Culture

Mitochondria are the energy suppliers of our body cells. These tiny cell components have their own genetic material, which triggers an inflammatory response when released into the interior of the cell. The reasons for the release are not yet known, but some cardiac and neurodegenerative diseases as well as the ageing process are linked to the mitochondrial genome. Researchers at the Max Planck Institute for Biology of Ageing and the CECAD Cluster of Excellence in Ageing research have investigated the reasons for the release of mitochondrial genetic material and found a direct link to cellular metabolism: when the cell's DNA building blocks are in short supply, mitochondria release their genetic material and trigger inflammation. The researchers hope to find new therapeutic approaches by influencing this metabolic pathway.

Our body needs energy - for every metabolic process, every movement and for breathing. This energy is produced in tiny components of our body cells, the so-called mitochondria. Unlike other cell components, mitochondria have their own genetic material, mitochondrial DNA. However, in certain situations, mitochondria release their DNA into the interior of the cell, causing a reaction from the cell's own immune system and being associated with various diseases as well as the ageing process. The reasons for the release of mitochondrial DNA are not yet known.

Shortage of DNA building blocks triggers inflammatory reaction

To answer the question of when mitochondria release their DNA, researchers at the Max Planck Institute for Biology of Ageing have focused on the mitochondrial protein YME1L, which owes its name to yeast mutants that release their mitochondrial DNA - yeast mitochondrial escape 1. "In cells lacking YME1L, we observed the release of mitochondrial DNA into the cell interior and a related immune response in the cells", said Thomas MacVicar, one of the study's two first authors. Closer examination revealed a direct link to the building blocks of DNA. "If the cells lack YME1L, there is a deficiency of DNA building blocks inside the cell", Thomas MacVicar describes. "This deficiency triggers the release of mitochondrial DNA, which in turn causes an inflammatory response in the cell: the cell stimulates similar inflammatory reactions as it does during a bacterial or viral infection. If we add DNA building blocks to the cells from the outside, that also stops the inflammation."

New therapeutic approaches based on the metabolism of DNA building blocks

The discovered link between the cellular inflammatory response and the metabolism of DNA building blocks could have far-reaching consequences, explains Thomas MacVicar: "Some viral inhibitors stop the production of certain DNA building blocks, thereby triggering an inflammatory response. The release of mitochondrial DNA could be a crucial factor in this, contributing to the effect of these inhibitors." Several ageing-associated inflammatory diseases, including cardiac and neurodegenerative diseases, as well as obesity and cancer, are linked to mitochondrial DNA. The authors hope that modulating the metabolism of DNA building blocks will offer new therapeutic opportunities in such diseases.

Scientists at the University of Nottingham have developed an ultrasonic imaging system, which can be deployed on the tip of a hair-thin optical fibre, and will be insertable into the human body to visualise cell abnormalities in 3D.

The new technology produces microscopic and nanoscopic resolution images that will one day help clinicians to examine cells inhabiting hard-to-reach parts of the body, such as the gastrointestinal tract, and offer more effective diagnoses for diseases ranging from gastric cancer to bacterial meningitis.

The high level of performance the technology delivers is currently only possible in state-of-the-art research labs with large, scientific instruments - whereas this compact system has the potential to bring it into clinical settings to improve patient care.

The Engineering and Physical Sciences Research Council (EPSRC)-funded innovation also reduces the need for conventional fluorescent labels - chemicals used to examine cell biology under a microscope - which can be harmful to human cells in large doses.

The findings are being reported in a new paper, entitled 'Phonon imaging in 3D with a fibre probe' published in the Nature journal, Light: Science & Applications.

Paper author, Salvatore La Cavera, an EPSRC Doctoral Prize Fellow from the University of Nottingham Optics and Photonics Research Group, said of the ultrasonic imaging system: "We believe its ability to measure the stiffness of a specimen, its bio-compatibility, and its endoscopic-potential, all while accessing the nanoscale, are what set it apart. These features set the technology up for future measurements inside the body; towards the ultimate goal of minimally invasive point-of-care diagnostics."

Currently at prototype stage, the non-invasive imaging tool, described by the researchers as a "phonon probe", is capable of being inserted into a standard optical endoscope, which is a thin tube with a powerful light and camera at the end that is navigated into the body to find, analyse, and operate on cancerous lesions, among many other diseases. Combining optical and phonon technologies could be advantageous; speeding up the clinical workflow process and reducing the number of invasive test procedures for patients.

3D mapping capabilities

Just as a physician might conduct a physical examination to feel for abnormal 'stiffness' in tissue under the skin that could indicate tumours, the phonon probe will take this '3D mapping' concept to a cellular level.

By scanning the ultrasonic probe in space, it can reproduce a three-dimensional map of stiffness and spatial features of microscopic structures at, and below, the surface of a specimen (e.g. tissue); it does this with the power to image small objects like a large-scale microscope, and the contrast to differentiate objects like an ultrasonic probe.

"Techniques capable of measuring if a tumour cell is stiff have been realised with laboratory microscopes, but these powerful tools are cumbersome, immobile, and unadaptable to patient-facing clinical settings. Nanoscale ultrasonic technology in an endoscopic capacity is poised to make that leap," adds Salvatore La Cavera.

How it works

The new ultrasonic imaging system uses two lasers that emit short pulses of energy to stimulate and detect vibrations in a specimen. One of the laser pulses is absorbed by a layer of metal - a nano-transducer (which works by converting energy from one form to another) - fabricated on the tip of the fibre; a process which results in high-frequency phonons (sound particles) getting pumped into the specimen. Then a second laser pulse collides with the sound waves, a process known as Brillouin scattering. By detecting these "collided" laser pulses, the shape of the travelling sound wave can be recreated and displayed visually.

The detected sound wave encodes information about the stiffness of a material, and even its geometry. The Nottingham team was the first to demonstrate this dual-capability using pulsed lasers and optical fibres.

The power of an imaging device is typically measured by the smallest object that can be seen by the system, i.e. the resolution. In two dimensions the phonon probe can "resolve" objects on the order of 1 micrometre, similar to a microscope; but in the third dimension (height) it provides measurements on the scale of nanometres, which is unprecedented for a fibre-optic imaging system.

Future applications

In the paper, the researchers demonstrate that the technology is compatible with both a single optical fibre and the 10-20,000 fibres of an imaging bundle (1mm in diameter), as used in conventional endoscopes.

Consequently, superior spatial resolution and wide fields of view could routinely be achieved by collecting stiffness and spatial information from multiple different points on a sample, without needing to move the device - bringing a new class of phonon endoscopes within reach.

Beyond clinical healthcare, fields such as precision manufacturing and metrology could use this high-resolution tool for surface inspections and material characterisation; a complementary or replacement measurement for existing scientific instruments. Burgeoning technologies such as 3D bio-printing and tissue engineering could also use the phonon probe as an inline inspection tool by integrating it directly to the outer diameter of the print-needle.

Next, the team will be developing a series of biological cell and tissue imaging applications in collaboration with the Nottingham Digestive Diseases Centre and the Institute of Biophysics, Imaging and Optical Science at the University of Nottingham; with the aim to create a viable clinical tool in the coming years.

Successful navigation requires the ability to separate memories in a context-dependent manner. For example, to find lost keys, one must first remember whether the keys were left in the kitchen or the office. How does the human brain retrieve the contextual memories that drive behavior? J.B. Julian of the Princeton Neuroscience Institute at Princeton University, USA, and Christian F. Doeller of the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, found in a recent study that modulation of map-like representations in our brain's hippocampal formation can predict contextual memory retrieval in an ambiguous environment.

The researchers developed a novel virtual reality navigation task in which human participants learned object positions in two different virtual environments and then had their memory tested during a functional MRI scan. Memory for object locations was also tested in a third ambiguous context, which the researchers defined as a "squircle" - a cross between a square and a circle. There were no "correct" object positions there; instead, study participants had to rely solely on their memory. "The result of our study confirms the theory, long held by several neuroscientists, that a critical function of the hippocampal formation is to represent the contextual information that guides behavior. Cognitive maps in the brain help us to act according to a specific situation. ", explains Christian Doeller.

Although decades of research indicate that the human hippocampus is critical for contextual memory, no previous studies have linked context-specific signals in this formation of the brain to spatial behavior in a way that clearly separates memory from non-memory factors. This research was performed in collaboration with the Kavli Institute for Systems Neuroscience, NTNU, Trondheim, Norway and supported by the European Research Council (ERC-CoG GEOCOG).

The human immune system comprises functionally specialised cellular defence mechanisms that protect the body against disease. These include the dendritic cells. Their main function is to present antigens to other immune cells, especially T cells, thereby activating a primary immune response. Dendritic cells are divided into Type 1 (DC1) and Type 2 (DC2) dendritic cells. Each type fulfils different functions: DC1 provide an immune response to bacteria and viruses, DC2 protect against fungal or parasitic infections. In a recent study conducted at MedUni Vienna's Institute of Cancer Research, researchers found that a particular group of proteins plays a major role in the development of Type 1 dendritic cells. This could open up new therapeutic options in the defence against viruses or bacteria but also for cancer immunity.

Dendritic cells are formed from multipotent progenitor cells in the bone marrow. However, it was hitherto unclear which proteins are responsible for this transition from stem cells to differentiated cells. The study, which has now been published in Cell Death and Differentiation, used animal models and molecular biology techniques such as RNA sequencing to show that a combination of two proteins known as "c-Jun" and "JunB" are essential factors in the development of Type 1 dendritic cells. "Both proteins are transcription factors, DNA-binding molecules belonging to the Activator-Protein-1 (AP-1) family," explains study author Philipp Novoszel, who is also associated with the Comprehensive Cancer Center (CCC) of MedUni Vienna and Vienna General Hospital.

In order to analyse the role of these proteins, the c-Jun- and/or JunB gene was deleted in dendritic cells. "This showed that c-Jun and JunB are jointly, but not individually, essential for DC1 development," says second study author, Barbara Drobits from the Institute of Cancer Research and CCC. The mechanism in detail: working in a never previously described synergy, the c-Jun/JunB transcription factor pair together controls the development of DC1. "An expression analysis of DC1 lacking c-Jun/JunB, showed changes in the cellular identity, and a shift towards DC2." At the same time, the immunological functions of DC1 were greatly reduced when c-Jun/JunB were lacking. Differences were also found in an infection model. In the animal model, deactivation of c-Jun/JunB protected against infection with the bacterium Listeria monocytogenes.

"The results describe a previously unknown function of c-Jun/JunB in the development of dendritic cells. It has already been shown in previous studies that another member of the

AP-1 family known as Batf3 is necessary for DC1 development, in that it regulates the expression of the transcription factor IRF8. However, it was not clear with which AP-1 protein Batf3 interacts to perform this function. Our data now provide this "missing link", in that they point to c-Jun/JunB as being Batf3's tango partner," summarise the study authors.

DC1 are essential for defending against bacteria and viruses as well as for immunity to cancers - a better understanding of the underlying biology could therefore provide new, promising therapeutic approaches for future clinical application.

CHICAGO --- Itch torments its sufferers and can be as debilitating as chronic pain.

But it's a hard symptom to measure -- particularly for the 10 million U.S. children with atopic dermatitis, also known as eczema. They can't always verbalize or quantify their suffering via a survey or scale.

It can also be difficult to objectively measure itch for adults with liver disease, kidney disease and certain cancers who experience its symptoms.

So, it's hard to track how well treatments and drugs are working.

But now there is a soft, wearable sensor that actually quantifies itch by measuring scratching when placed on the hand developed by Northwestern University scientists. While it was tested in patients with atopic dermatitis, it can be used in any condition that causes itch. The novel sensor can support clinical trials for new treatments, track treatment response and monitor for disease worsening -- all in the home setting.

This is the first sensor able to capture all forms of scratching -- finger, wrist and elbow motion related. It also is the first validated in a pediatric population where conditions like atopic dermatitis are the most common.

"Itch torments so many patients across so many conditions. It can be as debilitating as chronic pain," said lead author Dr. Shuai "Steve" Xu, assistant professor of dermatology and of pediatrics at Northwestern University Feinberg School of Medicine. "If we're able to quantify scratching accurately, then we have the ability to objectively quantify itching. This is really important in patients -- like children -- who can't always verbalize or quantify their suffering."

The paper will be published April 30 in Science Advances.

Xu also is an assistant professor of biomedical engineering at McCormick School of Engineering and Applied Science and medical director of the Querrey Simpson Institute for Bioelectronics, both at Northwestern.

About 10 million U.S. children have atopic dermatitis. The hallmark symptom is itch leading to sleep disturbance, poor neurocognitive development and, on average, a full night of sleep lost per week.

"Atopic dermatitis is so much more than just itchy skin," Xu said. "It is a devastating disease that causes tremendous suffering worldwide. The quality of life of severe atopic dermatitis (not only for the child but also the parent) is equivalent to many life-threatening diseases.

"Patients with atopic dermatitis are 44% more likely to report suicidal thoughts as a result of the itch compared to controls. Thus, the ability to quantify their symptoms is really important to help new drugs get approved, but also support their day to day lives. In some ways -- it's like measuring glucose for diabetes...measuring itching in an atopic dermatitis patient may be just as important."

"This is an exciting time for children and adults with atopic dermatitis -- or eczema -- because of the flurry of activity in developing new therapeutics," said Dr. Amy Paller, chair of dermatology at Northwestern. "Nothing is more important to measure a medication's effectiveness for eczema than itch, the symptom that both defines eczema and has the greatest impact on quality of life. This sensor could play a critical role in this regard, especially for children."

In addition, clinicians and parents have the ability to track how well itch is being controlled in patients at home to monitor for treatment response, as well as early signs of worsening disease, Xu said.

This sensor marries advances in soft, flexible electronics that wrap seamlessly around the hand with machine learning algorithms that specifically identifies scratching without being tricked by similar motion-related movements (e.g. hand waving). The sensor measures both low-frequency motion and high-frequency vibrations from the hand to significantly improve accuracy compared to wrist-watch tools.

The sensor was accepted into the Food and Drug Administration's Drug Discovery Tool program. This program allows novel devices like this sensor to be qualified to aid in the approval of new drugs.

The study was conducted in two parts. The first part involved training the sensor to pick up scratching in healthy adults doing voluntary scratching behaviors. The second part tested the sensors on pediatric patients with atopic dermatitis. Parents set up an infrared camera to serve as the "gold standard". The algorithm and sensor were then used to count scratches in this pediatric patient population. More than 300 hours of sleep data was manually reviewed and scored for scratching and linked to the sensors.

eNeuro is publishing a special collection of commentaries on April 30, 2021 on the neuroscience documentary In Silico. The collection, titled "Epistemological Lessons from the Blue and Human Brain Projects," features reactions to the documentary from leading neuroscientists as well as a discussion on brain modelling and massive research collaborations in general.

Noah Hutton's In Silico follows neuroscientist Henry Markram and his attempt to develop a computer model of the brain. The collaboration, called The Human Brain Project, received €1 billion in funding and pledged to build a full model within ten years. The documentary chronicles Markram and his team as the project stirs up controversy and fails to meet its deadline.

The special collection from eNeuro discusses the documentary and the larger issues surrounding brain modelling. The commentaries include:

What In Silico got wrong, from the perspective of Human Brain Project scientists

Next steps for large-scale, collaborative neuroscience initiatives

How charismatic leaders shape the field

The history and science of building brain models

"The movie is an excuse to think more broadly about how to approach the study of brain function," said Christophe Bernard, editor-in-chief of eNeuro, "and what modelling the brain means." The eNeuro special collection and In Silico will be available online on April 30, 2021.

Boston, MA (April 30, 2021) - Research presented today at the AATS 101st Annual Meeting, shows that the six year Integrated Cardiothoracic (CT I-6) residency continues to be the most challenging to match, while the pool of applicants has become more diverse. The study, which aimed to identify applicant characteristics associated with a successful match, used data from the National Residency Matching Program (NRMP), Electronic Residency Application Service (ERAS), and Association of American Medical Colleges (AAMC) for Thoracic Surgery, Orthopaedic Surgery, Neurological Surgery, Otolaryngology (ENT), Plastic Surgery, and Vascular Surgery for 2010-2020.

Data compared number of applicants and residency positions, gender, race, and qualifications among CT I-6 applicants with those of other competitive surgical subspecialties, including Orthopaedic Surgery, Neurological Surgery, Otolaryngology, Plastic Surgery, and Vascular Surgery. Competitive subspecialties analyzed included those that had (1) more United States (US) senior applicants than positions offered; (2) ? 5 positions available in the Supplemental Offer and Acceptance Program (SOAP); and (3) United States Medical Licensing Examination (USMLE) Step 1 score average of ?235 in the 2020 NRMP Match.

Number of applicants, number of positions, match rates, gender, race, and objective metrics including Alpha Omega Alpha (AOA) membership, USMLE Step 1 and 2 CK scores, research productivity, and graduation from a top-40 NIH-funded US medical school were recorded. Descriptive statistics and Student t tests were calculated to compare applicant gender and race between surgical subspecialties.

Despite growth of 280 percent in PGY-1 positions over the ten-year period, CT I-6 continued to be the most difficult to match among all competitive surgical subspecialties, with the lowest match rates among total applicants. The number of female applicants has risen from 16 percent in 2015 to 28 percent in 2020. Furthermore, the diversity among I-6 program applicants has increased in all race and ethnicity categories from 2015 to 2019: White (+0.2 percent), Black (+2.1 percent), Asian (+2.1 percent), and Hispanic (+0.9 percent).

For all applicants, the greatest predictors of a successful match appear to be Step-2 CK, AOA membership, and graduation from a top-40 NIH-funded US medical school.

"Over the last 10 years, trends in the CT I-6 match have been very exciting," explained Lead Author Lauren Bougioukas, medical student at the University of Vermont Larner College of Medicine. "I-6 has been recruiting very competitive, talented applicants. In particular, I am thrilled to see increased numbers of racially diverse and female applicants. I hope this study serves as a springboard for future research regarding the I-6 match, and also better informs aspiring cardiothoracic surgeons looking to pursue an I-6 residency."

Boston, MA (April 30, 2021) - A new set of guidelines, developed by AATS and ESTS (European Society for Thoracic Surgery) presented today at the AATS 101st Annual Meeting, recommends a 30-day course of Venous Thromboembolism (VTE) prophylaxis post-discharge for patients undergoing surgical resection for lung or esophagus cancer. The AATS and ESTS formed a multidisciplinary guideline panel that included broad membership to minimize potential bias when formulating recommendations. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic reviews and meta-analyses. The results are endorsed by the American Society of Hematology (ASH) and the International Society on Thrombosis and Haemostasis, Inc (ISTH).

VTE is a potentially preventable postoperative complication for thoracic surgery patients, occurring in up to 14% of cases where patients underwent surgical resection for cancer. The panel made conditional recommendations for use of parenteral anticoagulation for VTE prevention, in combination with mechanical methods, over no prophylaxis for cancer patients undergoing anatomic lung resection or esophagectomy. Other key recommendations included conditional recommendations for using parenteral anticoagulants over direct oral anticoagulants (DOACs), with use of DOACs suggested only in the context of clinical trials and using extended prophylaxis for 28-35 days over in-hospital prophylaxis for patients at high risk of thrombosis, including those undergoing pneumonectomy and esophagectomy. Future research priorities include the role of preoperative thromboprophylaxis and the role of risk stratification to guide use of extended prophylaxis.

"The two largest thoracic surgery groups combined forces using the highest levels of diligence to develop a potentially practice-changing guidelines that meet the unique profile of thoracic surgery patients," said Dr. Yaron Shargall, professor and thoracic surgery division head, McMaster University. "Until now, guidelines provided the same standard of care for both cardiac and thoracic patients. Now, we are able to provide revised guidance based on real-world evidence working specifically with thoracic patients."

The guideline panel undertook a survey of thoracic surgeons and found that 95 percent indicated a willingness to accept new evidence-based guidelines in their practices. According to Shargall and Dr. Virginia Litle, Chief of Thoracic Surgery at Boston Medical Center and
Professor of Surgery, Boston University School of Medicine, "This indicated to us that the Cardio Thoracic community was awaiting new guidelines. Clearly, there is value in applying a systematic, evidence-based approach to add weight to the guidelines."

Global sea level rise associated with the possible collapse of the West Antarctic Ice Sheet has been significantly underestimated in previous studies, meaning sea level in a warming world will be greater than anticipated, according to a new study from Harvard researchers.

The report, published in Science Advances, features new calculations for what researchers refer to as a water expulsion mechanism. This occurs when the solid bedrock the West Antarctic Ice Sheet sits on rebounds upward as the ice melts and the total weight of the ice sheet decreases. The bedrock sits below sea level so when it lifts, it pushes water from the surrounding area into the ocean, adding to global sea level rise.

The new predictions show that in the case of a total collapse of the ice sheet, global sea level rise estimates would be amplified by an additional meter within 1,000 years.

"The magnitude of the effect shocked us," said Linda Pan, a Ph.D. in earth and planetary science in GSAS who co-led the study with fellow graduate student Evelyn Powell. "Previous studies that had considered the mechanism dismissed it as inconsequential."

"If the West Antarctic Ice Sheet collapsed, the most widely cited estimate of the resulting global mean sea level rise that would result is 3.2 meters," said Powell. "What we've shown is that the water expulsion mechanism will add an additional meter, or 30 percent, to the total."

But this is not just a story about impact that will be felt in hundreds of years. One of the simulations Pan and Powell performed indicated that by the end of this century global sea level rise caused by melting of the West Antarctic Ice Sheet would increase 20 percent by the water expulsion mechanism.

"Every published projection of sea level rise due to melting of the West Antarctic ice sheet that has been based on climate modeling, whether the projection extends to the end of this century or longer into the future, is going to have to be revised upward because of their work," said Jerry X. Mitrovica, the Frank B. Baird Jr. Professor of Science in the Department of Earth and Planetary Sciences and a senior author on the paper. "Every single one."

Pan and Powell, both researchers in Mitrovica's lab, started this research while working on another sea level change project but switched to this one when they noticed more water expulsion from the West Antarctic ice sheet than they were expecting.

The researchers wanted to investigate how the expulsion mechanism affected sea level change when the low viscosity, or the easy flowing material of the Earth's mantle beneath West Antarctica, is considered. When they incorporated this low viscosity into their calculations they realized water expulsion occurred much faster than previous models had predicted.

"No matter what scenario we used for the collapse of the West Antarctic Ice Sheet, we always found that this extra one meter of global sea level rise took place," Pan said.

The researchers hope their calculations show that, in order to accurately estimate global sea level rise associated with melting ice sheets, scientists need to incorporate both the water expulsion effect and the mantle's low viscosity beneath Antarctica.

"Sea level rise doesn't stop when the ice stops melting," Pan said. "The damage we are doing to our coastlines will continue for centuries."

An international research group led by Prof. WANG Bo and Prof. SHI Gongle from the Nanjing Institute of Geology and Palaeontology of the Chinese Academy of Sciences (NIGPAS) collected approximately 25,000 fossil-containing amber samples and about 5,000 fossil plants in Zhangpu County, Fujian Province, southeast China from 2010 to 2019.

Their findings were published in Science Advances on April 30.

The Zhangpu biota, including amber biota and co-occurring megafossils, is the richest tropical seasonal rainforest biota discovered so far. It reveals that extraordinary species diversity existed within a 14.7 million-year-old tropical rainforest and sheds light on the evolution of the rainforest.

Diverse winged fruits of Dipterocarpaceae and legumes as well as leaves of 78 different broadleaf trees show that tropical seasonal rainforests extended further north than today, offering an insight into what changes might take place in a future warmer world if ecosystems are able to adapt.

The Zhangpu amber biota contains a diverse, exquisitely preserved fossil arthropod fauna and abundant botanical and other inclusions such as fungi, snails, and even feathers. Botanical inclusions include bryophytes (liverworts and mosses) and flowering plants.

Arthropod inclusions cover an impressive array of more than 250 families including various spiders, mites, millipedes, and at least 200 families of insects in 20 orders. The extremely high variety of arthropods renders the Zhangpu amber biota one of the world's four richest, along with the widely known Cretaceous Burmese amber biota (> 568 families), Eocene Baltic amber biota (> 550 families), and Miocene Dominican amber biota (205 families).

The insect fauna in Zhangpu amber include many ants, bees, lacewings, stick insects, termites, and grasshoppers that are today restricted to tropical Southeast Asia and/or New Guinea.

"The most unexpected finding is that the high diversity of ants and springtails all belong to living genera. In addition, the vast majority of previously identified insects in Zhangpu amber, such as bark lice, grasshoppers, beetles, and bees, also belong to living genera," said Prof. WANG.

These results suggest that Asian rainforest insect communities have remained stable since the middle Miocene (at least 15 million years ago). It also highlights that tropical rainforests act as museums of biological diversity at the generic level. The relative ecological stability of such "megathermal" environments facilitates the continued accumulation of species diversity and makes them even more precious than previously realized.

The Zhangpu amber biota is unique because the samples are not commercially extracted and consequently the species census is minimally skewed by human selective bias. Moreover, its precise age is well-constrained by radioisotopic dating and the associated plant compression/impression fossils allow quantitative reconstruction of the ancient climate.

Compared to the modern climate of Zhangpu, the most notable difference is that the middle Miocene climate had a warmer winter, leading to a relatively stable temperature throughout the year.

In scenarios of global warming, winter warming is commonly more pronounced than summer warming, and has larger and more widespread effects on terrestrial and marine ecosystems. It reduces "winterkills" and is beneficial for reproduction and growth of tropical animals and plants.

"Winter warming is likely to have been a major driver of the northern expansion of the megathermal biota in South China during the Mid-Miocene Climatic Optimum," said Prof. SHI.

WILMINGTON, Del. (April 30, 2021) - Social, economic, and demographic factors that can influence health did not affect families' acceptance of telehealth for their children's cardiac care during the COVID-19 pandemic, according to a study presented at the Pediatric Academic Society 2021 Virtual Meeting. The study, by research team members at the Nemours Children's Health System, suggests that telehealth is a feasible tool for families regardless of household income, language, or insurance type.

"When we saw that the use of telehealth would be necessary for maintaining children's cardiac care during COVID, we worried that some of our families would face barriers in using it," said lead author Carissa M. Baker-Smith, MD, MPH, director of Preventive Cardiology at Nemours. "We saw that these factors were not a barrier in families' choice to use telehealth and in fact may have been a welcome option."

A total of 849 pediatric patients were scheduled for cardiac visits at Nemours Cardiac Center, Wilmington, Del., between March 30 and May 8, 2020. When all non-urgent care was paused, families were given the option of using telehealth for their visit, or rescheduling the visit until a future date. The study team found that 52 percent agreed to telehealth visits, while 48 percent chose to reschedule. Patients with a primary diagnosis of abnormal heart rhythm, acquired heart disease, chest pain, dysautonomia/dizziness, and dyslipidemia, as well as families of children of Hispanic ethnicity were more likely to accept telehealth appointments. Families of older children, children scheduled for follow-up rather than new visits, and families who lived in Delaware, the same state as the care facility, were less likely to accept telehealth care.

Based on the high acceptance levels, the Cardiac Center has continued to offer telehealth appointments for certain appointment types even as in-person care has largely resumed.

Key takeaways

The basis of the ACS Quality Verification Program rests on 12 standards; all of which are being reviewed in the medical literature to demonstrate evidence for the program.
Five principles key in on the role of data surveillance, standardized process, and systems; all are interrelated.
The most robust evidence has been identified around the standards for data and use of data.

CHICAGO (April 30, 2021): Evidence from the medical literature that contributes to adopting a new practice into clinical care is integral for surgical quality improvement. Part II of a comprehensive review of five key principles of the American College of Surgeons (ACS) Quality Verification Program demonstrates the role of data surveillance and standardized processes and systems to identify problems and improve the quality and safety of surgical patient care. The peer-reviewed article is published on the Journal of the American College of Surgeons (JACS) website in advance of print.

"Data is critical to quality improvement because it's impossible to know your problems without objective measures of what they may be. However, the existence of data alone is not enough to further quality improvement. That's where processes come into play; processes of focused review help to find problems and provide appropriate avenues to address them," said Chelsea Fischer, MD, MS, ACS Clinical Scholar in Residence and co-first author of the literature review.

"Systems, in turn, are needed to accompany data review in order to make it useful to clinicians and anyone involved in surgical quality improvement. A system may be a process of how often data is reviewed--and in what format--along with the outputs of that review, meaning who looks at it and how it's dealt with," she explained.

The ACS Quality Verification Program helps surgeons and hospitals identify the resources needed for robust surgical quality improvement. The program is based on a set of principles or standards at the foundation of surgical quality. These principles were gleaned from the knowledge and experience of surgical experts as well as the ACS experience with 3,000 hospitals that participate in ACS Quality Programs. The principles were published in the Optimal Resources for Surgical Quality and Safety, also known as the "ACS Red Book."

The basis of the Quality Verification Program rests on 12 standards: leadership commitment and engagement, surgical quality officer, surgical quality and safety committee, safety culture, data collection and surveillance, continuous quality improvement using data, case review, surgeon review, surgical credentialing and privileging, standardized and team-based processes of care, disease-based management, and compliance with regulatory performance metrics.

"The Red Book, which serves as the framework for the ACS Quality Verification Program, provides a detailed overview of the essential elements that any hospital or surgical practice should have in place to deliver safe, reliable, quality care. Through its 12 standards, it provides the resources and support that surgeons and their institutions need as they traverse the road to surgical quality improvement," said article coauthor, David B. Hoyt, MD, FACS, ACS Executive Director.

This new literature review in JACS is the second of three investigations to examine the evidence that supports these standards. The study group gathered and analyzed evidence associated with five principles that address processes for identification and resolution of quality improvement issues: case review, peer review, credentialing and privileging, data for surveillance, and continuous quality improvement using data.

"This article furthers our understanding of the evidence that forms the foundation for the ACS Quality Verification Program. Using 12 standards, the program can be implemented by any hospital regardless of location or size. Real and demonstrable achievements have been demonstrated by participating hospitals including increasing value and reliability and improving the resource and infrastructure that leads to even better care and results for their surgical patients. Interestingly, benefits have been appreciated by the operating surgeons, the surgical team members, and surgeon and hospital leadership," said article coauthor, Clifford Y. Ko, MD, MSHS, FACS, FASCRS, Director of the ACS Division of Research and Optimal Patient Care.

For this analysis, the U.S. National Library of Medicine's Medline database was searched for articles published between its inception in 1964 and January 2019. Articles evaluated the relationship between one of the Red Book principles and patient or organizational quality outcomes. Two reviewers synthesized and summarized information in a hierarchical fashion from these studies.

After identifying 9,098 studies involving the five principles, a total of 184 were selected for systematic review for this portion of the research. Several primary studies also were included for assessment. The authors primarily looked at observational, retrospective studies; not all were directly related to surgery, some came from other procedural specialties. A summary of the evidence follows.

Case review
A review of individual surgeon cases

Evidence from these investigations showed that outcomes can be improved through the implementation of case reviews in two areas: quantitative outcomes and in identifying systems issues for quality improvement. Authors note that "characteristics of effective [case] review include standardized data-driven case identification, multidisciplinary input, and follow-up status of issues."

A total of 79 unique studies were included in this review; 14 included a prospective analysis from one single institution, 12 were retrospective single-institution studies, and one was a mixed-methods analysis.

Peer review
A review of surgeon and performance

The evidence reviewed supports peer review as a means to improve patient outcomes and contribute to quality improvement projects. Potential challenges identified included process variability, reviewer agreement of performance, and a long implementation time for the process. Authors note that, "Despite challenges, a well-implemented program is found to be useful by providers."

Ten studies were reviewed for this category encompassing a collective of 24 studies. All looked at peer review from a quality improvement perspective.

Credentialing and privileging
The process of ensuring proper credentialing, privileging, and onboarding

The evidence supports standardized credential and privileging processes for surgeons to potentially improve patient outcomes, but the authors note that "current processes have considerable variation and opportunities for improvement."

This analysis included 73 articles: a collective of 70 unique studies, two multi-institutional surveys, a single-institution retrospective review, and one multi-institutional retrospective review.

Data for surveillance and quality improvement
Effective use of data to surveil for potential quality and safety issues

In all articles analyzed, the evidence supports the use of registries to identify clinical problems. Furthermore, one-half of the articles supported using registries for implementation and surveillance of quality improvement initiatives.

This analysis used 20 articles: one systematic review, 10 multi-institutional retrospective reviews, four single-institutional retrospective reviews, and four descriptive case studies.

Continuous quality improvement using data
Driving continuous quality improvement

The authors also focused on three of the data surveillance studies (noted above) to look at how surveillance contributes to continuous quality improvement over time, which they write "can be just as important to quality and safety as the initial identification of problems." Registries were cited as the tool of implementation for this practice when used to provide a clinical practice audit paired with feedback to clinicians.

In terms of the role of administrative claims data, the authors noted that "combining administrative claims data with prospectively collected clinical data through EHR linkages can allow providers real-time data for continuous monitoring of quality issues." However, while data is an important tool, they note that it's "likely insufficient" by itself, and "development of quality improvement initiatives is essential to drive patient care improvement."

"While there's some face validity to these quality improvement concepts, our analysis of the medical literature does supply the evidence supporting the framework for these concepts as well. This is particularly true around the standards of data and use of data. We found robust literature supporting these data concepts for the program standards, and certainly evidence in the areas of case review, peer review, and credentialing and privileging too," Dr. Fischer concluded.

In addition to Dr. Ko and Dr. Hoyt, Dr. Fischer's other study authors include Q. Lina Hu, MD, MS, ACS Clinical Scholar in Residence and co-first author, Annie B. Wescott, MLIS, and Melinda Maggard-Gibbons, MD, MSHS.

"FACS" designates that a surgeon is a Fellow of the American College of Surgeons.

Authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Citation: Evidence Review for the American College of Surgeons Quality Verification. Part II: Processes for Reliable Quality Improvement. DOI: /10.1016/j.jamcollsurg.2021.03.028.

For many of us, adding salt to a meal is a perfectly normal thing to do. We don't really think about it. But actually, we should. As well as raising our blood pressure, too much salt can severely disrupt the energy balance in immune cells and stop them from working properly.

Back in 2015, the research group led by Professor Dominik Müller of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and the Experimental and Clinical Research Center (ECRC) found that elevated sodium concentrations in the blood affect both the activation and the function of patrolling monocytes, which are the precursors to macrophages. "But we didn't know exactly what was happening in the cells," says Dr. Sabrina Geisberger of the Berlin Institute for Medical Systems Biology (BIMSB) at the MDC. She is lead author of the study of an international research team led by MDC scientists together with colleagues from University of Regensburg and from Flanders Institute for Biotechnology (VIB) /Hasselt University in Belgium. It was funded by the German Center for Cardiovascular Research (DZHK) and has now been published in the journal Circulation.

Salt disrupts the respiratory chain in cells

Working with biochemist and metabolomics expert Dr. Stefan Kempa of BIMSB, the researchers began in the lab by looking at the metabolism of immune cells that had been exposed to high salt concentrations. Changes appeared after just three hours. "It disrupts the respiratory chain, causing the cells to produce less ATP and consume less oxygen," explains Geisberger. ATP (adenosine triphosphate) is the universal fuel that powers all cells. It provides energy for the "chemical work" - synthesizing proteins and other molecules - required for muscle power and metabolic regulation. ATP is produced in the mitochondria, the cell's "power plant," using a complex series of biochemical reactions known as the respiratory chain. "Salt very specifically inhibits complex II in the respiratory chain."

This has consequences: The lack of energy causes the monocytes to mature differently. "The phagocytes, whose task is to identify and eliminate pathogens in the body, were able to fight off infections more effectively. But this could also promote inflammation, which might increase cardiovascular risk," explains Müller.

Effects of salt are reversible

Professor Markus Kleinewietfeld of Hasselt University and VIB, and Professor Jonathan Jantsch of Universität Regensburg, were heavily involved in the work investigating human monocytes and macrophages. They were able to show that salt affects the functioning of human phagocytes in the same way.

Researchers at the ECRC, which is run jointly by the MDC and Charité - Universitätsmedizin Berlin, then conducted a study in which healthy male participants supplemented their usual diets with six grams of salt in tablet form every day for 14 days. In another clinical study, the researchers investigated a familiar scenario: eating a pizza delivered by an Italian restaurant. They then analyzed the monocytes in the participants' blood. The findings showed that the dampening effect on mitochondria doesn't just occur after an extended period of increased salt intake - it also happens after a single pizza. Data from the pizza experiment showed how long the effect lasted: Blood was taken from the participants after three and eight hours, and the effect was barely measurable in the second sample.

"That's a good thing. If it had been a prolonged disturbance, we'd be worried about the cells not getting enough energy for a long time," says Müller. The mitochondrial activity is therefore not permanently inhibited. That said, the continuous risk of sodium on mitochondrial function if a person eats very salty food several times a day cannot be ruled out, but needs to be tested in the future. The pizza, incidentally, contained ten grams of salt. Nutrition experts recommend that adults limit their daily intake to five or six grams at most. The calculation includes the salt that is hidden in processed foods.

Small ion, big effect

"The fundamental finding of our study is that a molecule as small as the sodium ion can be extremely efficient at inhibiting an enzyme that plays a crucial role in the respiratory chain," says Kempa. "When these ions flood into the mitochondria - and they do this under a variety of physiological conditions - they regulate the central part of the electron transport chain." It therefore appears to be a very fundamental regulatory mechanism in cells.

Now the task is to investigate whether salt can also influence this mechanism in other types of cells. Kleinewietfeld believes that this is extremely likely because mitochondria aren't just present in immune cells; with the exception of red blood cells, they exist in every cell of the body. They can be found in particularly high numbers wherever a lot of energy is consumed - in muscle cells, neurons, receptors, and egg cells.

It is still not fully elucidated how different cell types regulate the influx of sodium into the mitochondria. Nevertheless, the study confirms that consuming too much salt can be bad for our health. "Of course the first thing you think of is the cardiovascular risk. But multiple studies have shown that salt can affect immune cells in a variety of ways. If such an important cellular mechanism is disrupted for a long period, it could have a negative impact - and could potentially drive inflammatory diseases of the blood vessels or joints, or autoimmune diseases," says Kleinewietfeld.

A research team at the University of Cologne has discovered previously undescribed bacteria in amoebae that are related to Legionella and may even cause disease. The researchers from Professor Dr Michael Bonkowski's working group at the Institute of Zoology have named one of the newly discovered bacteria 'Pokemonas' because they live in spherical amoebae, comparable to Pokémon in the video game, which are caught in balls. The results of their research have been published in the journal Frontiers in Cellular and Infection Microbiology.

Bacteria of the order Legionellales have long been of scientific interest because some of these bacteria are known to cause lung disease in humans and animals - such as 'Legionnaires' disease', which is caused by the species Legionella pneumophila and can sometimes be fatal. Legionellales bacteria live and multiply as intracellular parasites in the cells of organisms as hosts. In particular, the hosts of Legionellales are amoebae. The term 'amoeba' is used to describe a variety of microorganisms that are not closely related, but share a variable shape and crawling locomotion by means of pseudopods. 'We wanted to screen amoebae for Legionellales and chose a group of amoebae for our research that had no close relationship to the hosts that were previously studied. The choice fell on the amoeba group Thecofilosea, which is often overlooked by researchers,' explains Marcel Dominik Solbach.

And indeed, the spherical Thecofilosea serve as host organisms for Legionellales. In Thecofilosea amoebae from environmental samples, the scientists were able to detect various Legionellales species, including two previously undescribed genera and one undescribed species from the genus Legionella. 'The results show that the range of known host organisms of these bacteria is considerably wider than previously thought. In addition, these findings suggest that many more amoebae may serve as hosts for Legionellales - and thus potentially as vectors of disease. To investigate this further, we are now sequencing the complete genome of these bacteria,' said Dr Kenneth Dumack, who led the project.

In the future, these new findings should help to better understand how Legionellales bacteria are related amongst each other, and clarify their interactions with their hosts as well as the routes of infection in order to prevent outbreaks of the diseases in humans.

The researchers named one of the genera of bacteria they discovered 'Pokemonas.' The genus name 'Pokemonas' is a play on words based on the video game franchise 'Pokémon,' which celebrates its 25th anniversary this year and which most schoolchildren, students, and their parents should be familiar with. The name alludes to the intracellular lifestyle of the bacteria in the ball-shaped Thecofilosea amoebae, because in the 'Pokémon' series games, little monsters are caught in balls, much like 'Pokemonas' in the Thecofilosea.

Humans have significantly altered biodiversity in all climate zones of the Earth. This has been shown by a study now published in Science. Led by Prof. Dr. Manuel Steinbauer at the University of Bayreuth, and Dr. Sandra Nogué at the University of Southampton, an international team has investigated how the flora on 27 islands in different regions has developed over the last 5,000 years. Almost everywhere, the arrival of humans has triggered a markedly accelerated change in species composition in previously pristine ecosystems. This dynamic was particularly pronounced on islands colonised in the last 1,500 years.

The 27 islands selected for this study were never connected to the mainland and had been colonised by humans during the study period. Within these islands, pollen of wind-pollinated plants lies since millenia deposited in the sediments of lakes and bogs. The pollen was extracted from the sediment layers, dated, and identified to a respective plant species.

"For each of the 27 islands, our study shows how vegetation composition has changed over the last 5,000 years. Humans' colonisation of the previously undisturbed islands falls within this period. We can therefore trace how natural systems change as a result of human arrival. This transformation from a natural to a human-dominated system can only be observed on islands. On continents, humans have been extensively changing ecological systems for a very long time. What a natural ecosystem would look like here, we can often no longer tell," says Steinbauer.

The researchers compared the data obtained through pollen analyses with archaeological findings that provide information about when the islands were first settled by humans. The result provide a clear message. On 24 of the 27 islands studied, the arrival of humans marked a turning point in vegetation turnover. From this point on, vegetation changed at a significantly higher rate, its rate of change was accelerated by a factor of eleven.

The species composition changed particularly on islands that were colonised in the past 1,500 years, such as the Galapagos Islands and Robinson Crusoe Island off Chile. If, on the other hand, the first settlement took place longer ago, the increase in the rate of species turnover was less pronounced. The authors attribute this difference to an increasing technical know-how of agriculture and the associated effects on biodiversity. In addition, as a result of their increasing mobility, people may have introduced plant species from the mainland, compeating with native species on the islands.

"The results of the study highlight the extensive changes we humans are causing in ecological systems. The change in pollen composition in our study mainly reflects human land use over millennia. With the beginning of the industrial age, human induced transformation of ecological systems has accelerated even further. Adding to this, ecological systems are now additionally affected by human induced climate change" explains Prof. Dr. Manuel Steinbauer, corresponding author of the study. He is a member of the Bayreuth Centre for Ecology and Environmental Research (BayCEER), a research centre of the University of Bayreuth, and has been working here for several years on human influences on ecological systems. In this context, he is also leading a DFG (German Research Foundation) project that is investigating how climate change of geological time periods has influenced the risk of extinction of species.