First steps towards a stable neon compound: observation and bonding analysis of [B 12 (CN) 11 Ne] −

Noble gas (Ng) containing molecular anions are much scarcer than Ng containing cations. No neon containing anion has been reported so far. Here, the experimental observation of the molecular anion [B12(CN)11Ne]− and a theoretical analysis of the boron–neon bond is reported

Fe II lifetimes and transition probabilities

Fe II radiative lifetimes were measured applying the time-resolved nonlinear laser-induced fluoresence technique. We investigated 21 levels of up to 47000 1/cm. The uncertainties are typically 2-3%. The lifetimes provide an improved absolute scale to our branching fractions which were measured with a Fourier transform spectrometer and a high-resolution grating spectrometer and which have been published earlier. We report absolute transition probabilities of 140 Fe II lines in the wavelength range 220-780 nm. The overall uncertainties are estimated to be 6% for the strong and up to 26% for the weak transitions. The results are compared with recent experimental data from the literature. Our large set of accurate data can be used for a reliability check of theoretical data calculated for iron abundances in astrophysical plasmas

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health

Anti-leukemia T cells in AML: TNF-α(+) CD8(+) T cells may escape detection and possibly reflect a stage of functional impairment

Leukemia-associated antigens such as proteinase-3 (PR3) and Wilms' tumor protein-1 (WT-1) are potential targets of T-cell responses, which can be monitored by T-cell assays within vaccination trials and after allogeneic stem cell transplantation (SCT). In chronic myeloid leukemia (CML) an aberrant cytokine profile of antigen-specific T-cells with predominant TNF-{alpha} secretion has previously been described. The aim of this study was to investigate whether these TNF-{alpha}(+)/IFN-{gamma}(-) CD8(+) T-cells can also be observed in AML patients after SCT. Eight HLA-A2(+) AML patients at different time points after SCT were evaluated for HLA-A2-restricted CD8(+) T-cell responses against PR3, WT-1 and influenza-A using pentamer staining and different cytokine-based T-cell assays. Antigen-specific T-cell immune responses against influenza-A and PR3 were observed in 4/8 patients, WT-1-specific T-cells could be detected in 3/8 patients. Interestingly, four different cytokine secretion profiles of antigen-specific T-cells were detected: (1) IFN-{gamma}(+)/TNF-{alpha}(+), (2) IFN-{gamma}(+)/TNF-{alpha}(-), (3) TNF-{alpha}(+)/IFN-{gamma}(-) and (4) IFN-{gamma}(-)/TNF-{alpha}(-). TNF-{alpha}(+)/IFN-{gamma}(-) CD8(+) T-cells are an interesting biological phenomenon which can obviously be observed also in AML patients. This finding has important implications for both T-cell biology and monitoring within immunotherapy trials. The functional characterization of these TNF-{alpha}(+)/IFN-{gamma}(-) CD8(+) T-cells needs further investigations

Peripheral blood sCD3(-) CD4(+) T cells: a useful diagnostic tool in angioimmunoblastic T cell lymphoma

Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important information for the differential diagnosis of AITL. sCD3(-) CD4(+) T cells are a typical feature of AILT in flow cytometry of peripheral blood. In this retrospective study, the diagnostic value of flow cytometry for the diagnosis 'AITL' was assessed by comparing the frequency of sCD3(-) CD4(+) T cells in leukemic AITL patients and in patients with other leukemic CD4(+) T cell lymphomas. Immunophenotyping of peripheral blood by flow cytometry was performed in a lymphocyte gate using fluorochrome-labelled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD10, CD14, CD16, CD19, CD56, CD57 and T cell receptor. In 17/17 leukemic AITL patients, a small but distinct population of sCD3(-) CD4(+) T cells was detected (mean percentage of sCD3(-) CD4(+) T cells in the lymphocyte gate: 11.9 ± 15.4%, range 0.1-51.8%). In contrast, sCD3(-) CD4(+) T cells were found in only 1/40 patients with other leukemic CD4(+) T cell lymphomas (one patient with mycosis fungoides). sCD3(-) CD4(+) T cells have a high positive predictive value (94%) for the diagnosis 'AITL'. Flow cytometry is particularly useful in the differential diagnosis of AITL, even if the aberrant T cell population has a very low frequency. Further biological characterization of this subfraction of lymphoma cells is warranted

Efficacy of Bariatric Surgery in Type 2 Diabetes Mellitus Remission: the Role of Mini Gastric Bypass/One Anastomosis Gastric Bypass and Sleeve Gastrectomy at 1 Year of Follow-up. A European survey

BACKGROUND: A retrospective study was undertaken to define the efficacy of both mini gastric bypass or one anastomosis gastric bypass (MGB/OAGB) and sleeve gastrectomy (SG) in type 2 diabetes mellitus (T2DM) remission in morbidly obese patients (pts). METHODS: Eight European centers were involved in this survey. T2DM was preoperatively diagnosed in 313/3252 pts (9.62%). In 175/313 patients, 55.9% underwent MGB/OAGB, while in 138/313 patients, 44.1% received SG between January 2006 and December 2014. RESULTS: Two hundred six out of 313 (63.7 %) pts reached 1 year of follow-up. The mean body mass index (BMI) for MGB/OAGB pts was 33.1 ± 6.6, and the mean BMI for SG pts was 35.9 ± 5.9 (p < 0.001). Eighty-two out of 96 (85.4%) MGB/OAGB pts vs. 67/110 (60.9%) SG pts are in remission (p < 0.001). No correlation was found in the % change vs. baseline values for hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) in relation to BMI reduction, for both MGB/OAGB or SG (ΔFPG 0.7 and ΔHbA1c 0.4 for MGB/OAGB; ΔFPG 0.7 and ΔHbA1c 0.1 for SG). At multivariate analysis, high baseline HbA1c [odds ratio (OR) = 0.623, 95% confidence interval (CI) 0.419-0.925, p = 0.01], preoperative consumption of insulin or oral antidiabetic agents (OR = 0.256, 95% CI 0.137-0.478, p = <0.001), and T2DM duration >10 years (OR = 0.752, 95% CI 0.512-0.976, p = 0.01) were negative predictors whereas MGB/OAGB resulted as a positive predictor (OR = 3.888, 95% CI 1.654-9.143, p = 0.002) of diabetes remission. CONCLUSIONS: A significant BMI decrease and T2DM remission unrelated from weight loss were recorded for both procedures if compared to baseline values. At univariate and multivariate analyses, MGB/OAGB seems to outperform significantly SG. Four independent variables able to influence T2DM remission at 12 months have been identified.info:eu-repo/semantics/publishedVersio

Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain

International audiencePerivascular macrophages (pvMs) are associated with cerebral vasculature and mediate brain drainage and immune regulation. Here, using reporter mouse models, whole brain and section immunofluorescence, flow cytometry, and single cell RNA sequencing, besides the Lyve1 + F4/80 + CD206 + CX3CR1 + pvMs, we identify a CX3CR1-pvM population that shares phagocytic functions and location. Furthermore, the brain parenchyma vasculature mostly hosts Lyve1 + MHCII-pvMs with low to intermediate CD45 expression. Using the double Cx3cr1 GFP x Cx3cr1-Cre;Rosa tdT reporter mice for finer mapping of the lineages, we establish that CD45 low CX3CR1-pvMs are derived from CX3CR1 + precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26 tdT lineage tracing model support a bone marrowindependent replenishment of all Lyve1 + pvMs in the adult mouse brain. Lastly, flow cytometry and 3D immunofluorescence analysis uncover increased percentage of pvMs following photothrombotic induced stroke. Our results thus show that the parenchymal pvM population is more heterogenous than previously described, and includes a CD45 low and CX3CR1-pvM population

Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain

International audiencePerivascular macrophages (pvMs) are associated with cerebral vasculature and mediate brain drainage and immune regulation. Here, using reporter mouse models, whole brain and section immunofluorescence, flow cytometry, and single cell RNA sequencing, besides the Lyve1 + F4/80 + CD206 + CX3CR1 + pvMs, we identify a CX3CR1-pvM population that shares phagocytic functions and location. Furthermore, the brain parenchyma vasculature mostly hosts Lyve1 + MHCII-pvMs with low to intermediate CD45 expression. Using the double Cx3cr1 GFP x Cx3cr1-Cre;Rosa tdT reporter mice for finer mapping of the lineages, we establish that CD45 low CX3CR1-pvMs are derived from CX3CR1 + precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26 tdT lineage tracing model support a bone marrowindependent replenishment of all Lyve1 + pvMs in the adult mouse brain. Lastly, flow cytometry and 3D immunofluorescence analysis uncover increased percentage of pvMs following photothrombotic induced stroke. Our results thus show that the parenchymal pvM population is more heterogenous than previously described, and includes a CD45 low and CX3CR1-pvM population