Culture

Depressive symptoms linked to rapid kidney function decline

Highlight

Among individuals with healthy kidneys, those with more frequent depressive symptoms were more likely to show signs of rapid kidney function decline over a median follow-up of 4 years.

Washington, DC (May 28, 2021) -- In a study of adults with normal kidney function, those who had frequent depressive symptoms were more likely to later experience a rapid decline in kidney function. The study will appear in an upcoming issue of CJASN.

Depression is a common condition in middle-aged and older adults, and it can contribute to a variety of mental and physical problems. Previous research has found a link between depressive symptoms and rapid kidney function decline in patients with chronic kidney disease (CKD). To look for a potential link in adults with normal kidney function as well, a team led by Xianhui Qin, MD (Nanfang Hospital, Southern Medical University, in China) examined information on 4,763 individuals with healthy kidneys when they enrolled in the China Health and Retirement Longitudinal Study (CHARLS).

At the start of the study, 39% of participants had high depressive symptoms, and during a median follow-up of 4 years, 260 (6%) participants experienced rapid kidney function decline. There was a significant association between depressive symptoms at the start of the study and rapid decline in kidney function during follow-up. Participants with frequent depressive symptoms were 1.4-times more likely to experience rapid kidney function decline than participants with infrequent depressive symptoms, after adjustments.

"CKD is a leading risk factor for cardiovascular disease, kidney failure, and mortality worldwide. Therefore, the identification of more modifiable risk factors may possibly reduce the huge burden of CKD and its related complications by leading to early detection and prevention," said Dr. Qin. "While our study does not show causality, it demonstrated that high depressive symptoms were significantly associated with rapid decline in kidney function among Chinese adults with normal kidney function. If further confirmed, our data provide some evidence for depressive symptom screening and effective psychosocial interventions to improve the prevention of CKD."

An accompanying Pantiet Voice article provides the perspective of a two-time kidney transplant recipient with an American-Born Chinese background.

Credit: 
American Society of Nephrology

Socioeconomic disparities in respiratory health in US

What The Study Did: Socioeconomic disparities in respiratory health over the past six decades in the United States are described in this study.

Authors: Adam W. Gaffney, M.D., of the Cambridge Health Alliance in Cambridge, Massachusetts, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.2441)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full study and commentary are linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2021.2441?guestAccessKey=392909c8-2e27-4134-ae14-6286c11e6843&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=052821

Credit: 
JAMA Network

Assessment of SARS-CoV-2 reinfection 1 year after primary infection in Lombardy, Italy

What The Study Did: Study results suggest that reinfections are rare events and that patients who have recovered from COVID-19 have a lower risk of reinfection. However, the observation ended before SARS-CoV-2 variants began to spread, and it is unknown how well natural immunity to the wild-type virus will protect against variants. .

Authors: Nicola Mumoli, M.D., of the Ospedale Fornaroli in Magenta, Italy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.2959)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Applying private insurer rules to Medicare Part B

What The Study Did: Researchers estimated the extent Medicare Part B medical services would have been subject to prior authorization under private insurance coverage policies and calculated the associated spending.

Authors: Aaron L. Schwartz, M.D., Ph.D., of the University of Pennsylvania in Philadelphia, is the corresponding author.

To access the embargoed study:  Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamahealthforum.2021.0859)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jama-health-forum/fullarticle/10.1001/jamahealthforum.2021.0859?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=052821

About JAMA Heath Forum: JAMA Health Forum has transitioned from an information channel to an international, peer-reviewed, online, open access journal that addresses health policy and strategies affecting medicine, health and health care. The journal publishes original research, evidence-based reports and opinion about national and global health policy; innovative approaches to health care delivery; and health care economics, access, quality, safety, equity and reform. Its distribution will be solely digital and all content will be freely available for anyone to read.

Credit: 
JAMA Network

Providing more low-value care doesn't lead to higher patient experience ratings

As hospitals, insurance companies and policy makers seek to improve healthcare quality and reduce rising medical costs, one important metric used to assess clinicians hinges on how patients feel about their healthcare experience. Many healthcare providers and policy makers fear that increased pressure to please patients -- and ensure high satisfaction ratings as a result -- could lead to overuse of low-value care that doesn't provide any clinical benefit while unnecessarily ratcheting up medical bills.

But new research from the University of Chicago and Harvard Medical School may alleviate some of those concerns. The study, published May 28 in JAMA Internal Medicine, found no relationship between favorable patient ratings and exposure to more low-value care.

"Some believe that much low-value care is provided by doctors because they feel like they have to appease patients. This worry has become bigger as patient ratings are increasingly used in new payment models and public reporting of healthcare rankings," said lead author Prachi Sanghavi, PhD, Assistant Professor of Public Health Sciences at UChicago. "For example, if a patient asks for extra testing or screening when it's not medically indicated, should doctors worry they will be rated poorly if they don't comply? At the same time, physicians feel pressure to reduce unnecessary testing and procedures when possible, because they are wasteful and can lead to harm downstream."

At least one often-cited study supports the concern that a focus on patient ratings will lead to more low-value care, finding patients with higher satisfaction ratings had higher odds of inpatient admission, higher healthcare and prescription drug costs and higher mortality. This study implied that catering to patient satisfaction may lead to worse outcomes. But, Sanghavi says, these results are likely a reflection of the methods used in the study.

"The past research didn't adequately adjust for certain key factors, like how sick a patient might be, which could be a confounding factor," said Sanghavi. "For example, people who are chronically or terminally ill may use more care and may develop closer relationships with their doctors, which could in turn lead to higher patient satisfaction ratings."

In their new study, Sanghavi and her team examined data from the federal Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey, which uses patient-provided observations to measure things like communication with a physician, timeliness of scheduling an appointment and time spent in the waiting room. They also analyzed Medicare claims to measure the amount of low-value care received by a physician's patient panel. Unlike past studies, the researchers' approach relied on sampling independence and little overlap between the patients in the CAHPS and claims datasets. With this innovative methodology, the researchers were able to eliminate patient-level, unconnected factors that could influence the results and gain a less-biased look at the relationship between patient satisfaction and low-value care exposure.

"While we found a wide range of low-value care across physician patient panels, there was no systematic association between low-value care exposure and favorable patient ratings," said Sanghavi. "So the physicians whose patients get more low-value care are not getting higher ratings."

These results, the investigators say, should help ease the concern that reducing the number of unnecessary care offerings will negatively impact patients' opinions of their physicians or healthcare organizations.

"In short, the concern is overblown," said study co-investigator Michael McWilliams, Professor of Health Care Policy at Harvard Medical School and a general internist at Brigham and Women's Hospital. "Whether it's because less wasteful physicians are adept at informing patients why a requested test or procedure is unnecessary, or because most low-value care is due to provider practice patterns and not patient demand, we should be reassured that we can tackle waste in the system without great patient backlash or flunking providers on their 'scorecards.'"

The researchers said they weren't surprised by the findings, since previous studies relied so heavily on anecdotal evidence.

"In fact, it is not settled whether patients even advocate for low-value services," Sanghavi said. "Either way, it is reasonable to imagine patients base their experience ratings on a range of quality dimensions and not just on how well their physicians give in to demands, should they be making them."

Understanding how patient experiences and ratings are impacted by the types of care they receive has important implications for future policies and funding models geared at reducing wasteful healthcare spending while improving the overall quality of care.

"These results should help alleviate the stress that physicians may feel around possibly leaving patients dissatisfied because they didn't do something the patient asked for," said Sanghavi. "It should also relieve pressure to provide unnecessary care in order to boost ratings."

Credit: 
University of Chicago Medical Center

UM research suggests social factors important for human-wildlife coexistence

image: One thing bears and people have in common? Their love of a tasty snack. Here, a black bear wanders in the Ninemile Valley of Montana.

Image: 
Charlie Durrant

MISSOULA - In bear country, it's normal to find bruins munching down on temptations left out by humans - from a backyard apple tree to leftovers in the trash bin - but these encounters can cause trouble for humans and bears alike. One method to reduce human-bear conflicts is to secure attractants like garbage and livestock feed.

While effective when implemented, this approach requires people to change their behavior, and that makes things a little more complicated.

University of Montana researchers recently published a new study in the Journal of Wildlife Management analyzing why landowners do or don't secure attractants in bear country. The results suggest that collective or socially motivated factors may be a missing and important piece of the puzzle for encouraging voluntary steps to secure attractants and improve wildlife-human coexistence. The researchers also offer suggestions for how wildlife managers might help increase these behaviors through improved messaging and outreach.

Social scientists in UM's Human Dimensions Lab, housed in UM's W. A. Franke College of Forestry and Conservation, classify human-wildlife interactions as a public-good, collective-action problem - a problem where solutions require contributions from many people and where people's actions affect others. For the study, they applied this theory in Montana's black bear and grizzly bear ranges to investigate how individual and collective factors work together to influence whether landowners secure bear attractants on their land.

"A collective-action problem requires the efforts of two or more individuals to solve," said Holly Nesbitt, a doctoral candidate in the College of Forestry and Conservation and the study's lead author. "We're arguing that securing bear attractants - that coexistence with wildlife - is a collective-action problem because you need multiple people - land owners specifically - to pull it off. Their actions protect themselves and their neighbors."

Nesbitt and her coauthors analyzed data from a 2018 survey of Montana landowners meant to understand their attitudes and behaviors related to bears. Among other questions, the survey asked people about their willingness to secure different attractants, like using bear-resistant garbage bins and removing bird feeders.

Researchers found that the most important factor in determining if a landowner would secure attractants was whether that landowner had talked to a wildlife professional.

"We think that landowners who have talked to a wildlife professional have received information more easily than those who haven't," Nesbitt said. "In theory, they have reduced the time costs of securing attractants, so we think that's why they are more likely to use bear-proof garbage cans, for example."

Other collective factors, like whether their neighbors secure attractants, and the existence of discussion networks (for example, how much social influence an individual has) were equally as important as individual factors like beliefs, age or gender.

"The fact that this is a collective-action problem - that we're in it together, that it needs all of us to solve it, that our behavior has impact on our neighbors, too - leads us to the conclusion that what people are doing around us matters and influences our own behavior," says UM Assistant Professor Alex Metcalf, a coauthor on the study.

The researchers hope the results help wildlife managers reimagine how they communicate with landowners.

For example, wildlife managers and outreach coordinators could potentially increase attractant securing behavior by emphasizing collective factors in addition to individual factors.

"With any sort of outreach or messaging to landowners, there's maybe another opportunity to lean on these other collective factors and include more normative messaging. It might be more effective," Nesbitt said. "Instead of saying, 'Bears are dangerous. Secure your attractants,' say, 'It's really important to your neighbors that you secure your attractants. Your neighbor is doing it, too.' Our data suggests that kind of messaging is likely to be more effective at promoting voluntary behaviors."

The researchers also say, based on the findings, that wildlife agencies would be justified in increasing their efforts to connect with landowners in person, as well as with members of the public who play an important role in discussion networks.

"Our wildlife professionals are critical in connecting with the public, playing an integral role in educating, listening and empowering landowners," said co-author Libby Metcalf, UM's Joel Meier Distinguished Professor of Wildland Management.

While large carnivore populations are decreasing across most of the globe, grizzly and black bear populations are increasing in Montana, offering a unique locale to study how humans and wildlife interact. Nesbitt and her co-authors say understanding how to manage conflict with large carnivores has never been more pressing.

"We need a more comprehensive understanding of how people behave in these situations, and it's often not as simple as we think," Alex Metcalf said.

Credit: 
The University of Montana

Pollen-sized technology protects bees from deadly insecticides

image: A Beemmunity employee, Abraham McCauley, applies a pollen patty containing microsponges to a hive as part of colony trials.

Image: 
Nathan Reid

ITHACA, N.Y. - A Cornell University-developed technology provides beekeepers, consumers and farmers with an antidote for deadly pesticides, which kill wild bees and cause beekeepers to lose around a third of their hives every year on average.

An early version of the technology ¬- which detoxified a widely-used group of insecticides called organophosphates - is described in a new study, "Pollen-Inspired Enzymatic Microparticles to Reduce Organophosphate Toxicity in Managed Pollinators," published in Nature Food. The antidote delivery method has now been adapted to effectively protect bees from all insecticides, and has inspired a new company, Beemmunity, based in New York state.

Studies show that wax and pollen in 98% of hives in the U.S. are contaminated with an average of six pesticides, which also lower a bee's immunity to devastating varroa mites and pathogens. At the same time, pollinators provide vital services by helping to fertilize crops that lead to production of a third of the food we consume, according to the paper.

"We have a solution whereby beekeepers can feed their bees our microparticle products in pollen patties or in a sugar syrup, and it allows them to detoxify the hive of any pesticides that they might find," said James Webb, a co-author of the paper and CEO of Beemmunity.

First author Jing Chen is a postdoctoral researcher in the lab of senior author Minglin Ma, associate professor in the Department of Biological and Environmental Engineering in the College of Agriculture and Life Sciences (CALS). Scott McArt, assistant professor of entomology in CALS, is also a co-author.

The paper focuses on organophosphate-based insecticides, which account for about a third of the insecticides on the market. A recent worldwide meta-analysis of in-hive pesticide residue studies found that, under current use patterns, five insecticides posed substantial risks to bees, two of which were organophosphates, McArt said.

The researchers developed a uniform pollen-sized microparticle filled with enzymes that detoxify organophosphate insecticides before they are absorbed and harm the bee. The particle's protective casing allows the enzymes to move past the bee's crop (stomach), which is acidic and breaks down enzymes.

Microparticles can be mixed with pollen patties or sugar water, and once ingested, the safe-guarded enzymes pass through the acidic crop to the midgut, where digestion occurs and where toxins and nutrients are absorbed. There, the enzymes can act to break down and detoxify the organophosphates.

After a series of in vitro experiments, the researchers tested the system on live bees in the lab. They fed a pod of bees malathion, an organophosphate pesticide, in contaminated pollen and also fed them the microparticles with enzyme. A control group was simultaneously fed the toxic pollen, without the enzyme-filled microparticles.

Bees that were fed the microparticles with a high dose of the enzyme had a 100% survival rate after exposure to malathion. Meanwhile, unprotected control bees died in a matter of days.

Beemmunity takes the concept a step further, where instead of filling the microparticles with enzymes that break down an insecticide, the particles have a shell made with insect proteins and are filled with a special absorptive oil, creating a kind of micro-sponge. Many insecticides, including widely-used neonicotinoids, are designed to target insect proteins, so the microparticle shell draws in the insecticide where it is sequestered inert within the casing. Eventually, the bees simply defecate the sequestered toxin.

The company is running colony-scale trials this summer on 240 hives in New Jersey and plans to publicly launch its products starting in February 2022. Products include microparticle sponges in a dry sugar medium that can be added to pollen patties or sugar water, and consumer bee feeders in development.

"This is a low-cost, scalable solution which we hope will be a first step to address the insecticide toxicity issue and contribute to the protection of managed pollinators," Ma said.

Credit: 
Cornell University

Study of Fe2+ ions contributes to further understanding of magnetoelectric coupling

image: An example of a scheme of virtual excitations corresponding to the coupling of spins of chromium and iron ions with an electric field. The iron ion, due to the interaction with the electric field, transfers from the ground state 5 Eθ to the excited state 5 Eξ , which then interacts with the ground states of three chrome ions through the oxygen ion 2. At the final (third) stage of the process, the iron ion passes into the ground state due to the spin-orbit interaction.

Image: 
Kazan Federal University

The authors, Kirill Vasin and Mikhail Eremin, contribute to the theory of electronic and structural properties of FeCr2O4 ferrimagnet. Due to the specific quantum state and the symmetry of FeO4 fragment, it has unusual electric and magnetic properties. Below TOO~150K, it lowers the symmetry with the macroscopic deformations due to the cooperative Jahn-Teller effect. The coupling between macroscopic deformation of the crystal FeCr2O4 and its inner ions shifts was revealed. The team enhanced the microscopic crystal field theory for 3D electrons with Kleiner's correction - the effect of penetrating charges density. It allows to have better prediction of electron-deformation coupling parameters, which is important for magnetostriction applications and critical temperature TOO. A FeO4 fragment has no inversion symmetry, therefore, the magnetization couples to the electric field (magnetoelectric coupling) via a crystal field from the nearest oxygen ions. Experimentally it was discovered by Chinese and German physicists, however, the nature of this effect had been mysterious.

The researchers developed a microscopic theory of magnetoelectric effect involved Fe2+ and Cr3+ spins. They found two effective mechanisms: the single-ion which demands at least a short-range order of Fe spins (spin-liquid or spin-glass, for instance), and the two-ions mechanism, where the canting between Fe and Cr spins is required. Both reproduce the existing experimental data on the electric polarization measurements by the order of the magnitude and the optical absorption spectrum.

Multiferroics are fascinating multifunctional materials which have a wide range of applications in electronics and spintronics, such as actuators, new types of non-volatile energy efficient memory, electric valves driven by magnetic field. etc. Putting this simply, we can magnetize the medium using electric field and vice versa. Magnetoelectric coupling depends on many competing interactions, and the theory is still unclear. The paper provides a method of calculations of the magnetoelectric and electron-deformation coupling parameters for 3D ions. The latter is also used to calculate magnetostriction, which is important for building sensors (like sonars) and actuators.

One of the important consequences is that the magnetic anisotropy can maintain not only the magnetic "memory", but also the electric "memory" of the material. The spin structure must have no inversion symmetry to maintain the electric polarization in the ground state. Also, the interplay of electric and magnetic domains may have a significant impact on electric polarization. To solve these issues, it is necessary to study the magnetic subsystem more accurate as well, which is unclear due to the lack of the experimental data and the complexity of the compound.

Credit: 
Kazan Federal University

Alzheimer's: Blood oxygen levels could explain why memory loss is an early symptom

In a world first, scientists from the University of Sussex have recorded blood oxygen levels in the hippocampus and provided experimental proof for why the area, commonly referred to as 'the brain's memory centre', is vulnerable to damage and degeneration, a precursor to Alzheimer's disease.

To understand why this region is so sensitive, the University of Sussex researchers, headed up by Dr Catherine Hall from the School of Psychology and Sussex Neuroscience, studied brain activity and blood flow in the hippocampus of mice. The researchers then used simulations to predict that the amount of oxygen supplied to hippocampal neurons furthest from blood vessels is only just enough for the cells to keep working normally.

Dr Catherine Hall, Senior Lecturer in Psychology at the University of Sussex says:

"These findings are an important step in the search for preventative measures and treatments for Alzheimer's, because they suggest that increasing blood flow in the hippocampus might be really effective at preventing damage from happening.

"If it's right that increasing blood flow in the hippocampus is important in protecting the brain from diseases like Alzheimer's, then it will throw further weight behind the importance of regular exercise and a low-cholesterol diet to long-term brain health.

"We think that the hippocampus exists at a watershed. It's just about OK normally, but when anything else happens to decrease brain blood flow, oxygen levels in the hippocampus reduce to levels that stop neurons working. We think that's probably why Alzheimer's disease first causes memory problems - because the early decrease in blood flow stops the hippocampus from working properly.

"The same factors that put you at risk of having a heart attack make you more likely to develop dementia. That's because our brains need enough blood flow to provide energy - in the form of oxygen and glucose - so brain cells can work properly, and because blood flow can clear away waste products such as the beta amyloid proteins that build up in Alzheimer's disease.

"Now we want to discover whether the lower blood flow and oxygen levels in the hippocampus are what causes beta amyloid to start to build up in Alzheimer's disease. Understanding what causes early damage will be really important to help us learn how to treat or prevent disease."

Dr Kira Shaw, a psychology researcher at the University of Sussex who undertook the main experiments, reported:

"We found that blood flow and oxygen levels in the hippocampus were lower than those in the visual cortex. Also, when neurons are active, there is a large increase in blood flow and oxygen levels in the visual cortex. This provides energy to hungry neurons. But in the hippocampus, these responses were much smaller."

The scientists also found that blood vessels in the hippocampus contained fewer mRNA transcripts (codes for making proteins) for proteins that shape blood vessel dilation. Additionally, the cells that dilate small blood vessels, called pericytes, were a different shape in the hippocampus than in the visual cortex.

Dr Shaw concluded: "We think blood vessels in the hippocampus are less able to dilate than in the visual cortex".

Credit: 
University of Sussex

Chimaeroid from Early Cretaceous reassessed in light of new data

The basis for this new take on the classification was laid in 1985, when John Long attributed a fossil tooth plate to a new species, Edaphodon eyrensis. The species was named after Lake Eyre, near which the tooth was found in 1978.

Asscoiate Professor Evgeny Popov had his doubts about the attribution. However, he had to study the fossil personally to advance his theory. The opportunity presented itself during a trip to Australia in 2010. The tooth plate was stored in a museum in Adelaide, South Australia.

"I didn't plan to go there, but I was able to negotiate a temporary transfer of the fossil to Victoria, where I was working with another collection of chimaeroid fossils. The tooth plate was photographed, drawn, measured and studied under a microscope," says Popov.

To further solidify his takeaways, Popov also visited Brisbane, Queensland, where he studied more chimaeroid specimens. As a result, the plate was attributed to Ptyktoptychion Lees, and the species received a new name - Ptyktoptychion eyrensis.

Interestingly, the place of discovery, which is now in the Australian moderate climate, was in polar latitudes during the Aptian age of the Cretaceous (125 to 113 Ma). The changes of polar day and night and frosty weather were not a hindrance for this fish in the shallow waters of prehistoric Australian seas.

Credit: 
Kazan Federal University

New insights into switchable MOF structures

Metal-organic framework compounds (MOFs) consist of inorganic and organic groups and are characterised by a large number of pores into which other molecules can be incorporated. MOFs are therefore interesting for many applications, for example for the storage of gases, but also for substance separation, sensor technology or catalysis. Some of these MOF structures react to different guest molecules by changing their structures. They are thus considered switchable.

One of these is "DUT-8", a material that has now been studied at the MX beamlines of BESSY II. "MOF crystals can be analysed very well at the MX beamlines," says HZB expert Dr. Manfred Weiss, who heads the MX team. "MOF crystals have many things in common with protein crystals. For example, both are interspersed with large pores, which are filled with liquid in the protein crystals, while those in MOFs provide space for guest molecules," Weiss explains.

"The diffraction patterns that DUT-8 showed on the HZB-MX beamlines were extremely complex. We were now able to attribute this to various transitions between ordered and less ordered phases," explains Stefan Kaskel. The enclosed guest molecule directs the network into one of over a thousand possible disorder configurations. The results contribute to a better understanding of switching processes and gas exchange reactions in such MOF structures, so that future functional MOF materials can be developed in a targeted manner.

Credit: 
Helmholtz-Zentrum Berlin für Materialien und Energie

A new light-sheet microscopy unit enables an extended field of view and reduced photodamage

image: Observation of a lymphatic vessel development over three days using a FLT4-EGFP embryo which expressed green fluorescent protein in the lymphatic endothelial cells.

Image: 
© Nature Communications

A research group led by Takashi Saito, of the Ehime University Graduate School of Medicine, developed a 2-photon excitation light-sheet fluorescence microscope which (1) lowers phototoxicity, (2) extends the field of view, and (3) heightens spatial resolution. This microscope, when used for the observation of medaka fish, made it possible to observe the whole body of the embryo (an extended field of view) at a cellular level resolution (high spatial resolution) without affecting the growth of the fish (low phototoxicity) over a three-day span of embryonic development. This result was published in the scientific journal Nature Communications (Springer Nature).

1. Background

The fluorescence microscope is widely used in the field of life science to observe molecules inside a cell in a non-invasive way. Light-sheet fluorescence microscopy makes it possible to record three-dimensional images with high acquisition speed and high spatial resolution. However, in conventional light-sheet microscopes, it is difficult to limit photodamage to living tissues, and also difficult to simultaneously achieve wide FOV and high (cell level) spatial resolution.

2. Development of a two-photon excitation wide-field, light-sheet microscope

The Ehime University research group of Takashi Saitou, Sota Takanezawa, and Takeshi Imamura utilized the two-photon excitation phenomenon as a key to solving this problem. The two-photon excitation microscope with infrared lasers enables gentle (low phototoxic) imaging of living organisms. However, because the light must be focused on a narrow range to induce two-photon excitation, the excitation range (in light-sheet microscope, the field of view) is narrow. In order to solve this, we developed simple illumination optics unit with a Bessel beam that expands the laser propagation range in the direction of the optic axis (Fig. 1A). This unit can stretch the beam length to 600-1000 μm while maintaining a 2-3 μm axial resolution when using a 10x magnification NA0.3 objective lens. Using this optical unit, we constructed a two-photon excitation light-sheet microscopy (Fig. 1B), which makes it possible to perform whole-body imaging of medaka larvae with cellular resolution (Fig. 1C).

3. Application to live imaging

The medaka is widely used as a model organism for vertebrate. It is suitable for fluorescent imaging since it is small and transparent. To evaluate the applicability of our microscope for use on living organisms, we performed a phototoxicity assessment. This revealed reduced photodamage compared with the conventional Gaussian beam light-sheet sheet microscope. It is therefore suggested to be suitable for long-term live imaging. We then applied long-term time-lapse imaging of the transgenic medaka in which lymphatic endothelium is labelled with green fluorescent protein, and succeeded in live imaging over three days at intervals of 5 minutes (Fig. 2).

4. Significance of the research

In this study, we developed a new high performance light-sheet fluorescence microscope. Using this technology, we can observe almost all the embryonic growth processes of medaka fish with high cellular resolution over the whole body of the fish. This technology is expected to contribute to the molecular level understanding of embryonic development, the elucidation of pathogenesis for lifestyle-related diseases, and to further the technology of drug development.

Credit: 
Ehime University

'Good' bacteria show promise for clinical treatment of Crohn's disease, ulcerative colitis

image: Balfour Sartor, MD

Image: 
UNC School of Medicine

CHAPEL HILL, NC - A new study published in Nature Communications demonstrates that a consortium of bacteria designed to complement missing or underrepresented functions in the imbalanced microbiome of inflammatory bowel disease (IBD) patients, prevented and treated chronic immune-mediated colitis in humanized mouse models. The study's senior author, Balfour Sartor, MD, Midget Distinguished Professor of Medicine, Microbiology and Immunology, Co-Director of the UNC Multidisciplinary IBD Center, said the results are encouraging for future use treating Crohn's disease and ulcerative colitis patients.

"The idea with this treatment is to restore the normal function of the protective bacteria in the gut, targeting the source of IBD, instead of treating its symptoms with traditional immunosuppressants that can cause side effects like infections or tumors," Sartor said.

The live bacteria consortia, called GUT-103 and GUT-108, were developed by biotech firm Gusto Global. GUT-103 is comprised of 17 strains of bacteria that work together to protect and feed each other. GUT-108 is a refined version of GUT-103, using 11 human isolates related to the 17 strains. These combinations permit the bacteria to stay in the colon for an extended amount of time, as opposed to other probiotics that are not capable of living in the gut and pass through the system quickly.

GUT-103 and GUT-108 were given orally three times a week to "germ-free" mice (no bacteria present) that had been specially developed and treated with specific human bacteria, creating a humanized mouse model. The therapeutic bacteria consortia worked by addressing upstream targets, rather than targeting a single cytokine to block downstream inflammation responses, and reversed established inflammation.

"It also decreased pathobionts - bacteria that can cause harm - while expanding resident protective bacteria, and produced metabolites promoting mucosal healing and immunoregulatory responses," Sartor said. "Simply put - the treatment increased the good guys and decreased the bad guys."

Because of the robust results seen in this study, and the need for more alternative therapies for Crohn's disease, Sartor would like to see GUT-103 and GUT-108 studied in Phase 1 and 2 clinical trials in the future. He plans to continue his work with Gusto Global to further explore uses of the bacterial consortia.

Credit: 
University of North Carolina Health Care

Open, expressive family life may reduce social deprivation effects among adopted children

WHAT:

An environment in which family members support one another and express their feelings can reduce the effects of social deprivation on cognitive ability and development among adopted children, suggests a small study by researchers at the National Institutes of Health. In contrast, rule-driven households where family members are in conflict may increase an adopted child's chances for cognitive, behavioral and emotional difficulties.

The study was conducted by Margaret F. Keil, Ph.D., and colleagues in the Section on Endocrinology and Genetics at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in Pediatric Research.

Researchers enrolled children who had spent at least eight months in Eastern European orphanages before their adoption by American families. The children ranged from 14 to 40 months of age and were evaluated with physical, psychological and developmental tests twice during the following two years. Families also responded to questionnaires on the children's development and on various aspects of their home lives. The study included 10 adopted children and 19 similar children born to American families.

Overall, the adopted children had significant deficits in growth, cognitive ability and development in comparison to the American-born children. However, differences were smaller among children from families scoring higher in cohesion, where family members provided help and support for each other, and expressiveness--families whose members are encouraged to express their feelings. Children had greater deficits if their families scored higher in conflict--open expression of anger and aggression--and in control--a family life run according to set rules and procedures.

The authors concluded that family cohesion and expressiveness could moderate the effects of pre-adoption adversity, while family conflict and adherence to rules could increase the risk for behavioral problems. The authors added that larger studies are needed to verify their findings.

Credit: 
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Better choice of contraceptives can prevent breast cancer

image: Fluorescence stereo micrograph of a mouse mammary gland intraductally injected with normal human breast epithelial cells. Credit: Marie Shamseddin (EPFL).

Image: 
EPFL

Hormonal contraceptives, e.g. the pill, the patch, and the vaginal ring, contain synthetic hormones that prevent pregnancy by either stopping ovulation, changing the cervical mucus to stop sperm from passing through the cervix and finding an egg, or changing the womb's lining to prevent a fertilized egg from being implanted in it.

Despite their widespread use, hormonal contraceptives are known to increase the risk of breast cancer, which is the most common cause of cancer-related death among women worldwide, and also topped the list of most commonly diagnosed cancers in 2020.

The main component of hormonal contraceptives are progestins, which, mimic the female sex hormone progesterone. Progesterone is involved in a number of biological processes, including the menstrual cycle, pregnancy, and various aspects of fetal development, like brain programming.

Now, a team of scientists led by Professor Cathrin Brisken at EPFL's School of Life Sciences, have taken a thorough and close look at the different biological effects that different progestins in hormonal contraceptives have on the breast tissue - the mammary epithelium. The work is published in EMBO Molecular Medicine.

"Although we know how different contraceptive formulations affect the cardiovascular system, we know little about their effects on the breast," says Brisken. "So we developed new approaches to compare the most commonly used progestins in different hormonal contraceptives and were surprised to find that some of them stimulate cell proliferation in the breast - while others do not."

The researchers tested the effects of prolonged exposure to different progestins on human breast epithelial cells or HBECs, which line the inner layer of the breast. To do this, they developed "humanized" mouse mammary glands by grafting breast epithelial cells from donated human breast tissue from reduction mammoplasty samples into the animals' milk ducts and monitoring their growth in vivo.

"We found that HBECs engraft and proliferate in mouse milk ducts, maintaining hormone receptor expression and hormone responsiveness, which are crucial factors for establishing a relevant preclinical model and thereby to foster translational research," says Brisken.

The team realized that what distinguished the stimulatory and the innocuous progestins were their "androgenic properties" - a technical term for substances that trigger the development of male characteristics, such as body hair, muscle mass etc. This isn't as strange as it sounds: progesterone, mostly known as a female hormone, is used for the production of the famous male hormone testosterone in both women and men.

Some progestins have androgenic properties, acting like testosterone; some actually block them. The key is a protein known as the androgen receptor, which, when activated by an androgenic progestin, travels into the cell's nucleus where it regulates the expression of certain genes.

Working with the epithelial cells in a mouse model, the researchers found that androgenic progestins act through the androgen receptor to induce the expression of the protein Rankl, which plays an important role in cell proliferation in the mammary epithelium. This effect was not seen with anti-androgenic progestins.

The study showed that androgenic - but not anti-androgenic - progestins promote cell proliferation. "Exposing human breast epithelia to androgenic progestins for prolonged periods of time caused hyperproliferation and changes in the cells that are associated with early, pre-malignant lesions - at least in xenografted human breast epithelia," says De Martino.

"Hormonal contraception exposes women to different progestins with or without estrogen," says Brisken. "The androgenic properties of progestins determine their biological activity in the breast epithelium, and reveal an unexpected role for androgen receptor activity in the proliferation of breast epithelial cells."

The crucial insight of the study is that progestins with anti-androgenic activity may be a safer option with regards to breast cancer risk than testosterone-related compounds, e.g. the widely used contraceptive levonorgestrel ("Plan B"). "It might be possible to prevent breast cancer associated with contraception by making more informed choices taking the molecular composition of a contraceptive into account," concludes Brisken.

Credit: 
Ecole Polytechnique Fédérale de Lausanne