Culture

New strategies for managing bowel and bladder dysfunction after spinal cord injury

East Hanover, NJ. March 12, 2020. Among the many challenges to independence and quality of life after spinal cord injury, two complications have emerged as top priorities for researchers - neurogenic bowel and neurogenic bladder. With funding from the Craig H. Neilsen Foundation, researchers formulated a framework for planning and executing the research needed in these areas, and established recommendations for translating research findings into practical recommendations for community use by individuals with spinal cord injury.

The development of metric standards was fundamental to their objectives, which included updating clinical recommendations for clinicians and consumers, understanding bowel physiology and establishing targets for therapeutic intervention, utilizing sensory technology to signal the need to void, optimizing neuromodulation to replace or restore functional control, and measuring the associations between diet and activity on bowel and bladder function.

The March issue of the Journal of Spinal Cord Medicine features this Open Access content: a commentary and two articles describing the bowel and bladder evaluation strategies that can be applied to the continuum of preclinical and clinical research and implementation in the community. In "Recommendations for evaluation of bladder and bowel function in preclinical spinal cord injury research," Holmes and associates focus on the appropriateness of various outcome metrics in the study of neurogenic bowel and bladder dysfunction, emphasizing metrics fundamental to the development of effective interventions.

For the next step on the continuum, in "Recommendations for evaluation of neurogenic bladder and bowel dysfunction after spinal cord injury and/or disease," Tate and colleagues rigorously assess the use of clinical tools and metrics in clinical trials. They recommend 15 clinical assessments for bladder dysfunction and 12 objective assessments of bowel dysfunction and identify eight measures for the self-report of bladder and bowel dysfunction.

In the accompanying commentary, "Neurogenic bowel and bladder evaluation strategies in spinal cord injury: New directions," David R. Gater, Jr., MD, PhD, MS, advises preclinical and clinical researchers, "...to take heed of these recommendations as they consider methodology for their studies and trials in neurogenic bladder and bowel, recognizing the importance of solid methodology to the development of clinical interventions that will enable people with disabilities to participate fully in their communities."

Credit: 
Kessler Foundation

Bursts of diversity in the gut microbiota

Scientists have been realizing that bacteria can mutate and evolve in our intestines much faster than previously thought. But know, researchers from the Instituto Gulbenkian de Ciência, have found that certain bacteria cells can evolve to mutate at rates 1000-fold higher than normal - called mutators - and thus generate bursts of diversity at unprecedented amounts.

Using laboratory mice and focusing on a gut bacteria that colonizes all humans, they show that amongst sea of rubbish, caused by many mutations which reduced the fitness of the mutators, a ruby was found: a beneficial mutation that increases the ability of the bacteria to eat a specific sugar in the gut and is responsible for the burst of diversity observed. This finding helps to explain the uniqueness of the microbiome within each person and the variation observed after some therapeutic interventions.

The study, published in PLoS Biology, carried out at Instituto Gulbenkian de Ciência. Ricardo Ramiro, first author of the study, states "we colonized mice with bacteria isolated from humans and observed the natural emergence of bacteria with extremely high mutation rates, which was perplexing to us." Akin to "bacterial cancer", these bacteria evolve at high speed but will carry hundreds of harmful mutations. The latter should render them unable to compete with the other microbiota members. However, these speedy bacteria could persist for long periods of time. "This was because the effect of the harmful mutations is much weaker than previously thought, but also because the lineages that acquire beneficial mutations do not become dominant", concluded Ricardo Ramiro.

Isabel Gordo, leader of the research group at IGC, states that "in the future, we want to find ways to modulate the effects of mutations, via diet interventions or chemical compounds, so that we can make harmful mutations more harmful for pathogenic bacteria and beneficial mutations more beneficial to help to keep the good bacteria in our guts".

Credit: 
Instituto Gulbenkian de Ciencia

New aflatoxin biocontrol product lowers contamination of groundnut and maize in Senegal

image: Ranajit Bandyopadhyay? in front of groundnut pile.

Image: 
Ranajit Bandyopadhyay?

In Senegal, groundnut and maize are commonly contaminated with highly toxic, cancer-causing chemicals called aflatoxins, which are produced by fungi in the genus Aspergillus when they infect crops. The main aflatoxin-producing species is A. flavus. This contamination typically occurs before harvest and can worsen depending on storage conditions. Consumption of these crops when containing high aflatoxin levels can result in rapid death.

However, not all Aspergillus flavus produce aflatoxins--about 20% of the species are non-toxin producing and known as atoxigenic. Atoxigenic isolates can be used as biocontrol agents to reduce aflatoxin content in crops when they are applied before crop flowering. The isolates then reproduce and become dominant in the fungal populations of treated fields, reducing the amount of aflatoxin-producers. Aflatoxin biocontrol products containing atoxigenic A. flavus isolates have been developed for use in the United States, Italy and several African countries.

Recently a team of plant pathologists have developed an aflatoxin biocontrol product, Aflasafe SN01, for use in Senegal, which includes four atoxigenic isolates native to Senegal and distinct from active ingredients used in other biocontrol products in Africa and elsewhere. Tests conducted in important crop production areas of Senegal for 5 years in more than 500 fields found that this product is highly efficient in reducing aflatoxin contamination in groundnut and maize.

"Based on the large volume of data systematically generated over 5 years from more than 500 trials conducted on smallholder farms, the article leaves no doubt that Aflasafe SN01 is extremely effective in hot, drought-prone areas even under difficult farming conditions across Senegal," says scientist Ranajit Bandyopadhyay. "Large-scale use of Aflasafe SN01 should provide health, trade, and economic benefits for Senegal."

This is an important advancement as aflatoxin contamination is a serious problem in Senegal and the neighboring The Gambia. Medical professionals have linked aflatoxin contamination with liver cancer. It has also been shown to interfere with immunity and is associated with stunting in children. Additionally, the contamination has devastating economic effects on Senegal, which produced a quarter of the world's groundnut exports in the 1960s but only one percent in 2013.

According to Bandyopadhyay, the most surprising element of this research was the high effectiveness of the multi-strain product in trials completely managed by resource-poor smallholder farmers and eagerness of public- and private-sector stakeholders to adopt the technology.

"Thousands of farmers in Senegal and The Gambia now use Aflasafe SN01 to reduce the aflatoxin burden in their groundnut and maize crops."

This research, published in the February issue of Plant Disease, is a component of the Africa-wide Aflasafe initiative, which develops and implements aflatoxin management strategies centered on the biocontrol technology. As of now, 14 Aflasafe products have been developed and registered for use in 10 African nations, with development in progress for 10 other nations.

Credit: 
American Phytopathological Society

Capping out-of-network hospital bills could create big savings

Placing limits on what hospitals can collect for out-of-network care could yield savings similar to more-sweeping proposals such as Medicare for All or setting global health spending caps, according to a new RAND Corporation report.

Because such an approach has the possibility to sharply cut hospital revenues, any cap would need to be set carefully as to not overly disrupt hospital operations, according to the study.

Modeling four approaches to setting caps on out-of-network hospital billing, researchers found there could be broad cost savings across the health system by creating pressure to drive down the amount providers could seek during negotiations for in-network payment rates with private insurers.

Under strict proposals such as limiting out-of-network charges to 125% of Medicare rates, in-network negotiated hospital prices could be cut by 31% to 40%, saving an estimated $108 billion to $124 billion annually.

"Among the many bold proposals to contain the cost of hospital care, limiting out-of-network payments arguably is less heavy-handed as it does not impose rates on all providers or shift the source of health insurance coverage for a large share of the nation's population," said Erin L. Duffy, the study's lead author and an adjunct researcher at RAND, a nonprofit research organization.

"While cost containment can benefit patients who face rising health costs, such changes also would disrupt hospital revenues," Duffy said. "A policy that reduces revenue so much that hospitals close or the quality of care is disrupted would not be in the best interests of patients."

There is growing interest among U.S. policymakers to use out-of-network payment limits not only to curb surprise medical bills, but as a tool to control rising health care costs. Such policies would cap the total amount that hospitals can be paid when they are not in-network and prevent providers from billing patients for a balance.

In addition to limiting surprise medical bills, out-of-network payment caps would reduce a hospital's leverage during contract negotiations by shifting the threat-point of out-of-network services from its self-imposed charges to the level of the legal payment limit.

Some government insurance plans, most notably Medicare Advantage, already place caps on out-of-network payments, and broad limits on out-of-network payments were proposed by several Democratic presidential candidates and in proposed Senate legislation. But there is limited information available about the role that out-of-network limits play in the negotiation process for in-network prices and the role that such limits might play in driving down payment rates nationally.

RAND researchers examined the potential impact of four proposals for out-of-network payment limits: 125% of Medicare payment rates (a strict limit), 200% of Medicare payment rates (a moderate limit), the average of payments made by private health plans in a state (a moderate limit), and 80% of average billed charges in a state (a loose limit).

They used information from the 2017 Centers for Medicare & Medicaid Services Hospital Cost Report Information System -- compiled and processed through the RAND Hospital Data repository - to estimate status-quo hospital operating expenses, Medicare payments, payments by private plans and hospital charges.

The analysis found that limiting out-of-network payments to 125% of Medicare would create the biggest drop in hospital payments.

A more-moderate payment limit set at 200% of Medicare rates would reduce negotiated hospital payments by 8% or 23%, depending on the modeling assumptions, while using the average private payment prices in a state are estimated to reduce negotiated hospital prices by 16% or 30%.

A payment limit of 80% of average billed charges in a state would be expected to create a modest price increase of 4% or a decrease of 3%, depending on the estimation approach used.

"Under the strict and moderate scenarios, the cost savings created by placing limits on out-of-network hospital bills creates savings that are similar to ideas such as Medicare for All, statewide rate setting and creating global health care budgets, without the particular potential disruption that could come from implementing these plans, although the limits would admittedly create some as-yet unknown level of disruption of their own," said Christopher Whaley, co-author of the report and a policy researcher at RAND.

Credit: 
RAND Corporation

Sound can directly affect balance and lead to risk of falling

What people hear and do not hear can have a direct effect on their balance, according to new research from the New York Eye and Ear Infirmary of Mount Sinai (NYEE). The research, published in the March 12 issue of JAMA Otolaryngology-Head & Neck Surgery, provides a better understanding of the relationship between hearing loss and why people fall, especially in the elderly population. The findings could lead doctors to screen for hearing loss in patients at high risk for falls, detect hearing loss in its early stages, and treat it quickly.

Falls are the leading cause of deadly injuries in the United States.

"Prior studies have shown that hearing loss is an independent risk factor for falls, even for those who were not dizzy. However, the reason why has never been completely understood, although it is believed to be related to the inner ear. This study found that the sounds we hear affect our balance by giving us important information about the environment. We use sound information to keep ourselves balanced, especially in cases where other senses--such as vision or proprioception--are compromised," said senior author Maura Cosetti, MD, Associate Professor of Otolaryngology at the Icahn School of Medicine at Mount Sinai, and Director of the Ear Institute at NYEE. "Balance is complicated and involves the coordination of many different sensory inputs. When people fall, doctors typically focus on vision issues, check for neuropathy in their feet and bone issues, and fully ignore issues related to hearing. This review highlights the importance of hearing for our sense of balance. And because hearing loss is treatable, getting hearing checked is a crucial first step."

In this study, a team of researchers from Mount Sinai and New York University's Steinhardt School of Culture conducted a comprehensive analysis of all published research since inception (PubMed, Cochran Database of Scopus) that investigated the association between sound and standing balance. They looked at 28 medical articles involving more than 700 patients. Many of the studies focused on fields that clinicians who treat falls would not typically encounter, such as sound engineering, computer science, physics, and psychology. The authors combined all of the studies and looked for trends in the data.

The studies analyzed mostly healthy adults, but also looked at patients with congenital blindness, vestibular loss (damage to the inner ear causing balance and eye issues, including vertigo), and different levels of hearing loss. All research examined how sounds affected someone's ability to keep their balance while standing still, often with their eyes closed and when standing on a pliable, squishy surface. They also looked at how wearing noise-canceling headphones (a complete lack of sound) affected balance. Some studies played white noise or static, while others used environmental sounds such as cocktail party chatter or running water. They found that people had more difficulty staying balanced or standing still on an uneven surface when it was quiet, but had better balance while listening to sounds.

The authors found that the type of sound was important when it comes to balance. More specifically, continuous background noise (usually static) was the most helpful for subjects to keep their center of gravity. Some types of sounds actually caused poor balance; for example, some people who listened to sound jumping back and forth through headphones (i.e. beeping that went from left to right) had difficulty standing upright. The authors believe this may be because sound can act as an "auditory anchor." More specifically, people use sounds like white noise to help unconsciously create a mental image of the environment to keep ourselves grounded. The research analysis also showed that sound became more important for balance when the subjects were given difficult balancing tasks (e.g., standing on a moving floor) or if the patients had pre-existing sensory issues. When people with vision loss, hearing loss, or balance problems heard stationary sounds, their posture dramatically improved. This suggests people rely more on hearing when other senses are impaired.

"This research suggests that sounds can have a stabilizing effect on balance--maybe acting as an anchor that patients can lean on when other senses are less reliable--and shows that being unable to hear sounds resulted in poorer balance. Ultimately an inability to hear puts patients at higher risk for instability and falls," adds Dr. Cosetti. "Elderly patients have a number of factors that put them at greater risk of falling, and hearing loss is a significant and under-recognized contributor. Age related hearing loss is prevalent, affecting up to two-thirds of those over the age of 70, and should be considered and checked in those at high risk for falls. Future research will confirm whether treating that hearing loss (with hearing aids or other implants) will also serve as a type of 'balance aid' like a cane, giving access to important information that could be used to improve balance and decrease fall risk."

The analysis highlighted large gaps in research on hearing loss and balance. Future studies are needed that look at different levels of hearing loss, and how hearing aids and cochlear implants affect balance. The researchers added that more studies using everyday sounds like traffic or shopping malls or airports are necessary to understand more about fall risks in people with hearing loss. Also, more studies focused on older adults need to be conducted.

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

Estimating adults at high risk for vision loss, evaluating care use

Bottom Line: The estimated number of U.S. adults at high risk for vision loss increased from 2002 to 2017 in this observational study based on national survey data. Adults at high risk for vision loss included those who were 65 or older, had a self-reported diagnosis of diabetes, or had eye or vision problems. Researchers estimated there were more than 93 million adults in 2017 at high risk for vision loss compared with almost 65 million in 2002, an increase attributed in part to an aging population. About 57% of adults reported visiting an eye care professional annually; almost 60% reported having a dilated eye exam; and 9 out of 100 adults who needed eyeglasses said they couldn't afford them. This analysis included survey responses from nearly 31,000 adults in 2002 and 33,000 in 2017. Limitations of the study include those inherent with the use of self-reported data. Public health efforts to improve awareness of the importance of eye care could reduce unnecessary vision loss.

Authors: Sharon H. Saydah, Ph.D., Centers for Disease Control and Prevention, Hyattsville, Maryland, and coauthors.

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

(doi:10.1001/jamaophthalmol.2020.0273)

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

Credit: 
JAMA Network

Poor physical health a barrier for job seekers with serious mental illness

People with serious mental illness believe their physical health problems rather than psychological health make it difficult for them to find jobs, according to a Rutgers study.

"The study underscores the urgent need for integrated mental health and physical health care for people with serious mental illness, especially those with long-term, chronic conditions," said lead author Ni Gao, an associate professor at Rutgers School of Health Professions.

"Without addressing physical health problems, people with serious mental illness will continue to experience more health problems and diseases and do not seek employment that could improve their quality of life."

About 11.4 million U.S. adults have a serious mental illness -- such as schizophrenia, anxiety, major depression and bipolar disorder -- and up to 90 percent are unemployed, with about three million that are dependent on public assistance, including Supplemental Security Income and Social Security Disability Insurance.

Chronic unemployment is a major concern since it can exasperate stress, anxiety, depression and cardiovascular disease and reduce access to the care they need to manage their physical and mental conditions.

The goal of the Rutgers study, published in The Journal of Vocational Rehabilitation, was to better understand how a person's perception of their mental and physical health affects job seeking. The study was funded by a grant by the National Institute on Disability, Independent Living and Rehabilitation Research of the U.S. Department of Health and Human Services.

Researchers met over one year with 162 people with serious mental illness living in supportive housing programs. At each meeting, they assessed the participants' physical health and employment-related activities, such as the number of applications submitted, interviews they had gone to, job offers that were made and what these individuals identified as their barrier to getting a job.

Almost half of the participants had a high school diploma and 27 percent were college-educated. About 60 percent had not been employed during the previous five years, but all expressed a desire to seek employment when enrolled in the study.

In each of the monthly check-ins, 11 to 26 percent of the participants reported that their long-term physical health conditions -- such as diabetes, chronic pain and obesity -- prevented them from job seeking versus zero to 2 percent who reported barriers due to long-term mental illness, such as lack of energy in job seeking due to depression or anxiety symptoms.

According to Gao, people with serious mental illness often do not receive the same physical care as the general public for many reasons, such as lack access to high-quality and affordable health care, and physical health problems of this population often being under-recognized and under-treated by health care providers.

"Studies have shown that the life expectancy of people with serious mental illness may be reduced by up to 25 years compared with the general population, but that employment may be one of key elements to improving and maintaining both their mental health and physical health. Employment increases their resources for better living conditions and access to quality health care, promotes positive self-identity and peer respect," said Gao. "These are people who are unemployed despite having a desire to work."

Therefore, the integration of mental health, physical health and vocational rehabilitation for this underserved group deserve public attention, she said.

Credit: 
Rutgers University

A molecular map for the plant sciences

image: By mapping more than 18,000 proteins, TUM scientists have created an extensive molecular reference for the popular model plant Arabidopsis thaliana, which is freely accessible via the online database "ProteomicsDB".

Image: 
Chair of Proteomics and Bioanalytics

Every cell of any organism contains the complete genetic information, or the "blueprint", of a living being, encoded in the sequence of the so-called nucleotide building blocks of DNA. But how does a plant create tissues as diverse as a leaf that converts light into chemical energy and produces oxygen, or a root that absorbs nutrients from the soil?

The answer lies in the protein pattern of the cells of the respective tissue. Proteins are the main molecular players in every cell. They are biocatalysts, transmit signals inside and between cells, form the structure of a cell and much more.

"To form the protein pattern, it is not only important which proteins are present in a tissue, but, more importantly, in what quantities," explains Bernhard Kuster, Professor of Proteomics and Bioanalytics at TUM. For example, proteins of the photosynthesis machinery are found primarily in leaves, but also in seeds, yet at a thousand times lower levels.

Laboratory plants as a model for basic research

The team around Dr. Julia Mergner and Prof. Bernhard Kuster examined the model plant Arabidopsis thaliana, or thale cress, using biochemical and analytical high-throughput methods to find out more about the molecular composition.

For 40 years, this rather inconspicuous weed with small white flowers has been the "laboratory mouse" of plant biology. It is small, generally undemanding and easy to grow. These properties have paved the way for its frequent us in genetics and molecular biology. The fact that insights from basic research on Arabidopsis can often be transferred to crop plants also makes Arabidopsis interesting for plant breeding research.

Most of the data was generated using a method called liquid chromatography-tandem mass spectrometry, which enables the analysis of thousands of proteins in parallel in one experiment and bioinformatics methods helped analyze the huge amounts of data.

Arabidopsis-Atlas for the global scientific community

"For the first time, we have comprehensively mapped the proteome, that is, all proteins from the tissues of the model plant Arabidopsis," explains Bernhard Kuster. "This allows new insights into the complex biology of plants."

All results of the research work were summarized in a virtual atlas which provides initial answers to the questions:

How many of the approximately 27,000 genes exist in the plant as proteins (> 18,000)?

Where are they located within the organism (e.g. flower, leaf or stem)?

In what approximate quantities do they occur?

All data is freely available in the online database ProteomicsDB, which already contains a protein catalog for the human proteome, which the same team at TUM decoded in 2014.

Research results as the basis for future analysis of crop plants

One can anticipate that there are similarities between Arabidopsis and the molecular maps of other plants. "The Atlas should, therefore, also inspire research on other plants," says Kuster.

In the future, the researchers will turn their attention to the analysis of crops. Of particular interest will be to investigate how the proteome changes when plants are attacked by pests or how plants can adapt to climate change.

Credit: 
Technical University of Munich (TUM)

Novel IR-LEGO system enables single-cell labeling and tracking in zebrafish embryos

video: Time-lapse live imaging of labeling a single caudal aorta endothelium cell in zebrafish.

Image: 
HKUST

Heterogeneity broadly exists in various cell types both during development and at homeostasis. Investigating heterogeneity is crucial for understanding the complexity of ontogeny, dynamics, and function of specific cell types.

However, traditional bulk-labeling techniques are incompetent to dissect heterogeneity within cell population, while the new single-cell lineage tracing methods invented in the last decade can hardly achieve high-fidelity single-cell labeling and long-term in-vivo observation simultaneously.

To tackle these problems, a team of scientists, led by Prof. QU Jianan and Prof. WEN Zilong from the Hong Kong University of Science and Technology (HKUST), has developed a novel optical technique, which enables them to label a single hemogenic endothelium cell in a zebrafish embryo and track the cell and its descendants.

"We develop an infrared laser-evoked gene operator (IRLEGO) technology, in which a two-photon fluorescent thermometer is utilized to measure the temperature rise in-vivo to achieve precise single-cell labeling," said Prof. Qu, Professor at the Department of Electronic and Computer Engineering at HKUST. "The two-photon microscopy-based thermometry could perform in-vivo and non-invasive imaging of a temperature rise in the region around the Infrared laser focal point in the tissue with an accuracy of about 0.5?C. Using this state-of-the-art fluorescent thermometer, we successfully measured the temperature distributions in the region close to the infrared laser focal point in live zebrafish. The results show that the temperature can be raised to 40-50?C for heat-shock induction in a well-defined small 3D volume (~15-20 μm), which is about the size of one or two cells."

In addition, the background noise - common issue among various single-cell lineage tracing technologies and namely the appearance of green fluorescent protein signals in zebrafish without heat shock - creates a major challenge to single-cell lineage tracing. To minimize the effect of this background noise, the team developed a statistical algorithm to determine the lineage distribution derived from a single cell.

"Using this tool, we documented that the hemogenic endothelium (HE) cells in the posterior blood island of zebrafish are heterogeneous in terms of hematopoietic potential. Our study demonstrated that the high-precision single-cell IRLEGO technology has outstanding capacity to perform single-cell labeling and long-term in-vivo lineage tracing," Prof. Wen, Professor at the Division of Life Science at HKUST said.

The research team - in collaboration with Prof. XU Jin of the Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology - also revealed that there are at least two distinct populations of hemogenic endothelium cells. One of them can give rise to both lymphoid and myeloid cells, while the other can only give rise to myeloid cells.

"These findings shed light on the mechanisms of blood formation, and potentially could provide useful tools to study the development of diseases such as leukemia. Additionally, the single-cell labeling technology could be applied to study the development of other tissues and organs and to answer many important questions related to stem cell biology, including cancer stem cells," Prof. Wen added.

The research findings were recently published in the scientific journal eLife.

"In future, we aim to apply the single-cell labeling technology to answer fundamental biological questions and develop therapeutic strategy against a variety of diseases, such as developmental origin(s) of different types of tissues, tracing single cell movement in vivo, e.g. immune cell responses to a variety of induction signals, monitoring cell competition in tissue homeostasis and cancer formation and etc.," Prof. Qu added.

Credit: 
Hong Kong University of Science and Technology

Learning how cancer cells coordinate and collaborate to multiply and metastasize

image: A large-scale network structure formed in vitro by cancer cells. The diameter of the image is 14 mm.

Image: 
Osaka University

Osaka, Japan - Cancer cells are known to migrate and collaborate to form networks that function as conduits providing access to nutrients and blood vessels. Now, researchers in Japan have generated similar large-scale structures from cancer cells in the laboratory and thus gained a better understanding of the underlying forces and their interactions.

Proliferating cells often cooperate in order to form self-beneficial large-scale structures; these include bacterial biofilms, protective epithelial monolayers or even more complex configurations such as endothelial capillaries. Malignant cells, in a process called vasculogenic mimicry, form structures that facilitate access to nutrients for tumor growth and to blood vessels for metastasis. The biochemical and biophysical mechanisms are not well understood, as this purposive behavior was difficult to reproduce experimentally until now.

In a study published in the Biophysical Journal in March 2020, researchers from Osaka University in collaboration with Advanced ICT Research Institute, the National Institute of Information and Communications Technology (NICT), have demonstrated migration and large-scale structure formation by cancer cells grown on Matrigel substrate, and have developed simple simulated models that reproduce their observations.

The research team first cultured HeLa cells, a strain of epithelial-like cervical cancer cells, on Matrigel, a gelatinous protein mixture resembling the extracellular environment of many tissues, and showed that the cells migrate aggressively and form large-scale structures. This was previously difficult to achieve in vitro as HeLa cells are relatively non-motile on glass. Using time-lapse imaging they analyzed the cell migration patterns and quantified the large-scale structures with a two-point correlation function.

"We observed that HeLa cells first exhibited increased motility on Matrigel, which later decreased after they integrated into a spatially distinct structure," explains Dr. Tokuko Haraguchi, senior researcher at NICT. "We also noted that HeLa cells in close proximity formed bridges between cell aggregates, and that structures were formed in a cell-density dependent manner."

To explain these results, the researchers developed a simulated model in which cells migrate and interact using two distinct forces: remote forces that act at a distance through substrate deformation, and contact forces between cells in physical proximity. By selectively enabling these forces, they modelled the three types of structures formed—islands, network-like structures and continents—according to cell density.

Tadashi Nakano, lead author, explains the potential implications of their findings. "Cancer cells may rely on vasculogenic mimicry for survival and proliferation," he says. "A complete understanding of this process can, by manipulation of the relevant cell density and force parameters, inhibit these network-like structures. This may have great potential for combating cancer."

Credit: 
Osaka University

Special report highlights potential therapeutic agents, vaccines for COVID-19

Since the first reports of a new coronavirus disease in Wuhan, China, in December 2019, COVID-19 has spread rapidly across the globe, threatening a pandemic. Now, researchers from CAS, a division of the American Chemical Society specializing in scientific information solutions, have issued a special report in ACS Central Science. In the report, they provide an overview of published scientific information on potential therapeutic agents and vaccines for the virus, with an emphasis on patents.

According to the World Health Organization, as of March 2, 2020, COVID-19 caused almost 90,000 confirmed illnesses and more than 3,000 deaths. The responsible virus, known as SARS-CoV-2, primarily attacks the lower respiratory system to cause viral pneumonia, but it may also affect the gastrointestinal system, heart, kidney, liver and central nervous system. If SARS-CoV-2 is not quickly contained, the virus could have devastating effects on people's lives, worldwide health systems and the global economy. To assist with research efforts to discover therapies and vaccines for COVID-19, Cynthia Liu led a group of CAS scientists who analyzed the published scientific data on SARS-CoV-2 and related coronaviruses.

The researchers reviewed the rapidly growing body of journal articles related to COVID-19 and SARS-CoV-2, as well as patents having to do with human coronaviruses. From the last week of 2019 through March 1, 2020, more than 500 journal articles related to the virus were published electronically or in print, with numbers steadily increasing week-by-week. Topics included clinical manifestations, treatment regimens, viral structure and mechanisms, antiviral agents, and diagnostics. To date, more than 500 patents have been issued for vaccines and for therapeutic agents, such as antibodies, cytokines and nucleic acids, that could help prevent or treat coronavirus infections. Because SARS-CoV-2 is similar to other coronaviruses, such as SARS-CoV-1 and MERS-CoV, the researchers highlighted therapies previously explored for these other viruses that could also be applicable to SARS-CoV-2.

The authors do not acknowledge any funding sources for this study.

Credit: 
American Chemical Society

Preterm babies are more likely to be diagnosed with reactive attachment disorder

A new study by the Research Centre for Child Psychiatry of the University of Turku, Finland, suggests that premature babies have the risk of reactive attachment disorder that can impair child's ability to function in normal situations and their social interactions and it is connected with later child protection issues, psychiatric and substance use disorders, and social exclusion.

- The study showed that children's risk of being diagnosed with reactive attachment disorder increases by three times if their gestational age at birth is less than 32 weeks. The risk was twofold if the birth weight was less than 2.5 kilos, or if the newborn required monitoring in a Neonatal Intensive Care Unit, says lead author, researcher Subina Upadhyaya.

The results acknowledged parental age and psychiatric and substance abuse diagnoses, and mother's socio-economic status and smoking. Therefore, the association between attachment disorder and early preterm birth is not due to differences in these parental background or lifestyle differences between the diagnosed and the control group.

This is the first population study to report perinatal and obstetric risk factors for RAD. Previously, the research group discovered an association between parental mental health diagnosis, parental substance abuse and RAD.

Results support family-centered treatment

According to Professor in Child Psychiatry Andre Sourander from the University of Turku, the results benefit the planning of preventive and early mental health services.

- The fact that premature birth is so strongly associated with reactive attachment disorder is an important finding. It indicates that family-centered support of early parent-infant interactions and need for care should be taken into account when treating premature babies, says Sourander, who led the study.

Sourander says that most of the children in the study were born in the 1990s and early 2000s. Treatment practices have changed since then in many countries.

- The management of premature infants should be multidisciplinary and personalised. Parent-infant interaction and family-centered care have recently received attention, and the care of premature infants has become increasingly comprehensive. The practice of skin-to-skin care is increasingly becoming popular worldwide. Early parental-infant closeness should be encouraged in centers that care for preterm infants.

- In the future, it is important to determine whether the independent relationship of prematurity to RAD has decreased as treatment practices have changed, Professor Sourander concludes.

All the children who were born in Finland between 1991-2012 and diagnosed with RAD were included in the study. There were a total of 614 cases and 2423 controls. The study was part of Inequalities, Interventions, and New Welfare State research flagship funded by Academy of Finland.

Credit: 
University of Turku

GARDP partners with Japanese pharmaceutical in pursuit of new antibiotics

[Geneva/Tokyo - 12 March 2020] The Global Antibiotic Research and Development Partnership (GARDP) has today announced an agreement with Daiichi Sankyo for GARDP to access and screen the Daiichi Sankyo chemical library. The library will be tested by Institut Pasteur Korea with the goal of discovering novel antibacterial compounds. The agreement sees Daiichi Sankyo join Eisai and Takeda as part of an AMR Screening Consortium, which aims to accelerate GARDP efforts to identify compounds for development into treatments for drug-resistant infections.

Antimicrobial resistance is a major and rapidly growing public health concern and has been identified by the World Health Organization (WHO) as among the greatest threats to global health. Each year 700,000 people die due to drug-resistant infections. Without urgent action to develop new antimicrobial treatments, this number is projected to increase exponentially.

GARDP will test compounds from the Daiichi Sankyo chemical library, which have never been screened for antibacterial activity, against drug-resistant bacteria identified as a critical priority on the WHO priority pathogens list. Through the screening, GARDP hopes to identify novel compounds for further optimization and development.

"GARDP's partnership with Daiichi Sankyo gives GARDP the opportunity to screen a proprietary library that otherwise would not be tested for antibacterial activity," said Laura Piddock, GARDP Director of Scientific Affairs. "The AMR Screening Consortium is a wonderful opportunity to discover novel compounds to potentially develop into life-saving treatments for drug-resistant infections."

Credit: 
Global Antibiotic Research & Development Partnership

Misinformation on vaccines readily available online

image: Dr Lucy Elkin, MBChB (Otago)
PhD Candidate
Department of Primary Care and General Practice
University of Otago, Wellington.

Image: 
University of Otago

Parents researching childhood vaccinations online are likely to encounter significant levels of negative information, researchers at the University of Otago, Wellington, have found.

Lead researcher Dr Lucy Elkin says negative information about vaccines remains readily available on Google, Facebook and YouTube, despite attempts by the internet platforms to better control access to misinformation through algorithm and policy changes.

The researchers searched the three platforms for information on vaccines, mimicking the kind of 'real-life' search that would be conducted by a parent looking for information on childhood vaccinations. Their research is published in the leading scientific journal Vaccine.

Dr Elkin says that while most of the websites generated by Google (80 per cent) and videos published on YouTube (75 per cent) were positive about vaccines, half of the Facebook pages were negative towards vaccines.

"Parents would be able to find information encouraging or discouraging vaccination on the vast majority of the websites, Facebook pages and YouTube videos analysed, but popular pages on Facebook containing vaccine information were more polarised."

She says steps being taken to reduce the amount of "vaccine misinformation" shared on websites are likely to be improving the quality of information available on Google and YouTube.

"The greater proportion of vaccine negative content on Facebook compared to YouTube may reflect the different degrees to which providers are censoring vaccine-negative content.

"Facebook state that the purpose of their platform is to 'build community' and to 'connect with others'. This could mean that Facebook may intentionally connect people with like-minded views on vaccination and therefore have little interest in censoring vaccine-negative content.

"This is significant because, typically, when browsing anything on the internet, a person's search history is remembered and further similar content will be generated. Those reading vaccine-critical information on Facebook are more likely to come across vaccine-critical information in subsequent searches on any platform, regardless of whether they are looking on social media, or on a search engine."

Dr Elkin says the level of vaccine critical information on Facebook is concerning because evidence shows those viewing vaccine-critical information online are more likely to be hesitant about getting their children vaccinated.

"It is important that vaccine-promoting agencies continue to make every effort to maximize their presence online so that parents who are researching whether or not to vaccinate their children will encounter evidence-based information online."

She says health professionals can also help to accurately inform and support parents by referring them to credible websites containing well-validated information.

The research paper, 'Should I vaccinate my child? comparing the displayed stances of vaccine information retrieved from Google, Facebook and YouTube' is published in the international journal Vaccine.

Credit: 
University of Otago

Corporate social irresponsibility: Which cases are critically reported -- and which aren't?

Print media do not report corporate misconduct - such as environmental offences, corruption, or the violation of social standards - consistently and independently. Instead, the media are often influenced by their own interests, such as advertising revenues. That is the result of a new study by Dr. Marc Fischer, Professor of Marketing at the University of Cologne (Germany), and Dr. Samuel Stäbler, Assistant Professor of Marketing at Tilburg University (Netherlands). It will appear in the May issue of the Journal of Marketing, the world's leading academic journal in marketing.

Cases of corporate misconduct, summarized in the term Corporate Social Irresponsibility (CSI), are usually newsworthy events with high news value for the media. For the companies and shareholders concerned, such negative reporting can have significant financial consequences.

For the current study, the two marketing experts examined media coverage of 1,054 CSI events in 77 leading media from five countries (USA, Mexico, Germany, Great Britain and France). They wanted to find out when corporate misconduct is reported - and when it is not. To this end, they read, coded and assessed over 50,000 articles.

The results are explosive because, according to the authors, the extent of the reporting is by no means impartial: in general, the examined newspapers and magazines frequently report on the ethical misconduct of popular companies with well-known brands, as well as misconduct by foreign companies. However, if they have close advertising partnerships with a company, for example, they will report significantly less often on its CSI events. In cases where there is a close advertising partnership, the probability of reporting falls to less than 10 percent. However, almost twice as many newspapers report on the misconduct if it involves a foreign brand with misconduct in their country. According to the authors, liberal media moreover report more frequently on CSI than conservative media.

Interestingly, the media seem to be unaware of this distortion. Interviews with editors of leading media in Germany confirmed many findings even before the actual study was conducted. The editors claimed that neither advertising revenues nor the political orientation of the newspaper influenced reporting. However, the statistical results of the Cologne study, which are based on the evaluation of actual reporting on corporate misconduct, show the opposite.

Critical reporting has economic consequences: According to the study, the average financial loss on the U.S. stock exchange due to a CSI event amounts to around 321 million US dollars. The extent of the damage a CSI event does to a company strongly depends on how much media attention it gets. For example, the market only reacted to CSI cases if four or more U.S. media reported on them.

Therefore, it is important for companies to understand the underlying mechanisms by which news media select events in order to predict bad press and find ways to prevent it.

Professor Dr. Marc Fischer remarked: 'Our results call into question the self-proclaimed independence of the media. Among other things, it was astonishing how much more frequently the misconduct of foreign companies is reported, while in comparison, domestic companies are less frequently the subject of CSI reporting. Besides politicians, who sometimes behave opportunistically, the media exert a great deal of pressure and demand compliance with the highest ethical standards and social norms from public figures and companies. Our research on CSI reporting shows that media companies themselves do not always adhere to the high ethical standards they demand of others.'

Credit: 
University of Cologne