The study aimed to evaluate sensory laterality and concentration of faecal immunoglobulin A (IgA) as non-invasive measures of stress in horses by comparing them with the already established measures ...of motor laterality and faecal glucocorticoid metabolites (FGMs). Eleven three-year-old horses were exposed to known stressful situations (change of housing, initial training) to assess the two new parameters. Sensory laterality initially shifted significantly to the left and faecal FGMs were significantly increased on the change from group to individual housing and remained high through initial training. Motor laterality shifted significantly to the left after one week of individual stabling. Faecal IgA remained unchanged throughout the experiment. We therefore suggest that sensory laterality may be helpful in assessing acute stress in horses, especially on an individual level, as it proved to be an objective behavioural parameter that is easy to observe. Comparably, motor laterality may be helpful in assessing long-lasting stress. The results indicate that stress changes sensory laterality in horses, but further research is needed on a larger sample to evaluate elevated chronic stress, as it was not clear whether the horses of the present study experienced compromised welfare, which it has been proposed may affect faecal IgA.
The Pi Cloud Chamber offers a unique opportunity to study aerosol‐cloud microphysics interactions in a steady‐state, turbulent environment. In this work, an atmospheric large‐eddy simulation (LES) ...model with spectral bin microphysics is scaled down to simulate these interactions, allowing comparison with experimental results. A simple scalar flux budget model is developed and used to explore the effect of sidewalls on the bulk mixing temperature, water vapor mixing ratio, and supersaturation. The scaled simulation and the simple scalar flux budget model produce comparable bulk mixing scalar values. The LES dynamics results are compared with particle image velocimetry measurements of turbulent kinetic energy, energy dissipation rates, and large‐scale oscillation frequencies from the cloud chamber. These simulated results match quantitatively to experimental results. Finally, with the bin microphysics included the LES is able to simulate steady‐state cloud conditions and broadening of the cloud droplet size distributions with decreasing droplet number concentration, as observed in the experiments. The results further suggest that collision‐coalescence does not contribute significantly to this broadening. This opens a path for further detailed intercomparison of laboratory and simulation results for model validation and exploration of specific physical processes.
Key Points
A large‐eddy simulation with spectral bin cloud microphysics is scaled to simulate a laboratory convection chamber
The simulated mixing state and turbulence properties reasonably compare with a simple flux model and with measurements
The simulation replicates published observations from the Pi Chamber, including steady‐state clouds and size distribution broadening.
Forecasting fire growth, plume rise and smoke impacts on air quality remains a challenging task. Wildland fires dynamically interact with the atmosphere, which can impact fire behavior, plume rises, ...and smoke dispersion. For understory fires, the fire propagation is driven by winds attenuated by the forest canopy. However, most numerical weather prediction models providing meteorological forcing for fire models are unable to resolve canopy winds. In this study, an improved canopy model parameterization was implemented within a coupled fire-atmosphere model (WRF-SFIRE) to simulate a prescribed burn within a forested plot. Simulations with and without a canopy wind model were generated to determine the sensitivity of fire growth, plume rise, and smoke dispersion to canopy effects on near-surface wind flow. Results presented here found strong linkages between the simulated fire rate of spread, heat release and smoke plume evolution. The standard WRF-SFIRE configuration, which uses a logarithmic interpolation to estimate sub-canopy winds, overestimated wind speeds (by a factor 2), fire growth rates and plume rise heights. WRF-SFIRE simulations that implemented a canopy model based on a non-dimensional wind profile, saw significant improvements in sub-canopy winds, fire growth rates and smoke dispersion when evaluated with observations.
Plaque-type psoriasis produces significant morbidity, has negative effects on patients' health-related quality of life (HRQoL), and represents an economic burden.
The assessment of disease severity, ...HRQoL and health care in plaque-type psoriasis in everyday German medical practice.
Details of patients with plaque-type psoriasis were recorded by 48 dermatologists in Germany. During the visit, demographic data, medical history, previous and current treatments, occupational impairment, the current state of the disease (measured by the Psoriasis Area and Severity Index; PASI), overall lesion severity, and HRQoL were evaluated.
In total, 1,511 plaque-type psoriasis patients were included. The average PASI score was 12.0. The average Dermatology Life Quality Index score was 8.6. Among the patients with the severest psoriasis (PASI >20), only 45.4% had ever been prescribed systemic treatments.
Psoriasis patients have a reduced HRQoL and are not sufficiently treated in practice. A more widespread use of systemic treatment and the definition of treatment goals are essential to improve the standard of care for psoriasis patients.
FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzoapyrene (BaP), dibenzodef,pchrysene (DBC), and coal tar extract (CTE, SRM 1597a). ...Following 20weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzodef,pchrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators.
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•Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE.•Cyp1b1 expression impacts expression of other PAH metabolizing enzymes.•cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver•Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.
PCMR is used to evaluate the Chiari I malformation. We compared quantitative PCMR in symptomatic and asymptomatic patients with Chiari I.
PCMR image data in an axial section near the foramen magnum ...in a consecutive series of patients with Chiari I malformations were evaluated. Patients were classified as symptomatic for a Chiari I if they had apnea spells and/or exertional headaches and as asymptomatic if they had symptoms not considered specific for a Chiari I malformation. The PCMR CSF flow study was obtained with the same protocol for all patients and with the neck in neutral, flexed, and extended positions. Images were inspected for CSF flow jets and synchronous bidirectional flow. Peak CSF flow velocities were calculated with commercial software. Differences between the 2 groups were tested with mixed-effects ANOVA and Wilcoxon rank sum or Fisher exact probability tests with significance set at the .05 level.
Twenty-six patients with Chiari I were classified as symptomatic, and 24, as asymptomatic. Abnormal flow jets tended to occur more often in the symptomatic than in the asymptomatic patients (P = .054). Peak CSF velocities ranged from 2 to 20 cm/s in the symptomatic and the asymptomatic groups and did not differ significantly between the 2 groups or with neck position.
Peak CSF flow velocities near the foramen magnum did not differentiate symptomatic and asymptomatic patients with Chiari I.
Leading CRISPR-Cas technologies employ Cas9 and Cas12 enzymes that generate RNA-guided dsDNA breaks. Yet, the most abundant microbial adaptive immune systems, Type I CRISPRs, are under-exploited for ...eukaryotic applications. Here, we report the adoption of a minimal CRISPR-Cas3 from Neisseria lactamica (Nla) type I-C system to create targeted large deletions in the human genome. RNP delivery of its processive Cas3 nuclease and target recognition complex Cascade can confer ∼95% editing efficiency. Unexpectedly, NlaCascade assembly in bacteria requires internal translation of a hidden component Cas11 from within the cas8 gene. Furthermore, expressing a separately encoded NlaCas11 is the key to enable plasmid- and mRNA-based editing in human cells. Finally, we demonstrate that supplying cas11 is a universal strategy to systematically implement divergent I-C, I-D, and I-B CRISPR-Cas3 editors with compact sizes, distinct PAM preferences, and guide orthogonality. These findings greatly expand our ability to engineer long-range genome edits.
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•A miniature CRISPR-Cas3 from N. lactamica confers bacterial immunity•NlaCascade-Cas3 RNP enables high-efficiency, targeted large deletions in human cells•Cas11, a hidden internal translation product, is essential for genome editing•Supplying Cas11 as a framework to harness divergent compact CRISPR-Cas3 editors
Tan et al. discover a miniature CRISPR-Cas3 system that can efficiently create targeted large deletions in human genome. An inconspicuous subunit of its Cas machinery, Cas11, is encoded by a hidden ORF embedded in the cas operon. In human cells, Cas11 is the key enabler for compact CRISPR-Cas3 gene editors.
To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy.
Patients in 62 German rheumatology centres were ...evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon-γ release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT).
A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no previous Bacille Calmette-Guérin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defined as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p<0.001) and BCG vaccination status (OR 2.9; CI 2.00 to 4.35, p<0.001). QFT and TSPOT were only influenced by CRF (QFT: OR 2.6; CI 1.15 to 5.98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82, p<0.001). ORs and the agreement of TST and IGRA test results varied by rheumatological disease.
LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.
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