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

Perivascular 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 Cx3cr1GFP x Cx3cr1-Cre;RosatdT reporter mice for finer mapping of the lineages, we establish that CD45lowCX3CR1– pvMs are derived from CX3CR1+ precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26tdT lineage tracing model support a bone marrow-independent 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 CD45low and CX3CR1– pvM population

Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development

The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain

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

Cerebrovascular endothelial cells form transient Notch‐dependent cystic structures in zebrafish

We identify a novel endothelial membrane behaviour in transgenic zebrafish. Cerebral blood vessels extrude large transient spherical structures that persist for an average of 23 min before regressing into the parent vessel. We term these structures “kugeln”, after the German for sphere. Kugeln are only observed arising from the cerebral vessels and are present as late as 28 days post fertilization. Kugeln do not communicate with the vessel lumen and can form in the absence of blood flow. They contain little or no cytoplasm, but the majority are highly positive for nitric oxide reactivity. Kugeln do not interact with brain lymphatic endothelial cells (BLECs) and can form in their absence, nor do they perform a scavenging role or interact with macrophages. Inhibition of actin polymerization, Myosin II, or Notch signalling reduces kugel formation, while inhibition of VEGF or Wnt dysregulation (either inhibition or activation) increases kugel formation. Kugeln represent a novel Notch‐dependent NO‐containing endothelial organelle restricted to the cerebral vessels, of currently unknown function

Acute Surgical Pulmonary Embolectomy: A 9-Year Retrospective Analysis

Acute pulmonary embolism is a substantial cause of morbidity and death. Although the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend surgical pulmonary embolectomy in patients with acute pulmonary embolism associated with hypotension, there are few reports of 30-day mortality rates. We performed a retrospective review of acute pulmonary embolectomy procedures performed in 96 consecutive patients who had severe, globally hypokinetic right ventricular dysfunction as determined by transthoracic echocardiography. Data on patients who were treated from January 2003 through December 2011 were derived from health system databases of the New York State Cardiac Surgery Reporting System and the Society of Thoracic Surgeons. The data represent procedures performed at 3 tertiary care facilities within a large health system operating in the New York City metropolitan area. The overall 30-day mortality rate was 4.2%. Most patients (68 [73.9%]) were discharged home or to rehabilitation facilities (23 [25%]). Hemodynamically stable patients with severe, globally hypokinetic right ventricular dysfunction had a 30-day mortality rate of 1.4%, with a postoperative mean length of stay of 9.1 days. Comparable findings for hemodynamically unstable patients were 12.5% and 13.4 days, respectively. Acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise; however, caution is warranted. Our outcomes might be dependent upon institutional capability, experience, surgical ability, and careful patient selection

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

Rural-urban differences on the rates and factors associated with early initiation of breastfeeding in Nigeria: further analysis of the Nigeria demographic and health survey, 2013

Background This study investigates and compares the rates and factors associated with early initiation of breastfeeding (EIBF) within one hour of birth in rural and urban Nigeria. Methods Data from the 2013 Nigeria Demographic and Health Survey (NDHS) were analyzed. The rates of EIBF were reported using frequency tabulation. Associated factors were examined using Chi-Square test and further assessed on multivariable logistic regression analysis. Results The rates of EIBF were 30.8% (95% confidence interval [CI] 29.0, 32.6) and 41.9% (95% CI 39.6, 44.3) in rural and urban residences, respectively (p < 0.001). The North-Central region had the highest EIBF rates both in rural (43.5%) and urban (63.5%) residences. Greater odds of EIBF in rural residence were significantly associated with higher birth order (Adjusted Odds Ratio [AOR] 1.29, 95% CI 1.10, 1.60), large birth size (AOR 1.33, 95% CI 1.10, 1.60), and health facility delivery (AOR 1.46, 95% CI 1.23, 1.72). Rural mothers in the rich wealth index, not working and whose husbands obtained at least a secondary school education had significantly higher odds of early initiation of breastfeeding. Regardless of residence, greater odds of EIBF were significantly associated with non-cesarean delivery (Rural AOR 3.50, 95% CI 1.84, 6.62; Urban AOR 2.48, 95% CI 1.60, 3.80) and living in North-Central (Rural AOR 1.84, 95% CI 1.34, 2.52; Urban AOR 4.40, 95% CI 3.15, 6.15) region. Also, higher odds of EIBF were significantly associated with living in North-East (Rural AOR 1.48, 95% CI 1.05, 2.08; Urban AOR 3.50, 95% CI 2.55, 4.83), South-South (Rural AOR 1.51, 95% CI 1.11, 2.10; Urban AOR 2.84, 95% CI 2.03, 3.97) and North-West (Urban residence only AOR 2.08, 95% CI 1.54, 2.80) regions. Conclusions Rural-urban differences in the rates and factors associated with EIBF exist in Nigeria with rural residence having significantly lower rates. Intervention efforts which address the risk factors identified in this study may contribute to improved EIBF rates. Efforts need to prioritize rural mothers generally, (particularly, those in rural North-West region) as well as mothers in urban South-West region of Nigeria