Among US veterans, screening led to earlier lung cancer diagnoses and improved survival.
Small cell lung cancer cells (green and blue) that metastasised to the brain in a laboratory mouse recruit brain cells called astrocytes (red) for their protection. Credit: Fangfei Qu
Among US veterans diagnosed with lung cancer through the Veterans Health Administration healthcare system, those who underwent screening before diagnosis were more likely to be diagnosed with earlier stage disease and had a higher cure rate than those who had not been screened. The findings come from an observational study published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
Lung cancer is the leading cause of cancer deaths worldwide, and most patients are diagnosed at an advanced stage. Early detection through screening could save lives, and current recommendations state that adults 50–80 years old with at least a 20-pack-year smoking history who currently smoke or have quit within the past 15 years should undergo annual imaging tests for lung cancer.
Such screening has been shown to be beneficial in clinical trials, but there are limited data on the real-world effectiveness of lung cancer screening. To investigate, researchers assessed the impact of screening among patients in the Veterans Health Administration healthcare system diagnosed with lung cancer from 2011–2018.
Among 57,919 individuals diagnosed with lung cancer, 2167 (3.9%) underwent screening before diagnosis. Patients who underwent screening had higher rates of early (stage I) diagnoses compared with those who had no screening (52% versus 27%), lower rates of death from any cause (49.8% versus 72.1%), and death from cancer (41.0% versus 70.3%) over 5 years.
“It is incredible to witness how dedicated national efforts to increase lung cancer screening from the Lung Precision Oncology Program can lead to substantial improvements in lung cancer outcomes,” said co–corresponding author Michael Green, MD, PhD, of the University of Michigan and the Veterans Affairs Ann Arbor Healthcare System.
By month end, South Africa will have a new Minister of Health. Ufrieda Ho asked some academics and activists what qualities that person should have to tackle the key health issues the country faces.
The precise health minister South Africa needs right now may not exist. But the portfolio still demands that the person appointed to this critical position be up to the job.
The appointment, when it happens, will come against a radically shifted political backdrop. Firstly, the elections results of the May 29 point to a coalition government for the first time in 30 years of democracy. The final configurations of a likely government of national unity is still anyone’s guess. And secondly, the National Health Insurance (NHI) bill is now an Act. President Cyril Ramaphosa signed off on the bill just a fortnight before the elections. It means by law, the work on the advancement of NHI must begin even as the contentions and contestations remain as thorny as ever.
Another reason why getting the right person matters is the money that comes with the portfolio. Annual government spending on health is in the region of R270 billion. Most of this spend is currently directed via provincial health departments, but flows under NHI will be nationalised and the NHI Act gives the minister extensive powers over NHI, and indirectly, the NHI fund.
At the same time, problems like entrenched health sector corruption and high levels of medico-legal claims against the state remain acute. Health budgets have been shrinking in real terms over the last decade. Financial shortfalls and shortages of healthcare workers in our health facilities are dire, while health needs enlarge.
Bridging ideological divides
Fatima Hassan, a human rights lawyer and founder of the Health Justice Initiative, says: “Policymaking in a coalition government is going to be so difficult – a Herculean task. And the place where you’re going to feel it most acutely is in health, because we have a dual health system and because NHI is sitting on the table.”
She says the role of minister will call for an astute politician. She says: “It must be someone who can work with different parties as well as constituencies in different sectors to try to bridge a number of these ideological divides.
“Health is a lightning rod for the differences between the different political parties; we saw this in how the parties campaigned for or against NHI,” she says.
Hassan says the worst case scenario will be someone in the position who is a “placeholder minister” who stalls on reforms, is a person more concerned with “calming the markets” and someone who will simply play the political long game waiting it out until the next elections.
“It must be someone who is able to work on creating a fairer system for access to proper healthcare services across the country, not just in specific provinces. They must invest in health infrastructure, invest in human resources for health, and invest in some of the more positive aspects of preparing for national health insurance,” she says. She adds that the person must prioritise fixing the “glaring issues in the NHI Act” to avert looming law suits.
In addition, Hassan says the minister must be someone who can stand up to the bullying of private sector power, including the likes of big pharma, and must be able to show leadership on domestic health issues while also being a strong Global South voice on international platforms to champion global health equity.
‘Health is more than a biomedical response’
Professor Scott Drimie is a researcher at the University of Stellenbosch and director of the Southern African Food Lab. Drimie works on food systems and food security and how these intersect with the social determinants of health.
For Drimie, South Africa’s health minister must be a person with an expansive leadership style; a person who is able to work across government departments and also be awake to the grassroots realities people face. Around 85% of people in South Africa rely on public healthcare.
“The minister must be able to grapple with the lived reality of most poor people and put in place a health system that supports the most vulnerable.
At the same time, that person should be someone who understands that health is more than a biomedical response – health is also issues like food security, sanitation, stable livelihoods and safety,” he says.
Another quality Drimie highlights is that the minister should be open to collaboration and experimentation. He says there has to be a “whole-of-government” approach and a “whole-of-society” approach. The Department of Health cannot achieve its key performance indicators on its own; it needs to collaborate with departments including social development, education and basic education.
“It must also be able to be bold with programmes and work with communities directly as well as with civil society, health advocates and health activists,” he says.
Reform of bureaucracies in the health department must also be something the minister tackles, Drimie says. He says it means appointing effective managers who are not micro-managed or politically influenced. Effective implementers of policies and programme, he says, can be a counterweight to politics.
“Politicians can come with very short-term, very narrow party politics,” says Drimie. But, he adds, enduring and relevant health programmes survive beyond political tenure and are more likely to achieve positive health outcomes.
Put people first and ‘show humility’
For activist Anele Yawa, who is secretary general of the Treatment Action Campaign, we need someone who puts people first. He says the minister must serve the interests of people and show humility for the office.
“The minister must not be someone who pushes his or her agenda. A minister is appointed; he or she did not submit a CV to us. So a minister must understand that there will be times when we as citizens and civil society will disagree with them. It’s because we will continue to speak truth to power, we will continue to hold them accountable; whatever the new coalitions will look like,” he says.
“Our ministers must not be arrogant and think it’s because we hate them. We will disagree and we will fight because it is an effort to make sure that things are done the right way and we can bring health services to the majority – it’s that person who is working class, black and is a woman,” says Yawa.
He says it means a strong minister must be one who maintains an open-door policy; who arrives at community meetings in person; take calls personally and engages.
Yawa says it’s also critical that the seventh administration is one that works cohesively. “We voted on the 29 May for a contractual agreement with government; not a fashion show. It means that we don’t just need a good health minister, we need a good administration that delivers on water and sanitation, on education and on social development, and so on.”
Motivate and inspire
Professor Lucy Gilson is head of health policy and systems division in the School of Public Health at the University of Cape Town. Her top qualities for a good minister also centre on people skills. She says the health minister in South Africa must be an inspiring leader.
“The person must be able to motivate health workers and managers to be the best public servants they can be.
“The person must also inspire the public to trust in the public health sector,” Gilson says.
The new health minister must have strategic management skills, she says. These will be necessary to navigate the complexity of power and interests in a coalition government and to figure out how the NHI will take shape.
In the end, she says the person in the post should have patience and persistence. She adds: “Bringing change to the health system is a collective and sustained effort over time. The minister must be able to strengthen capacity, assemble coalitions and networks of learning, experience and mutual accountability.”
A new study has discovered that even very mild, non-lethal head injuries early in life can lead to neurodegenerative conditions later in life upon ageing. Using fruit flies as a model, the researchers found that chronic immune suppression after mating might make female fruit flies susceptible to delayed brain deterioration following early-life head injuries, which may lead to insights for humans.
The study, published as a Reviewed Preprint in eLife, is described by the editors as fundamental work that advances our understanding of how sex-dependent responses to traumatic brain injury occurs. The work, by a team at Emory University provides what they call compelling results showing the immune and reproductive pathways that may contribute to these differences.
Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration later in life. However, identifying a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegeneration is challenging, and it remains unclear as to how sex and age compound the outcomes.
“With their short lives, fruit flies allow scientists to track brain-injury-related changes across their entire lifespan,” says lead author Changtian Ye, a graduate student in the Emory Neuroscience Program, and a member of senior author James Zheng’s lab, at the Emory University School of Medicine. “We recently developed a fruit fly model of mild traumatic brain injury that allows us to deliver mild headfirst impacts and then track what happens in male and female flies from the moment of injury to the occurrence of brain impairments later in life.”
Using their model, Ye and colleagues monitored the impact of mild traumatic brain injury on the flies’ behaviour. Whilst injury initially caused minimal acute deficits in the flies, it led to more profound brain-associated behavioural deficits and degeneration later in life, and these conditions worsened with age. Additionally, they were disproportionately elevated in females, affecting their climbing speed and ability, and leading them to have more damaged brain tissue than their male counterparts.
The researchers also found that female flies that had mated had worse outcomes than unmated (virgin) flies. They identified a protein called ‘sex peptide’ – which is transferred to the female reproductive tract through semen during mating – as a key player in making these flies more susceptible to the harmful effects of brain injury.
“Our analysis of the flies’ RNA data suggested that the chronic suppression of innate immune defence networks in mated females exposed to sex peptide makes them disproportionately vulnerable to neurodegeneration after mild head trauma,” Ye explains.
Together, the findings support the idea that a head injury can pose a major threat for brain health, even if it is mild, and that females can be disproportionately affected. The authors say that additional studies are now needed to determine if similar processes occur in other species.
“Our work establishes a causal relationship between early head trauma and late-life neurodegeneration, emphasising sex differences in injury response and the impact of age during and after injury,” concludes senior author James Zheng, Principle Investigator at the Zheng Lab, Emory University School of Medicine. “It will be interesting to understand if this relationship occurs in other organisms, and to dissect the genetic components and molecular players involved in the sex-different development of neurodegenerative conditions following mild head trauma.”
Colourised scanning electron micrograph of a breast cancer cell. Credit: NIH
A study led by researchers from the University of Arizona Cancer Center at UArizona Health Sciences identified a biological mechanism that could lead to more effective treatments for breast cancer that has metastasised to the brain.
By studying the metabolic differences between primary breast cancer cells and those that metastasise to the brain, they determined that autophagy was significantly upregulated in brain metastases. Autophagy is a cellular recycling process that cancer cells can use to stay alive when faced with stressful conditions such as those triggered by anticancer drugs.
“The prognosis for individuals with brain metastases from breast cancer is extremely unfavourable, and the management of breast cancer metastases in the brain remains a formidable challenge,” said senior author Jennifer Carew, PhD. “We were able to disrupt breast cancer cells’ ability to form brain metastases by impairing the autophagy pathway.”
In the study published in Clinical and Translational Medicine, the researchers first showed that targeting the key autophagy regulating gene ATG7 significantly reduced the ability of breast cancer cells to form brain metastases in mouse models.
With the goal of developing a strategy to bring this discovery to patients, the research team investigated whether hydroxychloroquine, a Food and Drug Administration-approved drug, could potentially be used to treat breast cancer brain metastases. Hydroxychloroquine inhibits autophagy at a later point in the pathway and, importantly, readily crosses the blood-brain barrier.
“Most drugs do not efficiently cross the blood-brain barrier, and that is one of the key reasons why brain metastases are so difficult to treat,” said Carew, who is a professor of medicine at UArizona.
The research team combined hydroxychloroquine with lapatinib, which is FDA-approved to treat breast cancer. They showed that this drug combination successfully reduced the number and size of breast cancer brain metastases in mouse models.
Hydroxychloroquine has been combined with a number of other anticancer agents in early phase clinical trials, but this is the first time researchers have studied its effectiveness when combined with lapatinib for breast cancer therapy.
Carew said the team was amazed by how significantly they were able to diminish the ability of breast cancer cells to form brain metastases by targeting a single pathway.
“Cancer cells, unfortunately, have evolved so many ways that make it difficult for us to stop their growth or kill them,” Carew said. “It is always somewhat surprising when you see how changing only one thing can have an impact.”
“Our group and others have shown that activation of autophagy makes it harder for many different types of cancer therapies to kill cancer cells and this promotes drug resistance,” said first author Steffan Nawrocki, PhD, UArizona professor. “Because hydroxychloroquine and lapatinib are already FDA approved, we can advance this drug combination quickly into a clinical trial for patients with breast cancer brain metastases.”
Brain metastases are the most prevalent adult central nervous system tumours, with 20% to 30% of cases resulting from breast cancer patients, particularly those with triple negative and HER2 amplified disease. Managing breast cancer metastases in the brain is challenging, with only 20% of patients with breast cancer brain metastases surviving beyond five years.
Maternal obesity impacts the eating behaviours of offspring via long-term overexpression of the microRNA miR-505-5p, according to a study publishing June 4 in the open-access journal PLOS Biology by Laura Dearden and Susan Ozanne from the MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, UK, and colleagues.
Previous studies in both humans and animal models have shown that the offspring of obese mothers have a higher risk of obesity and type 2 diabetes.
While this relationship is likely the result of a complex relationship between genetics and environment, emerging evidence has implicated that maternal obesity can disrupt the hypothalamus – the region of the brain responsible for nutrition sensing and energy homeostasis.
In animal models, offspring exposed to overnutrition during key periods of development eat more, but little is known about the molecular mechanisms that lead to these changes in eating behaviour.
In this study, researchers found that mice born from obese mothers had higher levels of the microRNA miR-505-5p in their hypothalamus – from as early as the foetal stage into adulthood.
The researchers found that the mice ate more and showed a preference for high-fat foods.
Interestingly, the effect of maternal obesity on miR-505-5p and eating behaviours was mitigated if the mothers exercised during pregnancy.
Cell culture experiments showed that miR-505-5p expression could be induced by exposing hypothalamic neurons to long-chain fatty acids and insulin, which are both high in pregnancies complicated by obesity.
The researchers identified miR-505-5p as a novel regulator of pathways involved in fatty acid uptake and metabolism, therefore high levels of the miRNA make the offspring brain unable to sense when eating high fat foods.
Several of the genes that miR-505-5p regulates have been associated with high body mass index in human genetic studies.
The study is one of the first to demonstrate the molecular mechanism linking nutritional exposure in utero to eating behaviour.
The authors add, “Our results show that obesity during pregnancy causes changes to the baby’s brain that makes them eat more high fat food in adulthood and more likely to develop obesity. Importantly we showed that moderate exercise, without weight loss, during pregnancies complicated by obesity prevented the changes to the baby’s brain. This helps us understand why the children of mothers living with obesity are more likely to become obese themselves, with early life exposures, genetics and current environment all being contributing factors.”
Besides preventing illness and death, tuberculosis prevention therapy is estimated to be highly cost effective. Yet, uptake of the medication is not what it could be in South Africa. Tiyese Jeranji asks how much has changed since the Department of Health last year decided to make TB prevention therapy much more widely available.
Many people who have the TB bug in their lungs are not ill with TB disease. Having the bug in your body, does mean however that you are at risk of falling ill, should the TB bacteria get the overhand in its battle with your immune system.
Fortunately, we have medications that can kill TB bacteria before one falls ill. A recent World Health Organization (WHO) investment case, suggests such TB prevention therapy, commonly called TPT, reduces the risk of falling ill with TB in those exposed to the bug by 60% to 90% compared to people who do not get the treatment.
In South Africa, TPT has been available in the public sector for years, but until the publication of new government guidelines last year, only kids aged five or younger and people living with HIV could get the medication. Under the new guidelines, everyone who has had close contact with someone with TB should be offered a TB test and if they test negative be offered TPT – if they test positive they should be offered TB treatment. These changes dramatically expanded the number of people in South Africa who are eligible for TPT.
The antibiotics used for TPT has also changed in recent years. For many years, the only option was a medication called isoniazid taken for six or more months. We now also have two three-month options – isoniazid and rifapentine given once weekly and rifampicin and isoniazid given daily. These shorter duration treatment courses should help more people complete the treatment.
Down and up?
Dr Norbert Ndjeka, Chief Director of TB Control and Management at the National Department of Health, tells Spotlight that in recent years, South Africa has seen a steady decline in the number of people initiated on TPT.
The decline has been substantial. In people living with HIV, initiation on TPT dropped from 454 000 in 2018 to around 241 000 in 2023. In children aged five and younger who have had contact with someone with TB, it fell from 25 357 in 2018 to 15 775 in 2023.
TPT enrolments per province for 2023
Province
People living with HIV
Contacts < 5 Years
Contacts > 5 Years
Eastern Cape
34 623
2 551
4 771
Free State
14 535
562
1 027
Gauteng
67 333
1 368
4 241
KwaZulu-Natal
62 362
3 168
8 519
Limpopo
15 871
391
452
Mpumalanga
25 618
669
2 006
Northern Cape
3 178
855
1 595
North West
9 433
596
1 425
Western Cape
8 532
5 615
1 278
South Africa
241 485
15 775
25 314
*Typically, provinces with higher numbers of people diagnosed with TB or those with high numbers of people living with HIV will report higher TPT initiations.
There are two significant reasons for this decline, according to Ndjeka. Firstly, declining TB incidence, and secondly, declining HIV incidence.
“With fewer people diagnosed with TB disease, fewer contacts will need TPT, and with fewer people being diagnosed with HIV, fewer people will initiate TPT regardless of TB exposure,” he says.
WHO figures have shown a significant downward trend in the estimated TB cases per year in South Africa and according to Thembisa, the leading mathematical model of HIV in South Africa, the number of people newly starting HIV treatment has dropped from a peak of over 700 000 in 2011, to well under 300 000 in 2023.
But the recent downward trend in people taking TPT may be coming to an end. “We believe that the implementation of the new guidelines within the current strategic framework will lead to increases in TPT enrolment,” says Ndjeka.
In line with the new guidelines, there are also changes to what TPT data is being collected. “For example, we never used to report on TPT provision to contacts 5 years and older, but now we do and in 2023 at least 25 314 TB contacts 5 years and older were initiated on TPT,” he says.
20% increase expected in 2024
Based on the data reported for January and February of this year, Ndjeka expects that overall TPT initiations will increase by at least 20% in 2024 compared to 2023. Moreover, as documented in the National Strategic Plan for HIV, TB and STIs 2023-2028, there is a plan to have a steady annual increase in TPT enrolments leading up to 2028.
Ndjeka says based on the NSP TPT targets, South Africa is exceeding TPT targets for people living with HIV, but reaching less than 25% of targets for TB contacts. He points out that performance varies by province, but that all provinces have a long way to go in terms of reaching TB contacts.
‘Cost saving over time’
“The aim of offering TPT is to reduce the TB incidence,” Ndjeka says. “So, if everyone eligible is offered TPT there will obviously be increased costs initially but cost saving over time. This looks at cost of treating people with TB, lives saved/ deaths prevented as well as costs to patients.”
For South Africa, he says, it is estimated that we can reduce the number of people with TB by 138 000 by 2050 at an estimated cost of R23 226.90 per TB episode prevented.
Ndjeka says it costs the health department an estimated at R1 498.51 to treat one person with drug-susceptible TB for 6 months and R16 612.82 to treat one person with the standard drug-resistant TB treatment for 6 months. “These costs are for medications alone, which can also go beyond R70 000 depending on the patient and the type of resistant TB. Moreover, when factoring in clinical consultations, hospitalisations, and costs to patients the costs go up considerably,” he says.
The cost of providing TPT also depends on the regimen. One person on TPT can cost as little as R608.77 for a course of three months of isoniazid and rifapentine given once weekly, and up to R1 358.02 for 12 months of isoniazid. “TPT also has much lower associated costs for example there is no hospitalisation, fewer clinic visits and consultations,” Ndjeka says.
“By preventing TB, the cost of TB treatment is avoided along with the costs of treating some of the acute and chronic conditions that someone with TB may experience even after being cured of TB. These include chronic obstructive pulmonary disease, bronchiectasis and pneumonia,” says Alison Best, communication manager at Cape Town-based NGO TB HIV Care.
“For children under five in particular, who are at increased risk of disseminated TB like TB meningitis, the cost of not preventing TB could be death or severe lifelong disability,” she says, adding that preventing TB in a single individual also prevents the costs associated with any onwards transmission of TB from that individual to others.
Questions over implementation
Expanded TPT eligibility has been widely welcomed, but questions have been raised over how well the new guidelines are being implemented.
Best says government austerity measures have made implementing new initiatives in the healthcare setting challenging.
“There is not much political will to implement the guidelines (to expand eligibility for TPT) at provincial and district levels and this has translated into the slow release of circulars, delays in training health workers, poor knowledge of the policy and its low prioritisation,” she says.
Ingrid Schoeman, Director of Advocacy and Strategy at TB Proof (a local advocacy group), says often when a national policy is released, there are delays at provincial-level in releasing circulars to enable health worker training.
“This results in these services not being available at district-level. In the Western Cape, civil society organisations, the [provincial] Department of Health, City of Cape Town and implementing partners are now all working together to support health worker training, and implementing community-led awareness campaigns so that all close TB contacts know they are eligible for TPT,” she says.
Best adds that tracking the data to show how many people are starting and completing TPT tends to be difficult. She notes there are many gaps in capturing the information. This includes, at times, the limited recording of information in patient folders by clinicians and suboptimal inputting of data by data capturers.
Ndjeka says the national department of health has been conducting training on the new guidelines with provincial and district TB and HIV programme managers, district support partners and other trainers.
“They are then responsible for training health care workers. The antiretroviral therapy guideline training also includes TPT. Webinars on the knowledge hub (an online training platform) have also conducted,” he says.
However, Ndjeka conceded that there is a lack of awareness about the value of TPT. “Additionally,” he says, “there is reluctance from clinicians to provide TPT. This result in poor demand for TPT. Treatment adherence is another problem especially for people on the long regimen (12 months)”.
Plans to address these challenges, among other things, include marketing TPT as treatment for TB infection rather than prevention, targeted communication strategies, community mobilisation, and ongoing training and mentoring of healthcare workers, says Ndjeka.
New research in mice has demonstrated that not having too much of a certain amino acid – present in many foods commonly eaten by overweight or obese individuals – extends their lifespan and reduces the incidence of diseases such as cancers.
“We like to say a calorie is not just a calorie,” says Dudley Lamming, a professor and metabolism researcher at the University of Wisconsin School of Medicine and Public Health. “Different components of your diet have value and impact beyond their function as a calorie, and we’ve been digging in on one component that many people may be eating too much of.”
Lamming is the lead author of a new study in mice, published recently in the journalCell Metabolism showing that cutting down the amount of a single amino acid called isoleucine can, among other benefits, extend their lifespan, make them leaner and less frail as they age and reduce cancer and prostate problems, all while the mice ate more calories.
Amino acids are the molecular building blocks of proteins, and Lamming and his colleagues are interested in their connection to healthy aging.
In earlier research, data from UW–Madison’s Survey of the Health of Wisconsin showed the scientists that Wisconsinites with higher body mass index measurements tend to consume more isoleucine, an essential amino acid. Isoleucine is plentiful in foods including eggs, dairy, soy protein and many kinds of meat.
To better understand its health effects, Lamming and collaborators from across disciplines at UW–Madison fed genetically diverse mice either a balanced control diet, a version of the balanced diet that was low in a group of about 20 amino acids, or a diet formulated to cut out two-thirds of the diet’s isoleucine. The mice, which began the study at about six months of age (equivalent to a 30-year-old person) got to eat as much as they wanted.
“Very quickly, we saw the mice on the reduced isoleucine diet lose adiposity – their bodies got leaner, they lost fat,” says Lamming, while the bodies of the mice on the low-amino-acid diet also got leaner to start, but eventually regained weight and fat.
Mice on the low-isoleucine diet lived longer – on average 33% longer for males and 7% longer for females. And, based on 26 measures of health, including assessments ranging from muscle strength and endurance to tail use and even hair loss, the low-isoleucine mice were in much better shape during their extended lives.
“Previous research has shown lifespan increase with low-calorie and low-protein or low-amino-acid diets starting in very young mice,” says Lamming, whose work is supported by the National Institutes of Health. “We started with mice that were already getting older. It’s interesting and encouraging to think a dietary change could still make such a big difference in lifespan and what we call ‘healthspan,’ even when it started closer to mid-life.”
The mice on the low-isoleucine diets chowed down, eating significantly more calories than their study counterparts – probably to try to make up for getting less isoleucine, according to Lamming. But they also burned far more calories, losing and then maintaining leaner body weights simply through adjustments in metabolism, not by getting more exercise.
At the same time, Lamming says, they maintained steadier blood sugar levels and male mice experienced less age-related prostate enlargement. And while cancer is the leading cause of death for the diverse strain of mice in the study, the low-isoleucine males were less likely to develop a tumour.
Dietary amino acids are linked to a gene called mTOR that appears to be a lever on the aging process in mice and other animals as well as to a hormone that manages the body’s response to cold and has been considered a potential diabetes drug candidate for human patients. But the mechanism behind the stark benefits of low-isoleucine intake is not well understood. Lamming thinks the new study’s results may help future research pick apart causes.
“That we see less benefit for female mice than male mice is something we may be able to use to get to that mechanism,” he says.
While the results are promising, humans do need isoleucine to live, and reducing isoleucine from a diet that hasn’t been preformulated by a mouse chow company is not an easy task.
“We can’t just switch everyone to a low-isoleucine diet,” Lamming says. “But narrowing these benefits down to a single amino acid gets us closer to understanding the biological processes and maybe potential interventions for humans, like an isoleucine-blocking drug.”
The Survey of the Health of Wisconsin showed that people vary in isoleucine intake, with leaner participants tending to eat a diet lower in isoleucine. Other data from Lamming’s lab suggest that overweight and obese Americans may be eating significantly more isoleucine than they need.
“It could be that by choosing healthier foods and healthier eating in general, we might be able to lower isoleucine enough to make a difference,” Lamming says.
Researchers at The University of Texas at El Paso are developing a new therapeutic approach that uses nanoparticles for the treatment of skin and lung fibrosis, conditions that can result in severe damage to the body’s tissues.
Md Nurunnabi, PhD, is an associate professor in UTEP’s School of Pharmacy and the lead researcher on two studies published this June in the Journal of Controlled Release; one study focuses on skin fibrosis and the other on lung fibrosis.
“We are closer than ever to developing a safe, effective and reliable approach to treating fibrosis,” Nurunnabi said.
Fibrosis is a condition in which the tissues in an organ become thicker and stiffer, Nurunnabi says. This can have multiple damaging effects, such as the lungs not being able to hold enough oxygen or blood vessels becoming narrower, leading to high blood pressure.
“I studied fibrosis during my postdoctoral training but became interested in focusing on it in my lab during the COVID-19 pandemic,” Nurunnabi said. “I observed that many people were passing away not because of COVID itself, but because of the inflammation and fibrosis caused by the viral infection in the lungs. Our lab focuses on developing nanotechnology that can target specific cells.”
Fibrosis can occur as a side effect of chemotherapy or the result of a viral infection or autoimmune disease, a condition in which the body’s immune system attacks its own cells. For example, with an autoimmune condition, the body kills fibroblasts, the cells that help form connective tissue. The body then produces more collagen than it needs, which leads to fibrosis.
Nurunnabi’s team focused on designing a nanoparticle that could target the cells that are responsible for fibrosis development and progression without disturbing the “good” cells necessary for the body’s healthy functioning. Rather than killing the ”bad” cells, the team was successful in modifying them so that they no longer produced excess collagen, in effect rehabilitating the cells. The studies were conducted in the test tube and in mice.
“Dr Nurunnabi’s research into skin and lung fibrosis sheds light on the devastating impact of these conditions, whether acute or chronic,” said José Rivera, PharmD, founding dean of the School of Pharmacy. “His findings offer hope for improved treatments that could significantly increase life expectancy and enhance the quality of life for affected individuals.”
Guideline recommends vitamin D higher than the recommended daily allowance for children, pregnant people, adults over 75 and adults with prediabetes
Photo by Michele Blackwell on Unsplash
Healthy adults under the age of 75 are unlikely to benefit from taking more than the daily intake of vitamin D recommended by the Institutes of Medicine (IOM) and do not require testing for vitamin D levels, according to a new Clinical Practice Guideline issued today by the Endocrine Society. For children, pregnant people, adults older than 75 years and adults with high-risk prediabetes, the guideline recommends vitamin D higher than the IOM recommended daily allowance.
Vitamin D use and blood vitamin D levels have been associated with many common diseases. However, whether vitamin D supplementation lowers the risk of these diseases and what vitamin D blood levels are needed for better health have been debated for years.
In this new guideline, the panel of experts established guidelines for vitamin D use and testing for vitamin D levels in healthy persons without established indications for vitamin D treatment or testing. The guideline relied on clinical trials to develop the recommendations.
“The goal of this guideline was to address the vitamin D requirements for disease prevention in a generally healthy population with no underlying conditions that would put them at risk of impaired vitamin D absorption or action,” said Marie Demay, M.D., of Harvard Medical School and Massachusetts General Hospital in Boston, Mass. Demay is the chair of the panel that developed the guideline. “Healthy populations who may benefit from higher dose vitamin D supplements are those 75 and older, pregnant people, adults with prediabetes, and children and adolescents 18 and younger, but we do not recommend routine testing for vitamin D levels in any of these groups.”
Key recommendations from the guideline include:
We suggest against vitamin D supplements at doses beyond the reference dietary intakes recommended by the IOM in healthy adults under 75 years old.
We identified the following populations that may benefit from supplementation above the intakes recommended by the IOM because of the potential to reduce specific health risks:
Children and adolescents 18 and younger—potential to prevent nutritional rickets and to reduce the chance of respiratory infections.
Individuals 75 and older—potential to lower mortality risk.
Pregnant people—potential to reduce risk of pre-eclampsia, intra-uterine mortality, preterm birth, small-for-gestational age birth and neonatal mortality.
People with prediabetes—potential to reduce progression to diabetes.
In adults ages 50 years and older who have indications for vitamin D supplementation or treatment, we suggest daily, lower-dose vitamin D instead of non-daily, higher-dose vitamin D.
We suggest against routine testing for 25-hydroxyvitamin D levels in any of the populations studied, since outcome-specific benefits based on these levels have not been identified. This includes 25-hydroxyvitamin D screening in people with dark complexion or obesity.
Even though the evidence on the role of vitamin D in health and disease has increased over the last decade, the panel noted many limitations in the available evidence. For example, many of the large clinical trials were not designed for several of the outcomes that they reported, and the studied populations had vitamin D blood levels that most would consider adequate to begin with. Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.
Evidence suggests serotonin-boosting actions relieve depression by restoring normal communication and connections in the brain
Photo by Sydney Sims on Unsplash
Researchers at the University of Colorado Anschutz Medical Campus have established a new framework for understanding how classic antidepressants work in treating major depressive disorder (MDD), reemphasising their importance and aiming to reframe clinical conversation around their role in treatment.
The nature of the dysfunction at the root of MDD has been under investigation for decades. Classic antidepressants, such as SSRIs (selective serotonin reuptake inhibitors, such as fluoxetine) cause an elevation in serotonin levels, a key neurotransmitter. This observation led to the idea that antidepressants work because they restore a chemical imbalance, such as a lack of serotonin.
But subsequent years of research showed no significant decrease in serotonin in people with depression. While experts have moved away from this hypothesis due to lack of concrete evidence, this has led to a shift in public opinion on the effectiveness of these medications.
Antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), are still effective in alleviating depressive episodes in many patients, however. In a paper published in Molecular Psychiatry, researchers outline a new framework for understanding how antidepressants are efficacious in treating MDD. This framework helps clarify how antidepressants like SSRIs can still be helpful, even if MDD isn’t caused by a lack of serotonin.
Evidence points to a communication problem
“The best evidence of changes in the brain in people suffering from MDD is that some brain regions are not communicating with each other normally,” said Scott Thompson, PhD, professor in the Department of Psychiatry and senior author. “When the parts of the brain responsible for reward, happiness, mood, self-esteem, even problem-solving in some cases, are not communicating with each other properly, then they can’t do their jobs properly,” Thompson said.
“There is good evidence that antidepressants that increase serotonin, like SSRIs, all work by restoring the strength of the connections between these regions of the brain. So do novel therapeutics such as esketamine and psychedelics. This form of neuroplasticity helps release brain circuits from being ‘stuck’ in a pathological state, ultimately leading to a restoration of healthy brain function,” Thompson said.
Thompson and colleagues liken this theory to a car running off the road and getting stuck in a ditch, requiring the help of a tow truck to pull the car out of its stuck state, allowing it to move freely down the road again. Researchers are hoping healthcare providers will use their examples to bolster conversations with apprehensive patients about these treatments, helping them better understand their condition and how to treat it.
Study aims to reshape the conversation
“We are hoping this framework provides clinicians new ways to communicate the way these treatments work in combating MDD,” said C. Neill Epperson, MD, co-author of the paper and professor of the Department of Psychiatry at the CU School of Medicine.
“Much of the public conversation around the effectiveness of antidepressants, and the role serotonin plays in diagnosis and treatment, has been negative and largely dangerous,” Epperson said. “While MDD is a heterogenous disorder with no one-fits-all solution, it is important to emphasise that if treatments or medications are working for you, then they are lifesaving. Understanding how these medications promote neuroplasticity can help strengthen that message.”
