Publications

@article{Lin2024-pt,

title = {Investigations towards tryptophan uptake and transport across an 

 in vitro model of the oral mucosa epithelium},

author = {Grace C Lin and Julia Tevini and Lisa Mair and Heinz-Peter Friedl and Dietmar Fuchs and Thomas Felder and Johanna M Gostner and Winfried Neuhaus},

year  = {2024},

date = {2024-07-01},

journal = {Int. J. Tryptophan Res.},

volume = {17},

pages = {11786469241266312},

publisher = {SAGE Publications},

abstract = {Tryptophan is an essential amino acid and plays an important 

 role in several metabolic processes relevant for the human 

 health. As the main metabolic pathway for tryptophan along the 

 kynurenine axis is involved in inflammatory responses, changed 

 metabolite levels can be used to monitor inflammatory diseases 

 such as ulcerative colitis. As a progenitor of serotonin, 

 altered tryptophan levels have been related to several 

 neurogenerative diseases as well as depression or anxiety. While 

 tryptophan concentrations are commonly evaluated in serum, a 

 non-invasive detection approach using saliva might offer 

 significant advantages, especially during long-term treatments 

 of patients or elderly. In order to estimate whether active 

 transport processes for tryptophan might contribute to a 

 potential correlation between blood and saliva tryptophan 

 concentrations, we investigated tryptophan's transport across an 

 established oral mucosa in vitro model. Interestingly, treatment 

 with tryptophan revealed a concentration dependent secretion of 

 tryptophan and the presence of a saturable transporter while 

 transport studies with deuterated tryptophan displayed increased 

 permeability from the saliva to the blood compartment. Protein 

 analysis demonstrated a distinct expression of L-type amino acid 

 transporter 1 (LAT1), the major transporter for tryptophan, and 

 exposure to inhibitors (2 -amino-2-norbornanecarboxylic acid 

 (BCH), L-leucine) led to increased tryptophan levels on the 

 saliva side. Additionally, exposure to tryptophan in equilibrium 

 studies resulted in a regulation of LAT1 at the mRNA level. The 

 data collected in this study suggest the participation of active 

 transport mechanisms for tryptophan across the oral mucosa 

 epithelium. Future studies should investigate the transport of 

 tryptophan across salivary gland epithelia in order to enable a 

 comprehensive understanding of tryptophan exchange at the 

 blood-saliva barrier.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hargitai2024-fp,

title = {Chemical respiratory sensitization-Current status of mechanistic 

 understanding, knowledge gaps and possible identification 

 methods of sensitizers},

author = {Rita Hargitai and Lucia Parráková and Tünde Szatmári and Pablo Monfort-Lanzas and Valentina Galbiati and Karine Audouze and Florence Jornod and Yvonne C M Staal and Sabina Burla and Aline Chary and Arno C Gutleb and Katalin Lumniczky and Rob J Vandebriel and Johanna M Gostner},

year  = {2024},

date = {2024-07-01},

journal = {Front. Toxicol.},

volume = {6},

pages = {1331803},

publisher = {Frontiers Media SA},

abstract = {Respiratory sensitization is a complex immunological process 

 eventually leading to hypersensitivity following re-exposure to 

 the chemical. A frequent consequence is occupational asthma, 

 which may occur after long latency periods. Although 

 chemical-induced respiratory hypersensitivity has been known for 

 decades, there are currently no comprehensive and validated 

 approaches available for the prospective identification of 

 chemicals that induce respiratory sensitization, while the 

 expectations of new approach methodologies (NAMs) are high. A 

 great hope is that due to a better understanding of the 

 molecular key events, new methods can be developed now. However, 

 this is a big challenge due to the different chemical classes to 

 which respiratory sensitizers belong, as well as because of the 

 complexity of the response and the late manifestation of 

 symptoms. In this review article, the current information on 

 respiratory sensitization related processes is summarized by 

 introducing it in the available adverse outcome pathway (AOP) 

 concept. Potentially useful models for prediction are discussed. 

 Knowledge gaps and gaps of regulatory concern are identified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Monfort-Lanzas2024-bw,

title = {ExonSurfer: a web-tool to design primers at exon-exon 

 junctions},

author = {Pablo Monfort-Lanzas and Elena Cristina Rusu and Lucia Parrakova and Cornelia A Karg and Dorina-Elina Kernbichler and Dietmar Rieder and Peter Lackner and Hubert Hackl and Johanna M Gostner},

year  = {2024},

date = {2024-06-01},

journal = {BMC Genomics},

volume = {25},

number = {1},

pages = {594},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) 

 with intercalating dyes is one of the main techniques to assess 

 gene expression levels used in basic and applied research as 

 well as in diagnostics. However, primer design for RT-qPCR can 

 be complex due to the high demands on primer quality. Primers 

 are best placed on exon junctions, should avoid polymorphic 

 regions, be specific to the target transcripts and also prevent 

 genomic amplification accurately, among others. Current software 

 tools manage to meet all the necessary criteria only 

 insufficiently. Here, we present ExonSurfer, a novel, 

 user-friendly web-tool for qPCR primer design. RESULTS: 

 ExonSurfer combines the different steps of the primer design 

 process, encompassing target selection, specificity and 

 self-complementarity assessment, and the avoidance of issues 

 arising from polymorphisms. Amplification of potentially 

 contaminating genomic DNA is avoided by designing primers on 

 exon-exon junctions, moreover, a genomic alignment is performed 

 to filter the primers accordingly and inform the user of any 

 predicted interaction. In order to test the whole performance of 

 the application, we designed primer pairs for 26 targets and 

 checked both primer efficiency, amplicon melting temperature and 

 length and confirmed the targeted amplicon by Sanger sequencing. 

 Most of the tested primers accurately and selectively amplified 

 the corresponding targets. CONCLUSION: ExonSurfer offers a 

 comprehensive end-to-end primer design, guaranteeing 

 transcript-specific amplification. The user interface is 

 intuitive, providing essential specificity and amplicon details. 

 The tool can also be used by command line and the source code is 

 available. Overall, we expect ExonSurfer to facilitate RT-qPCR 

 set-up for researchers in many fields.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wagner2024-be,

title = {CRP/Neopterin ratio and neuropsychiatric symptoms in patients 

 with different forms of pneumonia: Results of a pilot study},

author = {Katharina Konstanze Lilly Wagner and Daniele Corda and Andreas Steinmayr and Francesco Burkert and Dietmar Fuchs and Johanna Gostner and Stefanie Hofer and Lucia Parrakova and Irina Gasslitter and Günter Weiss and Christian Irsara and Sarah Maier and Andrea Griesmacher and Rosa Bellmann-Weiler and Katharina Kurz},

year  = {2024},

date = {2024-05-01},

journal = {Microorganisms},

volume = {12},

number = {6},

pages = {1099},

publisher = {MDPI AG},

abstract = {BACKGROUND: Pneumonia is one of the most common infectious 

 diseases, mostly caused by viruses or bacteria. In response to 

 bacteria or viruses which are different but which also are 

 partly overlapping, innate and adaptive immune responses are 

 induced, which can be quantified using the determination of 

 specific biomarkers. Among these, C-reactive protein (CRP) has 

 been established as a marker of innate immune function, whereas 

 Neopterin, which is mainly produced upon stimulation with 

 interferon-gamma, reflects cellular immune activation. AIM: We 

 investigated inflammation markers in patients with 

 microbiologically confirmed viral or bacterial pneumonia, and 

 studied the potential of CRP, Neopterin, and the CRP/Neopterin 

 ratio to distinguish between viral and bacterial pathogenesis. 

 Furthermore, we examined, how often neuropsychiatric symptoms 

 occur in patients suffering from different kinds of pneumonia. 

 PATIENTS AND METHOD: A total of 194 patients diagnosed with either coronavirus disease 2019 (COVID-19) (n = 63), bacterial pneumonia (n = 58), Influenza infection (n = 10), Influenza and a bacterial superinfection (n = 9), and COVID-19 patients with a bacterial superinfection (n = 54) were included in our pilot 

 study. Clinical as well as laboratory parameters were determined 

 shortly after admission. RESULTS: We found significantly higher 

 CRP/Neopterin ratios in patients with bacterial pneumonia 

 (median: 0.34) and lower CRP/Neopterin ratios in patients 

 hospitalized with COVID-19 infection (median: 0.03; p < 0.001). 

 Both in men and in women, the CRP/Neopterin ratio was able to 

 distinguish between viral and bacterial pathogens, but also was 

 able to detect bacterial super-infection (BSI) in subjects with 

 initial viral pneumonia (p < 0.001). Patients with BSI presented 

 with significantly lower CRP/Neopterin ratios (median 0.08) than 

 patients with bacterial infection only (median 0.34; p < 0.001). 

 Interestingly, COVID-19 patients had a decreased physical 

 functioning (as reflected in the ECOG score) and a higher 

 frequency of fatigue (84.1%) and neurological symptoms (54.8%) 

 than patients with pneumonia, due to other underlying pathogens. 

 Patients that reported fatigue during viral and bacterial 

 pneumonia presented with lower CRP concentrations than patients 

 without it. CONCLUSIONS: The CRP/Neopterin ratio is useful to 

 differentiate between viral and bacterial pathogenesis. The 

 occurrence of neuropsychiatric symptoms in pneumonia appears to 

 depend on the kind of pathogen causing the infection. Lower CRP 

 concentrations at admission appear to be related to fatigue 

 during acute viral and bacterial infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hu2024-df,

title = {Changes in cerebrospinal fluid proteins across the spectrum of 

 untreated and treated chronic HIV-1 infection},

author = {Zicheng Hu and Paola Cinque and Ameet Dravid and Lars Hagberg and Aylin Yilmaz and Henrik Zetterberg and Dietmar Fuchs and Johanna Gostner and Kaj Blennow and Serena S Spudich and Laura Kincer and Shuntai Zhou and Sarah Joseph and Ronald Swanstrom and Richard W Price and Magnus Gisslén},

year  = {2024},

date = {2024-05-01},

journal = {bioRxivorg},

abstract = {Using the Olink Explore 1536 platform, we measured 1,463 unique 

 proteins in 303 cerebrospinal fluid (CSF) specimens from four 

 clinical centers that included uninfected controls and 12 groups 

 of people living with HIV-1 infection representing the spectrum 

 of progressive untreated and treated chronic infection. We 

 present three initial analyses of these measurements: an overview 

 of the CSF protein features of the sample; correlations of the 

 CSF proteins with CSF HIV-1 RNA and neurofilament light chain 

 protein (NfL) concentrations; and comparison of the CSF proteins 

 in HIV-associated dementia ( HAD ) and neurosymptomatic CSF 

 escape ( NSE ). These reveal a complex but coherent picture of 

 CSF protein changes that includes highest concentrations of many 

 proteins during CNS injury in the HAD and NSE groups and variable 

 protein changes across the course of neuroasymptomatic systemic 

 HIV-1 progression, including two common patterns, designated as 

 lymphoid and myeloid patterns, related to the principal 

 involvement of their underlying inflammatory cell lineages. 

 Antiretroviral therapy reduced CSF protein perturbations, though 

 not always to control levels. The dataset of these CSF protein 

 measurements, along with background clinical information, is 

 posted online. Extended studies of this unique dataset will 

 provide more detailed characterization of the dynamic impact of 

 HIV-1 infection on the CSF proteome across the spectrum of HIV-1 

 infection, and further the mechanistic understanding of 

 HIV-1-related CNS pathobiology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gietl2024-ng,

title = {Laboratory parameters related to disease severity and physical 

 performance after reconvalescence of acute COVID-19 infection},

author = {Mario Gietl and Francesco Burkert and Stefanie Hofer and Johanna M Gostner and Thomas Sonnweber and Ivan Tancevski and Alex Pizzini and Sabina Sahanic and Andrea Schroll and Natascha Brigo and Alexander Egger and Rosa Bellmann-Weiler and Judith Löffler-Ragg and Günter Weiss and Katharina Kurz},

year  = {2024},

date = {2024-05-01},

journal = {Sci. Rep.},

volume = {14},

number = {1},

pages = {10388},

publisher = {Springer Science and Business Media LLC},

abstract = {Research into the molecular basis of disease trajectory and 

 Long-COVID is important to get insights toward underlying 

 pathophysiological processes. The objective of this study was to 

 investigate inflammation-mediated changes of metabolism in 

 patients with acute COVID-19 infection and throughout a one-year 

 follow up period. The study enrolled 34 patients with moderate 

 to severe COVID-19 infection admitted to the University Clinic 

 of Innsbruck in early 2020. The dynamics of multiple laboratory 

 parameters (including inflammatory markers [C-reactive protein 

 (CRP), interleukin-6 (IL-6), neopterin] as well as amino acids 

 [tryptophan (Trp), phenylalanine (Phe) and tyrosine (Tyr)], and 

 parameters of iron and vitamin B metabolism) was related to 

 disease severity and patients' physical performance. Also, 

 symptom load during acute illness and at approximately 60 days 

 (FU1), and one year after symptom onset (FU2) were monitored and 

 related with changes of the investigated laboratory parameters: 

 During acute infection many investigated laboratory parameters 

 were elevated (e.g., inflammatory markers, ferritin, kynurenine, 

 phenylalanine) and enhanced tryptophan catabolism and 

 phenylalanine accumulation were found. At FU2 nearly all 

 laboratory markers had declined back to reference ranges. 

 However, kynurenine/tryptophan ratio (Kyn/Trp) and the 

 phenylalanine/tyrosine ratio (Phe/Tyr) were still exceeding the 

 95th percentile of healthy controls in about two thirds of our 

 cohort at FU2. Lower tryptophan concentrations were associated 

 with B vitamin availability (during acute infection and at FU1), 

 patients with lower vitamin B12 levels at FU1 had a prolonged 

 and more severe impairment of their physical functioning 

 ability. Patients who had fully recovered (ECOG 0) presented 

 with higher concentrations of iron parameters (ferritin, 

 hepcidin, transferrin) and amino acids (phenylalanine, tyrosine) 

 at FU2 compared to patients with restricted ability to work. 

 Persistent symptoms at FU2 were tendentially associated with 

 IFN-γ related parameters. Women were affected by 

 long-term symptoms more frequently. Conclusively, 

 inflammation-mediated biochemical changes appear to be related 

 to symptoms of patients with acute and Long Covid.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Snapkow2024-eo,

title = {New approach methodologies to enhance human health risk 

 assessment of immunotoxic properties of chemicals - a PARC 

 (Partnership for the Assessment of Risk from Chemicals) project},

author = {Igor Snapkow and Nicola M Smith and Emma Arnesdotter and Karsten Beekmann and Etienne B Blanc and Albert Braeuning and Emanuela Corsini and Marija Sollner Dolenc and Loes P M Duivenvoorde and Gunnar Sundstøl Eriksen and Nina Franko and Valentina Galbiati and Johanna M Gostner and Nathalie Grova and Arno C Gutleb and Rita Hargitai and Aafke W F Janssen and Solveig A Krapf and Birgitte Lindeman and Katalin Lumniczky and Ambra Maddalon and Steen Mollerup and Lucia Parráková and Arkadiusz Pierzchalski and Raymond H H Pieters and Maria J Silva and Anita Solhaug and Yvonne C M Staal and Anne Straumfors and Tünde Szatmári and Jonathan D Turner and Rob J Vandebriel and Ana Claudia Zenclussen and Robert Barouki},

year  = {2024},

date = {2024-04-01},

journal = {Front. Toxicol.},

volume = {6},

pages = {1339104},

abstract = {As a complex system governing and interconnecting numerous 

 functions within the human body, the immune system is 

 unsurprisingly susceptible to the impact of toxic chemicals. 

 Toxicants can influence the immune system through a multitude of 

 mechanisms, resulting in immunosuppression, hypersensitivity, 

 increased risk of autoimmune diseases and cancer development. At 

 present, the regulatory assessment of the immunotoxicity of 

 chemicals relies heavily on rodent models and a limited number of 

 Organisation for Economic Co-operation and Development (OECD) 

 test guidelines, which only capture a fraction of potential toxic 

 properties. Due to this limitation, various authorities, 

 including the World Health Organization and the European Food 

 Safety Authority have highlighted the need for the development of 

 novel approaches without the use of animals for immunotoxicity 

 testing of chemicals. In this paper, we present a concise 

 overview of ongoing efforts dedicated to developing and 

 standardizing methodologies for a comprehensive characterization 

 of the immunotoxic effects of chemicals, which are performed 

 under the EU-funded Partnership for the Assessment of Risk from 

 Chemicals (PARC).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Netzer2024-xq,

title = {Oxidative stress reaction to hypobaric-hyperoxic civilian flight 

 conditions},

author = {Nikolaus C Netzer and Heidelinde Jaekel and Roland Popp and Johanna M Gostner and Michael Decker and Frederik Eisendle and Rachel Turner and Petra Netzer and Carsten Patzelt and Christian Steurer and Marco Cavalli and Florian Forstner and Stephan Pramsohler and Hypoxiflight Study Group},

year  = {2024},

date = {2024-04-01},

journal = {Biomolecules},

volume = {14},

number = {4},

abstract = {BACKGROUND: In military flight operations, during flights, 

 fighter pilots constantly work under hyperoxic breathing 

 conditions with supplemental oxygen in varying hypobaric 

 environments. These conditions are suspected to cause oxidative 

 stress to neuronal organ tissues. For civilian flight operations, 

 the Federal Aviation Administration (FAA) also recommends 

 supplemental oxygen for flying under hypobaric conditions 

 equivalent to higher than 3048 m altitude, and has made it 

 mandatory for conditions equivalent to more than 3657 m altitude. 

 AIM: We hypothesized that hypobaric-hyperoxic civilian commercial 

 and private flight conditions with supplemental oxygen in a 

 flight simulation in a hypobaric chamber at 2500 m and 4500 m 

 equivalent altitude would cause significant oxidative stress in 

 healthy individuals. METHODS: Twelve healthy, COVID-19-vaccinated 

 (third portion of vaccination 15 months before study onset) 

 subjects (six male, six female, mean age 35.7 years) from a 

 larger cohort were selected to perform a 3 h flight simulation in 

 a hypobaric chamber with increasing supplemental oxygen levels 

 (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO2, 

 via venturi valve-equipped face mask), switching back and forth 

 between simulated altitudes of 2500 m and 4500 m. Arterial blood 

 pressure and oxygen saturation were constantly measured via 

 radial catheter and blood samples for blood gases taken from the 

 catheter at each altitude and oxygen level. Additional blood 

 samples from the arterial catheter at baseline and 60% oxygen at 

 both altitudes were centrifuged inside the chamber and the serum 

 was frozen instantly at -21 °C for later analysis of the 

 oxidative stress markers malondialdehyde low-density lipoprotein 

 (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test. 

 RESULTS: Eleven subjects finished the study without adverse 

 events. Whereas the partial pressure of oxygen (PO2) levels 

 increased in the mean with increasing oxygen levels from baseline 

 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% 

 FiO2 and 113.2 mmHg at 4500 m altitude and 60% FiO2, there was 

 no significant increase in both oxidative markers from baseline 

 to 60% FiO2 at these simulated altitudes. Some individuals had a 

 slight increase, whereas some showed no increase at all or even a 

 slight decrease. A moderate correlation (Pearson correlation 

 coefficient 0.55) existed between subject age and glutathione 

 peroxidase levels at 60% FiO2 at 4500 m altitude. CONCLUSION: 

 Supplemental oxygen of 60% FiO2 in a flight simulation, compared 

 to flying in cabin pressure levels equivalent to 2500 m-4500 m 

 altitude, does not lead to a significant increase or decrease in 

 the oxidative stress markers M-LDL and GPX1 in the serum of 

 arterial blood.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jaylet2024-rc,

title = {Comprehensive mapping of the AOP-Wiki database: identifying 

 biological and disease gaps},

author = {Thomas Jaylet and Thibaut Coustillet and Nicola M Smith and Barbara Viviani and Birgitte Lindeman and Lucia Vergauwen and Oddvar Myhre and Nurettin Yarar and Johanna M Gostner and Pablo Monfort-Lanzas and Florence Jornod and Henrik Holbech and Xavier Coumoul and Dimosthenis A Sarigiannis and Philipp Antczak and Anna Bal-Price and Ellen Fritsche and Eliska Kuchovska and Antonios K Stratidakis and Robert Barouki and Min Ji Kim and Olivier Taboureau and Marcin W Wojewodzic and Dries Knapen and Karine Audouze},

year  = {2024},

date = {2024-03-01},

journal = {Front. Toxicol.},

volume = {6},

pages = {1285768},

publisher = {Frontiers Media SA},

abstract = {Introduction: The Adverse Outcome Pathway (AOP) concept 

 facilitates rapid hazard assessment for human health risks. AOPs 

 are constantly evolving, their number is growing, and they are 

 referenced in the AOP-Wiki database, which is supported by the 

 OECD. Here, we present a study that aims at identifying 

 well-defined biological areas, as well as gaps within the 

 AOP-Wiki for future research needs. It does not intend to 

 provide a systematic and comprehensive summary of the available 

 literature on AOPs but summarizes and maps biological knowledge 

 and diseases represented by the already developed AOPs (with 

 OECD endorsed status or under validation). Methods: Knowledge 

 from the AOP-Wiki database were extracted and prepared for 

 analysis using a multi-step procedure. An automatic mapping of 

 the existing information on AOPs (i.e., genes/proteins and 

 diseases) was performed using bioinformatics tools (i.e., 

 overrepresentation analysis using Gene Ontology and DisGeNET), 

 allowing both the classification of AOPs and the development of 

 AOP networks (AOPN). Results: AOPs related to diseases of the 

 genitourinary system, neoplasms and developmental anomalies are 

 the most frequently investigated on the AOP-Wiki. An evaluation 

 of the three priority cases (i.e., immunotoxicity and 

 non-genotoxic carcinogenesis, endocrine and metabolic 

 disruption, and developmental and adult neurotoxicity) of the 

 EU-funded PARC project (Partnership for the Risk Assessment of 

 Chemicals) are presented. These were used to highlight under- 

 and over-represented adverse outcomes and to identify and 

 prioritize gaps for further research. Discussion: These results 

 contribute to a more comprehensive understanding of the adverse 

 effects associated with the molecular events in AOPs, and aid in 

 refining risk assessment for stressors and mitigation 

 strategies. Moreover, the FAIRness (i.e., data which meets 

 principles of findability, accessibility, interoperability, and 

 reusability (FAIR)) of the AOPs appears to be an important 

 consideration for further development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mohyuddin2024-pp,

title = {Toxoplasma gondii IgG serointensity is positively associated 

 with frailty},

author = {Hira Mohyuddin and Blanca Laffon and João P Teixeira and Solange Costa and Armanda Teixeira-Gomes and Eduardo Pásaro and Niel Constantine and Aline Dagdag and Heidi K Ortmeyer and Boris Tizenberg and Liubov Afram and Poyu Yen and Christopher Marano and Christopher A Lowry and Andrew J Hoisington and Jill A RachBeisel and Vanessa Valdiglesias and Carlota Lema-Arranz and Natalia Fernández-Bertólez and Ana Maseda and José C Millán-Calenti and Elizabeth J Kovacs and Johanna M Gostner and Dietmar Fuchs and Lisa A Brenner and Laura Lorenzo-López and Teodor T Postolache},

year  = {2024},

date = {2024-03-01},

journal = {J. Gerontol. A Biol. Sci. Med. Sci.},

volume = {79},

number = {3},

publisher = {Oxford University Press (OUP)},

abstract = {BACKGROUND: Persistent inflammation related to aging 

 (``inflammaging'') is exacerbated by chronic infections and 

 contributes to frailty in older adults. We hypothesized 

 associations between Toxoplasma gondii (T. gondii), a common 

 parasite causing an oligosymptomatic unremitting infection, and 

 frailty, and secondarily between T. gondii and previously 

 reported markers of immune activation in frailty. METHODS: We 

 analyzed available demographic, social, and clinical data in Spanish and Portuguese older adults [N = 601; age: mean (SD) 

 77.3 (8.0); 61% women]. Plasma T. gondii immunoglobulin G (IgG) 

 serointensity was measured with an enzyme-linked immunosorbent 

 assay. The Fried criteria were used to define frailty status. 

 Validated translations of Mini-Mental State Examination, 

 Geriatric Depression Scale, and the Charlson Comorbidity Index 

 were used to evaluate confounders. Previously analyzed 

 biomarkers that were significantly associated with frailty in 

 both prior reports and the current study, and also related to T. 

 gondii serointensity, were further accounted for in 

 multivariable logistic models with frailty as outcome. RESULTS: 

 In T. gondii-seropositives, there was a significant positive 

 association between T. gondii IgG serointensity and frailty, accounting for age (p = .0002), and resisting adjustment for 

 multiple successive confounders. Among biomarkers linked with 

 frailty, kynurenine/tryptophan and soluble tumor necrosis factor 

 receptor II were positively associated with T. gondii 

 serointensity in seropositives (p < .05). Associations with 

 other biomarkers were not significant. CONCLUSIONS: This first 

 reported association between T. gondii and frailty is limited by 

 a cross-sectional design and warrants replication. While certain 

 biomarkers of inflammaging were associated with both T. gondii 

 IgG serointensity and frailty, they did not fully mediate the T. 

 gondii-frailty association.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}