associate professor on the George W. Woodruff School of Mechanical Engineering.
BMI systems are a rehabilitation technology that analyzes a person’s brain signals and translates that neural activity into commands, turning intentions into actions. The most common non-invasive method for acquiring those signals is ElectroEncephaloGraphy, EEG, which typically requires a cumbersome electrode skull cap and a tangled web of wires.
These devices generally rely heavily on gels and pastes to help maintain skin contact, require extensive set-up times, are generally inconvenient and uncomfortable to use. The devices also often suffer from poor signal acquisition due to material degradation or motion artifacts — the ancillary “noise” which may be caused by something like teeth grinding or eye blinking. This noise shows up in brain-data and must be filtered out.

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Toxicity testing on the placenta and embryo

Drugs must be safe not just for the patients; in the case of pregnant patients, drugs must also be safe for the unborn children still in the womb. Therefore, at an early stage in the development of new medicines, candidate substances are tested in the Petri dish on embryonic stem cells from mouse cell lines. This is to avoid that an embryo-damaging effect would only be noticed at a later stage during tests with pregnant mice.
However, these cell culture tests are a highly simplified version of what takes place in the uterus. Researchers just add the test material to a culture of embryonic stem cells in a Petri dish, and can identify substances that have a direct adverse effect on embryonic cells. By contrast, in the body of a pregnant woman, active pharmaceutical ingredients may be modified by the mother’s metabolism and enter the embryo’s bloodstream via the placenta. Moreover, standard cell culture tests can’t detect substances that have indirect effects on the embryo, for example, in that they interfere with the functioning of the placenta or generate stress responses.
A chip with different cell types
Researchers in the Department of Biosystems Science and Engineering at ETH Zurich in Basel have now devised a laboratory test that incorporates the role of the placenta into embryotoxicity assessments. To do so, Julia Boos, a doctoral student in the group of ETH Professor Andreas Hierlemann, and her colleagues developed a new chip. This chip contains several compartments, all interconnected by miniature channels. On this chip, the scientists combined human placental cells taken from cell lines with microtissue spheroids derived from mouse embryonic stem cell lines, known as “embryoid bodies,” which reflect the early development of the embryo. Test substances first encounter a layer of placental cells, which they have to pass before reaching the embryonic cells, thereby reproducing the situation in utero.
Incidentally, these experiments do not produce viable embryos. The embryonic cells from cell lines only undergo the very first steps of embryonal development over a period of ten days.
Test detects indirect damage
To demonstrate the functioning of the new test, the researchers used microparticles that did not harm the embryoid bodies if they came into direct contact. With the new test, which also includes placental cells, however, the scientists observed a potential indirect adverse effect. Although the placental cells managed to hold the microparticles back, meaning the particles did not get through to the embryonic cells, the placental cells showed a detectable stress response.
Now the researchers would like to further develop their system with regard to more suitable plastic materials. It is also conceivable to use human stem cell lines, instead of mouse cells, to form embryoid bodies in the future. “There are significant differences between lab animals and humans, particularly in terms of embryonic development and the processes taking place in the placenta,” Boos says, continuing: “Of all the organs, the placenta is where differences between the species are most pronounced.”
The group aims at creating a new test that is also easy to use for the pharmaceutical industry. Being able to detect — and eliminate — substances that are harmful to the embryo at an early stage of drug development means that fewer substances will subsequently be tested on animals in in-vivo studies.
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Materials provided by ETH Zurich. Original written by Fabio Bergamin. Note: Content may be edited for style and length.

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