Publisher Health

Athletes and the general population alike train to promote health and physical fitness. With repeated exposure to the minimal stress of exercise, the body adapts. Researchers at the University of Tsukuba have sought to paint a detailed picture of the physiological stress response to moderate-intensity exercise that occurs after the lactate threshold is surpassed. In a recently published study in Neuroendocrinology, the researchers have confirmed that arginine vasopressin and corticotrophin-releasing hormone regulate an important indicator of stress: the adrenocorticotropic hormone.
With sufficiently lengthy moderate-intensity exercise, anaerobic respiration processes contribute to producing fuel for the brain and muscles. Lactic acid can build up in the blood, at which point the stress response kicks in.
The researchers confirmed that, in response to exercise stress in rats, adrenocorticotropic hormone (ACTH) is secreted, which involves the release of arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) from hypothalamic neurons into the pituitary portal vessels. They used an established animal exercise-stress model to represent human physiological responses and blockers for each factor. “This avoided the difficulties of earlier studies that had used blood samples only, and were unable to identify the causal relationship between ACTH and AVP and CRH responses during exercise stress,” explains Professor Hideaki Soya. Because of the study’s design, the research team could evaluate each factor’s contribution separately and in combination, as well as factor-related activation in the brain, in response to the exercise protocol.
AVP blockers and CRH blockers had an effect on ACTH release from the anterior pituitary only during running (not before running). Each blocker had an effect alone, yet a larger effect was observed when blockers were administered in combination. Furthermore, both arginine vasopressin and corticotrophin-releasing hormone neurons were activated with exercise stress; however, concentrations of adrenocorticotropic hormone in the blood were only correlated with activation of arginine vasopressin neurons. “Thus, both arginine vasopressin and corticotrophin-releasing hormone may contribute to regulating adrenocorticotropic hormone secretion, in different ways, but may do so cooperatively, and therefore together play an important role in the stress response,” says first author Kanako Takahashi.
By uncovering this piece of the puzzle, the precise point at which the stress response is activated by exercise is one step closer to being fully understood. Because excessive stress has profound physiological effects, like delaying recovery from exercise, continued research may provide a clearer picture of the stress response, which could contribute to improved athletic and fitness training efficiency and outcomes.
Story Source:
Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

Patients who develop cervical cancer are often infected not only with the human papillomavirus (HPV) but also simultaneously with the bacterial pathogen Chlamydia trachomatis. The suspicion is, therefore, that the two pathogens work together in a kind of team to “reprogram” the cells they infect in such a way that they degenerate and multiply uncontrollably.
Dr. Cindrilla Chumduri, head of the research group, Department of Microbiology at the Julius Maximilians University of Würzburg (JMU) and her team, has now demonstrated for the first time that this is not just a suspicion but a concretely verifiable effect.
They have developed lifelike organ replicas — so-called 3D organoids — on which they investigate the interactions between the pathogens and the tissues they affect and the disease processes. She has published the results of her research in the journal Nature Communications.
Multiple infections alter cells.
“Our study uses organoid models to show the danger of multiple infections. These create a unique cellular microenvironment that potentially contributes to the reprogramming of tissues and thus to the development of cancer,” says Chumduri, summarizing the central result of her investigations. To do this, the infectious disease biologist used cells from healthy donors to create an almost physiological organoid model of the cervix.
In particular, her research focuses on two tissue types: First, the so-called ectocervix — the part of the cervical mucosa that extends into the vagina. And second is the endocervix — the part of the mucosa that lines the cervix further inside, connecting the uterus. Their essential task is to prevent pathogens from entering the uterus and thus help keep the upper female reproductive tract sterile.

Drug resistance is a major obstacle in the treatment of cancers. In an aggressive type of pancreatic cancer, for instance, drug resistance is associated with the suppression of programmed cell death, which results in the uncontrolled growth of cancer cells. Until recently, the process underlying this phenomenon had remained unknown. A team of researchers from Charité — Universitätsmedizin Berlin have now elucidated the way in which different factors interact in order to enable these cancer cells to survive. They were able to show that inhibition of a key protein limits cancer growth. The researchers’ findings, which have been published in PNAS, may herald a new treatment target for aggressive cancers.
Some types of cancer are particularly difficult to treat, due to their ability to evade existing therapies. Pancreatic cancer is one such cancer — specifically, an aggressive subtype known as pancreatic ductal adenocarcinoma (PDAC). Every year, approximately 19,000 people in Germany develop pancreatic cancer. The most common reason for treatment resistance is the suppression of the process of programmed cell death, known as apoptosis. Targeted treatment therefore requires the use of new treatment strategies. “In addition to identifying a new treatment target, we were able to elucidate a mechanism which enables us to circumvent cancer cell resistance. This enabled us to propose a new strategy for the treatment of particularly aggressive forms of cancer,” says PD Dr. Matthias Wirth of Charité’s Department of Hematology, Oncology and Cancer Immunology on Campus Benjamin Franklin.
Working alongside colleagues from other research organizations in Germany, the United States and the Netherlands, PD Dr. Wirth and his team undertook a detailed study of the processes involved in apoptosis. They discovered that the NOXA protein — which is a key proapoptotic factor — appears to be suppressed in particularly aggressive forms of pancreatic cancer. The mechanism responsible for this suppression had remained unknown until now. “Our approach was therefore to identify drug candidates which might be capable of unleashing NOXA’s cancer-suppressing potential. Using an unbiased drug screening experiment to systematically test substances in genetically altered cell lines, we were able to identify one effective substance,” explains PD Dr. Wirth. He continues: “The substance in question was an inhibitor of the transcription factor known as RUNX1, which is usually present in large quantities in patients with pancreatic cancer and is associated with an inferior prognosis.” The researchers performed a comprehensive series of genome-wide gene expression analyses in order to identify gene activity. This enabled the researchers to show that loss of the RUNX1 gene cancels the suppression of the NOXA protein, which suggests that the RUNX1 protein prevents apoptosis, meaning it has a cancer-promoting effect.
The researchers also found that NOXA gene activity is controlled through spatial interaction with a distant, non-coding DNA sequence to which the transcription factor RUNX1 can bind. As part of a nationwide collaboration, the researchers were then able to demonstrate the same apoptosis-inducing effect of RUNX1 inhibition in both a mouse model and in organoids (cancer patient-derived, three-dimensional cell cultures). Summing up the research, PD Dr. Wirth says: “Our findings therefore direct our focus towards effective RUNX1 inhibitors as a potential new option in the treatment of pancreatic cancer.” He adds: “We are now investigating the degree to which this newly discovered mechanism might translate to other types of cancers. Our next step will be to test more substances, in particular ones already in clinical use. We hope this will enable us to uncover potential combination therapies which would then be tested in clinical studies and ultimately expand the treatment options available to patients with cancer.”
Story Source:
Materials provided by Charité – Universitätsmedizin Berlin. Note: Content may be edited for style and length.

Metastasis, the ability of cancer cells to spread to other parts of the body, is notoriously difficult to treat and is the leading cause of death, meaning that early diagnosis and treatment are vital.
Cancer starts when certain changes take place within the genes inside the nucleus of a cell — the cell’s command centre which contains its DNA.
When examined under a microscope cancer cells look abnormal, and for over 150 years scientists have used changes in the size of the cell’s nucleus to diagnose cancer and its severity.
In many types of cancer these size changes are linked to increased metastasis, the ability of cancer cells to spread, reducing the chances of survival. Yet, few treatments specifically target metastasis.
To tackle this, researchers at the Universities of Edinburgh, Montreal, and Eastern Finland screened drugs in the lab that reversed nucleus size changes in cells from three cancers — prostate, colon and lung.
The screen identified many existing cancer drugs, but also uncovered drugs not previously used to treat cancer, including those used for depression, heart disease and killing parasitic worms.

The agency’s expected lawsuit against the deal for a health technology company would be the latest move by the Biden administration to quash corporate consolidation.WASHINGTON — The Justice Department plans on Thursday to sue to block a $13 billion acquisition of a health technology company by a subsidiary of UnitedHealth Group, said two people familiar with the matter said, in the latest move by the Biden administration to clamp down on corporate consolidation.The agency plans to argue that a deal by UnitedHealth to buy the health tech firm Change Healthcare would give UnitedHealth sensitive data that it could wield against its competitors in the insurance business, said the two people, who were not authorized to publicly discuss the matter. The suit is expected to be filed in the U.S. District Court for the District of Columbia.A spokeswoman for the Justice Department declined to comment. The companies did not immediately respond to requests for comment.The deal would be the latest transaction to run into opposition from the Biden administration, which has made countering corporate consolidation a central part of its economic agenda. President Biden signed an executive order last year to spur competition in different industries. He also appointed Lina Khan, a prominent critic of the tech giants, to lead the Federal Trade Commission, and Jonathan Kanter, a lawyer who has represented large companies, as chief of antitrust efforts at the Justice Department.Since then, the F.T.C. has blocked Lockheed Martin from buying a maker of missile propulsion systems and the chip giant Nvidia from purchasing the design firm Arm. Even before Mr. Kanter was confirmed, the Justice Department sued to block the merger of two major insurance brokers; the purchase of Simon & Schuster by the publisher Penguin Random House; and a deal that would have married some of JetBlue’s operations with American Airlines’s.The planned lawsuit on Thursday is set to challenge a deal made by Optum, a subsidiary of UnitedHealth that said last year it would buy Change Healthcare, which offers technology services to insurers. UnitedHealth is one of the largest health corporations in the country, with $287.6 billion in revenue in 2021. In addition to its health care information technology business, its Optum unit owns physician practices, a large chain of surgery centers and one of the nation’s largest pharmacy benefit managers.At the center of the D.O.J.’s planned lawsuit is the data that Change Healthcare gathers when it helps process insurance claims. The Justice Department plans to argue that the deal would enable UnitedHealth to see the rules that its competitors use to process claims and undercut them. UnitedHealth could also crunch data about patients at other insurers to gain a competitive advantage, the lawsuit is expected to say, according to the two people familiar with the matter.The lawsuit is also expected to say that UnitedHealth could withhold Change Healthcare’s products — which are used by other insurers — from its rivals or save some of its new innovations for itself, the people said. The Justice Department plans to add that the deal would give UnitedHealth a monopoly over a type of service that is used to screen insurance claims for errors and speed up processing, the two people said.The companies have said that the acquisition will improve efficiency in the industry. They also explored selling the part of Change Healthcare that the Justice Department said would give UnitedHealth a new monopoly.Lawmakers and regulators have increasingly worried that big businesses could use troves of data to hurt their rivals. A congressional committee has investigated whether Amazon uses data from outside merchants who use its platform to develop competing products, for example. Critics of Facebook have also argued that the company having years of user data makes it difficult for an upstart service to challenge its dominance.Since Mr. Kanter joined the antitrust division at the Justice Department, critics have said that he should not oversee cases against companies whose rivals he represented while in private practice. According to a financial disclosure form he filed last year, he once represented Cigna, a major insurer that competes with UnitedHealth, and the remote health care company Teladoc.Mr. Kanter has not participated in the lawsuit against UnitedHealth, one of the people with knowledge of the Justice Department’s case said.Reed Abelson

The number of women in the United States who died during pregnancy or shortly after giving birth increased sharply during the first year of the coronavirus pandemic, according to a new study, an increase that health officials attribute partly to Covid and pandemic-related disruptions.The new report, from the National Center for Health Statistics, found that the number of maternal deaths rose 14 percent, to 861 in 2020 from 754 in 2019.The United States already has a much higher maternal mortality rate than other developed countries, and the increase in deaths pushes the nation’s maternal mortality rate to 23.8 deaths per 100,000 live births in 2020 from 20.1 deaths in 2019. Maternal mortality rates in developed countries have in recent years ranged from fewer than two deaths per 100,000 live births in Norway and New Zealand to just below nine deaths per 100,000 live births in France and Canada.Black women in America experienced the most deaths: One-third of the pregnant women and new mothers who died in 2020 were Black, though Black Americans make up just over 13 percent of the population. Their mortality rate was nearly three times that of white women.The mortality rate for Hispanic women, which has historically been lower than for white women, also increased significantly in 2020 and is now almost on par with the rate for white women. Death rates increased among all pregnant women older than 24, but particularly in those 40 and over, whose mortality rate was nearly eight times that of women younger than 25.Although the new report is sparse on details — no maternal mortality figures were provided for American Indian/Alaska Native women, who have higher pregnancy-related deaths than white, Hispanic and Asian/Pacific Islander women — experts said some of the deaths were most likely related to the coronavirus pandemic. Pregnancy puts women at risk for more severe disease if they are infected with the SARS-CoV-2 virus, which causes Covid, and vaccines were not available for them in 2020.

For more than 30 years, scientists have been trying to unravel the mystery of how a key biological molecule self assembles into a rogue protein-like substance known as amyloid, which is thought to play a role in the development of type-2 diabetes — a disease that affects 300 million people worldwide.
A team of scientists at the University of Leeds has, for the first time, been able to identify the step-by-step changes that take place in the molecule known as human islet amyloid polypeptide, or hIAPP, as it changes into amyloid.
They have also discovered new compounds that are able to speed up or slow down the process.
In healthy people, hIAPP is secreted by islets in the pancreas alongside the hormone insulin and it helps to regulate blood glucose levels and the amount of food in the stomach. When hIAPP malfunctions, it forms clumps of a protein-like substance called amyloid fibrils that kill the insulin-producing islets in the pancreas.
The build-up of amyloid fibrils is seen in people with type-2 diabetes although the exact mechanism of how it triggers disease is not known.
The research findings — Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly — are published today in the journal Nature Communications.
The paper not only describes the complex molecular changes seen in hIAPP molecules as they transform into amyloid fibrils, but the scientists also announce that they have discovered two compounds, described as molecule modulators, which can control the process: one of the compounds delays it, the other accelerates it.

People who live in walkable neighborhoods with access to parks and other outdoor activities are more active and less likely to have diabetes or obesity, according to a new paper published in the Endocrine Society’s journal, Endocrine Reviews.
Nearly half of the adults in the United States have obesity, and over 11 percent of the U.S. population has diabetes. Researchers and policymakers have been searching for an effective way to promote healthy lifestyles at a population level to address these dual epidemics.
The built environment is the humanmade structures that provide people with living, working and recreational spaces. This environment includes buildings, neighborhoods, parks, bike paths, restaurants, shops, roads and public transportation. Human health is affected by the physical environments we construct.
“The built environment can influence physical activity levels by promoting active forms of transportation, such as walking and cycling over passive ones, such as car use,” said Gillian L. Booth, M.D., M.Sc., of the University of Toronto, St. Michael’s Hospital of Unity Health Toronto and ICES in Ontario, Canada. “Shifting the transportation choices of local residents may mean that more members of the population can participate in physical activity during their daily routine without structured exercise programs.”
The researchers reviewed several studies on the built environment and their effects on public health and found walkable, activity-friendly cities and neighborhoods were associated with a lower risk of obesity and diabetes. One large population-based study of 32,767 people found the prevalence of obesity among adults living in highly walkable neighborhoods compared to those living in low walkability areas was 43% vs. 53%.
A study of 1.1 million adults with normal blood sugar levels found the incidence of pre-diabetes was 20% higher among people living in less walkable areas after 8 years of follow up. Another study of 1.6 million adults found a 30% to 50% higher likelihood of developing diabetes among people living in low versus highly walkable areas. In a population-based Canadian study, moving from an unwalkable to a highly walkable neighborhood was associated with a 54% lower likelihood of being diagnosed with high blood pressure.
The paper also noted that air pollution and high concentrations of fast-food restaurants are risk factors for diabetes and can substantially reduce the benefits of living in a walkable neighborhood.
“We need policies that promote healthier eating habits and opportunities to engage in active forms of transportation,” said Booth. “Designing neighborhoods that have safe and effective public transit options, cycling infrastructure and walking paths may reduce traffic related pollution.”
The co-lead author of this study is Nicholas A. Howell, M.D., Ph.D., of the University of Toronto.
The study received funding from the Canadian Institutes of Health Research.
Story Source:
Materials provided by The Endocrine Society. Note: Content may be edited for style and length.

An unexpected discovery at UVA Cancer Center has allowed scientists to halt the development of small-cell lung cancer in lab mice, and the surprise finding could open the door to a new treatment approach in people.
The researchers, led by UVA’s Kwon-Sik Park, PhD, and John H. Bushweller, PhD, were seeking to understand the role of a mutation in the EP300 gene in the formation of small-cell lung cancer tumors. Their experiments revealed that the gene makes a protein with surprising properties that can both foster or prevent the development of small-cell lung cancer. By preventing the gene from acting as a tumor-promoter, the researchers were able to stop the cancer from forming and spreading. This held true in both cell samples and lab mice.
The protein’s essential role in tumor formation makes it an enticing target for researchers seeking to development new treatments for small-cell lung cancer (SCLC), an exceptionally dangerous form of cancer. Overall five-year survival for patients diagnosed with SCLC is only about 7%.
“The most remarkable aspect of our findings is that we explained the unique vulnerability of EP300 at the molecular level, down to a single amino acid,” said Park, of the University of Virginia School of Medicine’s Department of Microbiology, Immunology and Cancer Biology. “Given the frequent EP300 mutations found in a wide range of cancer types, I hope that the concept of targeting the EP300 KIX domain will have a more general applicability for cancer therapy.”
About Small-Cell Lung Cancer
Small-cell lung cancer is responsible for approximately 13% of lung cancer diagnoses. Patients typically have better outcomes when it is caught early, before it has spread outside the lung, but it is a fast-growing cancer and is often discovered after it has already spread. Smoking is a major risk factor. Current treatment options include surgery, chemotherapy, radiation and immunotherapy, but, for most patients, treatments do not cure the cancer. That means better options are urgently needed.

Older adults are open to using smart packaging to improve their medication-taking experience, a new study finds.
Smart packages are used to electronically monitor when patients take their medication. When the prescription is not followed as advised by their physician the smart system can notify patients and their caregivers.
Approximately half of the patients with chronic diseases in developed nations do not take their medication properly. With an aging population where taking multiple medications is common, incorrect medication-taking — called medication non-adherence — is a problem impacting the health of patients and costs the healthcare system billions of dollars.
There has been a surge of telehealth technology to address this issue in the last two decades, from complex at-home medication dispensing devices to reminder apps.
“Many of these products are advertised as user-friendly and efficient, but not all are tested with seniors in mind. So how would we know if older adults are able to use them for their day-to-day medication intake and are there any factors that can impact their in-home utilization?” said Sadaf Faisal, a PhD candidate at the University of Waterloo School of Pharmacy and lead author of the study.
The researchers visited and studied 10 participants in their homes with a mean age of 76. On average, each took 11 medications for at least five chronic diseases. The participants were provided with a smart blister pack that synchronized with a web portal and recorded each time a participant opened a blister to take medications.
The researchers then interviewed the participants to assess their experience with the smart blister package. They were also asked to rank the usability of the technology against standardized scales used in product assessment.
“Across participants, we found fairly consistent pros and cons to the technology,” said Tejal Patel, a pharmacy professor and co-author of the study. “The ability to learn the product easily was important for the participants to use it consistently. Feedback from their social circle — such as supportive children, partners or health-care providers — also helped reinforce using the technology.”
In general, participants who were more comfortable with technology were more open to using and liking the smart blister pack. However, device size and lack of portability were a significant downside, and if the product behaved inconsistently — sending reminders one day but not another, for example — participants became frustrated. Participants also said cost was a barrier to use and that they would be less likely to consider smart technology if it was not covered by a drug plan or funded by the government.
“For technology to be effective, it has to be accepted by the end-users,” Faisal said. “Smart, technology-based adherence products have the potential to support patients, but health-care providers should assess older adults’ medication intake behaviours and barriers and facilitators to using a product before recommending them.”
Story Source:
Materials provided by University of Waterloo. Note: Content may be edited for style and length.