Publisher Health

Researchers are exploring a potential new therapeutic approach for triple negative breast cancer treatment. Amir Abdo Alsharabasy, a CÚRAM doctoral candidate working in the laboratory of Professor Abhay Pandit, is working on the design of nitric oxide scavengers to form a new treatment approach for this aggressive form of breast cancer.
Triple-negative breast cancer is invasive breast cancer that does not respond to hormonal therapy medicines or the current medicines that target the HER2 protein. Triple-negative breast cancer is usually more aggressive, harder to treat, and more likely to recur than cancers that are hormone receptor-positive or HER2-positive.
“Nitric oxide is one of the prominent free radicals produced by the tumor tissue,” explains Amir, “It, at certain concentrations, plays a significant role in breast cancer progression by inducing the cancer cells to spread to other parts of the body Our goal is to develop injectable hydrogel formulations, which can reduce the levels of, or ‘scavenge’ the nitric oxide, while enhancing the generation of carbon monoxide, so that we can potentially design a new treatment approach for triple negative breast cancer.”
Nitric oxide interacts with different components of the large network of proteins and other molecules that surround, support, and give structure to tumor cells and tissues in the body. Hyaluronic acid is one of the main components of this network and is the material of choice for fabricating these hydrogels.
“HA plays multiple roles in tumour tissues” says Amir. “However, its interactions with nitric oxide have not been thoroughly investigated. The study, recently published in Biomacromolecules, attempts to understand the mechanism of these interactions and the different effects on nitric oxide levels and migration of breast cancer cells.”
The study is supervised by Prof Abhay Pandit, Scientific Director of CÚRAM, and was published with collaborators Dr Sharon Glynn from the Lambe Institute for Translational Research and Dr Pau Farras from the School of Biological and Chemical Sciences in the Ryan Institute at the National University of Ireland Galway,
The work investigated the ability of HA to scavenge nitric oxide. The team found that the conversion of nitric oxide to certain nitrogen centred free radicals causes the HA to break down, which further inhibits the nitric oxide induced migration of cancer cells in the tumor environment.
Collectively, these results help toward understanding the involvement of HA in nitric oxide induced cell migration and suggests the potential use of modified HA, as a key material in different biomedical applications.
Commenting on the study, Professor Abhay Pandit, said: “While the recent progress in research about the roles of nitric oxide with tumour progression resulted ultimately in a number of ongoing clinical trials for evaluating the effects of NO-synthase inhibitors, we are focusing on NO itself trying to avoid the side effects/reactions of these inhibitors.”
Amir Abdo Alsharabasy received a BSc in Chemistry & Biochemistry, Mansoura University, Egypt, MSc in Biochemistry, Helwan University, Egypt and MSc in Biological and Bioprocess Engineering, Sheffield University, U.K. He spent some time working as a research assistant in Radiation Chemistry Department at NCRRT, Egypt. He was recently awarded two awards for his research. The first was a presentation award from the Second International Conference “Therapeutic Applications of Nitric Oxide in Cancer and Inflammatory-related Diseases for his talk on the interactions between nitric oxide and hemin and their implications in the nitration of proteins in breast cancer cells. The second was an EMBO Scientific Exchange Grant to support a visit of the laboratory of Dr. Lasse Jensen in Linköping Univ., Sweden.

A UC Davis Health study finds that the antiviral tecovirimat appears to be safe and effective for the treatment of monkeypox symptoms and skin lesions. The study is one of the earliest studies to assess and report the outcomes of treating patients with monkeypox with this antiviral.
Tecovirimat (TPOXX) is an FDA-approved antiviral drug for the treatment of smallpox. It limits viral spread in the body by inhibiting the work of the protein involved in the release of the enveloped virus. Recently, the Centers for Disease Control and Prevention (CDC) allowed physicians to prescribe tecovirimat on a compassionate use basis to treat adults and children with orthopoxvirus infections, including monkeypox.
In a research letter published in JAMA, UC Davis infectious disease experts presented insights on 25 patients with monkeypox who were given tecovirimat therapy.
“We have very limited clinical data on the use of tecovirimat for monkeypox infection. There is much to learn about the natural progression of the disease and how tecovirimat and other antivirals may affect it,” said lead author Angel Desai. She is an adult infectious disease specialist at UC Davis Health.
Treating monkeypox with tecovirimat
The recent global outbreak of monkeypox has led to more than 45,500 cases as of August 22, 2022. While symptoms usually resolve on their own in 2-4 weeks, a recent study showed that 13% of patients needed hospitalization.

In September 2020, during the height of the first wave of the Covid-19 outbreak, Italians voted on a constitutional amendment to reduce the number of parliamentary members. Furthermore, in seven of the 20 Italian regions, citizens also voted to elect regional governments and regional assembly representatives; finally, in 955 of the 7,903 Italian municipalities, citizens were asked to select a new mayor. This increased level of election activity resulted in a 22 per cent rise in voter turnout in municipalities that voted for both referendum and local elections, compared to municipalities voting only for the referendum.
The Surrey team analysed weekly Covid-19 infections across Italy (at the municipality level) before and after the September poll and found that a 1 per cent increase in turnout amounted to an average of a 1.1 per cent increase in post-election infections.
Dr Giuseppe Moscelli, co-author of the study and Reader of Economics at the University of Surrey, said:
“With the recent political turmoil in Italy culminating with the end of Mario Draghi’s government, it is important to reflect on the past two and a half years, which have been an immensely tragic period for all of Italy.
“The 2020 referendum came as the world was dealing with the unprecedented threat of Covid-19, and our model shows that something as fundamental as casting a vote can come at a cost.”
Along with saving approximately 23,000 lives, Surrey’s researchers found that delaying the 2021 Italian general election saved the country €362 million in additional hospital costs for patients that would have been admitted to inpatient care and Intensive Care Units.
Dr Marco Mello, co-author of the study and a Research Fellow at the University of Surrey, added:
“The decision whether to postpone an election or a general referendum due to a pandemic event poses a clear trade-off between human lives and health on the one hand, and political rights on the other hand. With our research, we propose an economic framework for such an important evaluation to be undertaken in similar future situations.”
The research has been published in the Journal of Economic Behavior & Organization
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The distress of doctors and nurses working in hospitals during the COVID-19 pandemic has received much attention in news media and academic research, including their moral distress witnessing so many deaths at times when they could offer so little. Much less attention has been paid to the moral distress of clinicians working in other settings during the pandemic.
Using data from a survey of more than 2,000 primary care, dental, and behavioral health clinicians who work with low income patients in safety net clinics, UNC School of Medicine’s Donald Pathman, MD, MPH, found that nearly 72 percent reported experiencing either mild or intense levels of moral distress during the first year of the pandemic due to limits on what they could do for their patients, witnessing their patients’ struggles and the challenges of their own work situations.
This analysis, published in BMJ Open, was conducted from data late in 2020 from practices in 20 states.
“Most people receive their health care in office settings, and many clinicians working there experienced moral distress from how the pandemic limited the care they could provide to patients and from witnessing the pandemic’s effects on patients and coworkers,” said lead author Donald Pathman, MD, MPH, a professor in the UNC Department of Family Medicine.
Moral distress was defined in the survey as when one witnesses or does things that contradict deeply held moral and ethical beliefs and expectations. “Moral distress is a concept developed to understand the consequences of disturbing situations nurses can experience in hospitals, but the concept of moral distress is likely just as useful in understanding a type of distress clinicians in all disciplines and work settings experience,” Pathman said.
Respondents in the survey were 2,073 clinicians who work in community health centers, mental health facilities and other types of safety net clinics that provide care to low income patients who face barriers to receiving care in the mainstream U.S. healthcare system. Many of these patients are also members of racial-ethnic minority groups.

A three-drug medication known as a “polypill,” developed by the Spanish National Center for Cardiovascular Research (CNIC) and Ferrer, is effective in preventing secondary adverse cardiovascular events in people who have previously had a heart attack, reducing cardiovascular mortality by 33 percent in this patient population. These are findings from the SECURE trial led by Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital, and General Director of CNIC.
The study results were announced Friday, August 26, in a Hot Line session at the European Society of Cardiology Congress (ESC 2022) in Barcelona, Spain, and published in The New England Journal of Medicine.
“The results of the SECURE study show that for the first time that the polypill, which contains aspirin, ramipril, and atorvastatin, achieves clinically relevant reductions in the recurrent cardiovascular events among people who have recovered from a previous heart attack because of better adherence to this simplified approach with a simple polypill, rather than taking them separately as conventional,” says Dr. Fuster.
Patients recovering from a heart attack — also known as myocardial infarction — are prescribed specific treatments to prevent subsequent cardiovascular events. Standard therapy includes three different drugs: an antiplatelet agent (like aspirin); ramipril or a similar drug to control blood pressure; and a lipid-reducing drug, such as a statin. However, fewer than 50 percent of patients consistently adhere to their medication regimen.
“Although most patients initially adhere to treatment after an acute event such as an infarction, adherence drops off after the first few months. Our goal was to have an impact right from the start, and most of the patients in the study began taking a simple polypill in the first week after having a heart attack,” Dr. Fuster explains.
“Adherence to treatment after an acute myocardial infarction is essential for effective secondary prevention,” said José María Castellano, MD, study first author and Scientific Director of Fundación de Investigación HM Hospitales.

Nine in ten people do not get a good night’s sleep, according to research presented at ESC Congress 2022.1 The study found that suboptimal sleep was associated with a higher likelihood of heart disease and stroke. The authors estimated that seven in ten of these cardiovascular conditions could be prevented if everyone was a good sleeper.
“The low prevalence of good sleepers was expected given our busy, 24/7 lives,” said study author Dr. Aboubakari Nambiema of INSERM (the French National Institute of Health and Medical Research), Paris, France. “The importance of sleep quality and quantity for heart health should be taught early in life when healthy behaviours become established. Minimising night-time noise and stress at work can both help improve sleep.”
Previous studies on sleep and heart disease have generally focused on one sleep habit, such as sleep duration or sleep apnoea, where breathing stops and starts while sleeping. In addition, prior studies have often assessed sleep at baseline only. The current study used a healthy sleep score combining five sleep habits. The researchers investigated the association between the baseline sleep score, and changes over time in the sleep score, and incident cardiovascular disease.
This study included 7,200 participants of the Paris Prospective Study III (PPP3), an observational community-based prospective cohort. Men and women aged 50 to 75 years and free of cardiovascular disease were recruited in a preventive medical centre between 2008 and 2011. The average age was 59.7 years and 62% were men. Participants underwent a physical examination and completed questionnaires on lifestyle, personal and family medical history, and medical conditions.
Questionnaires were used to collect information on five sleep habits at baseline and two follow up visits. Each factor was given 1 point if optimal and 0 if not. A healthy sleep score ranging from 0 to 5 was calculated, with 0 or 1 considered poor and 5 considered optimal. Those with an optimal score reported sleeping 7 to 8 hours per night, never or rarely having insomnia, no frequent excessive daytime sleepiness, no sleep apnoea, and an early chronotype (being a morning person). The researchers checked for incident coronary heart disease and stroke every two years for a total of 10 years.
At baseline, 10% of participants had an optimal sleep score and 8% had a poor score. During a median follow up of eight years, 274 participants developed coronary heart disease or stroke. The researchers analysed the association between sleep scores and cardiovascular events after adjusting for age, sex, alcohol consumption, occupation, smoking, body mass index, physical activity, cholesterol level, diabetes, and family history of heart attack, stroke or sudden cardiac death. They found that the risk of coronary heart disease and stroke decreased by 22% for every 1 point rise in the sleep score at baseline. More specifically, compared to those with a score of 0 or 1, participants with a score of 5 had a 75% lower risk of heart disease or stroke.
The researchers estimated the proportion of cardiovascular events that could be prevented with healthier sleep. They found that if all participants had an optimal sleep score, 72% of new cases of coronary heart disease and stroke might be avoided each year.
Over two follow ups, almost half of participants (48%) changed their sleep score: in 25% it decreased whereas in 23% it improved. When the researchers examined the association between the change in score and cardiovascular events, they found that a 1 point increment over time was associated with a 7% reduction in the risk of coronary heart disease or stroke.
Dr. Nambiema said: “Our study illustrates the potential for sleeping well to preserve heart health and suggests that improving sleep is linked with lower risks of coronary heart disease and stroke. We also found that the vast majority of people have sleep difficulties. Given that cardiovascular disease is the top cause of death worldwide, greater awareness is needed on the importance of good sleep for maintaining a healthy heart.”
1The abstract “Healthy sleep score and incident cardiovascular diseases: the Paris Prospective Study III (PPS3)” will be presented during the session Sleep disorders and apnoea, physical inactivity on Saturday 27 August at 14:15 to 15:00 CEST at Station 4.
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An analysis in nearly 2.3 million Europeans has found detrimental associations between cold weather and deaths from heart disease, particularly in poor neighbourhoods. The late-breaking research is presented at ESC Congress 2022.1 Hot weather was linked with excess deaths from heart disease and stroke in patients with heart conditions.
Study author Professor Stefan Agewall of the University of Oslo, Norway said: “Climate change is leading to a rise in the average global temperature but also extreme cold in some regions. More than 70,000 excess deaths occurred across Europe during the summer of 2003 due to intense heatwaves.2 Cold weather also accounts for excess deaths and hospital admissions.3,4 Previously studies on the cardiovascular effects of heat and cold mainly used aggregated data, such as daily deaths in a city. The EXHAUSTION project used individual data, enabling us to identify vulnerable subgroups for protective interventions, thereby increasing resilience for future weather events.”
The analysis included 2.28 million adults from five cohort studies conducted in Italy, Germany, the UK, Norway, and Sweden between 1994 and 2010. The average age ranged from 49.7 years to 71.7 years and the proportion of women ranged from 36.0% to 54.5%. Participants with and without cardiovascular disease at baseline were included. Data on mortality and new-onset disease were collected through death and disease registries and follow up surveys. Daily average air temperatures at participants’ home addresses were collected from local weather stations or estimated using modelling of temperature data from weather stations
The relationships between temperature and cardiovascular conditions and death were analysed for all participants and in subgroups with particular characteristics. A time-stratified case-crossover study design was used where for each participant, the researchers compared the temperature on the day of the week an adverse event occurred (e.g. Monday) with the temperature on the same day of the week without an adverse event (e.g. all remaining Mondays) within the same month. Using within-participant comparisons between days in the same month eliminated the potential confounding effects of participant characteristics and time trends.
The analysis found increased risks of death from cardiovascular disease overall and ischaemic heart disease in particular, as well as an elevated risk of new-onset ischaemic heart disease, associated with cold weather. With an approximately 10°C temperature drop, from 5°C to -5°C, there was a 19% greater risk of death from cardiovascular disease (relative risk [RR] 1.19; 95% confidence interval [CI] 1.04-1.36) and a 22% elevated likelihood of death from ischaemic heart disease (RR 1.22; 95% CI 1.07-1.38). There was a 4% higher risk of new-onset ischaemic heart disease associated with an approximately 11°C temperature drop, from 2°C to -9°C (RR 1.04; 95% CI: 1.01-1.08).
Professor Agewall said: “The relationships between cold temperatures and deaths were more pronounced in men and people living in neighbourhoods with a low socioeconomic status. The links between cold and new-onset ischaemic heart disease were stronger among women and people older than 65 years.”
Heat was not related to detrimental effects in the overall study population. However, temperature rises from 15°C to 24°C were associated with 25% (RR 1.25; 95% CI 1.12-1.39) and 30% (RR 1.30; 95% CI 1.10-1.53) elevated risks of death from cardiovascular disease and stroke, respectively, in people with heart disease at baseline.

A review of decades of research revealed more than a dozen kinds of animals in addition to slugs and snails have caused rat lungworm disease in people around the world.
Researchers from the University of Hawai’i at Mānoa and the University of London (UK) combed through nearly 140 scientific studies published between 1962 and 2022 and found 32 species of freshwater prawns/shrimp, crayfish, crabs, flatworms, fish, sea snakes, frogs, toads, lizards, centipedes, cattle, pigs, and snails can act as carriers of the rat lungworm parasite (Angiostrongylus cantonensis). Of these, at least 13 species of prawns/shrimp, crabs, flatworms, fish, frogs, toads, lizards, and centipedes have been associated with causing rat lungworm disease in humans.
This work was the master’s degree thesis research of the first author, Helena Turck, as part of a graduate program in One Health jointly run by the Royal Veterinary College and the London School of Hygiene and Tropical Medicine, both part of the University of London, UK. Robert Cowie, senior author on the study and faculty member in the UH Mānoa School of Ocean and Earth Science and Technology (SOEST), supervised Turck’s research remotely during the pandemic and co-authored the new publication. Professor Mark Fox of the Royal Veterinary College is also a co-author of the study.
Cowie explained that the rat lungworm has a complex life cycle that involves slugs and snails as so-called “intermediate” hosts and rats as “definitive” hosts in which the worms reach maturity and reproduce. Rats become infected when they eat an infected snail or slug. People also become infected when they eat an infected snail or slug, and this can lead to serious illness and occasionally death.
Humans, accidental hosts
“But people can also get infected if they eat so-called paratenic hosts, which are also known as carrier hosts,” said Cowie, who is a research professor in the Pacific Biosciences Research Center at SOEST. “These are animals that become infected by eating infected snails or slugs, but in which the worms cannot develop to maturity as they do in a rat. However, in such hosts the worms become dormant, but still infective. And if one of these hosts, or part of one, is then eaten raw by a person — an accidental host — development can continue, but only up to a point.”
That point is when they are in the person’s brain, where they are moving around, feeding, and growing. But then the worms die. The damage to the brain and the massive inflammation that results when they die is primarily what causes the symptoms of rat lungworm disease.

Scientists have published new evidence showing that selective planting of vegetation between roads and playgrounds can substantially cut toxic traffic-derived air pollution reaching school children.
The new findings, published this week in the journal Scientific Reports, demonstrate that roadside vegetation can be designed, installed and maintained to achieve rapid, significant and cost-effective improvement of air quality.
Exposure to traffic-related air pollution has been linked with a range of health risks including cardiovascular, respiratory and neurological health. These risks are likely to be exacerbated in young children attending primary schools next to busy roads as their major organs are still developing and children have a higher breathing rate than adults.
Exposure to fine particulate matter in air pollution is reportedly the largest environmental risk factor contributing to cardiovascular deaths and disease globally, and is linked to around six to nine million premature deaths each year.
A team of researchers led by Barbara Maher, Emeritus Professor at Lancaster University, and supported by Groundwork Greater Manchester, installed ‘tredges’ (trees managed as a head-high hedge) at three Manchester primary schools during the summer school holidays of 2019.
One school had an ivy screen installed, another had western red cedar and the third school had a mixture of western red cedar, Swedish birch and an inner juniper hedge. A fourth school, with no planting, was used as a control.

Dying reefs and once-vibrant corals that have since lost all colour: climate change is having massive effects on the architects of undersea cities. As waters grow warmer, the phenomenon of “coral bleaching” continues to spread. Yet not all corals are equally susceptible. An international team led by Cesar Pacherres and Moritz Holtappels from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) in Bremerhaven and Soeren Ahmerkamp from the Max Planck Institute for Marine Microbiology in Bremen may have found the explanation: using minuscule filaments (cilia), corals can influence the currents in their immediate vicinity, protecting themselves from harmful oxygen concentrations, as the experts report in the journal Current Biology.
Coral reefs are not only one of the most biodiverse ecosystems on our planet; they are also among the most economically important ones. “For example, they’re extremely important for fishing and tourism,” says Moritz Holtappels. “And as wave breakers, they provide essential services for coastal management.” Accordingly, the experts are very concerned about the current status of these valuable undersea cities, which are simultaneously facing a variety of threats: the overfertilization and acidification of the ocean, as well as overly intensive fishing. Making matters worse, climate change is increasingly leading to the dreaded “coral bleaching.”
This happens when the water gets too warm for the reef-builders. Most of the small polyps that create these impressive calcium carbonate formations live in symbiosis with algae belonging to the dinoflagellates. They offer these organisms protection, and in return receive energy-rich sugar and other products that their “flatmates” produce from carbon dioxide and water with the aid of sunlight. But this process, known as photosynthesis, can become problematic when temperatures climb too high. Instead of providing the corals with energy, the algae release harmful substances. In response, the polyps “evict” them, causing the corals to lose their colour — and in many cases, to die off completely. “But this doesn’t happen to all the corals in a reef,” Cesar Pacherres explains. “Some bleach out quickly, others, not at all.” What explains the difference in responses?
In order to find out, the researchers took a closer look at the complex relationship between the stony coral Porites lutea and its green neighbours. Apparently, one problem facing this underwater “shared flat” is that the algae’s photosynthesis releases large amounts of oxygen. Although vital for most flora and fauna, too much oxygen can be dangerous, particularly in warm water. When the concentration is too high, the algae’s photosynthesis organ increasingly processes oxygen instead of carbon dioxide. This is not only less efficient in terms of generating energy; it also produces dangerous oxygen radicals, which can harm cells. “When there’s too much sunlight, it’s hard for corals to get rid of this surplus oxygen,” says Pacherres. “Low water movement and high temperatures worsen this effect, known as oxidative stress, which is widely considered to be the main cause of coral bleaching.”
Using innovative new methods, the experts followed the oxygen’s trail. What they learned: the algae producing the oxygen were by no means uniformly distributed among the corals examined. The algae were far denser in some areas than in others. “We expected to find the highest oxygen concentrations in the water above these photosynthesis hotspots,” says Soeren Ahmerkamp. “But much to our surprise, just the opposite was true.”
This finding contradicts the conventional theory regarding mass transfer between corals and their environs: until recently, the assumption had been that, once released substances left the tissue in question, they simply moved from regions with higher concentrations to those with lower concentrations via diffusion. But if that were true, the researchers should have found the highest oxygen concentrations where the most oxygen was produced. The only explanation for a different pattern is if the corals actively transport the element elsewhere. And thanks to cutting-edge surveillance technologies, they now know exactly how it’s done.
“The trick is that the tiny hairs, or cilia, on the corals’ surface, when moved in unison, create small eddies,” Ahmerkamp explains. In this way, the polyps can shape local currents in order to specifically ventilate those areas that are rich in algae. To do so, they direct oxygen-poor water from above to those areas with the highest algal densities, where it becomes charged with oxygen. In turn, the upward portion of the eddy produced flows away from the corals and releases its load higher up in the water column. Using a computer model, the researchers simulated the interplay between diffusion and ciliary action on the corals’ surface. As the simulation shows, by producing these local eddies near the algae, stony corals can cut the area of their surface exposed to critical oxygen concentrations in half.
“Accordingly, these sessile corals aren’t completely at the mercy of their marine environment, as was previously believed,” summarises Moritz Holtappels. Influencing the mass transfer with their surroundings in a targeted manner, and fanning away surplus oxygen, can be vital for these organisms — especially those growing in waters with little or no current. However, most likely not all corals have such a refined ventilation system. This could explain why some undergo more extreme bleaching than others in response to adverse conditions.