In a large multi-ethnic group of adults in the United States without cardiovascular disease, those with work-related stress were more likely to have unfavourable measures of cardiovascular health. The findings are published in the Journal of the American Heart Association.
For the analysis, investigators assessed data collected between 2000 and 2002 for 3579 community-based men and women aged 45–84 years enrolled in the Multi-Ethnic Study of Atherosclerosis. Cardiovascular health was determined based on seven metrics – smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, and blood glucose – with each metric contributing zero points, one point, or two points if in the poor, intermediate, or ideal range, respectively, for a range of 0–14 points.
Work-related stress, which was assessed through a questionnaire, was reported by 20% of participants. After adjusting for potentially influencing factors, individuals with work-related stress, had 25% and 27% lower odds of having average (9–10 points) and optimal (11–14 points) cardiovascular health scores, respectively, compared with individuals without work-related stress.
“To address the public health issue of work-related stress and its detrimental effects on cardiovascular health, future research should prioritise the use of longitudinal studies to identify the mechanisms underlying this association,” said first author Oluseye Ogunmoroti, MD, MPH, of Emory University and senior author Erin Michos, MD, MHS, of Johns Hopkins University. “Additionally, conducting thorough workplace intervention studies is essential for the development and implementation of effective stress management strategies that can enhance employee well-being and improve cardiovascular health.”
During missions into outer space, galactic cosmic radiation (GCR) will penetrate current spacecraft shielding and thus pose a significant risk to human health. Previous studies have shown that GCR can cause short-term cognitive deficits in male rodents. Now a study published in the Journal of Neurochemistry reveals that GCR exposure can also cause long-lasting learning deficits in female rodents.
The impact of GCR on cognition was lessened when mice were fed an antioxidant and anti-inflammatory compound called CDDO-EA.
Beyond its immediate implications for space exploration, the findings contribute to a broader understanding of radiation’s long-term impact on cognitive health.
“Our study lays the groundwork for future causal delineation of how the brain responds to complex GCR exposure and how these brain adaptations result in altered behaviours,” said co-corresponding author Sanghee Yun, PhD, of the Children’s Hospital of Philadelphia Research Institute and the University of Pennsylvania Perelman School of Medicine.
Skin pigmentation may act as a “sponge” for some medications ranging from antibiotics to nicotine patches, potentially influencing the speed with which active drugs reach their intended targets, a pair of scientists report in a perspective article published in the journal Human Genomics.
There has been a growing awareness of genetic susceptibility or tolerance to medications. Redheads for example had been shown to need more inhalational anaesthetic than dark-haired individuals. The researchers argue that a sizable proportion of drugs and other compounds can bind to melanin pigments in the skin, leading to differences in how bioavailable and efficacious these drugs and other compounds are in people with varying skin tones.
“Our review paper concludes that melanin, the pigment responsible for skin colour, shows a surprising affinity for certain drug compounds,” said paper coauthor Simon Groen, an assistant professor of evolutionary systems biology at the University of California, Riverside. “Melanin’s implications for drug safety and dosing have been largely overlooked, raising alarming questions about the efficacy of standard dosing since people vary a lot in skin tones.”
According to Groen and coauthor Sophie Zaaijer, a consultant and researcher affiliated with UC Riverside who specialises in diversity, equity, and inclusion (DEI) in preclinical R&D and clinical trials, current FDA guidelines for toxicity testing fail to adequately address the impact of skin pigmentation on drug interactions.
“This oversight is particularly concerning given the push for more diverse clinical trials, as outlined in the agency’s Diversity Action Plan,” Zaaijer said. “But current early-stage drug development practices still primarily focus on drug testing in white populations of Northern European descent.”
In one example, the researchers found evidence of nicotine affinity for skin pigments, potentially affecting smoking habits across people with a variety of skin tones and raising questions about the efficacy of skin-adhered nicotine patches for smoking cessation.
“Are we inadvertently shortchanging smokers with darker skin tones if they turn to these patches in their attempts to quit?” Groen said.
Groen and Zaaijer propose utilising a new workflow involving human 3D skin models with varying pigmentation levels that could offer pharmaceutical companies an efficient method to assess drug binding properties across different skin types.
“Skin pigmentation should be considered as a factor in safety and dosing estimates,” Zaaijer said. “We stand on the brink of a transformative era in the biomedical industry, where embracing inclusivity is not just an option anymore but a necessity.”
According to the researchers, skin pigmentation is just one example. Genetic variations among minority groups can lead to starkly different drug responses across races and ethnicities, affecting up to 20% of all medications, they said.
“Yet, our molecular understanding of these differences remains very limited,” Zaaijer said.
For example, a study on acetaminophen – a drug that binds melanin – found no difference in total plasma levels of acetaminophen between individuals of African- and European-American ancestries. Oxidation clearance of acetaminophen did however show ancestry-based differences and was 37% lower in African–versus European-Americans, which could have been partially explained by polymorphisms in CYP2E1.
The researchers point out that a shift towards inclusive drug development is set to take place as instigated by a new law, the Food and Drug Omnibus Reform Act, enacted in 2022, which will mandate considering patient diversity in R&D and clinical trials.
The researchers hope to activate the pharmaceutical industry and academia to start doing systematic experimental evaluations in preclinical research in relation to skin pigmentation and drug kinetics. They also encourage patients and advocacy groups to start asking about ancestry-related testing and efficacy of drugs.
Sometimes you have to take a step backward to move forward. Or, in the case of patients recovering from ACL reconstruction, a hop backward may help them know if they are ready to return to the field of play.
A University of Kansas researcher is leading studies examining how single leg backward hopping can help determine recovery progress of patients who have had the anterior cruciate ligament of the knee reconstructed. Initial studies have shown backward hopping distance can tell practitioners, therapists and researchers about strength, force and recovery in the affected joint.
Research so far has shown that backwards hopping it is an effective way of measuring the strength of a person’s knee function and quadriceps strength. And unlike some commonly used measures like vertical jump, it does not take additional equipment to measure – simply a floor and tape measure.
“The goal is to help practitioners have an easy way to measure where people are after an ACL injury and during recovery,” said Yu Song, assistant professor of health, sport & exercise sciences at KU and lead author of the study. “One of the most common ways to measure recovery now is forward hopping distance. However, studies reported that the forward hopping distance masked the real knee recovery status. We want to be able to evaluate more closely with more exact measures.”
For the study, researchers recruited participants who have not suffered ACL injuries in order to initiate the first step of using backward hopping to measure the knee function and quadriceps strength deficits. To simulate a reconstructed ACL, participants performed single leg backwards hops both before and after their quadriceps muscle were fatigued through exercise on one leg. Those in the study stood on a force plate, a device that can measure the amount of force exerted, when performing the hops.
Hip, knee and ankle mechanics were measured in all three movements. Knee mechanics showed significant decrease in all three after fatigue, only in the fatigued leg. Backward hopping distances showed the most significant change, as participants were only able to hop at about 84% of their pre-fatigue force and distance. Subjects were able to perform at more than 90% of their pre-fatigue measures in other hops.
“The knee contribution is very small, especially compared to the hip in forward hops,” Song said. “That is not the case in backward hopping, the knee work is significantly greater (two times) in that motion.”
Single leg backward hopping recorded the greatest peak knee torque, peak knee power and knee work compared to forward and vertical hopping. The fact that backward hopping showed such stark difference in the knee indicates that it could likely be at least an equal, if not superior, method of measuring quadriceps strength deficiency in people recovering from ACL reconstruction, Song said.
The results warrant further study with individuals who are recovering from ACL construction. Work is underway to recruit patients doing rehabilitation from the injury to take part in further studies. That research could help further validate single leg backward hopping as a measure of where they are at in recovery and ultimately, help patients and medical practitioners partner for better recovery and a quicker, safe return to the field of play.
And while hopping from one leg backward may not sound intuitive, it could indeed be the key to a step forward.
“People may not think of knee function or hopping backward as a natural part of movement, but people do use backward direction, such as walking backwards regularly in rehab,” Song said. “Single-leg hopping is something we want to better understand and have found it can significantly and accurately tell us about knee strength.”
Without immediate action, humanity will potentially face further escalation in resistance in fungal disease, a renowned group of scientists from the across the world has warned. The commentary – published in ‘The Lancet’ this week – was coordinated by scientists at The University of Manchester, the Westerdijk Institute and the University of Amsterdam. According to the scientists most fungal pathogens identified by the World Health Organization – accounting for around 3.8 million deaths a year – are either already resistant or rapidly acquiring resistance to antifungal drugs.
The authors argue that the currently narrow focus on bacteria will not fully combat antimicrobial resistance (AMR). September’s United Nations meeting on antimicrobial resistance (AMR) must, they demand, include resistance developed in many fungal pathogens.
Devastating health impacts
Resistance is nowadays the rule rather than the exception for the four currently available antifungal classes, making it difficult – if not impossible – to treat many invasive fungal infections. Fungicide resistant infections include Aspergillus, Candida, Nakaseomyces glabratus, and Trichophyton indotineae, all of which can have devastating health impacts on older or immunocompromised people.
Dr Norman van Rhijn from The University of Manchester coordinated the comment with Professor Ferry Hagen from the University of Amsterdam and the Westerdijk Institute in the Netherlands.
Dr van Rhijn said: “Most people agree that resistant bacterial infections constitute a significant part of the AMR problem. However many drug resistance problems over the past decades have also been the result of invasive fungal diseases largely underrecognized by scientists, governments, clinicians and pharmaceutical companies. The threat of fungal pathogens and antifungal resistance, even though it is a growing global issue, is being left out of the debate.”
Unlike bacteria, the close similarities between fungal and human cells which, say the experts, means it is hard to find treatments that selectively inhibit fungi with minimal toxicity to patients.
Back to square one
Professor Ferry Hagen added: “Despite the huge difficulties in developing them, several promising new agents including entirely new classes of molecules, have entered clinical trials in recent years. But even before they reach the market after years of development, fungicides with similar modes of action are developed by the agrochemical industry resulting in cross-resistance. That sets us back to square one again. It is true many essential crops are affected by fungi, so antifungal protection is required for food security. But the question is, at what price?”
The scientists recommend:
Worldwide agreement on restricting the use of certain classes of antifungal molecules for specific applications.
Collaboration on solutions and regulations that ensure food security and universal health for animals, plants, and humans.
Adding priority to AMR to fungal infections at the UN’s meeting in September.
A group of more than 70 experts from all branches of medicine say they are all owed money for professional services from the Road Accident Fund – some for as long as seven years.
They have now written to Minister of Transport Barbara Creecy asking for her urgent intervention in what they say is a “disastrous situation”.
“We implore you to intervene and install a leadership in the RAF which is able to carry out its proper functioning with integrity and honesty … we are hopeless and tired,” they said in a letter to the minister.
The letter to Minister Creecy, dated 12 July, was a follow-up to one written in early June to the previous minister Sindisiwe Chikunga. There was no response to that.
Since then, dozens more specialists, including surgeons, psychologists and occupational therapists – who are collectively owed more than R150-million – have added their signatures to the document.
But the fund says it owes them nothing.
“The same people rehash this topic every time there’s a new Minister of Transport,” RAF head of corporate communications, McIntosh Polela said.
He said the experts had not been appointed by the fund but “allegedly by its former panel of attorneys”. The Service Level Agreement with the attorneys specifically stated that medical experts could only be engaged upon written authorisation of the fund. And the fund would not be liable for any fees charged without this authorisation.
He said the vast majority of the experts’ unpaid claims had not been authorised by the fund. This was due to the negligence of former panel attorneys.
In the letter to Creecy, clinical psychologist Monique Kok said the expert appointments were legal.
And, she said, their reports were being used in courts to assist in settling matters.
The fund, she said, was “finding new and cunning ways of explaining and nullifying the expert’s authority to have performed such assessment”.
She said each assessment had been done after some form of written instruction, either from the RAF directly or their panel of attorneys.
“The experts have never acted on their own accord and gone out and somehow magically found the current claimants and performed assessments that cost time and resources without instruction from the RAF or their attorneys.”
Kok said the fund’s refusal to pay their invoices had had a dire impact with some going out of business and losing their homes.
In the follow-up letter to Creecy, psychologist Chris Sampson said the experts wanted a meeting with the minister.
“We have diligently serviced the public for many years by assisting the RAF and the courts in determining appropriate compensation for claimants who were injured in serious motor vehicle accidents.
“It would appear that the organisation (and its leader’s) treatment of its own appointed experts gives us the impression that it has been allowed to become a law unto itself and from court cases it further appears that it refuses to pay claimants, experts or abide by court orders.”
Sampson said the experts conducted “painstaking investigations” and did extensive reports which were being used by the fund and yet were waiting seven years later to be paid.
They had paid out of their own pockets the significant costs of translators, transcribers, equipment and testing material.
“We believe that the state and specifically, your ministry, has a duty to intervene in what has become a well-documented failure, where this statutory body has not carried out its stipulated functions due to either, incompetence, poor leadership, arrogance and/or a fundamental evasion of responsibility and fiduciary duties,” he said.
Speaking to GroundUp, Sampson said he personally was owed about R3-million. Payments had become sporadic since about 2017, and after the Covid pandemic, had completely dried up.
“They come up with a multitude of excuses. They claim we didn’t deliver the reports on time. They repeatedly lose invoices. They say the payments are not loaded on their system , and so there must be something wrong but they don’t tell us what’s wrong. They also accuse us of charging above the tariff when they set the tariff.”
Sampson said litigation, for most, was not an option. “We don’t have deep pockets. And because we have not been paid there is nothing rattling in them.
“But we cannot throw away seven years of hard slog. We have nothing left to lose and we just hope the new minister has the zeal and energy to finally deal with the problems at the fund.”
Creecy’s office has acknowledged receipt of the two letters but attempts by GroundUp to get comment from were unsuccessful.
Two new species of psychoactive mushrooms in the genus Psilocybe have been described from southern Africa, bringing the list to six known species indigenous to Africa.
This is even though Psilocybe species are amongst the most well-known and well-studied species of psychoactive mushrooms in the world, with around 140 described species.
In a paper published in the journal Mycologia this week, researchers from Stellenbosch University (SU) and citizen mycologists describe the two new species as Psilocybe ingeli and Psilocybe maluti.
Psilocybe ingeli was first found in 2023 growing in pastureland in KwaZulu-Natal by Talan Moult, a self-taught citizen mycologist. Psilocybe maluti was first found on a Free State small holding in 2021 by Daniella Mulder, who sent photos of the mushrooms for identification to Andrew Killian, one of South Africa’s leading citizen mycologists based in Somerset West.
In both instances, the unusual looking specimens were sent to Breyten van der Merwe for DNA sequencing and analysis in the lab of Prof. Karin Jacobs in SU’s Department of Microbiology. Van der Merwe, now a postgraduate student in chemical engineering at SU, is a trained mycologist and first author of the paper.
The paper also contains information on the traditional use of P. maluti by Basotho traditional healers from the mountain kingdom of Lesotho. According to the researchers, this appears to be the only recorded first-hand report of hallucinogenic mushrooms being used traditionally in Africa.
Cullen Taylor Clark, a citizen mycologist and co-author, worked with Mamosebetsi Sethathi, a Mosotho traditional healer, to document the use of P. maluti (locally known as koae-ea-lekhoaba) in traditional healing practices. This forms part of a larger effort, led by Clark, to document the use of mushrooms by indigenous groups in southern Africa.
Van der Merwe says there are very likely more southern African species in this genus, and that more citizen scientists need to become involved: “These two species were sent to me by citizen scientists. It would be impossible for a single researcher to cover a fraction of an area these mushroom enthusiasts have access to. This is the only way we will be able to further studies in African mycology.”
Jacobs echoes this sentiment: “There are only a handful of mycologists in Africa documenting local biodiversity. Considering the vast mycological diversity on the continent, it is a daunting task. Collaborating with citizen mycologists is therefore hugely beneficial. In addition to more material, collaboration also opens avenues for conversation and exploration, which can lead to documenting mycophilia (the love of mushrooms) on the African continent.”
Increased use of blood transfusions after major traumatic brain injury could help patients in intensive care units to regain greater functional independence and a better quality of life.
Six months after a major traumatic brain injury (TBI), patients who benefited from this approach regained more functional independence and had a better quality of life than those subjected to a more restrictive approach, even though the combined incidence of death and major disability was not significantly different between the two treatment groups.
This is the conclusion of an international research team led by Alexis Turgeon, professor at Université Laval, Canada Research Chair in Neurological Critical Care and Trauma, critical care physician and researcher at CHU de Québec-Université Laval, whose work is published today in the New England Journal of Medicine.
“This randomized clinical trial, initiated in 2017, was carried out in 34 hospital centres in Canada, the United Kingdom, France and Brazil. Its aim was to compare two blood transfusion strategies – one so-called restrictive and the other liberal – employed to care for people hospitalized in an intensive care unit following a TBI. These approaches differ in the degree of anemia, or the minimum hemoglobin concentration that must be present in patients’ blood before a blood transfusion can be given,” explains Professor Turgeon.
“Most patients hospitalised after a TBI suffer from anemia, defined as low haemoglobin concentration, which could reduce oxygen transport to the brain during a period when it is most vulnerable,” points out François Lauzier, also a professor at Université Laval and who co-led the study with Professor Dean Fergusson of the Ottawa Hospital Research Institute.
The restrictive approach consists in tolerating a low haemoglobin level before giving a transfusion, while a liberal approach aims to maintain high haemoglobin levels, thus giving more blood transfusion.
“By improving oxygen transport to the brain during the acute phase of care, it may be possible to save more nerve cells in the days following a TBI, thereby preventing additional brain damage,” says Professor Turgeon.
To conduct the study, the research team recruited 742 critically ill patients with moderate or severe TBI and anaemia defined as a haemoglobin level of 10g/dL or less during hospitalisation. Randomly divided into two groups, these individuals were subjected to one or other of the transfusion strategies during their stay in the intensive care unit. To maintain these thresholds, the care teams administered blood transfusions whenever necessary.
Six months after TBI, the research team assessed the level of overall recovery for each group, including neurovegetative status, dependence on activities of daily living and impairments preventing resumption of activities that had been performed prior to TBI. “The combined incidence of death and major disability was not statistically different between the two groups, but seemed favouring the liberal strategy in all analyses,” says Professor Turgeon. What’s more, those treated using the liberal approach showed a higher functional independence measure and quality of life index than those treated using the restrictive approach.
“In light of the overall results of our study and considering the safety of current blood transfusions, the liberal strategy is probably the option that should be preferred in the acute phase of care to improve long-term prognosis following TBI,” concludes Professor Turgeon.
For years, Prof Bozhi Tian’s lab has been learning how to integrate the rigid, metallic and bulky world of electronics with the soft, flexible and delicate world of the body. In their latest work, published in Science, they have created a prototype for what they call “living bioelectronics”: a combination of living cells, gel, and electronics that can integrate with living tissue and treat psoriasis.
The patches are made of sensors, bacterial cells, and a gel made from starch and gelatin. Tests in mice found that the devices could continuously monitor and improve psoriasis-like symptoms, without irritating skin.
“This is a bridge from traditional bioelectronics, which incorporates living cells as part of the therapy,” said Jiuyun Shi, the co-first author of the paper and a former PhD student in Tian’s lab (now with Stanford University).
“We’re very excited because it’s been a decade and a half in the making,” said Tian.
The researchers hope the principles can also be applied to other parts of the body, such as cardiological or neural stimulation.
A third layer: cells
Pairing electronics with the human body has always been difficult. Though devices like pacemakers have improved countless lives, they have their drawbacks; electronics tend to be bulky and rigid, and can cause irritation.
But Tian’s lab specialises in uncovering the fundamental principles behind how living cells and tissue interact with synthetic materials; their previous work has included a tiny pacemaker that can be controlled with light and strong but flexible materials that could form the basis of bone implants.
In this study, they took a new approach. Typically, bioelectronics consist of the electronics themselves, plus a soft layer to make them less irritating to the body.
But Tian’s group wondered if they could add new capabilities by integrating a third component: living cells themselves. The group was intrigued with the healing properties of certain bacteria such as S. epidermidis, a microbe that naturally lives on human skin and has been shown to reduce inflammation.
They created a device with three components. The framework is a thin, flexible electronic circuit with sensors. It is overlaid with a gel created from tapioca starch and gelatin, which is ultrasoft and mimics the makeup of tissue itself. Lastly, S. epidermidis microbes are tucked into the gel.
When the device is placed on skin, the bacteria secrete compounds that reduce inflammation, and the sensor monitors the skin for signals like skin temperature and humidity. In tests with mice prone to psoriasis-like skin conditions, there was a significant reduction in symptoms.
Their initial tests ran for a week, but the researchers hope the system, which they term the ABLE platform, for Active Biointegrated Living Electronics, could be used for a half-year or more. To make the treatment more convenient, they said, the device can be freeze-dried for storage and easily rehydrated when needed.
Since the healing effects are provided by microbes, “It’s like a living drug – you don’t have to refill it,” said Saehyun Kim, the other co-first author of the paper and a current PhD student in Tian’s lab.
In addition to treating psoriasis, the scientists can envision applications such as patches to speed wound healing on patients with diabetes.
They also hope to extend the approach to other tissue types and cell types. “For example, could you create an insulin-producing device, or a device that interfaces with neurons?” said Tian. “There are many potential applications.”
A multidisciplinary research team at the University of California, Irvine has revealed that the circadian clock can be leveraged to enhance the efficacy of checkpoint inhibitor cancer therapy. Checkpoint inhibitors block different proteins from binding to tumour cells, allowing the immune system’s T cells to kill the tumour.
The study, published online today in the journal Nature Immunology, provides deeper insights into the intricate relationship among the circadian clock, immune regulation and tumour development and found that a therapeutic approach optimising time-of-day delivery based on an individual’s unique circadian patterns offers new avenues for prevention and treatment.
“Disruption of the internal biological pacemaker is an inherent aspect of modern society that may contribute to the rising incidence of many cancer types. We found that proper regulation of circadian rhythms is necessary to suppress inflammation and support peak immune function,” said corresponding author Selma Masri, UC Irvine associate professor of biological chemistry. “Understanding precisely how circadian disruption promotes disease progression could lead to behaviour modification to reduce cancer risk.”
Team members used an advanced single-cell RNA sequencing technique in a genetic model of colorectal cancer and identified clock-dependent changes controlling the number of myeloid-derived cells that suppress T cell activation. They discovered that disruption of the internal clock in the epithelial cells lining the intestine alters secretion of cytokine proteins, leading to heightened inflammation, increased numbers of immunosuppressive myeloid cells and cancer progression. These findings were leveraged to demonstrate that providing immunotherapy at the time of day when these immunosuppressive myeloid cells are most abundant significantly enhanced the efficacy of immune checkpoint blockades in solid tumours.
“As we enhance our understanding of the fundamental mechanism of circadian regulation of immunity, we will be able to harness the power of the body’s natural rhythms to fight cancer and develop more personalised and effective treatment strategies,” said lead author Bridget Fortin, a UC Irvine doctoral student in the Department of Biological Chemistry.
While this study represents a significant step forward in defining circadian control of anti-tumour immunity, the team believes future research should focus on exploring additional factors and cell types influencing time-of-day response to checkpoint inhibitor therapy.
