Month: May 2021

Reviewing 50 Years of Progress in Women’s Health

Woman receiving a mammogram. Photo by National Cancer Institute on Unsplash

As abortion comes under threat in the United States, a perspective article looks back at the progress made in women’s health, seeing significant improvements in areas like equitable access to health care and survivorship.

However, the article’s authors argue there is still a long road ahead, despite all of the progress.

The United States, for example, still has the highest rate of maternal death among high-income countries, particularly among African American women.

As the United States Supreme Court prepares to hear a Mississippi abortion case challenging the landmark 1973 Roe v. Wade decision, some experts are questioning whether the progress made in women’s health may be winding back.

Cynthia A Stuenkel, MD, clinical professor of medicine at University of California San Diego School of Medicine, and JoAnn E Manson, MD, DrPH, professor of epidemiology at Harvard TH Chan School Of Public Health, review 50 years of progress in women’s health in a perspective article published online in New England Journal of Medicine.

“Reproductive justice is broader than the pro-choice movement and encompasses equity and accessibility of reproductive health care, as well as enhanced pathways to parenthood,” wrote the authors.

In addition to Roe v. Wade, they authors reviewed advances in reproductive health including:

  • The 1972 US Supreme Court ruling on Eisenstadt vs Baird ensuring unmarried persons equal access to contraception
  • The 2010 Affordable Care Act in the US made contraceptives an insured preventive health benefit
  • The Reproductive technology advances, including in vitro fertilisation, genetic testing and fertility preservation by cancer specialists

Advances in women’s health encompass more than reproduction, the authors wrote. As interest and focus has expanded to all stages of a woman’s life, science has begun to catch up to the specialised needs of women and sex-specific risk factors for chronic diseases that disproportionately affect women’s health, such as autoimmune diseases, mental health, osteoporosis and coronary heart disease.

  • Progress in breast cancer care and prevention resulted in a five-year overall survival rate of 90%
  • The human papillomavirus (HPV) vaccine reduced cervical cancer mortality fell by 50%

“Moving forward, it will be essential to recognise and study intersectional health disparities, including disparities based on sex, race, ethnicity, gender identity, sexual orientation, income and disability status. Overcoming these challenges and addressing these inequities will contribute to improved health for everyone,” wrote the authors.

Source: News-Medical.Net

Journal information: Stuenkel, C. A., et al. (2021) Women’s Health — Traversing Medicine and Public Policy. New England Journal of Medicine.

Gene Drive to Control Mosquito-borne Disease a Step Closer

Image source: Ekamalev at Unsplash

Scientists have developed a set of tools that will help create a gene drive to control mosquito-borne diseases such as the West Nile virus, which has received less attention than controlling mosquitoes that transmit malaria.

Since the advent of CRISPR genetic editing revolution, scientists have been working to use the technology to develop gene drives that target pathogen-spreading mosquitoes such as Anopheles and Aedes species, which spread malaria, dengue and other life-threatening diseases.

Much less genetic engineering work has focused on Culex genus mosquitoes, which spread devastating afflictions stemming from West Nile virus, as well as other viruses such as the Japanese encephalitis virus (JEV). Culex mosquitoes are a significant health risk in Africa and Asia, where they transmit the worm causing filariasis, a disease that can lead to a chronic debilitating condition known as elephantiasis.

University of California San Diego scientists have now developed a number of genetic editing tools that will help create a gene drive designed to stop Culex mosquitoes from spreading disease. Gene drives are designed to spread modified genes, in this case those that disable the ability to transmit pathogens, throughout the targeted wild population. The new study is published in the journal Nature Communications,

The researchers developed a Cas9/guide-RNA expression ‘toolkit’ designed for Culex mosquitoes. Since so little genetic engineering work has been done on Culex mosquitoes, the researchers were required to develop their toolkit from scratch, starting with a careful examination of the Culex genome.

“My coauthors and I believe that our work will be impactful for scientists working on the biology of the Culex disease vector since new genetic tools are deeply needed in this field,” said Gantz, an assistant research scientist in the Division of Biological Sciences at UC San Diego. “We also believe the scientific community beyond the gene drive field will welcome these findings since they could be of broad interest.”

The researchers also demonstrated the applicability of their tools in other insects.

“These modified gRNAs can increase gene drive performance in the fruit fly and could potentially offer better alternatives for future gene drive and gene-editing products in other species,” said Gantz.

Gantz and his colleagues have now tested their new tools to ensure proper genetic expression of the CRISPR components and are now on the verge of applying them to a gene drive in Culex mosquitoes. This could be used to stop pathogen transmission by Culex mosquitoes, or alternatively employed to suppress the mosquito population to prevent biting.

Source: University of California San Diego

Precise Ultrasound Heating of Neurons Could Treat Neurological Disorders

Image source: Fakurian Design on Unsplash

A multidisciplinary team at Washington University in St. Louis has developed a new brain stimulation technique using focused ultrasound that is able to turn specific types of neurons in the brain on and off and precisely control motor activity without surgical device implantation.

Being able to turn neurons on and off can treat certain neurological disorders such as Parkinson’s disease and epilepsy. Used for over six decades, deep brain stimulation techniques have had some treatment success in neurological disorders, but those require surgical device implantation. 

The team, led by Hong Chen, assistant professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology at the School of Medicine, is the first to provide direct evidence showing noninvasive activation of specific neuron types in mammalian brains by combining an ultrasound-induced heating effect and genetics, which they have named sonothermogenetics. It is also the first work to show that the ultrasound- genetics combination can robustly control behaviour by stimulating a specific target deep in the brain.

The results of the three years of research were published online in Brain Stimulation

“Our work provided evidence that sonothermogenetics evokes behavioural responses in freely moving mice while targeting a deep brain site,” Chen said. “Sonothermogenetics has the potential to transform our approaches for neuroscience research and uncover new methods to understand and treat human brain disorders.”

Chen and colleagues delivered a viral construct containing TRPV1 ion channels to genetically-selected neurons in a mouse model. Then, they delivered small pulses of heat generated by low-intensity focused ultrasound to the selected neurons in the brain via a wearable device. The heat, only a few degrees warmer than body temperature, activated the TRPV1 ion channel, which then acted as a switch to turn the neurons on or off.

“We can move the ultrasound device worn on the head of free-moving mice around to target different locations in the whole brain,” said Yaoheng Yang, first author of the paper and a graduate student in biomedical engineering. “Because it is noninvasive, this technique has the potential to be scaled up to large animals and potentially humans in the future.”

Building on prior research from his lab, professor of biomedical engineering Jianmin Cui and his team found for the first time that ion channel activity can be influenced by ultrasound alone, possibly leading to new and noninvasive ways to control the activity of specific cells. They discovered that focused ultrasound modulated the currents flowing through the ion channels on average by up to 23%, depending on channel and stimulus intensity. Following this work, researchers found close to 10 ion channels with this capability, but all of them are mechanosensitive, not thermosensitive.

The work also builds on the concept of optogenetics, the combination of the targeted expression of light-sensitive ion channels and the precise delivery of light to stimulate neurons deep in the brain. While optogenetics has increased discovery of new neural circuits, it has limited penetration depth due to light scattering, requiring surgical implantation of optical fibres to reach deeper into the brain.

Sonothermogenetics has the promise to target any location in the mouse brain with millimetre-scale resolution without causing any damage to the brain, Chen said. She and her team are further refining the technique and validating their work.

Source: Sci Tech Daily

Journal information: Yaoheng Yang et al, Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation, Brain Stimulation (2021). DOI: 10.1016/j.brs.2021.04.021

Lab Finds Benzene in Many Sunscreen Products

Some sunscreen products have been found to contain benzene, a known carcinogen. Photo by from Pexels

An online pharmacy company that also conducts independent testing of consumer products has detected benzene in several sunscreen products.

The company, Valisure LLC, has issued a petition to the Food and Drug Administration in the US to enact stricter rules regarding the presence of benzene in sunscreen products. 

Benzene is a colourless or light-yellow liquid chemical at room temperature. A widely used chemical, it has been used primarily as a solvent in the chemical and pharmaceutical industries and is a known carcinogen. Trace levels of benzene may be found in cigarette smoke, gasoline, glues, cleaning products, and paint strippers.

The FDA has forbidden the intentional introduction of the chemical into commercial products due to its toxic properties. The agency does, however, allow benzene-containing products to be sold if the product provides a “substantial therapeutic advance”, on the condition that levels in the product are at or below 2% and that the introduction of benzene into the product is unavoidable. Currently the agency has no guidelines regarding benzene levels in sunscreen products.

Over the past several years, Valisure has become a respected name in product testing—they were behind efforts to have the carcinogen NDMA removed from heartburn medications in 2018, and more recently led the effort to recall hand sanitizers that contained benzene. In 2020, they detected NDMA in metformin, leading to widespread product recalls.
In this new effort, the company tested 294 unique batches from 69 different companies. They found significant variability from batch to batch, even within a single company. Fourteen lots of sunscreen and after-sun care products from four different brands contained between 2.78 – 6.26 ppm of benzene; 26 lots from eight brands contained detectable benzene between 0.11 – 1.99 ppm; and 38 lots from 17 brands contained detectable benzene at < 0.1 ppm. 
There was no detection of benzene in an additional 217 batches of sunscreen from 66 different brands through initial analysis of at least one sample. 
The company also noted that some of the products they tested had levels that were higher than the 2% cap mandated by the FDA. They also noted that since most of the products they tested did not have any detectable amounts of benzene, it clearly is not an unavoidable byproduct of production. The FDA recently discovered that sunscreen chemicals can be readily absorbed through the skin, they added.

Their petition asks the FDA to ban any amount of benzene in sunscreen and after-tanning care products and issue a recall for those that have measurable levels of benzene that have already been sold. They have also published a table [PDF] that lists sunscreens brands with no detectable levels of benzene in them.

Source: Medical Xpress

Tooth Loss may Decrease the Capacity to Perform Everyday Tasks

Photo by Yusuf Belek on Unsplash

Older adults with more natural teeth are better able to perform everyday tasks such as cooking a meal, making a telephone call or going shopping, according to a new study. 

The study, conducted by researchers from UCL and the Tokyo Medical and Dental University, was published in the Journal of American Geriatrics Society, The researchers analysed data from 5631 adults from the English Longitudinal Study of Ageing (ELSA) with ages between 50 and 70 years old.

Previous research had established a link between tooth loss and various reductions in capacity, such as cognitive decline. However, such research could not tease out any kind of causal link: did the tooth loss cause the decline, or did the decline result in tooth loss?

In this study the research team wanted to investigate the causal effect of tooth loss on someone’s ability to carry out daily activities. After controlling for factors such as participants’ socioeconomic status and health status, they nevertheless found evidence of an independent link between tooth loss and the ability to carry out everyday tasks.

The participants in the study were asked how many natural teeth they had, with older adults usually having up to 32 natural teeth that are lost over time. Using data gathered in 2014-2015, the researchers measured how tooth loss affected people’s ability to carry out key instrumental activities of daily living (IADL). The activities included preparing a hot meal, shopping for groceries, making telephone calls, taking medications, doing work around the house or garden, or managing money.

Senior author Georgios Tsakos, professor at UCL Institute of Epidemiology and Health, explained: “We know from previous studies that tooth loss is associated with reduced functional capacity, but this study is the first to provide evidence about the causal effect of tooth loss on the instrumental activities of daily living (IADL) among older adults in England. And this effect is considerable.

“For example, older adults with 10 natural teeth are 30% more likely to have difficulties with key activities of daily living such as shopping for groceries or working around the house or garden compared to those with 20 natural teeth.

“Even after taking in factors such as participant’s education qualification, self-rated health and their parent’s education level for example, we still found a positive association between the number of natural teeth a person had and their functional ability.”

The researchers had a number of possible explanations for this relationship, noting that having more natural teeth is linked to delaying the onset of disability and death and that tooth loss can also hamper social interactions, which is also linked to poorer quality of life. Tooth loss could be linked to having a poorer diet with less nutrients, they suggested.

However the researchers cautioned that the results should be considered carefully due to the study’s complex design. Further studies are needed to investigate the causal relationship between tooth loss and functional ability.

First author, Dr Yusuke Matsuyama, at Tokyo Medical and Dental University, said: “Preventing tooth loss is important for maintaining functional capacity among older adults in England. Given the high prevalence of tooth loss, this effect is considerable and maintaining good oral health throughout the life course could be one strategy to prevent or delay loss of functional competence.

“The health gain from retaining natural teeth may not be limited to oral health outcomes but have wider relevance for promoting functional capacity and improving overall quality of life.”

Source: University College London

Journal information: Yusuke Matsuyama et al, Causal Effect of Tooth Loss on Functional Capacity in Older Adults in England: A Natural Experiment, Journal of the American Geriatrics Society (2021). DOI: 10.1111/jgs.17021

South Africa Moves to Level 2 Lockdown

Image by Quicknews

President Cyril Ramaphosa said on Sunday that he did not know “how long or how severe the third wave will be” as he tightened restrictions in response to rising COVID infections.

In a national address on Sunday, President Cyril Ramaphosa announced that Level 2 COVID restrictions would in place from Monday in response to rising cases, saying that he did not know “how long or how severe the third wave will be”.

The new restrictions mostly target social gatherings as well as moving the night-time curfew forward by one hour to 11pm.

No more than 100 people can attend indoor events, while the number for outside was halved to 250. However, to the relief of the liquor industry and many South Africans, no alcohol restrictions have been put in place. This demonstrates a less economically restrictive approach than the initial lockdowns, which caused the economy to shrink by 7% last year.

COVID hospitalisations increased 17% in recent days and the Free State, the Northern Cape, the North West and Gauteng are already seeing a third wave, Ramaphosa said.

A third wave is considered to be underway when the seven-day moving average of new cases exceeds 30% of the previous wave’s peak, according to the definition used by the SA Covid-19 Modelling Consortium.

“It is only a matter of time before the whole country enters a third wave … gatherings are the biggest source of transmission and we urge South Africans to social distance,” Ramaphosa said.

The daily infection rate is sharply higher than the averages of between 1000 and 1500 for most of the year. 

President Ramaphosa said cases averaged about 3700 in the past week, a 31% increase compared to the previous seven days, which he partly attributed to people’s increasing complacency over following health protocols.

“Because rates of infection have been low for some time, and because we are all suffering from pandemic fatigue, we have tended to become complacent.

“We have not been as vigilant about wearing our masks all the time, we have not been avoiding crowded places, and we have been socialising more,” the president said.

Due to the delay in infections and subsequent COVID testing, it may take several days for the new restrictions to have any noticeable impact on the daily number of new cases reported. The case positivity rate is now 11.9%, according to the most recent statistics for SA, now well above the 10% level which is considered acceptable.

Source: Business Day

How Air Pollution Causes Loss of Smell

Photo by Kouji Tsuru on Unsplash

Johns Hopkins Medicine researchers have studied how long-term exposure to air pollution causes loss of smell, or anosmia, to better understand how it can rob someone of the ability to smell and taste.

Anosmia can severely impact a person’s quality of life, making it extremely difficult to taste foods, detect airborne hazards in the environment, and other functions. People with anosmia may experience weight concerns, decreased social interaction, depression and general anxiety. Loss of smell has been linked in some cases to death in older adults. 

“We included participants from a variety of areas in our study; however, most lived in urban areas where pollution levels are highest,” says lead author Murugappan “Murray” Ramanathan, MD, rhinologist and associate professor of otolaryngology–head and neck surgery at the Johns Hopkins University School of Medicine. “We wanted to assess how their exposure to PM2.5 air pollution—inhalable, particulate matter less than 2.5 micrometers in size or about 30 times smaller than the diameter of a human hair—might cause them to lose their sense of smell.”

According to the US Environmental Protection Agency (EPA), PM2.5 (the PM stands for ‘particulate matter’) is the term for a mixture of solid particles and liquid droplets found in the air, and are smaller even than pollen grains. PM2.5 can be made of many materials depending on the location, such as dust, dirt, soot, smoke, organic compounds and metals. These particulated have been linked to cardiovascular disease, lung cancer, cognitive decline, chronic obstructive pulmonary disease, asthma and premature death. Previous studies have suggested PM2.5 is a likely culprit in loss of smell—a connection that Prof Ramanathan and his team decided to explore in greater detail.

In their study, the researchers examined data for 2690 people, aged 18 years and older, who were evaluated by otolaryngologists between January 2013 and December 2016. Of these, 538 were diagnosed with anosmia, with an average age of 54, the majority being men (63%).

The EPA’s Air Quality System provided air pollution data for the study. The researchers entered the data into a detailed computer simulation to estimate the PM2.5 pollution levels within the participants’ residential ZIP codes. The model was created by Zhenyu Zhang, a Johns Hopkins Medicine otolaryngology postdoctoral fellow.

The researchers found that long-term airborne exposure to PM2.5 nearly doubles (a 1.6- to 1.7-fold increase) the risk of losing one’s ability to smell. They believe this may occur due to the location of the olfactory nerve—which contains the sensory nerve fibres associated with the sense of smell—being directly in the path of inhaled PM2.5 materials.

“Based on this result, we feel that long-term exposure to high levels of PM2.5 represents a common risk factor for the loss of sense of smell, especially in vulnerable populations such as older people—but also one that is potentially modifiable if sources of PM2.5 components can be better controlled,” says Ramanathan.

The researchers next steps are to study anosmia patients’ socioeconomic factors to find out if they affect the chances of exposure to PM2.5 air pollution. They also hope to evaluate other air pollution components that may contribute to loss of smell, such as ozone.

Source: Medical Xpress

Journal information: Zhenyu Zhang et al, Exposure to Particulate Matter Air Pollution and Anosmia, JAMA Network Open (2021). DOI: 10.1001/jamanetworkopen.2021.11606

Surprising Mechanism of Action Discovered for Stem Cell Drugs

Two cytotoxic T cells (red) attacking an oral squamous cancer cell. Photo by National Cancer Institute on Unsplash

A new study revealed surprising insights into how specialised drugs that regenerate immune cells lost to chemotherapy actually work. 

In cancer patients following chemotherapy, there is a decrease in immune cells because chemotherapy also impacts the stem cells in bone marrow, which were meant to develop into new immune cells. This means that the immune system is then left short of immune cells to fight new infections.

Certain drugs exist, such as plerixafor, that can stimulate the release of stem cells from the bone marrow into the blood stream, so that they can be harvested and then reintroduced into the patients after treatment. These stem cells develop into new immune cells, bolstering the immune system. However, there was a lack of detailed knowledge of how these drugs actually worked.

Now, a study conducted in mice by researchers at the University of Copenhagen demonstrates how the medicine works at the cell level—and, surprisingly, how plerixafor, one of the two applied and tested drugs, is more effective than the other, despite the fact that the other drug, on paper, appears to be the most effective of the two. This discovery may not just help improve stem cell transplantation; it may also lead to improved drugs in the future.

“We have tested two drugs for stem cell transplantation which appear to have the same effect. What they do is block a receptor, causing the bone marrow to release stem cells into the blood. What the new study shows, though, is that they do not just block the receptor; one of the two drugs also affects other signaling pathways in the cell. And in short, that makes it more effective than the other of the two drugs,” explained PhD student Astrid Sissel Jørgensen from the Department of Biomedical Sciences at the University of Copenhagen.

“We used to believe that all we had to do was block the receptor, and that the two drugs had the same effect. It now appears that there is more to it,” she said.

The drugs tested by the researchers mobilise stem cells by acting as CXCR4 receptor antagonists. There are several drugs that target this receptor, including drugs inhibiting HIV replication.

“The drugs not only block the receptor’s normal signaling. One of the two drugs we have tested also affect some of the other cell pathways and even make the receptor withdraw into the cell and disappear from the surface,” explained corresponding author Professor Mette Rosenkilde. The study results revealed that one of the two drugs makes the bone marrow release more stem cells into the blood.

These findings on how the drugs affect cell pathways differently is also known as biased signalling. Mechanisms like these are what make the one drug more effective in practice than on paper, and they challenge the current view of these drugs.

“The results of our study directly influence our view of drugs used for stem cell transplantation. In the long term, though, it may also affect our view of future drugs, and how new drugs should be designed to have the best possible effect, both in connection with stem cell mobilisation, but also for treating HIV infections, where this particular receptor also plays a main role,” said Prof Rosenkilde.

Source: Medical Xpress

Journal information: Astrid S. Jørgensen et al, Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization, Communications Biology (2021). DOI: 10.1038/s42003-021-02070-9

Lifestyle Interventions Reverse the DNA Methylation Ageing ‘Clock’

Source: Pixabay/CC0

The results of a clinical trial showed that appropriate diet and exercise are able, to some extent, to reverse the DNA methylation ageing ‘clock’.

Lead author Kara Fitzgerald, ND IFMCP, at The Institute for Functional Medicine, explained: “Advanced age is the largest risk factor for impaired mental and physical function and many non-communicable diseases including cancer, neurodegeneration, type 2 diabetes, and cardiovascular disease.”

Methylation clocks are based on systematic methylation changes with age. DNAmAge clock specifically demonstrates about 60% of CpG sites losing methylation with age and 40% gaining methylation.

The researchers conducted a randomised controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment programme included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients.

Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock tool.

The researchers found that the diet and lifestyle treatment resulted in a 3.23 years decrease in DNAmAge compared with controls.

With a strong trend to significance, DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to those individuals’ baseline.

Nearly a quarter of the DNAmAge CpG sites are located in glucocorticoid response elements, indicating a likely relationship between stress and accelerated ageing. Cumulative lifetime stress has been shown to be linked to accelerated ageing of the methylome.

Other findings include that PTSD contributes to accelerated methylation age; and that greater infant distress is associated with an underdeveloped, younger epigenetic age.

The researchers tentatively accepted the hypothesis that the methylation pattern, from which the DNAmAge clock is computed, is a driver of ageing, thus they expect that attempting to directly influence the DNA methylome using diet and lifestyle to set back DNAmAge should lead to a healthier, more ‘youthful’ metabolism.

The Fitzgerald Research Team concluded, “it may be that emerging ‘omics’ approaches continue to evolve our understanding of biological age prediction and reversal beyond DNA methylation alone. Integration of our future understanding of multi-omics data should therefore be considered in the future trials of candidate age-delaying interventions.”

Source: Aging

Journal information: Fitzgerald, K. N., et al. (2021) Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. AGING-US.

French President Macron in SA for Talks on COVID

French President Emmanuel Macron arrived in South Africa today for talks with President Cyril Ramaphosa on a range of issues including possible technological assistance to aid South Africa’s response to the COVID pandemic.

On the agenda of the visit is the economic, health, research and manufacturing responses to the COVID pandemic.

Arriving from Rwanda, where he acknowledged France’s role in the 1994 genocide, Macron held talks in Pretoria with President Ramaphosa, whom he met last week in Paris at a summit on African economies.

The pair were also due to attend an event to support vaccine production on the continent, sponsored by the European Union, the United States and the World Bank. 

So far South Africa is the country worst hit by COVID on the continent as far available monitoring can determine, and has vaccinated just 1 percent of its population of 59 million people.

South Africa’s immunisation efforts have been hampered by delayed procurement, and then selling off its AstraZeneca vaccines obtained via Covax to other African countries after trial results showed drastically reduced effectiveness against the local B.1.351 variant. Rollout of the replacement Johnson & Johnson vaccine was paused for two weeks in April due to blood clot fears.

Now, along with India, South Africa is campaigning for a waiver of intellectual property rights on COVID vaccines, so that each country may produce its own doses. This effort has met with stiff resistance so far.

Macron has voiced support for a technology transfer to enable vaccine production sites to be set up in poorer countries.

Visit long delayed

Macron’s visit to South Africa has been long delayed due to the COVID pandemic.
The initial purpose for the trip had been to discuss multilateral cooperation with South Africa, an important G20 partner which is also a regular guest at G7 summits.

According to Foreign Policy, the French leader will also seek to establish greater influence in a region that is experiencing greater instability, marked by recent insurgencies in Mozambique.   

Jihadist attacks forced French energy giant Total to suspend work on a multi-billion euro gas project in Cabo Delgado province after a nearby town was targeted.

Before he returns to France, he will pay a visit to the Nelson Mandela Foundation, whose main missions are the fight against AIDS and education in rural areas.

Source: RFI