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Current prosthetic heart valves for children with congenital heart disease are fixed in size, requiring repeated open-heart surgeries during childhood to replace the valve with a larger version. But a surprising new design created at Boston Children's Hospital could allow children to keep the same prosthetic valve until adulthood, and could also benefit adults with heart valve defects. The new device is described in Science Translational Medicine, published online February 19.

Benchtop studies, computer simulations and extensive testing in large animal models demonstrate that the new prosthetic valve design works across a wide range of sizes, and that the valve retains its functionality when expanded via a minimally invasive balloon catheter procedure.

"We hope to bring this new device into clinical testing fairly rapidly," says Pedro J. del Nido, MD, Chairman of Cardiovascular Surgery at Boston Children's Hospital and senior author on the paper. "If our preclinical results hold up in human testing, this could transform the field."

Less is more: Two valve leaflets versus three

More than 330,000 children worldwide are born with a heart valve defect, and millions of others develop rheumatic heart disease requiring early valve replacement. Current prosthetic heart valves are fixed in diameter, so typically need to be replaced every few years; children receiving their first replacement before age 2 will need as many as five high-risk open-heart operations before reaching adulthood.

Commercially available prosthetic heart valves have three leaflets, tiny flaps that provide a one-way inlet or outlet for blood to keep it flowing in the right direction. The new design was inspired by human venous valves, located in the deep veins of the leg. Unlike our hearts' native outflow valves, our venous valves have just two leaflets, and a geometry that is optimized to maintain closure and one-way flow even when the veins expand in diameter to accommodate larger volumes of blood passing through.

"Veins carry approximately 70 percent of our blood volume," says Sophie C. Hofferberth, MD, a surgical resident at Brigham and Women's Hospital who led the research in del Nido's lab at Boston Children's. "The vein dimensions can change dramatically depending on body position, yet the valves must remain functional. We mimicked the geometric profile of the human venous valve to design a bileaflet valve of programmed dimensions that is adaptable to growth without loss of one-way flow control."

In multiple rounds of testing, in both benchtop and large animal models, valve prototypes with the biomimetic two-leaflet design were able to expand to accommodate growth and structural asymmetries within the heart. The valves remained fully functional across a wide range of dimensions, at a range of pressure and flow rates.

Because the valve is designed to expand without requiring the frame and leaflet to stretch or enlarge, it is compatible with a range of off-the-shelf materials, the researchers say. The study showed the device could be effectively expanded at multiple timepoints in a growing animal model, using a minimally invasive balloon catheter approach.

Potential for fewer blood clots

The researchers also observed that their "geometrically adaptable" design encourages a favorable blood flow profile through the valve, potentially reducing the risk for blood clot formation often seen with existing valve replacement devices. In the growing sheep model, there was no evidence of blood clot formation over 10 weeks of observation, even without the use of blood-thinning medication typically given to prosthetic valve recipients.

"A shortcoming of many existing devices is the presence of flow disruptions that lead to blood clot formation and early valve deterioration," says Hofferberth, who is first author on the paper. "Our design achieves a favorable flow profile that seems to facilitate effective valve washout and minimize flow stagnation, which is likely to be an important determinant of long-term device durability."

The research team believes their data support initiation of a clinical study within one to two years.

Oakland, Calif. - In a study published in JAMA Network Open today, Kaiser Permanente scientists report that diabetes patients who used the Kaiser Permanente patient portal and mobile phone app improved their diabetes management outcomes. The large study, involving more than 111,000 patients, was unique in assessing the relationship between the use of online tools and medication adherence and blood glucose levels.

"This is an example of how the health care system, by offering patients access to their own information and the ability to manage their health care online, can improve their health," said senior author Mary Reed, DrPH, a research scientist with the Kaiser Permanente Division of Research. "Offering this in a mobile-friendly way can give even more patients the ability to engage with their health care. It literally puts the access to these tools in the patient's own pocket wherever they go," Reed said.

The study looked at Kaiser Permanente Northern California members with diabetes who were taking an oral diabetes medication but not insulin. The researchers compared patients' portal use from 2015 to 2017. Online tools available to Kaiser Permanente members include prescription management, viewing test results, corresponding by secure message with clinicians, making appointments, and access to general health information.

Over the 33-month study period, the proportion of patients using the portal from both a computer and a mobile device increased from 34% to 62%. The greatest improvement in health outcomes was among patients with a higher baseline HbA1c (hemoglobin A1c) level; in these patients, moving from no portal access to both computer and mobile app was associated with a 5.09 percentage point increase in medication adherence and 0.19 percentage point lower HbA1c level.

The study's lead author was Ilana Graetz, PhD, an associate professor in the Rollins School of Health Policy and Management at Emory University. "Patients with greater clinical need were able to benefit even more from mobile portal access, both in taking their medications more often and in actually improving blood sugar levels," Graetz said.

Among all patients studied, moving from no portal use to using both methods was associated with a 1.67 percentage point increase in medication adherence and 0.13 percentage point lower HbA1c level.

"These modest but clinically meaningful improvements in HbA1c associated with gaining mobile portal access may result in potential downstream prevention or reduction in complications or other adverse clinical health events," the authors wrote.

A strength of the study design was that patients served as their own controls, comparing the behavior of individuals before and after access to the portal and mobile app.

In previously published research, Graetz reported that patients who accessed the tools only on mobile devices were more likely to belong to racial and ethnic minorities, live in lower socioeconomic status neighborhoods, or have lower medication adherence. Reed said this insight suggests an opportunity for health systems to use mobile apps to reach vulnerable patients who might have barriers to engaging with health care.

The study was the latest publication to result from a 10-year project headed by Reed and funded by the National Institute of Diabetes and Digestive and Kidney Diseases, to examine the role of health information technology in managing diabetes. Reed and colleagues explored how medical providers use electronic health records to collaborate and improve patient care. As time went on and patients gained more access to health information online, the study shifted focus.

"In an earlier study, we found that when a physician uses an electronic health record, their patients have better control of their diabetes and have their care managed so they don't end up in the emergency room as often," Reed said. "And we are now also finding that patients can use technology to better manage their own care, their medications, and their diabetes."

Reed's group is continuing this line of inquiry to study the impact of video telemedicine visits on diabetes care and self-management.

Taking a step towards a major goal in heart valve prosthetics, scientists have created an adaptable heart valve replacement that can be expanded over time as the heart grows. The artificial valve safely worked in growing young lambs for a period of up to 10 weeks. Although studies with longer follow-up times are needed to further validate the design, the device could offer a superior alternative to traditional, fixed-diameter heart valve prostheses that cannot grow along with a child's heart. More than 1.35 million children worldwide are born with a congenital heart disorder each year, resulting in an annual expense of around $6 billion. Of these disorders, most that involve heart valves are treated with prosthetic replacements. But children with these valves must undergo up to five invasive open-heart surgeries to replace their valves before reaching adulthood, leaving them at risk of stroke, hospital stays and even death. To provide a more permanent solution that reduces surgical burden, Sophie Hofferberth and colleagues created a heart valve that draws inspiration from valves in human veins, which can expand and contract to handle large changes in blood flow volume. Their valve is composed of two synthetic leaflets attached to a stent and can be manually expanded with a balloon catheter to accommodate larger volumes of blood moving through the heart. When implanted into four young lambs and four adult sheep, the prosthetic valves showed good performance without impeding blood flow. In a separate test in seven other lambs, the valves remained functional for 10 weeks without causing injury or major inflammation. The scientists caution that longer-term animal studies should assess the valve's durability and effects on the heart, as well as the structural integrity of the expandable leaflet design.

People living in Balkan farming villages along the Danube River have long suffered from a unique type of kidney disease known as Balkan endemic nephropathy. Recently, scientists linked the disorder to compounds from a local weed that could be taken up into food crops from the soil. Now, researchers reporting in ACS' journal Environmental Science & Technology have discovered that contaminated groundwater could be another important source of human exposure.

Aristolochic acids (AAs) were recognized as potent kidney toxins after people taking herbal medicines containing the compounds developed kidney disease. A weed that is widespread in the Balkan regions, Aristolochia clematitis L., produces AAs, and when the plant decays, it releases the toxic compounds into the soil. As a result, scientists have detected AAs in Balkan food products. Nikola Pavlovi?, Wan Chan and colleagues wondered if the weed-derived compounds could also leach into groundwater, polluting the drinking water of local residents.

To measure AAs in water, the researchers used a positively charged silica-based sorbent to collect AAs, which are negatively charged, from water samples. They released the AAs from the sorbent and then converted the substances to aristolactams for detection by mass spectrometry. The team applied this new method to the analysis of 123 water samples collected from wells in rural Serbia. They found that the groundwater was extensively contaminated with one form of AA at nanogram/liter levels. These results suggest that drinking, cooking and irrigating with the contaminated water is a highly important, but previously unrecognized, source of AA exposure. Weed control of A. clematitis is urgently needed to reduce the incidence of Balkan endemic nephropathy, the researchers say.

The authors acknowledge funding from the TUYF Charitable Trust and the University Grants Committee of Hong Kong.

The abstract that accompanies this study is available here.

For more research news, journalists and public information officers are encouraged to apply for complimentary press registration for the ACS Spring 2020 National Meeting & Exposition in Philadelphia.

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Current tests for male fertility include measuring the concentration and motility of spermatozoa. However, other characteristics of sperm, such as their ability to follow a chemical trail to the egg, can influence the likelihood of fertilization. Now, researchers reporting in Analytical Chemistry have devised a quick and convenient microfluidic chip to assess this chemotactic response of spermatozoa, which could help provide a more complete picture of a man's fertility.

Sperm use chemotaxis, or movement toward increasing or decreasing concentrations of a substance, to guide their journey through the fallopian tube to the egg. Progesterone is present at high concentrations in the fluid that surrounds the egg, and previous studies have indicated that the hormone can attract and activate spermatozoa of some mammalian species. Scientists have used microfluidic devices -- plastic or hydrogel chips with tiny channels through which liquids flow in a highly controlled manner --to study sperm chemotaxis. But the devices have had various limitations, such as the need for pumps to drive the flow of fluid, which could affect sperm motility. Loes Segerink, Johanna Berendsen and colleagues wanted to develop an improved, pump-free microfluidic device that could quickly identify small differences in the chemotactic behavior of sperm.

The researchers designed a microfluidic chip about the size of a postage stamp. The chip, which they made with an agarose/gelatin material, contained various channels and side chambers. The researchers created a concentration gradient of progesterone in the device from left to right, and saw that more boar spermatozoa added to the device swam to the right side chambers (high progesterone) than the left (low progesterone), which shows chemotactic movement. In addition to fertility testing, the device could be used to investigate other substances that could also contribute to sperm's guidance mechanism, the researchers say.

Researchers at the University Of Liverpool, in collaboration with NUI Galway and TU Berlin, have identified the key technological and scientific challenges of producing hydrogen through seawater electrolysis.

In an article published in Nature Energy, researchers assessed the various issues hindering the development of electrolyser technologies capable of carrying out direct water electrolysis using low grade water, such as seawater, as opposed to ultrapure water.

Generating hydrogen using saline water electrolysis provides an attractive route towards energy sustainability. Hydrogen is a clean and storable fuel which provides a viable fuel option for transport amongst other uses, and would be highly beneficial for coastal, rural and offshore installations.

Researchers undertook a review of recent developments in the field of saline water electrolysis and examined the challenges in the design of electrolysers.

They found there was an urgent need for new catalysts and electrode materials that can overcome the competition between chlorine chemistry and water oxidation in seawater.

Whilst some progress has been made towards this goal in recent years, long-term stability and selectivity has not been achieved.

They also identified a real need for standardisation of testing conditions to ensure that meaningful comparisons between those materials discovered can be made.

Professor Alex Cowan from the University of Liverpool's Stephenson Institute for Renewable Energy, said: "This paper, which is an important part of the SEAFUEL project, identifies the key issues and critical barriers hindering the development of seawater electrolysis for hydrogen production.

"There is a strong need for further research programmes, such as those being delivered in the labs at Liverpool, Galway and Berlin, to overcome these challenges

"It is clear that an urgent need exists for new advanced electrode materials and catalysts and at Liverpool we have exciting research to directly address this issue which is beginning to deliver chloride tolerant catalysts."

The research at Liverpool and Galway was funded by the SEAFUEL (Sustainable integration of renewable fuels in local transportation) project which aims to demonstrate the feasibility of powering local transportation using fuels produced by renewable energy and seawater, with no net carbon footprint.

The Suzuki-Miyaura reaction is a well-known chemical process in which a reaction between organic boronic acids and aryl halides leads to the synthesis of "biaryl" compounds, which are important components of various drugs and chemical products. This is also called cross-coupling, as two aryl molecules are combined, or cross-coupled, in this process. Because the organic aromatic molecules--which are formed as a result of this reaction--have various applications, such as in solvents and drugs, finding a way of optimizing the existing cross-coupling reactions is crucial. This is why, in a new study published in ACS Catalysts, a team of scientists from Japan, including Junior Assoc Prof Yuichiro Mutoh and Prof Shinichi Saito of Tokyo University of Science, wanted to check if this reaction can be made more efficient.

"Protected" organic boronic acid, which is an organic boronic acid with a "masking group," is frequently used as a precursor for boronic acid in the Suzuki-Miyaura reaction. Because the reactivity of the protected boronic acid is low, it does not take part in this reaction. Thus, the masking group needs to be removed for the reaction to proceed, which adds another step to the process. This made these scientists wonder: what if the masked molecules were directly used in the reaction? It would lead us to a much faster, cheaper technique! Prof Saito explains, "Because the removal of the masking group is necessary to provide the latent boronic acids that engage in subsequent Suzuki-Miyaura reactions, the direct use of the protected boronic acid in a Suzuki-Miyaura reaction would be highly desirable in terms number of steps and atom economy. This would help streamline the synthesis of complex molecules." The only challenge was that until now, there was no known way to directly use protected boronic acids without removing the masking group first, and thus, the scientists set out to find ways to do this.

The scientists knew that the process required a palladium catalyst (a molecule or compound that can speed up a reaction), a base, and two starting aryl molecules. They proceeded to check if the reaction takes place with a protected molecule. To begin with, they examined the impact of various bases on the reaction. They saw that when a particular potassium base, called KOτ-Bu, was used, it resulted in a high yield of products, and this effect as not seen with other bases. Then, they tested various palladium-based catalysts and saw that all catalysts produced a similar yield, indicating that common palladium-based catalyst systems can be used for the cross-coupling. This led them to conclude that the KOτ-Bu base played a crucial role if one was to use protected boronic acid directly. After over a dozen successful Suzuki-Miyaura reactions with high yield for different biaryl compounds, the team conducted "control" experiments to check for other variables and to gain insight into the underlying mechanisms of the KOτ-Bu base. Specifically, they checked if the chemical species were present in the reaction mixture before the reaction was complete, which uncovered an intermediate compound involving the KOτ-Bu base and the boronic acid reagent. Using techniques like NMR spectroscopy and single-crystal X-ray diffraction analysis, the scientists confirmed that the key to the success of these cross-coupling reactions is the use of KOτ-Bu as the base, as it enables the formation of an active borate, essential for the reaction.

The methodology discovered in this study provides insight into the Suzuki-Miyaura reaction and proposes a novel way in which the required steps to use protected boronic acids can be minimized. The entire process to obtain biaryl molecules was carried in one single pot, which is advantageous in terms of space and cost. Prof Saito concludes, "We developed a way for the reaction to be step- and pot-economic, features that have received considerable attention in recent years. Thus, this study opens up new possibilities for the use of protected boronic acids in various coupling reactions."

Owing to its novel findings, this study was even selected to be on the cover of the January 2020 issue of ACS Catalysis. These findings will hopefully help simplify the synthesis of important complex molecules, including pharmaceutical drugs, so that more people can benefit from advances in the chemical sciences.

The old story of a farmer trying to get a stubborn mule to pull a wagon by dangling a carrot in front of its nose, or hitting its rump with a stick, may not seem to have much to do with the practice of medicine.

But a new study suggests that when it comes to making the best use of health care dollars, it will take a combination of carrots and sticks to move things forward.

The study looks at the effects of two initiatives that aimed to reduce the use of two blood tests that experts consider "low value" for most patients: Routine vitamin D tests, and an unnecessary thyroid test for tracking thyroid hormone levels.

After an organization that advises the health care system in Ontario, Canada reported in 2010 that population-based Vitamin D screening does not improve outcomes, the province's health plan for all residents declared it wouldn't pay for low-value vitamin D tests.

Soon after, the rate of testing dropped nearly 93 percent, the study shows. Patients who had a condition or medication that might lower their vitamin D levels could still get tested.

But in the U.S., where no such payment change took place, 2.6 million unnecessary vitamin D screening tests happened in just one year, according to the researchers from the University of Michigan, University of Toronto and VA Ann Arbor Healthcare System who published the new findings in JAMA Internal Medicine.

A few years later, as part of an education campaign called Choosing Wisely, physician professional societies issued recommendations on when not to use Vitamin D and T3 testing. And while use of the test in Ontario dropped an additional 4.5%, the use in U.S. patients covered by Veterans Health benefits or commercial insurance dropped about 14%.

"Our study found small reductions in the use of unnecessary vitamin D screenings in response to recommendations from the Choosing Wisely campaign, but much greater reductions in Ontario when recommendations were complemented by policy change," says Eve Kerr, M.D., M.P.H., senior author of the new paper and a professor in the U-M Department of Internal Medicine. "The biggest lesson is that while recommendations alone can work to reduce low value care, recommendations have greater impact when they are reinforced by changes to policy and practice."

Improving value

Kerr heads a program at the U-M Institute for Healthcare Policy and Innovation called the Michigan Program on Value Enhancement. She and her colleagues used the same Choosing Wisely guideline to build an alert for clinicians who had ordered a vitamin D test of low potential value into the electronic health record at Michigan Medicine, U-M's academic medical center.

In 2018, they reported that this guideline-based "carrot" had led to a positive and sustained change in orders for low-value vitamin D tests.

James Henderson, Ph.D., the first author of the new paper, assistant director of MPrOVE and a data science consultant at U-M's Consulting for Statistics, Computing and Analytics Research unit, notes that the new paper's findings show that Choosing Wisely recommendations for T3 testing did not appear to have had the desired impact.

T3 testing, which is no longer recommended for patients with known thyroid issues because a test called TSH is more accurate, did not decline in either the U.S. or Canada after Choosing Wisely guidelines were issued. In fact, in the study population of U.S. patients with private insurance, the rate of testing actually went up slightly.

Handle with care

Kerr, Henderson and their colleagues from IHPI and the VA Center for Clinical Management Research note that policy decisions for low-value care - including payment changes - must be made with care, to avoid problems with access to that type of care for patients who could benefit.

For instance, the Ontario payment change exempted patients who have bone or digestive disorders that can change vitamin D levels, and patients who take certain medications that can change vitamin D absorption from food and supplements.

"Payment policies are not the only effective means for reducing low-value care," says Kerr. "Indeed, sometimes restricting payment may be too blunt an approach and could lead to underuse."

She adds, "Other effective policies that can be coupled with recommendations include population based education programs, communication approaches to help patients and physicians make more patient-centered decisions, decision support for doctors about low-value care, and most importantly, culture change initiatives that emphasize the responsibility of health care institutions, clinicians, and patients to provide and seek high-value, evidence-based care while avoiding low-value services."

Increased resources, surveillance, and capacity building should be urgently prioritised in African countries with moderate risk of importing cases of novel coronavirus disease 2019 (COVID-19), as these countries are estimated to be ill-prepared to detect cases and limit transmission.

The new findings are from a modelling study published in The Lancet that estimates the preparedness (ie, health system capacity) and vulnerability (ie, demographic, environmental, socioeconomic and political conditions that could impact a country's ability to respond) of African countries, as well as their likelihood of importing COVID-19 cases from China. The authors note that their findings need to be interpreted in context, and they estimate that the overall risk of importing COVID-19 cases to Africa is lower than to Europe (1% vs 11% of people travelling out of China go to Africa or Europe, respectively) but that the response and reaction capacity is more limited in Africa.

Algeria, Ethiopia, South Africa, and Nigeria were included in the 13 top priority countries identified by the World Health Organization (WHO), based on their direct links and volume of travel to China [1]. The first case of COVID-19 in Africa was confirmed in Egypt on Friday 14 February 2020.

China is Africa's leading commercial partner with high volumes of travel between the two locations through which the novel coronavirus could reach the continent.

Several measures to prevent importing cases from China have already been implemented in many African countries. However, limiting and controlling transmission after importation requires additional measures (such as heightened surveillance, rapid identification of suspected cases, patient transfer and isolation, rapid diagnosis, contact tracing, and follow-up of potential contacts). These measures require technical and operational expertise and resources, which rely heavily on health systems, meaning that transmission in countries with weaker health systems is a major public health concern.

"African countries have recently strengthened their preparedness to manage importations of COVID-19 cases, including airport surveillance, temperature screening at ports of entry, recommendations to avoid travel to China, and improved health information provided to health professionals and the general public. However, some countries remain ill-equipped," says study author Dr Vittoria Colizza, Inserm, Sorbonne Université, France. [2]

She explains: "While almost three-quarters of all African countries have an influenza pandemic preparedness plan, most are outdated and considered inadequate to deal with a global pandemic. In addition, despite efforts to improve diagnostic capacity from WHO, some countries do not have the resources to test for the virus rapidly, meaning that tests would need to be done in other countries. It is essential to train, equip, and strengthen the diagnostic capacities of hospital laboratories close to infectious disease and emergency departments to reduce the time to deliver results, manage confirmed cases and contacts more rapidly, and preserve strict infection control measures. Equally, increasing the number of available beds and supplies in resource-limited countries is crucial in preparation for possible local transmission following importation." [2]

In the study, the authors estimated the risk of African countries importing a COVID-19 case from China using data on the volume of air travel from infected Chinese provinces to Africa and the proportion of COVID-19 cases in the Chinese provinces as of 11 February 2020. The Hubei province was not included, given the travel ban introduced by Chinese authorities on 23 and 24 January 2020.

The authors estimated each country's potential capacity to detect and respond to cases based on two WHO indicators: preparedness (ie, functional capacity to manage emerging epidemics, using the WHO International Health Regulations Monitoring and Evaluation Framework State Party Self-Assessment Annual Reporting) and vulnerability (ie, ability to manage emerging epidemics based on demographic, environmental, socioeconomic and political conditions, using the Infectious Disease Vulnerability Index). The African countries at risk of importing cases were grouped by the Chinese provinces estimated to contribute most to their risk.

Egypt, Algeria and South Africa were at the highest risk of importing a COVID-19 case from China, but had moderate to high preparedness and low vulnerability.

There were several countries in the group with the second highest risk of importing a case from China, and their levels of preparedness and vulnerability varied. For example, Nigeria and Ethiopia had moderate preparedness, but high vulnerability, and their countries had substantially larger populations that could be potentially exposed. However, Morocco, Sudan, Angola, Tanzania, Ghana, and Kenya had similar importation risk and population sizes, but variable levels of preparedness and high vulnerability (except Morocco which had low vulnerability).

All other African countries had low to moderate importation risk with low to moderate vulnerability and mostly low preparedness, except for Tunisia and Rwanda.

The authors grouped the at-risk African countries by the Chinese provinces that could potentially lead to the cases being imported. Cluster number 1 (18 countries) was highly exposed to Beijing, and moderately exposed to Guangdong province and Shanghai, cluster number 3 (Botswana and Lesotho only) was exposed exclusively to the potential risk from airports in the Fujian province, and cluster number 2 (7 countries) was heavily exposed to risk from Guangdong province and weakly to Zhejiang province. [3]

The authors warn that although certain Chinese provinces potentially pose higher risk of importing cases to Africa, enhanced surveillance at airports should still consider possible importations from lower-risk provinces. In addition, shifts in local and widespread transmission in Beijing, Guangdong, and Fujian provinces could have profound implications for risk in Africa.

Dr Colizza concludes: "The aftermath of recent epidemics and pandemics (eg, severe acute respiratory syndrome, H1N1 pandemic, Middle East respiratory syndrome, and Ebola) have highlighted the need to reinforce national public health capabilities and infrastructure. These factors remain at the core of global health security, because they are the first line of defence in infectious disease emergencies. Crisis management plans should be ready in each African country, and involvement of the international community should catalyse such preparedness. We hope that our estimates help to inform prioritisation for intensified support in African countries expected to be at moderate to high risk of importation of COVID-19 cases and with relatively low capacity to manage the health emergency." [2]

The authors note some limitations in their study, including that it only used air travel data, and the risk of importation from other points of entry, such as seaports, was not evaluated. In addition, there was insufficient passenger data (reason for travel [tourism vs business], nationality, age, sex, and socioeconomic status) to allow the authors to assess differences in risk for different types of travellers.

When you look through a microscope, whatever is on the stage is magnified to a degree the naked eye can hardly imagine. While traditional microscopy techniques allow miniscule details to come into view, standard equipment doesn't provide us with the full picture.

Most optical microscopes have a limited field of view, only one to two millimeters. This is a major inconvenience for life scientists and pathologists who rely on microscopy to analyze and diagnose disease since prepared tissue samples have dimension in the centimeter range.

To address this unmet clinical need, a new microscopy platform developed at UConn removes a central component of traditional microscopes - objective lenses. By going lensless, researchers can actually provide clinicians a fuller picture, leading to more accurate diagnoses.

Guoan Zheng, a University of Connecticut professor of biomedical engineering, recently published his findings on a successful demonstration of a lensless on-chip microscopy platform in Lab on a Chip. This platform eliminates several of the most common problems with conventional optical microscopy and provides a low-cost option for the diagnosis of disease.

Rather than using lenses to magnify the tissue sample, Zheng's platform relies on a diffuser that goes between the specimen and the image sensor or camera. The diffuser randomly moves to different positions while the sensor acquires the images, gathering the encoded object information that will later be used to recover an image for viewing by clinicians or researchers.

At the heart of the object recovery process is an imaging technique called ptychography. Ptychographic imaging typically uses a focused beam to illuminate a sample and record the pattern created by the diffracted light. To recover an entire complex image - like a tissue sample - for viewing, ptychography requires thousands of patterns to be recorded while scanning the sample to different positions.

"Although ptychography has been of increasing interest to scientists around the world, broad implementation of the method has been hampered by its slow speed and the requirement of precise mechanical scanning," says Shaowei Jiang, a UConn graduate student and the lead author of the study.

Zheng's new ptychographic technology addresses these issues by bringing the sample close to the image sensor. This new configuration allows the team to have the entire image sensor area as the imaging field of view. In addition, it no longer requires the precise mechanical scanning needed for traditional ptychography. This is because the new configuration has the highest Fresnel number ever tested for ptychography, approximately 50,000. The Fresnel number characterizes how a light wave travels over a distance after passing through an opening, such as a pinhole. The ultra-high Fresnel number used in Zheng's experiments indicates that there is very little light diffraction from the object plane to the sensor plane. Low levels of diffraction mean that the motion of the diffuser can be directly tracked from the captured raw images, eliminating the need for a precise motion stage, which is critical for conventional ptychography.

"This approach cuts down on processing time, cost, and allows for a more complete image to be produced of the sample," says Zheng.

With conventional lensed microscopy, scientists can only view a small portion of a slide during each viewing. Zheng's platform offers a major improvement by effectively expanding the microscope's field of view. Zheng's current prototype offers a 30 mm2 field of view, compared to the standard ~2 mm2. By using a full-frame image sensor in a regular photography camera, Zheng's technology allows physicians to analyze two entire slides at once.

"Imagine being able to read a whole book at once instead of just a page at a time. That's essentially what we hope our technology will allow clinicians to do," says Zheng.

Adding to its already long list of improvements, Zheng's platform eliminates the need for cell staining. Normally, scientists stain parts of cells, like the nucleus, to identify how many there are. Zheng tested this platform's ability to perform automatic cell segmentation using the recovered label-free phase maps.

Due to its compact configuration and robust performance, Zheng and his team envision that their platform would be a good fit for use in a range of point-of-care, global health, and telemedicine applications. Their technology can also be useful for X-ray and electron microscopy.

"By using our lensless, turnkey imaging system, we can bypass the physical limitations of optics and acquire high-resolution quantitative information for on-chip microscopy. We're excited to continue to refine this technology for commercial and clinical applications to have a tangible impact for patients and researchers," Zheng says.

The Himalayan wolf is considered an ancient wolf as it evolved prior to the contemporary grey wolf which is found in large parts of North America and Eurasia. Very little is known about the Himalayan wolf, because science and conservation have overlooked these high-altitude wolves as just another grey wolf until recently. As a result, very little research had been conducted on this wolf and no conservation action has been in place, risking a silent population decline of this wolf. This research, published today in the Journal of Biogeography, reveals this wolf's evolutionary uniqueness based on many different genetic markers; including a genetic adaptation to cope with the high-altitude environment, which is an adaptation that is not found in any other wolf. The Himalayan wolf is a top carnivore in the Asian high-altitudes, which hold some of the last intact large wilderness areas on our planet. The protection of the Himalayan wolves is critical to preserve these ecosystems given that top carnivores are key to keep an ecosystem healthy and balanced. This becomes even more relevant when considering that the Asian high-altitudes hold the water resources for billions of people in south-east Asia and it is of global interest to keep those ecosystems and their wildlife populations healthy.

The insights gained in this research by scientists at the University of Oxford's Department of Zoology further inform the development of long-term sustainable conservation plans for these wolves and their high-altitude ecosystems.

Lead researcher, Dr Geraldine Werhahn of WildCRU, Department of Zoology, says: 'The outcome of this research is absolutely astonishing. When we started out in 2014 it was surprising how little was known about these wolves inhabiting a relatively large region of our planet. At the time the scarce data available was indicating a genetic difference, but we had no explanation for why these wolves are different from a grey wolf.'

'Now we know that these wolves are different from genetics to ecology, and we have an indication of what the reason may be: the evolutionary fitness challenge posed by the low oxygen levels in the extreme high altitudes. When we started this research we thought this wolf is found only in the Himalayas, but now we know that they are found in the entire high altitude regions of Asia comprising the habitats of the Himalayas and the Tibetan Plateau. Much still remains to be revealed about their ecology, behaviour and population size. But the time to protect them is now!'

The researchers observed where the wolves chose their den sites and found that in Nepal the Himalayan wolf pack sizes are on average five animals and hence smaller than usual grey wolf packs. These insights into the wolves' social life combined with observations on the livestock herding practices in these high-altitudes helps to identify areas of immediate conflict between herding and wolf pup rearing and propose mitigation action. The researchers observed exclusive denning behaviour of Himalayan wolves and their pups.

The studies used wolf scat sampling for genetic and genomic research to understand their evolutionary history based on a wide array of different genetic regions. It also used the scats for a dietary study, investigating what prey species the wolves and other carnivores have eaten. The researchers studied which prey species and at which amount were eaten by the wolves and compared that to the abundance of these same prey species in the landscape to understand what the wolves had available and what they have actually taken.

The researchers found that the Himalayan wolf use more wild prey species than livestock when considering their availability and identified the main prey species for the Himalayan wolf. Livestock is seasonally often more abundant in the habitats than wild prey species, which poses two problems. Firstly, the wolves encounter much more livestock than wild prey. Secondly, livestock competes with wild prey for food and space and often displaces wild prey species. As a result, the wolves are left with little choice but to kill livestock. This is a key finding for developing conservation action for the Himalayan wolf, with solutions being to restore and protect wild prey populations and working towards sustainable livestock herding practices.

The main conservation threats appear to be the killing of wolves to retaliate livestock depredation, as well as for selling body parts in the flourishing illegal wildlife trade. Livestock is a major livelihood of many local communities in these harsh high-altitude environments, and losses of livestock has serious financial consequences for people. Improving livestock protection and sustainable management can mitigate depredation conflict substantially. Illegal wildlife trade involves many wildlife species found in these high-altitude regions, with the animal parts often traded for high prices. This illegal wildlife trade needs to be drastically combated from political to ground level across the countries to the benefit of many wild species.

In addition, a social survey study with local communities helps to understand what people want and need to be able to commit to wildlife protection in these regions.

Local people expressed the wish to be closely involved in conservation work. Community conservation groups have proven successful in Himalayan areas.

These research findings can now be used as data basis to formerly recognize the Himalayan wolf as an own wolf taxon (giving it a scientific (Latin) name). This formal taxonomic recognition paves the way to assign it an IUCN conservation status. These are the two pivotal steps now required to advance the conservation of these wolves and their habitats.

With these fundamental researches now accomplished, moving forward research is planned to explore behavioural and more detailed ecological aspects around these wolves, while also piloting a conservation action plan with the local communities to develop a plan for the Himalayan wolf that shall be applicable across the Himalayan region in the long term.

Atopic dermatitis, a chronic inflammatory disorder, affects some 30 million Americans every year. It is the most common cause of eczema, a condition marked by unbearably itchy, flaky patches of skin.

A new Tel Aviv University study identifies the precise receptor chain involved in the development of atopic dermatitis. The researchers hope to develop an antibody based on this research to create a therapeutic drug.

Research for the study was led by Prof. Ariel Munitz of the Department of Clinical Microbiology and Immunology at TAU's Sackler School of Medicine and Prof. Itai Benhar of the School of Molecular Cell Biology and Biotechnology at TAU's George S. Wise Faculty of Life Sciences and their PhD students Almog Bitton and Shmuel Avlas. It was published in Science Immunology on February 14.

"Atopic dermatitis is a serious, chronic condition that is usually detected in childhood. It's also associated with the development of such allergic diseases as asthma," Prof. Munitz explains. "We have now identified the chain of receptors involved in the pathology of this chronic condition that places such a burden on so many millions of people, not to mention health systems worldwide."

The clinical symptoms of atopic dermatitis are caused by two proteins, which are associated with multiple allergic diseases: interleukin 4 (IL-4) and interleukin 13 (IL-13). "The role of these proteins is so important that many pharmaceutical companies have targeted them for drug development for atopic dermatitis and for asthma," Prof. Munitz says. "In fact, recently the FDA has approved the use of an anti-IL-4 receptor antibody for the treatment of this condition."

While IL-4 and IL-13 mediate atopic dermatitis, the precise contribution of each of these proteins to the development of the disease was unknown. Both proteins use a complicated, often overlapping and complex set of receptors to mediate their activities.

In an attempt to better understand the pathology of atopic dermatitis and to identify new drug targets for treatment of the condition, the TAU researchers set out to identify the precise contribution of IL-4 versus that of IL-13 in atopic dermatitis. To do so, they harnessed mouse models that lacked the specific receptor chain: IL-13 receptor α 1, as well as various preclinical mouse models of atopic dermatitis.

"We identified that the IL-13 receptor alpha chain plays a critical role in atopic dermatitis," Prof. Benhar says. "In fact, we show that IL-13Rα1 mice that lack the IL-13 receptor α 1 do not develop the disease at all.

"Finally, we showed that a newly generated antibody was capable of reducing atopic dermatitis in mice. To translate our findings into human atopic dermatitis, we generated a novel antibody targeting the human IL-13 receptor α 1 and demonstrated that this antibody may serve as a prototype to treat the disease as well as other allergic diseases such as asthma or eosinophilic esophagitis," Prof. Benhar concludes.

Risky drinking is a significant problem for youth and young adults, and mass media messages--such as TV commercials--are frequently used in campaigns aimed at warning them about alcohol use. But how these videos effectively increase awareness of risky drinking, or if they reduce alcohol use in an audience, is not always clear. A new study published in NeuroImage has applied the science of brain synchronisation to assessing the success of alcohol risk campaigns. The results show that the stronger, more engaging videos led to more synchronised brain activity in viewers and that this was associated with subsequent reductions in risky drinking. By showing that neural measures can help to predict alcohol message success, the study shows promise for applications in public health.

Irvine, Calif., Feb. 19, 2020 -- A secret to survival amid rising global temperatures could be dwelling in the tidepools of the U.S. West Coast. Findings by University of California, Irvine biologists studying the genome of an unusual fish residing in those waters offer new possibilities for humans to obtain dietary protein as climate change imperils traditional sources. Their paper appears in Proceedings of the Royal Society B.

The fish, Cebidichthys violaceus, is colloquially known as the monkeyface prickleback. With an acidic stomach and small and large intestines, it has a digestive system similar to that of humans. The monkeyface prickleback is among just five percent of the 30-thousand fish species that are vegetarian, nourishing themselves only with the specialized algae in the tidepools where they live.

This characteristic captured the attention of Donovan German, associate professor of ecology & evolutionary biology, researcher Joseph Heras and colleagues. They wanted to figure out how the monkeyface prickleback survives on a food source containing a low level of lipids, which are essential for all living beings. By sequencing and assembling a high-quality genome for the fish, the team discovered the secret.

"We found that the monkeyface prickleback's digestive system is excellent at breaking down starch, which we anticipated," said German. "But we also learned it has adapted to be very efficient at breaking down lipids, even though lipids comprise just five percent of the algae's composition. It is a compelling example of what we call 'digestive specialization' in the genome."

With climate change making the raising of livestock less sustainable, the discovery holds promise for developing new sources of protein for human consumption. In particular, it could be important for aquaculture, which is a possible alternative but is contending with the issue of what to feed the fish being raised.

"Using plant-based food ingredients reduces pollution and costs less," said Heras, the paper's first author. "However, most aquaculture fish are carnivores and can't handle plant lipids. Sequencing this genome has provided us a better understanding of what types of genes are necessary for breaking down plant material. If we scan additional fish genomes, we may find omnivorous fish with the right genes that could provide new candidates for sustainable aquaculture."

The monkeyface prickleback grows to as much as three feet long and six pounds in weight. It can live on land for up to 37 straight hours, thanks to the ability to breathe above water as well as under. In the past decade, it has become a culinary delicacy, appearing on plates in a number of high-end restaurants. Its flavor belies its imposing appearance.

"The taste is actually delicate and mild," said German.

New Rochelle, NY, February 19, 2020--Challenging the U.S. Food and Drug Administration's current approach to evaluating and approving adipose-based cell therapies used in reparative medicine, a group of researchers proposes a new path forward that focuses on patient safety and includes evidence-based medical practice. Details of this new path forward and a response from the FDA are both published in Stem Cells and Development, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article for free on the Stem Cells and Development through March 19, 2020.

The article entitled "Arguments for a Different Regulatory Categorization and Framework for Stromal Vascular Fraction" was coauthored by Jeffrey Gimble, LaCell, Obatala Sciences, and Tulane University School of Medicine, New Orleans, LA, and an international team of colleagues. They argue that to bring adipose-based regenerative therapies to market in a more efficient way, the two types of cell populations produced -- adipose-derived stromal/stem cells (ASCs) and stromal vascular fraction (SVF) -- should be evaluated differently. One is an allogeneic product and one is autologous, while one is a cultured homogeneous product and the other is a freshly harvested heterogeneous product. These are different cell preparations that vary in cell function and differentiation potential. The researchers contend that they should be evaluated based on their different risk profiles. An additional aspect of this new path forward includes protecting patients by keeping out "rogue clinics" and accrediting regenerative therapy facilities and physicians.

In the Commentary entitled "Clear Evidence of Safety and Efficacy Is Needed for Stromal Vascular Fraction Products," Peter Marks, MD, PHD, U.S. Food and Drug Administration, Silvery Spring, MD, writes that the arguments made by Gimble et al., and the path they propose "overlook several key aspects relevant to promoting scientific advancement of the field of regenerative medicine and ensuring that autologous SVF is safe and effective for the treatment of various specific conditions before it is marketed to patients." He concludes that "autologous cellular therapies do hold tremendous promise, but they will only fund their way into routine clinical practice to bring benefit to all patients if they are held to the same standards to demonstrate safety and efficacy as other unproven medical products".

Graham C. Parker, PhD, Editor-in-Chief of Stem Cells and Development and The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI states: "Stem Cells and Development values honest opinions on these difficult issues, and encourages all stakeholders -- patients, clinicians, researchers and regulators alike -- to look to us as a venue for considered debate and safe progress in reparative medicine."