Volatile organic compounds (VOCs) are reported to cause adverse effects on pulmonary function in occupationally exposed workers. However, evidence is lacking on the effect in the general population. ...We hypothesised that VOCs impair pulmonary function through enhancing oxidative stress, especially in the elderly population. A longitudinal panel study of 154 elderly people was performed in South Korea. Repeated spirometric tests were performed up to eight times on different days for each subject. We also measured urinary concentrations of metabolites of the VOC and markers of oxidative stress (malondialdehyde and 8-oxo-2'-deoxyguanosine) on the same day of spirometric tests. A mixed linear regression model was used to evaluate the association among the VOC metabolites, oxidative stress markers and spirometric tests. We found that the urinary levels of hippuric acid and methylhippuric acid, which are metabolites of toluene and xylene, respectively, were significantly associated with reduction of forced expiratory volume in 1 s (FEV₁), FEV₁/forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC. We also found significant associations between the metabolites of VOCs and the markers of oxidative stress. In addition, the oxidative stress markers were associated with pulmonary function parameters. This study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people.
Frustrated systems are ubiquitous, and they are interesting because their behaviour is difficult to predict; frustration can lead to macroscopic degeneracies and qualitatively new states of matter. ...Magnetic systems offer good examples in the form of spin lattices, where all interactions between spins cannot be simultaneously satisfied. Here we report how unusual composite spin degrees of freedom can emerge from frustrated magnetic interactions in the cubic spinel ZnCr2O4. Upon cooling, groups of six spins self-organize into weakly interacting antiferromagnetic loops, whose directors-the unique direction along which the spins are aligned, parallel or antiparallel-govern all low-temperature dynamics. The experimental evidence comes from a measurement of the magnetic form factor by inelastic neutron scattering; the data show that neutrons scatter from hexagonal spin clusters rather than individual spins. The hexagon directors are, to a first approximation, decoupled from each other, and hence their reorientations embody the long-sought local zero energy modes for the pyrochlore lattice.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next ...generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.
Spin-orbit coupling results in technologically-crucial phenomena underlying magnetic devices like magnetic memories and energy-efficient motors. In heavy element materials, the strength of spin-orbit ...coupling becomes large to affect the overall electronic nature and induces novel states such as topological insulators and spin-orbit-integrated Mott states. Here we report an unprecedented charge-ordering cascade in IrTe2 without the loss of metallicity, which involves localized spin-orbit Mott states with diamagnetic Ir(4+)-Ir(4+) dimers. The cascade in cooling, uncompensated in heating, consists of first order-type consecutive transitions from a pure Ir(3+) phase to Ir(3+)-Ir(4+) charge-ordered phases, which originate from Ir 5d to Te 5p charge transfer involving anionic polymeric bond breaking. Considering that the system exhibits superconductivity with suppression of the charge order by doping, analogously to cuprates, these results provide a new electronic paradigm of localized charge-ordered states interacting with itinerant electrons through large spin-orbit coupling.
The objectives of this study were to obtain prevalence estimates for subclinical endometritis (SCE), determine cow- and herd-level risk factors, and evaluate the reproductive consequences of SCE. A ...cross-sectional study was used to determine prevalence and risk factors with cows followed in a prospective study to determine reproductive outcomes. Lactating Holstein cows were sampled between 40 and 60 d in milk using low-volume uterine lavage, and cytology was evaluated to determine SCE status. In total, 779 cows from 38 herds were used in the analysis. The cow-level prevalence of SCE was 25.9%. Within-herd level prevalence ranged from 4.8 to 52.6% (median 26.3%, interquartile range 15.6 to 33.3%). Cow-level risk factors identified were ketosis odds ratio (OR) 3.83; 95% confidence interval (CI) 1.82–8.07, acute metritis (OR 1.86; 95% CI 1.05–3.30, and the interaction between milk production and parity. Primiparous cows that produced more milk had increased odds of having SCE, whereas multiparous cows that produced more milk had decreased odds of having SCE. Herd-level risk factors identified were housing early postpartum cows on bedded packs (herd-level SCE=36.1%), which increased herd prevalence of SCE by 16.7% (SE 5.58) compared with early postpartum cows housed in freestalls (herd-level SCE=19.4%), and straw bedding in the calving pen, which decreased herd prevalence of SCE by 10.7% (SE 3.59) compared with herds that used other bedding material. In this study, primiparous cows with and without SCE had similar reproductive performance; however, multiparous cows with SCE had median days open 44 d longer (159 d; 95% CI 126–186 d) compared with unaffected multiparous cows (115 d; 95% CI 106–132 d).
The current study examined the relationships among temporal processing speed, spatial visual span and Chinese character reading speed in normal central and peripheral vision. Maximum reading speed ...(MRS) and critical print size (CPS) of 26 native Chinese readers (13 young and 13 older adults) were determined at three visual field locations: central vision, 10° left and 10° below fixation using a rapid serial visual presentation (RSVP) task. Temporal processing speed was measured using trigrams of randomly selected Chinese characters presented at a range of exposure durations, while spatial visual span was measured using trigrams presented at different spatial positions. It was found that shorter temporal processing speed and larger spatial visual span were associated with faster MRS at the central and inferior visual field locations, but not at the left of fixation location. As expected, reading and visual span metrics were better in central vision compared to both peripheral locations. In addition, reading, temporal processing, and spatial visual span metrics were better in the young than older subjects (except for similar temporal processing speed at two peripheral locations). The results for central and inferior presentation locations support the hypothesis that temporal processing speed and spatial visual span were associated with Chinese character reading speed. Surprisingly, no correlation was observed for the 10° left of the fixation location, suggesting that the factors affecting reading speed might differ for inferior and lateral peripheral viewing locations.
Background and purpose
Vaccination against infection becomes important in patients with neuromyelitis optica spectrum disorder (NMOSD) because they are at an increased risk of infection due to ...long‐term immunosuppressive therapy. However, it is unclear whether NMOSD patients under immunosuppression therapy show proper antibody formation after vaccination. Thus the antibody formation after influenza A (H1N1) vaccination in patients with NMOSD receiving rituximab was evaluated.
Methods
The study enrolled 26 patients with NMOSD, nine with multiple sclerosis and eight healthy controls. The enrolled patients had been treated with rituximab (n = 16), mycophenolate mofetil (n = 5), azathioprine (n = 6) and interferon‐β (IFN‐β) (n = 8). Antibodies against the H1N1 influenza virus were measured in the serum drawn just before (T0) and between 3 and 5 weeks after (T1) vaccination. The immunization states for hepatitis B virus surface antigen, measles and tetanus during the treatment period were also tested.
Results
The rituximab group showed significantly lower geometric mean titer, seroprotection rate and mean fold increase than the azathioprine group, IFN‐β group and healthy controls, and a lower seroconversion rate than the IFN‐β group. This decrease in vaccination efficacy was also shown in patients receiving mycophenolate mofetil. The immunization state for hepatitis B virus surface antigen, measles and tetanus remained the same during the treatment period with each drug, suggesting that these treatments do not affect previously formed immunity.
Conclusion
This study shows a severely hampered humoral immune response to H1N1 influenza vaccine in patients with NMOSD treated with rituximab, although the vaccination itself is safe in these patients.
Choroidal thickness measurements are reported to differ between swept source optical coherence tomography (SS-OCT) and spectral domain OCT (SD-OCT). This study aimed to assess the comparability of ...choroidal thickness measurements using SS-OCT and SD-OCT devices among patients with retinal diseases and normal participants.
In a prospective cohort study of 100 subjects, comprising patients with retinal disease and normal volunteers, OCT scans were performed sequentially with the DRI OCT-1 and Spectralis OCT using standardised imaging protocols. Subfoveal choroidal thicknesses were independently measured by masked reading-centre certified graders. Paired t tests and intraclass correlation coefficients (ICCs) were used to compare the measurements.
Among all 100 participants, mean subfoveal choroidal thickness was 264.3 µm and 272.4 µm for DRI OCT-1 and Spectralis OCT respectively (p=0.001), with ICC of 0.989. The mean difference in choroidal thickness between OCT devices was larger among eyes with retinal diseases compared with normal eyes (8.4 µm vs 7.3 µm). Eyes with choroidal thickness ≤200 µm had smaller differences between OCT devices compared with those with thicker choroids (mean 3.6 µm vs 10.0 µm, p=0.021).
Subfoveal choroidal thickness measurements are comparable between DRI OCT-1 and Spectralis OCT. The presence of retinal disease increases the variability of choroidal thickness measurements between OCT devices.
Activation of the extensive cross-talk among the receptor tyrosine kinases (RTKs), particularly ErbB family-Met cross-talk, has emerged as a likely source of drug resistance. Notwithstanding ...brilliant successes were attained while using small-molecule inhibitors or antibody therapeutics against specific RTKs in multiple cancers over recent decades, a high recurrence rate remains unsolved in patients treated with these targeted inhibitors. It is well aligned with multifaceted properties of cancer and cross-talk and convergence of signaling pathways of RTKs. Thereby many therapeutic interventions have been actively developed to overcome inherent or acquired resistance. To date, no bispecific antibody (BsAb) showed complete depletion of dual RTKs from the plasma membrane and efficient dual degradation. In this manuscript, we report the first findings of a target-specific dual internalization and degradation of membrane RTKs induced by designed BsAbs based on the internalizing monoclonal antibodies and the therapeutic values of these BsAbs. Leveraging the anti-Met mAb able to internalize and degrade by a unique mechanism, we generated the BsAbs for Met/epidermal growth factor receptor (EGFR) and Met/HER2 to induce an efficient EGFR or HER2 internalization and degradation in the presence of Met that is frequently overexpressed in the invasive tumors and involved in the resistance against EGFR- or HER2-targeted therapies. We found that Met/EGFR BsAb ME22S induces dissociation of the Met-EGFR complex from Hsp90, followed by significant degradation of Met and EGFR. By employing patient-derived tumor models we demonstrate therapeutic potential of the BsAb-mediated dual degradation in various cancers.
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