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)
Monday, April 29, 2024
The double-fanged adolescence of saber-toothed cats
Evidence suggests saber-toothed cats held onto their baby teeth to stabilize their sabers
UNIVERSITY OF CALIFORNIA - BERKELEY
IMAGE:
A MECHANICAL ANALYSIS OF THE DISTINCTIVE CANINES OF CALIFORNIA'S SABER-TOOTHED CAT (SMILODON FATALIS) SUGGESTS THAT THE BABY TOOTH THAT PRECEDED EACH SABER STAYED IN PLACE FOR YEARS TO STABILIZE THE GROWING PERMANENT SABER TOOTH, PERHAPS ALLOWING ADOLESCENTS TO LEARN HOW TO HUNT WITHOUT BREAKING THEM.
The fearsome, saber-like teeth of Smilodon fatalis — California's state fossil — are familiar to anyone who has ever visited Los Angeles' La Brea Tar Pits, a sticky trap from which more than 2,000 saber-toothed cat skulls have been excavated over more than a century.
Though few of the recovered skulls had sabers attached, a handful exhibited a peculiar feature: the tooth socket for the saber was occupied by two teeth, with the permanent tooth slotted into a groove in the baby tooth.
Paleontologist Jack Tseng, associate professor of integrative biology at the University of California, Berkeley, doesn't think the double fangs were a fluke.
Nine years ago, he joined a few colleagues in speculating that the baby tooth helped to stabilize the permanent tooth against sideways breakage as it erupted. The researchers interpreted growth data for the saber-toothed cat to imply that the two teeth existed side by side for up to 30 months during the animal's adolescence, after which the baby tooth fell out.
In a new paper accepted for publication in the journal The Anatomical Record, Tseng provides the first evidence that the saber tooth alone would have been increasingly vulnerable to lateral breakage during eruption, but that a baby or milk tooth alongside it would have made it much more stable. The evidence consists of computer modeling of saber-tooth strength and stiffness against sideways bending, and actual testing and breaking of plastic models of saber teeth.
"This new study is a confirmation — a physical and simulation test — of an idea some collaborators and I published a couple of years ago: that the timing of the eruption of the sabers has been tweaked to allow a double-fang stage," said Tseng, who is a curator in the UC Museum of Paleontology. "Imagine a timeline where you have the milk canine coming out, and when they finish erupting, the permanent canine comes out and overtakes the milk canine, eventually pushing it out. What if this milk tooth, for the 30 or so months that it was inside the mouth right next to this permanent tooth, was a mechanical buttress?"
He speculates that the unusual presence of the baby canine — one of the deciduous teeth all mammals grow and lose by adulthood — long after the permanent saber tooth erupted protected the saber while the maturing cats learned how to hunt without damaging them. Eventually, the baby tooth would fall out and the adult would lose the saber support, presumably having learned how to be careful with its saber. Paleontologists still do not know how saber-toothed animals like Smilodon hunted prey without breaking their unwieldy sabers.
"The double-fang stage is probably worth a rethinking now that I've shown there's this potential insurance policy, this larger range of protection," he said. "It allows the equivalent of our teenagers to experiment, to take risks, essentially to learn how to be a full-grown, fully fledged predator. I think that this refines, though it doesn't solve, thinking about the growth of saber tooth use and hunting through a mechanical lens."
The study also has implications for how saber-toothed cats and other saber-toothed animals hunted as adults, presumably using their predatory skills and strong muscles to compensate for vulnerable canines.
Beam theory
Thanks to the wealth of saber-toothed cat fossils, which includes many thousands of skeletal parts in addition to skulls, unearthed from the La Brea Tar Pits, scientists know a lot more about Smilodon fatalis than about any other saber-toothed animal, even though at least five separate lineages of saber-toothed animals evolved around the world. Smilodon roamed widely across North America and into Central America, going extinct about 10,000 years ago.
Yet paleontologists are still confounded by that fact that adult animals with thin-bladed knives for canines apparently avoided breaking them frequently despite the sideways forces likely generated during biting. One study of the La Brea predator fossils found that during periods of animal scarcity, saber-toothed cats did break their teeth more often than in times of plenty, perhaps because of altered feeding strategies.
The double-fanged specimens from La Brea, which have been considered rare cases of individuals with delayed loss of the baby tooth, gave Tseng a different idea — that they had an evolutionary purpose. To test his hypothesis, he used beam theory — a type of engineering analysis employed widely to model structures ranging from bridges to building materials — to model real-life saber teeth. This is combined with finite element analysis, which uses computer models to simulate the sideways forces a saber tooth could withstand before breaking.
"According to beam theory, when you bend a blade-like structure laterally sideways in the direction of their narrower dimension, they are quite a lot weaker compared to the main direction of strength," Tseng said. "Prior interpretations of how saber tooths may have hunted use this as a constraint. No matter how they use their teeth, they could not have bent them a lot in a lateral direction."
He found that while the saber's bending strength — how much force it can withstand before breaking — remained about the same throughout its elongation, the saber's stiffness — its deflection under a given force — decreased with increasing length. In essence, as the tooth got longer, it was easier to bend, increasing the chance of breakage.
By adding a supportive baby tooth in the beam theory model, however, the stiffness of the permanent saber kept pace with the bending strength, reducing the chance of breaking.
"During the time period when the permanent tooth is erupting alongside the milk one, it is around the time when you switch from maximum width to the relatively narrower width, when that tooth will be getting weaker," Tseng said. "When you add an additional width back into the beam theory equation to account for the baby saber, the overall stiffness more closely aligned with theoretical optimal."
Though not reported in the paper, he also 3D-printed resin replicas of saber teeth and tested their bending strength and stiffness on a machine designed to measure tensile strength. The results of these tests mirrored the conclusions from the computer simulations. He is hoping to 3D-print replicas from more life-like dental material to more accurately simulate the strength of real teeth.
Tseng noted that the same canine stabilization system may have evolved in other saber-toothed animals. While no examples of double fangs in other species have been found in the fossil record, some skulls have been found with adult teeth elsewhere in the jaws but milk teeth where the saber would erupt.
"What we do see is milk canines preserved on specimens with otherwise adult dentition, which suggests a prolonged retention of those milk canines while the adult tooth, the sabers, are either about to erupt or erupting," he said.
Tseng is supported by the National Science Foundation's Division of Biological infrastructure (2128146).
Double-fanged specimen from La Brea Tar Pits
A portion of the right maxilla of a saber-toothed cat, Smilodon fatalis, showing a fully erupted baby saber tooth with the adult tooth just erupting. Based on Tseng's tooth eruption timing table, he estimates that the animal was between 12 and 19 months of age at the time of death. The fossil is from the La Brea Tar Pits and is housed at the Natural History Museum of Los Angeles County.
Mechanical stresses in a saber tooth
A finite element model of an adult saber tooth indicating saber bending stress. The warmer the color, the higher the stress and the more likely failure will occur in a particular area of the tooth model. The red dot near the tip is where the force was applied to measure the sideways bending stress.
Bending performance changes during prolonged canine eruption in saber-toothed carnivores: A case study of Smilodon fatalis
Fentanyl inhalation may cause potentially irreversible brain damage, warn doctors
Toxic leukoencephalopathy seen with heroin inhalation, but this is first reported fentanyl case
BMJ
Inhaling the synthetic opioid fentanyl may cause potentially irreversible brain damage (toxic leukoencephalopathy), warn doctors in the journal BMJ Case Reports, after treating a middle aged man found unresponsive in his hotel room after snorting the drug.
Leukoencephalopathy refers to inflammation and damage to the brain’s white matter—the network of nerve fibres that enable the exchange of information and communication between different areas of the brain’s grey matter.
Toxic leukoencephalopathy is a sudden or longstanding neurological syndrome, which has been reported after heroin inhalation, known as ‘chasing the dragon’. But this is the first reported case associated with fentanyl, say the report authors.
The condition is manifest in various signs and symptoms, the most obvious of which are neurological and behavioural changes, ranging from mild confusion to stupor, coma, and death.
The outlook for those affected generally depends on the extent of white matter injury, explain the report authors: some people will recover fully; others will progressively get worse.
In this case, the man had no previous medical problems of any note, and had been unconscious for an unknown period of time in his hotel room, where unidentified crushed pills and a white residue were found on a nearby table.
On arrival at hospital, he wasn’t able to answer questions or follow commands. He responded to pain stimuli to his legs, but not his arms.
A brain scan revealed white matter inflammation and swelling and cerebellar injury. The cerebellum is the part of the brain responsible for gait and balance. He tested negative for epilepsy.
A drug screen returned negative results, but a separate urine test indicated a very high level of fentanyl, prompting a diagnosis of toxic leukoencephalopathy induced by fentanyl inhalation.
Eighteen days later, he remained bedbound and still required tube feeding. He was given several different drugs to treat urinary incontinence, kidney injury, cognitive impairment, suspected opioid withdrawal, pain and agitation, and pneumonia.
After 26 days he was discharged to a rehabilitation facility, and after another month returned home with the support of outpatient physiotherapy and occupational therapy.
Less than a year after his hospital admission he had fully recovered and had returned to work full time.
Commenting on the incident, he describes his recovery as “miraculous”, adding: “Early on it was looking like I would need 24 hour care after being discharged, but I focused and worked hard in my therapy session and was determined not to leave the hospital only to be checked into a group facility for ongoing care.”
Expressing gratitude to all the healthcare professionals who not only saved his life, but enabled him to get back to the life he had before, he says: “I have regrets often about what I did to myself, my wife, and my family.”
The report authors conclude: “This case illustrates the need for inclusion of fentanyl in routine urine drug screens for earlier identification and appropriate management.”
Clinical and neuro radiographic features of fentanyl inhalation-induced Leukoencephalopathy
ARTICLE PUBLICATION DATE
29-Apr-2024
OHSU patient is world’s first documented case of brain disease from fentanyl inhalation
Case study highlights added danger of illicit fentanyl, especially to first-time users
OREGON HEALTH & SCIENCE UNIVERSITY
The man arrived unconscious and near death.
Previously healthy with no known medical history, the 47-year-old arrived by ambulance to the emergency department at Oregon Health & Science University on Feb. 25, 2023. He was found collapsed in his hotel room, where he was staying during a business trip. As clinicians began administering life-saving treatment, they searched for the cause.
In a case report published online today in the journal BMJ Case Reports, clinicians laid out the surprising and unprecedented diagnosis: toxic leukoencephalopathy by fentanyl inhalation.
In other words, inhaling fentanyl caused large sections of white matter in the patient’s brain to become inflamed to the point where he had lost consciousness and risked irreversible loss of brain function, or possibly death.
Medical experts had documented previous cases caused by inhaling heroin, but the OHSU patient is believed to be the first documented case involving inhalation of illicit fentanyl. The lead author of the study says it should be taken as a warning about the danger of a substance that is cheap, readily available and 50 times more potent than heroin.
“Opioid use, especially fentanyl, has become very stigmatized,” said lead author Chris Eden, M.D., now a second-year resident in internal medicine in the OHSU School of Medicine who was part of the patient’s treatment team. “This is a case of a middle-class man, in his late 40s, with kids, who used fentanyl for the first time. It demonstrates that fentanyl can affect everyone in our society.”
Although this is the first documented case, Eden said it’s likely other cases simply weren’t recognized due in part to the fact that relatively little is known about the syndrome’s physiology. In addition, he said hospitals haven’t traditionally included fentanyl in their standard urinalysis drug screens.
At the same time, fatal and nonfatal overdoses due to fentanyl and other opioids are all too common.
“We know very well the classic opiate side effects: respiratory depression, loss of consciousness, disorientation,” Eden noted. “But we don’t classically think of it causing possibly irreversible brain damage and affecting the brain, as it did in this case.”
Magnetic resonance imaging revealed inflammation in the brain. However, the patient’s lingering loss of consciousness, memory and function could have been due to any number of causes — stroke, carbon monoxide exposure or metabolic disease among them. Ultimately, a nonstandard drug test revealed the presence of fentanyl in his system.
Slow recovery
Fortunately for the patient, he slowly recovered after 26 days in the hospital, followed by a stay in a skilled nursing facility to help regain his speech and function. He is now home with his family in the Seattle area and back to work. To this day, he has no memory of the episode.
The successful outcome involved wraparound treatment with numerous clinicians and support at Oregon’s academic health center and single largest hospital, all operating with a patient-centered approach.
“This case involved internal medicine, neurology, neuroradiology and palliative care physicians, in addition to nurses, social workers, discharge planners, physical therapists, dieticians and pharmacists,” Eden said. “I’m proud of these multidisciplinary teams at OHSU working together to take care of complex patients, both from a medical and social perspective.”
Today’s publication in BMJ Case Reports also includes a perspective from the patient.
“I have regrets often about what I did to myself, my wife and my family,” he said. “I’m grateful to all the doctors, nurses and EMTs who saved my life, and the therapists who got me back to a functioning member of society.”
In addition to Eden, co-authors include Duna Alkhalaileh, D.O., M.P.H., David Pettersson, M.D., and Alan Hunter M.D., of OHSU; and Asad Arastu, M.D., previously of OHSU and now with Penn Medicine.
Clinical and neuroradiographic features of fentanyl inhalation-induced leukoencephalopathy
ARTICLE PUBLICATION DATE
29-Apr-2024
Frequent teen vaping might boost risk of toxic lead and uranium exposure
Potentially harmful to brain and organ development, suggest researchers. Findings underscore need for implementation of regulations and targeted prevention
BMJ
Frequent teen vaping might boost the risk of exposure to lead and uranium, potentially harming brain and organ development, suggests research published online in the journal Tobacco Control.
The findings underscore the need for implementation of regulations and prevention efforts targeting teens, emphasise the researchers.
Vaping is popular with teens. In 2022, an estimated 14% of US high school students—around 2.14 million—and more than 3% of middle school students—around 380,000—reported vaping in the preceding month, note the researchers.
Certain metals have been identified in e-cigarette aerosols and liquids. Their absorption is especially harmful during periods of development, say the researchers, citing research showing that increased levels of exposure are linked to cognitive impairment, behavioural disturbances, respiratory complications, cancer, and cardiovascular disease in children.
The researchers wanted to find out whether potentially toxic metal levels might be associated with vaping frequency and whether flavour might be influential.
They drew on responses to the nationally representative Wave 5 (December 2018 to November 2019) of the PATH Youth Study, involving 1607 teens between the ages of 13 and 17. After exclusions, 200 vapers were included in the final analysis.
Their urine samples were tested for the presence of cadmium, lead, and uranium, and vaping frequency was designated as occasional (1–5 days/month), intermittent (6–19 days), and frequent (20+ days).
Vape flavours were grouped into four mutually exclusive categories: menthol or mint; fruit; sweet, such as chocolate or desserts; and others, such as tobacco, clove or spice, and alcoholic or non-alcoholic drinks.
Among the 200 exclusive vapers (63% female), 65 reported occasional use, 45 intermittent, and 81 frequent use; vaping frequency information was missing for 9.
The average number of recent puffs per day increased in tandem with vaping frequency: occasional = 0.9 puffs; intermittent = 7.9 puffs; frequent = 27 puffs.
In the preceding 30 days 1 in 3 (33%) vapers said they used menthol/mint flavours; half (50%) favoured fruit flavours; just over 15% opted for sweet flavours; and 2% used other flavours.
Analysis of the urine samples showed that lead levels were 40% higher among intermittent vapers, and 30% higher among frequent vapers than they were among occasional vapers. Urinary uranium levels were also twice as high among frequent vapers than among occasional vapers
Comparison of flavour types indicated 90% higher uranium levels among vapers who preferred sweet flavours than among those opting for menthol/mint.
No statistically significant differences were found in urinary cadmium levels between vaping frequency or flavour types.
This is an observational study, and as such no definitive conclusions can be drawn about toxic metal levels and vaping frequency/flavours, acknowledge the researchers, who also caution that the levels of toxic metals in vapes will vary by brand and type of vaporiser used (tank, pod, mod).
Although urinary levels indicate chronic exposure, they were assessed at just one point in time, added to which the presence of uranium in the urine may be attributable to various sources including environmental exposure from natural deposits, industrial activities, and dietary intake, they add.
“None the less,these compounds are known to cause harm in humans,” they write. Of particular concern were the increased uranium levels found within the sweet flavour category, they add.
“Candy-flavoured e-cigarette products make up a substantial proportion of adolescent vapers, and sweet taste in e-cigarettes can suppress the harsh effects of nicotine and enhance its reinforcing effects, resulting in heightened brain cue-reactivity.”
And they conclude: “E-cigarette use during adolescence may increase the likelihood of metal exposure, which could adversely affect brain and organ development.
“These findings call for further research, vaping regulation, and targeted public health interventions to mitigate the potential harms of e-cigarette use, particularly among adolescents.”
Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring
ARTICLE PUBLICATION DATE
29-Apr-2024
COI STATEMENT
Pathogens, including multi-drug resistant “superbugs”, found on floors, ceilings and door handles of hospital toilets, UK study finds
Patient toilets were worst affected
EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES
Flushing of toilets without lids likely responsible for ceiling contamination
Put lid down before flushing at home, say the researchers
**ECCMID has now changed name to ESCMID Global, please credit ESCMID Global Congress in all future stories**
Pathogenic bacteria and fungi, including multi-drug resistant “superbugs” have been found on the floors, ceilings, door handles and other surfaces of hospital toilets in the UK, with patient toilets the worst affected, the ESCMID Global Congress (formerly ECCMID) in Barcelona, Spain (27-30 April) will hear.
Professor Stephanie Dancer, a consultant microbiologist at NHS Lanarkshire, UK wondered whether toilets without lids spread microbes to other surfaces in the bathroom when flushed, as well as whether some toilets are more contaminated than others.
She says: “The move to convert traditional male and female facilities to unisex facilities in some hospitals raises concern that people might be exposed to higher risks of contamination.
“For example, hand hygiene surveys show that women are more likely to clean their hands after bathroom use than men, so we decided to investigate which microbes were present on different surfaces in toilets and how many of them there were.
“Our results appear to confirm what is generally thought in society: women clean because their perception of dirt and disgust entices action whereas men either don’t notice a dirty environment or don’t care. It follows that women are more likely to leave a bathroom ‘clean’, while men assume someone will clean up after them.”
For the study, Professor Stephane Dancer and colleagues collected samples from toilets in three general hospitals in NHS Lanarkshire.
Ten different surfaces in six types of toilets were swabbed >4 hours after cleaning on four different days one week apart in each hospital.
The surfaces were: hand-touch surfaces (toilet flush; handrail; tap; door handle); floor surfaces; and high sites (door tops; shelves; air vents).
The six types of toilets were: male staff, female staff, male patient, female patient, disabled and unisex.
480 samples were collected from each hospital and the aerobic bioburden (amount of bacteria and fungi) calculated for each type of surface. Background flora and healthcare pathogens were isolated and identified and antimicrobial susceptibility testing was carried out.
The pathogens detected include: Staphylococcus aureus (which causes wound and other infections), Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae (bloodstream and urinary tract infections); Acinetobacter baumannii, Citrobacter and Serrati (bloodstream infections in compromised patients); Enterococci (urinary tract and wound infections); Burkholderia cepacia (chest infections in patients with cystic fibrosis); Pseudomonas aeruginosa and Stenotrophomonas maltophilia (chest infections and ventilator-associated pneumonia); Staphylococcus saprophyticus (common cause of urinary tract infections) and Aspergillus fungi (chest infections in immunocompromised patients).
A substantial proportion of isolated pathogens were multidrug-resistant and these organisms were concentrated in both male and female patient toilets. No MRSA was detected.
Professor Dancer says: “Every type of toilet in all three hospitals receives the same cleaning (type and frequency) every day but given our findings, we think that patient toilets should be cleaned more often.”
Overall, floors and high surfaces yielded higher levels of aerobic bacteria and fungi than hand-touch sites. It is likely that hand-touch sites are cleaned more thoroughly than other surfaces, says Professor Dancer.
She adds: “In contrast with hand-touch sites, floors are a major repository of dirt. Anything in the air eventually ends up on the floor, along with whatever is brought in on people’s footwear or shed from skin and clothes when they use the toilet.”
To the researchers’ surprise, Gram-negative pathogens such as E.coli, Stenotrophomonas maltophilia and Klebsiella pneumoniae were as likely to be found on air vents, ceilings and the top of doors as on floors.
“We think that the only logical explanation for this is that toilet flushing aerosolises whatever is in the toilet bowl, whereupon tiny water particles carrying these organisms fly up to the ceiling and contaminate high sites,” says Professor Dancer.
Female toilets had fewer microbes than male toilets (for example, samples from the handles inside the doors of male staff toilets had approximately eight times more microbes than those from the same handles in female staff toilets) and female staff toilets had the fewest microbes of all toilet types.
This might be due to more frequent handwashing among females, says Professor Dancer.
Gender-neutral toilets (unisex and disabled) had the highest microbial burden overall. This may reflect heavier overall use, as well as different attitudes to cleanliness between men and women, says Professor Dancer.
Professor Dancer concludes: “Airborne microorganisms and contaminated surfaces carry a potential risk for infection. Hospital toilets should have lids, which should be closed before you flush, and patient toilets should be cleaned more frequently than other toilets.
“Single sex and disabled toilets should be retained; with additional facilities labelled unisex and available for anyone. But based on this study’s findings, I don’t believe we should be abandoning single sex toilets in favour of unisex toilets, since these toilets had the highest microbial burden overall.”
“None of the toilets sampled in the study had a window. I would be very interested to repeat the study in toilets with open windows providing an abundant supply of fresh air.
“There is no doubt everyone could do with more education on hand hygiene. The more we all understand about how to protect ourselves and others from germs, the better.”
She also advises closing the toilet lid before flushing at home.
“Put the lid down before you flush and then wash your hands well and dry them with a clean towel,” says Professor Dancer.
“If you can, open a window in the bathroom, before using the toilet, and that’s not just to get rid of the smell.”
Similar findings are likely in other hospitals, depending on the type and frequency of cleaning and how often they are used, adds Professor Dancer.
For more information, or to arrange an interview, please contact Professor Dancer by email:
Alternative contact in the ESCMID Global Media Centre: Tony Kirby T) + 44(0)7834 385827 E) tony@tonykirby.comNotes to editors:
The authors declare no conflicts of interest.
This press release is based on abstract EW0104 at the ESCMID Global Congress (formerly ECCMID). All accepted abstracts have been extensively peer reviewed by the congress selection committee. There is no full paper at this stage but the authors are happy to answer your questions. The research has not yet been submitted to a medical journal for publication. The poster contains more up to date information so only the poster is included here.
Antimicrobial resistance prevalence varies by age and sex in bloodstream infections in European hospitals
EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES
New research presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024, Barcelona 27-30 April) shows that levels of resistance to antimicrobials (AMR) varies with age and sex, with age in particular showing substantial variation both between and within countries. The study is by Gwen Knight, Associate Professor at the London School of Hygiene and Tropical Medicine and co-Director of the LSHTMAMR Centre, London, UK, and colleagues, and published in PLOS Medicine.
Remarkably little is known about how antimicrobial resistance (AMR) prevalence in infection varies with age and sex for different bacterial species and resistance phenotypes and how these associations vary spatially. Understanding such associations has the potential to shed new light on AMR epidemiology, inform forecasts, and support intervention targeting. Using data from 29 European countries* the researchers aimed to characterise this burden for bloodstream infections.
They analysed routine surveillance data from bloodstream infections collected by the European Antimicrobial Resistance Surveillance Network (EARS-Net). They included 6,862,577 susceptibility results from isolates from 2015-2019 with age, sex and spatial information used to characterise resistance trends by age and sex. Computer modelling was used to estimate any potential resistance variance by sex and age between the young (1 year old) and the very old (100 years old)
They found substantial variation in AMR prevalence by age sub-nationally and between countries, with four main association forms: (i) u-shaped with monotonic increase with age after infancy, (ii) constant, (iii) n-shaped with resistance peaking at intermediate ages and (iv) monotonic decline with age. Sex was less often associated with resistance, apart from in E. coli, K. pneumoniae and at younger ages for Acinetobacter sp., in which men were more likely to have a resistant infection.
Trends at the European level varied more within an antibiotic family than within a bacterial species. For methicillin-resistant Staphylococcus aureus (MRSA), a clear increase in resistance prevalence by age was seen (72% of countries seeing an increased resistance between younger and older males), whilst resistance to several antibiotics within Pseudomonas aeruginosa peaked at around 30 years of age
Age trends for aminopenicillin resistance in Escherichia coli which were mostly negative (93% of countries show decreased resistance between younger and older males) With a smaller change in resistance in females.
Commenting on the findings, Dr Knight says: “Most experts assume that resistance prevalence would increase with age due to cumulative antibiotic exposure effects and contact with healthcare settings, but it was not the case with all pathogens. I am also surprised by the fact that women, despite having more risk factors - such as childbirth and higher urinary tract infection incidence - and hence antibiotic exposures had a lower prevalence of resistant bloodstream infections.”
The authors conclude: “AMR prevalence in bloodstream infection varies by age and sex, with diverse patterns of association that vary widely with bacterial species and resistance phenotype. These unexpected findings, which may have important implications for intervention targeting, reveal important gaps in our understanding of AMR drivers in Europe. There is also much variation in antibiotic use guidelines between and within countries, that could be related to some of these observed trends.”
JOURNAL
PLoS Medicine
ARTICLE TITLE
Antimicrobial resistance prevalence in bloodstream infection in 29 European countries by age and sex: An observational study
Identification and exploration of transcripts involved in antibiotic resistance mechanism of two critical superbugs
Infectious diseases caused by pathogenic strains of bacteria are a global cause of morbidity and mortality. Hospital-acquired infections caused by Klebsiella pneumonia and Pseudomonas aeruginosa were found vulnerable during the COVID-19 pandemic. They are also responsible for the onset of certain life-threatening infectious diseases such as cystic fibrosis, endocarditis, bacteremia, and sepsis. Looking into the importance of these two superbugs there is a strong need for extensive comparative differential gene expression analysis among the wild-type and mutant for betterment of intensive care unit patients especially as such pathogenic bacterial strains have a dangerous role in the intensive care unit.
Methods
This study revealed the RNA microarray gene expression profiles of GSE24688, GSE4026, and GSE117438. The study compared all genes from three different datasets and all drug resistance genes from two divergent organisms, Klebsiella pneumonia and Pseudomonas aeruginosa.
Results
10 numbers of shared significant genes and five drug resistance genes were obtained in this study. These putative genes may show intriguing patterns of connection with resistance mechanisms and can be used in the field of diagnostics and treatment. Our divergent analysis also revealed a very clear distinct relation between Klebsiella pneumoniae and Pseudomonas aeruginosa at the genetic level, though they both function under antimicrobial resistance.
Conclusions
We observed interesting phenomena of nonsimilarity between common significant genes and common drug resistance genes that led to conclusions about genetic divergence due to which its physical properties have been changed but chemically involved in similar drug resistance mechanisms. Our study used a robust integrative bioinformatics analysis of microarray data to investigate the DEG of AMR superbugs. Through a comparative analysis supported by functional enrichment results, diverse pathways and distinct biological processes, molecular function, and cellular components were highlighted. Interestingly, we observed 10 common genes in all three datasets that are highly expressed and significant, five genes that are present in both KP and PA and are involved in drug resistance in both superbugs. Our findings provide a detailed account of the drug resistance gene’s divergent evolution, which could open new vistas for MDR prognosis and can be informative in antimicrobial therapeutics research. The candidate gene approach can be used to validate AMR to know the potential interesting association patterns with resistance mechanisms.
Gene Expression (GE) is an open-access journal. It was launched in 1991 by Chicago Medical School Press, and transferred to Cognizant Communication Corporation in 1994. From August 2022, GE is published by Xia & He Publishing Inc.
GE publishes peer-reviewed and high-quality original articles, reviews, editorials, commentaries, and opinions on its primary research topics including cell biology, molecular biology, genes, and genetics, especially on the cellular and molecular mechanisms of human diseases.
GE has been indexed in Medline (1991-2021), Scopus, Biological Abstracts, Biosis Previews, ProQuest, etc.
CREDIT: UNIVERSITY HOSPITAL BONN (UKB) / JAN-SAMUEL PULS
Many bacteria produce substances to gain an advantage over competitors in their highly competitive natural environment. Researchers at the University Hospital Bonn (UKB), the University of Bonn and the German Center for Infection Research (DZIF) have discovered a new so-called lantibiotic, namely epilancin A37. It is produced by staphylococci that colonize the skin and acts specifically against their main competitors there, the corynebacteria. This specificity is presumably mediated by a very special mechanism of action, which the researchers were able to decipher in detail. Their results have now been published in the renowned ISME Journal.
Due to increasing antibiotic resistance in pathogens causing infections, the development of new antibacterial substances is important. Hopes are pinned on a new group of substances produced by gram-positive bacteria, the lantibiotics. These are antimicrobial peptides that often have a very narrow spectrum of activity. "Such compounds are highly interesting from a medical point of view, as they could specifically attack individual groups of organisms without affecting the entire bacterial flora, as is the case with broad-spectrum antibiotics, for example," says corresponding author Dr. Fabian Grein, until recently head of the DZIF research group "Bacterial Interference" at the Institute of Pharmaceutical Microbiology at the UKB and member of the Transdisciplinary Research Area (TRA) "Life & Health" at the University of Bonn.
Essential competitive advantage over corynebacteria
The UKB research team led by Fabian Grein and Tanja Schneider, together with the team led by Ulrich Kubitscheck, Professor of Biophysical Chemistry at the University of Bonn, have now discovered a new lantibiotic, namely epilancin A37. It is produced by staphylococci, which are typical colonizers of the skin and mucous membranes. Little is known about these antimicrobial peptides. "We were able to show that epilancins are widespread in staphylococci, which underlines their ecological importance," says first author Jan-Samuel Puls, a doctoral student from the University of Bonn at the Institute of Pharmaceutical Microbiology at the UKB. This is because staphylococci and corynebacteria are important genera of the human microbiota - i.e. the totality of all microorganisms such as bacteria and viruses - in the nose and skin, which are closely linked to health and disease. The need to produce such a compound indicates a pronounced competition between the species. The researchers were able to show that the newly discovered epilancin A37 acts very specifically against corynebacteria, which are among the main competitors of staphylococci within the skin microbiome.
New mode of action in the "bacterial war" decoded
"This specificity is presumably mediated by a very special mechanism of action that we were able to decipher in detail," says Grein. Epilancin A37 penetrates the corynebacterial cell, initially without destroying it. The antimicrobial peptides accumulate in the cell and then dissolve the cell membrane from the inside, thus killing the corynebacterium. Co-author Dr. Thomas Fließwasser from the Institute of Pharmaceutical Microbiology at the UKB, postdoctoral researcher at the University of Bonn and acting head of the DZIF research group "Bacterial Interference" adds: "Our study shows how a specific mechanism of action can be used to specifically combat a single bacterial species. It therefore serves us as a 'proof of concept'".
Promotion: This project was funded by the German Center for Infection Research and the Transregio SFB TRR 261 "Antibiotic CellMAP" of the German Research Foundation.
