The study, “A National Mental Health Profile of Parents of Children with Medical Complexity,” examined parent-reported data from the National Survey of Children’s Health, and compared three groups: households of children with medical complexity (CMC), households of noncomplex children with special health care needs, and households of children without special health care needs.

CMC are defined as the 1 percent of children with the most complex medical conditions. They tend to have multiple chronic health conditions and disabilities, and frequently utilize health care services. Examples of CMC include those with cerebral palsy, serious congenital heart defects, or genetic disorders. Given these children’s significant needs, their caregivers are challenged to balance treating their child with completing other family responsibilities.

The study found the following:

-About 20 percent of parents of CMC reported poor or fair mental health, more than 5 times the proportion of parents of children who did not have medical problems.

-In addition, 36 percent of parents of CMC reported not knowing where to go for help in their community when they encounter difficulties, which was more than 2 times the proportion of parents of children who did not have medical problems.

These findings indicate that health care systems should be proactive in trying to serve parents of CMC and provide support resources, and that mental health should be prioritized, according to Nathaniel Bayer, M.D., assistant professor and pediatric hospitalist at Golisano Children’s Hospital in the URMC Department of Pediatrics and lead author of the study.

“As we partner with these families, we need to make sure we’re taking care of the parents as well as the children,” said Bayer, “It is our job as pediatricians and health care teams to recognize the parents’ needs and connect them to services.”

Only 15 percent of parents of CMC reported access to peer support groups, which are critical for families to be able to exchange ideas and support each other, according to Bayer. To help address these gaps, hospitals should offer peer-to-peer support groups and grow family advisory councils to support the health and emotional wellness of caregivers of CMC.

“Having a child with this level of needs affects families in so many different ways. With the right support, these families thrive and fulfill their goals,” said Bayer. “Without enough support, these families often struggle with the emotional and physical demands of constant caregiving, financial stressors, and employment issues. They may also be unable to find assistance from community services and home nurses, which are under-funded and under-reimbursed.”

Research on families and parents of CMC is an emerging field, because kids with complex conditions are living longer as healthcare interventions have improved in the 21st century. “In the last decade, there’s a heightened interest in discussing and focusing on these children and their families because we are increasingly recognizing that they need more support to successfully navigate the complicated health, education, and community systems.”

The study also found that families of lower socio-economic status (SES) reported feeling significantly more isolated and unaware of how to seek support. “Families of lower SES often do not have the resources to easily access services. They may lack the transportation to travel to the clinic or struggle to find community resources in their area. If your family is also struggling to put food on the table or keep the lights on, it’s harder to manage your child’s medical needs and take care of yourself,” said Bayer.

In addition to health care systems providing more peer-to-peer services, more federal and state support of CMC parents — including greater reimbursement for home-health services and caregivers, expanded services and access for kids with disabilities, and improved early intervention support — can all help parents of CMC, according to Bayer. Behavioral health and wellness services — both for children and parents — should also be expanded.

“Mental health is a part of health,” said Bayer, “Parent and caregiver mental health is a major issue that has a significant impact on children’s health. We need to talk more about parent mental health, screen for it more, and proactively support it.”

Bayer and his research team plans to continue studying the mental health of CMC parents, the resilience of their families, and their abilities to adapt to challenges. The team is currently surveying and interviewing local families of CMC in the Rochester region to examine these topics. After studying how resilience and emotional wellness develop in families of children with complex medical conditions, he is planning to build family support programs and study their impact on child and caregiver health.

Additional study co-authors include Justin Yu, M.D., M.S. of University of Pittsburgh; Dennis Kuo, M.D., M.H.S. of University at Buffalo; and Hongyue Wang, Ph.D., Jill Halterman, M.D., M.P.H., and Yue Li, Ph.D. of URMC.

Golden jackals, for example, were spotted foraging in broad daylight in urban Tel Aviv, Israel, and mountain lions were seen strolling through downtown Santiago, Chile. Urban environments had suddenly become quiet and empty as shelter-in-place orders brought human movement to a grinding halt — an effect some researchers have called the “anthropause.” Wildlife seemed to be taking advantage. The new study shows this was certainly true for pumas in the Santa Cruz Mountains. Researchers were able to clearly connect changes in the cats’ habitat use with reduced human mobility during shelter-in-place orders.

Chris Wilmers, an environmental studies professor at UC Santa Cruz, led this research. Wilmers is the principal investigator for the Santa Cruz Puma Project, and he has been studying local mountain lion populations for over a decade. In particular, his research uses data from GPS tracking collars placed on wild pumas to show how fear of humans affects mountain lion behavior and ecology. When the pandemic hit, his team was already tracking data from several collared cats, and he recognized a unique research opportunity.

“When the shelter-in-place orders started, it was immediately clear that things were very different,” Wilmers said. “You’d go outside and there were very few cars. Entire neighborhoods were completely quiet. So we wondered how this might affect the mountain lion population. Would they respond this quickly to reduced human presence?”

To answer that question, the team analyzed about two years worth of mountain lion tracking data for a set of six collared cats to see where the pumas roamed and what types of habitats they used. Researchers compared these tracks with the distribution of housing density and the geographic boundaries of the “urban edge,” which indicates where vehicle and pedestrian traffic is heightened. During regional shelter-in-place orders, they found that cats were significantly more likely to move into or closer to the urban edge. And these changes happened rapidly: within days or weeks of the beginning of COVID-19 lockdowns.

In an effort to hone in on the cause of this change, the team ruled out any influence of natural factors — like topography, vegetation cover, or distance to the nearest water source — that might affect the cats’ choice of habitats. They also compared year-over-year tracking data to show that seasonal variability wasn’t affecting the results. Pumas do have a strong preference for habitats with lower housing density, but this factor did not change significantly during the study period. The key difference that appeared to be driving the trend of mountain lions moving into urban areas was reduced human mobility during the pandemic.

After regional shelter-in-place orders went into effect on March 17, 2020, local human mobility declined more than 50 percent, according to Apple mobility data, which show the number of navigation requests for driving and walking trips received through Apple Maps. During this time period, when people confined themselves in their homes, the data showed a strong relationship between declining levels of human mobility and pumas’ increased willingness to venture closer to or into urban areas.

“We found that they totally relaxed their fear of the urban edge,” Wilmers said. “It’s not that they weren’t scared of cities; they were still scared, but only of high housing density, not the extra impact of human mobility. If you take all the car trips and pedestrian trips and human mobility out of it, then, all of a sudden, mountain lions don’t fear the city as much.”

Wilmers says this finding helps to build understanding of the unique impacts of human mobility on wildlife. Conservation efforts often focus on the ways that humans are destroying habitats — through development and pollution, for example — but the mere presence of people moving across a landscape also takes a toll on animals that fear humans. And this too is a conservation challenge.

“It’s important because our mobility just keeps increasing,” Wilmers explained. “In the early part of the 20th century, we got cars, and that really increased our mobility. Now we have things like ride-sharing apps, mountain bikes, and electric bikes, and these are all ways that we’re becoming more and more mobile across more types of landscapes. It’s an important thing to think about as we try to conserve and manage ecosystems.”

Another key point this research illustrates is that fear, or the removal of a source of fear, can bring about rapid changes in animal behavior that ripple out through ecosystems. Ecologists call this concept the “landscape of fear.” And the pandemic showed just how integrated into this landscape humans really are. People are usually the ones exerting the influence of fear upon other animals, but there are some things that even we fear.

“Humans have always been the top dog in landscapes of fear, but this study shows that those influences of humans can be reversed relatively quickly by a pathogen, particularly a pandemic-causing pathogen,” Wilmers said. “It’s interesting from a theoretical perspective, and it’s also important in a practical sense because it shows that, not only are pandemics going to have major health consequences for people, but there are also going to be important ecological impacts.”

In a paper published in the Journal of Nutritional Biochemistry by College of Agriculture, Health, and Natural Resources faculty Young-Ki Park, assistant research professor in the Department of Nutritional Sciences, and Ji-Young Lee, professor and head of the Department of Nutritional Sciences, the researchers reported significant findings supporting the nutritional benefits of Connecticut-grown sugar kelp. They found brown sugar kelp (Saccharina latissima) inhibits hepatic inflammation and fibrosis in a mouse model of diet-induced non-alcoholic steatohepatitis, a fatty liver disease.

They studied the differences between three groups of mouse models. They placed two on high-fat diets but incorporated sugar kelp, a kind of seaweed, into the diet of one. The third group was on a low-fat diet as a healthy control. The group that ate sugar kelp had lower body weight and less adipose tissue inflammation — a key factor in a host of obesity-related diseases — than the other high-fat group.

Consuming sugar kelp also helped prevent the development of steatosis, the accumulation of fat in the liver. Nonalcoholic steatohepatitis (NASH) is a condition often associated with obesity that can cause inflammation and reduced functionality in the liver.

The mice on the sugar kelp diet also had healthier gut microbiomes. The microbiome is a collection of bacteria and other microorganisms in and on our bodies. The diversity and composition of the microbiome are key to maintaining a host of health functions.

“I wasn’t surprised to see the data, as we know seaweeds are healthy,” Lee says. “But it’s still pretty amazing data as this is the first scientific evidence for health benefits of the Connecticut-grown sugar kelp.”

This study is the first time researchers have looked at the link between the US-grown sugar kelp and obesity.

“There hadn’t been a study about this kind of aspect before,” Park says.

Park and Lee saw an opportunity to conduct research on the nutritional science of seaweed, a growing agricultural industry in the United States. They hoped that, by gathering concrete data on the health benefits of sugar kelp, it could encourage people to consume seaweed.

“Consumers these days are getting smarter and smarter,” Lee says. “The nutritional aspect is really important for the growth of the seaweed industry in Connecticut.”

The researchers specifically used Connecticut-grown sugar kelp, as Connecticut regulates the safety of seaweeds. This is important for monitoring heavy metals that seaweed may absorb from the water.

Most of the seaweed consumed in the US is imported. Park and Lee hope more research on the benefits of locally grown seaweed will prompt consumers to support the industry stateside.

“It’s really an ever-growing industry in the world,” Lee says.

After completing this pre-clinical study, the researchers now hope to move into clinical studies to investigate the benefits sugar kelp may have for other health concerns. They also want to work on reaching out to people to teach them how to incorporate sugar kelp into their diet.

This work represents a fruitful collaboration between researchers, farmers, and the state.

“Farmers need to know what we’re doing is a good thing to help boost their sales,” Park says. “We can be a partner.”

In collaboration with Anoushka Concepcion, an extension educator with the Connecticut Sea Grant and UConn Extension Program, Park and Lee hope to build stronger partnerships with seaweed growers in Connecticut.

Story Source:

Materials provided by University of Connecticut. Original written by Anna Zarra Aldrich. Note: Content may be edited for style and length.

Chemist Han Xiao at Rice and biologist Xiang Zhang at Baylor and their labs have developed an antibody conjugate called BonTarg that delivers drugs to bone tumors and inhibits metastasis.

Their open-access study, which appears in Science Advances, shows how Xiao’s pClick technology can be used to link bone-targeting antibodies and therapeutic molecules.

In experiments, they used pClick to couple a molecule used to treat osteoporosis, alendronate, with the HER2-targeting antibody trastuzumab used to treat breast cancer and found it significantly enhanced the concentration of the antibody at tumor sites.

They reported the combination also inhibited secondary metastasis from infected organs seeded by bone tumors.

“Bone cancer is really challenging to treat, and clinical trials of different treatments have been disappointing for people with bone metastasis,” said Xiao, who joined Rice in 2017 with funding from the Cancer Prevention and Research Institute of Texas (CPRIT). “We feel our strategy is a real game changer.”

“Getting effective concentrations of drugs to bone tumors has been challenging because bones are hard, their networks of blood vessels is limited and drugs have tended to attach to adjacent healthy tissues,” Zhang said.

The new strategy employs bisphosphonates, a class of drugs typically used to treat osteoporosis. Bisphosphonates have a high binding affinity for hydroxyapatite, the main component of hard bone, and help overcome physical and biological barriers in the bone microenvironment.

They’re also amenable to binding with drugs through pClick, which uses a cross-linker to snap to specific sites on antibodies without having to re-engineer them with harmful chemicals, enzymes or ultraviolet light.

The result is a molecule that seeks out bone tumors and stays put, giving the drug time to kill tumor cells. It helps that bisphosphonate molecules prefer acidic sites like bone tumors, keeping the drug concentration higher there than in surrounding healthy tissue.

The researchers chose breast cancer drugs because while many recover from the disease, 20 to 40% of breast cancer survivors eventually suffer metastases to distant organs, with metastasis to bone occurring in about 70% of these cases, significantly increasing mortality, they said.

While chemotherapy, hormone and radiation therapy used to treat women with bone metastatic breast cancers can shrink or slow bone metastasis, they usually do not eliminate the metastases, Xiao said.

“Bone is kind of a fertile soil for cancer cell,” Xiao said. “If a cancer cell reaches it, then it has a really good chance to grow and to further migrate, for example to the brain, the heart, the liver or to other tissues. That’s a really bad situation for a patient.”

Xiao hopes to get the compound into a clinical trial, and sees potential for custom conjugates that treat other tumors prone to metastasis, including prostate cancer.

Postdoctoral researchers Zeru Tian of Rice and Ling Wu of Baylor are co-lead authors of the paper. Co-authors are graduate students Chenfei Yu, Yuda Chen, Axel Loredo and Kuan-Lin Wu and postdoctoral researcher Lushun Wang of Rice; and postdoctoral fellows Zhan Xu, Igor Bado and Weijie Zhang and instructor Hai Wang of Baylor.

Xiao is the Norman Hackerman-Welch Young Investigator, the Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research and an assistant professor of chemistry, bioengineering and biosciences. Zhang is the William T. Butler, M.D., Endowed Chair for Distinguished Faculty, McNair Scholar, associate director of the Lester and Sue Smith Breast Center, professor of molecular and cellular biology and member of the Dan L Duncan Comprehensive Cancer Center.

The research was supported by CPRIT, the National Institutes of Health, the Robert A. Welch Foundation, the U.S. Department of Defense, the John S. Dunn Foundation, the Hamill Foundation, the Breast Cancer Research Foundation and the McNair Medical Institute.

Cancer is no different. Within a growing tumor, cancer cells with the best ability to compete for resources and withstand environmental stressors will come to dominate in frequency. It’s “survival of the fittest” on a microscopic scale.

But fitness — how well suited any particular individual is to its environment — isn’t set in stone; it can change when the environment changes. The cancer cells that might do best in an environment saturated with chemotherapy drugs are likely to be different than the ones that will thrive in an environment without those drugs. So, predicting how tumors will evolve over time, especially in response to treatment, is a major challenge for scientists.

A new study by researchers at Memorial Sloan Kettering in collaboration with researchers at the University of British Columbia/BC Cancer in Canada suggests that one day it may be possible to make those predictions. The study, published June 23, 2021, in the journal Nature, was led by MSK computational biologist Sohrab Shah and BC Cancer breast cancer researcher Samuel Aparicio. The scientists showed that a machine-learning approach, built using principles of population genetics that describe how populations change over time, could accurately predict how human breast cancer tumors will evolve.

“Population genetic models of evolution match up nicely to cancer, but for a number of practical reasons it’s been a challenge to apply these to the evolution of real human cancers,” says Dr. Shah, Chief of Computational Oncology at MSK. “In this study, we show it’s possible to overcome some of those barriers.”

Ultimately, the approach could provide a means to predict whether a patient’s tumor is likely to stop responding to a particular treatment and identify the cells that are likely to be responsible for a relapse. This could mean highly tailored treatments, delivered at the optimal time, to produce better outcomes for people with cancer.

A Trifecta of Innovations

Three separate innovations came together to make these findings possible. The first was using realistic cancer models called patient xenografts, which are human cancers that have been removed from patients and transplanted into mice. The scientists analyzed these tumor models repeatedly over extended timeframes of up to three years, exploring the effects of platinum-based chemotherapy treatment and treatment withdrawal.

“Historically, the field has focused on the evolutionary history of a cancer from a single snapshot,” Dr. Shah says. “That approach is inherently error prone. By taking many snapshots over time, we can obtain a much clearer picture.”

The second key innovation was applying single-cell sequencing technology to document the genetic makeup of thousands of individual cancer cells in the tumor at the same time. A previously developed platform allowed the team to perform these operations in an efficient and automated fashion.

The final component was a machine-learning tool, dubbed fitClone, developed in collaboration with UBC statistics professor Alexandre Bouchard-Côté, which applies the mathematics of population genetics to cancer cells in the tumor. These equations describe how a population will evolve given certain starting frequencies of individuals with different fitnesses within that population.

With these innovations in place, the scientists were able to create a model of how individual cells and their offspring, or clones, will behave. When the team conducted experiments to measure evolution, they found close agreement between these data and their model.

“The beauty of this model is it can be run forwards to predict which clones are likely to expand and which clones are likely to get outcompeted,” Dr. Shah says.

In other words, how the cancer will evolve is predictable.

A Foundation for the Future

The particular types of genetic changes the team looked at are called copy number changes. These are differences in the number of particular DNA segments in cancer cells. Up until now, the significance of these sorts of changes hasn’t been clear, and researchers have had doubts about their importance in cancer progression.

“Our results show that copy number changes have a measurable impact on fitness,” Dr. Shah says.

For example, the scientists found that, in their mouse models, treatment of tumors with platinum chemotherapy led to the eventual emergence of drug-resistant tumor cells — similar to what happens in patients undergoing treatment. These drug-resistant cells had distinct copy number variants.

The team wondered: What would happen to the tumor if they stopped treatment? Turns out the cells that took over the tumor in the presence of chemotherapy declined or disappeared when the chemotherapy was taken away; the drug-resistant cells were outmatched by the original drug-sensitive cells. This behavior indicates that drug resistance has an evolutionary cost. In other words, the traits that are good for resisting drugs aren’t necessarily the best for thriving in an environment without those drugs.

Ultimately, Dr. Shah says, the goal is to one day be able to use this approach on blood samples to identify the particular clones in a person’s tumor, predict how they are likely to evolve, and tailor medicines accordingly.

“This study is an important conceptual advance,” Dr. Shah says. “It demonstrates that the fitness trajectories of cancer cells are predictable and reproducible.”