Tag: 10/5/24

Categories : Cancer GastrointestinalTags :

Intermittent Fasting Protects against Liver Inflammation and Liver Cancer

On By ModernMedia
Photo by jamie he

Fatty liver disease often leads to chronic liver inflammation and can even result in liver cancer. Scientists from the German Cancer Research Center (DKFZ) and the University of Tübingen have now shown in mice* that intermittent fasting on a five days on, two days off schedule can halt this development.

In mice with pre-existing liver inflammation, this fasting regime reduces the development of liver cancer . The researchers also identified two proteins in liver cells that are jointly responsible for the protective effect of fasting. An existing drug can partially mimic this effect.

The most common chronic liver condition is non-alcoholic fatty liver disease. If left untreated, it can lead to liver inflammation (metabolic dysfunction-associated steatohepatitis, MASH), liver cirrhosis and even liver cancer. Fatty liver disease is largely considered to be a direct consequence of obesity.

“The vicious circle of an unhealthy diet, obesity, liver inflammation and liver cancer is associated with major restrictions and suffering for those affected and also represents a considerable burden on healthcare systems,” says Mathias Heikenwälder, DKFZ and University of Tübingen. “We have therefore investigated whether simple dietary changes can specifically interrupt this fatal process.”

Intermittent fasting has already been shown in several studies to be an effective means of reducing weight and alleviating certain metabolic disorders. Heikenwälder’s team has now tested in mice whether this approach can also protect the liver from fatty degeneration and chronic inflammation. Their results are published in Cell Metabolism.

Resistance to liver inflammation is independent of calorie intake

The animals were fed with a high-sugar and high-fat diet corresponding to the typical Western diet. One group of mice had constant access to the food. As expected, these animals gained weight and body fat and developed chronic liver inflammation.

The mice in the other group were given nothing to eat on two days a week (5:2 intermittent fasting, or 5:2 IF for short), but were allowed to eat as much as they wished on the other days. Despite the high-calorie diet, these animals did not put on weight, showed fewer signs of liver disease and had lower levels of biomarkers that indicate liver damage. In short, they were resistant to the development of MASH.

Interestingly, resistance to the development of a fatty liver was independent of the total calorie intake, as the animals immediately made up for the lost rations after the end of the fasting periods.

When experimenting with different variants of intermittent fasting, it was found that several parameters determine protection against liver inflammation: The number and duration of fasting cycles play a role, as does the start of the fasting phase. A 5:2 dietary pattern works better than 6:1; 24-hour fasting phases better than 12-hour ones. A particularly unhealthy diet requires more frequent dieting cycles.

Heikenwälder’s team now wanted to find out the molecular background of the response to fasting. To this end, the researchers compared protein composition, metabolic pathways and gene activity in the liver of fasting and non-fasting mice. Two main players responsible for the protective fasting response emerged: the transcription factor PPARα and the enzyme PCK1. The two molecular players work together to increase the breakdown of fatty acids and gluconeogenesis and inhibit the build-up of fats.

“The fasting cycles lead to profound metabolic changes, which together act as beneficial detoxification mechanisms and help to combat MASH,” says Heikenwälder, summarizing the molecular details.

The fact that these correlations are not just a mouse phenomenon was shown when tissue samples from MASH patients were examined: Here, too, the researchers found the same molecular pattern with reduced PPAR α and PCK1. Are PPAR α and PCK1 actually responsible for the beneficial effects of fasting? When both proteins were genetically switched off simultaneously in the liver cells of the mice, intermittent fasting was unable to prevent either chronic inflammation or fibrosis.

The drug pemafibrate mimics the effects of PPARα in the cell. Can the substance also mimic the protective effect of fasting? The researchers investigated this question in mice. Pemafibrate induced some of the favourable metabolic changes that were observed with 5:2 fasting. However, it was only able to partially mimic the protective effects of fasting. “This is hardly surprising, as we can only influence one of the two key players with pemafibrate. Unfortunately, a drug that mimics the effects of PCK1 is not yet available,” explains Mathias Heikenwälder.

Intermittent fasting as liver therapy

While Heikenwälder and his team initially focused on the effects of intermittent fasting on MASH prevention, then investigated whether the 5:2 diet could also alleviate existing chronic liver inflammation.

To this end, the team examined mice that had developed MASH after months of being fed a high-sugar, high-fat diet. After a further four months of 5:2 intermittent fasting (on the same diet), these animals were compared with the non-fasting control group. The fasting mice had better blood values, less fatty liver and liver inflammation and above all: they developed less liver cancer and had fewer cancer foci in the liver.

“This shows us that 5:2 intermittent fasting has great potential – both in the prevention of MASH and liver cancer, as well as in the treatment of established chronic liver inflammation,” summarises principal investigator Heikenwälder. “The promising results justify studies in patients to find out whether intermittent fasting protects against chronic liver inflammation as well as in the mouse model.”

The 5:2 fasting regimen is popular. It is considered comparatively easy to integrate into everyday life, as the fasting days can be tailored to personal needs and no specific foods are prohibited. “Nevertheless, there will always be people who can’t stick to a strict diet in the long term,” says Heikenwälder. “That’s why we want to continue to investigate which combinations of drugs we can use to fully mimic the protective effects of fasting.”

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Categories : Genetics Obstetrics & GynaecologyTags :

A Tiny Chromosomal Deletion is Linked to Spina Bifida

On By ModernMedia
Photo by Mart Production on Pexels

A group of researchers at the University of California San Diego School of Medicine led an investigation that offers new insight into the causes of spina bifida, the most common structural disorder of the human nervous system.

The group’s work reveals the first link between spina bifida and a common chromosomal microdeletion in humans. The study demonstrates that individuals carrying this chromosomal deletion – present in one of 2500 live births – demonstrate a risk of spina bifida more than 10 times greater than the general public.

The study, published in Science, also underscores the potential role of folic acid (aka vitamin B-9) in reducing the risk of spina bifida.

Professor Joseph G. Gleeson at Rady Children’s Institute for Genomic Medicine, is the senior author of the study. He explained that spina bifida, also known as meningomyelocele, affects one in every 3000 newborns. Unfortunately, the causes are mostly unknown. A few mutations were reported but could only explain a tiny fraction of risk, Gleeson added.

To uncover the genetic causes of the disease, Gleeson’s UC lab joined with colleagues around the world to establish the Spina Bifida Sequencing Consortium in 2015. The consortium began focusing on a tiny deletion in chromosome 22. Chromosome microdeletions refer to a condition in which several genes in a chromosome are missing. The group’s target condition, known as 22q11.2del, has been implicated in a number of other disorders. They began looking for 22q11.2del in spinal bifida patients.

“All patients we recruited have the most severe form of spina bifida, and all underwent best-practice comprehensive genomic sequencing,” Gleeson said. “We identified 22q11.2del in 6 out of 715 patients. This may not seem a high percentage, but this is by far the most common single genetic variation that could contribute to spina bifida.”

He went on to say the group identified eight additional spina bifida patients who carried the deletion from a cohort of approximately 1500 individuals recruited because of the presence of the common 22q11.2 deletion, Gleeson said.

The researchers then narrowed the cause among the many genes in the 22q11.2 deletion to a single gene known as CRKL. Gleeson explained that there are nine other genes in this chromosomal region that could have been the cause. He said the team began a process of elimination, “knocking out” each of the mouse genes one-by-one, when they received a fortuitous email from Dolores Lamb from Weil Cornell College of Medicine. Lamb had noted some of the mice in their vivarium that were missing Crkl and showed spina bifida. (Study co-first author Keng Ioi Vong, PhD, explained that researchers use all capital letters to describe the gene in humans, and lower-case for mice.) Lamb’s group heard about the Gleeson lab project through the Spina Bifida Association.

“This finding really got us excited because it meant that CRKL disruption might be sufficient for spina bifida,” said Vong. “We removed the mouse Crkl gene ourselves and confirmed that some of the mice developed neural tube defects, including spina bifida.” Most of the other genes in 22q11.2 deletion were subsequently excluded, he added.

They next turned their attention to how folic acid may modulate CRKL-mediated spina bifida. Vong noted that prior studies in humans demonstrated that folic acid supplementation prior to conception reduces the incidence of spina bifida and other neural tube defects by up to 30-50 %, but the mechanisms are still a mystery.

“When we deprived the Crkl mutant female mice of folic acid in their chow, many more of their offspring had neural tube defects, and the severity increased dramatically,” Vong explained. “This suggests that folic acid taken by pregnant women may not only reduce the risk, but also the severity of neural tube defects in their offspring.”

“We hope our findings can help the research community to better understand causes of neural tube defects, especially the causes attributable to common genetic findings like 22q11.2 deletion,” Gleeson said. “We also hope our findings can contribute to healthy pregnancies, improved women’s health, and improved outcomes for children.”

Source: University of California – San Diego

Categories : General Interest Healthcare Politics and RegulationsTags :

A Humanist with an Unblinking gaze – Professor Ntobeko Ntusi Takes the Hot-seat at the South African Medical Research Council

On By ModernMedia
Professor Ntobeko Ntusi in front of a painting depicting student protests inside his office at Groote Schuur Hospital – the same office that once housed his mentor, the late Professor Bongani Mayosi. (Photo: Biénne Huisman/Spotlight)

Professor Ntobeko Ntusi may be softspoken, but he is not afraid to stand by his strongly held views. As he is set to take up the hot-seat at the country’s primary health research funder, he tells Spotlight’s Biénne Huisman about his background and his priorities for the new job.

Professor Ntobeko Ntusi’s bearing brings to mind the aphorism “speak softly and carry a big stick” cited by the 26th president of the United States Theodore Roosevelt.

Inside his office at Groote Schuur’s Old Main Building, department head of medicine at the hospital; Ntusi is soft spoken, his words a few decibels above a whisper. However his observations are thoughtful and sharp, crafted with precision. Known to call out issues around race and racism at South African universities – “inbuilt biases” even amongst young students – his level, unblinking gaze commands attention.

Born in Umthatha to academic parents, Ntusi at age 13 was named South African Junior Ballroom Dance Champion at an event in Sasolburg. Some three decades later, the cardiologist with qualifications from around the world, does not sidestep public healthcare debate in favour of keeping the peace.

Catastrophic budget cuts

Earlier this year, Ntusi publicly criticised healthcare budget cuts. R200 million was shaved off Groote Schuur’s coffers just last year, as the Western Cape Department of Health and Wellness announced an R807.8 million shortfall for the coming year. Speaking to Spotlight, Ntusi described communication on the matter by provincial government officials (with healthcare professionals) as “appalling”.

In February, Ntusi was one of a group of executives at the hospital – affiliated to the University of Cape Town (UCT) – who spearheaded a petition to national and provincial treasury, decrying “crippling austerity” and “catastrophic budget cuts”; saying how clinicians with multiplying work hours are watching patients deteriorate, as waiting lists for lifesaving elective surgery grow longer.

At a boardroom table inside his office, he says: “How we ration limited resources, this is causing real moral injury to our front-facing clinicians. I mean, we’re having to deal with complaints from patients who no longer have access to services they have grown accustomed to. This is causing a lot of distress, especially among young doctors, and medical registrars – the engine of our operation – who are increasingly anxious and taking time out for mental health reasons.”

In his present position, Ntusi’s voice has clout. He oversees thirteen divisions – from cardiology to pulmonology, and infectious diseases and HIV medicine – and corresponding research units such as the Desmond Tutu HIV Centre, directed by Professor Linda-Gail Bekker.

‘Hope cannot be a strategy’

Reflecting on how Groote Schuur’s management are responding to these challenges, Ntusi says the hospital’s CEO (since February) Shaheem de Vries, while new, in time ought to bring concrete priorities to the table. “It’s important to have hope, but hope cannot be a strategy,” he says.

This insight may well inform how he approaches his own new job as CEO and President of the South African Medical Research Council (SAMRC), taking over from Professor Glenda Gray. From July, Ntusi will give up his Groote Schuur office, putting away his clinician’s stethoscope, to take up the hot-seat at the country’s primary health research funder at its headquarters behind a facebrick facade in Parow. The SAMRC employs 718 employees and will see Ntusi answer to the National Department of Health, the SAMRC board, and the Parliamentary Portfolio Committee on Health (you can see the latest report to the committee here).

Across medical bureaucracies, budget remains an issue. The South African government allocated R1.35 billion to the SAMRC for 2023/24. In the council’s latest annual report, diminishing funding from government is listed as a threat; while the ability to attract external funding is listed as a strength.

“A key role of the President of the SAMRC is to engage with organisations like the Wellcome Trust [in the United Kingdom] and the NIH [the National Institutes of Health in the United States] and high worth individuals to attract funding,” says Ntusi.

He points out that the SAMRC has had clean audits for several years running – a remarkable achievement for a South African parastatal. Indeed, the council’s annual performance plan for 2024/2025 states: “Despite interruptions of COVID-19, SAMRC’s exemplary performance and good governance led to the organisation achieving four consecutive clean audits… It is the organisation’s intention to continue on the same path.”

On the SAMRC’s functions, Ntusi explains: “For government, the SAMRC plays a critical role in bridging the gap between strategy and policy, and implementation. In science, it plays a critical role in providing priorities for the funding of research, and capacity building…”

In the SAMRC’s last financial year, R61.6 million was allocated to funding 171 “research capacity development” grants, including 120 to women. The annual report describes this as funding “the next generation of health researchers… with most of these awards aimed at individuals from historically disadvantaged backgrounds.”

For Ntusi, points of focus to be expanded on at the SAMRC include health issues relating to climate or planetary change, epidemic preparedness, “restoring trust in science in an age of misinformation”, digital health and artificial intelligence; and projects linking South African scholars with research entities across Africa. “In many of these countries, they don’t have the research infrastructure and budgets we have in South Africa – it is important to assist them with projects.”

To the US and back home

When he was 14, Ntusi’s family – he is one of three boys – moved to the United States where his mother pursued a PhD in social work. In Philadelphia, Pennsylvania, he continued competitive ballroom dancing while attending Lower Merion High School, where a video on child birth showed in a biology class stirred his passions.

At liberal arts college Haverford, in Pennsylvania, he completed a BSc Honours in cellular and molecular biology, before returning “home” to South Africa in 1999, to enrol in medical school at UCT. Here his initial interest in obstetrics was disappointed – “it was loud and messy, an anti-climax” – seeing him drawn to internal medicine and cardiology instead. In following years, he would study cardiovascular medicine under mentorship of the late Professor Bongani Mayosi.

Like Mayosi, Ntusi was awarded the Oxford Nuffield Medical Scholarship, which funded his D.Phil at the University of Oxford in the United Kingdom. His doctoral research looked at cardiovascular magnetic resonance (CMR – noninvasive tests that produce images of a beating heart) to study inflammatory heart disease.

In 2016, Ntusi took over from Mayosi as head of Groote Schuur’s department of medicine, as Mayosi became dean of the university’s faculty of health sciences. At the time Ntusi continued treating cardiology patients, with ongoing research projects including on HIV-related heart disease.

Seven years later, against pale yellow walls (the same walls decorated by Mayosi back when it was his office) several art works and certificates attest to Ntusi’s time here. He points out one painting of student protestors made by a friend – based on the #FeesMustFall protests at the university in 2016 – “a difficult time”, he says.

In 2018, Mayosi’s suicide was partially attributed by some to pressures relating to the violent protests; while also putting a spotlight on pressure on prominent black academics at UCT, and other tertiary institutions in South Africa. An enquiry found that the “sometimes disrespectful manner” in which protest was conducted, and “instigation of students’ action by some of his colleagues”, caused Mayosi “a lot of distress”.

Displayed on a shelf, beside a stuffed doll of the Archbishop Desmond Tutu and a 2021 SAMRC gold trophy for “scientific achievement”, a burgundy-bound book recounts Mayosi’s legacy. Ntusi penned the introduction, where he writes: “Bongani Mayosi – as a leader, he was awesome. He is one of the most inspiring people I will ever know. He always reminded me: ‘a journey of a thousand miles begins with a few steps’.”

Asked about following in the footsteps of a star such as Mayosi, Ntusi replies: “I am his protégée. There were always room for me to build my own scientific investigations.”

Precarious times

As Ntusi is poised to depart from Groote Schuur, present dean of UCT health sciences Associate Professor Lionel Green-Thompson points out how the cardiologist cared for critically ill patients in COVID-19 high-care wards, particularly during the fear and uncertainty of hard lockdown.

“Sometimes we would work up to 16 hour shifts in the high-care wards; upon finally leaving I’d go outside to find anti-vaccine protestors in front of the hospital. I mean, they were just annoying,” Ntusi recalls.

“Communication around the AstraZeneca vaccine went very badly – increasing confusion and vaccine hesitancy. It is really, really important to advocate for vaccines. And this brings me back to the point of restoring people’s faith in science; redressing the public image of science, a priority I have for the SAMRC going forward.” (After procuring the AstraZeneca SARS-CoV-2 vaccine, the South African government decided early in 2021 not to use it after it showed limited efficacy against mild to moderate COVID-19 in a study.)

Foremost, Ntusi describes himself as a “humanist”. Apart from science, medicine and health equity, his interests include art, wine and dogs. Ntusi lives in Milnerton. A keen runner, he is a member of the Gugulethu Athletics Club.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight

Categories : Expert Opinion HospitalsTags :

Our Nurses, Our future: Addressing the Critical Issue of Sustainability in SA’s Healthcare Sector

On By ModernMedia
Photo by Hush Naidoo on Unsplash

With only 22 090 nurses to serve the country’s public health sector of more than 50 million citizens1, urgent intervention is required to bolster their numbers and protect the wellbeing of our nation. After all, without their tireless dedication, who will be there to guide you through the corridors back to health? writes Bada Pharasi, CEO of the Innovative Pharmaceutical Association of South Africa (IPASA)

As the global healthcare industry commemorates International Nurses Day on 12 May, it is an opportune moment to reflect on the role of nurses as the heartbeat of healthcare systems globally. Amid turmoil and triumph, nurses stand as the unsung heroes and compassionate caretakers who embody empathy, endurance and expertise. 

In South Africa, where healthcare challenges often loom large and resources are stretched thin, nurses serve as the frontline warriors, bridging the gap between suffering and healing. Yet, despite the invaluable role they play, a concerning trend looms.

Minister of Health, Joe Phaahla, recently revealed a pressing concern – the anticipation of a staggering 30% of South African nurses retiring within the next decade, and 38% retiring the decade thereafter. Compounding the issue, 5060 vacancies remain unfilled on the back of crippling budget constraints1. 

Representing over 90% of global healthcare workers2, nurses are indispensable in the healthcare ecosystem, and addressing this impending crisis of their reducing numbers demands comprehensive and multifaceted solutions that approach the challenge from every angle.

The nurse shortage crisis in South Africa stems from multiple factors. Firstly, the escalating healthcare needs of a growing population, compounded by the burden of infectious diseases such as HIV/AIDS, have strained the healthcare system to breaking point.

Another factor is the restricted capacity of the private sector to train nurses comprehensively due to existing regulations. Moreover, poor working conditions, particularly in the public sector, and comparatively low salaries have led to high turnover rates, prompting nurses to explore alternative career paths or seek employment opportunities abroad3. 

While there are many challenges to defusing the proverbial ticking time bomb which is the declining number of qualified nurses in South Africa, increased investment across the board is critical to strengthening their ranks. 

Despite financial investment being central in realising this, addressing the problem demands a focus on improving the working conditions of nurses. Healthcare facilities must prioritise nurses’ well-being by offering competitive salaries, manageable workloads, and opportunities for career growth. By creating a supportive work environment, South Africa can retain more nurses and deter them from seeking opportunities abroad3.

Furthermore, granting private hospitals full participation in nurse training programmes is crucial. Private sector entities, such as Netcare, have the capacity to train as many as 3,500 nurses annually. However, limited accreditation from the government hampers their potential contribution to resolving the nurse shortage. Expanding private sector involvement in nurse training could substantially increase the number of trained nurses in the country3.

In addition to these measures, collaborative efforts between the government, healthcare institutions, and nursing organisations are essential. Such partnerships can identify and implement strategies to alleviate the shortage, including targeted recruitment drives, mentorship programmes, and initiatives to improve nurses’ job satisfaction and work-life balance3.

Innovative approaches to addressing the nurse shortage in South Africa extend beyond traditional solutions. Telemedicine platforms are emerging as a promising tool, allowing nurses to deliver care remotely and reach patients in underserved areas. 

Additionally, community health worker programmes are being expanded to complement nursing services and extend healthcare access to marginalised communities. Furthermore, initiatives to empower and support nurse entrepreneurs are gaining traction, encouraging the development of innovative care models and healthcare solutions. 

These diverse approaches reflect a multifaceted response to the nurse shortage crisis, leveraging technology, community engagement, and entrepreneurship to strengthen the healthcare workforce and improve access to care for all South Africans.

References:

1. Only 22 000 nurses for 50 million South Africans [Internet]. Democratic Alliance. [cited 2024 May 2]. Available from: https://www.da.org.za/2023/06/only-22-000-nurses-for-50-million-south-africans

2. Experiences of nurses and midwives in policy development in low- and middle-income countries: Qualitative systematic review. International Journal of Nursing Studies Advances. 2023 Dec 1;5:100116.

3. [Opinion] Nurse shortage crisis in South Africa [Internet]. Centre for Risk Analysis. 2023 [cited 2024 May 2]. Available from: https://cra-sa.com/media/opinion-nurse-shortage-crisis-in-south-africa

Categories : Cancer General InterestTags :

Years after His Passing, Researcher’s Cancer Target Discovery Bears Fruit

On By ModernMedia

Some of the final work of a late University of Virginia School of Medicine scientist has opened the door for life-saving new treatments for solid cancer tumours, including breast cancer, lung cancer and melanoma.

Prior to his sudden death in 2016, John Herr, PhD, had been collaborating with Craig L. Slingluff Jr, MD, to investigate the possibility that a protein recently discovered at Herr’s lab could be a viable cancer treatment target.

Eight years of research has borne that idea out: Herr’s research into the SAS1B protein could lead to “broad and profound” new treatments for multiple cancers, many of which are very difficult to treat, Slingluff reports in a new scientific paper in the Journal for ImmunoTherapy of Cancer. Herr is listed as a senior author on the paper.

“John was very excited about this protein SAS1B to be a valuable new target on human cancers, and I am delighted that our findings together further support his hope to make such a difference,” said Slingluff, a surgical oncologist and translational immunologist at UVA Health and the UVA School of Medicine. “The work we published included work done by Dr Herr and his team over a period of years, as well as our subsequent work together; so, I am glad that the journal agreed with our request to include John as a senior author.”

Promising New Cancer Target

Herr’s lab was not originally focused on cancer – he was the head of UVA’s Center for Research in Contraceptive and Reproductive Health. In that role, he developed the first home fertility test for men, SpermCheck, which is available in pharmacies across the country. But his discoveries about the SAS1B protein found in developing eggs in women could pave the way for new cancer immunotherapies.

While SAS1B is found inside female reproductive cells called oocytes, it is also found on the surface of many different solid cancer cells, Slingluff’s new research verifies. Importantly, it did not appear on the surface of any of the other normal cells Slingluff’s laboratory tested. That suggests that doctors may be able to develop use antibody-based immunotherapy – such as antibody-drug conjugates or CAR T-cell therapy, a strength of UVA Health – to attack the cancer cells while sparing healthy tissue.

“Selectively targeting SAS1B has the potential to have broad and profound impact on the treatment, and therefore reduction in mortality, of multiple malignancies,” Slingluff and his colleagues write in their new paper.

While much more work needs to be done, the new findings are promising. If the approach is successful, it could be a big step forward in cancer care. Many solid-organ cancers are extremely difficult to treat, and patients often have few good treatment options, Slingluff notes.

“Immune therapy is revolutionising treatment of human cancers,” Slingluff said. “But some cancers have been particularly resistant to immune therapy because of the lack of good targets on those cancers. We hope that this work that John Herr started will bring new hope to patients with those cancers.”

Source: University of Virginia Health System