Day: October 28, 2022

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