Day: October 12, 2023

Brain Changes from Shift Work Increase Appetite

Photo by Ernest Brillo on Unsplash

Scientists have uncovered why night shift work is associated with changes in appetite in a new University of Bristol-led study. The study shows that circadian disruption can disrupt the brain’s regulation of appetite hormones. The findings, published in Communications Biology, could help the millions of people that work through the night and struggle with weight gain.

Scientists from Bristol and the University of Occupational and Environmental Health in Japan, sought to understand how ‘circadian misalignment’ – a phenomenon commonly associated with ‘jet-lag’ whereby the body’s biological clock is disrupted – affects the hormones responsible for regulating appetite.

Prevalent in night shift workers, in this new study, the international team reveal how circadian misalignment can profoundly alter the brain’s regulation of hormones controlling hunger to the detriment of metabolic health.

The team focused on glucocorticoid hormones in the adrenal gland which regulate many physiological functions including metabolism and appetite. Glucocorticoids are known to directly regulate a group of brain peptides controlling appetitive behaviour, with some increasing appetite (orexigenic) and some decreasing appetite (anorexigenic).

In an experiment using animal models, comprising a control group and a out-of-phase ‘jet-lagged’ group, the team found misalignment between light and dark cues led the out-of-phase group’s orexigenic hypothalamic neuropeptides (NPY) to become dysregulated, driving an increased desire to eat significantly more during the inactive phase of the day.

Strikingly, the team discovered that rats in the control group ate 88.4% of their daily intake during their active phase, and only 11.6% during their inactive phase. In contrast, the ‘jet-lagged’ group consumed 53.8% of their daily calories during their inactive phase (without an increase in activity during this time). This equated to nearly five-times more (460% more) than what the control group consumed during the inactive phase. These results show that it is timing of consumption that has been affected.

This new discovery revealed how completely, and significantly, disordered the neuropeptides become when daily glucocorticoid levels are out of synch with light and dark cues. However, the authors suggest the neuropeptides identified in this study may be promising targets for pharmacological treatments for eating disorders and obesity.

Research Fellow Dr Becky Conway-Campbell, the study’s senior author, said: “For people working throughout the night, a reversed body clock can play havoc with their health.

“For those who are working night shifts long-term, we recommend they try to maintain daylight exposure, cardiovascular exercise and mealtimes at regulated hours. However, internal brain messages to drive increased appetite are difficult to override with ‘discipline’ or ‘routine’ so we are currently designing studies to assess rescue strategies and pharmacological intervention drugs. We hope our findings also provide new insight into how chronic stress and sleep disruption leads to caloric overconsumption.”

Professor Stafford Lightman, co-senior author on the study, added: “The adrenal hormone corticosterone, which is normally secreted in a circadian manner, is a major factor in the daily control of brain peptides that regulate appetite. Furthermore when we disturb the normal relationship of corticosterone with the day to night light cycle it results in abnormal gene regulation and appetite during the period of time that the animals normally sleep.

“Our study shows that when we disturb our normal bodily rhythms this in turn disrupts normal appetite regulation in a way that is at least in part a result of desynchrony between adrenal steroid hormone production and the timing of the light and dark cycle.”

Dr Benjamin Flynn, one of the study’s co-authors who conducted the study while at Bristol but is now based at the University of Bath, added: “This is further evidence of how phase shift ‘jet-lag’ affects feeding behaviours and neuronal gene expression – data important for shift work co-morbidity research.”

Source: University of Bristol

Study Dispels Safety Fears over the Antihypertensive Drug Amlodipine

Pexels Photo by Thirdman

A new paper in the journal Function finds that a widely prescribed drug for treating hypertension, amlodipine, is not dangerous for patients, despite recent concerns from researchers and clinicians that there may be risks associated with taking amlodipine. 

Approximately one in five adults worldwide have the disease, which is responsible for 7.6 million deaths per year. If untreated, hypertension significantly increases the risk of premature death through heart attack, stroke, or kidney disease. 

One widely prescribed drug for treating hypertension is amlodipine, now taken regularly in pill form by over 70 million Americans. Amlodipine inhibits an L-type calcium channel that is found on blood vessels. When the calcium channel opens, calcium enters the muscle and causes it to constrict, increasing blood pressure. Amlodipine prevents calcium from coming in, leading to vessel relaxation and a decrease in blood pressure. 

Recently some researchers have questioned the benefit of amlodipine for treating hypertension. Studies suggested that amlodipine may activate a different type of calcium channel, resulting in changes to blood vessels and an increase in heart failure in patients. Removing amlodipine as a prescribed anti-hypertensive medication carries significant health implications, since hypertension is such a common health condition.

A new study by research teams from National Institutes of Health and Glasgow University finds that taking amlodipine is unlikely to result in an increase in heart failure in patients. The researchers found that amlodipine appears to have unique chemical properties that caused the drug to mimic the calcium channel activation, without in fact opening the channels as clinicians worried. When the study’s authors controlled for these chemical properties, they found that amlodipine did not activate calcium channels. A meta-analysis combining clinical trials and a prospective real-world analysis both showed that amlodipine was not associated with increased heart failure or other cardiovascular problems.

“Removal of amlodipine as a front-line therapy would most likely increase deaths from hypertension dramatically,” said Anant Parekh, one of the study’s authors. “The study recommends that amlodipine remain a first-line treatment for high blood pressure.”

Source: EurekAlert!

Turning Everyday Vaccines into Cancer Killers

Photo by National Cancer Institute

A study in Frontiers in Immunology has demonstrated that, in animal models, a protein antigen from a childhood vaccine can be delivered into the cells of a malignant tumour to refocus the body’s immune system against the cancer, effectively halting it and preventing its recurrence.

Instead of using vaccines tailored with tumour-specific antigens to prime the immune system to attack a particular cancer, this method makes use of the immune system’s encounter with common vaccines. The bacteria-based intracellular delivering (ID) system uses a non-toxic form of Salmonella that releases a drug, in this case a vaccine antigen, after it’s inside a solid-tumour cancer cell.

“As an off-the-shelf immunotherapy, this bacterial system has the potential to be effective in a broad range of cancer patients,” writes senior author Neil Forbes, professor of chemical engineering, in the recently published article.

The research, carried out in Forbes’s lab, offers promise toward tackling difficult-to-treat cancers, including liver, metastatic breast and pancreatic tumours.

“The idea is that everybody is vaccinated with a whole bunch of things, and if you could take that immunisation and target it towards a cancer, you could use it to eliminate the cancer,” Forbes explains. “But cancers obviously aren’t going to display viral molecules on their surface. So the question was, could we take a molecule inside the cancer cell using Salmonella and then have the immune system attack that cancer cell as if it was an invading virus?”

To test their theory that this immune treatment could work, Forbes and team genetically engineered ID Salmonella to deliver ovalbumin (chicken egg protein) into the pancreatic tumour cells of mice that had been immunised with the ovalbumin ‘vaccine’. The researchers showed that the ovalbumin disperses throughout the cytoplasm of cells in both culture and tumours.

The ovalbumin then triggered an antigen-specific T-cell response in the cytoplasm that attacked the cancer cells. The therapy cleared 43% of established pancreatic tumours, increased survival and prevented tumour re-implantation, the paper states.

“We had complete cure in three out of seven of the pancreatic mice models,” Forbes says. “We’re really excited about that; it dramatically extended survival.”

The team then attempted to re-introduce pancreatic tumours in the immunised mice. The results were exceedingly positive. “None of the tumours grew, meaning that the mice had developed an immunity, not just to the ovalbumin but to the cancer itself,” Forbes says. “The immune system has learned that the tumour is an immunogenic. I’m doing further work to figure out how that’s actually happening.”

In preliminary research, the team previously showed that injecting the modified Salmonella into the bloodstream effectively treated liver tumours in mice. They advanced their findings with the current research on pancreatic tumours.

Before clinical trials can begin, the researchers will repeat the experiments on other animals and refine the ID Salmonella strain to ensure its safety for use in humans. Liver cancer would be the first target, followed by pancreatic cancer.

Source: University of Massachusetts Amherst

New Technique Enhances Clarity of Photoacoustic Imaging in Dark Skin

Photo by Nsey Benajah on Unsplash

In photoacoustic imaging, laser light is pulsed through the skin into tissues, which release ultrasound signals with which the internal structure can be imaged. This works well for people with light skin but has trouble getting clear pictures from patients with darker skin. A Johns Hopkins University-led team found a way to deliver clear pictures of internal anatomy, regardless of skin tone. Their technique is described in the journal Photoacoustics.

In experiments the new imaging technique produced significantly sharper images for all people – and excelled with darker skin tones. It produced much clearer images of arteries running through the forearms of all participants, compared to standard imaging methods where it was nearly impossible to distinguish the arteries in darker-skinned individuals.

“When you’re imaging through skin with light, it’s kind of like the elephant in the room that there are important biases and challenges for people with darker skin compared to those with lighter skin tones,” said co-senior author Muyinatu “Bisi” Bell, Associate Professor at Johns Hopkins. “Our work demonstrates that equitable imaging technology is possible.”

“We show not only there is a problem with current methods but, more importantly, what we can do to reduce this bias,” Bell said.

The findings advance a 2020 report that showed pulse oximeters, which measure oxygen rates in the blood, have higher error rates in Black patients.

“There were patients with darker skin tones who were basically being sent home to die because the sensor wasn’t calibrated toward their skin tone,” Bell said.

Bell’s team created a new algorithm to process information from photoacoustic imaging, a method that combines ultrasound and light waves to render medical images. Body tissue absorbing this light expands, producing subtle sound waves that ultrasound devices turn into images of blood vessels, tumours, and other internal structures. But in people with darker skin tones, melanin absorbs more of this light, which yields cluttered or noisy signals for ultrasound machines.

The team was able to filter the unwanted signals from images of darker skin, in the way a camera filter sharpens a blurry picture, to provide more accurate details about the location and presence of internal biological structures.

The researchers are now working to apply the new findings to breast cancer imaging, since blood vessels can accumulate in and around tumours. Bell believes the work will improve surgical navigation as well as medical diagnostics.

“We’re aiming to mitigate, and ideally eliminate, bias in imaging technologies by considering a wider diversity of people, whether it’s skin tones, breast densities, body mass indexes – these are currently outliers for standard imaging techniques,” Bell said. “Our goal is to maximise the capabilities of our imaging systems for a wider range of our patient population.”

Source: John Hopkins University

Only with Both the Private and Public Sectors Working Together Will NHI Succeed

Photo by Hush Naidoo Jade Photography on Unsplash

For National Health Insurance to succeed in South Africa, a meaningful collaboration needs to take place between private and public health care so as to speed up the implementation of the initiative and overcome major obstacles.

This was the opinion of the five panellists who on the first day of the Hospital Association of South Africa conference in Cape Town spoke of how best the NHI could be rolled out by calling on private health care for assistance.

“’It’s fundamental to the economic growth that we so desperately need in South Africa, and a productive nation needs access to health care. So we do need to address the inequalities, we need to address the gap and do not need to preserve the status quo,” said Professor Roseanne Harris, of Discovery Health.

But a concern she raised is the risk of the introduction of a single funding model reliant on taxes, and the introduction of a monopoly market.

“And one of the implications of the bill is centralisation (of health care). There is a need for planning to ensure that it won’t have an unintended consequence of impacting service delivery and impacting on the rights of the healthcare personnel,” she added.

Harris said that both the private sector and public sector needed to go through a consultative process and that sustainable critical milestones needed to be put in place to hold the process to account.

Another panellist at the event Dr Simon Strachan of the South African Private Practitioners Forum (SAPPF), pointed out that the COVID pandemic showed how public and private health care could collaborate successfully.  Here service agreements between the two entities were met and were focused solely on fighting the pandemic.

“So to create the way forward, what we need to be able to do is to have a very clear understanding of what it is we’re trying to achieve, that there is robust trust, and that there is a groundwork for sustainable collaboration,” he explained.

An urgent need for this collaboration he said was the recent introduction of Section 33 of the NHI bill, which in its present form would have health care professionals working for the state at a fee the state sets, with benefits not included.

A second issue he said was the need for a successful funding model that will be acceptable to all South Africans.

Economist Nicola Theron of FTI consulting told the audience that structures already in place and used in the private sector could make for a smoother transition for the NHI. In particular when it comes to issues like the pricing of medicines.

“We are now at a point with the current NHI that there are talks about the lowest possible price at a reasonable return for healthcare providers. There is no indication of what return means,” she said.

“But what we have is an existing system of pricing which has been developed over time, and which should form the basis of pricing going forward,” said Theron.

By not getting the pricing right could lead to investment leaving South Africa, she warned.  She suggested in turn that it would be a better model to have multiple buyers that will stimulate competition.

Dr Ali Hamdulay, CEO, Metropolitan Health, said that a way forward would be to implement the suggestions that came out of the Health Marketing Inquiry that took a hard look at both the public and private health care systems, outlining the problems with both.

“So effectively by addressing the recommendations of the Health Market Inquiry  you’re actually foster an environment of culture and direction to work towards universal health care,” said Hamdulay.

Barry Childs, of Insight Actuaries, said that while fundraising mechanisms in the public sector needed to be improved, the introduction of the NHI offers a great opportunity to reform the healthcare system.

“As much as we talk about the need for reform of the private sector side, there’s been no meaningful reform of the public sector for many decades. And the NHI is a wonderful opportunity for them to introduce some better, more responsive financing mechanisms.” he said.

But for NHI to ultimately provide the services it promises, Childs said South Africa’s economy needed to improve, and more jobs to be created.

Source: Hospitals Association of South Africa