Culture

New movement monitoring system helping prevent falls in the elderly

image: 53 Assisted Living Facility (ALF) residents wore the wristbands for one-year to help researchers determine changes to their walking patterns.

Image: 
University of South Florida

ST. PETERSBURG, Fla. (May 7, 2018)- Technology that allows BMW's assembly lines to run more efficiently is now being used to accurately indicate when residents in Assisted Living Facilities (ALF) are at increased risk of falling.

William Kearns, president of the International Society for Gerontechnology and associate professor at the University of South Florida College of Behavioral and Community Sciences, collected 43 million pieces of location data by monitoring the movements of 53 ALF residents for a year. He did so by tracking their wristbands with a Real Time Location System (RTLS) sensor network. The technology was created by Ubisense and is currently used by BMW. Dr. Kearns calculated the straightness of their walk in near real-time using fractal dimension, a mathematical tool used to explain how complex travel patterns change based on the scale of measurement.

"From my previous research, my colleagues and I found the poorer the score on the Mini Mental State Exam, which assesses cognitive function, the higher the fractal dimension value," said Dr. Kearns. "It's through this calculation I learned that increased errors navigating the environment are related to long-term cognitive impairment due to dementia."

Dr. Kearns makes this conclusion following his study at the Sunrise Village Assisted Living Facility in Tampa, where automated computerized reports on each resident's fractal dimension value were generated. Future daily reports will allow administrators to more closely monitor increasing signs of wandering and investigate the potential causes, such as changes to a resident's diet, medication or sleeping habits. By making adjustments, fractal dimension values can be reduced, improving their navigation and ultimately prevent an impending fall.

Most ALFs have high turnover rates, some exceeding 150% per year. So the "corporate memory" about an elder's health status may be erased after just a few months. ALFs are also generally understaffed and cannot provide continuous individualized attention and care.

"We found the study by Dr. Kearns to be eye-opening," said Bunny Markarian, former administrator at Sunrise Village Assisted Living. "By monitoring our residents' walking pattern and any deviation, we, along with the visiting physician or ARNP, could intercede after investigating the cause. In many cases, this intervention prevented hospitalization of the resident or re-admission. And the residents involved in the study were excited to have a role."

RTLS is much more accurate than GPS and updates 100 times per second. It pinpoints one's location, indoors or outdoors, within six inches. GPS is limited to the outdoors and has a one-meter resolution. RTLS is most effective for open floorplans, typically found in ALFs, since there are typically fewer obstacles to negatively affect accuracy.

Dr. Kearns believes the wristband technology will eventually be used in at-home care. He'll present his findings at the International Society for Gerontechnology 11th World Conference tonight (May 7) at 5PM (EST) in St. Petersburg, Florida.

Credit: 
University of South Florida (USF Health)

Reflecting on possessions can curb people's impulse buying

HOUSTON - (May 7, 2018) - Consumers who reflected on their recently used personal belongings experienced less desire for an unexpectedly encountered product, were less likely to buy impulsively and expressed a lower willingness to pay for new products, according to a new paper by marketing and consumer behavior experts at Rice University.

"Should I Buy This When I Have So Much? Reflection on Personal Possessions as an Anti-Consumption Strategy" advances the theory that the desire to consume, like willpower, may function as a limited motivational resource that becomes depleted upon reflecting about favored personal possessions and leaves less desire for subsequent shopping urges.

The study was authored by Utpal Dholakia, the George R. Brown Professor of Marketing at Rice's Jones Graduate School of Business, and Rice doctoral students Jihye Jung and Nivriti Chowdhry. It will appear in the Journal of Public Policy and Marketing later this year.

"Reflection is about thinking deeply and remembering in detail how you used any one of your possessions recently," Dholakia said. "In our research, we've found it helps if the reflected-upon possession is something functional, like a kitchen implement, a lawn mower or a wristwatch."

The researchers conducted four studies. One of them was an online survey that included 165 United States-based participants, with an average age of 37 and consisting of equal male and female participation. Participants were prompted to "describe your recent experience with a product. Specifically, we would like you to think of any product that you purchased, currently own and have used recently."

Two examples of participants' reflections give a sense of the exercise:

"I have a pair of light Nike running shoes I used this morning. I bought them about a year ago for about $80. The reason I bought them was because my brother has a same pair which I tried on and really liked ... I used them this morning to go for a run. I went for a run around the neighborhood for half an hour. I really like these shoes because they're really light and they breathe easy. ... Sometimes I use them at work since I do a lot of walking and they are so comfortable." -- 25-year-old male
"I just purchased a Kindle Fire. It is black. I can read books and access the internet. It opens a world of novelty to me. I read a book in bed and checked the weather this morning before even getting up. I spent about 45 mins. I also downloaded several apps. I was lying down and the ease of Kindle use allowed me to comfortably read without noise to wake up my partner." -- 29-year-old female

The study had two other conditions. One was a control condition in which participants didn't do anything. In the other condition, participants formed a plan to use a possession they hadn't recently used, which is a common situation many people face because they have so many things they haven't used lately, the authors said.

After this experimental manipulation, study participants were given five products: a cashmere sweater, a stainless steel watch, a coffee maker, a chair and a box of high-quality chocolates. For each item, participants indicated how much they were willing to pay (WTP) for it. The researchers calculated a WTP index for each participant by standardizing each item's WTP and then adding the values.

The researchers found that those who had reflected on using their possession recently had a much lower WTP for a basket of products than either the control or the plan conditions. The total WTP for the five items of those who reflected was $227, compared with $265 for the control group and $281 for the planning group. In other words, reflection about recently used possessions lowered the person's willingness to pay for new items by about 14 percent compared with the control condition, the researchers found.

The other three studies - online surveys including a total of 867 U.S.-based participants, with about equal gender representation -- tested whether recalling the recent use of a personal possession would affect consumers' desire for and likelihood of purchasing an item impulsively; investigated the moderating role of hedonic (pleasurable) versus utilitarian (practical) possessions in producing consumption desire depletion; and ruled out an alternative explanation for the moderating role of the type of possession.

"The findings of these studies show that reflection about the recent use of one's possessions provides an effective method to quell the shopping urge and to reduce consumption," the authors wrote.

Credit: 
Rice University

New study links strong pupillary light reflex in infancy to later autism diagnosis

A new study published in Nature Communications shows that infants who are later diagnosed with autism react more strongly to sudden changes in light. This finding provides support for the view that sensory processing plays an important role in the development of the disorder.

Despite being defined by symptoms in social communication, researchers are increasingly embracing the view that the earliest signs of autism may reside in more basic processes of brain development. Also, in the latest edition of the diagnostic manual used to diagnose the condition in many countries, sensory symptoms have been included as defining features.

In the new study, the researchers investigated the pupillary light reflex in 9-to-10 month old infants - this reflex is a basic regulatory mechanism controlling the amount of light that reaches the retina. The infants who fulfilled criteria for autism at three years of age constricted their pupils more than infants who did not fulfill autism criteria at follow up. Further, the amount of pupil restriction in infancy was associated with the strength of autism symptoms at follow up.

"Earlier studies on older children with autism has suggested a weak pupillary light reflex in this group. These findings motivated us to assess the reflex in infant siblings of children with autism. Most of these infants develop typically, yet the probability of later being diagnosed with autism is considerably higher in this group than in the general population. Surprisingly, we found that in infancy, the group differences were in the opposite direction than in older children: We found stronger reflexes in the infants later diagnosed with autism than in controls" says Terje Falck-Ytter, Associate Professor at the Department of Psychology at Uppsala University and Principal Investigator for the study.

"We believe the findings are important because they point to a very basic function that has not been studied before in infants with later autism diagnosis."

The study is a part of the larger project Early Autism Sweden (EASE) (http://www.smasyskon.se), which is a collaboration between Uppsala University and the Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND) in Sweden. In this particular experiment, data from Sweden were combined with data from a similar longitudinal study of siblings with an older sibling with autism conducted at Birkbeck, University of London (UK). The participants in the current experiment were 9-10-months old when their pupillary light reflexes were examined and were followed until three years, when the diagnostic evaluation was conducted. In total, 147 infants with an older sibling with autism took part in the study, of whom 29 met criteria for autism at follow-up. The study also included a control group consisting of 40 infants from the general population.

"Currently, autism cannot be reliably diagnosed before 2-3 years of age, but we hope that with more knowledge about the early development of the condition, reliable diagnosis will be possible earlier, which should facilitate early access to intervention and support for the families. New knowledge about early development in autism may also provide new leads on strategies for early intervention" Falck-Ytter says. "Yet, the results in this study demonstrated significant group differences only, and it is too early to say whether the method can facilitate early detection in a clinical context."

Credit: 
Uppsala University

Breast cancer: Discovery of a protein linked to metastasis

Jean-François Côté, a researcher at the Montreal Clinical Research Institute (IRCM) and professor at Université de Montréal's Faculty of Medicine, studies metastasis, the leading cause of cancer-related death. Recently, his team uncovered a protein that, once deactivated, could prevent the development of metastases in an aggressive type of cancer, HER2-positive breast cancer.

One in eight women will be diagnosed with breast cancer in her lifetime and one in 30 is expected to die from it. The findings, published in the journal Cell Reports, could improve this prognosis.

'Cunning' cells

A cancerous tumour develops when cells proliferate at an abnormally high rate and agglomerate in healthy tissue. Some of these cells are even more cunning. "Sometimes, cancer cells manage to leave the tumour to spread in the body, which complicates the evolution of the disease," said Côté, director of the IRCM's Cytoskeletal Organization and Cell Migration Research Unit.

These cells move more easily than most of their peers. They detach from the tumour, enter the bloodstream and reach other organs, for example the lungs, bones or the brain. Called 'metastatic cells,' they are more difficult to destroy as they spread to other parts of the body and are more resistant to current treatments; 90 per cent of breast-cancer deaths are caused by metastases. Hence, one priority in oncology is to prevent tumour cells from spreading because it has the potential of saving many lives.

A promising target

Côté and his collaborators have taken a step towards actually blocking metastases. In their study, the IRCM team demonstrated that a protein, AXL, influences the occurrence of metastasis in HER2-positive cancer, an aggressive type that accounts for 20 per cent of breast cancers. In HER2-positive breast cancers, cells with high levels of AXL are more likely to detach from tumours to form metastases.

The research was done on mice and with samples of tumour cells taken from cancer patients in Montreal. Statistical indicators about patients are also encouraging. In women with HER2-positive cancer, it was found that the less AXL is present, the better the survival rate. Previously, researchers had linked the AXL protein to another type of cancer, triple negative breast cancer, but no one had examined its presence in HER2-positive cancer before Côté and his team.

"Based on this discovery, a treatment targeting AXL could reduce the risk of metastasis," said Côté.

It has already been shown that the action of AXL can be hindered. The IRCM researchers administered an AXL-inhibiting drug therapy to mice with HER2-positive tumours and found that metastases were less prone to develop. The drug is currently being tested in clinical trials for various therapeutic uses. If subsequent studies are as successful, this treatment could also be used to treat breast cancer patients. It would act as a complement to therapies targeting the HER2-positive tumour.

Further work is already underway in the IRCM laboratory.

"At the moment, we are checking whether the tumour's environment, such as blood vessels and the immune system, is affected when AXL is inhibited," said Côté. By getting a better picture of the phenomenon, it will be one more step towards treating the disease.

Credit: 
University of Montreal

New CRISPR technology 'knocks out' yeast genes with single-point precision

image: Illinois researchers created a system using CRISPR technology to selectively turn off any gene in Saccharomyces yeast. Pictured, from left: chemical and biomolecular engineering professor Huimin Zhao, graduate students Mohammad Hamedi Rad, Zehua Bao, Pa Xue and Ipek Tasan.

Image: 
L. Brian Stauffer

CHAMPAIGN, Ill. -- The CRISPR-Cas9 system has given researchers the power to precisely edit selected genes. Now, researchers have used it to develop a technology that can target any gene in the yeast Saccharomyces cerevisiae and turn it off by deleting single letters from its DNA sequence.

Such genome-scale engineering - in contrast to traditional strategies that only target a single gene or a limited number of genes - allows researchers to study the role of each gene individually, as well as in combination with other genes. It also could be useful for industry, where S. cerevisiae is widely used to produce ethanol, industrial chemicals, lubricants, pharmaceuticals and more.

Understanding and optimizing the genome could create yeast strains with increased productivity, said study leader Huimin Zhao, a University of Illinois professor of chemical and biomolecular engineering and a member of the Carl R. Woese Institute for Genomic Biology at the U. of I. Zhao's group published the new findings in the journal Nature Biotechnology.

"We want to use microorganisms as cellular factories to make valuable chemicals and biofuels," Zhao said. "The scale we have demonstrated in this study is unprecedented. CRISPR has been used to introduce point mutations - for example, to address genetic diseases - but Saccharomyces yeast has about 6,000 genes, and we want to be able to knock out each of these genes iteratively and find out how they affect the production of a target compound."

Researchers produce "knockout" yeast - where one gene has been deleted, or "knocked out" - to study how each gene contributes to the function of the cell. When a beneficial mutation is found, they can selectively breed yeast with that characteristic. Leading methods to produce knockout yeast excise the entirety of the targeted gene. This creates unintended problems, Zhao said, because many genes overlap each other. Deleting one gene also deletes portions of others, affecting multiple functions and making it difficult for researchers to truly isolate the effects of a single gene.

Each letter in a DNA sequence corresponds to a base, the building blocks that make up DNA chains. Zhao's group harnessed the precision of the CRISPR-Cas9 system to create a technique that allows them to delete just one base in a gene's DNA sequence. Since a cell "reads" DNA three bases at a time, this shifts the reading frame and knocks out the gene. Genes that overlap with the edited one remain unchanged and functional.

"We can introduce just one single base change on the entire chromosome. That makes a minimal disturbance in the function of the neighboring genes, so we can study how important the gene is in its cellular context. That kind of precision has not been achieved before," Zhao said.

Their technique, named CRISPR/Cas9 and homology-directed-repair assisted genome-scale engineering or CHAnGE, has the advantages of being quick, efficient and low-cost, in addition to its precision. Zhao's group developed a library of knockout yeast, one for each gene in the S. cerevisiae genome, and are making it available to other researchers for a $50 handling fee.

"In the past, teams of people would spend several years trying to knock out every gene in a yeast. With CHAnGE, one person can generate a library of yeast mutants covering the entire genome in about a month," Zhao said.

Zhao's group is working to develop libraries for other types of yeast, including ones that produce lipids used in lubricants, biofuels and other industrial applications.

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

For mothers with advanced cancer, parenting concerns affect emotional well-being

CHAPEL HILL - Parenting concerns contributed significantly to the psychological distress of mothers with late-stage cancer, according to a study by University of North Carolina Lineberger Comprehensive Cancer Center researchers.

Cancer is the leading cause of disease-specific death for parenting-age women in the United States, and women with incurable cancer who have children can have increased rates of depression and anxiety. To better understand how parenting concerns might relate to the quality of life for this group, UNC Lineberger researchers surveyed 224 mothers with advanced cancer. They found that parenting concerns were significantly associated with lower quality of life - almost as much as declines in day-to-day physical functioning. The findings, published in the journal Cancer, point to a need for greater support for mothers with metastatic cancer, researchers say.

"As part of cancer care, we ask about patients' functional status, and how they are responding to treatment, but we are not systematically asking how cancer impacts our patients as parents, yet we know being a parent is incredibly important to their identity and well-being," said UNC Lineberger's Eliza M. Park, MD, assistant professor in the UNC School of Medicine Department of Psychiatry and Department of Medicine. "Among women with metastatic cancer, their health-related quality of life is powerfully interlinked with their parenting concerns about the impact of their illness on their minor children. It appears to equally contribute to someone's assessment of their quality of life as some of the clinical variables we routinely ask about."

In this study, Park and her colleagues conducted an online survey of women who had stage IV solid tumor cancer -- cancer that had metastasized or spread elsewhere in the body -- and at least one child under the age of 18 years. They found mothers with metastatic cancer had, on average, higher depression and anxiety scores than did the general population in the United States. Their emotional well-being scores also were lower than for all adults with cancer.

The researchers determined a mother's emotional well-being was significantly linked with whether she had communicated with her children about her illness and her concerns about how her illness will financially impact her children.

When they took into account other factors that may contribute to a mother's lower quality of life, Park and her colleagues found parenting concerns made up 39 percent of the difference in the quality of life scores. This was almost the same impact on their quality of life score as the degree to which their illness was affecting their ability to carry out day-to-day tasks.

"We found is that parenting-related factors contributed to the amount of variation you see in quality of life almost equally as something like your functional status," Park said.

Based on these findings, Park and her colleagues are planning to investigate ways to address some of the concerns patients with children have and to better support the parents.

"We're working to develop interventions for parents with advanced cancer or another serious illness to help them and their families adjust to the changes that occur with the diagnosis," Park said. "Part of the strategy may be helping them to learn how to communicate effectively with their other family members as well as their children, identifying future care planning needs if their illness gets worse, and providing education about how families can cope and promote resilience in their children."

Credit: 
UNC Lineberger Comprehensive Cancer Center

Women's preference for masculine faces not linked with hormones

image: This image shows an example of a male face digitally altered to appear masculine.

Image: 
©Jones et al

Data from almost 600 participants show that women's perceptions of male attractiveness do not vary according to their hormone levels, in contrast with some previous research. The study findings are published in Psychological Science, a journal of the Association for Psychological Science.

"We found no evidence that changes in hormone levels influence the type of men women find attractive," say lead researcher Benedict C. Jones of the University of Glasgow.

"This study is noteworthy for its scale and scope -- previous studies typically examined small samples of women using limited measures," Jones explains. "With much larger sample sizes and direct measures of hormonal status, we weren't able to replicate effects of hormones on women's preferences for masculine faces."

To address the limitations of previous studies, Jones and coauthors recruited 584 heterosexual women to participate in a series of weekly test sessions. In each session, the participants reported whether they were currently in a romantic relationship and whether they were currently using hormonal contraceptives. They provided a saliva sample for hormone analyses and completed a task that measured their preferences for different types of male faces.

In each face-preference task, the participants saw 10 pairs of male faces and selected the face in each pair that they found more attractive, rating how strong their preference was. The two faces in each pair were digitally altered versions of the same photo - one face was altered to have somewhat feminized features and the other was altered to have somewhat masculinized features. To obscure the specific objective of the study, the researchers interspersed these attractiveness judgments among other filler questions.

As expected, women generally rated the masculinized faces as more attractive than the feminized faces. Preference for the more masculinized faces was also slightly stronger when women judged attractiveness in the context of a short-term relationship as opposed to a long-term relationship.

However, there was no evidence that women's preferences varied according to levels of fertility-related hormones, such as estradiol and progesterone. There was also no association between attractiveness judgments and levels of other potentially influential hormones, such as testosterone and cortisol.

These findings run counter to the hypothesis that sexual selection pressures lead women to prefer more masculine mates, who supposedly have greater genetic "fitness," when they are most fertile and most likely to conceive.

The data also showed that oral contraceptive use did not dampen women's preference for masculine faces, as has been shown previously.

"There has been increasing concern that the birth control pill might disrupt romantic relationships by altering women's mate preferences, but our findings do not provide evidence of this," says Jones.

In light of these findings, Jones and coauthors are continuing to investigate whether other fertility-related differences hold up in larger, more robust studies.

Credit: 
Association for Psychological Science

Impacts of windfarm construction on harbor porpoises

video: Jacob Nabe-Nielsen explains the model that predicts the impacts of anthropogenic disturbances on marine populations.

Image: 
Michael Strangholt, Aarhus University

Scientists from Germany, Denmark and the UK have built a model tool to predict what happens to marine animals when exposed to noise from the construction and operation of windfarms at sea. Using the North Sea harbor porpoise (Phocoena phocoena) population as a case study, they demonstrate how the model can be used to evaluate the impact of offshore wind farm construction noise. This type of noise is increasingly prevalent due to the high demand for green energy, and currently there are >900 offshore wind farms at various stages of development in Europe alone. Porpoises are strictly protected in European waters, so assessing the impacts of construction noise is critical for regulators. We demonstrate how the framework can be used for spatial planning to partly mitigate population impacts of disturbances.

The model - named DEPONS - builds directly on how disturbances influence animal movements, foraging and energetics, and is therefore applicable to a wide range of species. To demonstrate the model, the impact of wind farm construction noise on the North Sea harbor porpoise population was assesed. The scientists monitored the population density during construction of Gemini, a Dutch offshore wind farm, by recording the echolocation sounds that porpoises use for navigating. Afterwards a virtual Gemini landscape where wind turbines were built in the same order, and generating the same amount of noise, as in the wind farm where porpoises had been monitored. This landscape was used for running scenarios in the model.

Credit: 
Aarhus University

New approach in the fight against antibiotic resistance

According to the WHO, around 700,000 people die every year as a result of antibiotic resistance. In Germany, around 6,000 people die every year because treatment with antibiotics is not effective. Scientists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and the University of Oxford have now discovered that there is a point in the production process of the proteins at which it can be regulated by bacteria. This could be used as a starting point for the development of new antibiotics and help overcome resistance to antibiotics.

Antibiotics are used in the treatment of bacterial infections. They kill and inhibit the growth of bacteria, allowing the infection to subside and the patient to recover. However, during the last few years, increasing numbers of bacteria have developed so-called antibiotic resistance, which means they are resistant to the effects of antibiotics. Over time, these types of medication become ineffective and multi-resistant bacteria become even more widespread as a result.

Investigation of early phase of RNA synthesis

The discovery made by scientists, which has now been published in the scientific journal Nature Communications, could be a completely new starting point in developing antibiotics. 'New drugs could now be developed on the basis of our findings that kill the bacteria that cause illnesses', hopes Dr. David Dulin from the Interdisciplinary Centre for Clinical Research at FAU. The FAU team led by Dr. David Dulin and the team led by Achillefs Kapanidis at the University of Oxford have discovered that the early phase of ribonucleic acid (RNA) production is the key to controlling the regulation of bacterial gene expression. Gene expression is the term used to describe how a gene product coded by a gene is is formed . These products are often proteins, or RNA molecules.

In bacteria, the RNA is produced using a large protein complex called RNA polymerase (RNAP). The RNAP reads the DNA sequence and builds a copy of the RNA by joining nucleotides together - the fundamental building blocks of RNA - during a process called transcription. Since this production of RNA is fundamental for the survival of the bacteria, it has already been the subject of intensive research and used as the starting point for developing antibiotics, for example for the treatment of tuberculosis. However, it remained unclear how the production of RNA is also regulated at the stage of early transcription when RNAP has just begun to join together the first few RNA building blocks. This was the subject of the research carried out by the team of scientists.

The researchers used high-end fluorescence microscopy, which allowed them to monitor individual RNAP molecules as they started to produce RNA. They discovered that the initial RNA synthesis is strongly regulated - a certain sequence of DNA forces the RNAP to pause for several seconds. It can only continue with RNA production after this pause.

This discovery completely changes our previous understanding of initial RNA synthesis in bacteria. 'The fact that the RNAP can be simultaneously bound to the DNA and the short piece of RNA for a longer period of time was very surprising, as it contradicts current knowledge,' says Dr. Dulin. The discovery of this new checkpoint in gene expression could be used for the development of new antibiotics. 'For example, it may be possible to develop medication that locks the RNAP in the paused state, thus killing the bacteria that cause illnesses,' says Dr. Dulin. A glimmer of hope in the global struggle against antibiotic resistance.

Credit: 
Friedrich-Alexander-Universität Erlangen-Nürnberg

Proper burial of dead cells limits inflammation

image: Image of macrophage digesting apoptotic, or dead cell.

Image: 
UofL

If dead cells accumulate in the body, they can contribute to inflammation and pre-dispose individuals to multiple chronic inflammatory conditions such as rheumatoid arthritis, cardiovascular diseases, Crohn's disease or lupus by uncharacterized pathways.

"Billions of cells die daily as a consequence of regular wear and tear, tissue turnover and during an inflammatory response. The body dedicates a significant amount of energy in the specific recognition and uptake of these dead cells via specific pathways," said Juhi Bagaitkar, Ph.D., a researcher in the University of Louisville School of Dentistry's Department of Oral Immunology and Infectious Diseases. "If you don't bury the dead cells, they can burst open and cause harm, however the underlying mechanisms are incompletely characterized."

Bagaitkar, along with researchers at Washington University, Indiana University and University of Michigan, recently published a paper in blood, demonstrating the importance of oxidants in the digestion of apoptotic, or dead cells.

Specifically, the research uncovers how NADPH-oxidase is activated to generate reactive oxygen species (ROS) in macrophages, a kind of white blood cell that eats dead cells. These cells also are involved in getting rid of viruses and bacteria.

The presence of ROS is critical as its generation drives additional mechanisms involved in the digestion of cellular corpses to perform at an optimal level. This allows the macrophage to complete the digestion process of efferocytosis, meaning "to bury the dead".

"Independent of their role in microbial killing, we are gaining even greater appreciation of ROS for their huge role in the regulation of host immune response," Bagaitkar said. "Uncovering this role of ROS in the clearance of dead cells sheds some mechanistic insights on how oxidants function in limiting of host inflammation rather than activating it.

"When our bodies produce too much or too little ROS we become pre-disposed to autoimmune disease and chronic inflammation. Producing just enough - the optimal level -- is what's needed," she said.

Credit: 
University of Louisville

COstatus monitor provides direct measure of neonates' cardiac output

image: This is Khodayar Rais-Bahrami, M.D., a Children's neonatologist and senior author for the research.

Image: 
Children's National Health System

TORONTO-(May 5, 2018)-Clinicians caring for vulnerable babies in the neonatal intensive care unit (NICU) need to closely monitor their vital signs, but precisely gauging the function of their tiny hearts has remained elusive.

Clinical markers like blood pressure, heart rate and urine output are available, but they are indirect measures of cardiac output, how much blood the heart pumps per minute. Less invasive techniques, such as Doppler ultrasound, can be imprecise. Respiratory mass spectrometry or catherization would provide more precision by directly calcuating cardiac output but carry risks or are not feasible for neonates.

Clinicians at Children's National Health System hypothesized that COstatus monitors could offer a way to directly measure cardiac output among neonates. The COstatus monitor--a minimally invasive way to measure hemodynamics--captures cardiac output, total end diastolic volume, active circulation volume and central blood volume.

The research team tested the approach by leveraging ultrasound dilution: Injecting saline, which has an ultrasound velocity of 1533m/second, slows the ultrasound velocity of blood from its normal rate of 1580m/second and produces a dilution curve.

"It is feasible to directly measure neonatal cardiac output by ultrasound dilution via the COstatus monitor in the first two weeks of life with no adverse events," says Khodayar Rais-Bahrami, M.D., a Children's neonatologist and senior author for the research presented during the Pediatric Academic Societies 2018 annual meeting. "When we took consecutive measurements, we saw very little variance in the parameters."

The COstatus monitor uses an extracorporeal loop that is connected to arterial and venous catheters. The 12 neonates included in the study already had umbilical venous catheters as well as either a peripheral arterial line or umbilical arterial catheter. The infants ranged in weight from 0.72 to 3.74 kg and were born at 24 to 41.3 gestational weeks.

The infants' cardiac output was measured 54 times from 1 to 13 days of life. Up to two measurement sessions occurred daily for a maximum of four days. The mean cardiac output was 0.43 L/minute with a mean cardiac index of 197mL/kg/minute.

Future research will describe normal cardiac output ranges for neonates as well as how these measurements evolve during the first week of life.

Credit: 
Children's National Hospital

Few transgender teens and parents willing to delay hormone therapy to preserve fertility

image: Adjusted odds of willingness to delay treatment among youth.

Image: 
Dr. Rebecca Persky

TORONTO, May 5, 2018 - Research on transgender teens' and their parents' attitudes regarding fertility preservation will be presented during the Pediatric Academic Societies (PAS) 2018 Meeting in Toronto. A new study found that while more research is needed on the subject, fertility preservation is a major factor for only a minority of transgender teens and their parents in deciding to delay hormone therapy.

Fertility preservation is an important issue to address with transgender and gender non-conforming youth and their families, prior to undergoing hormone therapy. However, little is known about transgender teens' and their parents' attitudes on fertility preservation.

The authors surveyed 66 youth and 52 parents of youth receiving gender-affirming medical care at Children's Hospital of Philadelphia's Gender and Sexuality Development Clinic. The average age of youth participating in the study was 16 and the majority (63 percent) was assigned female sex at birth. Surveys were administered electronically and contained 36 items about knowledge of fertility preservation, desire to have biologic children and other factors that may influence the decision to pursue fertility preservation.

"While hormone therapy has drastically improved the lives of countless transgender and gender non-conforming youth, its impact on fertility can unfairly force individuals to decide at a very early age whether or not they should preserve the ability to be a biological parent one day," said Rebecca Persky, MD, former Children's Hospital of Philadelphia resident, and lead author on the study. Dr. Persky now is a pediatric endocrinology fellow at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health. "These are difficult conversations for physicians to have with youth and families, and we hope our findings on how adolescents and parents approach these decisions will ultimately help providers counsel patients on hormone therapy with their fertility desires in mind."

While the majority of youth and parents were not willing to delay therapy to preserve biologic fertility, parents were significantly more likely to be willing to delay treatment and cited wanting more information as a major factor.

Credit: 
Pediatric Academic Societies

Long-term effects of pre-birth exposure to anti-depressants 12 years later

image: The PAS 2018 Meeting, taking place in Toronto on May 5-8, 2018, brings together thousands of pediatric scientists and other health care providers to improve the health and well-being of children worldwide.

Image: 
Pediatric Academic Societies

TORONTO, May 5, 2018 - Selective serotonin reuptake (SSRI) antidepressant treatment during pregnancy is associated with better performance on a computerized task to measure cognitive skills in 12 year olds, according to a new study being presented during the Pediatric Academic Societies (PAS) 2018 Meeting.

This study, led by Dr. Sarah Hutchison and senior author, Dr. Tim Oberlander, investigates the complex relationships between pre-birth exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants, and thinking and attention skills in 12-year-olds. Dr. Oberlander is a developmental pediatrician and investigator at BC Children's Hospital and BC Women's Hospital + Health Centre, and a professor in the UBC Department of Pediatrics. Dr. Hutchison is a UBC postdoctoral fellow at BC Children's.

Dr. Oberlander, in collaboration with Dr. Adele Diamond, UBC professor and a Canada Research Chair, followed 51 children from 26 weeks of pregnancy to 12 years of age. In this part of the longitudinal cohort study the investigators assessed mom's mood during and after pregnancy and the child's executive functions (EFs) at 12 years of age. EFs consist of a series of skills that help kids thrive in the classroom and workplace, including flexible, creative problem solving, the ability to focus and pay attention, and self-control.

SSRIs are a popular class of antidepressants commonly used to treat a mothers' mood disorder during pregnancy. They affect the brain's level of serotonin, a chemical that plays a critical role in the regulation of mood and attention.

Researchers found that children's performance varied depending on whether they were exposed to SSRIs before birth: Children with SSRI exposure had better EF skills, even when controlling for mother's mood during pregnancy and when the child was 12 years old. Interestingly, better EFs were also observed in the same children at 6 years (Weikum et al 2013). At 12 years, though (unlike at 6 years), differences in SSRI exposure while in utero and differences in the child's EFs did not vary with measures of the child's mood (anxiety or depression) or verbal ability.

"These are important early findings and further research is needed to examine whether 'better' cognitive skills in children with antidepressant exposure reflect a developmental advantage in some ways but also perhaps a risk in other ways, such as perhaps increased anxiety (Hanley et al, 2015)," said Dr. Oberlander. "Our findings when the children were 3 and 6 years of age indicated increased anxiety, though the absence of this at 12 years might indicate that as EFs improve further children are able to use them to help calm themselves."

At this time, researchers are continuing to study these outcomes in a larger cohort (n~=120 children) where they will be able to further examine links between EFs, mood and early development.

"The impact of prenatal antidepressant exposure is not a simple cause and effect," says Dr. Oberlander. "When it comes to assessing the long-term impact of SSRI exposure before birth, genes and family-life play a powerful role in influencing how a child will be affected."

"Depression during pregnancy and beyond is a major public health problem for mothers and their children," Dr. Oberlander added. "Non-treatment is never an option. It is really important that pregnant women discuss all treatment options with their physicians or midwives."

These findings build on Dr. Oberlander's broader research program, in collaboration with other researchers with the Brain Behavior and Development Research Theme at BC Children's, examining the developmental effects of maternal depression on babies and children. They also build on Dr. Diamond's research program, conducted in collaboration with other Neuroscience researchers at UBC and elsewhere, examining how EFs are affected by biological factors (such as genes and neurochemistry) and environmental ones (for example, impaired by stress or improved by interventions).

Dr. Hutchison will present the abstract, "Prenatal Serotonin Reuptake Inhibitor (SRI) Antidepressant Exposure Influences Executive Functions at 12 Years of Age," during the PAS 2018 Meeting on Sunday, May 6 at 5:45 p.m. EDT. Additional co-authors include Dr. Louise Mâsse, Dr. Ruth Grunau, Dr. Whitney Weikum, Ms. Ursula Brain and Mr. Cecil Chau.

Credit: 
Pediatric Academic Societies

EPO protects preemies' brains by modifying genes essential for generating new brain cells

image: This is An Massaro, M.D., an attending neonatologist at Children's National Health System and lead author of the research

Image: 
Children's National Health System

TORONTO-(May 5, 2018) - Erythropoietin (EPO) helps to protect and repair vulnerable brains though it remains a mystery how the anemia drug does so. Genetic analyses conducted by a multi-institutional research team finds that EPO may work its neuroprotective magic by modifying genes essential for regulating growth and development of nervous tissue as well as genes that respond to inflammation and hypoxia. Findings from the pilot study will be presented during the Pediatric Academic Societies 2018 annual meeting.

"During the last trimester of pregnancy, the fetal brain undergoes tremendous growth. When infants are born weeks before their due dates, these newborns' developing brains are vulnerable to many potential insults as they are supported in the neonatal intensive care unit during this critical time," says An Massaro, M.D., an attending neonatologist at Children's National Health System and lead author of the research. "EPO, a cytokine that protects and repairs neurons, is a very promising therapeutic approach to support the developing brains of extremely low gestational age neonates."

The research team investigated whether micro-preemies treated with EPO had distinct DNA methylation profiles and related changes in expression of genes that regulate how the body responds to such environmental stressors as inflammation, hypoxia and oxidative stress. They also investigated changes in genes involved in glial differentiation and myelination, production of an insulating layer essential for a properly functioning nervous system. The genetic analyses are an offshoot of a large, randomized clinical trial of EPO to treat preterm infants born between 24 and 27 gestational weeks.

The DNA of 18 newborns enrolled in the clinical trial was isolated from specimens drawn within 24 hours of birth and at day 14 of life. Eleven newborns were treated with EPO; a seven-infant control group received placebo.

DNA methylation and whole transcriptome analyses identified 240 candidate differentially methylated regions and more than 50 associated genes that were expressed differentially in infants treated with EPO compared with the control group. Gene ontology testing further narrowed the list to five candidate genes that are essential for normal neurodevelopment and for repairing brain injury:

Neurogenin 1, a transcription factor that governs the progression of neurogenesis

FOS like 1, implicated in development of cognitive deficits after oxygen depravation (hypoxia)

Mitogen-activated protein kinase 8 interacting protein 2, encodes a scaffolding protein broadly expressed in the brain. Experimental models that lack this protein display autistic tendencies.

Resistance to inhibitors of cholinesterase 8 homolog A, an essential player in generating new brain cells

Major histocompatibility complex, class II, DR alpha, a central player in proper immune system function.

"These findings suggest that EPO's neuroprotective effect may be mediated by epigenetic regulation of genes involved in the development of the nervous system and that play pivotal roles in how the body responds to inflammation and hypoxia," Dr. Massaro says.

Credit: 
Children's National Hospital

Reduction in federal funding could reduce quality of specialized pediatric care

image: This table shows the number of discharges, percent of discharges, total bed days, and percent of bed days for major hospitals* by payor status, United States and California.

Image: 
Dr. Lisa Chamberlain

TORONTO, May 5, 2018 - Hospitals caring for children with serious, chronic illness are highly dependent on public payers, according to a new study. The research found that proposals to dramatically reduce federal expenditures on Medicaid and Children's Health Insurance Program (CHIP) could destabilize current specialty care referral networks serving all children, including the majority of privately-insured children in greatest need of high quality, specialized, pediatric care. Findings from the research will be presented during the Pediatric Academic Societies (PAS) 2018 Meeting in Toronto.

Although Medicaid and CHIP are directed at providing health services for low-income children, the potential impact of reduced Medicaid and CHIP spending on regionalized systems of hospital care for seriously ill children remains unexplored. The objectives of the study were to assess the role of Medicaid and CHIP in regional hospitals serving large numbers of seriously ill children; to assess the importance of these regional hospitals to privately-insured, seriously ill children; and to assess the characteristics of the hospitals with the highest patient volume and Medicaid and CHIP dependence.

Researchers conducted a retrospective analysis between the 2012 national KID inpatient database and the 2012 California confidential, unmasked Patient Discharge Database from the Office of Statewide Health Planning and Development. Public payers were defined as Medicaid and CHIP, and major pediatric hospitals as those with >500 discharges of children

Nationally, major pediatric hospitals reported over 50 percent of bed days covered by public payers with the 10 highest volume hospitals ranging from 36 percent to 100 percent. Similarly in California, 69 percent of bed days were covered by public payers with the six highest volume hospitals reporting >50 percent public payers. One in three privately-insured children were discharged from major hospitals with >50 percent public payers.

The characteristics of hospitals in the top quintile of Medicaid bed days and had >50 percent publicly insured discharges were 63 percent urban, most often in the south (36 percent) and least often in the northeast (12 percent), 21 percent urban teaching hospitals, and 70 percent children's hospitals.

Dr. Lisa Chamberlain, one of the authors of the study, will present the abstract, "Dependence of Privately-insured, Chronically Ill Children on Medicaid Reliant Hospitals," during the PAS 2018 Meeting on Monday, May 7 at 3:30 p.m. EDT. Reporters interested in an interview with Dr. Chamberlain should contact PAS2018@piercom.com.

Please note: Only the abstract is being presented at the meeting. In some cases, the researcher may have additional data to share with media.

The PAS 2018 Meeting, taking place in Toronto on May 5-8, 2018, brings together thousands of pediatric scientists and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2018 Meeting, please visit http://www.pas-meeting.org.

Credit: 
Pediatric Academic Societies