Stroke care during the COVID-19 pandemic: case numbers, treatments, and mortality in two large German stroke registries

Background and purposeAt the beginning of the SARS-CoV-2 pandemic, an alarming decline in hospitalizations for stroke was reported in several countries, including Germany. We assessed hospitalization numbers and indicators of the quality of stroke care in 2020 during the pandemic containment measures.Materials and methodsThe analysis was based on data of two large stroke quality assurance registries in the north and the south of Germany (Qualitätssicherung Schlaganfall Nordwestdeutschland and Bayerische Arbeitsgemeinschaft für Qualitätssicherung in der stationären Versorgung). We included 395 hospitals with 467,931 documented cases in 2018–2020. The time interval between admission and thrombolysis, frequency of systemic thrombolysis and intra-arterial therapy (IAT), National Institutes of Health Stroke Scale (NIHSS) score on admission and in-hospital mortality were assessed. Changes in the second (Q2) and fourth (Q4) quarters of 2020 were compared to corresponding quarters in 2019 by chi-squared tests.ResultsHospitalization numbers decreased in the two stroke registries by 8% and 10% in Q2 of 2020 and by 5% and 15% in Q4 of 2020 compared to the same quarters in 2019, respectively. The decline was particularly seen in women and patients with transient ischemic attacks. In cases with cerebral infarction, no increase in NIHSS scores on admission was observed, and the proportion of patients with a time interval between admission and thrombolysis of ≤60 min was unchanged. No clear pattern was found in the frequency of systemic thrombolysis and IAT. In one of the registries, in-hospital mortality of patients with cerebral infarction increased in Q2 of 2020 compared to Q2 of 2019.ConclusionCase numbers slightly decreased under pandemic conditions, while our quarterly analysis indicated that the quality of stroke care was largely unchanged throughout the year 2020

Multispectral electroluminescence enhancement of single-walled carbon nanotubes coupled to periodic nanodisk arrays

The integration of periodic nanodisk arrays into the channel of a light-emitting field-effect transistor leads to enhanced and directional electroluminescence from thin films of purified semiconducting single-walled carbon nanotubes. The maximum enhancement wavelength is tunable across the near-infrared and is directly linked to the periodicity of the arrays. Numerical calculations confirm the role of increased local electric fields in the observed emission modification. Large current densities are easily achieved due to the high charge carrier mobilities of carbon nanotubes and will facilitate new electrically driven plasmonic devices

Synthesis and antiplasmodial evaluation of novel mefloquine-based fumardiamides

The paper is focused on the synthesis and screening of the antiplasmodial activity of novel fumardiamides 5–10 with the mefloquine pharmacophore and a Michael acceptor motif. Multi-step reactions leading to the title compounds included two amide bond formations. The first amide bond was achieved by the reaction of (E)-ethyl 4-chloro-4-oxobut-2-enoate (1) and N1-(2,8-bis(trifluoromethyl)quinolin-4-yl)butane-1,4-diamine (2). The obtained ester 3 was hydrolysed and gave acid 4, which then reacted with the selected halogenanilines in the presence of HATU/DIEA and formed products 5–10. Title compounds showed marked, dose dependent activity in vitro against hepatic stages of Plasmodium berghei. IC50 values of the most active compounds 5, 7 and 9 bearing 3-fluoro, 3-chloro and 3-trifluoromethyl substituents were 3.04–4.16 µmol L–1, respectively. On the other hand, the compounds exerted only weak activity against the erythrocytic stages of two P. falciparum strains (Pf3D7 and PfDd2) in vitro, with the exception of compound 5 (IC50 = 2.9 µmol L–1)

Species and genotype diversity of Plasmodium in malaria patients from Gabon analysed by next generation sequencing

Background Six Plasmodium species are known to naturally infect humans. Mixed species infections occur regularly but morphological discrimination by microscopy is difficult and multiplicity of infection (MOI) can only be evaluated by molecular methods. This study investigated the complexity of Plasmodium infections in patients treated for microscopically detected non- falciparum or mixed species malaria in Gabon. Methods Ultra-deep sequencing of nucleus (18S rRNA), mitochondrion, and apicoplast encoded genes was used to evaluate Plasmodium species diversity and MOI in 46 symptomatic Gabonese patients with microscopically diagnosed non-falciparum or mixed species malaria. Results Deep sequencing revealed a large complexity of coinfections in patients with uncomplicated malaria, both on species and genotype levels. Mixed infections involved up to four parasite species (Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale curtisi, and P. ovale wallikeri). Multiple genotypes from each species were determined from the asexual 18S rRNA gene. 17 of 46 samples (37%) harboured multiple genotypes of at least one Plasmodium species. The number of genotypes per sample (MOI) was highest in P. malariae (n = 4), followed by P. ovale curtisi (n = 3), P. ovale wallikeri (n = 3), and P. falciparum (n = 2). The highest combined genotype complexity in samples that contained mixed-species infections was seven. Conclusions Ultra- deep sequencing showed an unexpected breadth of Plasmodium species and within species diversity in clinical samples. MOI of P. ovale curtisi, P. ovale wallikeri and P. malariae infections were higher than anticipated and contribute significantly to the burden of malaria in Gabon

Electrical pumping and tuning of exciton-polaritons in carbon nanotube microcavities

This research was financially supported by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 306298 (EN-LUMINATE) and under the European Union’s Horizon 2020 Framework Programme (FP/2014-2020)/ERC Grant Agreement No. 640012 (ABLASE) and by the Scottish Funding Council (through SUPA). L.T. thanks the EPSRC for support through the CM-DTC (EP/L015110/1). J.Z. thanks the Alfried Krupp von Bohlen und Halbach-Stiftung via the “Alfried Krupp Förderpreis für junge Hochschullehrer” for general support.Exciton-polaritons are hybrid light–matter particles that form upon strong coupling of an excitonic transition to a cavity mode. As bosons, polaritons can form condensates with coherent laser-like emission. For organic materials, optically pumped condensation was achieved at room temperature but electrically pumped condensation remains elusive due to insufficient polariton densities. Here we combine the outstanding optical and electronic properties of purified, solution-processed semiconducting (6,5) single-walled carbon nanotubes (SWCNTs) in a microcavity-integrated light-emitting field-effect transistor to realize efficient electrical pumping of exciton-polaritons at room temperature with high current densities (>10 kA cm−2) and tunability in the near-infrared (1,060 nm to 1,530 nm). We demonstrate thermalization of SWCNT polaritons, exciton-polariton pumping rates ~104 times higher than in current organic polariton devices, direct control over the coupling strength (Rabi splitting) via the applied gate voltage, and a tenfold enhancement of polaritonic over excitonic emission. This powerful material–device combination paves the way to carbon-based polariton emitters and possibly lasers.PostprintPostprintPeer reviewe

Ultrastrong coupling of electrically pumped near-infrared exciton-polaritons in high mobility polymers

This research was financially supported by the European Research Council under the European Union's Seventh Framework Programme (FP/2007- 2013)/ERC Grant Agreement No. 306298 (EN -LUMINATE) and under the European Union’s Horizon 2020 Framework Programme (FP/2014- 2020)/ERC Grant Agreement No. 640012 (ABLASE) and by the EPSRC Programme Grant EP/P030017/1. L.T. thanks EPSRC for support through the CM -DTC (EP/L015110/1).Exciton-polaritons are quasiparticles with hybrid light–matter properties that may be used in new optoelectronic devices. Here, electrically pumped ultrastrongly coupled exciton-polaritons in a high-mobility donor–acceptor copolymer are demonstrated by integrating a light-emitting field-effect transistor into a metal-clad microcavity. Near-infrared electroluminescence is emitted exclusively from the lower polariton branch, which indicates efficient relaxation. A coupling strength of 24% of the exciton transition energy implies the system is in the ultrastrong coupling regime with a narrow and almost angle-independent emission. The lower polariton energy, which can be adjusted by the cavity detuning, strongly influences the external quantum efficiency of the device. Driving the transistors at ambipolar current densities of up to 4000 A cm−2 does not decrease the coupling strength or polariton emission efficiency. Cavity-integrated light-emitting field-effect transistors thus represent a versatile platform for polariton emission and polaritonic devices.Publisher PDFPeer reviewe

Harmicens, Novel Harmine and Ferrocene Hybrids: Design, Synthesis and Biological Activity

Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the β-carboline ring and ferrocene, as well as its position on the β-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biological assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC50 in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range, SI > 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116- selective compound 28, which clearly entered the nucleus. A cell cycle analysis revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell

Novel Harmicines with Improved Potency against Plasmodium

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1, 2, 3-triazolo [4, 5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N, N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents

Regional Variation of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacterales, Fluoroquinolone-ResistantSalmonella entericaand Methicillin-ResistantStaphylococcus aureusAmong Febrile Patients in Sub-Saharan Africa

Background: Antimicrobial resistance (AMR) thwarts the curative power of drugs and is a present-time global problem. We present data on antimicrobial susceptibility and resistance determinants of bacteria the WHO has highlighted as being key antimicrobial resistance concerns in Africa, to strengthen knowledge of AMR patterns in the region. Methods: Blood, stool, and urine specimens of febrile patients, aged between ≥ 30 days and ≤ 15 years and hospitalized in Burkina Faso, Gabon, Ghana, and Tanzania were cultured from November 2013 to March 2017 (Patients > 15 years were included in Tanzania). Antimicrobial susceptibility testing was performed for all Enterobacterales and Staphylococcus aureus isolates using disk diffusion method. Extended-spectrum beta-lactamase (ESBL) production was confirmed by double-disk diffusion test and the detection of blaCTX–M, blaTEM and blaSHV. Multilocus sequence typing was conducted for ESBL-producing Escherichia coli and Klebsiella pneumoniae, ciprofloxacin-resistant Salmonella enterica and S. aureus. Ciprofloxacin-resistant Salmonella enterica were screened for plasmid-mediated resistance genes and mutations in gyrA, gyrB, parC, and parE. S. aureus isolates were tested for the presence of mecA and Panton-Valentine Leukocidin (PVL) and further genotyped by spa typing. Results: Among 4,052 specimens from 3,012 patients, 219 cultures were positive of which 88.1% (n = 193) were Enterobacterales and 7.3% (n = 16) S. aureus. The prevalence of ESBL-producing Enterobacterales (all CTX-M15 genotype) was 45.2% (14/31; 95% CI: 27.3, 64.0) in Burkina Faso, 25.8% (8/31; 95% CI: 11.9, 44.6) in Gabon, 15.1% (18/119; 95% CI: 9.2, 22.8) in Ghana and 0.0% (0/12; 95% CI: 0.0, 26.5) in Tanzania. ESBL positive non-typhoid Salmonella (n = 3) were detected in Burkina Faso only and methicillin-resistant S. aureus (n = 2) were detected in Ghana only. While sequence type (ST)131 predominated among ESBL E. coli (39.1%;9/23), STs among ESBL K. pneumoniae were highly heterogenous. Ciprofloxacin resistant nt Salmonella were commonest in Burkina Faso (50.0%; 6/12) and all harbored qnrB genes. PVL were found in 81.3% S. aureus. Conclusion: Our findings reveal a distinct susceptibility pattern across the various study regions in Africa, with notably high rates of ESBL-producing Enterobacterales and ciprofloxacin-resistant nt Salmonella in Burkina Faso. This highlights the need for local AMR surveillance and reporting of resistances to support appropriate action