It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Wednesday, December 06, 2023
What smoking does to oral bacteria
A study shows the effects of cigarette use and what happens when you stop
The father of Biotechnologist Giacomo Antonello, a dentist, sometimes amazed patients with his seemingly clairvoyant diagnostic abilities: one look in their mouth and he would advise them to see a specialist, because, he explained, they might have a problem with their heart or diabetes. He often turned out to be correct. While his patients were always very impressed, for experts, the dentist’s diagnoses were justified: empirical studies show that there is often a connection between periodontitis and various cardiovascular diseases, even if the exact mechanisms are not fully understood. Giacomo, who is currently conducting research for his PhD at the Institute of Biomedicine, has now just completed a study with colleagues at the Eurac Research Institute for Biomedicine that points to one possible factor: in people who smoke, the alteration of the healthy community of oral bacteria could contribute to the increased risk of these diseases.
The study, which was conducted as part of the CHRIS study in Val Venosta, asks two central questions: What exactly happens to the bacterial community in the mouth, the so-called oral microbiome, when we smoke? And what effect does quitting have on these same communities?
To find out, the research team in Bolzano, together with epidemiologist Betsy Foxman from the University of Michigan, analyzed saliva samples from more than 1600 people – a huge number of subjects for this research field, as bioinformatician Christian Fuchsberger, Giacomo’s doctoral advisor, emphasizes: “There are hardly any large studies on the salivary microbiome. This is a young research field in which a lot is happening right now and one in which not everything is conducted so clearly. Many of the current studies are working with very small numbers of cases, for example, which means their results are not broadly applicable.”
Microbiome research is a fairly young field: just a few decades ago, the communities of trillions of microorganisms that live on and in humans – mostly in the digestive tract – were considered of little significance by scientists. Now, the microbiome is taking center stage and is recognized to be of massive importance to our development and health. The intestinal microbiome is the subject of intensive research with a major study currently underway at the Institute of Biomedicine (see box).
Compared to the microbial density of the intestine, where thousands of strains of different bacteria live, our mouth is only sparsely populated. However, saliva has a particular advantage for studies: it is relatively easy to sample. Researchers can therefore acquire the data they need to investigate whether it is possible to identify changes in the oral flora (biomarkers) that indicate certain diseases, which, if found, could provide a valuable diagnostic tool that healthcare systems could easily employ.
In the CHRIS Study’s examination, CHRIS participants were requested to spit 5 milliliters of saliva into a special collection tube. The participants were divided into groups according to whether they were current smokers, had stopped smoking, or had never started. Those who had quit were asked exactly when they had quit, and those who still smoked were asked about the number of cigarettes they smoked per day. To get a picture of the microbial community in each mouth – which species were represented and at what frequency – the research team employed a universally used technology for identifying bacteria, namely sequence analysis of the 16S rRNA gene, a gene which represents something like an “identity card” for each different species.
Giacomo’s research using the microbiome data collected in the CHRIS Study showed clear results. People who have never smoked carry a significantly different microbial community in their mouths than people who still smoke or have recently given up. Cigarette consumption primarily affects the bacteria that need oxygen:aerobic bacteria. The number of these bacteria decreases continuously the more cigarettes one smokes; if one stops smoking, these aerobic bacteria gradually increase again. And the longer the smoke-free period, the more aerobic bacteria are found in the saliva. Only after five years of not smoking are former smokers indistinguishable, in terms of aerobic bacteria in their oral microbiome, from people who have never smoked. “We have observed that the effects of smoking persist for years,” Fuchsberger says. “So then, of course, it’s interesting to ask whether these effects are related to certain diseases.”
Smokers are known to have an increased risk of both periodontitis and cardiovascular disease. Could the changes in the oral microbiome caused by cigarettes use play a role in this? This is where a function of the bacteria that live in the mouth comes into play, and like everything to do with our microbiome, it has been receiving increasing attention for some time – some of these bacteria, mainly aerobic ones, convert the nitrate we ingest with food into nitrite, which then become nitric oxide. Nitric oxide is an important substance for regulating blood pressure, among other things. If too little nitric oxide is available, this could contribute to poorly perfused gums and cardiovascular disease. Now, the study in theVenosta valley did not measure nitric oxide in saliva, but it did examine the microbes in it; all the research team can say, therefore, is that the more the subjects smoked, the fewer nitrate-reducing bacteria lived in their mouths. That this could be an additional explanation for why smokers have a higher risk of periodontal disease and cardiovascular disease is “a hypothesis that needs to be tested in further studies,” Giacomo emphasizes.
He is already pursuing the next question based on the CHRIS samples. Namely, what are some of the other factors that influence our oral flora and to what extent? What role does genetics play, and what role do the people we share households with also play? He will only be able to answer this question in about a year’s time, but one thing is already very clear: who we live with is very important.
Ransomware attacks can paralyse organisations or entire countries by hacking into a network and encrypting critical data. The attackers then demand a ransom; if their demands aren’t met, the data will not be decrypted and may be lost forever. Depending on the given situation, the financial and logistical damage can be enormous. In January 2022, the International Committee of the Red Cross (ICRC) was the victim of a cyberattack. Data belonging to more than 500,000 people around the world was stored on the affected servers. This included data on people who needed special protection, such as missing persons, refugees from war zones and prisoners. “The ICRC’s digital infrastructure has grown considerably in recent years – and so has the number of cyberattacks on our systems,” says Mauro Vignati, Adviser Digital Technologies of Warfare at the ICRC. Particularly during wars and armed conflicts, such cyberattacks could also have catastrophic humanitarian consequences, for example if the digital infrastructure of a hospital is paralysed by the enemy.
Trusted emblem for protection against attacks
For conflicts beyond cyberspace, the ICRC has employed protective emblems since the Geneva Conventions of 1949, the core of international humanitarian law. The red cross, red crescent and red crystal provide protection for hospitals, vehicles and employees of organisations in the International Red Cross and Red Crescent Movement network (including the ICRC). Today, the network has over 80 million members who are active in 192 countries. As a matter of principle, bearers of these emblems are protected by international humanitarian law, especially in conflicts. Warring parties are not allowed to attack them. “That’s why we’ve been wondering for some time whether we could also develop an emblem to protect our digital infrastructure,” Vignati says. Such a system would have to fulfil a number of requirements: “It should be easy and cost-effective to integrate into existing digital systems worldwide and easy to maintain. It would also have to bridge linguistic, technological and cultural differences.” What’s more, the emblem ought to be as flexible as possible. In certain situations, it’s important for ICRC staff to mask the emblem, Vignati says.
Three years ago, the ICRC contacted the Centre for Cyber Trust, a research collaboration between ETH Zurich and the University of Bonn in the field of cybersecurity, with this idea of establishing a digital emblem. One of the people working on this since then is Felix Linker, who is currently writing his doctoral thesis in the group led by David Basin, Professor of Information Security at the Department of Computer Science at ETH Zurich. “A digital emblem has a unique combination of security requirements, namely authenticity, accountability and a property that we call covert inspection,” Linker says. The Authentic Digital EMblem (ADEM), which he has developed together with Basin, is based on the web PKI and CT ecosystem (Web PKI and CT stand for Web Public Key Infrastructure and Certificate Transparency). “We rely on existing best practices on the internet. What makes our work innovative is how we’ve combined different solutions to meet the technical requirements,” Linker says. In an article recently published in the Proceedings of the 2023 ACM SIGSAC Conference on Computer and Communications Security, Linker and Basin describe in detail for the first time how ADEM works.
Machine-readable and decentralised
The emblem they have developed is cryptographically secured using a digital signature – a long sequence of bits that can be read by a program developed for this purpose. This makes it possible to retrieve information about the owner, the IP or domain worthy of protection, as well as the publisher of the emblem. “It’s important that the emblem can be read by machines, because most cyberattacks today are automated,” Linker says. In other words, hacker software needs to automatically load and read the emblem, so it can recognise that it is accessing a system belonging to an organisation that is protected by international humanitarian law. And that needs to happen during the software’s first reconnaissance, before it does any damage to the system.
Another key requirement is for the digital emblem to be managed in a decentralised way rather than by a central authority. States that are committed to international humanitarian law should be able to verify that a certain digital infrastructure on their territory is entitled to protection and therefore bears an emblem. To this end, ADEM is based on an open standard, so governments can adapt the emblem’s implementation as flexibly as possible to their own requirements.
Hackers remain undetected
Potential attacks on servers and networks can come from hacker groups, but also from states during a war. These want to remain undetected at all costs. “That’s why attackers must be able to view the emblem without either the protected institution or the issuer of the digital signature being able to tell that the emblem has been looked at.” Only then will potential attackers be prepared to have their systems run the scanner for detecting the emblem. “Standard internet authentication protocols aren’t suitable for this because they require interaction between the two parties involved,” Linker says. “That attracts attention, which means it won’t work in a conflict.” He managed to come up with a combination of suitable internet protocols (UDP, TLS and DNS) to mask the distribution of the emblem.
Linker has now evaluated the system in a security analysis under a comprehensive threat model. His evaluation shows that the digital emblem cannot be misused by attackers and acts as a security guarantee. He says that this provides proof of concept. He is now developing the first prototypes further, while colleagues from the Centre for Cyber Trust in Bonn will conduct interviews with hackers to find out how willing people are to respect such an emblem. After all, only then will they bother to run a program that can recognise emblems. But this is something Linker is confident about: in the past, hackers have been known to avoid humanitarian targets on occasion, “for ethical reasons or simply to avoid attracting too much attention.”
Difficult legal implementation
Vignati from the ICRC is satisfied: “ADEM fulfils all our original requirements for a digital emblem.” The main task now is to further optimise the emblem’s visibility to potential attackers. However, it will probably be several years before the digital emblem actually starts helping to protect the ICRC’s critical digital infrastructure and hospitals in war zones. “The legal implementation is very challenging,” Vignati says. Implementing the emblem in the legal framework calls for adjustments to the Geneva Conventions: “Either through a new additional protocol or through an addition to the existing protocols.” The ICRC plans to showcase ADEM, along with another system designed at John Hopkins University, at an international humanitarian law conference to be held in October 2024. It will also present legal pathways for bringing the digital emblem into operation. “That would be an important first step in strengthening humanitarian protection in cyberspace,” Vignati says.
Blood tests are a common, yet often painful, step in health care. But what if we could skip the needles altogether? Saliva and blood contain many of the same biomarkers, and collecting spit is as simple as drooling into a container. Researchers reporting in ACS Sensors have developed a device that detects glucose and adenosine monophosphate (AMP) biomarkers in saliva with high sensitivity, which could help make at-home health monitoring easier and without a poke.
Blood tests provide critical information about a person’s health. But they also rely on uncomfortable procedures, ranging from collecting small blood samples through frequent finger pricks to blood draws from a trained phlebotomist. Saliva has been explored as an alternative way to track important biomarkers, including glucose. However, most methods for analyzing saliva samples for small molecules require laboratory equipment. To make the analyses convenient for at-home testing, a simple, yet accurate, sensing platform is needed. One possibility is the electrochemical aptamer-based (E-AB) biosensor, which produces a measurable, electrochemical change when a specially designed piece of DNA or RNA, known as an aptamer, binds to its desired target. This type of device has previously been used on blood samples, but this time, Philippe Dauphin-Ducharme and colleagues adapted E-AB biosensors for saliva samples. The team wanted to measure the concentration of glucose and AMP — a small molecule biomarker associated with gum disease — in real saliva specimens.
The team took previously reported DNA aptamers that bound to either AMP or glucose, then re-engineered them to improve their sensitivity. They created their E-AB biosensors by mounting the aptamers on a gold electrode. Saliva samples were collected from a group of participants and pooled together. The sensors were then immersed in the saliva, with no additional preparation steps or reagents needed. This simplicity makes the test easy enough to be performed by a patient in their home. In experiments, the researchers found that their devices returned a result within 30 seconds, remained stable in undiluted saliva for up to three days and retained sensitivity for up to a week, if washed after each use. Additionally, the glucose sensor shows high selectivity towards its target, and both the AMP and glucose sensors are sensitive enough to detect the biomarkers at much lower concentrations than typically found in saliva. The researchers say that this simple technology is the first of its kind to detect glucose in human saliva, and they hope it can make at-home health monitoring less invasive and easier to complete, especially for people with chronic diseases such as diabetes.
The authors acknowledge funding from Colgate-Palmolive Company and the Alliance Grant program of the Natural Sciences and Engineering Research Council of Canada. Some authors are employees of Colgate-Palmolive’s Research and Development Center.
The authors have patents pending on this technology.
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TOP: A PERSON IS INFECTED BY THE ALPHA VARIANT OF SARS-COV-2. WITHIN A FEW WEEKS, ANTIBODIES ARE MADE THAT PROTECT THE PERSON AGAINST THE ALPHA VARIANT AS WELL AS BETA AND GAMMA VARIANTS WHICH ARE VERY SIMILAR TO THE ALPHA VARIANT. BOTTOM: A PERSON WHO (1) HAS RECOVERED FROM COVID-19 AND WHO (2) HAS RECEIVED MRNA VACCINE WITH COMPONENTS OF THE ALPHA VARIANT DEVELOPS A STRONG IMMUNE RESPONSE WITHIN A FEW WEEKS. THE ANTIBODIES THAT ARE MADE IN THE BODY PROTECT AGAINST THE ALPHA VARIANT, THE CLOSELY RELATED BETA AND GAMMA VARIANTS AS WELL AS THE MORE DISTANTLY RELATED DELTA AND OMICRON VARIANTS. PEOPLE WHO HAVE RECOVERED FROM COVID-19 AND THEN RECEIVED THE MRNA VACCINE ARE ALSO PROTECTED AGAINST NEW VARIANTS OF SARS-COV-2. ILL: GERDA KAYNOVA
“Vaccines help boost the production of antibodies, providing effective protection against serious illness and death,” says Mona Høysæter Fenstad.
Fenstad is a senior consultant at the blood bank at St. Olavs Hospital in Trondheim.
We are already well into autumn, and the COVID-19 virus is rife all over Norway. The Norwegian Institute of Public Health recommends people in risk groups to get vaccinated.
They point out that elderly people in particular will be vulnerable to serious illness if they are infected with COVID-19. However, since the vast majority of us have already had COVID-19 at least once, do we really need to think about getting vaccinated?
Yes, say the scientists.
“The saying ‘what doesn’t kill you makes you stronger’ is not true in this context. The inflammation that occurs in the body during infections such as influenza, COVID-19 and pneumonia can be harmful. Especially for people with heart or lung disease, or where other risk factors are involved,” says Fenstad.
Searching for medicine to combat COVID-19
Fenstand and her international colleagues have recently published a study that looked at the effect of vaccination on people who became ill with COVID-19 before vaccines were available. This work has been closely linked to the search for antibodies that can be used as medicine against COVID-19.
“At the beginning of 2020, the World Health Organization (WHO) asked scientists and therapists around the world to look for treatments for COVID-19. Among the treatments proposed was ‘convalescent plasma therapy’, which uses plasma from blood donors who have recovered from the illness. Along with colleagues from NTNU (the Norwegian University of Science and Technology), we chose to take a closer look at how the antibodies in this plasma were able to neutralize new virus variants that emerged,” says Fenstad.
While big pharmaceutical companies were working hard to develop vaccines and medicines, scientists had already begun to look at the use of blood plasma from COVID-19 patients as a possible treatment.
“Many of these patients had large amounts of antibodies in their blood. Plasma containing these antibodies was therefore given to seriously ill patients to help them fight the virus. It turned out that convalescent plasma therapy was primarily effective in patients who had immunodeficiencies,” says Fenstad.
A constantly changing virus
“We were looking for so-called ‘super-neutralizers’, people who develop specific antibodies that effectively neutralize different variants of SARS-CoV-2,” says Denis Kainov, a professor in NTNU’s Department of Clinical and Molecular Medicine who was part of the research team.
These antibodies were eventually cultivated and cloned, and then turned into medicines used to fight COVID-19.
In Norway, the first COVID-19 outbreak occurred in February 2020. The first Alpha variant was quickly followed by new, mutated variants named Beta and Delta. Omicron, which is currently the prevailing variant, was first reported in late 2021.
By April 2020, blood banks across Norway had begun collecting blood plasma from patients who had recovered from COVID-19. At St. Olavs Hospital, 72 patients were selected for a more detailed study of the antibodies in their blood plasma.
“It turned out that half of these patients had serum containing antibodies that effectively neutralized the Beta variant,” says Kainov.
Found the dream patient
Kainov has been searching for active substances to use in the treatment of COVID-19 and other viral diseases.
He is now looking for antibodies that could provide wider protection, including against new COVID-19 variants that might emerge.
They noticed that four patients had antibodies that effectively neutralized the COVID-19 variant that was dominant in Trondheim at the time.
“We followed up by taking new samples from these patients and found that their antibodies also neutralized other COVID-19 variants. In fact, they were also effective on new virus variants,” says Kainov.
The conclusion is thus that it is a good idea to get vaccinated even if you have already had COVID-19 and even if the virus has mutated since the vaccine was made.
Out of the four patients, the scientists picked the one whose antibodies had been least effective against the Omicron variant. This patient had received their first vaccine dose four months after recovering from COVID-19. The efficacy of the vaccine was striking.
“The vaccine boosted the production of immune cells and antibodies against all tested variants of the virus, including Omicron,” says Kainov.
The virus is always one step ahead
Kainov’s colleagues in Estonia could then proceed with blood plasma from the patient, cloning and cultivating antibodies that neutralised COVID-19 viruses on a wide scale.
The results have also provided the scientists with useful knowledge about the effect of the vaccine on convalescents.
“When it comes to vaccines, it is always a race. The virus is always one step ahead, and the vaccines and medicines will never be completely up to date,” Fenstad said
“Our study is an in-depth study of just one patient, and it constitutes only a tiny piece of research in this field. However, large studies in other countries confirm our findings. Vaccines boost the production of antibodies that are also effective against new variants of the virus,” she said.
The finding demonstrate that it is a good idea to get vaccinated even if you have already had COVID-19 and even if the virus has mutated since the vaccine was made. It may not prevent you from being reinfected, but it will provide protection against serious illness and death.
“When you get sick with COVID-19, you develop antibodies, but the effects of these diminish and are gone after six to nine months. This is why people can get infected again and again by new variants of SARS-CoV-2. The virus mutates to avoid the immune response we have developed through previous infections or vaccines,” says Kainov.
That is why vaccination is important now that we are heading towards winter.
“The studies we have conducted here on COVID-19 patients are extremely important, because there will be new outbreaks of the virus. Almost seven million people have died from COVID-19. We must avoid getting into the same situation again,” says Kainov.
Boosted production of antibodies that neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following messenger RNA vaccination - a case study
Eye-safe laser technology to diagnose traumatic brain injury
Researchers from the University of Birmingham have designed and developed a novel diagnostic device to detect traumatic brain injury (TBI) by shining a safe laser into the eye.
Described in Science Advances, the technique is dramatically different from other diagnostic methods and is expected to be developed into a hand-held device for use in the critical ‘golden hour’ after traumatic brain injury, when life critical decisions on treatment must be made.
The device incorporates a class 1, CE marked, eye-safe laser and a unique Raman spectroscopy system, which uses light to reveal the biochemical and structural properties of molecules by detecting how they scatter light, to detect the presence and levels of known biomarkers for brain injury.
There is an urgent need for new technologies to improve the timeliness of TBI diagnosis, which is a leading cause of death worldwide. TBI is caused by sudden shock or impact to the head, which can cause mild to severe injury to the brain, and although it needs diagnosis and treatment as soon as possible to prevent further irreversible damage, it is hard to diagnose at the point of injury. Moreover, radiological investigations such as X-ray or MRI are very expensive and slow to show results.
Birmingham researchers, led by Professor Pola Goldberg Oppenheimer from the School of Chemical Engineering, designed and developed the novel diagnostic hand-held device to assess patients as soon as injury occurs. It is fast, precise and non-invasive for the patient, causing no additional discomfort, can provide information on the severity of the trauma, and will be suitable to be used on-site - at the roadside, on the battlefield or on the sports pitch - to assess TBI.
Professor Pola Goldberg Oppenheimer said: “Early diagnosis of TBI is crucial, as life-critical decisions on treatment must be made with the first ‘golden hour’ after injury. However current diagnostic procedure relies on observation by ambulance crews, and MRI or CT scans at a hospital – which may be some distance away.”
The device works by scanning the back of the eye where the optic nerve sits. Because the optic nerve is so closely linked to the brain, it carries the same biological information in the form of protein and lipid biomarkers. These biomarkers exist in a very tightly regulated balance, meaning even the slightest change may have serious effects on the ‘brain-health’. TBI causes these biomarkers to change, indicating that something is wrong.
Previous research has demonstrated the technology can accurately detect the changes in animal brain and eye tissues with different levels of brain injuries - picking up the slightest changes.1,2,3
The device detailed in the current paper detects and analyses the composition and balance of these biomarkers to create ‘molecular fingerprints’.
The current study details the development, manufacture, and optimisation of a proof-of-concept prototype, and its use in reading biochemical fingerprints of brain injury on the optic nerve, to see whether it is a viable and effective approach for initial ‘on the scene’ diagnosis of TBI.
The researchers constructed a phantom eye to test its alignment and ability to focus on the back of the eye, used animal tissue to test whether it could discern between TBI and non-TBI states, and also developed decision support tools for the device, using AI, to rapidly classify TBIs.
The device is now ready for further evaluation including clinical feasibility and efficacy studies, and patient acceptability.
The researchers expect the diagnostic device to be developed into a portable technology which is suitable for use in point-of-care conditions capable to rapidly determine whether TBI occurs as well as classify whether it is mild, moderate or severe, and therefore, direct triage appropriately and in timely manner.
C.B., M.C., R.J.B., J.J.S.R., and P.G.O. are inventors on patent application (US20220338788A1/WO2018/138488) submitted by the University of Birmingham that covers the device optical comments and engineering
More than $13M awarded to study childhood obesity interventions in rural and minority communities in Louisiana and Tennessee
Pennington Biomedical’s Amanda Staiano and Vanderbilt University Medical Center’s Bill Heerman are co-principal investigators on the research study
BATON ROUGE – Pennington Biomedical Research Center and Vanderbilt University Medical Center have received $13.8 million for five years of research funding from the Patient-Centered Outcomes Research Institute to study the ideal “dose” of behavioral interventions to treat childhood obesity in rural and minority communities across Louisiana and Tennessee.
Pennington Biomedical’s Amanda Staiano and Vanderbilt University Medical Center’s Bill Heerman are co-principal investigators on the randomized, multisite trial.
Despite ongoing efforts, childhood obesity rates have continued to increase over the last 10 years, with about 1 in 5 children across the U.S. affected by obesity. The prevalence of childhood obesity is higher among children who are underrepresented minorities and those who live in rural areas due to health disparities and limited access to interventions. Across the U.S., about 22 percent of Hispanic or Latin American and 20 percent of African American children have obesity compared to about 14 percent of white children. Additionally, obesity affects about 22 percent of children who live in rural areas.
Researchers in the Dose Childhood Obesity Trial will study the optimal duration of behavioral interventions, including number of sessions and length of sessions, which are best in treating childhood obesity among these groups.
“We know that one-size fits all approaches to treating childhood obesity don’t work. This trial is an opportunity to understand what works best and for whom,” said Heerman, associate professor of Pediatrics and a general pediatrician at Monroe Carell Jr. Children’s Hospital at Vanderbilt.
Researchers plan to enroll 900 parent-child pairs, with children ages 5 to 17 who have obesity and are from rural and minority communities in Tennessee and Louisiana, where childhood obesity rates are among the highest in the country. Underserved communities often have unequal access to evidence-based obesity interventions, contributing to the higher rates among these populations.
“With Louisiana ranking near the top on lists for both children and adults living with obesity, this is an important study for families in our state to be involved in,” Staiano said. “We are gaining momentum in helping with the obesity crisis with programs like the upcoming Greaux Healthy initiative and this new grant that will help expand access to evidence-based obesity treatments to families throughout Louisiana.”
Children are diagnosed with obesity if their body mass index is at or above the 95th percentile for their age and gender category. The long-term risks associated with childhood obesity include Type 2 diabetes, hypertension and heart disease.
Current American Academy of Pediatrics, or AAP, recommendations, on which Staiano helped author, call for children with obesity to receive an intensive behavioral intervention of 26 hours of face-to-face, family-based treatment over six months. These evidence-based behavioral and lifestyle interventions can include regular check-ins with primary care physicians, personalized nutrition plans, healthy learning modules and more.
“At Pennington Biomedical, our scientists are not only working on cutting-edge research to fight chronic diseases like obesity, but they are helping define the best practices for medical professionals to follow,” said Dr. John Kirwan, Pennington Biomedical executive director. Evidence has shown that obesity treatment should begin early and at the highest intensity necessary, and having Pennington Biomedical partner with Vanderbilt University Medical Center on this project will help so many families in both Louisiana and Tennessee as we learn more about various methods to treat childhood obesity.”
In the study, researchers will compare how different “dosing” combinations of face-to-face intervention time may be optimized to help reduce a child’s weight over 12 months and impact a child’s diet, physical activity, sleep, media use and quality of life. Specifically, they want to examine: is the intensity of the AAP-recommended 26 hours needed, or can a reduced-intensity behavioral intervention between 13 and 22 hours be effective in treating childhood obesity and increasing reach to underserved communities?
The parent-child pairs will be randomly assigned to one of five study arms (26, 22, 19, 16 and 13 hours) of the trial. The types of interventions for each arm will be the same and include primary care physician visits; on-demand web-based content that includes learning modules on topics such as choosing healthy foods, being an active family, the importance of sleep; community resource counseling with social or community health workers; and parent-child personalized nutrition services with certified nutritionists. The difference between the arms will be in the frequency and duration of the personalized nutrition counseling.
Speaking about the potential impact of this study, Heerman said, “By testing the optimal dose of behavioral interventions for childhood obesity, we hope to inform future treatment recommendations and build pragmatic solutions that can reach the millions of children with obesity in the United States.”
The research team and scientific advisory board includes researchers from Vanderbilt and Pennington Biomedical, representatives from the American Academy of Pediatrics, multiple international experts in childhood obesity interventions, and patient representatives.
The grant is awarded by PCORI, which is an independent, nonprofit organization authorized by Congress with a mission to fund patient-centered comparative clinical effectiveness research that provides patients, their caregivers and clinicians with the evidence-based information they need to make better informed health and health care decisions.
About the Pennington Biomedical Research Center The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the triggers of obesity, diabetes, cardiovascular disease, cancer and dementia. Pennington Biomedical has the vision to lead the world in promoting metabolic health and eliminating metabolic disease through scientific discoveries that create solutions from cells to society. The Center conducts basic, clinical, and population research, and is affiliated with LSU.
The research enterprise at Pennington Biomedical includes over 480 employees within a network of 40 clinics and research laboratories, and 13 highly specialized core service facilities. Its scientists and physician/scientists are supported by research trainees, lab technicians, nurses, dietitians, and other support personnel. Pennington Biomedical a state-of-the-art research facility on a 222-acre campus in Baton Rouge.
CHICAGO – Youth baseball players are prone to elbow pain and injuries, including repetitive overuse changes and fractures, based on the maturity of their bones, according to a new study being presented today at the annual meeting of the Radiological Society of North America (RSNA).
The repetitive motion and force of throwing a baseball places a large amount of stress on the growing bones, joints and muscles of the elbows of baseball players. Youth baseball players who have not yet reached skeletal maturity might be especially vulnerable to elbow pain and injuries.
“When we look at the forces that baseball players, even Little League baseball players, deal with during routine practice and games, it becomes apparent why elbow injuries are so common amongst this group,” said study co-author Vandan Patel, B.S., a radiology-orthopedics research scholar at Children’s Hospital of Philadelphia (CHOP) in Pennsylvania.
Most recent estimates show that 20 to 40% of youth baseball players between the ages of nine and 12 complain of elbow pain at least once during the season.
Skeletally immature children have growth plates, which are areas of bone that are made up of cartilage, a rubbery and flexible connective tissue, that allows the bones to grow and change in shape as a child ages. Growth plates are weaker than the surrounding muscles and bones and prone to injury that can lead to either reversible changes or permanent deformity.
Skeletal maturity occurs when the growth plates have closed, and no more bone (or growth) is being made. This usually occurs at the end of puberty, typically around age 13 to 15 for girls and 15 to 17 for boys.
In this retrospective study, the researchers reviewed elbow MRI exams from 130 youth players (18 years of age and younger) being evaluated for elbow pain. MRI is an ideal method for identifying joint problems, because it can non-invasively show cross-sectional details of soft tissues (cartilage, tendons and ligaments) and bone.
“We conducted this study in order to better understand the patterns of injuries that can occur among youth baseball players with elbow pain,” said senior author Jie C. Nguyen, M.D., M.S., director for the Section of Musculoskeletal Imaging in the Department of Radiology at CHOP. “Tissue vulnerability and, thus, sites at risk for injury, change with growth and maturation. A younger player injures differently than an older player. It is our hope that this data will help us continue to improve and individualize the care of current and future generations of youth baseball players.”
The average age of this study group of patients was 13.9 years, with 115 boys and 15 girls included. The frequency with which the patients played baseball varied from daily to recreationally.
Two radiologists independently reviewed the MRI exams to categorize the skeletal maturity and different findings of each patient’s elbow. They classified 85 patients as skeletally mature and 45 patients as skeletally immature.
The most common MRI findings in skeletally immature players included fluid build-up around the joint, stress injuries near the growth plate, fractures, and osteochondritis dissecans (OCD) lesions, where a piece of bone and the overlying cartilage is injured and can detach, leading to reduced range of motion and risk for premature osteoarthritis in adulthood.
Conversely, in skeletally mature players, the injury pattern shifts from the growth plates to the soft tissue. These players most often had triceps tendinosis—a condition in which the tendon connecting the triceps muscle to the elbow bone becomes strained, irritated or torn—and fluid build-up in the bony area of the elbow where the ulnar collateral ligament attaches. The ulnar collateral ligament runs on the inner side of the elbow and helps stabilize it.
Injuries that required surgery included intra-articular bodies (small fragments inside the joint), and unstable OCD.
“In terms of the skeletally immature children, 9 patients (11%) had intra-articular bodies, and 19 patients (22%) had OCD lesions,” Patel said.
The researchers hope that the results of this study will help to identify elbow injuries in children who play baseball and to individualize treatment based on skeletal maturity.
“This information is critically important not only to physicians, but also to parents and team coaches, all of whom provide crucial support for these children, reducing injury and preventing permanent damage on and off the field,” said co-author Theodore J. Ganley, M.D., director of Sports Medicine and Performance Center in the Division of Orthopaedics at CHOP. “As parents, caregivers and coaches, it is important to be aware of these findings in order to ensure that symptoms of pain are not overlooked during the baseball season.”
Although they did find that prevalence of injury was linked to prolonged play, the researchers said further studies are needed to identify exactly which injuries are more time dependent compared to others.
“This does not mean that elbow injuries are inevitable in baseball,” Patel said. “With proper technique and proper rest, these injuries could potentially be avoided.”
Additional co-authors are Shahwar M. Tariq, B.S., Liya Gendler, D.O., Apurva S. Shah, M.D., M.B.A., and Adam C. Zoga, M.D., M.B.A.
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Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23.
RSNA is an association of radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Illinois. (RSNA.org)
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New study: Lost brain function restored after stroke
Researchers have succeeded in restoring lost brain function in mouse models of stroke using small molecules that in the future could potentially be developed into a stroke recovery therapy. “Communication between nerve cells in large parts of the brain changes after a stroke and we show that it can be partially restored with the treatment”, says Tadeusz Wieloch, senior professor of neurobiology at Lund University in Sweden.
“Concomitantly, the rodents regain lost somatosensory functions, something that around 60 per cent of all stroke patients experience today. The most remarkable result is that the treatment began several days after a stroke,” Wieloch continues.
In an ischemic stroke, lack of blood flow to the brain causes damage, which rapidly leads to nerve cell loss that affects large parts of the the vast network of nerve cells in the brain. This may lead to loss of function such as paralysis, sensorimotor impairment and vision and speech difficulties, but also to pain and depression. There are currently no approved drugs that improve or restore the functions after a stroke, apart from clot-dissolving treatment in the acute phase (within 4.5 hours of the stroke). Some spontaneous improvements occur, but many stroke patients suffer chronic loss of function. For example, about 60 per cent of stroke sufferers, experience lost somatosensori functions such as touch and position sense.
An international study published recently in the journal Brain and led by a research team from Lund University in collaboration with University of Rome La Sapeinza and Washington University at St. Louis, shows promising results in mice and rats that were treated with a class of substances that inhibit the metabotropic glutamate receptor (mGluR5), a receptor that regulates communication in the brain’s nerve cell network.
“Rodents treated with the GluR5 inhibitor regained their somatosensori functions,” says Tadeusz Wieloch, who led the study published in BRAIN.
Two days after the stroke, i.e. when the damage had developed and function impairment was most prominent, the researchers started treating the rodents that exhibited the greatest impaired function.
“A temporary treatment effect was seen after just 30 minutes, but treatment for several weeks is needed to achieve a permanent recovery effect. Some function improvement was observed even when the treatment started 10 days after a stroke,” says Tadeusz Wieloch.
Importantly, sensorimotor functions improved, even though the extent of the brain damage was not diminished. This, explains Tadeusz Wieloch, is due to the intricate network of nerve cells in the brain, known as the connectome, i.e. how various areas of the brain are connected and communicate with each to form the basis for various brain functions.
“Impaired function after a stroke is due to cell loss, but also because of reduced activity in large parts of the connectome in the undamaged brain. The receptor mGluR5 is apparently an important factor in the reduced activity in the connectome, which is prevented by the inhibitor which therefore restores the lost brain function,” says Tadeusz Wieloch.
The results also showed that sensorimotor function was further improved if treatment with the mGluR5 inhibitor is combined with somatosensory training by housing several rodents in cages enriched with toys, chains, grids, and plastic tubes.
The researchers hope that in the future their results could lead to a clinical treatment that could be initiated a few days after an ischemic stroke.
“Combined with rehabilitation training, it could eventually be a new promising treatment. However, more studies are needed. The study was conducted on mice and rats, and of course needs to be repeated in humans. This should be possible since several mGluR5 inhibitors have been studied in humans for the treatment of neurological diseases other than stroke, and shown to be tolerated by humans,” says Tadeusz Wieloch.
The research is conducted with support from the Swedish Research Council, Alborada Trust, Hans-Gabriel and Alice Wachtmeister Foundation, and Multipark Strategic Research Area.
