Month: October 2022

Arthritis Link in Immune Response Against Gut Bacteria Protein

Photo by Cara Shelton on Unsplash

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is associated with aberrant immune responses. In a recent analysis published in Arthritis & Rheumatology, people with RA and those at risk for the disease had higher blood levels of antibodies against a protein expressed by Prevotella copri, a common gut bacteria. 

The study compared 98 participants with established RA who were compared with 98 controls without the condition, as well as 67 participants at high risk for RA who were compared with 67 controls. The researchers measured levels of antibodies against Pc-p27, a protein expressed by P. copri.

Participants with RA had significantly higher levels of IgA anti-Pc-p27 antibodies and trends towards higher levels of IgG anti-Pc-p27 antibodies when compared to their matched controls. When stratified by early versus established RA, early RA participants had median values of IgG anti-Pc-p27 antibodies that were overall higher, whereas median values of IgA anti-Pc-p27 were statistically significantly higher in participants with established RA, compared with their matched controls.

The authors noted that additional research into the roles of this and other microorganisms in rheumatoid arthritis is warranted.

“Our hope is that these findings can help to further elucidate the complex etiologic role of bacterial commensals in people who are at-risk of developing RA and in those with RA so that targeted therapies can be developed with the goals of providing better treatment and ultimately, prevention of the disease,” said corresponding author Jennifer A. Seifert, MPH, of the University of Colorado Denver.

Source: Wiley

The Micromort: A Simple Way to Convey Mortality Risk

When dealing with risks, the often-used metric of “deaths per 100 000 population” can be a bit unwieldy, especially when explaining risk to patients. During the COVID pandemic, this became something of a problem when trying to convey the risks of vaccination to the general public. Many felt that the risk of adverse effects outweighed the protection that the vaccination conferred against the coronavirus.

But there is a different, more approachable metric – in 1979, Ronald A. Howard introduced the ‘micromort’ – defined as one chance of death in a million. One in a million is about the same odds as flipping a coin 20 times a row and getting the same result.

Though its name is sure to make some people giggle, the micromort is commonly used in actuarial sciences and decision analyses to quantify the risk of death per unit of exposure to a risk factor or event (Howard, 1980). micromorts have the advantage of being easier to interpret and comprehend than abstract numerical figures, and have been used to convey risks associated with surgical operations and medical treatments.

For example, the mortality risk of general anaesthesia is 10 micromorts per procedure (ie, a 0.001% chance of dying), which is comparable to the mortality risk of an experienced skydiver takes when doing a parachute jump. Chronic cigarette smoking reduces adult life expectancy by 6.5 years on average; said differently, averaged over a lifetime, smoking reduces life expectancy by 7 micromorts per day (3.5 hours per day) (Shaw et al., 2000).

Simply being being alive carries a risk in itself: it is highest on the first day of lift at around 500 micromorts, drops rapidly in childhood and then increases steadily throughout adult life until the 90s, when each day is as risky as that person’s first day.

MicroMorts per day for average person in England and Wales—dashed line shows rate for first day of life. (Spiegelhalter, 2014)

Perhaps unsurprisingly, one UK estimate showed that travelling by motorbike carries the highest risk of death at 9.6km for each MicroMort. Travelling by car is far safer at 400km per MicroMort. But somewhat counterintuitively, walking is not much safer than travelling by motorbike: hitting the pavement results in one MicroMort per 27.2km walked. This can be partly explained by the greater amount of time spent walking and exposed to environmental hazards such as traffic, air pollution, crime and so on.

The concept of micromorts can also be applied to pregnancies and risks to the foetus. The risk per unit due to stillbirth is only about 19 or 3710 micromorts when drinking 5 units/week throughout pregnancy. For low risk women in the UK, planned first birth at home carries an additional 843 (-200 to 2620) micromorts compared with in hospital, and planned vaginal breech birth an additional 5870 (-4400 to 18 500), compared with planned caesarean. By contrast, the risk from the mother eating a serving of unpasteurised cheese, is negligible at 0.00026 micromorts (Hickson et al., 2020).

Hopeful IVF Parents Should Skip the Drinks

People clinking wine glasses
Photo by Jep Gambardella on Pexels

In a recent analysis published in Acta Obstetricia et Gynecologica Scandinavica, researchers found no link between women’s caffeine consumption and pregnancy or live birth rate after fertility treatments – but alcohol consumption was linked to decreased pregnancy rate after treatments with more than 84g of alcohol a week (approximately 7 standard drinks).

The link held true for their spouses as well: men’s alcohol consumption was associated with decreased live birth rate after fertility treatments in women when weekly consumption was greater than 84g.

The researchers searched the available literature and found a total of 7 studies on caffeine consumption and 9 studies on alcohol consumption were included, with a total of 26 922 women and/or their spouse who underwent fertility treatment.

Compared with those abstaining from alcohol, the chance of achieving a pregnancy after fertility treatment decreased by 7% for women who consumed 84g of alcohol per week, and the chance of partners achieving a live birth decreased by 9% for men who consumed 84g of alcohol per week.

“Couples should be aware that some modifiable lifestyle factors such as drinking habits may affect their fertility treatment outcomes. But how these factors impact the reproductive system still needs more research to elucidate,” said corresponding author Yufeng Li, MD, of Tongji Hospital, in China.

Source: Wiley

Fixing Spinal Cord Injuries with Stem Cell Grafts and Rehabilitation

Photo by Cottonbro on Pexels

In recent years, researchers have made strides in promoting tissue regeneration in spinal cord injuries (SCI) through implanted neural stem cells or grafts in animal models. Separate efforts have shown that intensive physical rehabilitation can improve function after SCI by promoting greater or new roles for undamaged cells and neural circuits.

University of California San Diego researchers tested whether rehabilitation can pair with pro-regenerative therapies, such as stem cell grafting. They published their findings in in JCI Insight, 

The researchers induced a cervical lesion in rats that impaired the animals’ ability to grasp with its forelimbs. The animals were divided into four groups: animals who underwent the lesion alone; animals who received a subsequent grafting of neural stem cells designed to grow and connect with existing nerves; animals who received rehabilitation only; and animals who received both stem cell therapy and rehabilitation.

Rehabilitation therapy for some animals began one month after initial injury, a time point that approximates when most human patients are admitted to SCI rehabilitation centers. Rehabilitation consisted of daily activities that rewarded them with food pellets if they performed grasping skills.

The researchers found that rehabilitation enhanced regeneration of injured corticospinal axons at the lesion site in rats, and that a combination of rehabilitation and grafting produced significant recovery in forelimb grasping when both treatments occurred one month after injury.

“These new findings indicate that rehabilitation plays a critically important role in amplifying functional recovery when combined with a pro-regenerative therapy, such as a neural stem cell transplant,” said first author Paul Lu, PhD, associate adjunct professor of neuroscience at UC San Diego School of Medicine and research health science specialist at the Veterans Administration San Diego Healthcare System.

“Indeed, we found a surprisingly potent benefit of intensive physical rehabilitation when administered as a daily regimen that substantially exceeds what humans are now provided after SCI.”

Senior author Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, and colleagues have long worked to address the complex challenges of repairing SCIs and restoring function.

In 2020, for example, they reported on the observed benefits of neural stem cell grafts in mice and in 2019, described 3D-printed implantable scaffolding that would promote nerve cell growth.

“There is a great unmet need to improve regenerative therapies after SCI,” said Tuszynski. “We hope that our findings point the way to a new potential combination treatment consisting of neural stem cell grafts plus rehabilitation, a strategy that we hope to move to human clinical trials over the next two years.”

Source: University of California – San Diego

Intensive Blood Pressure Reduction after Ischaemic Stroke Increases Disability

Credit: American Heart Association

The largest ever randomised controlled trial of intensive blood pressure lowering after thrombectomy in ischaemic stroke patients found that it led to deterioration in surrounding brain tissue and higher rates of disability, compared to less intensive treatment.

The results of the ENCHANTED2/MT trial were presented in a late-breaking session at the World Stroke Congress and simultaneously published in The Lancet. The trial was stopped early due to the significance of the findings.

Professor Craig Anderson, Director of Global Brain Health at The George Institute for Global Health, said the rapid emergence of this effect suggested the more aggressive approach was compromising the return of blood flow to the affected area.

“Our study provides a strong indication that this increasingly common treatment strategy should now be avoided in clinical practice,” he said.

Endovascular thrombectomy is an increasingly used non-surgical treatment for ischaemic stroke, in which x-ray guided microcatheters are inserted into the blood clot to dissolve it.

“A potential downside of this now widely used and effective treatment is that the rapid return of blood supply to an area that has been deprived of oxygen for a while can cause tissue damage known as reperfusion injury,” said Professor Anderson.

“This has resulted in a shift in medical practice towards more intensive lowering of blood pressure after clot removal to try and minimise this damage, but without evidence to support the benefits versus potential harms.”

To this end, researchers recruited 816 adults with acute ischaemic stroke who had elevated blood pressure after clot removal from 44 centres in China between July 2020 and March 2022. They had an average age of 67 and just over a third were female.

Of these, 407 were assigned to more-intensive (target < 120mmHg) and 409 to the less-intensive (target 140–180mmHg) systolic blood pressure control, with the target to be achieved within one hour of entering the study and sustained for 72 hours.

Researchers looked at how well the patients in both groups recovered according to a standard measure of disability, ranging from 0–1 for a good outcome without or with symptoms but no disability, scores of 2–5 reflecting increasing disability levels, and 6 being death.

Patients in the more-intensively treated group had significantly worse scores on the scale compared to those allocated to those treated less intensively.

Compared to the less-intensive group, they had more early brain tissue deterioration and major disability at 90 days but there were no significant differences in brain bleeds, mortality, or serious adverse events.

Patients who had their blood pressure more intensively controlled also rated their quality of life as significantly worse due to limitations on their physical abilities resulting from their stroke.

Prof Anderson said that after scouring the medical literature the research team had been unable to find strong enough evidence to recommend the ideal target for blood pressure control after blood clot removal in patients with acute ischaemic stroke.

“While our study has now shown intensive blood pressure control to a systolic target of less than 120mmHg to be harmful, the optimal level of control is yet to be defined,” he said.

Source: George Institute for Global Health

Antibodies can Prevent Bacteria from Infiltrating Cells

Adhesion of Bartonella henselae to human cells. B. henselae  (strain Marseille) bacteria (light blue) in an early stage infection process (30 min) to human HeLa-229 cells (red). Adhesion to host cells is mediated by specific interactions between B. henselae  surface proteins and components of the host extracellular matrix including molecules such as fibronectin or collagen. Scale bar: 8 μm.

Using Bartonella henselae bacteria, the cause of cat scratch disease, researchers have demonstrated for the first time that antibodies can prevent certain surface proteins of bacterial pathogens from entering host cells. The findings are important for the development of new drugs against highly resistant infectious agents.

Infections pose a significant threat to human health, especially when pathogens manage to colonise the organism and subsequently cause severe infections. The first step in such an infection always consists of the pathogens attaching themselves to the host cells’ surface. From here, the infections spread, resulting, for example, in infections of deeper tissue layers and organs.

A group of scientists surrounding Prof. Volkhard Kempf from Frankfurt University Hospital’s Institute of Microbiology and Hospital Hygiene has now succeeded in blocking this adhesion mechanism in a bacterium, thereby preventing the infection of host cells. For this purpose, the researchers examined the pathogen Bartonella henselae, usually causing cat scratch disease. Transmitted by cats, the disease mainly affects young children, whose symptoms include swollen and hardened lymph nodes around the site of infection, usually after a scratch or bite injury caused by infected cats.

Bartonella bacteria infect so-called endothelial cells, which line the blood vessels. Via their surface protein Bartonella adhesin A (BadA), they attach themselves to a protein (fibronectin) of the so-called “extracellular matrix,” a network of protein fibers that lie on top of the endothelial cells.

Breaking BadA

To determine which parts of the BadA protein are important in the bacterial adhesion process, the researchers equipped Bartonella bacteria with various genetically modified BadA variants, among others, and then analysed the extent to which these variants were still able to bind fibronectin. Once it was clear which BadA segments were responsible for the binding, the team produced antibodies against them, demonstrating for the first time that such antibodies can prevent infection by such bacteria.

Prof. Volkhard Kempf explains: “Bartonella henselae is not a very dangerous pathogen, and in most cases, cat scratch disease does not require any specific medical treatment. However, for us Bartonella henselae is a very important model organism for far more dangerous pathogens such as Acinetobacter baumannii, a serious pathogen that usually causes wound infection or pneumonia and often shows resistance to several last-choice antibiotics. The BadA protein of Bartonella henselae belongs to the so-called ‘trimeric autotransporter adhesins’, which are also responsible for adhesion to human cells in Acinetobacter and a number of other pathogens. A drug-induced blocking of these adhesins is therefore a promising novel and future approach to combat dangerous bacterial infections.”

The researchers published their findings in Diagnostics.

Source: Goethe University Frankfurt

Intermittent Fasting does not Impact Female Sex Hormones

Bathroom scale
Photo by I Yunmai on Unsplash

Intermittent fasting has been shown to be an effective way to lose weight, but critics have worried that the practice may have a negative impact on women’s reproductive hormones. Now, researchers bring new evidence to the table in a study published in Obesity.

The researchers, led by Krista Varady, University of Illinois Chicago professor of nutrition, followed a group of pre- and post-menopausal obese women for a period of eight weeks on the ‘warrior diet’ method of intermittent fasting.

The warrior diet prescribes a time-restricted feeding window of four hours per day, during which dieters can eat without counting calories before resuming a water fast until the next day.

They measured the differences in hormone levels, obtained by analysing blood sample data, in groups of dieters who stuck to four- and six-hour feeding windows against a control group that followed no diet restrictions.

Varady and her team found that levels of sex-binding globulin hormone, a protein that carries reproductive hormones throughout the body, was unchanged in the dieters after eight weeks. The same held true for both testosterone and androstenedione, a steroid hormone that the body uses to produce both testosterone and oestrogen.

However, dehydroepiandrosterone or DHEA, a hormone that fertility clinics prescribe to improve ovarian function and egg quality, was significantly lower in both pre-menopausal and post-menopausal women at the end of the trial, dropping by about 14%.

While the drop in DHEA levels was the most significant finding of the study, in both pre- and post-menopausal women, DHEA levels remained within the normal range by the end of the eight-week period.

“This suggests that in pre-menopausal women, the minor drop in DHEA levels has to be weighed against the proven fertility benefits of lower body mass,” Varady said. “The drop in DHEA levels in post-menopausal women could be concerning because menopause already causes a dramatic drop in estrogen, and DHEA is a primary component of estrogen. However, a survey of the participants reported no negative side effects associated with low estrogen post-menopause, such as sexual dysfunction or skin changes.”

As an added benefit, since high DHEA has been linked to breast cancer risk, Varady said a moderate drop in levels might be helpful in reducing that risk for both pre- and post-menopausal women.

The study measured levels of oestradiol, oestrone and progesterone as well, but only in post-menopausal women, due to the changing levels of these hormones throughout pre-menopausal women’s menstrual cycles. Among post-menopausal women, there was no change in these hormones at the end of eight weeks.

Women in both the four-hour and six-hour dieting groups experienced weight loss of 3% to 4% of their baseline weight throughout the course of the study, compared with the control group, which had almost no weight loss. The dieters also saw a drop in insulin resistance and in biomarkers of oxidative stress.

Perimenopausal women, who are typically in their 40s, were excluded from the study.

Still, Varady said, “I think this is a great first step. We’ve observed thousands of pre- and post-menopausal women through different alternate-day fasting and time-restricted eating strategies. All it’s doing is making people eat less. By shortening that eating window, you’re just naturally cutting calories. Much of the negative information on intermittent fasting reported has come from studies on mice or rats. We need more studies to look at the effects of intermittent fasting on humans.”

Source: University of Illinois Chicago

Axial Spondyloarthritis Association of South Africa wins Excellence Award at EULAR PARE Assembly 2022

Maranda Van Dam, Chairperson of ASASA (left) accepting award, with Souzi Makri President of PARE (middle) and Nikos Sleeks, ELEANA Greece (right)

Maranda van Dam, Chairman of the Axial Spondyloarthritis Association of South Africa (ASASA) won an award of excellence at the EULAR PARE (People with Arthritis/Rheumatism across Europe) Congress 2022, for work performed by ASASA around axial spondyloarthritis (AxSpA) in South Africa. The PARE congress took place from 20 – 22 October 2022, in Brussels, and included a Representation Committee consisting of members of the PARE, of which van Dam is an associate.

The award was based on strides made by ASASA towards improving the quality of life of people living with AxSpa, as well as training done to build awareness in the medical fraternity around AxSpA in the country. With 36 posters entered into the awards by organisations across the globe, ASASA came out tops.

When asked about the award, van Dam said, “This was a real honour to represent South Africa at PARE. 2022 is also the first year that an African country was invited to attend PARE. Winning this award sheds light on our country and our unique problems. The delay to diagnosis of 10.8 years is just unacceptable. The access to the correct medication in both the private and public sector is also not sufficient for a debilitating, progressive disease that can lead to disability if left untreated.”

ASASA estimates that there are approximately 160 000 people suffering from the AxSpA in South Africa, with many of these sufferers undiagnosed. ASASA has made significant strides this year in the training of over 100 General Practitioners and over 250 optometrists around AxSpA diagnosis and the effects it can have on other parts of the body, like the eyes. In addition, ASASA, along with other partners, assisted in gathering data from South African respondents in the first ever live patient survey, called the International Map of Axial Spondyloarthritis (IMAS) survey, which is run by the Axial Spondyloarthritis International Federation that surveys people diagnosed with AxSpA and assesses the impact and burden that AxSpA has on the lives of patients, from their perspective.

Van Dam concluded, “There is still a lot we can do in South Africa and ASASA is busy growing its team of volunteers to help to build awareness around AxSpA in the country. We aim to continue to build support structures for patients in the country, as well as continually working with the medical fraternity, assisting with early diagnosis and access to treatment.”

A New Pacemaker that Works with Light, not Electricity

Pacemakers regulate the heartbeats of people with chronic heart diseases like atrial fibrillation and other forms of arrhythmia. However, pacemaker implantation is an invasive procedure, and the lifesaving pacing the devices provide can be extremely painful. Pacemakers also can only be used to treat a few specific types of disease.

In Science Advances, researchers describe their new pacemaker design that uses light and optogenetics that could be implanted with a less invasive procedure, also causing less pain in operation. As well as triggering cardiac neurons with light, the new design can also be powered by light, removing the need for a battery which has to be surgically replaced.

The study was helmed by researchers in the Gutruf Lab, led by biomedical engineering assistant professor and Craig M. Berge Faculty Fellow Philipp Gutruf.

Currently available pacemakers work by implanting one or two leads, or points of contact, into the heart with hooks or screws. If the sensors on these leads detect a dangerous irregularity, they send an electrical shock through the heart to reset the beat.

“All of the cells inside the heart get hit at one time, including the pain receptors, and that’s what makes pacing or defibrillation painful,” Gutruf said. “It affects the heart muscle as a whole.”

The device Gutruf’s team has developed, yet to be tested in humans, would use a digitally created mesh that would send much more targeted signals.

Modifying cardiac neurons to respond to light

Optogenetics modifies cells, usually neurons, to make them responsive to light. This technique only targets cardiomyocytes, the cells of the muscle that trigger contraction and make up the beat of the heart. This precision will not only reduce pain for pacemaker patients by bypassing the heart’s pain receptors, it will also allow the pacemaker to respond to different kinds of irregularities in more appropriate ways. For example, during atrial fibrillation, the upper and lower chambers of the heart beat asynchronously, and a pacemaker’s role is to get the two parts back in line.

“Whereas right now, we have to shock the whole heart to do this, these new devices can do much more precise targeting, making defibrillation both more effective and less painful,” said Igor Efimov, professor of biomedical engineering and medicine at Northwestern University, where the devices were lab-tested. “This technology could make life easier for patients all over the world, while also helping scientists and physicians learn more about how to monitor and treat the disease.”

To ensure the light signals can reach many different parts of the heart, the team created a design that involves encompassing the organ, rather than implanting leads that provide limited points of contact.

The new pacemaker model consists of four petallike structures made of thin, flexible film, which contain light sources and a recording electrode. The petals, specially designed to accommodate the way the heart changes shape as it beats, fold up around the sides of the organ to envelop it, like a flower closing up at night.

“Current pacemakers record basically a simple threshold, and they will tell you, ‘This is going into arrhythmia, now shock!'” Gutruf said. “But this device has a computer on board where you can input different algorithms that allow you to pace in a more sophisticated way. It’s made for research.”

Because the system uses light to affect the heart, rather than electrical signals, the device can continue recording information even when the pacemaker needs to defibrillate. In current pacemakers, the electrical signal from the defibrillation can interfere with recording capabilities, leaving physicians with an incomplete picture of cardiac episodes. Additionally, the device does not require a battery, which could save pacemaker patients from needing to replace the battery in their device every five to seven years, as is currently the norm.

Gutruf’s team collaborated with researchers at Northwestern University on the project. While the current version of the device has been successfully demonstrated in animal models, the researchers look forward to furthering their work, which could improve the quality of life for millions of people.

Source: University of Arizona

Women with Autism have a Greater Mental Illness Risk

Mirror symbolising schizophrenia
Source: Vince Fleming on Unsplash

Autistic young men and women are more affected by psychiatric conditions and have an increased risk of hospitalisation as a result of their mental illness. Autistic women are particularly vulnerable, as shown in a study published in JAMA Psychiatry.

Autistic people have an increased risk of suffering from mental illness. Current data indicates that autistic women are more vulnerable than autistic men, but few studies have been able to establish that there are sex differences.

The researchers, from Karolinska Institutet, conducted a register-based cohort study with more than 1.3 million people in Sweden who were followed from the age of 16 to 24 between 2001 and 2013. Just over 20 000 of these were diagnosed with autism.

“We saw an increased risk of eleven different psychiatric conditions, including depression, anxiety disorders, self-harm and difficulty sleeping,” says Miriam Martini, a doctoral student in psychiatric epidemiology at Karolinska Institutet and first author of the study.  

High hospitalisation rates 

Something that Miriam Martini finds particularly worrying is that 32 out of 100 autistic women had been hospitalised as a result of their mental illness, compared with 19 out of 100 autistic men. For non-autistic people, the corresponding figure was less than five out of 100.   

The study focuses on young adults who are at a crucial time in their life when many mental health problems increase, while the transition to adulthood often means poorer access to care, says Miriam Martini.   

“Healthcare for young adults needs to be expanded, especially for autistic women, so that mental illness can be detected in time to avoid worsening of symptoms resulting in hospitalization,” says Miriam Martini.  

The reason why autistic women are more affected by mental illness than autistic men is not clear, but in the study, the researchers point to several possible factors. Previous research has shown that autistic women to a greater extent use compensatory behaviours to camouflage their autism, which may be due to the fact that women generally tend to adapt to the expectations of those around them. This delays diagnosis and the provision of assistance, which can negatively affect their mental health.  

Overlooked by the healthcare system 

Another possible explanation may be that it could be difficult to detect autism in women using diagnostic criteria.  

“It may be that autism manifests differently in women than in men, which means that women are not detected using today’s diagnostic criteria. This is something we need to do more research on,” says Miriam Martini.  

Source: Karolinska Institutet