Smiling is secret to seeing happiness, new research reveals

Smiling for just a split second makes people more likely to see happiness in expressionless faces, new University of Essex research has revealed.

The study led by Dr Sebastian Korb, from the Department of Psychology, shows that even a brief weak grin makes faces appear more joyful.

The pioneering experiment used electrical stimulation to spark smiles and was inspired by photographs made famous by Charles Darwin.

A painless current manipulated muscles momentarily into action — creating a short uncontrollable smile.

This is the first time facial electrical stimulation has been shown to affect emotional perception.

Dr Korb hopes the research can explore potential treatments for depression or disorders that affect expression, like Parkinson’s and autism.

He said: “The finding that a controlled, brief and weak activation of facial muscles can literally create the illusion of happiness in an otherwise neutral or even slightly sad looking face, is ground-breaking.

“It is relevant for theoretical debates about the role of facial feedback in emotion perception and has potential for future clinical applications.”

Dr Korb used a modernised version of a technique first developed in the 19th century by the French physician Duchenne de Boulogne.

Darwin published drawings of Duchenne’s work in The Expression of the Emotions in Man and Animals — his third major work on evolution.

However, the voltage was dialled down for the new experiments to ensure the safety of participants and better control the smiles.

By using computers, the team were able to control the onset of smiles with millisecond precision.

In total 47 people took part in the Essex study which was published in Social Cognitive and Affective Neuroscience.

They were shown digital avatars and asked to assess whether they looked happy or sad.

In half the trials, smiling muscles were activated at the onset of the face.

It emerged that producing a weak smile for 500 milliseconds was enough to induce the perception of happiness.

Dr Korb says the results help us understand facial feedback and he hopes to expand the study.

He said: “We are currently conducting more al research to further explore the phenomenon in healthy participants.

“In the future, however, we hope to apply this technique to explore facial emotion recognition, for people with conditions like Parkinson’s, who are known to have reduced spontaneous facial mimicry and impaired facial emotion recognition.

“Moreover, we have published guidelines to allow other researchers to safely start using electrical facial muscle stimulation.”

Reference:

Themis Nikolas Efthimiou, Joshua Baker, Alasdair Clarke, Arthur Elsenaar, Marc Mehu, Sebastian Korb. Zygomaticus activation through facial neuromuscular electrical stimulation (fNMES) induces happiness perception in ambiguous facial expressions and affects neural correlates of face processing. Social Cognitive and Affective Neuroscience, 2024; 19 (1) DOI: 10.1093/scan/nsae013.

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Use of ultrahigh spatial-resolution photon-counting detector CT improves assessment of calcified stenoses: Study

Germany: A recent study published in the journal Radiology showed improvement in vivo and in vitro coronary stenosis assessment for calcified stenoses using ultrahigh spatial-resolution photon-counting detector (PCD) computed tomography (CT) reconstructions. This leads to a lower percentage of diameter stenosis (DS) compared with standard resolution and clinically relevant reclassification rates.

“Ultrahigh-spatial-resolution reconstructions led to the reclassification of 54.4% patients to lower CAD-RADS (Coronary Artery Disease Reporting and Data System) category than that assigned using standard resolution,” the researchers reported.

Coronary CT angiography is a first-line test in coronary artery disease (CAD) but is limited by severe calcifications. Photon-counting–detector CT improves spatial resolution. Therefore, Moritz C. Halfmann, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr 1, Mainz, Germany, and colleagues aimed to investigate the effect of improved spatial resolution on coronary stenosis assessment and reclassification.

For this purpose, the researchers performed a prospective evaluation of coronary stenoses in a vessel phantom (in vitro) containing two stenoses (25%, 50%), and coronary stenoses were evaluated retrospectively in patients (in vivo) who underwent ultrahigh-spatial-resolution cardiac PCD CT (from July 2022 to April 2023).

Image reconstruction was done at standard resolution (section thickness, 0.6 mm; increment, 0.4 mm; Bv44 kernel), high spatial resolution (section thickness, 0.4 mm; increment, 0.2 mm; Bv44 kernel), and ultrahigh spatial resolution (section thickness, 0.2; increment, 0.1 mm; Bv64 kernel). Percentages of DS were compared between reconstructions.

In vitro values were compared with the manufacturer specifications of the phantom, and patient results were assessed regarding the impact on CAD-RADS reclassification.

The in vivo sample included 114 patients (mean age, 68 years; 71 male patients).

The study led to the following findings:

  • In vitro, percentage DS measurements were more accurate with increasing spatial resolution for 25% and 50% stenoses (mean bias for standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 10.1%, 8.0%, and 2.3%).
  • In vivo, results confirmed decreasing median percentage DS with increasing spatial resolution for calcified stenoses (n = 161) (standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 41.5%, 34.8%, and 26.7%), whereas noncalcified (n = 13) and mixed plaques (n = 19) did not show evidence of a difference.
  • Ultrahigh-spatial-resolution reconstructions led to a reclassification of 54.4% of patients to a lower CAD-RADS category than that assigned using standard resolution.

“Ultrahigh spatial resolution at photon-counting detector coronary CT angiography (CCTA) results in relevant rates of stenosis reclassification, which may impact the rate of downstream testing in patients with stable chest pain and may improve the role of CCTA as a gatekeeper for follow-up studies,” the researchers concluded.

Reference:

Halfmann MC, Bockius S, Emrich T, Hell M, Schoepf UJ, Laux GS, Kavermann L, Graafen D, Gori T, Yang Y, Klöckner R, Maurovich-Horvat P, Ricke J, Müller L, Varga-Szemes A, Fink N. Ultrahigh-Spatial-Resolution Photon-counting Detector CT Angiography of Coronary Artery Disease for Stenosis Assessment. Radiology. 2024 Feb;310(2):e231956. doi: 10.1148/radiol.231956. PMID: 38376407.

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Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in CAC more than 1,000: Study

USA: Among asymptomatic patients with coronary artery calcium (CAC) score > 1,000, those with severe calcium in the left main coronary artery and diabetes have more than a sevenfold greater risk of death from atherosclerotic cardiovascular disease (ASCVD) versus those who have a high CAC score alone, a recent study has shown.

Not all patients with very high levels of CAC are created equal when it comes to CV risk, with the research published in JACC: Cardiovascular Imaging providing some clues on how to identify a particularly high-risk patient who could benefit from aggressive primary prevention strategies across several domains, including low-density lipoprotein-cholesterol lowering.

Although coronary artery calcium of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high ASCVD risk in this patient population is not well-defined. Therefore, Alexander C. Razavi, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia, USA, and colleagues aimed to identify risk factors equating with very high-risk ASCVD mortality rates among people with a CAC of ≥1,000.

For this purpose, the researchers studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. The mean age was 66.6 years; 14% were female, and 10% were non-White. During a median follow-up of 11.3 years, Cox proportional hazards regression modelling was performed for ASCVD mortality.

Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years).

The study led to the following findings:

  • The median CAC score was 1,592, and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300).
  • Diabetes (HR: 2.04) and severe LM CAC (HR: 2.32) were associated with ASCVD mortality.
  • The ASCVD mortality per 100 person-years for all patients was 0.8, although higher rates were observed for diabetes (1.4), severe LM CAC (1.3), and both diabetes and severe LM CAC (7.1).

“Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high-risk atherosclerotic cardiovascular disease, identifying individuals who may benefit from more intensive prevention therapies across several domains, including LDL-cholesterol lowering,” the researchers wrote.

Reference:

Razavi AC, Shaw LJ, Berman DS, Budoff MJ, Wong ND, Vaccarino V, van Assen M, De Cecco CN, Quyyumi AA, Mehta A, Muntner P, Miedema MD, Rozanski A, Rumberger JA, Nasir K, Blumenthal RS, Sperling LS, Mortensen MB, Whelton SP, Blaha MJ, Dzaye O. Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000. JACC Cardiovasc Imaging. 2024 Feb 12:S1936-878X(24)00026-3. doi: 10.1016/j.jcmg.2023.12.006. Epub ahead of print. PMID: 38385932.

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Dysfunctional blood monocytes may predict CVD risk in patients with type 2 diabetes: Study

France: A recent study published in Circulation Research has revealed that frequency and monocyte phenotypic profile are closely associated with cardiovascular (CV) risk in patients with type 2 diabetes (T2D).

The findings imply that assessing monocyte count and frequency is a valuable predictive marker for the risk of CV events in diabetes patients.

Previous studies have shown diabetes to be a major risk factor for atherosclerotic cardiovascular diseases (ASCVD) with a 2-fold higher risk of CV events in patients with diabetes compared with those without. However, there is cardiovascular risk heterogeneity among patients with T2D that cardiovascular risk scores fail to detect. None of these cardiovascular risk scores considers proatherogenic immune effector, monocyte blood count.

Circulating monocytes are inflammatory effector cells involved in type 2 diabetes and atherogenesis. Nicolas Venteclef, IMMEDIAB Laboratory, Paris, France, and colleagues investigated the relationship between circulating monocytes and CV risk progression in people with T2D, using phenotypic, metabolomic, and transcriptomic analyses in a cross-sectional study population of 672 participants with T2D.

The study led to the following findings:

· Coronary artery calcium score was positively correlated with blood monocyte count and frequency of the classical monocyte subtype.

· Unsupervised k-means clustering based on monocyte subtype profiles revealed 3 main endotypes of people with type 2 diabetes at varying risk of cardiovascular events. These observations were confirmed in a validation cohort of 279 T2D participants.

· The predictive association between monocyte count and major adverse cardiovascular events was validated through an independent prospective cohort of 757 patients with T2D.

· Integration of monocyte transcriptome analyses and plasma metabolomes showed a disruption of mitochondrial pathways (tricarboxylic acid cycle, oxidative phosphorylation pathway) that underlined a proatherogenic phenotype.

The findings reveal an association between routine white blood cell-derived monocyte counts and CV risk among patients with T2D. By combining monocyte immunophenotypic, immunophenotypic, and plasma metabolomic analyses, the researchers showed an oxidative phosphorylation and mitochondrial modulation in a specific monocyte subtype, linked to an endotype of type 2 diabetes patients that are at higher cardiovascular risk.

We show an association of 2 phenomena: an increase in the monocyte pool, resulting in more ready infiltration of atherosclerotic plaques promoting progression,” the researchers wrote. “Mitochondrial dysfunction was apparent in these monocytes, providing a potential explanation for the increased CV risk associated with T2D.”

“Our findings present monocytes as good candidates for predicting cardiovascular complication development among type 2 diabetes patients and highlight the relevance of phenotyping circulating monocytes to assess CV risk in T2D,” they concluded.

Reference:

Julla JB, Girard D, Diedisheim M, Saulnier PJ, Tran Vuong B, Blériot C, Carcarino E, De Keizer J, Orliaguet L, Nemazanyy I, Potier C, Khider K, Tonui DC, Ejlalmanesh T, Ballaire R, Mambu Mambueni H, Germain S, Gaborit B, Vidal-Trécan T, Riveline JP, Garchon HJ, Fenaille F, Lemoine S, Carlier A, Castelli F, Potier L, Masson D, Roussel R, Vandiedonck C, Hadjadj S, Alzaid F, Gautier JF, Venteclef N. Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes. Circ Res. 2024 Jan 19;134(2):189-202. doi: 10.1161/CIRCRESAHA.123.322757. Epub 2023 Dec 28. PMID: 38152893.

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Low birthweight and overweight in young adulthood tied to elevated risk of early type 2 diabetes in men: Study

Sweden: A recent study has revealed low birth weight and overweight in young adulthood to be the major developmental determinants of adult type 2 diabetes risk in men.

“They contribute in an additive manner to the risk of type 2 diabetes,” the researchers wrote. “To reduce the risk of type 2 diabetes, young adult overweight should be avoided, particularly in boys with a low birthweight.”

The new research is being  presented at this year’s European Congress on Obesity (ECO) in Venice, Italy (12-15 May), and published in Diabetologia (the journal of th European Association for The Study of Diabetes [EASD]). 

Having a low birthweight together with being overweight in young adulthood (but not childhood) contributes to the development of type 2 diabetes at an early age (59 years or younger) in men, the study stated. 

Notably, the study involving over 34,000 Swedish men, found that those born with a low birthweight (<2.5 kg/5 lbs 8oz) who were also overweight at aged 20 years (BMI >25kg/m²) were 10 times more likely to develop early type 2 diabetes than those with a birthweight in the normal range (2.5-4.5 kg) who were normal weight as young adults (BMI <25 kg/m²).

Importantly, the researchers from the University of Gothenburg and Sahlgrenska University Hospital also found that babies with a low birthweight who were overweight at age 20 years had a 27% absolute risk of developing early type 2 diabetes, compared with an absolute risk of 6% for those with a birthweight in the normal range who were also normal weight at aged 20 years. This suggests that preventing excess weight gain during young adulthood in boys born with low birthweight could reduce the absolute risk of early type 2 diabetes by 21%.

Type 2 diabetes is being diagnosed at progressively younger ages, suggesting that significant risk may begin to accumulate during the developmental period. The association between low birthweight and overweight in childhood and/or young adulthood and type 2 diabetes in adults is already known, but it has been unclear how much influence the combination of these two factors exerts.

To find out more, researchers analysed data from 34,231 men born between 1945 and 1961 involved in the BMI Epidemiology Study (BEST) Gothenburg—a population-based cohort examining the associations between growth and BMI development in early life and the risk of disease in later life.

The researchers analysed birthweight and BMI of participants from school health care records (at the age of 8 years) and from medical examinations on enrolment in the military (at age 20), which was mandatory until 2010.

Participants were followed from 30 years of age until type 2 diabetes diagnosis, death, or emigration, or until 31st December 2019. Information on type 2 diabetes diagnoses was retrieved from Swedish national registers to estimate the risk of early (<59.4 years) and late (>59.4 years) type 2 diabetes. They also examined whether these associations were independent of, or modified by, socioeconomic factors such as level of education.

During an average 34 years follow up (after 30 years of age), a total of 2,733 cases of type 2 diabetes were diagnosed (1,367 cases of early diabetes and 1,366 cases of late diabetes). The analyses found that birthweight below the average (median; <3.6 kg/7lbs 9oz) and overweight at age 20 years (BMI >25 kg/m²), but not overweight at age 8 years (BMI >17.9 kg/m²), were associated with an increased risk of both early and late type 2 diabetes.

Furthermore, low birthweight and overweight in young adulthood were found to have an additive effect on the risk of type 2 diabetes. For example, having a below average birthweight (<3.6 kg/7lbs 9oz), followed by overweight at 20 years of age was associated with a six times greater risk of developing early type 2 diabetes. Whereas a lower birthweight (<2.5 kg/5 lbs 8oz) combined with later overweight at 20 years was linked with a 10 fold greater risk of developing early type 2 diabetes.

Adjusting for education, a known risk factor for type 2 diabetes, did little to change the results.

“Our findings establish low birthweight and overweight in young adulthood as the main developmental determinants, whereas overweight in childhood is of lesser importance for type 2 diabetes in adult men”, says lead author Dr Jimmy Celind, a researcher at Sahlgrenska Academy’s Institute of Medicine at the University of Gothenburg. “The combination of low birthweight followed by overweight at age 20 years is associated with a massive excess risk for early type 2 diabetes, which is substantially higher than the risk associated with low birthweight or being overweight as a young adult separately.”

Co-author Dr Jenny Kindblom from Sahlgrenska University Hospital adds, “It’s possible that the metabolic consequences of fetal growth restriction, which promotes resilience against starvation through fat storage and insulin resistance, when combined with a detrimental BMI trajectory during puberty when the insulin resistance is at a lifetime peak due to the surge of growth and sex hormones, result in an additive excess risk for later type 2 diabetes. Public health initiatives should target boys born with low birthweight to work on prevention of overweight as young adults, to reduce this huge excess risk for early type 2 diabetes.”

The authors acknowledge that the findings are associations only and that the study wasn’t designed to measure direct cause and effect, and point to several limitations, including that the participants were mainly white men which may limit the generalisability of the findings to other ethnicities and women. In addition, the analyses were unable to account for the influence of other known risk factors for type 2 diabetes such as smoking, dietary habits, and physical activity which could have influenced the results.

Reference:

Célind J, Bygdell M, Bramsved R, Martikainen J, Ohlsson C, Kindblom JM. Low birthweight and overweight during childhood and young adulthood and the risk of type 2 diabetes in men: a population-based cohort study. Diabetologia. 2024 Feb 22. doi: 10.1007/s00125-024-06101-y. 

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COVID-19 tied to elevated risk for autoimmune inflammatory rheumatic diseases up to 12 months after infection: Study

South Korea: A recent study published in Annals of Internal Medicine has revealed an association between SARS-CoV-2 infection and increased risk for incident autoimmune inflammatory rheumatic diseases (AIRDs) versus matched patients without SARS-CoV-2 infection or with influenza infection.

The risk for incident AIRD was higher with greater acute COVID-19 severity. 

The large, binational study found that SARS-CoV-2 infection was associated with an increased risk for autoimmune inflammatory rheumatic diseases (AIRDs) that extends up to 12 months after infection. The risk was found to be higher with greater severity of acute COVID-19, even among those who were vaccinated.

These findings suggest that care strategies for patients who survive COVID-19 should pay close attention to manifestations of AIRD, particularly after severe illness. 

Emerging data suggest a higher risk for AIRDs among persons with a history of COVID-19. However, these findings are based entirely on comparisons between groups infected with SARS-CoV-2 and those that are not, which might be biased by differences in health-seeking behavior and inherent risk factors within the groups. In addition, studies have not explored the effect of vaccination and other modifiable factors on prevention of long term COVID-19 complications.

Researchers from Kyung Hee University, Seoul, South Korea used data from two national, large-scale, general population-based cohort studies in Korea and Japan to investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. The data comprised of more than 10 million Korean and 12 million Japanese adults, including those with COVID-19 between January 2020 and December 2021, matched to patients with influenza infection and to uninfected control patients. The researchers assessed the data for onset of AIRD at 1, 6, and 12 months after COVID-19 or influenza infection, or the respective matched index date of uninfected control patients. They found increased risk for incident AIRD up to 12 months after COVID-19 diagnosis compared with the other two groups. Greater severity of acute COVID-19 was associated with higher risk for incident AIRD. The authors noted that COVID-19 vaccination was associated with reduced risk for incident AIRD after SARS-CoV-2 infection, except for among those who had severe COVID-19 despite vaccination.

Reference:

Min Seo Kim, Hayeon Lee, Seung Won Lee, Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19, Annals of Internal Medicine, https://doi.org/10.7326/M23-1831.

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EPIT with Viaskin milk viable therapeutic option for immunoglobulin E-mediated cow’s milk allergy: JAMA

Cow’s milk allergy (CMA) is a common childhood food allergy with no approved treatment. However, a recent clinical trial investigated the efficacy and safety of epicutaneous immunotherapy using Viaskin milk in children with IgE-mediated CMA.

IgE-mediated CMA poses significant challenges for affected children and their families, as it can lead to severe allergic reactions and impact quality of life. This study was published in the journal JAMA Pediatrics by Daniel P. and colleagues.

This phase 1/2 clinical trial enrolled 198 children aged 2 to 17 years with confirmed IgE-mediated CMA. The study evaluated the safety and efficacy of Viaskin milk at doses of 150 μg, 300 μg, and 500 μg compared to placebo over a 12-month treatment period. The primary outcome measure was the proportion of treatment responders based on the cumulative reactive dose of cow’s milk protein at the month 12 food challenge.

  • Among the participants, 95.5% completed the treatment regimen.

  • The highest treatment response rate (49.0%) was observed in children who received Viaskin milk at the 300-μg dose, compared to 30.2% in the placebo group.

  • This response was particularly notable in children aged 2 to 11 years, with a response rate of 57.9% in the 300-μg dose group compared to 32.5% in the placebo group.

  • Most adverse events were mild or moderate application-site reactions, with low rates of treatment-related anaphylaxis.

The findings of this trial suggest that 12 months of daily epicutaneous immunotherapy with Viaskin milk at a dose of 300 μg is associated with a statistically significant treatment response in children with IgE-mediated CMA. Treatment-related adverse events were generally mild, and discontinuation rates were low. Further research is warranted to confirm these findings and explore Viaskin milk as a potential treatment option for children with CMA.

Epicutaneous immunotherapy using Viaskin milk shows promise as a novel approach to treating cow’s milk allergy in children. The study’s findings underscore the need for additional research to validate these results and assess the long-term efficacy and safety of this therapeutic approach.

Reference:

Petroni, D., Bégin, P., Bird, J. A., Brown-Whitehorn, T., Chong, H. J., Fleischer, D. M., Gagnon, R., Jones, S. M., Leonard, S., Makhija, M. M., Oriel, R. C., Shreffler, W. G., Sindher, S. B., Sussman, G. L., Yang, W. H., Bee, K. J., Bois, T., Campbell, D. E., Green, T. D., … Wood, R. A. Varying doses of epicutaneous immunotherapy with Viaskin milk vs placebo in children with cow’s milk allergy: A randomized clinical trial. JAMA Pediatrics,2024. https://doi.org/10.1001/jamapediatrics.2023.6630

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Oocytes outsmart toxic proteins to preserve long-term female fertility

Oocytes are immature egg cells that develop in almost all female mammals before birth. The propagation of future generations depends on this finite reserve of cells surviving for many years without incurring damage. In mice, this can be a period of up to eighteen months, while in humans it can last almost half a century, the average time between birth and menopause. How the cells accomplish this remarkable feat of longevity has been a longstanding question.

Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have discovered a new mechanism which explains how oocytes remain in pristine conditions for decades without succumbing to the wear and tear that would cause other cell types to fail. The findings, reported today in the journal Cell, represent a new frontier to explore unexplained causes of infertility.

The researchers looked at protein aggregates, which are clumps of misfolded or damaged proteins. If left unchecked, these harmful substances accumulate in the cytoplasm and have highly toxic effects. Protein aggregates are known to accumulate in neurons and their effects have been linked to several neurodegenerative diseases. Cells usually manage aggregates by breaking them down with specialized enzymes. They can also divide into two new cells, concentrating aggregates in one of the cells and sparing the other.

But oocytes are not like the other cells. Their long life means they cannot dissipate toxic substances through cell division. Constantly breaking down protein aggregates is an inviable strategy, as it requires using a high amount of energy that may not be available. Oocytes also have the job of donating their entire cytoplasm to an embryo after fusing with a sperm, and so prefer to reduce their metabolic activity, a strategy which avoids generating by-products which can damage the maternal DNA and compromise future reproductive success. This makes oocytes particularly sensitive to the effects of misfolded or damaged proteins.

However, “in contrast to the tens of thousands of papers on protein aggregation in neurons, how mammalian oocytes cope with protein aggregation is essentially unstudied, despite having the same problem of being long-lived and non-dividing”, explains Dr. Elvan Böke, Group Leader of the Oocyte Biology & Cellular Dormancy programme at the Centre for Genomic Regulation and author of the study. “We wanted to explore how oocytes deal with these misfolded or damaged proteins”, adds Dr. Böke.

Patrolling ‘clean-up crews’

Dr. Böke’s team, led by Dr. Gabriele Zaffagnini, started by collecting thousands of immature oocytes, mature eggs, and early embryos from adult mice. Using special dyes, they observed how the protein aggregates behave in real-time using a technique called live-cell imaging. They also used electron microscopy to get a closer look and see nanoscopic details inside cells, work that took five and a half years to complete.

The researchers discovered special structures in the oocytes which they named EndoLysosomal Vesicular Assemblies-or ELVAs for short. These structures -there are about 50 per each oocyte – roam the cytoplasm, where they capture and hold onto protein aggregates, rendering them harmless. Cells have many subcellular structures known as organelles, which perform jobs much like an organ does in the body. The researchers conceptualise ELVAs as a “superorganelle” because it is a network of many different types of cellular components working together as a single unit.

The study revealed a crucial moment during the oocyte maturation stage, which is when an oocyte converts into a mature egg, preparing for ovulation and possible fertilisation. During this stage, the researchers observed ELVAs moving towards the cell’s surface and breaking down the protein aggregates, essentially deep-cleaning the cytoplasm. This is the first observation of the unique strategy oocytes employ to get rid of protein aggregates.

“An oocyte must donate all its cytoplasm to the embryo at fertilisation, so it cannot afford for garbage to accumulate, which would pose an existential risk for its function. In that sense, ELVAs are like a sophisticated waste disposal network or clean-up crew, patrolling the cytoplasm to ensure no aggregates are freely floating. ELVAs keep these aggregates in a confined environment until the oocyte is ready to dispose of them in one fell swoop. It’s an effective and energy-efficient strategy,” says Dr. Zaffagnini, postdoctoral researcher at the Centre for Genomic Regulation.

Protein aggregates may contribute to infertility

Fertility declines with age, and poor oocyte quality is the major cause of female infertility. Global infertility rates are also on the rise, with delayed motherhood being one of the contributing factors. Understanding how oocytes remain healthy, and what causes these strategies to fail with age, is critical for understanding unexplained causes of infertility and open up new avenues for treatment.

The findings of the study suggest that the presence of protein aggregates could interfere with both egg and embryo quality. When the researchers experimentally prevented the ability of ELVAs to degrade protein aggregates during the oocyte maturation process, it led to the formation of defective eggs. When the researchers intervened and “forced” the embryos to inherit aggregated proteins, 3 in 5 (60%) failed to complete very early stages of development.

“A lot of studies have historically focused on one small aspect of why oocyte quality declines, which are meiosis and euploidy. However, a recent review of eleven thousand embryo transfers has shown that the decline in female fertility with age are heavily influenced by other, yet unknown factors. Our research opens a fascinating future direction to explore whether protein degradation, and problems with how they are regulated in oocytes, could explain the age-related decline in embryo health,” concludes Dr. Böke.

Another type of long-lived cell which do not divide yet have to deal with protein aggregates are neurons. The accumulation of the harmful substances in these cells is linked to the development of several types of neurodegenerative diseases including Alzheimer’s. Could ELVA-like compartments also exist in neurons and other cell types? The study opens the door for future research avenues beyond the field of reproduction. 

Reference:

Gabriele Zaffagnini, Shiya Cheng, Marion C. Salzer, Manuel Irimia, Melina Schuh, Elvan Böke, Mouse oocytes sequester aggregated proteins in degradative super-organelles, Cell, DOI:https://doi.org/10.1016/j.cell.2024.01.031.

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Long-Term Ozone Exposure Linked to Increased Risk of Chronic Kidney Disease Mortality, reveals study

Chronic kidney disease (CKD) is a significant public health concern worldwide, with mortality rates continuing to rise. While the adverse effects of environmental pollutants on respiratory and cardiovascular health are well-documented, the impact on renal outcomes remains unclear.

Ozone, a major component of air pollution, is known to induce oxidative stress and inflammation, which may contribute to the progression of CKD. A recent study aimed to investigate the association between long-term ozone (O3) exposure and mortality in individuals with CKD. This study was published in the journal of BMC Nephrology by Ejin Kim and colleagues.

A cohort of 61,073 participants was included in this study, with researchers employing Cox proportional hazards models to analyze the association between ozone exposure and the risk of end-stage renal disease (ESRD) and mortality. Ozone concentrations were calculated based on exposure one year before enrollment using inverse distance weighting (IDW) for interpolation. Models were adjusted for socioeconomic status and other measured pollutants.

The key findings of the study were:

  • In both single and two-pollutant models, long-term ozone exposure was significantly associated with an increased risk of ESRD and all-cause mortality.

  • The hazard ratios (HR) for ozone exposure varied depending on the assessment method, with HR values of 1.025 (95% CI: 1.014–1.035) at the district level and 1.04 (95% CI: 1.035–1.045) at the individual address level for ESRD risk.

  • Similarly, HR values for all-cause mortality were 1.012 (95% CI: 1.008–1.017) at the district level and 1.04 (95% CI: 1.031–1.05) at the individual address level.

This study provides compelling evidence that long-term ambient ozone exposure increases the risk of end-stage renal disease and mortality in individuals with chronic kidney disease. The findings underscore the importance of implementing strategies to reduce ozone emissions, which would not only benefit public health but also contribute to environmental preservation. Efforts to mitigate ozone pollution are essential in safeguarding the health of vulnerable populations and promoting overall well-being.

Reference:

Kim, E., Huh, H., Mo, Y., Park, J. Y., Jung, J., Lee, H., Kim, S., Kim, D. K., Kim, Y. S., Lim, C. S., Lee, J. P., Kim, Y. C., & Kim, H. Long-term ozone exposure and mortality in patients with chronic kidney disease: a large cohort study. BMC Nephrology,2024;25(1). https://doi.org/10.1186/s12882-024-03500-6

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H. pylori Infection Linked to Increased Dementia Risk in Older Adults

Chronic infectious diseases are increasingly recognized as potential contributors to dementia risk, prompting researchers to explore the role of infections such as H. pylori in cognitive decline. The association between chronic infectious diseases and dementia risk, including Alzheimer’s disease, has gained attention in recent years. Helicobacter pylori, a common bacterial infection affecting the stomach lining, has been suggested as a potential contributor to dementia risk.

A recent study aimed to investigate the association between H. pylori infection and incident dementia in older adults. This study was published in the Journal Of The American Geriatrics Society by Virgilio H. and colleagues. Conducted on a prospective cohort of 689 older agricultural workers aged 65 years and above from Southwest France, this study assessed the association between H. pylori infection and incident dementia over a 7-year follow-up period.

Participants were categorized based on H. pylori status determined by serology at baseline, and cognitive performance was evaluated. Survival analyses, including Kaplan–Meier curves and Cox proportional hazards models, were used to explore the risk of incident dementia according to H. pylori status.

  • Among the participants, 29.0% were H. pylori-positive at baseline.

  • These individuals exhibited worse cognitive performance compared to H. pylori-negative participants at baseline.

  • Over the follow-up period, 85 incident dementia cases were diagnosed.

  • After adjusting for confounding factors such as age, sex, education, and cardiovascular risk factors, H. pylori infection remained significantly associated with an increased risk of dementia (HR 1.70, 95% CI 1.05–2.74).

  • The risk was particularly pronounced for Alzheimer’s disease (HR 2.85, 95% CI 1.58–5.12).

Despite a decrease in the prevalence of H. pylori infection, this study provides compelling evidence for the association between H. pylori infection and dementia, particularly Alzheimer’s disease, in older adults. These findings underscore the importance of further research to elucidate the mechanisms linking infectious diseases, gut inflammation, and pathological brain aging. Understanding these mechanisms could pave the way for novel preventive and therapeutic strategies to mitigate dementia risk in older populations.

Reference:

Hernández-Ruiz, V., Roubaud-Baudron, C., Von Campe, H., Retuerto, N., Mégraud, F., Helmer, C., Amieva, H., & Pérès, K. Association between Helicobacter pylori infection and incident risk of dementia: The AMI cohort. Journal of the American Geriatrics Society,2024. https://doi.org/10.1111/jgs.18748

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