Publisher Health

Researchers at The University of Texas MD Anderson Cancer Center have discovered that two distinct classes of cancer-associated fibroblasts (CAFs) accumulate in the pancreatic tumor microenvironment and play opposing roles to promote and restrain pancreatic cancer development.
The preclinical findings suggest that appropriately targeting these unique CAF populations may offer strategies to improve the use of other treatments, such as chemotherapy and immunotherapy. The results were published today in Cancer Discovery, a journal of the American Association for Cancer Research.
“Cancer-associated fibroblasts are known to regulate cancer progression, but targeting these cells in pancreatic cancer has largely failed to improve patient outcomes and has, in some cases, worsened response,” said lead author Kathleen McAndrews, Ph.D., postdoctoral fellow in Cancer Biology. “Our findings provide the first evidence of the functional heterogeneity of CAFs in pancreatic cancer that may explain the variations in patient outcomes.”
Fibroblasts, a type of cell found in connective tissue, are involved in important biological processes, such as wound repair. Cancer-associated fibroblasts are those that accumulate in tumors. These cells can be found in large numbers in pancreatic cancers, but their precise role in cancer development had remained unclear.
The researchers performed single-cell RNA sequencing to analyze gene expression and clarify the types of CAFs present in pancreatic tumors. They identified two distinct subsets of CAFs marked by expression of fibroblast activation protein (FAP) and alpha-smooth muscle actin (αSMA).
Interestingly, the researchers found that expression of these proteins in treatment-naïve human tumor samples correlated with eventual outcomes. Increased expression of αSMA was associated with significantly improved overall survival (OS), whereas elevated FAP levels were associated with significantly decreased OS.

Staying well-hydrated may be associated with a reduced risk for developing heart failure, according to researchers at the National Institutes of Health. Their findings, which appear in the European Heart Journal, suggest that consuming sufficient amounts of fluids throughout life not only supports essential body functioning but may also reduce the risk of severe heart problems in the future.
Heart failure, a chronic condition that develops when the heart does not pump enough blood for the body’s needs, affects more than 6.2 million Americans, a little more than 2% of the population. It is also more common among adults ages 65 and older.
“Similar to reducing salt intake, drinking enough water and staying hydrated are ways to support our hearts and may help reduce long-term risks for heart disease,” said Natalia Dmitrieva, Ph.D., the lead study author and a researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.
After conducting preclinical research that suggested connections between dehydration and cardiac fibrosis, a hardening of the heart muscles, Dmitrieva and researchers looked for similar associations in large-scale population studies. To start, they analyzed data from more than 15,000 adults, ages 45-66, who enrolled in the Atherosclerosis Risk in Communities (ARIC) study between 1987-1989 and shared information from medical visits over a 25-year period.
In selecting participants for their retrospective review, the scientists focused on those whose hydration levels were within a normal range and who did not have diabetes, obesity, or heart failure at the start of the study. Approximately 11,814 adults were included in the final analysis, and, of those, the researchers found 1,366 (11.56%) later developed heart failure.
To assess potential links with hydration, the team assessed the hydration status of the participants using several clinical measures. Looking at levels of serum sodium, which increases as the body’s fluid levels decrease, was especially useful in helping to identify participants with an increased risk for developing heart failure. It also helped identify older adults with an increased risk for developing both heart failure and left ventricular hypertrophy, an enlargement and thickening of the heart.

Researchers from Children’s Hospital of Philadelphia (CHOP) have found that dysfunction in an important cell subtype in the brain’s neuronal network contribute to chronic symptoms in the neurodevelopmental disorder Dravet syndrome. The findings were published today in the journal Cell Reports.
Dravet syndrome is a form of genetic epilepsy that is characterized by seizures that begin in the first year of life, along with differences in childhood development and features of autism spectrum disorder. Children with Dravet syndrome are also at an increased chance of early death, making proper diagnosis and treatment of the disorder critical. More than 90% of children with Dravet syndrome have a pathogenic, or disease-causing, variant in the SCN1A gene, which makes the protein Nav1.1, a sodium channel that is important for the activity of seizure-suppressing cells called interneurons and, in particular, a subtype of interneuron called the parvalbumin interneuron.
“Dravet syndrome affects 1 in 14,000 children in the world and has a profound impact on children and their families,” said Ethan Goldberg, MD, PhD, a pediatric neurologist and Director of the Epilepsy Neurogenetics Initiative (ENGIN) at CHOP and lead author of the study. “We can model Dravet syndrome in the laboratory to understand precisely how the loss of SCN1A produces the clinical features characteristic of the disease to drive development of novel therapies, and, one day, a cure.”
Prior work from the Goldberg lab showed that abnormal electrical activity of these parvalbumin neurons in a preclinical experimental model of Dravet syndrome was only transient, with these neurons recovering normal activity in the chronic phase of the disorder. This created a conundrum for the research community: why do patients with Dravet syndrome continue to have seizures, cognitive impairment, and features of autism spectrum disorder?
In this study, the researchers developed a method to assess parvalbumin interneuron function at two different points in time. Early disease severity is caused by abnormalities in parvalbumin interneuron electrical activity, which allows neurons to send a message to neighboring neurons. However, chronic dysfunction was due instead to impaired synaptic transmission; while parvalbumin interneurons recovered the ability to generate electrical activity, this activity did not spread down the nerve or “axon” to the synapse to inhibit of other neurons, which is required for seizure suppression.
While more work is needed to translate this research into direct human applications, the researchers note that SCN1A may be a viable therapeutic target for Dravet syndrome patients, particularly if there are ways to increase its expression in the axon to overcome impaired signaling and synaptic transmission.
“A prediction of our work is that the success of therapies under development may depend on the ability to increase expression of Nav1.1 at the parvalbumin interneuron axon,” Goldberg said.
This study was supported by the Dravet Syndrome Foundation and the National Institutes of Neurological Disorders and Stroke of the National Institutes of Health under grants K08NS097633, R01NS110869, and F31NS111803,
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Materials provided by Children’s Hospital of Philadelphia. Note: Content may be edited for style and length.

As advances in wearable devices push the amount of information they can provide consumers, sensors increasingly have to conform to the contours of the body. One approach applies the principles of kirigami to give sensors the added flexibility.
Researchers want to leverage the centuries-old art of cutting paper into designs to develop a sensor sheet that can stretch and breathe with the skin while collecting electrocardiographic data. In Applied Physics Reviews, by AIP Publishing, the sensor made by researchers in Japan uses cuts in a film made of polyethylene terephthalate (PET) printed with silver electrodes to fit on a person’s chest to monitor his or her heart.
“In terms of wearability, by applying kirigami structure in a PET film, due to PET deformation and bending, the film can be stretchable, so that the film can follow skin and body movement like a bandage,” said author Kuniharu Takei, from Osaka Prefecture University. “In addition, since kirigami structure has physical holes in a PET film, skin can be easily breathed through the holes.”
Unlike the related origami, which involves strictly paper folding, the art of kirigami extends its methods to paper cutting as well. Such a technique allows relatively stiff materials, like PET, to adapt to their surfaces.
As companies push for less noticeable wearables, attention has turned to optimizing picking out electrical signals from the heart out of background noise. Devices like the group’s that ensure a snugger fit are an attractive solution.
The team found the optimal size of the sensor is roughly 200 square millimeters with a distance of 1.5 centimeters between electrodes. At that size, they were able to detect enough signal from the heart to be used in a smartphone app.
“The major challenge was how to realize the kirigami structure without using a precise alignment process between the silver electrodes and kirigami cutting,” Takei said.
Their device with the sensor could accurately and reliably relay heart data across multiple people doing many types of everyday movements, such as walking or working while seated in a chair.
The group next aims to integrate more sensors to measure multiple types of data from the surface of the skin to help with early diagnosis of disease, including future medical trials.
“We understand that the new mechanism or new material developments makes better impact to the field,” Takei said. “However, without improving the stability, it cannot be used for the practical applications, even if the sensor performance is excellent.”
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Tips and tricks to get help now.Finding a therapist — let alone one who is a good fit — can take time and determination, especially during the pandemic, when many therapists report they cannot keep up with demand and must turn away patients.When The New York Times surveyed 1,320 mental health professionals in November, nine out of 10 therapists said the number of people seeking care was on the rise. During a Senate committee hearing in February to address the nation’s growing mental health and substance abuse problem, Senator Patty Murray of Washington noted that nearly 130 million Americans live in places with less than one mental health care provider per 30,000 people.Even therapists can have trouble finding help. Thomas Armstrong, a clinical psychologist in eastern Washington, waited more than a year to get treatment for his youngest child, who was 2 when they started searching. And it took more than two years to get the treatment that proved most beneficial, found only after he tapped into his academic network through Twitter.“All the stars had to align for me,” he said.If you are looking for a mental health care provider, don’t give up — there are several strategies that can help.Phone a friend.For some people — like those suffering from a debilitating bout of depression — the thought of spending weeks or months searching for a therapist can seem overwhelming.“It’s not something you’re doing wrong — it’s that the system is inherently broken and it needs fixing,” Jessi Gold, a psychiatrist at Washington University in St. Louis, said.If you don’t have the energy to get started, ask a friend or family member to help you contact providers and set up an appointment, Dr. Gold suggested. It is “one of the best ways that people who care about you can help with your mental heath,” she added.You can also try getting referrals directly from your personal network — whether it is someone from your local parenting group, your friend’s therapist, an obstetrician, your primary care doctor or a trusted colleague. For students, referrals can also come from on-campus counseling centers, health centers or a guidance counselor.Jeanie W. Shiau, a licensed clinical social worker in Georgia whose practice is usually about 90 percent full, often helps find providers for patients she cannot see individually.Her philosophy, she said, is that “connecting folks with resources is part of our ‘rent’ for being human on this planet.”Charity Rachelle for The New York TimesTake a chance on a provider who is new to the field.One of the best places to call is your local university’s psychology clinic, which trains graduate students, said Margaret E. Crane, a doctoral candidate in clinical psychology at Temple University whose dissertation compares strategies to help caregivers seek therapy for youth anxiety.These clinics offer evidence-based treatments to both children and adults, she added, and they often have shorter wait lists than community clinics or therapists in private practice. “They also can provide you with high-quality referrals in the area,” she said.You might also consider working with someone who has obtained a degree but is still gathering the supervised experience needed to earn a professional license. These clinicians are usually less expensive, and their work is continually being reviewed by a more experienced therapist.Finally, when looking for a provider, don’t assume that a higher degree equates to better therapy. Keep in mind that most licensed therapists in the United States — like licensed clinical social workers and licensed professional counselors — have master’s degrees, not doctoral degrees.“Rather than looking for a specific degree, look for therapists who have been trained in evidence-based treatments like cognitive behavioral therapy,” Ms. Crane said.Check your employee benefits.Arniece Stevenson, 34, a graduate student in Philadelphia who works for the Girl Scouts, used her Employee Assistance Program, or E.A.P., to locate a therapist faster than she ever expected.An E.A.P. is a free intervention program that can help employees resolve personal problems by connecting them with the right resources, and may also provide a small number of free therapy sessions.E.A.P.s are billed as confidential, but some employees feel wary of contacting them because of privacy concerns. Ms. Stevenson was hesitant, but she finally reached out one evening around midnight. “I just had to muster up the courage,” she said.The person she spoke with said someone would be calling her back soon. The following day she heard from a therapist who could begin seeing her right away.“I was shocked — I was like, ‘Wait, already?’” she said.The therapist she sees is white, and Ms. Stevenson, who is Black, said she would have preferred a provider who was African American. But the two of them “happened to click,” Ms. Stevenson added.Explore digital directories and virtual options.Many people start searching for a provider by scrolling through their insurance company’s list of providers, then cross-referencing those against another database like Psychology Today to learn more about each practitioner.The insurance company’s list may not be up to date, however, and some providers may not respond to your queries because they are already full.It may be more efficient in some cases to look at free online directories where you can filter results by who is currently taking new clients. Options include Alma, ZocDoc, Monarch and Headway.Companies like BetterHelp, 7 Cups of Tea and Talkspace offer online therapy and messaging with a licensed practitioner for a weekly or monthly membership fee.Look to nonprofits.Nonprofits focused on helping specific groups can also aid people in finding a therapist.Examples include the Beacon Tree Foundation, which assists parents in Virginia who have children with mental illness; the American Foundation for Suicide Prevention; and the Anxiety and Depression Association of America.Postpartum Support International took just two days to connect Melanie Vega, 39, with a provider on her insurance panel when she developed postpartum depression after the birth of her first child.“I knew that something was wrong when I kept saying to myself my family would be better off without me,” said Ms. Vega, who has now been seeing that therapist for four years. “She has helped me tremendously.”Other helpful nonprofits include The Trevor Project, which offers trained counselors to L.G.B.T.Q. youth; the Trans Lifeline; LatinxTherapy; Black Men Heal; and the Asian Mental Health Collective.What if you don’t have insurance?Some therapists are open to charging sliding-scale fees based on a patient’s income, so don’t hesitate to ask. And check out the nonprofits Open Path Collective and Therapy4thePeople for directories of therapists who charge as little as $30 a session.Sesame also provides low-cost mental health consultations that do not require insurance.Community-based mental health programs are another option. You can search for these via the Substance Abuse and Mental Health Services Administration’s treatment locator.You can often find free or low-cost programs at local hospitals and medical schools as well.FindTreatment.gov helps people locate treatment for substance use disorders and includes information on which organizations offer payment assistance.If there is a crisis, do not wait.Those who have tried to harm themselves — or are in the process of doing so — should go to an emergency room or call 911.If you or a loved one are having thoughts of suicide, call the National Suicide Prevention Lifeline: 1-800-273-8255 (TALK); en Español: 1-888-628-9454; for the deaf and hard of hearing: Dial 711, then 1-800-273-8255.You can also text HOME to 741-741 to be connected with a trained crisis counselor and receive free support via text message from the Crisis Text Line.The National Alliance on Mental Illness has information on other types of mental health crisis services, like mobile crisis teams and crisis stabilization units. And a list of additional resources can be found at SpeakingofSuicide.com/resources.

When Selena Wiley signed the lease for an older rental home in South Bend, Ind., she asked the property manager about lead paint and was assured the house was safe.But in November 2018 — almost two years after moving in with her partner and three children — Ms. Wiley noticed that their 2-year-old’s appetite had vanished and his constant chattering had stopped.A doctor soon discovered that the boy, Joevonne, known as J.J., had lead poisoning. The level was so high that he immediately began a 19-day treatment to help rid his body of the toxin, which can cause irreversible damage to a child’s brain and nervous system. A health inspector soon found lead paint and dust throughout the family’s rental home.As J.J. faces an uncertain future, no one has been held responsible so far — the firm that owns the home protected its assets in a tangle of limited liability companies, and the property insurer excluded lead from its coverage. These practices are now the norm across the United States, The New York Times has found, part of a decades-long campaign by the real estate and insurance industries to shield themselves from liability in lead-poisoning cases. The effort has helped allow what is often considered a problem of the past to remain a silent epidemic today.Although lead poisoning has decreased substantially since the late 1970s as a result of regulatory actions and public health initiatives, about 500,000 children under 6 have elevated blood lead levels in the United States and are at risk of harm. The issue has only intensified in the era of Covid-19: Rental inspections lagged, exposure increased as people spent more time at home and testing of children fell by 50 percent at times in 2020.“It’s a slow-moving catastrophe that people have just gotten used to,” said Sean M. Ryan, a state senator in western New York, where high rates of lead poisoning persist.Children in the U.S. With Elevated Blood Lead LevelsNo level of exposure to lead is considered safe. Even low levels have been shown to affect a child’s intelligence, learning ability and behavior. The U.S. Centers for Disease Control and Prevention recently lowered the threshold used to identify children with the highest lead levels.

Cancer often transfers from its primary lesion to other lesions — clinically referred to as metastasis. In early metastasis, cancer cells invade lymphatic vessels, reach lymph nodes, and proliferate. Conventional chemotherapy for metastatic lymph nodes has limitations because only part of anticancer drug administrated by intravenous injection reaches the metastatic lymph nodes, and the expanded tumors restrict the bloodstream, preventing anticancer drug delivery.
The lymphatic drug delivery system (LDDS) provides an alternative strategy to conventional chemotherapy. Anticancer drugs are injected directly into sentinel lymph nodes under ultrasound guidance. LDDS is also available during intra-operative or image-guided surgery.
Professor Tetsuya Kodama and assistant professor Ariunbuyan Sukhbaatar of the Tohoku University Graduate School of Medical Engineering investigated the effect of osmotic pressure and the viscosity of anticancer drugs on the efficacy of lymph node metastasis treatment in collaboration with Dr Shiro Mori of Tohoku University Hospital. The authors found that optimal osmotic pressure and viscosity ranges significantly improved an antitumor effect.
This improvement could be explained as follows: the hyperosmotic fluid injected into the tumor-draining lymph nodes may increase the inflow of liquid components from blood vessels and high endothelial venules. Anticancer drugs with higher osmotic fluid could also flow in the efferent lymphatic vessels and the case expansion of lymphatic channels and vessels, allowing anticancer drugs to target tumor cells. Moreover, the optimized anticancer drugs of LDDS could target not only sentinel lymph nodes but also downstream lymph nodes with a high risk of secondary metastasis.
In summary, treatment using LDDS optimizes the physical properties of anticancer drugs, osmotic pressure and viscosity; improves the treatment efficacy; and restricts the spread of tumors in lymph node metastasis. It is anticipated these optimal ranges will be a starting point for developing more effective drug regimens to treat metastatic lymph nodes with the LDDS.
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Materials provided by Tohoku University. Note: Content may be edited for style and length.

The diagnosis is rare, but devastating — children with congenital muscle disorders often never learn to walk. Until now, there was no chance of recovery, but researchers at the University of Basel and University Hospital Basel are now presenting a possible therapeutic approach for the first time.
Professor Susan Treves remembers seeing one child affected by the condition at the age of six months. The boy seemed more like a newborn, she recalls. Today, several years later and thanks to intensive physiotherapy, he is at least able sit. “He made it,” says the researcher. There is as yet no cure for children like this one. Their first priority is survival. Another child with mutations in the same gene as the boy mentioned above, did not survive. However, his genetic alterations now form the basis of a therapeutic approach presented by the research group led by Susan Treves and Professor Francesco Zorzato in the scientific journal eLife.
The affected gene contains the blueprint for a calcium channel called RYR1 in skeletal muscle. The mutations render the gene useless, and this has severe consequences for muscle function. The researchers used the gene alterations found in a patient, as a template to develop a mouse model for this type of congenital myopathy. “The mice don’t die, but their muscle system is severely impaired,” says Treves. “They’re smaller, and move much less.” With a combination of two drugs, however, the research team was able to significantly improve muscle function and movement of the mice.
Genetic material overload
The therapy is based on the observation that certain enzymes are produced in excessive quantities in the skeletal muscles of affected patients. These enzymes — histone deacetylases and DNA methyltransferases, to be specific — affect the density of the packaging of the genetic material. This makes genes less accessible to the cellular machinery that reads them and translates them into instructions for protein production.
Treves and her team used inhibitors against these enzymes, which are already approved as cancer drugs or are being tested in clinical trials. The treatment brought about a significant improvement in the ability of the mice to move, although they remained smaller than healthy animals from the same litter. Importantly, the researchers did not observe any adverse side effects during the study period.
From gene to therapy
The approach is still far from being a clinically applicable therapy, says Treves. “But it’s a first step in the right direction.” In their next step, the researchers aim to further optimize the treatment and test combinations of newly developed drugs targeting the same enzymes to achieve even better effects. “We anticipate around about two more years of optimization and testing before we can initiate a phase I clinical trial,” she says.
For Susan Treves and Francesco Zorzato, these first promising results represent a milestone victory after more than 10 years of research — especially as Zorzato was the one who first isolated the gene affected in these muscle disorders years ago. “We’ve now succeeded in bridging the gap from the isolation of the affected gene to a therapeutic approach,” says Treves.
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Materials provided by University of Basel. Note: Content may be edited for style and length.

Infections with hepatitis C and E are so common that, going only by statistics, many people should be infected with both viruses at the same time. However, only very few such cases have been reported. A research team has a guess as to why this is the case: The researchers found that the viruses inhibit each other when they infect at the same time.
It is well known that co-infections with hepatitis viruses do exist. “However, the co-infection of hepatitis C and E has not yet been systematically researched,” says Thomas Burkard. “Even though the possibility always looms that a simultaneous infection with two viruses could perhaps be particularly dangerous.”
A single protein suppresses infection
In order to find out more about simultaneous infection with the hepatitis C (HCV) and hepatitis E virus (HEV), the researchers infected liver cells in cell culture with both pathogens in the first step. It turned out that HCV is able to suppress an infection with hepatitis E. The team wanted to find out why. “HCV consists of ten proteins,” explains Thomas Burkard. “By producing individual ones in excess, we were able to study their effect.” This allowed the researchers to find that a single viral protein — called NS3/4A — successfully suppressed the replication of hepatitis E viruses in cell culture. “It seemed that co-infection with both viruses was only possible to a very limited extent,” says Thomas Burkard.
Experiments in animal models, however, presented a different pattern: genetically modified mice that have a human liver could become infected with both viruses. However, the infections proceeded in different ways depending on which one the mice were exposed to first. If HEV was present first, HCV could not successfully infect the animals. If HCV was present first, the infection course with HEV was often delayed. “Here, HCV did not turn out to be as dominant as in cell culture,” says Thomas Burkard. In-depth analyses of the liver cells should now shed light on the underlying causes: “Perhaps we will only find islets that are infected with one or the other virus,” speculates the researcher. “In any case, it is clear that the two viruses affect each other.”
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Materials provided by Ruhr-University Bochum. Original written by Meike Drießen. Note: Content may be edited for style and length.

In a cardiac arrest, everything comes down to how quickly you “get on the chest.” Every minute CPR is not initiated or an automated external defibrillator, or AED, is not utilized, the chance of survival decreases by 7-10%.
A new study finds that survival rates increase when first responders in police and fire departments intervene in out-of-hospital cardiac arrests. However, the paper published in Resuscitation suggests these non-medical first responders are likely underutilized as lifesaving resources.
Researchers from Michigan Medicine analyzed more than 25,000 cardiac arrest incidents in the state from 2014 to 2019. They found that police and fire first responders initiated CPR in 31.8% of out-of-hospital cardiac arrests, and police accounted for AED use in 6.1% of incidents. Those interventions were associated with significantly higher chances of survival and hospital discharge with good neurological outcomes.
“It is clear that these non-medical first responders play a critical role in time saved to chest compressions,” said Mahshid Abir, M.D., M.Sc., senior author of the paper and an emergency physician at University of Michigan Health, Michigan Medicine. “In fact, in communities that were the highest performing in the state as far as survival is concerned, those responders work closely with emergency medical services to cross-train and debrief after incidents. When these agencies see their role as not just preventing crime or stopping fires, but also saving lives, it improves the overall chain of survival for cardiac events.”
The likelihood of the return of a sustained heart rhythm for out-of-hospital cardiac arrest didn’t change significantly when CPR or defibrillation was initiated by an EMS provider versus a non-medical first responder. However, the survival rate for initiation by non-medical first responders was significantly higher.
In fact, for patients who had CPR initiated by non-medical first responders, the odds of survival were 1.25 times higher. Similarly, patients who had an AED applied by police were 1.4 times more likely to survive.