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Scientific Reports Jun 2024Sporting experience plays a pivotal role in shaping exercise habits, with a mutually reinforcing relationship that enhances cognitive performance. The acknowledged...
Sporting experience plays a pivotal role in shaping exercise habits, with a mutually reinforcing relationship that enhances cognitive performance. The acknowledged plasticity of cognition driven by sports necessitates a comprehensive examination. Hence, this study delves into the dynamic intricacies of the prefrontal cortex, exploring the impact of orienteering experience on cognitive performance. Our findings contribute empirical evidence regarding the functional activation of specific brain regions bridging the nexus between experiential factors and cognitive capabilities. In this cross-sectional study, a cohort of forty-nine athletes was enrolled to meticulously examine behavioral variances and prefrontal cortex dynamics among orienteering athletes of varying experience levels across diverse non-specialized scenarios. These investigations involved the utilization of functional near-infrared spectroscopy (fNIRS) to detect alterations in oxygenated hemoglobin (HbO2). The high-experience expert group exhibited neurological efficiency, demonstrating significantly diminished brain activation in the dorsolateral prefrontal, left ventral lateral prefrontal, and right orbitofrontal regions compared to the low-experience group. Within the low-experience novice group, superior performance in the spatial memory task was observed compared to the mental rotation task, with consistently lower reaction times across all conditions compared to the high-experience group. Notably, cerebral blood oxygenation activation exhibited a significant reduction in the high-experience expert group compared to the low-experience novice group, irrespective of task type. The dorsolateral prefrontal lobe exhibited activation upon task onset, irrespective of experience level. Correct rates in the spatial memory task were consistently higher than those in the mental rotation task, while brain region activation was significantly greater during the mental rotation task than the spatial memory task." This study elucidates disparities in prefrontal cortex dynamics between highly seasoned experts and neophyte novices, showcasing a cognitive edge within the highly experienced cohort and a spatial memory advantage in the inexperienced group. Our findings contribute to the comprehension of the neural mechanisms that underlie the observed cognitive advantage and provide insights into the forebrain resources mobilized by orienteering experience during spatial cognitive tasks."
Topics: Humans; Prefrontal Cortex; Spectroscopy, Near-Infrared; Cognition; Male; Female; Cross-Sectional Studies; Adult; Young Adult; Athletes; Brain Mapping; Oxyhemoglobins
PubMed: 38942820
DOI: 10.1038/s41598-024-65747-1 -
Scientific Reports Jun 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0-79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan-Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.
Topics: Humans; Male; COVID-19; Female; Middle Aged; Aged; SARS-CoV-2; RNA, Viral; Severity of Illness Index; Antigens, Viral; Coronavirus Nucleocapsid Proteins; Cohort Studies; Phosphoproteins
PubMed: 38942808
DOI: 10.1038/s41598-024-65489-0 -
Microbial Pathogenesis Jun 2024Campylobacter jejuni is one of the major causes of bacterial gastrointestinal disease in humans worldwide. This foodborne pathogen colonizes the intestinal tracts of...
Campylobacter jejuni is one of the major causes of bacterial gastrointestinal disease in humans worldwide. This foodborne pathogen colonizes the intestinal tracts of chickens, and consumption of chicken and poultry products is identified as a common route of transmission. We analyzed two C. jejuni strains after oral challenge with 10 CFU/ml of C. jejuni per chick; one strain was a robust colonizer (A74/C) and the other a poor colonizer (A74/O). We also found extensive phenotypic differences in growth rate, biofilm production, and in vitro adherence, invasion, intracellular survival, and transcytosis. Strains A74/C and A74/O were genotypically similar with respect to their whole genome alignment, core genome, and ribosomal MLST, MLST, flaA, porA, and PFGE typing. The global proteomes of the two congenic strains were quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and 618 and 453 proteins were identified from A74/C and A74/O isolates, respectively. Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that carbon metabolism and motility proteins were distinctively overexpressed in strain A74/C. The robust colonizer also exhibited a unique proteome profile characterized by significantly increased expression of proteins linked to adhesion, invasion, chemotaxis, energy, protein synthesis, heat shock proteins, iron regulation, two-component regulatory systems, and multidrug efflux pump. Our study underlines phenotypic, genotypic, and proteomic variations of the poor and robust colonizing C. jejuni strains, suggesting that several factors may contribute to mediating the different colonization potentials of the isogenic isolates.
PubMed: 38942248
DOI: 10.1016/j.micpath.2024.106766 -
Bioresource Technology Jun 2024This laboratory study reports results on the group particle combustion of pulverized bituminous coal and various types of torrefied biomass. Combustion of particle...
This laboratory study reports results on the group particle combustion of pulverized bituminous coal and various types of torrefied biomass. Combustion of particle streams in a drop tube furnace in air was concurrently monitored by a spectrometer and an electronic camera to obtain spectral emissivities and temperatures. As particle number density (PND) increased, biomass particles became more prone than coal to group combustion. Spectral emissivities increased with increasing PND from 0.2 to 0.4 for coal and from 0.1 to 0.3 for biomass, in the wavelength domain of λ = 600-1000 nm. Emissivities changed little with wavelength, giving credence to the gray body assumption. Particle cloud temperatures were in the range of 1650-1900 K, depending on PND, type of fuel, and location in the cloud; temperatures decreased with increasing PND. The radiative heat of the particle laden flames was predominantly attributed to burning chars in the flames and it increased with increasing PND.
PubMed: 38942214
DOI: 10.1016/j.biortech.2024.131040 -
American Journal of Veterinary Research Jun 2024To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing...
OBJECTIVE
To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age.
ANIMALS
16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old).
METHODS
Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant.
RESULTS
Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups.
CLINICAL RELEVANCE
The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.
PubMed: 38942059
DOI: 10.2460/ajvr.24.01.0012 -
EBioMedicine Jun 2024Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC,...
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking.
METHODS
We screened fourteen patient-derived PDAC cultures which reflect the intra- and intertumoural heterogeneity of PDAC for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H-1PV. Live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays and titration of viral progeny were conducted. Transcriptome profiling was employed to identify potential predictive biomarkers for response to OV treatment.
FINDINGS
Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the classical molecular subtype, the quasi-mesenchymal or basal-like subtype of PDAC was found to be more sensitive to H-1PV, jin-3, and T-VEC. Generally, expression of viral entry receptors did not correlate with sensitivity to OV treatment, with one exception: Expression of Galectin-1 (LGALS1), a factor involved in H-1PV entry, positively correlated with H-1PV induced cell killing. Rather, cellular pathways controlling immunological, metabolic and proliferative signaling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas low cyclic GMP-AMP synthase (cGAS) expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures and cells overexpressing cGAS were found to be less sensitive to MV oncolysis.
INTERPRETATION
Considering the heterogeneity of PDAC and the complexity of biological therapies such as OVs, no single biomarker can explain the spectrum of response patterns. For selection of a particular OV, PDAC molecular subtype, ISG expression as well as activation of distinct signaling and metabolic pathways should be considered. Combination therapies can overcome resistance in specific constellations. Overall, oncolytic virotherapy is a viable treatment option for PDAC, which warrants further development. This study highlights the need for personalised treatment in OVT. By providing all primary data, this study provides a rich source and guidance for ongoing developments.
FUNDING
German National Science Foundation (Deutsche Forschungsgemeinschaft, DFG), German Cancer Aid (Deutsche Krebshilfe), German National Academic Scholarship Foundation (Studienstiftung des deutschen Volkes), Survival with Pancreatic Cancer Foundation.
PubMed: 38941955
DOI: 10.1016/j.ebiom.2024.105219 -
Environment International Jun 2024The National Academies of Sciences, Engineering, and Medicine recommends per- and polyfluoroalkyl substance (PFAS) blood testing for patients with risk of elevated...
The National Academies of Sciences, Engineering, and Medicine recommends per- and polyfluoroalkyl substance (PFAS) blood testing for patients with risk of elevated exposure, and the Agency for Toxic Substances and Disease Registry (ATSDR) suggests PFAS blood testing based on exposure. Barriers to PFAS blood testing include cost, access to labs, and evolving laboratory methods. We quantify water and serum PFAS levels among a highly-exposed cohort in an area with groundwater contaminated by historical agricultural biosolid application. We compare the gold standard PFAS serum test with a commercial test and results from a one-compartment toxicokinetic model. Participants were adults (n = 30) whose household (n = 19) water had levels of the sum of six PFAS > 500 ng/L. Serum PFAS were measured using liquid chromatography-tandem mass spectrometry. Demographic and water consumption data were collected via telephone. Serum PFAS results from the commercial test were accessed via medical record. Statistical analysis included descriptive statistics and bivariate plots of serum levels. Perfluorohexanoic acid, perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorobutanesulfonic acid, perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were detected in 19 wells, and PFHpA, PFOA, PFNA, perfluorodecanoic acid, perfluoroundecanoic acid, PFHxS, and PFOS were detected in at least 19 participants' serum. In well water, PFOA and PFOS levels had geometric means (GMs) of 1749 ng/L (geometric standard deviation [GSD] 2.4) and 887 ng/L (GSD 19.7), respectively. In serum, PFOA and PFOS had GMs of 116.2 µg/L (GSD 13.5) and 58.3 µg/L (GSD 13.8), respectively. Our results are comparable with and had a wider mix of PFAS than other high-exposure cohorts. There was good agreement between the commercial and gold standard tests for PFOA, PFNA, and PFHxS, and mixed agreement between the gold standard test and modeled predictions, suggesting water-based toxicokinetic models of serum PFAS may be inadequate for assessing exposure in this population.
PubMed: 38941944
DOI: 10.1016/j.envint.2024.108850 -
Biophysical Chemistry Jun 2024Human islet amyloid polypeptide (hIAPP) forms amyloid deposits that contribute to β-cell death in pancreatic islets and are considered a hallmark of Type II diabetes...
Human islet amyloid polypeptide (hIAPP) forms amyloid deposits that contribute to β-cell death in pancreatic islets and are considered a hallmark of Type II diabetes Mellitus (T2DM). Evidence suggests that the early oligomers of hIAPP formed during the aggregation process are the primary pathological agent in islet amyloid induced β-cell death. The self-assembly mechanism of hIAPP, however, remains elusive, largely due to limitations in conventional biophysical techniques for probing the distribution or capturing detailed structures of the early, structurally dynamic oligomers. The advent of Ion-mobility Mass Spectrometry (IM-MS) has enabled the characterisation of hIAPP early oligomers in the gas phase, paving the way towards a deeper understanding of the oligomerisation mechanism and the correlation of structural information with the cytotoxicity of the oligomers. The sensitivity and the rapid structural characterisation provided by IM-MS also show promise in screening hIAPP inhibitors, categorising their modes of inhibition through "spectral fingerprints". This review delves into the application of IM-MS to the dissection of the complex steps of hIAPP oligomerisation, examining the inhibitory influence of metal ions, and exploring the characterisation of hetero-oligomerisation with different hIAPP variants. We highlight the potential of IM-MS as a tool for the high-throughput screening of hIAPP inhibitors, and for providing insights into their modes of action. Finally, we discuss advances afforded by recent advancements in tandem IM-MS and the combination of gas phase spectroscopy with IM-MS, which promise to deliver a more sensitive and higher-resolution structural portrait of hIAPP oligomers. Such information may help facilitate a new era of targeted therapeutic strategies for islet amyloidosis in T2DM.
PubMed: 38941872
DOI: 10.1016/j.bpc.2024.107285 -
NeuroImage. Clinical Jun 2024Advanced age is the most important risk factor for Alzheimer's disease (AD), and carrier-status of the Apolipoprotein E4 (APOE4) allele is the strongest known genetic...
Advanced age is the most important risk factor for Alzheimer's disease (AD), and carrier-status of the Apolipoprotein E4 (APOE4) allele is the strongest known genetic risk factor. Many studies have consistently shown a link between APOE4 and synaptic dysfunction, possibly reflecting pathologically accelerated biological aging in persons at risk for AD. To test the hypothesis that distinct functional connectivity patterns characterize APOE4 carriers across the clinical spectrum of AD, we investigated 128 resting state functional Magnetic Resonance Imaging (fMRI) datasets from the Alzheimer's Disease Neuroimaging Initiative database (ADNI), representing all disease stages from cognitive normal to clinical dementia. Brain region centralities within functional networks, computed as eigenvector centrality, were tested for multivariate associations with chronological age, APOE4 carrier status and clinical stage (as well as their interactions) by partial least square analysis (PLSC). By PLSC analysis two distinct brain activity patterns could be identified, which reflected interactive effects of age, APOE4 and clinical disease stage. A first component including sensorimotor regions and parietal regions correlated with age and AD clinical stage (p < 0.001). A second component focused on medial-frontal regions and was specifically related to the interaction between age and APOE4 (p = 0.032). Our findings are consistent with earlier reports on altered network connectivity in APOE4 carriers. Results of our study highlight promise of graph-theory based network centrality to identify brain connectivity linked to genetic risk, clinical stage and age. Our data suggest the existence of brain network activity patterns that characterize APOE4 carriers across clinical stages of AD.
PubMed: 38941766
DOI: 10.1016/j.nicl.2024.103635 -
Ecotoxicology and Environmental Safety Jun 2024Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults....
Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV and FVC by 35.26 mL (95 % CI: -60.75, -9.78) and 38.56 mL (95 % CI: -66.60, -10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.
PubMed: 38941662
DOI: 10.1016/j.ecoenv.2024.116594