Publisher Health

A breast cancer patient’s perspective on their physical well-being can provide a better indication of their response to cancer treatment than clinician-based tools, a new study has found, highlighting the importance of shared decision-making in the treatment process.
The research also identified differences between clinician-based data and the patient-reported data, with some clinicians overestimating their patient’s physical wellbeing.
“An essential component of patient-centred care, shared decision making is a process in which the clinician and patient collate and discuss the available evidence on the benefits and harms of treatments, ensuring the most appropriate and informed decision is made for the patient,” says study lead author Natansh Modi, an NHMRC PhD candidate in the Clinical Cancer Epidemiology Lab at Flinders University.
Two tools can be used during shared-decision making: the Eastern Cooperative Oncology Group performance status (ECOG PS), a tool interpreted by the doctor, and patient-reported outcomes (PROs), structured tools whereby a patient self-reports their perspective on their physical, social, emotional, and functional abilities.
“PROs are generally used as secondary data in clinical trials to help with interpreting results; however, they have recently shown to be important in providing a prognosis to the patient for cancer types including bladder, lung and skin cancers, but their value to HER2-positive advanced breast cancer had yet to be fully explored,” says Mr Modi.
Published in the journal ESMO Open, the study pooled data from several trials to look at almost 3000 patients who underwent drug treatments for human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Emotion-recognition among people with disorders such as Parkinson’s disease or schizophrenia may be affected by changes in the levels dopamine in the brain, say researchers at the University of Birmingham.
Dopamine is a chemical messenger — often known as the ‘happy hormone’ — that carries signals controlling mental and emotional responses in the brain.
Parkinson’s disease and other neurological disorders are known for their links with low or disrupted dopamine levels that causes those affected to struggle with a number of social skills. This is the first time, however, that a positive connection has been made between dopamine and the ability to recognise emotions in others.
In a new study, published in the Journal of Neuroscience, a team in the University’s Centre for Human Brain Health showed that manipulating levels of dopamine affected emotion recognition. More specifically, the research showed that while people with low baseline levels of the chemical messenger became better at emotion recognition after receiving a dopamine boost, those with higher baseline levels actually became worse.
Lead author Dr Bianca Schuster said: “The ability to recognise emotions in others is fundamental to our everyday social interactions and this is often atypical in people with neurological disorders. Our research shows that dopamine medication — even in small doses — can affect these abilities. That has important implications for fine tuning a patient’s medicine regime to ensure a balance between controlling their symptoms and preserving social functions.”
In the study, the team worked with 33 healthy male and female individuals and assessed their baseline dopamine levels. This was done by testing people’s working memory, a well-recognised proxy for dopamine levels that avoids invasive brain imaging.
Individuals were asked to gauge the emotions of a series of figures in three different video clips in two separate tests. In the first they were given a dose of haloperidol, a drug affecting brain dopamine levels which is commonly used to treat schizophrenia, and in the second they were given a placebo. The figures were seen walking, in outline only, and in three different gaits and postures, denoting angry, happy and sad emotions.
Participants with a lower working memory, and so assumed lower baseline levels of dopamine, improved their emotion recognition under haloperidol, whereas those with a higher working memory became worse at emotion recognition under the drug.
“Individuals with low baseline dopamine also slowed their own walking pace under haloperidol, and so we think the effects of the drug on movement and emotion recognition are connected,” says Dr Schuster. “It is not yet clear, however, why the drug actually impaired emotion recognition in the participants with high baseline dopamine. It’s likely that timing and movement are not the only mechanisms that are important.”
More work needs to be done to confirm whether these results predict the effects of dopamine in other emotion recognition tasks.
Story Source:
Materials provided by University of Birmingham. Note: Content may be edited for style and length.

Modern anesthesia is one of the most important medical achievements. Whereas before, patients had to suffer hellish agonies during every operation, today anesthesia enables completely painless procedures. One feels nothing and can remember nothing afterwards. It is already known from electroencephalography (EEG) studies on patients that during anesthesia the brain is put into a deep sleep-like state in which periods of rhythmic electrical activity alternate with periods of complete inactivity. This state is called burst-suppression. Until now, it was unclear where exactly this state happens in the brain and which brain areas are involved.
However, this question is important to better understand the phenomenon and thus how the brain functions under anesthesia. Researchers from the Functional Imaging Unit at the German Primate Center (DPZ) — Leibniz Institute for Primate Research in Göttingen have used functional magnetic resonance imaging (fMRI) to study the precise spatial distribution of synchronously working brain regions in anesthetized humans, long-tailed macaques, common marmosets and rats. They were able to show for the first time that the areas where burst-suppression is evident differ significantly in primates and rodents. While in rats large parts of the cerebral cortex synchronously show the burst-suppression pattern, in primates individual sensory regions, such as the visual cortex, are excluded from it.
“Our brain can be thought of as a full soccer stadium when we are awake,” explains Nikoloz Sirmpilatze, a scientist in the Functional Imaging Unit and lead author of the study. “Our active neurons are like tens of thousands of spectators all talking at once. Under anesthesia, however, neuronal activity is synchronized. You can measure this activity using EEG as uniform waves, as if all the spectators in the stadium were singing the same song. In deep anesthesia, this song is repeatedly interrupted by periods of silence. This is called burst-suppression. The deeper the anesthesia, the shorter the phases of uniform activity, the bursts, and the longer the periodically recurring inactive phases, the so-called suppressions.”
The phenomenon is caused by many different anesthetics, some of which vary in their mechanisms of action. And burst-suppression is also detectable in coma patients. However, it is not known whether this condition is a protective reaction of the brain or a sign of impaired functioning. It has also been unclear where in the brain burst-suppression occurs and which brain areas are involved, as localization by EEG alone is not possible.
To answer this question, Nikoloz Sirmpilatze and the researcher team used the imaging technique of fMRI. The method makes blood flow changes in the brain visible. The increased activity of neurons in a particular area of the brain leads to an increase in metabolism, followed by an increased blood and oxygen supply at this location, which is ultimately visible in the fMRI image.
In the first part of the study, the researchers established a system to evaluate fMRI data in humans, monkeys and rodents in a standardized manner using the same method. To do this, they used simultaneously-measured EEG and fMRI data from anesthetized patients that had been generated in a previously conducted study at the Technical University of Munich. “We first looked to see whether the burst-suppression detected in the EEG was also visible in the fMRI data and whether it showed a certain pattern,” says Nikoloz Sirmpilatze. “Based on that, we developed a new algorithm that allowed detecting burst-suppression events in the experimental animals using fMRI, without additional EEG measurement.”
The researchers then performed fMRI measurements in anesthetized long-tailed macaques, common marmosets and rats. In all animals, they were able to detect and precisely localize burst-suppression as a function of anesthetic concentration. The spatial distribution of burst-suppression showed that in both humans and monkey species, certain sensory areas, such as the visual cortex, were excluded from it. In contrast, in the rats, the entire cerebral cortex was affected by burst-suppression.
“At the moment, we can only speculate about the reasons,” says Nikoloz Sirmpilatze, who was awarded the German Primate Center’s 2021 PhD Thesis Award for his work. “Primates orient themselves mainly through their sense of sight. Therefore, the visual cortex is a highly specialized region that differs from other brain areas by special cell types and structures. In rats, this is not the case. In future studies, we will investigate what exactly happens in these regions during anesthesia to ultimately understand why burst-suppression is not detectable there with fMRI.”
Susann Boretius, head of the Functional Imaging Unit and senior author of the study adds: “The study not only raises the question of the extent to which rodents are suitable models for many areas of human brain research, especially when it comes to anesthesia, but the results also have many implications for neuroscience and the evolution of neural networks in general.”

An FDA-approved drug to lower blood sugar in adults with Type 2 diabetes also may decrease blood vessel dysfunction associated with aging, according to a new study from the University of Missouri School of Medicine.
Researchers initially examined the role aging plays in human blood vessel function and stiffness. Then they evaluated how treatment with the sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Empa) improved blood vessel function and reduced arterial stiffness in aged male mice.
“Cardiovascular disease is the main cause of death in older adults in the U.S.,” said Camila Manrique-Acevedo, MD, associate professor of medicine. “Weight loss, physical activity, antihypertensive therapy and lipid-lowering drugs have shown variable effectiveness at improving blood vessel function and reducing arterial stiffness. But additional approaches are needed to improve vascular health in older adults.”
The study first compared blood vessel function and stiffness in 18 healthy human patients — average age of 25 — with 18 patients who averaged 61 years old. They found the older patients had impaired endothelial function and increased aortic stiffness when compared to the younger patients.
“Our findings in young and older adults confirm previous clinical data demonstrating the impact of aging on blood vessel function and arterial stiffness,” Manrique-Acevedo said. “Importantly, we were able to replicate this data in a rodent model.”
In order to investigate the effects of Empa on vascular aging, 72-week-old male mice were divided into two groups. Twenty-nine were fed for six weeks with a diet enriched with Empa, while the other half were given standard food. After analyzing both groups six weeks later, researchers discovered the mice treated with Empa experienced improved blood vessel function, reduced arterial stiffness and other vascular benefits.
“To our knowledge, this is the first study to examine the potential role of SGLT2 inhibition in reversing vascular aging,” Manrique-Acevedo said. “And our findings highlight the need for further clinical investigations to determine the potential role of SGLT2 inhibition as a therapeutic tool to delay or reverse vascular aging in humans.”
The entire MU research team consisted of Jaume Padilla, PhD, associate professor of nutrition and exercise physiology and co-corresponding author of this work; Luis Martinez-Lemus, DVM, PhD, professor of medical pharmacology and physiology, and R. Scott Rector, PhD, associate professor of nutrition. It also included postdoctoral fellows Rogerio Soares, PhD, Francisco Ramirez-Perez, PhD, Thaysa Ghiarone, PhD, and Francisco Cabral-Amador, PhD; research specialist Mariana Morales Quinones; assistant research professors Christopher Foote, PhD, and Neekun Sharma, PhD; and graduate students James A. Smith and Gavin Power.
Story Source:
Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

Watching too much TV is associated with increased risk of coronary heart disease regardless of an individual’s genetic makeup, say a team of scientists at the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge and the University of Hong Kong.
In a study published today in BMC Medicine, the researchers show that — assuming a causal link — 11% of cases of coronary heart disease could be prevented if people watched less than an hour of TV each day.
According to the British Heart Foundation, coronary heart disease is one of the UK’s leading causes of death, responsible for around 64,000 deaths each year. In the UK, one in eight men and one in 15 women die from the disease. People with coronary heart disease are twice as likely to have a stroke.
One of the major risk factors for coronary heart disease is sedentary behaviour — in other words, sitting for long periods of time rather than being physically active. To examine the link between time spent in screen-based sedentary behaviours such as TV viewing and leisure-time computer use, an individual’s DNA, and their risk of coronary heart disease, researchers examined data from the UK Biobank, a study that includes over 500,000 adults who have been followed up prospectively for about 12 years.
The team created polygenic risk scores for each individual — that is, their genetic risk of developing coronary heart disease based on 300 genetic variants known to influence their chances of developing the condition. As expected, individuals with higher polygenic risk scores were at greatest risk of developing the condition.
People who watched more than four hours of TV per day were at greatest risk of the disease, regardless of their polygenic risk score. Compared to these individuals, people who watched two to three hours of TV a day had a relative 6% lower rate of developing the condition, while those who watched less than an hour of TV had a relative 16% lower rate. These associations were independent of genetic susceptibility and other known risk factors.

Researchers have boosted pioneering technology to show whether potential treatments are worth progressing into human trials, in a game-changing move that could dramatically reduce the high failure rates in drug discovery and development.
The WEHI-led team is using protein degrader technology to test the efficacy and safety of drugs by better mimicking clinical settings, with a collaborative Australian project already using the system to establish promising drug targets for a range of hard-to-treat cancers.
At a glance Pioneering technology can assess how effective and safe a drug target could be for patients, far earlier in the research process. A collaborative effort is currently leveraging the technology to validate drug targets for a range of cancers. The protein degrader technology offers a revolutionary approach for substantially reducing the pharmaceutical industry’s high drug development failure rate.Almost 95% of biomedical projects fail before entering human clinical trials with the average cost of bringing a new drug to market estimated to be around US$1.8bn. A key issue is the difficulty of assessing a drug’s true safety and effectiveness in preclinical studies.
While conventional drug development aims to inhibit the activity of disease-causing proteins, protein degrader technology looks to completely destroy those proteins, with precision targeting. The technology enables scientists to deliver far more relevant results from pre-clinical testing, to potentially bring safe and effective new treatments to patients faster.
In a new study published in Nature Communications, WEHI researchers Dr Charlene Magtoto, Dr Rebecca Feltham and Dr Christoph Grohmann (now at Nurix Therapeutics) have significantly extended our understanding of one type of protein degrader technology by expanding on current validation strategies, which could boost the number of drugs successfully entering human trials.

The desire for a son could mean Nepali mothers stop breastfeeding infant daughters sooner, says new research.
Girls in Nepal are breastfed for fewer months than boys on average, with girls with older sisters but no brothers being the most disadvantaged, says the study.
And this shorter breastfeeding time is linked to a greater risk of death for Nepali infants in the study.
‘Gender, Nutritional Disparities, and Child Survival in Nepal’ by Dr Jasmine Fledderjohann, of Lancaster University, and Dr Melanie Channon,from the University of Bath, is published in the journal, BMC Nutrition, today.
And, says the study, the desire to have a son may influence breastfeeding duration because if a woman has not had a son, she may feel greater pressure to try to conceive again in the hopes of having a boy.
The researchers explain that breastfeeding has a known contraceptive effect, and women who want to try for another child may stop breastfeeding sooner than women who are not trying to conceive again.

Cystic fibrosis is a rare genetic disease which can cause very serious symptoms. In particular, patients suffer from chronic bacterial infections that can lead to respiratory failure. It is caused by mutations in the CFTR gene, which regulates water movement across the cell membrane. Consequently, mucus quality is altered, it is no longer capable of capturing undesirable bacteria and expelling them. Using a model reproducing a respiratory epithelium — a protective tissue composed of a monolayer of cells — teams from the University of Geneva (UNIGE) have discovered that a simple film of liquid is sufficient to restore the airways’ seal and reduce the risk of bacterial infection.
These results, to be read in a special issue of the journal Cells, open the way to new therapies based on mucus hydration. A promising alternative to current therapies that are often not widely enough effective.
Despite recent therapeutic advances, people with cystic fibrosis — one in every 2,500 births in Europe — have a life expectancy of no more than 46 years and altered quality of life. The disease is caused by one or more mutations in the CFTR gene, which affects the proper functioning of an essential protective barrier. The epithelial cells that line the airways are usually sealed together and thus protect the airways from bacterial colonisation. They are also lined with a fluid, a slippery mucus that traps unwanted germs and carries them away. When the CFTR protein is altered, the junctions between the cells loosen and the dehydrated mucus tends to stagnate, both of which promote the development of respiratory infections.
“While it was already known that mucus hydration and the presence of sufficiently tight junctions preserved the integrity of the airways, the mechanisms involved and the links between these two mechanisms remained mysterious, which hindered the development of new therapies,” explains Marc Chanson, a professor in the Department of Cell Physiology and Metabolism and the Geneva Centre for Inflammation Research at the UNIGE Faculty of Medicine, who led this research.
Hydrating to restore tightness
The scientists first developed an in vitro model using human lung cells. This model, which was awarded the UNIGE 3R Prize in 2021 for reducing animal experimentation, reproduces airways epithelium of healthy and cystic fibrosis patients in a way that is both accurate and close to clinical reality. In collaboration with the team of Christian van Delden and Thilo Köhler from the Departments of Medicine and of Microbiology and Molecular Medicine at the UNIGE Faculty of Medicine, Marc Chanson and his team compared the response of epithelial cells invalidated for CFTR to bacterial infection, to which either hydrated, healthy mucus or physiological saline solution had been added.
“We observed a similar response in both cases: the presence of liquid, whatever its composition, restored the airways and protected them from infection,” explains Juliette Simonin, post-doctoral fellow in Marc Chanson’s laboratory and first author of the study. “Surface hydration is sufficient to tighten the junctions between cells and protects the epithelium integrity from bacterial colonisation, even when CFTR is not functioning.”
One treatment for all mutations?
A triple therapy pharmacologically targeting the CFTR protein has recently become available on the market. However, it only targets certain mutations of the CFTR gene and is only prescribed for a specific population of people with cystic fibrosis. More widely effective and safe treatments are still sorely lacking.
“Our results provide evidence that rehydration of the airway surface is beneficial. The challenge now is to find a simple way of doing this in all people with the disease, whatever the mutation involved,” concludes Marc Chanson.
Story Source:
Materials provided by Université de Genève. Note: Content may be edited for style and length.

Millions of years ago, all mammals lived on land, but at some point, several species left land and evolved to a life in the sea: think of seals and whales, which today are adapted to life underwater.
The rest who remained on land have similarly adapted to a life on land, and it can hardly come as a surprise that we humans today hear better on land than underwater — which is the conclusion from a group of scientists in a new study. But the study also reveals surprising news about human hearing..
Jakob Christensen-Dalsgaard is an expert in animal hearing and in his laboratory at University of Southern Denmark, he tirelessly throws himself into hearing studies of animals such as cormorants, geckos, frogs, crocodiles — and now also humans. This time, together with Ph.D. student Kenneth Sørensen and biologist Magnus Wahlberg, also from University of Southern Denmark, and an expert in animal underwater hearing.
Decades of hearing tests
Since the 1950s, several different attempts have been made to measure human hearing underwater. The US military, for example, has had an interest in understanding how divers are affected by underwater explosions, and in general, the hearing tests have been very different.
Some subjects have been tested with diving equipment on, others with neoprene caps and still others with air-filled diving masks — all of which can affect the test subjects’ hearing.

A new study from the University of Southampton has discovered that ‘crown-like structures’ surrounding breast tumours in overweight and obese patients could hinder their response to therapy.
The findings of this study could potentially be used to improve personalised treatment for patients with HER2 positive overexpressed breast cancer.
Adipose tissue, or body fat, is an important component of the healthy human breast and yet high body mass index (BMI) is associated with increased risk of developing breast cancer. Overweight patients also have worse survival rates than patients with healthy body weight.
In patients with a high BMI, increased body fat surrounding the breast can cause inflammatory immune cells, called macrophages, to gather in the breast’s fat tissue. These macrophages can then form what are called ‘crown-like structures’ by surrounding these fat cells (see picture below). This creates an inflammatory environment in the breast which can lead to the onset and growth of tumours.
How these crown-like structures go on to affect breast cancer progression and respond to therapy is largely unknown.
The research team, led by Professors Stephen Beers, Ramsey Cutress and Dr Charles Birts, assessed samples from a group of HER2+ breast cancer patients to investigate the link between high BMI and the formation of crown-like structures, and the subsequent effect of these on how patients responded to therapy with a drug called trastuzumab (Herceptin®).