Parkinson’s disease is induced by neuronal damage due to excessive production of reactive oxygen species. Suppression of reactive oxygen species generation is essential because it is fatal to dopaminergic neurons that manage dopamine neurotransmitters. Currently, only symptomatic treatment is available, so the development of treatment regimens and prevention methods is necessary.
Fortunately, Associate Professor Akiko Kojima-Yuasa of Osaka Metropolitan University’s Graduate School of Human Life and Ecology led a research group that has verified the physiological effect of Ecklonia cava polyphenols, seaweed antioxidants, on the prevention of Parkinson’s disease.
In this study, published in the journal Nutrients, two types of motor function tests were conducted using Parkinson’s disease model mice that were orally fed the antioxidants daily for one week and then administered rotenone. Results showed that motor function, which was decreased by rotenone, was restored. There was also improvement in intestinal motor function and the colon mucosa structure, a special tissue that covers the colon.
Further, cellular experiments using Parkinson’s disease model cells verified the biochemical interaction of the preventive effect of Ecklonia cava. Validation results showed that the antioxidants activate the AMPK enzyme (adenosine monophosphate-activated protein kinase), an intracellular energy sensor, and inhibit the production of reactive oxygen species that cause neuronal cell death.
“This study suggests that Ecklonia cava antioxidants may reduce neuronal damage by AMPK activation and inhibiting intracellular reactive oxygen species production,” stated Professor Kojima-Yuasa. “It is hoped that Ecklonia cava will be an effective ingredient in the prevention of Parkinson’s disease.”
A recent randomised clinical trial published in Developmental Medicine & Child Neurology assessed whether injections of botulinumtoxin-A in calf muscles benefit children with cerebral palsy.
“We hypothesised that injections with botulinumtoxin-A in the calf muscles would make walking easier, caused by improved ankle joint functioning following spasticity reduction,” the authors wrote.
In the trial, one botulinumtoxin-A treatment was not superior to placebo in making walking easier (measured as a reduction in energy cost or improved walking capacity); however, there was some evidence of a delayed improvement in energy cost. Moreover, there was some evidence of a decrease in calf pain intensity. No serious adverse events related to botulinumtoxin-A treatment were recorded.
Pneumonia diagnoses are marked by pronounced uncertainty, according to an AI-based analysis of over 2 million hospital visits. The study, published in Annals of Internal Medicine, found that more than half the time, a pneumonia diagnosis made in the hospital will change from a patient’s entrance to their discharge – either because someone who was initially diagnosed with pneumonia ended up with a different final diagnosis, or because a final diagnosis of pneumonia was missed when a patient entered the hospital (not including cases of hospital-acquired pneumonia).
Understanding that uncertainty could help improve care by prompting doctors to continue to monitor symptoms and adapt treatment accordingly, even after an initial diagnosis.
Barbara Jones, MD, pulmonary and critical care physician at University of Utah Health and the first author on the study, found the results by searching medical records from more than 100 VA medical centres across the country, using AI-based tools to identify mismatches between initial diagnoses and diagnoses upon discharge from the hospital. More than 10% of all such visits involved a pneumonia diagnosis, either when a patient entered the hospital, when they left, or both.
“Pneumonia can seem like a clear-cut diagnosis,” Jones says, “but there is actually quite a bit of overlap with other diagnoses that can mimic pneumonia.” A third of patients who were ultimately diagnosed with pneumonia did not receive a pneumonia diagnosis when they entered the hospital. And almost 40% of initial pneumonia diagnoses were later revised.
The study also found that this uncertainty was often evident in doctors’ notes on patient visits; clinical notes on pneumonia diagnoses in the emergency department expressed uncertainty more than half the time (58%), and notes on diagnosis at discharge expressed uncertainty almost half the time (48%). Simultaneous treatments for multiple potential diagnoses were also common.
When the initial diagnosis was pneumonia, but the discharge diagnosis was different, patients tended to receive a greater number of treatments in the hospital, but didn’t do worse than other patients as a general rule. However, patients who initially lacked a pneumonia diagnosis, but ultimately ended up diagnosed with pneumonia, had worse health outcomes than other patients.
A path forward
The new results call into question much of the existing research on pneumonia treatment, which tends to assume that initial and discharge diagnoses will be the same. Jones adds that doctors and patients should keep this high level of uncertainty in mind after an initial pneumonia diagnosis and be willing to adapt to new information throughout the treatment process. “Both patients and clinicians need to pay attention to their recovery and question the diagnosis if they don’t get better with treatment,” she says.
Products containing potentially hepatotoxic botanical ingredients are being widely consumed in the US, according to a study from University of Michigan researchers. The study, which was published in JAMA, examined national survey data from 2017–2020 and found that over a 30-day period, 4.7% of the adults surveyed 2020 took herbal and dietary supplements containing at least one of the hepatotoxic botanicals selected for the study.
Over 80 000 herbal and dietary supplement (HDS) products are available for purchase without a prescription for the purposes of promoting general health and treating minor ailments, and are largely unregulated. Most of these are products such as multivitamins, with well-defined ingredients on the label. But an estimated 5% to 12% of HDS products are plant-derived, complex multi-ingredient botanicals, some of which have been shown to have hepatotoxic properties. These included products containing turmeric, green tea, ashwagandha, black cohosh, garcinia cambogia, and red yeast rice.
Lead author Alisa Likhitsup, MD, MPH, clinical assistant professor of Medicine at U-M spoke about the motivation for the study. “Our interest started when we saw cases of liver toxicity from herbal and dietary supplement use in people enrolled into the ongoing NIH-funded DILIN study,” Likhitsup said.
“But it was difficult to say how many people were using these supplements and why. The major finding here is the large number of Americans taking these products with an estimated 15 million adult Americans taking them on a regular basis.”
Supplements are of particular concern for the researchers for several interrelated reasons: lack of government regulation, insufficient attention in medical screenings, and frequent mislabelling.
“In a previous study, we found that there was a great deal of mislabelling of some of these products,” said senior author Robert Fontana MD, U-Me hepatologist, professor of medicine.
“We performed analytical chemistry and found about a 50% mismatch between stated ingredients on the label and what they actually contained, which is quite alarming. If you buy a supplement and it says it has a certain ingredient, it’s basically a coin flip if that’s true or not.”
The mislabelling comes about from a lack of regulation, and since the effects are poorly understood, patients are not often asked what supplements they are taking.
Another study had found a 70% increase in liver transplants due to injury caused by supplements from 2010–2020, compared to 1994–2009.
“We weren’t aware that so many people were taking these supplements,” said Likhitsup, a transplant hepatologist.
“So, when doctors see patients in the office, they don’t necessarily ask about supplement use or take into consideration their effects.”
In the studied population, the highest proportion of people consumed turmeric (3.46%), followed by green tea (1.01%), ashwagandha and black cohosh (0.38%), garcinia cambogia (0.27%), and red yeast rice products (0.19%). Most of the users did not start consuming the botanicals on doctor’s advice, instead it was their own accord. They most commonly cited reason was the improvement or maintenance of health.
Of the turmeric users, 26.8% consumed the products specifically for supposed benefits for joint health or arthritis, while 27.2% of the green tea users were hoping to improve their energy levels.
The majority of the garcinia cambogia users hoped it would help them lose weight.
The JAMA study was not able to establish any kind of causal relationship between consumption of the six botanicals and liver injury since it was intended to assess supplement exposure in the general US population. Given the lack of regulation, however, the researchers still hope to make clinicians and patients aware of just how much is still unknown about these supplements.
“We’re not trying to create alarm,” Fontana said.
“We’re just trying to increase awareness that the over-the-counter supplements people are taking and buying have not been tested nor necessarily proven to be safe.”
Shared geographic origin between TB strain and human host could amplify risk for infection
Tuberculosis bacteria. Credit: CDC
For some forms of tuberculosis, the chances that an exposed person will get infected depend on whether the individual and the bacteria share a hometown, according to a new study comparing how different strains move through mixed populations in cosmopolitan cities.
Results of the research, led by Harvard Medical School scientists and published in Nature Microbiology, provide the first hard evidence of long-standing observations that have led scientists to suspect that pathogen, place, and human host collide in a distinctive interplay that influences infection risk and fuels differences in susceptibility to infection.
The study strengthens the case for a long-standing hypothesis in the field that specific bacteria and their human hosts likely coevolved over hundreds or thousands of years, the researchers said.
The findings may also help inform new prevention and treatment approaches for tuberculosis.
In the current analysis, believed to be the first controlled comparison of TB strains’ infectivity in populations of mixed geographic origins, the researchers custom built a study cohort by combining case files from patients with TB in New York City, Amsterdam, and Hamburg. Doing so gave them enough data to power their models.
The analysis showed that close household contacts of people diagnosed with a strain of TB from a geographically restricted lineage had a 14 percent lower rate of infection and a 45 percent lower rate of developing active TB disease compared with those exposed to a strain belonging to a widespread lineage.
The study also showed that strains with narrow geographic ranges are much more likely to infect people with roots in the bacteria’s native geographic region than people from outside the region.
The researchers found that the odds of infection dropped by 38 percent when a contact is exposed to a restricted pathogen from a geographic region that doesn’t match the person’s background, compared with when a person is exposed to a geographically restricted microbe from a region that does match their home country. This was true for people who had lived in the region themselves and for people whose two parents could each trace their heritage to the region.
This pathogen-host affinity points to a shared evolution between humans and microbes with certain biological features rendering both more compatible and fueling the risk for infection, the researchers said.
“The size of the effect is surprisingly large,” said Maha Farhat, the Gilbert S. Omenn, MD ’65, PhD Associate Professor of Biomedical Informatics in the Blavatnik Institute at HMS. “That’s a good indicator that the impact on public health is substantial.”
Why differences matter
Thanks to the growing use of genetic sequencing, researchers have observed not all circulating strains are created equal. Some lineages are widespread and responsible for much of the TB around the world, while others are prevalent only in a few restricted areas. Given that the complex nature of TB transmission in high-incidence settings where people often have multiple exposures to different lineages, researchers have not been able to compare strains under similar conditions and have been left to speculate about possible explanations for the differences between strains.
Many factors increase the risk of contracting tuberculosis from a close contact. One of the best predictors of whether a person will infect their close contacts is bacterial load, measured by a test called sputum smear microscopy, which shows how many bacteria a person carries in their respiratory system.
But the new study showed that for geographically restricted strains, whether a person has ancestors who lived where the strain is common was an even bigger predictor of infection risk than bacterial load in the sputum. In the cases analyzed in the study, this risk of common ancestry even outweighed the risk stemming from having diabetes and other chronic diseases previously shown to render people more susceptible to infection.
The findings add to a growing body of evidence of the importance of paying attention to the wide variation between different lineages of tuberculosis and to the details of how different lineages of tuberculosis interact with different host populations.
Previous studies have shown that some genetic groups of TB are more prone to developing drug resistance and that TB vaccines appear to work better in some places than others. There is also evidence that some treatment regimens might be better suited to some strains of TB than others.
“These findings emphasize how important it is to understand what makes different strains of TB behave so differently from one another, and why some strains have such a close affinity for specific, related groups of people,” said Matthias Groeschel, research fellow in biomedical informatics in Farhat’s lab at HMS; resident physician at Charité, a university hospital in Berlin; and the study’s first author.
In addition to the analysis of clinical, genomic, and public health data, the researchers also tested the ability of different strains of TB to infect human macrophages, a type of immune cell that TB hijacks to cause infection and disease. The researchers grew cells from donors from different regions. Once again, cell lines from people with ancestry that matched the native habitat of a restricted strain of tuberculosis bacteria were more susceptible to the germs than cells from people from outside the area, mirroring the results of their epidemiologic study.
Until now, most experiments of the interaction between human immune cells and TB have not compared how TB interacts with cells of hosts from different populations or places, the researchers said.
While this experiment was not designed to capture insights about the mechanism underlying the affinity between human and TB populations sharing geographic backgrounds, it highlights the importance of using multiple strains of TB and cells from diverse populations to inform treatment and prevention. It also points to the need for more basic research to understand the genomic and structural differences in how bacterial and host cells interface, the researchers said.
“It’s so important to appreciate that the great diversity of human and tuberculosis genetics can significantly impact how people and microbes respond to one another and to things like drugs and vaccines,” Farhat said. “We have to incorporate that into the way we think about the disease.”
“We’re at the very beginning of appreciating the importance of that diversity,” Groeschel said. “There’s so much more to learn about how it might impact the efficacy of drugs, vaccines, and the course that disease takes in different strains.”
Advances in gene sequencing create a new puzzle
While the closely related but distinct genetic groups of tuberculosis were discovered with more traditional methods of genotyping, the widespread use of whole genome sequencing by public health departments around the world allowed doctors and researchers to better profile TB germs and track outbreaks and drug resistance genetically.
The realization that highly localised stains didn’t spread well to other regions led researchers to speculate that regionally constrained strains were less infectious than widespread strains. Since the constrained strains persisted within their limited ranges, some researchers speculated that localised populations of the bacteria may have coevolved with their human hosts, making different human populations more susceptible to different types of TB. This could also mean, researchers hypothesised, that different strains of TB would have different susceptibility to different treatments and vaccines. For example, structural differences in the shape of the bacteria might prevent some drugs from binding effectively with bacteria from different strains.
Until recently, these hypotheses were nearly impossible to test, given the differences between cultural and environmental conditions that might affect infection rates in different communities and other parts of the world. Furthermore, the fact that the constrained stains strayed from home so rarely made it challenging to gather enough data to measure differences across strains.
Multidisciplinary science cracks the case
To overcome these obstacles, the research team collaborated with public health departments and research teams from the U.S., the Netherlands, and Germany to assemble a massive database integrating tuberculosis case reports, pathogen genetic profiles, and public health records of infection rates among close contacts. The analysis also incorporated demographic details about the social networks of infected people to assess how the different genetic lineages of tuberculosis spread in other populations. In total, the study included 5256 TB cases and 28 889 close contacts.
“This study is a great example of why it’s so important for researchers to collaborate with many different kinds of partners,” said Groeschel. “We were able to merge public health data from three big cities and use the powerful computational biology tools that we have access to in academic medicine to answer a complicated question that has important implications for public health and evolutionary biology, vaccine development, and drug research.”
