Tissue signals imprint ILC2 identity with anticipatory function.

Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25-, IL-33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number and expression in germ-free mice, suggesting that endogenous, tissue-derived signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific perturbations occurring later in life

Filling the void - enriching the feature space of successful stopping

The ability to inhibit behavior is crucial for adaptation in a fast changing environment and is commonly studied with the stop signal task. Current EEG research mainly focuses on the N200 and P300 ERPs and corresponding activity in the theta and delta frequency range, thereby leaving us with a limited understanding of the mechanisms of response inhibition. Here, 15 functional networks were estimated from time-frequency transformed EEG recorded during processing of a visual stop signal task. Cortical sources underlying these functional networks were reconstructed, and a total of 45 features, each representing spectrally and temporally coherent activity, were extracted to train a classifier to differentiate between go and stop trials. A classification accuracy of 85.55% for go and 83.85% for stop trials was achieved. Features capturing fronto-central delta- and theta activity, parieto-occipital alpha, fronto-central as well as right frontal beta activity were highly discriminating between trial-types. However, only a single network, comprising a feature defined by oscillatory activity below 12 Hz, was associated with a generator in the opercular region of the right inferior frontal cortex and showed the expected associations with behavioral inhibition performance. This study pioneers by providing a detailed ranking of neural features regarding their information content for stop and go differentiation at the single-trial level, and may further be the first to identify a scalp EEG marker of the inhibitory control network. This analysis allows for the characterization of the temporal dynamics of response inhibition by matching electrophysiological phenomena to cortical generators and behavioral inhibition performanc

Efficacy and safety outcomes for acute ischemic stroke patients treated with intravenous infusion of tirofiban after emergent carotid artery stenting

Introduction Emergent stenting of the extracranial internal carotid artery (ICA) in stroke patients requires antiplatelet therapy to prevent in-stent thrombosis with a higher risk of intracranial haemorrhage. Aim of the Study Assess the efficacy and safety of emergent carotid stenting with intravenous tirofiban in acute ischemic stroke patients. Methods Primary endpoint: symptomatic hemorrhage. Secondary endpoints: 90-day functional outcome and mortality. Results Of the 62 patients, 21 (34%) received tirofiban as a single antiplatelet, and 41 (66%) received combined therapy. Premedication with anticoagulants and antiplatelets was significantly more frequent in the tirofiban-only group. The rate of symptomatic haemorrhage was significantly lower in the tirofiban-only group than in the combined group (4.8% vs. 27%, p = 0.046). The patients with tirofiban alone had a significantly better functional outcome at day 90 than the combined group (52% vs. 24%, p = 0.028). Mortality was equal (24%) in both groups. Pre-interventional NIHSS score (p = 0.003), significant blood pressure fluctuations (p = 0.012), tandem occlusion (p = 0.023), and thrombolysis (p = 0.044) showed relevant influence on the rate of symptomatic hemorrhage in the entire patient cohort. Conclusions A single antiplatelet therapy with tirofiban regardless of the premedication may improve the functional outcome in patients with stroke due to acute extracranial carotid lesion and emergent carotid stenting with lower rates of serious intracranial haemorrhage. For patients with high pre-interventional NIHSS score, tandem occlusion and after pre-interventional thrombolysis, caution is advised. Additionally, strict blood pressure monitoring should be conducted during the first 72 h after intervention

The absence of a mature cell wall sacculus in stable Listeria monocytogenes L-form cells is independent of peptidoglycan synthesis

L-forms are cell wall-deficient variants of otherwise walled bacteria that maintain the ability to survive and proliferate in absence of the surrounding peptidoglycan sacculus. While transient or unstable L-forms can revert to the walled state and may still rely on residual peptidoglycan synthesis for multiplication, stable L-forms cannot revert to the walled form and are believed to propagate in the complete absence of peptidoglycan. L-forms are increasingly studied as a fundamental biological model system for cell wall synthesis. Here, we show that a stable L-form of the intracellular pathogen Listeria monocytogenes features a surprisingly intact peptidoglycan synthesis pathway including glycosyl transfer, in spite of the accumulation of multiple mutations during prolonged passage in the cell wall-deficient state. Microscopic and biochemical analysis revealed the presence of peptidoglycan precursors and functional glycosyl transferases, resulting in the formation of peptidoglycan polymers but without the synthesis of a mature cell wall sacculus. In conclusion, we found that stable, non-reverting L-forms, which do not require active PG synthesis for proliferation, may still continue to produce aberrant peptidoglycan

Assessing Lanthanide‐Dependent Methanol Dehydrogenase Activity: The Assay Matters

Artificial dye-coupled assays have been widely adopted as a rapid and convenient method to assess the activity of methanol dehydrogenases (MDH). Lanthanide(Ln)-dependent XoxF-MDHs are able to incorporate different lanthanides (Lns) in their active site. Dye-coupled assays showed that the earlier Lns exhibit a higher enzyme activity than the late Lns. Despite widespread use, there are limitations: oftentimes a pH of 9 and activators are required for the assay. Moreover, Ln-MDH variants are not obtained by isolation from the cells grown with the respective Ln, but by incubation of an apo-MDH with the Ln. Herein, we report the cultivation of Ln-dependent methanotroph Methylacidiphilum fumariolicum SolV with nine different Lns, the isolation of the respective MDHs and the assessment of the enzyme activity using the dye-coupled assay. We compare these results with a protein-coupled assay using its physiological electron acceptor cytochrome cGJ (cyt cGJ). Depending on the assay, two distinct trends are observed among the Ln series. The specific enzyme activity of La-, Ce- and Pr-MDH, as measured by the protein-coupled assay, exceeds that measured by the dye-coupled assay. This suggests that early Lns also have a positive effect on the interaction between XoxF-MDH and its cyt cGJ thereby increasing functional efficiency

Hydrocephalus, cerebral vasospasm, and delayed cerebral ischemia following non-aneurysmatic spontaneous subarachnoid hemorrhages: an underestimated problem

Non-aneurysmal subarachnoid hemorrhage (NASAH) is rare and mostly benign. However, complications such as cerebral vasospasm (CV), delayed cerebral ischemia (DCI), or post-hemorrhagic hydrocephalus (HC) may worsen the prognosis. The aim of this study was to evaluate the rate of these complications comparing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH. Monocentric, retrospective analysis of patients diagnosed with NASAH from 01/2010 to 01/2021. Diagnosis was set only if vascular pathologies were excluded in at least one digital subtraction angiography, and NASAH was confirmed by cranial computed tomography (cCT) or lumbar puncture (LP). One hundred patients (62 female) with a mean age of 54.9 years (27–84) were identified. Seventy-three percent had a World Federation of Neurological Surgeons (WFNS) grading scale score I, while 9% were WFNS score IV or V at the time of admission. SAH was diagnosed by cCT in 86%, in 14% by lumbar puncture. Twenty-five percent necessitated short-term CSF diversion by extraventricular drainage or lumbar drainage, whereof 7 suffered from long-term HC treated with ventriculoperitoneal shunting (VPS). One patient without a short-term CSF drainage developed long-term HC. Ten percent developed CV, four of whom received intraarterial spasmolysis. Radiological DCI was diagnosed in 2%; none of these correlated with CV. Despite a mortality of 3% occurring solely in NPM SAH, the analyzed complication rate was comparable in both groups. We observed post-hemorrhagic complications in 35% of cases during the first 3 weeks after bleeding, predominantly in patients with NPM SAH. For this reason, close observation and cranial imaging within this time may be indicated not to overlook these complications

Monitoring training and recovery responses with heart rate measures during standardized warm-up in elite badminton players

Purpose To investigate short-term training and recovery-related effects on heart rate during a standardized submaximal running test. Methods Ten elite badminton players (7 females and 3 males) were monitored during a 12-week training period in preparation for the World Championships. Exercise heart rate (HRex) and perceived exertion were measured in response to a 5-min submaximal shuttle-run test during the morning session warm-up. This test was repeatedly performed on Mondays after 1–2 days of pronounced recovery (‘recovered’ state; reference condition) and on Fridays following 4 consecutive days of training (‘strained’ state). In addition, the serum concentration of creatine kinase and urea, perceived recovery–stress states, and jump performance were assessed before warm-up. Results Creatine kinase increased in the strained compared to the recovered state and the perceived recovery–stress ratings decreased and increased, respectively (range of average effects sizes: |d| = 0.93–2.90). The overall HRex was 173 bpm and the observed within-player variability (i.e., standard deviation as a coefficient of variation [CV]) was 1.3% (90% confidence interval: 1.2% to 1.5%). A linear reduction of -1.4% (-3.0% to 0.3%) was observed in HRex over the 12-week observational period. HRex was -1.5% lower (-2.2% to -0.9%) in the strained compared to the recovered state, and the standard deviation (as a CV) representing interindividual variability in this response was 0.7% (-0.6% to 1.2%). Conclusions Our findings suggest that HRex measured during a standardized warm-up can be sensitive to short-term accumulation of training load, with HRex decreasing on average in response to consecutive days of training within repeated preparatory weekly microcycles. From a practical perspective, it seems advisable to determine intra-individual recovery–strain responses by repeated testing, as HRex responses may vary substantially between and within players

Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes

<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p> <p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p> <p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p> <p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p&gt