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Background In Germany, the telephone patient service 116,117 for callers with non-life-threatening health issues is available 24/7. Based on structured initial assessment, urgency and placement of suitable medical care offer have been offered since 2020. The service has been in increasing demand for several years: Depending on time and residence, this can result in longer waiting times. Methods Prospective, two-armed cohort study with two intervention groups and one control group, alternating between blinding and unblinding for employees of 116,117 regarding prioritization status. Two interventions based on automated voice dialogues (1: Simple self-rating tool, 2: Automated brief query of emergency symptoms). In case of high level of urgency, callers are prioritized. Validation of urgency and need for care is carried out routinely based on structured initial assessment. Discussion By creating and providing a largely reproducible documentation of the implemented solutions for a waiting queue management, the developed approach would be available for comparable projects in the German health care system or in the European context. This potentially leads to a reduction in the use of resources in the development of comparable technical solutions based on automated voice dialogs. Trial registration DRKS00031235, registered on 10th November 2023, https://drks.de/search/de/trial/DRKS00031235 .

Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on rigid or elastic encapsulation materials and stiff films of ductile metals that can be manipulated with microscopic precision to offer reliable electrical properties. In this study, we have engineered a surface microelectrode array that replaces the traditional encapsulation and conductive components with viscoelastic materials. Our array overcomes previous limitations in matching the stiffness and relaxation behaviour of soft biological tissues by using hydrogels as the outer layers. We have introduced a hydrogel-based conductor made from an ionically conductive alginate matrix enhanced with carbon nanomaterials, which provide electrical percolation even at low loading fractions. Our combination of conducting and insulating viscoelastic materials, with top-down manufacturing, allows for the fabrication of electrode arrays compatible with standard electrophysiology platforms. Our arrays intimately conform to the convoluted surface of the heart or brain cortex and offer promising bioengineering applications for recording and stimulation. Bioelectronic interfacing with living tissues should match the biomechanical properties of biological materials to reduce damage to the tissues. Here, the authors present a fully viscoelastic microelectrode array composed of an alginate matrix and carbon-based nanomaterials encapsulated in a viscoelastic hydrogel for electrical stimulation and signal recording of heart and brain activities in vivo.

Retroviruses are not expected to encode miRNAs because of the potential problem of self-cleavage of their genomic RNAs. This assumption has recently been challenged by experiments showing that bovine leukemia virus (BLV) encodes miRNAs from intragenomic Pol III promoters. The BLV miRNAs are abundantly expressed in B-cell tumors in the absence of significant levels of genomic and subgenomic viral RNAs. Using deep RNA sequencing and functional reporter assays, we show that miRNAs mediate the expression of genes involved in cell signaling, cancer and immunity. We further demonstrate that BLV miRNAs are essential to induce B-cell tumors in an experimental model and to promote efficient viral replication in the natural host.

Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the etiological agent of the current COVID-19 pandemic, a rapid and massive effort has been made to obtain the genomic sequences of this virus to monitor (in near real time) the phylodynamic and diversity of this new pathogen. However, less attention has been given to the assessment of intra-host diversity. RNA viruses such as SARS-CoV-2 inhabit the host as a population of variants called quasispecies. We studied the quasispecies diversity in four of the main SARS-CoV-2 genes (ORF1a, ORF1b, S and N genes), using a dataset consisting of 210 next-generation sequencing (NGS) samples collected between January and early April of 2020 in the State of Victoria, Australia. We found evidence of quasispecies diversity in 68% of the samples, 76% of which was nonsynonymous variants with a higher density in the spike (S) glycoprotein and ORF1a genes. About one-third of the nonsynonymous intra-host variants were shared among the samples, suggesting host-to-host transmission. Quasispecies diversity changed over time. Phylogenetic analysis showed that some of the intra-host single-nucleotide variants (iSNVs) were restricted to specific lineages, highlighting their potential importance in the epidemiology of this virus. A greater effort must be made to determine the magnitude of the genetic bottleneck during transmission and the epidemiological and/or evolutionary factors that may play a role in the changes in the diversity of quasispecies over time.

The French Poison Centers database is a tool of choice for the analysis of poisoning cases requiring the administration of an antidote although not all uses are systematically reported. This national retrospective study aims to report trends of use of antidotes in France over a 7-year period from 2015 to 2021. A total of 25,289 cases of poisoning required the administration of an antidote, among which 46.7% were moderate to severe. While 77.1% of poisonings progressed toward recovery, the observed mortality rate was 1.7%. The 3 most frequently used antidotes according to data from Poison Centers were N-acetylcysteine (n = 13,555 [53.6%]), flumazenil (n = 3102 [12.3%]) and naloxone (n = 1740 [6.9%]) reflecting the most common types of poisoning involving acetaminophen, benzodiazepines, and opioids. The observed use of methylthioninium chloride, hydroxocobalamin, cyanocobalamin and DOAC reversal agents increased, both in terms of absolute numbers and proportions, revealing new behaviors leading to poisoning, such as nitrous oxide consumption. Conversely, the observed use of ethanol-based therapy, L-carnitine, and dantrolene decreased over time, reflecting both current medical practices and shifts in guidelines. This study provides a novel insight into the typology (circumstances, severity, development) of poisonings requiring an antidote, as well as the description of the causative agents.

Light pollution could represent one of the main drivers behind the current biodiversity erosion. While the effects of many light components on biodiversity have already been studied, the influence of flicker remains poorly understood. The determination of the threshold frequency at which a flickering light is perceived as continuous by a species, usually called the Critical Fusion Frequency (CFF), could thus help further identify the impacts of artificial lighting on animals. This review aimed at answering the following questions: what is the distribution of CFF between species? Are there differences in how flicker is perceived between taxonomic classes? Which species are more at risk of being impacted by artificial lighting flicker? Citations were extracted from three literature databases and were then screened successively on their titles, abstracts and full-texts. Included studies were critically appraised to assess their validity. All relevant data were extracted and analysed to determine the distribution of CFF in the animal kingdom and the influence of experimental designs and species traits on CFF. At first, 4881 citations were found. Screening and critical appraisal provided 200 CFF values for 156 species. Reported values of CFF varied from a maximum of between 300 Hz and 500 Hz for the beetle Melanophila acuminata D. to a mean of 0.57 (± 0.08) Hz for the snail Lissachatina fulica B. Insects and birds had higher CFF than all other studied taxa. Irrespective of taxon, nocturnal species had lower CFF than diurnal and crepuscular ones. We identified nine crepuscular and nocturnal species that could be impacted by the potential adverse effects of anthropogenic light flicker. We emphasize that there remains a huge gap in our knowledge of flicker perception by animals, which could potentially be hampering our understanding of its impacts on biodiversity, especially in key taxa like bats, nocturnal birds and insects.

Introduction This study evaluates the gait analysis obtained by Inetial Measurement Units (IMU) before and after surgical management of Spastic Equino Varus Foot (SEVF) in hemiplegic post-stroke patients and to compare it with the functional results obtained in a monocentric prospective cohort. Methods Patients with post-stroke SEVF, who underwent surgery in a single hospital between November 2019 and December 2021 were included. The follow-up duration was 6 months and included a functional analysis using Goal Attainment Scaling (GAS) and a Gait analysis using an innovative Multidimensional Gait Evaluation using IMU: the semiogram. Results 20 patients had a gait analysis preoperatively and at 6 months postoperatively. 90% (18/20) patients had a functional improvement (GAS T score ≥ 50) and 50% (10/20) had an improvement in walking technique as evidenced by the cessation of the use of a walking aid (WA). In patients with functional improvement and modification of WA the change in the semiogram area was + 9.5%, sd = 27.5%, and it was + 15.4%, sd = 28%. In the group with functional improvement without change of WA. For the 3 experiences (two patients) with unfavorable results, the area under the curve changed by + 2.3%, -10.2% and − 9.5%. The measurement of the semiogram area weighted by average speed demonstrated very good reproducibility (ICC(1, 3) = 0.80). Discussion IMUs appear to be a promising solution for the assessment of post-stroke hemiplegic patients who have undergone SEVF surgery. They can provide a quantified, objective, reliable in individual longitudinal follow up automated gait analysis solution for routine clinical use. Combined with a functional scale such as the GAS, they can provide a global analysis of the effect of surgery.

Antimicrobial resistance (AMR) is a global public health threat. Quality data are needed to address the rise of multidrug-resistant clones, particularly in sub-Saharan Africa. In this study, we analysed the prevalence, antimicrobial resistance profile, and presence of genes encoding extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp) in environmental samples from Ouagadougou, Burkina Faso. Of 264 samples collected, 95 (36%) and 74 (28%) contained ESBL-Kp and ESBL-Ec, respectively. ESBL-Kp was more prevalent in runoff water and in treated and untreated wastewater, while ESBL-Ec was more prevalent in manure. Interestingly, wastewater treatment did not significantly reduce the recovery of ESBL bacteria. As expected, resistance to third- and fourth-generation cephalosporins was predominant, and rare for second generation cefoxitin. Interestingly, all the isolates from treated wastewater were susceptible to ampicillin and piperacillin, while all the other clones were resistant to these antibiotics. Regarding the ESBL-encoding genes, the blaCTX-M family was the most abundant, with the blaCTX-M1 subfamily being the most prevalent. Carriage of combinations of ESBL genes was common, with the majority of the isolates harbouring 2–4 different genes. This study highlights the need for active surveillance to manage the risk of exposure to ESBL bacteria in Burkina Faso.

Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility. In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5-91.3%) and ≥4 days (85.7%, 75.9-92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1-97.5%) and 96.5% (94.1-98.1%), respectively, compared to the other PCR. RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

Most cells produce latent transforming growth factor-beta 1 (TGF-β1), but only very few activate the cytokine via cell type-specific mechanisms. TGF-β1 favors cancer progression by suppressing anti-tumor T cell responses. Which cells produce this immunosuppressive TGF-β1 in human tumors is unknown. Putative sources include cells expressing the glycoprotein A repetitions predominant (GARP) protein, comprising mostly activated regulatory T cells (Tregs) (GARP + FOXP3 + cells) and blood endothelial cells (BECs). We performed multiplexed immunohistofluorescence and computerized image analyses on 186 tumor samples from 5 cancer types (colorectal, urothelial, lung and breast primary carcinomas and melanoma metastases), compared to patient-matched adjacent non-cancerous tissues. GARP + Tregs were present in 29–75% of the various types of tumor samples. Their proportion was higher in tumors than non-cancerous tissues but unexpectedly it did not correlate with that of tumor-infiltrating T lymphocytes (TILs). The density of blood vessels was similar across samples, with more than half expressing GARP. The proportion of cells undergoing TGF-β1 signaling, which express the phosphorylated form of mothers against decapentaplegic homolog 2 (pSMAD2), was approximately twice as high in tumors compared to non-cancerous tissues. In most tumor types, pSMAD2 + TILs were twice closer to the nearest FOXP3 + cell than after random repositioning, at a distance (~ 70 µm) consistent with short-range paracrine TGF-β1 signaling. In contrast, pSMAD2 + non-T cells and pSMAD2 − TILs were not closer to FOXP3 + cells, neither were pSMAD2 + cells (TILs and others) to BECs. We conclude that, in human tumors, GARP-expressing Tregs rather than BECs appear to represent a source of TGF-β1 suppressing nearby TILs. This local immunosuppression could be blocked with anti-GARP:TGF-β1 antibodies, particularly to treat patients with tumors heavily infiltrated by GARP-expressing Tregs.