New research published in the Journal of Internal Medicine demonstrates that optogenetics, a technique which uses light-sensitive proteins to control the activity of targeted cells. is a promising shock-free approach to treating atrial fibrillation (AF), or an irregular, often rapid heart rate, for immediate restoration of regular rhythm.
Current treatments for AF, which include medications and shocks to restore a regular heart rhythm, come with low success rates and/or serious side effects. In this new study, rats’ hearts were optogenetically modified to express light-gated ion channels. After AF was induced, the animals’ chests were illuminated resulting in acute restoration of regulation rhythm. This shows that sufficient light penetrated the chest wall, which suggests that full penetration of the human atrial wall may be feasible as well, if deemed necessary for clinical translation.
“Shock-free cardioversion of AF would allow restoration of regular rhythm at any place and time, which may improve the prognosis and quality of life of patients suffering from AF. We hope that our paper will contribute to the realization of this much desired option in clinical practice,” said corresponding author Daniël A. Pijnappels, PhD, of Leiden University Medical Center, in The Netherlands.
A number of service providers have voluntarily ended their contracts with the Gauteng Department of Health to provide food to hospitals. In response, Gauteng Health is looking at a multi-vendor approach to tackle the problem which it blames on vendors being unable to fulfil their orders.
Meanwhile, Gauteng continues to battle with surgical and cancer treatment backlogs. R784 million has been allocated to this end, with a portion allocated to cancer treatment services, some of which will be outsourced to the private sector and some of which is going to new radiotherapy equipment.
This year has seen a number of Gauteng hospitals battling to secure their food supplies. Responding to SA parliamentary questions, Gauteng Health MEC Nomantu Nkomo-Ralehoko wrote that 26 out of 34 Gauteng public hospitals have been affected by food shortages.
“The shortages were mostly due to suppliers not being paid, contracts expiring, or companies not delivering. It was so bad for two hospitals, Bronkhorstspruit and Lenasia South, they had to borrow food from other hospitals!” said DA Shadow MEC for Health, Jack Bloom, who posed the questions.
Hospitals have being going through long stretches of not being able to provide full meals: at George Mukhari Hospital, chicken, fish and frozen vegetables were unavailable for four months, and there was no milk from February to May. The petty cash budgets are woefully insufficient to cover the gap: Kalafong hospital can only spend R2000 a day, not nearly enough to feed its 700 patients, reports SA People.
According to News24, Gauteeng Health spokesperson, Motalatale Modiba, said that the main problem was down to vendors struggling to fulfil their orders on time.
Currently, Gauteng health is running a tender to outsource oncology services for the Charlotte Maxeke and Steve Biko hospitals. The outsourcing programme should be able to ensure that patients who are currently awaiting treatment in the public sector will be able to access private sector treatment instead.
In their announcement, Gauteng Health stated: “We recognise the urgency of the situation and want to assure the public that we are committed to handling the outsourcing of radiation oncology sources diligently and are nearing implementation.”
The open tendering process will last 14 days, and is divided into categories for oncology specialists, treatment services and radiation planning services.
The department has already procured 4 Llinac machines, and has recently closed a tender for a Brachytherapy, and have advertised a tender for another Linac machine for Charlotte Maxeke. Ongoing investigations by Spotlight have also revealed that the oncology procurement process is lagging behind. The GDoH aims to have the first treatments under the outsourcing programme to start in August 2023.
Scanning electron micrograph image of E. Coli bacteria. Credit: NIH
Scientists have found that pairing specific diets with disease-causing bacteria can create lasting immunity in mice without the costs of developing sickness, revealing a new potential vaccination strategy. Their findings, published in Science Advances, may lead to new vaccines that could promote immunity for those with diarrhoeal diseases and possibly other infections.
The body takes one of two defence strategies against bacterial infections: kill the intruders or impair the intruders but keep them around. If the body chooses to impair the bacteria, then the disease can occur without the diarrhoea, but the infection can still be transmitted – also known as asymptomatic carriage.
“We discovered that immunisation against diarrhoeal infections is possible if we allow the bacteria to retain some of its disease-causing behaviour,” says senior author Professor Janelle Ayres at Salk Institute. “This insight could lead to the development of vaccines that could reduce symptoms and mortality, as well as protect against future infections.”
In 2018, Ayres’ lab looked at how dietary interventions can create an asymptomatic infection, which Ayres calls a cooperative, asymptomatic relationship between bacteria and host. They discovered that an iron-rich diet enabled mice to survive a normally lethal bacterial infection without ever developing signs of sickness or disease. The high-iron diet increased unabsorbed glucose in the mice’s intestines, which the bacteria could feast on. The excess glucose served as a ‘bribe’ for the bacteria, keeping them full and incentivised to not attack the host.
This process produced long-term asymptomatic infection with the bacteria, leading the researchers to believe that the adaptive immune system (which ‘remembers’ infections) may be involved.
“Being able to generate lasting immunity against bacteria like C. rodentium or E. coli has not been possible using established vaccination strategies. We wanted to figure out what mechanism was sustaining this lasting immunity, so we could use that mechanism to create an impactful solution to these diarrheal diseases,” says first author Grischa Chen, a former postdoctoral researcher in Ayres’ lab.
The researchers moved to figure out how the body suppresses infection symptoms, whether infection without symptoms can create long-term immunity, and whether that immunity is reproducible as a vaccination strategy.
The team compared mice with iron-rich and normal diets after C. rodentium infection to find whether the diet impacted symptomless infection. Immediately after infection, mice fed an iron-rich diet had no symptoms whereas mice fed a normal diet did have symptoms. All mice were then put on a normal diet to see whether the asymptomatic infection would last.
Mice without functional adaptive immune systems, regardless of whether they had ever been on an iron-rich diet, could not continue maintaining a cooperative relationship with the bacteria. Although the iron-rich diet suppressed symptoms immediately after infection, the adaptive immune system was required for lasting cooperation. Importantly, the mice with functional adaptive immune systems had the disease without any symptoms, with lasting immunity, as demonstrated by survival upon reinfection after a month.
Ayres and team concluded that an iron-rich diet alone can prevent bacteria from creating deadly symptoms in mice during active infection. But a functional adaptive immune system is required for immunity against future infection in the absence of dietary supplementation.
Some bacterial strains, if mutated enough, don’t cause symptoms. To test whether such bacteria could produce lasting immunity, the team repeated their iron-diet versus normal-diet experiment in mice, but this time using bacteria that could cause disease and bacteria that could not cause disease. They found that only mice that received disease-causing, unmutated bacteria were able to support immunity upon reinfection.
The scientists note that this is only a preliminary study and people shouldn’t consume large amounts of iron after reading it. They also hope their insights will provide a basis for future research in humans and the creation of a vaccination regiment that protects and prevents against diarrhoeal illness.
Researchers studying mice to investigate scarring in kidneys and hearts have found that it is driven by a protein called Indian Hedgehog (IHH), which is produced and released by a subset of cells in aged and injured kidneys. They published their findings in the journal Science Translational Medicine.
The researchers believe that IHH could become a potential target for therapies to treat chronic kidney disease (CKD) – a condition that affects 10% of the world’s population.
Risk factor
CKD is a term used to cover any form of kidney disease that continues for more than a few months. It can affect people of any age, but older people are more likely to experience some level of CKD.
While CKD primarily causes damage to kidneys, it is also a major risk factor for accelerated cardiovascular disease and premature death.
Progressive fibrosis – scarring of the kidneys – is a common feature in all CKD, but the mechanism underlying this connection is not fully understood.
Reduced scarring
A team from the University of Edinburgh identified a subset of epithelial cells that produce IHH and are only present within aged or injured mouse kidneys. They showed that these cells produced IHH in response to being activated by the protein TNF – a well-recognised driver of inflammation.
When blocking the actions of TNF or IHH in mouse models of kidney scarring, the team found that scar production in the kidney was reduced and kidney function was also better preserved. Increased levels of scarring in the heart also returned to normal levels.
Blocking pathway
In humans, the team showed that circulating IHH levels were significantly raised in patients with CKD. Patients with cardiovascular disease also had higher levels of IHH than those without cardiac problems.
The findings offer hope that blocking the TNF/IHH signalling pathway could improve both kidney and heart fibrosis problems – the leading cause of morbidity and mortality in patients with CKD.
There is a major unmet need for better treatments to halt the progressive kidney scarring and cardiovascular problems which affect so many patients with CKD. I’m excited at the potential of this work, and the new insights to be gained into the role of IHH as a major driver of multi-organ fibrosis, which we hope can be a first step on the road towards better treatments for patients.
Dr David Ferenbach, MRC Senior Clinical Fellow at the University of Edinburgh
Around 20% of women who needed fertility treatment, such as IVF, to conceive their first child are likely to get pregnant naturally in the future, finds a new study published in Human Reproduction. University College London researchers analysed data from 11 studies of over 5000 women around the world between 1980 and 2021, to evaluate how common it is to get pregnant naturally after delivering a baby conceived by fertility treatment.
They found that at least one in five women conceived naturally after having had a baby using fertility treatment such as IVF mostly within three years. This figure remained unchanged, even when taking into account the different types and outcome of fertility treatment – alongside length of follow up.
Infertility is defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse, and it is estimated to affect one in seven heterosexual couples.
However, not all women seeking and undergoing fertility treatment are absolutely or permanently infertile. And half of couples who struggle to conceive naturally in the first year of trying will go on to do so in the second year.
Not so rare an occurrence
Although it is typically considered ‘rare’ for a woman to get pregnant naturally, if she has previously had fertility treatment, the researchers want to highlight how it is not in fact an unusual event.
The team consider the findings to be particularly important, as many women may not realise that they could conceive naturally following fertility treatment. This could lead to them becoming pregnant again quickly or when they aren’t ready – which could be problematic for both the health of the mother and child.
Lead author, Dr Annette Thwaites (UCL EGA Institute for Women’s Health) said: “Our findings suggest that natural pregnancy after having a baby by IVF is far from rare. This is in contrast with widely held views – by women and health professionals – and those commonly expressed in the media, that it is a highly unlikely event.”
Much has changed since the early days of IVF and it is now used for a wide range of causes of infertility, including cases where no cause is ever found.
In addition, some women may not have experienced infertility at all but used treatment for other reasons. This could include single women using donor sperm, women in same sex relationships, surrogates or those seeking to screen for serious genetic conditions.
So, it is important for those who have had successful IVF to know how likely they are to conceive naturally afterwards.
IVF was first used in 1978 and now, more than 10 million babies worldwide have been born using the treatment – equating to between 1% and 6% of all babies born per year in the developed world by 2020.
In order to track the data more accurately and analyse which factors make natural pregnancy after having a baby by fertility treatment more likely, the researchers are calling for linked national data sets.
They hope that this information could then be used to counsel people considering their options after successful fertility treatment.
Dr Thwaites said: “Knowing what is possible would empower women to plan their families and make informed choices regarding further fertility treatment and/or contraception.”
Study limitations
Some limitations were the included studies being mostly of moderate quality with wide variation in geography, cause of subfertility, type and outcome of fertility treatment and length of follow up making direct comparisons difficult.
Researchers have shown that the antihypertensive drug prazosin can prevent posttraumatic headaches, such as those caused by a concussion suffered by members of the military. Their findings were published in Headache: The Journal of Head and Face Pain.
Senior study author Dr Murray Raskind explained that few treatment options exist for this type of headache: “Persistent posttraumatic headaches are the most common long-term consequence of mild traumatic brain injuries (concussions) in Veterans and active-duty service members, causing substantial distress and disability at home and work. Although these headaches usually resemble migraine headaches symptomatically, they often fail to respond to the prevention treatments useful for migraines.”
The FDA approved prazosin to treat hypertension in 1976. It has been widely used off-label to treat conditions such as PTSD-associated nightmares and enlarged prostate. An earlier study by members of the research group suggested that prazosin could reduce the frequency and severity of headaches caused by traumatic brain injury (TBI).
To test this effect, researchers led by VA Puget Sound Health Care System conducted a pilot study with 48 Veterans and service members with headaches caused by mild TBI, also known as a concussion. Participants took gradually increasing doses of prazosin for five weeks before receiving the maximum dose for 12 weeks. The study showed that the drug was well-tolerated, and researchers reported that morning drowsiness was the only adverse effect.
Before the trial began, study participants had an average of 18 headache days each month. By the end of the 12-week period, those taking prazosin only had headaches for an average of six days a month. Participants receiving a placebo reported some reduction in headaches, but still had headaches about 12 days a month. Significantly more participants in the prazosin group had at least 50% fewer headaches during the 12 weeks of taking a full dose of medication.
Participants taking prazosin also saw significant decreases in how much headaches impacted their quality of life. By the end of the trial, those taking prazosin reported that headaches had “some impact” on their daily ability to function, while participants given a placebo continued to report “severe impact” of headaches.
Larger clinical trials are needed to confirm the extent of these promising results, according to the researchers, but these initial findings offer a potential relief for a common ailment faced by many Veterans.
“This study is the only clinical trial of an oral medication to demonstrate efficacy for posttraumatic headache. Because prazosin is widely used across VA and the Department of Defense to treat PTSD trauma nightmares and sleep disruption, many VA and DOD prescribers are familiar with prescribing this generically available, inexpensive medication,” said Raskind. “Prazosin now offers an evidence-based approach to alleviate the suffering of Veterans and service members who have struggled for years with frequent posttraumatic headaches.”
The bar in the middle is all one grey level, but it appears lighter on the left and darker on the right due to the background. Credit Jolyon Troscianko
Numerous visual illusions are caused by limits in the way our eyes and visual neurones work – rather than more complex psychological processes, as demonstrated by new research published in PLOS Computational Biology.
Researchers examined illusions in which an object’s surroundings affect the way we see its colour or pattern. Scientists and philosophers have long debated whether these illusions are caused by neural processing in the eye and low-level visual centres in the brain, or involve higher-level mental processes such as context and prior knowledge.
In the new study Dr Jolyon Troscianko, from the University of Exeter, co-developed a model that suggests simple limits to neural responses – not deeper psychological processes – explain these illusions.
“Our eyes send messages to the brain by making neurones fire faster or slower,” said Dr Troscianko. “However, there’s a limit to how quickly they can fire, and previous research hasn’t considered how the limit might affect the ways we see colour.”
The model combines this “limited bandwidth” with information on how humans perceive patterns at different scales, together with an assumption that our vision performs best when we are looking at natural scenes.
The model was developed by researchers from the Universities of Exeter and Sussex to predict how animals see colour, but it was also found to correctly predict many visual illusions seen by humans.
“This throws into the air a lot of long-held assumptions about how visual illusions work,” Dr Troscianko said.
He said the findings also shed light on the popularity of high-definition televisions.
“Modern high dynamic range televisions create bright white regions that are over 10 000 times brighter than their darkest black, approaching the contrast levels of natural scenes,” Dr Troscianko added.
“How our eyes and brains can handle this contrast is a puzzle because tests show that the highest contrasts we humans can see at a single spatial scale is around 200:1.
“Even more confusingly, the neurones connecting our eyes to our brains can only handle contrasts of about 10:1.
“Our model shows how neurones with such limited contrast bandwidth can combine their signals to allow us to see these enormous contrasts, but the information is ‘compressed’ – resulting in visual illusions.
“The model shows how our neurones are precisely evolved to use of every bit of capacity.
“For example, some neurones are sensitive to very tiny differences in grey levels at medium-sized scales, but are easily overwhelmed by high contrasts.
“Meanwhile, neurones coding for contrasts at larger or smaller scales are much less sensitive, but can work over a much wider range of contrasts, giving deep black-and-white differences.
“Ultimately this shows how a system with a severely limited neural bandwidth and sensitivity can perceive contrasts larger than 10 000:1.”
A research group from Nagoya University in Japan has discovered that using an antibiotic to target Fusobacterium reduced the formation of lesions associated with endometriosis, a gynaecological disorder characterised by endometrial tissue growing outside of the uterus. Their findings, published in Science Translational Medicine, suggest an alternative treatment for this disorder based on antibiotics.
Endometriosis affects one in ten women between the ages of 15 and 49. The disorder can cause lifelong health problems, including pelvic pain and infertility. Although it can be treated using hormone therapy and surgical resection, these procedures sometimes lead to side effects, recurrence, and a significant impact on pregnancy.
The group led by Professor Yutaka Kondo (he, him) and Assistant Professor Ayako Muraoka (she, her) from the Nagoya University Graduate School of Medicine, in collaboration with the National Cancer Center, found that the uterus of mice infected with Fusobacterium had more and heavier lesions. However, mice that had been given an antibiotic to eradicate Fusobacterium saw improved lesion formation.
The team’s findings strongly suggest that targeting Fusobacterium is an effective non-hormonal antibiotic treatment for endometriosis. Dr Kondo praised the potential for easier diagnosis and treatment. “Eradication of this bacterium by antibiotic treatment could be an approach to treat endometriosis for women who are positive for fusobacteria infection, and such women could be easily identified by vaginal swab or uterus swab,” he said.
This study also shows the benefit of looking at upstream events to determine causative agents. The initial finding was that a protein called transgelin (TAGLN) was often upregulated in patients with endometriosis. This was unsurprising because the protein is associated with processes that are important in the development of endometriosis. However, this finding led them to determine that transforming growth factor beta (TGF-β) seemed to cause the upregulation of TAGLN. Since TGF-β is released by macrophages, the natural anti-inflammatory response and immune regulation cells of the body, this led them to conclude that these macrophages were being activated in response to Fusobacterium.
“In this study, we demonstrated that the Fusobacterium-TAGLN-endometriosis axis is frequently dysregulated in endometriosis,” said Dr Kondo. “Our data provide a strong and novel rationale for targeting Fusobacterium as a non-hormonal antibiotic-based treatment for endometriosis.”
Clinical trials of antibiotic treatment for human patients are ongoing at the Department of Obstetrics and Gynecology at Nagoya University Hospital.
A new study showed that it may be necessary to rethink the genetic cause previously held to be behind very early menopause. Until now, variants in any one of more than 100 genes were thought to cause premature ovarian insufficiency (POI), which results in menopause before age 40. This affects around 1% of women, making it a leading cause of infertility. Under current guidance, a variation in one of these genes is cause for clinicians to consider a genetic diagnosis of POI.
Now, in the largest study to date, published in Nature Medicine, researchers analysed genetic data from more than 104 733 women in UK Biobank, of whom 2231 reported experiencing menopause before the age of 40.
The study found evidence that 98% of women carrying variations in the genes that were previously considered to be causes of premature menopause in fact had menopause over 40, therefore ruling out a diagnosis of POI in these women.
Anna Murray, Professor of Human Genetics at the University of Exeter Medical School is a senior author on the study. She said: “Our research means rethinking what causes very early menopause. The presence of specific genetic variants in multiple women who experience premature menopause has led to the assumption that they are causing the condition – but we have shown that these gene variations are also found in women with a normal age of menopause and therefore in many cases the link could just be coincidence. It now seems likely that premature menopause is caused by a combination of variants in many genes, as well as non-genetic factors. As genomic medicine evolves, we need to apply this standard of evidence to other conditions, so we can tailor diagnosis, treatment and support.”
Dr Julia Prague, Consultant Endocrinologist and Clinical Academic at the University of Exeter, and an author on the paper, said: “Having a very early menopause is often extremely distressing because it means losing fertility and treatment with hormone replacement is required to prevent negative health consequences. Clinicians need to understand the reasons why premature menopause occurs so that they do not miss the true underlying cause and can counsel patients appropriately. Misinterpreting genetic tests could have negative implications for women, such as suggesting that their relatives may also be at risk of very early menopause due to their genes, when in fact they may not be.”
Stasa Stankovic, of the University of Cambridge’s MRC Epidemiology Unit, and co-lead analyst of the study, said: “Each woman’s unique genetic combination shifts menopause timing, either earlier or later. Although genetic variation in the studied genes were not sufficient to cause very early menopause, we did identify genetic drivers that had a much more subtle impact on reproductive longevity. For example, women carrying genetic variation in TWNK and SOHLH2 genes experienced menopause up to three years earlier than the general population. Our future studies will continue using the power of human genomics to better understand the underlying biology of reproductive ageing in women and key genetic drivers of its extreme forms, including very early menopause. With this knowledge, we are also paving the path towards development of next-generation treatments for reproductive disorders.”
A Canadian study of more than 8 million adults suggests that even a modest loss of kidney function is associated with increased health risks. The study, published in The BMJ, could lead to better approaches to prevent chronic kidney disease and related conditions, particularly in younger adults.
“The dogma is that healthy, young adults don’t need to worry about kidney function unless it drops to around 50% of the normal level, but our research suggests that even a more modest 20–30% drop may have consequences and we may want to have earlier conversations about prevention and monitoring,” explained senior author Dr Manish Sood at the University of Ottawa.
The research team used health records from 2008 to 2021 for every Ontario, Canada adult aged 18–65 who had at least one blood test for kidney function, but no history of kidney disease. They found that 18% of those in the 18–39 age group had kidney function that was modestly below normal levels, but not low enough to be diagnosed with chronic kidney disease. Individuals in this ‘grey zone’ faced a modestly increased risk of kidney failure, death and cardiovascular events.
For example, in young adults (age 18–39), a 20–30% loss in kidney function was associated with a 1.4-fold increase in death, 1.3-fold increase in a cardiac event and a 6-fold increase in the risk of kidney failure. The absolute risk of any of these events was still low at less than 2 per 1000.
“Thankfully, the absolute risk for any one individual with kidney function in this grey zone is low, but when we look at the whole population, the impact could be quite significant,” said co-senior author Dr Greg Knoll, senior scientist, nephrologist and Head of the Department of Medicine at The Ottawa Hospital and the University of Ottawa. “We need further research to confirm these findings and then see if we can reduce the risk through lifestyle modification.”
While the blood creatine test for kidney function is relatively inexpensive and readily available, the researchers are not suggesting routine testing for all individuals at this time. However, if an individual has had a kidney test that shows a modest reduction in function, it could prompt consulting health care provider. All individuals can also reduce their risk of kidney disease by eating a healthy diet with lower salt, exercising regularly and limiting alcohol intake.
Dr. Sood and his colleagues previously developed the Project BigLife Chronic Kidney Disease calculator to help individuals calculate their kidney disease risk and see the impact of lifestyle changes. The calculator will continue to be refined as new research arises.
