Researchers share insights from US reduction of cigarette, sugar, and opioid consumption
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A case definition of market-driven epidemics (MDEs) could help address critical barriers to timely, effective prevention and mitigation, according to a study published this week in the open-access journal PLOS Global Public Health by Jonathan Quick from Duke University School of Medicine, US, and colleagues.
The misuse and overconsumption of certain consumer products have become major global risk factors for premature deaths at all ages, with their total costs in trillions of dollars. Progress in reducing such deaths has been difficult, slow, and too often unsuccessful. To address this challenge, Jonathan Quick and colleagues introduced a case definition of MDEs, which arise when companies aggressively market products with proven harms, deny these harms, and actively oppose mitigation efforts. To demonstrate the application of this concept, the researchers selected three MDE products: cigarettes, sugar, and prescription opioids. Based on the histories of these three epidemics, the researchers described five MDE phases: market expansion, evidence of harm, corporate resistance, mitigation, and market adaptation.
From the peak of consumption to the most recent available data, US cigarette sales fell by 82%, sugar consumption by 15%, and prescription opioid prescriptions by 62%. In each case, the consumption tipping point occurred when compelling evidence of harm, professional alarm, and an authoritative public health voice or public mobilisation overcame the impact of corporate marketing and resistance efforts. Among the three epidemics, the gap between suspicion of harm and the consumption tipping point ranged from one to five decades – much of which was attributable to the time required to generate sufficient evidence of harm. Market adaptation to the reduced consumption of target products had both negative impacts (eg, geographical shift of corporate marketing efforts) and positive impacts (eg, consumer shift away from sugar-sweetened beverages).
According to the authors, this is the first comparative analysis of three successful efforts to change the product consumption patterns of millions of people – and, over time, some of the associated adverse health impacts of these products. The MDE epidemiological approach of shortening the latent time between phases provides the global health community with a new method to address existing and emerging potentially harmful products and their health, social, and economic impacts.
While the specific product and circumstances are unique to each MDE, understanding the epidemiology of consumption and health impacts, and epidemic milestones, should help public health leaders combat current MDEs and more swiftly recognise future MDEs. Given the similar patterns among different MDEs, public health leaders, researchers, civil society and others can apply the mitigation strategies presented in the review article to save lives and lessen the impact of continuing and emerging MDEs.
The authors add: “The use of cigarettes and other unhealthy products costs the world millions of lives and trillions of dollars each year. An analysis of U.S. progress against three such market-driven epidemics demonstrates that we can save lives through earlier, more decisive action by public health leaders, researchers, and public mobilization,” concluding: “The use of cigarettes and other unhealthy products often follow patterns similar to infectious disease epidemics, causing widespread harm before any public health response. We can save lives by recognizing these market-driven epidemics earlier and acting more decisively to control them.”
A new paper surveying advances in diabetes pathogenesis and treatment explores the complex factors contributing to the onset and progression of the disease, suggesting that an understanding of these dynamics is key to developing targeted interventions to reduce the risk of developing diabetes and managing its complications.
In a paper in a special 50th anniversary issue of the peer-reviewed journal Cell, the authors surveyed hundreds of studies that have emerged over the years looking at the causes underpinning types 1 (T1D) and 2 (T2D) diabetes and new treatments for the disease. They examine the role that genes, environmental factors, and social determinants of health play and diabetes’ effect on cardiovascular and kidney disease.
What they found shows there are many advances in treatments that could stem the tide of a disease that has struck millions of people around the globe and continues to grow. In addition, some of these advances could be used to treat other disorders. But there are still challenges ahead.
“As the prevalence of diabetes continues to grow around the world, it is important to understand the latest advancements in research so that clinicians can provide the best care to their patients, and patients can make informed choices that support improved health outcomes,” said lead author Dr E. Dale Abel, chair of the UCLA Department of Medicine. “This is an educational resource that integrates the latest research and trends in diabetes management, which may have implications for clinical practice as the diabetic patient population continues to grow.
“This review will be the go-to reference for physicians and researchers, providing a state-of-the-art update of where the field is currently, and where it is headed,” Abel added.
Most people are affected by type 2 diabetes, for which inadequate diet and obesity are important underlying causes. Type 1 diabetes accounts for fewer than 5% of all cases. As of 2021 about 529 million people around the world were diagnosed with diabetes, representing about 6.1% of the global population, or about one in 16 people. Prevalence in some regions is as high as 12.3%. Type 2 diabetes comprises about 96% of cases, with more than half due to obesity. Some 1.31 billion people are projected to have the disease by 2050, with prevalence rising as high as 16.8% in North Africa and the Middle East and 11.3% in Latin America and the Caribbean, the researchers write.
Genetics, the central nervous system, and the interplay between various organs as well as social and environmental factors such as food insecurity and air pollution play a role in development of diabetes.
But some recent discoveries represent significant strides toward managing and perhaps even reversing the disease. For instance, a 2019 study found that a 14-day course of the antibody teplizumab delayed the progression of type 1 diabetes from stage 1 to stage 3 by 24 months. A follow-up analysis in 2021 showed that the delay could be up to 32.5 months.
Based on these results, the U.S. Food and Drug Administration approved teplizumab as the first disease-modifying therapy for type 1 diabetes, the researchers write.
Advances in insulins with optimised pharmacokinetics, algorithm-driven subcutaneous insulin pumps, continuous glucose monitoring, and improved tools for self-management have significantly improved the quality of life and outcomes for people with stage 3 type 1 diabetes.
In addition, stem cells could replace insulin-producing cells that are lost in type 1 diabetes, Abel said.
For type 2 diabetes, three classes of glucose-lowering medicines that were introduced in the last 20 years – GLP1RAs (glucagon like peptide-1 receptor agonists), DPP-4 inhibitors, and SGLT-2 inhibitors – have enabled people to control their glucose levels without gaining weight and with a low risk of developing hypoglycaemia. Personalised and precision medicine approaches are being explored to target the molecular mechanisms behind diabetes. However, they must demonstrate that benefits are clinically superior to standard care and are cost-effective. Also, it remains to be seen if precision approaches can be implemented in all settings worldwide, including those with few resources.
Combinations of GLP1Ras and with molecules that target other receptors such as GIP have shown even greater efficacy in treating diabetes. Recent trials have also shown that they are very effective in treating obesity, certain types of heart failure and even sleep apnoea, in part because of their potency to induce weight loss and reduce inflammation. Clinical trials are now underway to test their efficacy in treating other disorders such as Alzheimer’s disease, Abel said.
“Advances in therapy now raise the hope of preventing or curing T1D and treating T2D in ways that not only improve metabolic homeostasis, but also concretely reduce the risk and progression of cardio-renal disease,” the researchers write. “Finally, as we understand and develop tools for discerning the underlying heterogeneity leading to diabetes and its complications, the stage will be set for targeting therapies and prevention strategies to optimize their impact, in ways that will be broadly applicable across diverse populations and availability of health care resources.”
Researchers at UCLA Health uncovered new information about the role inflammation plays in mitigating liver fibrosis, which is associated with metabolic-associated fatty liver disease (MAFLD). While inflammation in the liver has long been considered a prerequisite to developing liver fibrosis, the scarring and thickening of tissue that can impair the liver’s ability to function, this new research, published in the Journal of Clinical Investigation, suggests that reducing inflammation may not influence the extent of fibrosis.
“Liver fibrosis is the critical feature that creates chronic liver disease and liver cancer. If we can keep fibrosis in check then we can meaningfully impact liver disease,” said Tamer Sallam, MD, corresponding author of the study and vice chair and associate professor in the department of medicine at the David Geffen School of Medicine at UCLA.
“For decades we have believed that targeting inflammation is one of the most important ways to reduce MAFLD. But this new research indicates that inflammation, while still important, may not be the main driver of fibrosis.”
The studylooked specifically at a protein called lipopolysaccharide binding protein (LBP), which is involved in the body’s immune response, and how LBP functions in mice. Findings showed that mice without LBP in their liver cells had lower levels of liver inflammation and better liver function but no change in fibrosis.
In addition to mouse models, the researchers also studied genetic analyses from large human datasets and human tissue samples from MAFLD patients at different stages in the disease, to examine the consequence of loss of LBP function. The evidence combined showed that the LBP does not alter scar tissue markers.
Sallam indicated a need to further explore how LBP influences inflammation and whether other factors can offer a more potent reduction in inflammation and have an impact on reducing fibrosis.
“Reducing scar burden is one of the holy grails in the treatment of advanced liver diseases,” Sallam said. “These results suggest that certain ways of targeting inflammation may not be a viable option and that more directed therapies against other pathways could help us better target fibrosis and improve outcomes for patients.”
Review of research suggests patients feel better when providers sit or crouch during bedside conversations
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Doctors and other healthcare workers, you may want to sit down for this news. A systematic review of studies suggests that getting at a patient’s eye level when talking with them about their diagnosis or care can really make a difference.
Their findings, published in the Journal of General Internal Medicine, revealed that sitting or crouching at a hospitalised patient’s bedside was associated with more trust, satisfaction and even better clinical outcomes than standing, according to the review of evidence.
The study’s authors, from the University of Michigan and VA Ann Arbor Healthcare System, note that most of the studies on this topic varied with their interventions and outcomes, and were found to have high risk of bias.
So, the researchers sat down and figured out how to study the issue as part of their own larger evaluation of how different nonverbal factors impact care, perceptions and outcomes.
Until their study ends, they say their systematic review should prompt clinicians and hospital administrators to encourage more sitting at the bedside.
Something as simple as making folding chairs and stools available in or near patient rooms could help – and in fact, the VA Ann Arbor has installed folding chairs in many hospital rooms at the Lieutenant Colonel Charles S. Kettles VA Medical Center.
Nathan Houchens, MD, the U-M Medical School faculty member and VA hospitalist who worked with U-M medical students to review the evidence on this topic, says they focused on physician posture because of the power dynamics and hierarchy of hospital-based care.
We hope our work will bring more recognition to the significance of sitting and the general conclusion that patients appreciate it.”
-Nathan Houchens, M.D.
An attending or resident physician can shift that relationship with a patient by getting down to eye level instead of standing over them, he notes.
He credits the idea for the study to two former medical students, who have now graduated and gone on to further medical training elsewhere: Rita Palanjian, M.D., and Mariam Nasrallah, M.D.
“It turns out that only 14 studies met criteria for evaluation in our systematic review of the impacts of moving to eye level, and only two of them were rigorous experiments,” said Houchens.
“Also, the studies measured many different things, from length of the patient encounter and patient impressions of empathy and compassion, to hospitals’ overall patient evaluation scores as measured by standardised surveys like the federal HCAHPS survey.”
In general, he says, the data paint the picture that patients prefer clinicians who are sitting or at eye level, although this wasn’t universally true.
And many studies acknowledged that even when physicians were assigned to sit with their patients, they didn’t always do so – especially if dedicated seating was not available.
Houchens knows from supervising U-M medical students and residents at the VA that clinicians may be worried that sitting down will prolong the interaction when they have other patients and duties to get to.
But the evidence the team reviewed suggests this is not the case.
He notes that other factors, such as concerns about infection transmission, can also make it harder to consistently get to eye level.
“We hope our work will bring more recognition to the significance of sitting and the general conclusion that patients appreciate it,” said Houchens.
Making seating available, encouraging physicians to get at eye level, and senior physicians making a point to sit as role models for their students and residents, could help too.
A recently launched VA/U-M study, funded by the Agency for Healthcare Research and Quality and called the M-Wellness Laboratory study, includes physician posture as part of a bundle of interventions aimed at making hospital environments more conducive to healing and forming bonds between patient and provider.
In addition to encouraging providers to sit by their patients’ bedsides, the intervention also includes encouraging warm greetings as providers enter patient rooms and posing questions to patients about their priorities and backgrounds during conversations.
The researchers will look for any differences in hospital length of stay, readmissions, patient satisfaction scores, and other measures between the units where the bundle of interventions is being rolled out, and those where it is not yet.
Like statins, cholesterol absorption inhibitors are linked with a lower risk of developing liver cancer.
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Past studies have suggested that taking cholesterol-lowering statin drugs may lower the risk of developing liver cancer. In a new study of non-statin cholesterol-lowering medications, one type was linked to lower risks of liver cancer. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
Cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids are types of non-statin cholesterol-lowering medications prescribed to manage cholesterol and lipid levels. The different classes of drugs work in different ways. A team led by Katherine A. McGlynn, PhD, MPH, of the National Cancer Institute, looked for associations between these five types of non-statin cholesterol-lowering medications and risk of liver cancer, the sixth most commonly occurring cancer globally and the third leading cause of cancer mortality.
The investigators used information from the Clinical Practice Research Datalink (CPRD), a primary care database that covers approximately 7% of the United Kingdom population. Their analysis included 3719 liver cancer cases and 14 876 matched controls without cancer. Additional matches were also made based on individuals’ type 2 diabetes and chronic liver disease status.
Use of cholesterol absorption inhibitors was associated with 31% lower odds of liver cancer risk in the overall analysis. These medications were also linked with a lower risk of liver cancer in analyses based on diabetes and liver disease status. The study also confirmed that statins were associated with 35% lower odds of liver cancer.
No associations with liver cancer risk were observed for fibrates, omega-3 fatty acids, or niacin. While bile acid sequestrant use was associated with higher odds of liver cancer risk in the overall analysis, the results of analyses based on diabetes and liver disease status were inconsistent, suggesting that replication of these observations is important.
“As few studies have examined the effects of non-statin cholesterol-lowering drugs on liver cancer risk, the results of our study require replication in other populations. If our findings are confirmed in other studies, however, our results may inform liver cancer prevention research,” said Dr. McGlynn.
Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/
By Nthusang Lefafa
Despite some improvement over the past three years, the North West province continues to experience medicine shortages, according to a survey by a community clinic monitoring initiative. We unpack the latest findings and ask why shortages persist in the province.
Some people in need of HIV or tuberculosis (TB) medicines were sent home empty handed after visiting clinics in the North West. This is according to the latest survey of public healthcare services in the province published by community-led clinic monitoring group Ritshidze. The survey data was collected in April and May this year.
Of the roughly 490 000 people living with HIV in North West, around 380 000 (77%) are on antiretroviral treatment, according to figures from Thembisa, the leading mathematical model of HIV in South Africa. Antiretroviral treatment is recommended for everyone living with the virus.
According to Ritshidze, besides HIV and TB medicines, other commonly reported stockouts at clinic-level include pain medicines (such as Paracetamol and Ibuprofen), cardiac medicines (such as Aspirin), contraceptives, dry stock (gauze, bandages, needles), maternal health medicines, psychiatric medicines, and different vaccines.
Out of the 72 facilities surveyed in the province, medicine stockouts lasting one to three months were reported at 20 and stockouts lasting three to six months were reported at six.
‘Failed to comply’
The North West health department, according to Ritshidze, has failed to comply with national guidelines recommending that people living with HIV should be provided with a three or more month supply of antiretrovirals at a time. They found that 71% of people surveyed in 2024 received antiretroviral refills of three to six months – in each of the previous three years this number was below 30%. There was large differences between districts, with 97% of people surveyed in Bojanala district reporting getting a 3 month supply of ARVs — compared to 37% in Dr Kenneth Kaunda.
Giving people longer antiretroviral refills like this means people do not have to visit health facilities as often to collect their medicines.
Various factors influence giving more people longer antiretroviral refills, Tebogo Lekgethwane, Director of Media and Communications in the province’s health department, told Spotlight.
A crucial factor, he said, is that patients must have a good track record of collecting their medication as well as a history of a documented undetectable viral load. “There’s therefore a criteria for multi-month supply which includes the fact that patients should have been on treatment for six months, they are compliant and clinically stable,” said Lekgethwane.
No “crisis” of medicine shortages
While the year-on-year comparisons should not be overinterpreted – Ritshidze themselves advise caution – the numbers nevertheless provide some indication that when it comes to medicines stockouts things are trending in the right direction. The total number of stockouts in the province reported to Ritshidze plunged from 895 in 2021 to 148 in 2024 – over the same period stockouts of HIV medicines went from 115 to 19 and stockouts of TB medicines from 28 to 7.
Lekgethwane was at pains to point out that Ritshidze’s findings do not necessarily represent the actual picture of the entire province. He said that the department believes that the Ritshidze report is subjective and relies on isolated incidents. These incidents, Lekgethwane said, are often quickly addressed.
“The current provincial medicine availability report shows that medicine availability has stabilised above 80%. As at the end of June 2024, ARV stock was at 89.5%, Expanded Programme on Immunisation and Contraceptives remained above 90%, TB treatment at 79%, Oncology treatment at 81.7% and Diabetes Mellitus at 85.8%. Therefore the province does not have a crisis of medicine shortages,” he said.
Asked what exactly these percentages mean, Lekgethwane said that it indicates the actual medicines stock available in the province in relation to what is required.
A pharmacy expert consulted by Spotlight further explained that the percentage indicates the percentage of medicines on a list or in a class that is available in the province.
The way these numbers are tracked is somewhat tricky. Firstly, if a clinic is supposed to have 10 different HIV medicines in stock, but they only have 8 in stock, then its HIV medicines availability would be at 80% (having a single pack of a medicine counts as having it in stock). When many facilities are considered together, as with an entire province like North West, the key indicator looks at what percentage of those facilities have medicines availability above 90%. We thus understand the figures shared by Lekgethwane to mean that 89.5% of facilities, depots and so on in the province have HIV medicines availability above 90%.
Catching up with payments
Past medicine shortages in the province were partly attributed to companies ceasing delivery of medicine due to non-payment of invoices. While the North West health department was under National Department of Health administration in 2020, the offices at the Mmabatho Medical Depot was raided. The search uncovered a number of unpaid invoices worth millions, some dating back to 2014. One unpaid invoice was for more than R16 million.
Bolstered by a Pharmaceutical Intervention Team to address medicine shortages, Lekgethwane said the department’s payments system is now in top shape.
“Payment of suppliers has remained a priority and the finance unit has assisted the team by making good progress on payments of supplier accounts. The unit continues to investigate and intervene when suppliers indicate their account status to the pharmacies.
“This has led to an increased number of deliveries from suppliers to the depot and increased direct deliveries to pharmacies from contracted companies as well as deliveries of main orders, allocation of orders and emergency orders from the depot to the pharmacies,” he said.
“The Department can confidently confirm that the financial management of pharmaceuticals has been improved resulting in 97% of 2024/2025 accruals being paid and remaining with only two accounts that are on hold. The two accounts that are on hold will only be paid once their compliance requirements are sorted,” said Lekgethwane.
He said that the intervention team has the capacity to assess and intervene, in among others, pharmaceutical supply chain issues, system effectiveness, distribution and delivery processes, storage capacity, human resource capacity and safety issues.
Lekgethwane said the team’s first priority was to assess the Mmabatho Medical Depot before moving onto pharmacies in hospitals and clinics across the province.
Getting medicines to rural areas
While Ritshidze also raised concern around transportation for the delivery of medicines, the department said transportation has never been a challenge.
“There are contracted service providers who deliver to the Mmabatho Medical Depot and the depot delivers to hospitals. Clinics receive their medicine from their referral hospital,” said Lekgethwane.
“However, the department is currently implementing the bulk pharmacies for districts to bring medicines closer to facilities”, he added. A bulk pharmacy is a medicine storage facility which serves as a medical depot. It is situated in the districts and helps with bringing medicines closer to rural areas so that medicines do not have to be transported from major towns.
In this regard, Lekgethwane said the Dr Kenneth District Bulk Pharmacy was recently opened and soon the General De la Rey Bulk Pharmacy will open.
He said the department is confident that the use of these bulk pharmacies will improve medicine storage and distribution capacity.
Shortage of pharmacists and pharmacy assistants
The Ritshidze report found that only 9% of surveyed facilities had a pharmacist and only 18% had a pharmacist assistant. Government regulations state that either pharmacists or pharmacy assistants should be responsible for stock receiving orders and updating the stock visibility system. However, Ritshidze found that enrolled nurses, enrolled nurse assistants, facility managers, and even cleaners acted in that capacity at some clinics.
The province has a 6% vacancy rate for pharmacists while 342 are currently employed, according to the 2024/2025 health department annual performance plan tabled in the North West Provincial Legislature earlier this month. The plan states that the department’s organisational structure makes provision for 10 pharmacists to be appointed in the province for every 100 000 uninsured individuals.
The DA’s Hendriette van Huyssteen says there is a challenge of pharmacists and pharmacy assistants where there are clusters of less than 10 000 uninsured individuals (where one pharmacist would be allocated for 10 000 uninsured individuals) and the clinics servicing them are far removed from one another.
“With the NHI [National Health Insurance] being signed into law, the number of pharmacists will become only a greater challenge. The cost per pharmacist employee stands at R765 000.00 per annum. It is unclear as to where the funding would come from for the remuneration of the additional pharmacists needed under the NHI, as even the NHI Act is unclear in this regard,” she said.
Notwithstanding the issue of budget constraints, the training of more pharmaceutical staff is integral to having fully functional health systems, said Professor Andrew Robinson. He is a deputy dean in the Faculty of Health Sciences at North West University (NWU). He was previously a deputy director general in the North West health department.
“To improve the pharmaceutical skills in the province, the NWU must ensure it aligns its pharmacy training to address the skill needs of the provincial health department to ensure equitable health service delivery to all, which is necessary for successful implementation of the NHI,” he said.
An international randomised multicentre study has shown that targeted physical training can improve the quality of life of patients with metastatic breast cancer and alleviate fatigue. In the course of the training programme, which included two sessions per week over nine months, disease- and therapy-related symptoms were markedly reduced, which was associated with a improved quality of life compared to the control group.
The German Cancer Research Center (DKFZ) was significantly involved in the study, together with the National Center for Tumor Diseases (NCT) Heidelberg and Heidelberg University Hospital.
Maintaining or improving quality of life and alleviating fatigue are important goals in the care of cancer patients. Not only the disease itself, but also the necessary therapies can severely impair quality of life. Many patients suffer from fatigue syndrome, which is characterised by persistent physical, emotional and mental exhaustion.
“Especially women with advanced cancers such as metastatic breast cancer, who usually receive long-term therapy, can benefit greatly from good management of disease- and therapy-related symptoms,” says Karen Steindorf, head of a research division at the DKFZ and NCT Heidelberg. “We hope that the encouraging results of our PREFERABLE-EFFECT study will help to ensure that as many patients as possible are offered the opportunity to take part in a targeted training programme.”
Targeted activation, rather than rest, is the appropriate measure to counter fatigue and other stressful symptoms. This has already been proven in studies for patients in the early stages of breast cancer, but there is still no evidence of a corresponding benefit for advanced disease. The PREFERABLE-EFFECT study has now provided this proof.
A total of 355 women and 2 men with metastatic breast cancer were included in the randomized controlled trial. All study participants received basic exercise recommendations and were fitted with an activity tracker to record the amount of exercise they did in everyday life. “The training group of 178 participants also took part in an individually adapted and therapeutically supervised training programme twice a week, which included exercises to strengthen balance, muscle strength and endurance. In the last three months, one of the two training sessions was also carried out with the help of an app,” explains Joachim Wiskemann from Heidelberg University Hospital, whose working group examined and supervised the Heidelberg study participants in terms of sports therapy.
At the start of the study and after 3, 6 and 9 months, the participants were asked about their quality of life using a standardised questionnaire that took into account physical, mental and emotional aspects of quality of life. In addition, a standardised questionnaire was used to objectify fatigue symptoms. Physical fitness was tested at the beginning and at three-month intervals on the bicycle ergometer.
The structured training programme led to a statistically significant improvement in quality of life and a significant reduction in fatigue. Complaints such as pain and shortness of breath decreased significantly over the course of the study. The fitness test was also better in the training group than in the control group.
“These are very encouraging training effects that the patients can feel in their everyday lives,” comments Karen Steindorf. “Structured training improves quality of life in a relevant way and enables women with advanced breast cancer to lead a more active life. We were also able to demonstrate greater participation in social life. Based on the PREFERABLE-EFFECT data, there is now good evidence to recommend that people in advanced stages of the disease should also take part in a targeted training programme.”
The “OnkoAktiv” network founded at the NCT Heidelberg supports cancer patients with training programmes close to home.
Why do new comorbidities arise because of ischaemic stroke? A study from Germany recently published in the journal Cell has discovered why this can happen – and ways in which it might be countered. The findings from the study show that the immune system is involved in damage to other organs, including the heart.
Besides the early mortality and morbidity resulting from the ischaemic brain injury itself, long-term morbidity after stroke is also due to the high prevalence of secondary comorbidities and complications, such as cognitive impairment and dementia, post-stroke depression, cardiac events, persistent vascular inflammation, and stroke-induced metabolic disturbances.
Liesz is the principal investigator of this new study. The researchers worked on the hypothesis that the high rate of comorbidities that develop after a stroke could have a common immunological cause. And they actually managed to find it: the origin of the dysfunctions in other parts of the body lies in the immunological memory of the blood-forming cells in bone marrow.
Using single-cell sequencing techniques, Liesz and his team demonstrated the presence of permanent proinflammatory changes in the transcriptome of certain immune cells (monocytes/macrophages) in several organs. In other words, certain gene segments are transcribed differently there after the stroke, which unbalances the proteome. These epigenetic modifications occur most frequently in the heart, where they can cause scarring and impair pumping function. “We managed to identify the protein IL-1b as the main culprit for the epigenetic modifications that affect immunological memory after a stroke,” says Liesz.
Promising therapeutic approaches on the horizon
The researchers demonstrated in a mouse model the connection between modified blood formation in bone marrow through overexpressed IL-1b and cardiac dysfunctions. Moreover, they showed that blocking IL-1b and inhibiting migration of the proinflammatory cells to the heart both successfully prevented cardiac problems after a stroke.
“These findings are hugely significant, as they open up the promise of effective therapeutic approaches for the prevention of secondary cardiac conditions after a stroke,” reckons Liesz.
The authors of the study believe that the epigenetic mechanisms they described for the reprogramming of the immune system in the brain-heart axis will create a new framework for explaining the development of various IL-1b-mediated comorbidities.
In the US, nearly 40 million adults have sleep apnoea, and more than 30 million of them use a continuous positive airway pressure (CPAP) machine while sleeping. But the machines tend to be expensive, clunky and uncomfortable – resulting in many users giving up on using them.
Hypertension is often linked with sleep apnoea because the brain works harder to regulate blood flow and breathing during sleep. A recent study at the University of Missouri (Mizzou) offers new insight into the underlying mechanisms within the brain contributing to hypertension for those with sleep apnoea.
The findings, which are published in the Journal of Physiology, can help pave the way for new drugs that target the brainstem to bring blood pressure back down to normal levels for those with sleep apnoea.
The study took place in the lab of David Kline, a professor in Mizzou’s College of Veterinary Medicine and researcher at the Dalton Cardiovascular Research Center.
“When oxygen levels in the blood drop during sleep apnoea, the forebrain sends warning signals to the brainstem area that controls heart and lung functions,” Kline said. “By studying these signals, we found that two neurochemicals, oxytocin and corticotropin-releasing hormone (CRH), cause the brainstem to become overactive. Over time, this leads to hypertension.”
Hypertension leads to an increased risk of stroke, complications in the metabolism and a variety of other health issues.
“Not only do those with sleep apnoea often have high blood pressure, but they also lose a lot of sleep, they have more cognitive and memory issues, and they are more prone to injury at work due to sleepiness,” Kline said.
By being the first to identify the role that oxytocin and CRH play in strengthening and overexciting the pathways and mechanisms involved in sleep apnoea, Kline and his fellow researchers hope to pave the way for the design of better therapeutic approaches for humans and animals.
“Our ultimate goal is to eventually help clinicians develop specific drugs to target either these neurochemicals or the proteins they bind to in a way that reduces high blood pressure,” Kline said. “This discovery opens the door for future research to block the pathways these neurochemicals use, ultimately helping to bring blood pressure back to normal levels.”
Colourised scanning electron micrograph of HIV (yellow) infecting a human T9 cell (blue). Credit: NIH
An experimental drug originally developed to treat cancer may help clear HIV from infected cells in the brain, according to a new study published in the journal Brain. For the first time, researchers at Tulane University found that a cancer drug significantly reduced levels of SIV, the nonhuman primate equivalent of HIV, in the brain by targeting and depleting certain immune cells that harbour the virus.
This discovery marks a significant step toward eliminating HIV from hard-to-reach reservoirs where the virus evades otherwise effective treatment.
“This research is an important step in tackling brain-related issues caused by HIV, which still affect people even when they are on effective HIV medication,” said lead study author Woong-Ki Kim, PhD, associate director for research at Tulane National Primate Research Center. “By specifically targeting the infected cells in the brain, we may be able to clear the virus from these hidden areas, which has been a major challenge in HIV treatment.”
Antiretroviral therapy (ART) is an essential component of successful HIV treatment, but the virus persists in “viral reservoirs” in the brain, liver, and lymph nodes, where it remains out of reach of ART.
The brain has been a particularly challenging area for treatment due to the blood-brain barrier preventing treatments from reaching the virus. In addition, macrophages are extremely long-lived, making them difficult to eradicate once they become infected.
Infection of macrophages is thought to contribute to neurocognitive dysfunction, experienced by nearly half of those living with HIV. Eradicating the virus from the brain is critical for comprehensive HIV treatment and could significantly improve the quality of life for those with HIV-related neurocognitive problems.
Researchers focused on macrophages, a type of white blood cell that harbours HIV in the brain. By using a small molecule inhibitor to block a receptor that increases in HIV-infected macrophages, the team successfully reduced the viral load in the brain. This approach essentially cleared the virus from brain tissue, providing a potential new treatment avenue for HIV.
The small molecule inhibitor used, BLZ945, has previously been studied for therapeutic use in amyotrophic lateral sclerosis (ALS) and brain cancer, but never before in the context of clearing HIV from the brain.
The study, which took place at the Tulane National Primate Research Center, utilised three groups to model human HIV infection and treatment: an untreated control group, and two groups treated with either a low or high dose of the small molecule inhibitor for 30 days. The high-dose treatment lead to a notable reduction in cells expressing HIV receptor sites, as well as a 95-99% decrease in viral DNA loads in the brain .
In addition to reducing viral loads, the treatment did not significantly impact microglia, the brain’s resident immune cells, which are essential for maintaining a healthy neuroimmune environment. It also did not show signs of liver toxicity at the doses tested.
The next step for the research team is to test this therapy in conjunction with ART to assess its efficacy in a combined treatment approach. This could pave the way for more comprehensive strategies to eradicate HIV from the body entirely.
