Single-Track Magnetic Tape Absolute Position Sensor with Self-Adaptivity.

In this study, we demonstrate a single-track magnetic code tape-based absolute position sensor system. Unlike traditional dual-track systems, our method simplifies manufacturing and avoids crosstalk between tracks, offering higher tolerance to alignment errors. The sensing system employs an array of magnetic field sensing elements that recognize the bit sequence encoded on the tape. This approach allows for accurate position determination even when the number of sensing elements is fewer than the number of bits covered, and without the need for specific spacing between sensing elements and bit length. We demonstrate the system's ability to learn and adapt to various magnetic code patterns, including those that are irregular or have been altered. Our method can identify and localize the sensed magnetic field pattern directly within a self-learned magnetic field map, providing robust performance in diverse conditions. This self-adaptive capability enhances operational safety and reliability, as the system can continue functioning even when the magnetic tape is misaligned or has undergone changes.

Placebo and Nocebo Effects on Sports and Exercise Performance: A Systematic Literature Review Update.

Sports performance could be affected by placebo and nocebo effects. The last literature review on placebo and nocebo effects on sports and exercise performance was published in 2019. In the past five years, several new studies have been published. This review aimed to update the previous synthesis and evaluate the results of new studies focusing on placebo or nocebo interventions in sports and exercise by determining the form and magnitude of their effect. Hence, we searched for empirical studies published from 2019 until the end of May 2024 indexed in PubMed, Medline, Web of Science, EBSCO, and Google Scholar databases. The search yielded 20 eligible studies with control or baseline-control conditions, focusing on nutritional, mechanical, and other mixed ergogenic aids. They yielded small to large placebo effects (Cohen's d) for nutritional (d = 0.86), mechanical (d = 0.38), cream and gel (d = 0.05), and open-label placebo (d = 0.16) interventions. The pooled effect size for placebo effects was moderate to large (d = 0.67), larger than in the earlier review, suggesting that placebo effects can improve motor performance even more than previously reported. However, based on five measures from three studies, the nocebo effects were almost twice as large (d = 1.20). Accordingly, the current findings support and expand the last review in the field by yielding additional support for placebo and nocebo effects in sports and exercise.

A Fullerton Functional Fitness Test-based exercise intervention for older adults yields quick physical and psychological benefits.

OBJECTIVES: Functional fitness is essential for healthy living in older adults. Specially targeted fitness programs might be the most beneficial. This intervention study aimed to assess the efficacy of a specific 16-week exercise program in improving functions as measured by the Fullerton Functional Fitness Test (FFFT), also known as the Senior Test, in older adults. PARTICIPANTS: Thirty-eight participants (66 % women, Mage = 80.15, SD = 7.21) were randomized into an exercise group (n = 24) and a waiting list control group (n = 14). The exercise group trained three times a week for 1 h. METHODS: Objective tests (FFFT and handgrip power) and subjective psychological measures (life satisfaction, resilience, happiness, perceived stress, and well-being) were obtained at baseline, after eight weeks, and after 16 weeks. The data were analyzed using mixed-effect regression models. RESULTS: The results yielded statistically significant group-by-time interactions in all models, indicating improvements in physical and psychological measures over time in the treatment group compared to the control group. Significant differences between the groups in the estimated marginal means (with adjusted 95 % confidence intervals) emerged after 16 weeks in happiness (-3.5 [-6.5, -0.4]), resilience (-5.5 [-9.9, -1.2]), perceived stress (2.2 [0.2, 4.2]), well-being (-5.8 [-7.9, -3.6]), upper limb strength (-5.7 [-9.0, -2.4]), upper body flexibility (-8.7 [-16.4, -1.0]), and agility and balance (4.6 [1.2, 8.1]). Except for happiness and resilience, these differences surfaced already after eight weeks. CONCLUSION: The here-employed 16-week exercise program, targeting the test elements of the FFFT, efficiently induced physical and mental improvements in older adults.

Profiling and assessing the risks of image- and performance-enhancing drugs use during the COVID-19 lockdown.

Background: Image and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one's overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an international sample of young adults. Methods: A cross-sectional observational study was carried out in eight countries (United Kingdom, Italy, Lithuania, Hungary, Portugal, Spain, Brazil, and Japan) between April and May 2020. The survey questionnaire included validated measurements such as Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI), and Self-Compassion Scale (SCS) as well as questions about the type of IPEDs, purchasing methods and socio-demographic information. Results: A total of 736 IPEDs users were included in the survey. Their mean age was 33.05 years (±SD = 10.06), and 64.2% were female participants. Overall, 6.8% were found at risk of exercise addiction (EAI >24), 27.6% presented high levels of appearance anxiety, and 24.9% revealed low levels of emotional regulation's self-compassion. Most participants (55.6%) purchased IPEDs through pharmacies/specialized shops, while 41.3% purchased IPEDs on the Internet. Online IPEDs buyers were mainly men who had higher scores on the Exercise Addiction Inventory. One or more IPEDs classifiable as "potentially risky" were used by 66.3% of the sample. Users of "potentially risky IPEDs" were younger and primarily men. They showed higher scores both on the Exercise Addiction Inventory and Appearance Anxiety Inventory. Conclusion: This study profiled users of IPEDs when the most restrictive COVID-19 lockdown policies were implemented in all the participating countries. More targeted post-COVID 19 prevention strategies should be implemented according to the emerged socio-demographic and psychopathological traits and cross-cultural differences emerged. Longitudinal studies will also be needed to determine the long-term effect of the COVID-19 lockdown on IPEDs consumption.

Whole lung lavage and GM-CSF use for pulmonary alveolar proteinosis in an infant with lysinuric protein intolerance: a case report.

BACKGROUND: Lysinuric protein intolerance (LPI) is a multi-organ metabolic disorder characterized by the imbalance in absorption and excretion of cationic amino acids like lysine, ornithine and arginine. Infants with LPI typically present with recurrent vomiting, poor growth, interstitial lung disease or renal impairment. The early onset of pulmonary alveolar proteinosis (PAP) has been reported to be associated with a severe form of LPI. Treatment of PAP most commonly consists of whole-lung lavage (WLL) and in autoimmune PAP, granulocyte-macrophage colony stimulating factor (GM-CSF) administration. Nevertheless, GM-CSF therapy in LPI-associated PAP has not been scientifically justified. CASE PRESENTATION: We describe the case of an 8-month-old infant presenting with respiratory failure due to LPI associated with PAP, who was twice treated with WLL; firstly, while on veno-venous ECMO assistance and then by the use of a selective bronchial blocker. After the two treatments with WLL, she was weaned from daytime respiratory support while on initially subcutaneous, then on inhaled GM-CSF therapy. CONCLUSIONS: This case supports the notion that GM-CSF therapy might be of benefit in patients with LPI-associated PAP. Further studies are needed to clarify the exact mechanism of GM-CSF in patients with LPI-associated PAP.

Perinatal asphyxia leads to acute kidney damage and increased renal susceptibility in adulthood.

Perinatal asphyxia (PA) poses a significant threat to multiple organs, particularly the kidneys. Diagnosing PA-associated kidney injury remains challenging and treatment options are inadequate. Furthermore, there is a lack of long-term follow-up data regarding the renal implications of PA. In this study, 7-day-old male Wistar rats were exposed to PA using a gas mixture (4% O2; 20% CO2 in N2 for 15 minutes) to investigate molecular pathways linked to renal tubular damage, hypoxia, angiogenesis, heat-shock response, inflammation, and fibrosis in the kidney. In a second experiment, adult rats with a history of PA were subjected to moderate renal ischemia-reperfusion (IR) injury to test the hypothesis that PA exacerbates renal susceptibility. Our results revealed an increased gene expression of renal injury markers (KIM-1, NGAL), hypoxic- and heat shock factors (HIF-1α, HSF-1, HSP-27), pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, MCP-1), and fibrotic markers (TGF-ß, CTGF, Fibronectin) promptly after PA. Moreover, a machine learning model was identified through Random Forest analysis, demonstrating an impressive classification accuracy (95.5%) for PA. Post-PA rats showed exacerbated functional decline and tubular injury and more intense hypoxic-, heat-shock-, pro-inflammatory-, and pro-fibrotic response after renal IRI compared to controls. In conclusion, PA leads to subclinical kidney injury, which may increase the susceptibility to subsequent renal damage later in life. Additionally, the parameters identified through Random Forest analysis provide a robust foundation for future biomarker research in the context of PA.

Airway management may influence postoperative ventilation need in preterm infants after laser eye treatment.

BACKGROUND: Retinopathy of prematurity is treated with laser photocoagulation under general anaesthesia with intubation using endotracheal tube (ETT), which carries a risk for postoperative mechanical ventilation (MV). Laryngeal mask airway (LMA) may provide a safe alternative. We assessed the need for postoperative MV in preterm infants who received LMA versus ETT. METHODS: In this single-centre, retrospective cohort study, preterm infants who underwent laser photocoagulation between 2014-2021 were enroled. For airway management, patients received either LMA (n = 224) or ETT (n = 47). The outcome was the rate of postoperative MV. RESULTS: Patients' age were 37 [35;39] weeks of postmenstrual age, median bodyweight of Group LMA was higher than Group ETT's (2110 [1800;2780] g versus 1350 [1230;1610] g, respectively, p < 0.0001). After laser photocoagulation, 8% of Group LMA and 74% of Group ETT left the operating theatre requiring MV. Multiple logistic regression revealed that the use of LMA and every 100 g increase in bodyweight significantly decreased the odds of mechanical ventilation (OR 0.21 [95% CI 0.07-0.60], and 0.73 [95% CI 0.63-0.84], respectively). Propensity score matching confirmed that LMA decreased the odds of postoperative MV (OR 0.30 [95% CI 0.11-0.70]). CONCLUSION: The use of LMA is associated with a reduced need for postoperative MV. IMPACT: Using laryngeal mask airway instead of endotracheal tube for airway management in preterm infants undergoing general anaesthesia for laser photocoagulation for treating retinopathy of prematurity could significantly decrease the postoperative need for mechanical ventilation. According to our current understanding, this has been the largest study investigating the effect of laryngeal mask airway during general anaesthesia in preterm infants. Our study suggests that the use of laryngeal mask airway is a viable alternative to intubation in the vulnerable population of preterm infants in need of laser treatment.

Could physical activity alleviate smartphone addiction in university students? A systematic literature review.

Objectives: Recently, the widespread surge in smartphone addiction (SA) has raised major global health concerns and prompted researchers to scrutinize the inverse relationship between physical activity (PA) and the risk of SA. This systematic literature review aims to synthesize the empirical research on the relationship between PA and SA among university students representing the most affected age group. Methods: Adopting the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we explored five databases: PubMed, Social Sciences Research Network (SSRN), Oxford Research Archive, Journal Storage (JSTOR), and Google Scholar. We used the Mixed Methods Appraisal Tools (MMAT) for quality assessment. Results: Thirty-one studies met the inclusion criteria. Twenty-eight of them were cross-sectional, and three were experimental. The 31 studies emerged from 12 countries, most stemming (45.16%) from China. Their findings suggest an inverse relationship between PA and SA in the examined population. However, the direct relationship may be weak based on correlational studies, while intervention research yields noteworthy effects. Still, other factors like resilience may mediate the studied relationship. Methodological concerns render the results of correlational studies tentative. Conclusions: Regular PA could be a promising preventive measure for SA. Future work should use objective PA indices in longitudinal research designs while assessing the type and duration of smartphone applications used via device meters. In correlational studies, interviews should follow up on the high SA risk or too much device use. In conclusion, moderate evidence indicates that PA can reduce SA among university students.

Exercise addiction in team sports: A systematic literature review.

While regular exercise should be part of the contemporary lifestyle, many people overindulge in it to the point of losing control over their behavior. This condition is known as exercise addiction (EA). Although addiction is an individual phenomenon, and most of the over 1,000 published studies on EA look at individual exercisers, there are studies on team sports athletes, too. Theoretically, these athletes should not manifest exercise addiction, but some studies are projecting the contrary. Therefore, in this literature review, we analyze EA in team athletes. Based on four databases (PsycINFO, SPORTDiscus, Web of Science, and Google Scholar), we located 22 articles conforming to inclusion criteria. These studies suggest a high risk of exercise addiction among team sports participants. While the figures are lower than for individual exercisers, they are in discord with the concept of addiction as a dysfunction, and the lack of a single case of exercise addiction reported (to date) in team sports athletes in the academic literature. In agreement with a recent position paper, we conclude that there are substantial conceptual and measurement errors in exercise addiction research.

Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-ß- and PDGF-B-Mediated Fibrotic Processes.

Among patients on peritoneal dialysis (PD), 50-80% will develop peritoneal fibrosis, and 0.5-4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-ß- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory PD. The impact of PDE-EVs on the epithelial-mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro and in vivo in the chlorhexidine digluconate (CG)-induced mice model of peritoneal fibrosis. PDE-EVs showed spherical morphology in the 100 nm size range, and their spectral features, CD63, and annexin positivity were characteristic of EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE- or PDGF-B-induced proliferation. Furthermore, PDE-EVs inhibited the PDE- or TGF-ß-induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased the submesothelial thickening of CG-treated mice. We demonstrated that PDE-EVs significantly inhibit the PDGF-B- or TGF-ß-induced fibrotic processes in vitro and in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases.

The Impact of Parental Electronic Health Literacy on Disease Management and Outcomes in Pediatric Type 1 Diabetes Mellitus: Cross-Sectional Clinical Study.

BACKGROUND: Despite the growing uptake of smart technologies in pediatric type 1 diabetes mellitus (T1DM) care, little is known about caregiving parents' skills to deal with electronic health information sources. OBJECTIVE: We aimed to assess the electronic health literacy of parents caring for children with T1DM and investigate its associations with disease management and children's outcomes. METHODS: A cross-sectional survey was performed involving 150 parent-child (8-14 years old with T1DM) dyads in a university pediatric diabetology center. Parents' electronic health literacy (eHealth Literacy Scale [eHEALS]), general health literacy (Chew questionnaire and Newest Vital Sign [NVS]), and attitudes toward T1DM care (Parental Self-Efficacy Scale for Diabetes Management [PSESDM] and Hypoglycemia Fear Survey [HFS]) were investigated. Children's treatment, HbA1c level, and quality of life (Pediatric Quality of Life Inventory Diabetes Module [PedsQL Diab] and EQ-5D-Y-3L) were assessed. Multiple linear regression analysis was performed to investigate the determining factors of 6-month average HbA1c. RESULTS: Of the 150 children, 38 (25.3%) used a pen, 55 (36.7%) used a pen plus a sensor, 6 (4.0%) used an insulin pump, and 51 (34.0%) used an insulin pump plus a sensor. Parents' average eHEALS score (mean 31.2, SD 4.9) differed significantly by educational level (P=.04) and the children's treatment (P=.005), being the highest in the pump + sensor subgroup. The eHEALS score showed significant Pearson correlations with the Chew score (r=-0.45; P<.001), NVS score (r=0.25; P=.002), and PSESDM score (r=0.35; P<.001) but not with the children's HbA1c (r=-0.143; P=.08), PedsQL Diab (r=-0.0002; P>.99), and EQ-5D-Y-3L outcomes (r=-0.13; P=.12). Regression analysis revealed significant associations of the child's HbA1c level with sex (ß=0.58; P=.008), treatment modality (pen + sensor: ß=-0.66; P=.03; pump + sensor: ß=-0.93; P=.007), and parents' self-efficacy (PSESDM; ß=-0.08; P=.001). CONCLUSIONS: Significantly higher parental electronic health literacy was found in T1DM children using a glucose sensor. The electronic health literacy level was associated with parents' diabetes management attitude but not with the child's glycemic control. Studies further investigating the role of parental electronic health literacy in T1DM children managed at different levels of care and the local context are encouraged.

Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain.

Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers (n = 25) associated with cognitive domains (n = 9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n = 10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n = 776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n = 474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high neuroinflammatory subgroup in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness.

Psychological Aspects of Motocross Racing Considering Expected, Perceived, and Actual Performance.

Motocross racing is a seldom-researched popular extreme sport. This field research aimed to investigate feeling states, perceived arousal, anxiety, and negative and positive affect in the anticipatory and recovery race periods and their relationship to expected and perceived performance. Twenty Motocross racers completed psychometric scales before and after a national championship race. Results revealed that objective performance was unrelated to psychological measures. Arousal, anxiety, and positive affect were lower after the race. Expected performance was unrelated to postrace measures. Still, perceived performance correlated significantly with the feeling state, anxiety, and positive affect after the race and the feeling state before the race. Furthermore, racers who performed as expected or better showed improved feeling states after the race compared with those who did worse than expected. The core affect of the latter group declined. This research on psychological states during Motocross races could motivate new initiatives for future studies.

Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss.

Background: SARS-CoV-2 infection during pregnancy increases the risk of severe obstetrical complications. Detailed evaluation of COVID-19-associated coagulopathy in a pregnancy with stillbirth hasn't been described so far. Besides knowledge gaps in the pathomechanism leading to stillbirth in COVID-19 pregnancies, currently, no prognostic biomarker is available to identify pregnant patients who are at imminent risk of COVID-19-associated maternal and fetal complications, requiring immediate medical attention. Case: Here we report the case of a 28-year-old SARS-CoV-2 infected pregnant patient, admitted to our hospital at 28 weeks of gestation with intrauterine fetal loss. The presence of SARS-CoV-2 placentitis was confirmed by immunohistological evaluation of the placenta. She had only mild upper respiratory symptoms and her vital signs were within reference throughout labor and postpartum. The stillborn infant was delivered per vias naturales. Fibrinogen concentrate was administered before and after labor due to markedly decreased fibrinogen levels (1.49 g/l) at admission and excessive bleeding during and after delivery. Although coagulation screening tests were not alarming at admission, the balance of hemostasis was strikingly distorted in the patient. As compared to healthy age- and gestational age-matched pregnant controls, increased D-dimer, low FVIII activity, low FXIII level, marked hypocoagulability as demonstrated by the thrombin generation assay, together with shortened clot lysis and decreased levels of fibrinolytic proteins were observed. These alterations most likely have contributed to the increased bleeding observed during labor and in the early postpartum period. Interestingly, at the same time, only moderately altered inflammatory cytokine levels were found at admission. Serum ACE2 activity did not differ in the patient from that of age- and gestational age-matched healthy controls, suggesting that despite previous speculations in the literature, ACE2 may not be used as a potential biomarker for the prediction of COVID-19 placentitis and threatening fetal loss in SARS-CoV-2-infected pregnancies. Conclusions: Although based on this case report no prognostic biomarker could be identified for use in pregnant patients with imminent risk of fetal loss associated with COVID-19 placentitis, the above-described hemostasis alterations warrant awareness of postpartum hemorrhagic complications and could be helpful to identify patients requiring intensified medical attention.

Toxoplasma gondii infection associated with inflammasome activation and neuronal injury.

Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p < 0.001). TOXO seropositive participants had significantly higher NSE (3713 vs. 2200 pg/ml, p < 0.001) and IL-18 levels (1068 vs. 674 pg/ml, p < 0.001) than seronegative participants, and evaluation within patients and HC separately showed similar results. Post-hoc analysis on cytomegalovirus and herpes simplex virus 1 IgG status showed no associations with NSE or IL-18 which may suggest TOXO specificity. These results may indicate ongoing inflammasome activation and neuronal injury in people with TOXO infections unrelated to diagnosis.

Get reliable laboratory findings - how to recognize the deceptive effects of angiotensin-converting enzyme inhibitor therapy in the laboratory diagnostics of sarcoidosis?

OBJECTIVES: Serum angiotensin-converting enzyme (ACE) is the only biomarker routinely used in the laboratory diagnostics of sarcoidosis, and ACE inhibitor (ACEi) drugs are among the most prescribed drugs worldwide. Taking ACEi can mislead medical teams by lowering ACE activity, delaying diagnosis and giving a false impression of disease activity of sarcoidosis. We aimed to develop a simple method to detect the presence of ACEi drugs in samples, to investigate the ACEi medication-caused interference and consequences in a retrospective study. METHODS: ACE activity and the level of ACE inhibition were determined for 1823 patients with suspected sarcoidosis. These values were compared with the therapeutic information at the first and follow-up visits. RESULTS: A total of 302 patients had biochemical evidence of an ACEi drug effect during diagnostic ACE activity testing. In their case, ACE activity was significantly lower (median(IQR): 4.41 U/L(2.93-6.72)) than in patients not taking ACEi (11.32 U/L(8.79-13.92), p<0.01). In 62 sarcoidosis patients, the ACEi reduced ACE activity to the reference range or below. Only in 40 % of the cases was the medication list recorded in the outpatient chart and only in 3 cases was low ACE activity associated with ACEi use. 67 % of the repeated ACE activity measurements were also performed during ACEi therapy. CONCLUSIONS: Our study revealed that the use of ACEi is common in patients with suspected sarcoidosis. The ACE activity lowering effect of ACEi drugs may escape the attention of medical teams which can lead to diagnostic errors and unnecessary tests. Nevertheless, these pitfalls can be avoided by using a method suggested by our team.

Divergent epigenetic responses to perinatal asphyxia in severe mental disorders.

Epigenetic modifications influenced by environmental exposures are molecular sources of phenotypic heterogeneity found in schizophrenia and bipolar disorder and may contribute to shared etiopathogenetic mechanisms of these two disorders. Newborns who experienced perinatal asphyxia have suffered reduced oxygen delivery to the brain around the time of birth, which increases the risk of later psychiatric diagnosis. This study aimed to investigate DNA methylation in blood cells for associations with a history of perinatal asphyxia, a neurologically harmful condition occurring within the biological environment of birth. We utilized prospective data from the Medical Birth Registry of Norway to identify incidents of perinatal asphyxia in 643 individuals with schizophrenia or bipolar disorder and 676 healthy controls. We performed an epigenome wide association study to distinguish differentially methylated positions associated with perinatal asphyxia. We found an interaction between methylation and exposure to perinatal asphyxia on case-control status, wherein having a history of perinatal asphyxia was associated with an increase of methylation in healthy controls and a decrease of methylation in patients on 4 regions of DNA important for brain development and function. The differentially methylated regions were observed in genes involved in oligodendrocyte survival and axonal myelination and functional recovery (LINGO3); assembly, maturation and maintenance of the brain (BLCAP;NNAT and NANOS2) and axonal transport processes and neural plasticity (SLC2A14). These findings are consistent with the notion that an opposite epigenetic response to perinatal asphyxia, in patients compared with controls, may contribute to molecular mechanisms of risk for schizophrenia and bipolar disorder.

Longitudinal Transcriptomic Analysis of Human Cortical Spheroids Identifies Axonal Dysregulation in the Prenatal Brain as a Mediator of Genetic Risk for Schizophrenia.

BACKGROUND: Schizophrenia (SCZ) has a known neurodevelopmental etiology, but limited access to human prenatal brain tissue hampers the investigation of basic disease mechanisms in early brain development. Here, we elucidate the molecular mechanisms contributing to SCZ risk in a disease-relevant model of the prenatal human brain. METHODS: We generated induced pluripotent stem cell-derived organoids, termed human cortical spheroids (hCSs), from a large, genetically stratified sample of 14 SCZ cases and 14 age- and sex-matched controls. The hCSs were differentiated for 150 days, and comprehensive molecular characterization across 4 time points was carried out. RESULTS: The transcriptional and cellular architecture of hCSs closely resembled that of fetal brain tissue at 10 to 24 postconception weeks, showing strongest spatial overlap with frontal regions of the cerebral cortex. A total of 3520 genes were differentially modulated between SCZ and control hCSs across organoid maturation, displaying a significant contribution of genetic loading, an overrepresentation of risk genes for autism spectrum disorder and SCZ, and the strongest enrichment for axonal processes in all hCS stages. The two axon guidance genes SEMA7A and SEMA5A, the first a promoter of synaptic functions and the second a repressor, were downregulated and upregulated, respectively, in SCZ hCSs. This expression pattern was confirmed at the protein level and replicated in a large postmortem sample. CONCLUSIONS: Applying a disease-relevant model of the developing fetal brain, we identified consistent dysregulation of axonal genes as an early risk factor for SCZ, providing novel insights into the effects of genetic predisposition on the neurodevelopmental origins of the disorder.

Physical Activity and Psychological Resilience in Older Adults: A Systematic Review of the Literature.

Older adults face numerous unfavorable functional changes caused by aging, but many exhibit resilience, which helps them cope with challenges. Physical activity is positively associated with resilience. Therefore, this systematic literature review aimed to uncover the relationships between physical activity and resilience in older adults. We have analyzed three freely and openly available databases: (a) PubMed/Medline, (b) ScienceDirect, and (c) Google Scholar, which yielded 20 eligible articles based on the inclusion and exclusion criteria. Most studies (14) were cross-sectional, three were longitudinal, and three others used mindfulness-based or endurance-enhancing physical activity interventions. Their results revealed increased resilience even after short-duration and low-frequency interventions. Cross-sectional research results also support the positive relationship between physical activity and resilience in older adults, suggesting that the relationship might depend on exercise volume. Still, further research is needed to design interventions, understand the mechanism(s) involved in altering resilience, and maximize physical activity's benefits in aging people.