At present, there is no specific active substance against hepatitis E. As the disease kills 70 000 people every year, researchers are actively searching for one. Researchers in Germany may have found what they’re looking for. The team showed that the compound K11777 prevents host cells from helping the virus out of its shell by cleaving the viral capsid, rendering it incapable of infecting cells.
“The compound is already being tested in clinical trials against other viruses such as Sars-Cov-2,” says lead author Mara Klöhn. “There’s still a lot of work to be done to find out whether it can be used as an active substance against hepatitis E, but it’s a first step.”
The team from the Department of Molecular and Medical Virology at Ruhr University Bochum, published their findings in the journal Hepatology.
In order to infect an organ, viruses need the help of the host cells.
“An effective approach is therefore to identify targets in the host that can be manipulated by drugs so that they no longer perform this helper function,” explains Mara Klöhn.
The researchers became aware of the compound K11777 in a roundabout way: during a control study conducted as part of cell culture studies on the hepatitis C virus with a known active ingredient, they discovered that this active ingredient was also effective against hepatitis E. “However, the drug wasn’t using the same pathway as with the hepatitis C virus, because the hepatitis E virus doesn’t have the target structure that this active substance attacks,” explains Mara Klöhn. This suggested that the drug may have an effect on host cells instead.
The research team narrowed down the possible target structures and turned their attention to cathepsins, which can process proteins, i.e. cleave them.
K11777 inhibits many cathepsin types, ie blocks their function. In vitro tests with human liver cells showed that the compound actually prevents infection with hepatitis E viruses.
“In follow-up experiments, we proved our hypothesis that the compound prevents cathepsin L from cleaving and opening up the viral capsid,” says Mara Klöhn. “This means that the virus can no longer infect host cells.”
Hepatitis E
The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. Approximately 70 000 people die from the disease every year. After the first documented epidemic outbreak between 1955 and 1956, more than 50 years passed before researchers began to address the issue in depth. Acute infections usually clear up spontaneously in patients with an intact immune system. In patients with a reduced or suppressed immune system, such as organ transplant recipients or people infected with HIV, HEV can become chronic. HEV also poses a serious threat to pregnant women. There aren’t any vaccines nor specific active substances against the virus.
President Cyril Ramaphosa at signing ceremony of the NHI Bill at the Union Buildings in Pretoria.
Speech by Cyril Ramaphosa, article from Spotlight
President Cyril Ramaphosa yesterday signed into law the National Health Insurance (NHI) Bill, which is the ANC-led government’s plan for universal health coverage, just 14 days before the country heads to the polls.
The NHI aims to unify the country’s fragmented health system, Ramaphosa said at the signing ceremony at the Union Buildings in Pretoria on Wednesday.
However, he also noted that processes are yet to be established and that the Act’s implementation will be incremental rather than a massive overnight overhaul.
Here are 8 noteworthy quotes from the President’s speech:
“[T]he NHI is a commitment to eradicating the stark inequalities that have long determined who receives adequate healthcare and who suffers from neglect”.
“[T]he NHI takes a bold stride towards a society where no individual must bear an untenable financial burden while seeking medical attention”.
“The real challenge in implementing the NHI lies not in the lack of funds, but in the misallocation of resources that currently favours the private health sector at the expense of public health needs.”
“The financial hurdles facing the NHI can be navigated with careful planning, strategic resource allocation and a steadfast commitment to achieving equity.”
“The NHI recognises the respective strengths and capabilities of the public and private health care systems. It aims to ensure that they complement and reinforce each other.”
“The NHI is an important instrument to tackle poverty. The rising cost of health care makes families poorer. By contrast, health care provided through the NHI frees up resources in poor families for other essential needs.”
“Following the signing of this Bill, we will be establishing the systems and putting in place the necessary governance structures to implement the NHI based on the primary health care approach.”
“The implementation of the NHI will be done in a phased approach, with key milestones in each phase, rather than an overnight event.”
Here is Ramaphosa’s full prepared speech:
REMARKS BY PRESIDENT CYRIL RAMAPOSA ON THE SIGNING OF THE NATIONAL HEALTH INSURANCE (NHI) BILL, UNION BUILDINGS, TSHWANE, 15 MAY 2024
Minister of Health, Dr Joe Phaahla, MECs of Health, Senior Officials, Representatives of the health fraternity, Representatives of civil society, Representatives of labour, Members of Parliament’s Portfolio and Select Committees, Public representatives, Members of the media, Distinguished Guests, Ladies and Gentlemen,
We are gathered here today to witness the signing into law of the National Health Insurance Bill, a pivotal moment in the transformation of our country.
It is a milestone in South Africa’s ongoing quest for a more just society.
This transformational health care initiative gives further effect to our constitutional commitment to progressively realise access to health care services for all its citizens.
At its essence, the NHI is a commitment to eradicate the stark inequalities that have long determined who receives adequate healthcare and who suffers from neglect.
By putting in place a system that ensures equal access to health care regardless of a person’s social and economic circumstances, the NHI takes a bold stride towards a society where no individual must bear an untenable financial burden while seeking medical attention.
This vision is not just about social justice. It is also about efficiency and quality.
The provision of health care in this country is currently fragmented, unsustainable and unacceptable.
The public sector serves a large majority of the population, but faces budget constraints. The private sector serves a fraction of society at a far higher cost without a proportional improvement in health outcomes.
Addressing this imbalance requires a radical reimagining of resource allocation and a steadfast commitment to universal healthcare, a commitment we made to the United Nations.
The real challenge in implementing the NHI lies not in the lack of funds, but in the misallocation of resources that currently favours the private health sector at the expense of public health needs.
The NHI Bill presents an innovative approach to funding universal healthcare based on social solidarity.
It proposes a comprehensive strategy that combines various financial resources, including both additional funding and reallocating funds already in the health system.
This approach ensures contributions from a broader spectrum of society, emphasising the shared responsibility and mutual benefits envisioned by the NHI.
The financial hurdles facing the NHI can be navigated with careful planning, strategic resource allocation and a steadfast commitment to achieving equity.
The NHI carries the potential to transform the healthcare landscape, making the dream of quality, accessible care a reality for all its citizens.
The NHI Fund will procure services from public and private service providers to ensure all South Africans have access to quality health care.
The NHI recognises the respective strengths and capabilities of the public and private health care systems. It aims to ensure that they complement and reinforce each other.
Through more effective collaboration between the public and private sectors, we can ensure that the whole is greater than the sum of its parts.
The effective implementation of the NHI depends on the collective will of the South African people.
We all need to embrace a future where healthcare is a shared national treasure, reflective of the dignity and value we accord to every South African life.
Preparations for the implementation of NHI necessarily require a focused drive to improve the quality of health care.
We have already begun implementing a national quality improvement plan in public and private health care facilities, and are now seeing vast improvement.
In signing this Bill, we are signalling our determination to advance the constitutional right to access health care as articulated in Section 27 of the Constitution.
The passage of the Bill sets the foundation for ending a parallel inequitable health system where those without means are relegated to poor health care.
Under the NHI, access to quality care will be determined by need not by ability to pay. This will produce better health outcomes and prevent avoidable deaths.
The NHI is an important instrument to tackle poverty.
The rising cost of health care makes families poorer.
By contrast, health care provided through the NHI frees up resources in poor families for other essential needs.
The NHI will make health care in the country as a whole more affordable.
The way health care services will be paid for is meant to contain comprehensive health care costs and to ensure the available resources are more efficiently used.
Through the NHI, we plan to improve the effectiveness of health care provision by requiring all health facilities to achieve minimum quality health standards and be accredited.
Following the signing of this Bill, we will be establishing the systems and putting in place the necessary governance structures to implement the NHI based on the primary health care approach.
The implementation of the NHI will be done in a phased approach, with key milestones in each phase, rather than an overnight event.
There has been much debate about this Bill. Some people have expressed concern. Many others have expressed support.
What we need to remember is that South Africa is a constitutional democracy.
The Parliament that adopted this legislation was democratically-elected and its Members carried an electoral mandate to establish a National Health Insurance.
South Africa is also a country governed by the rule of law in which no person may be unduly deprived of their rights.
We are a country that has been built on dialogue and partnership, on working together to overcome differences in pursuit of a better life for all its people.
The NHI is an opportunity to make a break with the inequality and inefficiency that has long characterised our approach to the health of the South African people.
Let us work together, in a spirit of cooperation and solidarity, to make the NHI work.
In the stomach, so-called parietal cells are responsible for acid production. They react not only to the body’s own messenger molecules, but also to bitter-tasting food constituents such as caffeine. In a study published in the Journal of Agricultural and Food Chemistry, researchers tested bitter compounds on a human gastric cell line. Their results help to clarify the molecular regulatory mechanisms by which bitter substances influence gastric acid production.
It is known that taste receptors for bitter substances are not only found on the tongue, but also on the surface of other tissues and cells. These include the parietal cells of the stomach, which secrete protons into the stomach – ie, produce gastric acid. Recent studies have already shown that the bitter taste receptors found in parietal cells are involved in the regulation of gastric acid release. However, the underlying molecular signaling pathways are not yet fully understood.
Gastric cells as a test system
To further clarify the molecular interaction between bitter substances, bitter taste receptors, and gastric acid production, a research team led by Veronika Somoza, Director of the Leibniz Institute in Freising, has carried out a study on a cellular test system. This involves human parietal HGT-1 cells, which are able to secrete protons and, like taste cells, have bitter taste receptors.
Veronika Somoza’s team initially developed a working hypothesis based on the results of previous studies and the findings on signal transduction pathways in taste cells. According to this hypothesis, bitter tasting food constituents stimulate bitter taste receptors that are embedded in the cell membrane. This releases calcium ions inside the cells, leading to ion channel opening. This, in turn, allows sodium ions to flow into the gastric cells from the outside, ultimately contributing to the release of protons.
Hypothesis confirmed
First author Phil Richter explains: “We have successfully tested this mechanism with the two bitter substances caffeine and l-arginine. As expected from previous results, both food constituents were shown to stimulate gastric cell proton secretion in our test system.” The PhD student adds: “For the first time, we were able to demonstrate that the transient receptor potential channelsM4 and M5 are involved in the signaling cascade not only in taste cells but also in gastric cells and ensure an influx of sodium ions into the cells.”
Senior Scientist Gaby Andersen says: “By using knock-out experiments, in which we specifically switched off one type of bitter taste receptor in the cells, we were also able to show for the first time that there is a link between bitter taste receptors and the activation of the ion channels.” The scientist emphasizes that the results not only contribute to a better understanding of the role of taste receptors in the stomach but would also show that HGT-1 cells could be suitable as a replacement model for taste cells.
The research team agrees that the results will provide new insights into the regulation of gastric acid production and thus lead to innovative approaches in treating gastric diseases in the long term. However, further studies are needed to deepen knowledge of the molecular regulatory mechanisms and intracellular signaling pathways.
Contact with nature can lift our well-being by affecting emotions, influencing thoughts, reducing stress and improving physical health, as shown by studies. Even brief exposure to nature can help. One well-known study found that hospital patients recovered faster if their room included a window view of a natural setting.
Knowing more about nature’s effects on our bodies could not only help our well-being, but could also improve how we care for land, preserve ecosystems and design cities, homes and parks. Yet studies on the benefits of contact with nature have typically focused primarily on how seeing nature affects us. There has been less focus on what the nose knows. That is something a group of researchers set out to change, publishing their approach in Science Advances.
“We are immersed in a world of odorants, and we have a sophisticated olfactory system that processes them, with resulting impacts on our emotions and behaviour,” said Gregory Bratman, a University of Washington assistant professor of environmental and forest sciences. “But compared to research on the benefits of seeing nature, we don’t know nearly as much about how the impacts of nature’s scents and olfactory cues affect us.”
Bratman and colleagues from around the world outline ways to expand research into how odours and scents from natural settings impact our health and well-being. The interdisciplinary group of experts in olfaction, psychology, ecology, public health, atmospheric science and other fields are based at institutions in the US., the UK, Taiwan, Germany, Poland and Cyprus.
At its core, the human sense of smell, or olfaction, is a complex chemical detection system in constant operation. The nose is packed with hundreds of olfactory receptors, which are sophisticated chemical sensors. Together, they can detect more than one trillion scents, and that information gets delivered directly to the nervous system for our minds to interpret – consciously or otherwise.
The natural world releases a steady stream of chemical compounds to keep our olfactory system busy. Plants in particular exude volatile organic compounds, or VOCs, that can persist in the air for hours or days. VOCs perform many functions for plants, such as repelling herbivores or attracting pollinators. Some researchers have studied the impact of exposures to plant VOCs on people.
“We know bits and pieces of the overall picture,” said Bratman. “But there is so much more to learn. We are proposing a framework, informed by important research from many others, on how to investigate the intimate links between olfaction, nature and human well-being.”
Nature’s smell-mediated impacts likely come through different routes, according to the authors. Some chemical compounds, including a subset of those from the invisible realm of plant VOCs, may be acting on us without our conscious knowledge. In these cases, olfactory receptors in the nose could be initiating a “subthreshold” response to molecules that people are largely unaware of. Bratman and his co-authors are calling for vastly expanded research on when, where and how these undetected biochemical processes related to natural VOCs may affect us.
Other olfactory cues are picked up consciously, but scientists still don’t fully understand all their impacts on our health and well-being. Some scents, for example, may have “universal” interpretations to humans — something that nearly always smells pleasant, like a sweet-smelling flower. Other scents are closely tied to specific memories, or have associations and interpretations that vary by culture and personal experience, as research by co-author Asifa Majid of the University of Oxford has shown.
“Understanding how olfaction mediates our relationships with the natural world and the benefits we receive from it are multi-disciplinary undertakings,” said Bratman. “It involves insights from olfactory function research, Indigenous knowledge, Western psychology, anthropology, atmospheric chemistry, forest ecology, Shinrin-yoku – or ‘forest bathing’ – neuroscience, and more.”
Investigation into the potential links between our sense of smell and positive experiences with nature includes research by co-author Cecilia Bembibre at University College London, which shows that the cultural significance of smells, including those from nature, can be passed down in communities to each new generation. Co-author Jieling Xiao at Birmingham City University has delved into the associations people have with scents in built environments and urban gardens.
Other co-authors have shown that nature leaves its signature in the very air we breathe. Forests, for example, release a complex chemical milieux into the air. Research by co-author Jonathan Williams at the Max Planck Institute for Chemistry and the Cyprus Institute shows how natural VOCs can react and mix in the atmosphere, with repercussions for olfactory environments.
The authors are also calling for more studies to investigate how human activity alters nature’s olfactory footprint — both by pollution, which can modify or destroy odorants in the air, and by reducing habitats that release beneficial scents.
“Human activity is modifying the environment so quickly in some cases that we’re learning about these benefits while we’re simultaneously making them more difficult for people to access,” said Bratman. “As research illuminates more of these links, our hope is that we can make more informed decisions about our impacts on the natural world and the volatile organic compounds that come from it. As we say in the paper, we live within the chemical contexts that nature creates. Understanding this more can contribute to human well-being and advance efforts to protect the natural world.”
A study by Rutgers Health experts of more than 31 million hospital records shows that infertility treatment patients were twice as likely as those who conceived naturally to be hospitalised with heart disease in the year after delivery. The results were published in the Journal of Internal Medicine.
Compared to those who conceived naturally, patients who underwent infertility treatment 2.16 times as likely be hospitalised for hypertension.
“Postpartum checkups are necessary for all patients, but this study indicates they are particularly important for patients who undergo infertility treatment to achieve a conception,” said Rei Yamada, an obstetrics and gynaecology resident at Rutgers Robert Wood Johnson Medical School and lead author of the study.
The study authors say their results support standards of care that now call for an initial postpartum checkup three weeks after delivery, standards that some health systems have yet to adopt. Much of the elevated risk came in the first month after delivery, particularly for patients who developed dangerously high blood pressure.
“And these results aren’t the only ones to indicate that follow-up should occur early,” said Cande Ananth, chief of the Division of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Rutgers Robert Wood Johnson Medical School and senior author of the study. “We have been involved in a series of studies over the past few years that have found serious risks of heart disease and stroke to various high-risk patient populations within those initial 30 days after delivery – risks that could be mitigated with earlier follow-up care.”
The study analysed the Nationwide Readmissions Database, which contains nationally representative data on about 31 million hospital discharges and readmissions per year. The database contains diagnosis codes, which let researchers find specific populations and identify reasons for readmission.
The researchers used data from more than 31 million patients who were discharged following delivery from 2010 to 2018, including 287 813 patients who had undergone any infertility treatment.
Although infertility treatment predicted a sharply elevated risk of heart disease, the study authors said the relative youth of infertility treatment patients kept their overall risk fairly low. Just 550 of every 100 000 women who received infertility treatment and 355 of every 100 000 who conceived naturally were hospitalized with cardiovascular disease in the year after delivery.
The cause of the elevated risk of heart disease associated with infertility treatment remains unclear. The increase in heart disease could stem from the infertility treatments themselves, the underlying medical issues that made patients infertile or some other cause.
“Looking forward, I’d like to see if different types of infertility treatment and, importantly, medications are associated with different risk levels,” said Yamada. “Our data gave no information about which patients had undergone which treatment. More detailed information might also provide insight into how infertility treatment impacts cardiovascular outcomes.”
