Variability in COVID-19 Symptom Presentation During Pregnancy and its Impact on Maternal and Infant Outcomes Across the Pandemic.

BACKGROUND: With the dominance of different SARS-CoV-2 variants, the severity of COVID-19 has evolved. We aimed to investigate the difference in symptom prevalence and the association between symptoms and adverse pregnancy outcomes during the dominance of Wild-type/Alpha, Delta, and Omicron. METHODS: COVID-19 related symptom prevalence, maternal and specific neonatal outcomes of 5431 pregnant women registered in this prospective study were compared considering the dominant virus variant. Logistic regression models analyzed the association between specific symptoms and intensive care unit (ICU) admission or preterm birth. RESULTS: Infection with the Delta variant led to an increase in the symptom burden compared to the Wild-type/Alpha variant and the highest risk for respiratory tract symptoms, feeling of sickness, headache, and dizziness/drowsiness. An infection with the Omicron variant was associated with the lowest risk of dyspnea and changes in smell/taste but the highest risk for nasal obstruction, expectoration, headaches, myalgia, and fatigue compared to the Wild-type/Alpha and Delta variant dominant periods. With the progression of the Wild-type/Alpha to the Delta variant neonatal outcomes worsened. Dyspnea and fever were strong predictors for maternal ICU admission and preterm birth independent of vaccination status or trimester of infection onset. CONCLUSION: The symptom burden increased during the Delta period and was associated with worse pregnancy outcomes than in the Wild-type/Alpha area. During the Omicron dominance there still was a high prevalence of less severe symptoms. Dyspnea and fever can predict a severe maternal illness.

Can you feel the force just right? Tactile force feedback for training of minimally invasive surgery-evaluation of vibration feedback for adequate force application.

BACKGROUND: Tissue handling is a crucial skill for surgeons and is challenging to learn. The aim of this study was to develop laparoscopic instruments with different integrated tactile vibration feedback by varying different tactile modalities and assess its effect on tissue handling skills. METHODS: Standard laparoscopic instruments were equipped with a vibration effector, which was controlled by a microcomputer attached to a force sensor platform. One of three different vibration feedbacks (F1: double vibration > 2 N; F2: increasing vibration relative to force; F3: one vibration > 1.5 N and double vibration > 2 N) was applied to the instruments. In this multicenter crossover trial, surgical novices and expert surgeons performed two laparoscopic tasks (Peg transfer, laparoscopic suture, and knot) each with all the three vibration feedback modalities and once without any feedback, in a randomized order. The primary endpoint was force exertion. RESULTS: A total of 57 subjects (15 surgeons, 42 surgical novices) were included in the trial. In the Peg transfer task, there were no differences between the tactile feedback modalities in terms of force application. However, in subgroup analysis, the use of F2 resulted in a significantly lower mean-force application (p-value = 0.02) among the student group. In the laparoscopic suture and knot task, all participants exerted significantly lower mean and peak forces using F2 (p-value < 0.01). These findings remained significant after subgroup analysis for both, the student and surgeon groups individually. The condition without tactile feedback led to the highest mean and peak force exertion compared to the three other feedback modalities. CONCLUSION: Continuous tactile vibration feedback decreases the mean and peak force applied during laparoscopic training tasks. This effect is more pronounced in demanding tasks such as laparoscopic suturing and knot tying and might be more beneficial for students. Laparoscopic tasks without feedback lead to increased force application.

Endoscopic Characterization and Outcome of COVID-19 Patients with Secondary Sclerosing Cholangitis: A Case Series of a Tertiary Center.

BACKGROUND AND AIMS: During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection developed secondary sclerosing cholangitis (SSC) as a hepatobiliary complication. METHODS: 17 patients were endoscopically diagnosed and treated with COVID-19 SSC from February 2020 until October 2022 at our center. We retrospectively reviewed and analyzed the data to define risk factors, establish endoscopic treatment options, and to estimate incidence and outcomes. RESULTS: 258 patients with COVID-19 infection were admitted to our tertiary center and mechanically ventilated. 10 patients developed COVID-19 SSC in-house, and 7 patients were transferred for further endoscopic treatment. All 17 patients were mechanically ventilated, received vasoactive substances and 12 of them were treated with extracorporeal membrane oxygenation therapy. Endoscopic retrograde cholangiography (ERC) was performed in all patients to establish the diagnosis of COVID-19 SSC and evaluate endoscopic treatment options. All ERCs revealed biliary casts. 9 patients had developed severe rarefication of the intrahepatic bile ducts and 4 showed biliary strictures. As endoscopic treatment approaches, casts were removed repeatedly, and strictures were dilated. During the study period, 14 patients died (82%). 3 patients are in follow-up to reassess the need for liver transplantation. CONCLUSIONS: COVID-19 SSC was observed in 2.6 % of the patients with severe COVID-19 in our center. We show that endoscopic approaches offer the opportunity to extract casts and to treat biliary strictures. As the mortality rate of COVID-19 SSC is high, endoscopic treatment can be of great clinical relevance as a bridge to liver transplantation.

A Bis(silylene)silole - synthesis, properties and reactivity.

A 1,1-bis(silylene)silole has been synthesised by a double salt-metathesis reaction from potassium silacyclopentadienediide, K2[1], and an amidinato-stabilized silylene chloride in a 1 : 2 ratio. The red colour of the title compound is due to the lp(Si)/π*(silole) transition. This band is bathochromically shifted compared to that of other 1,1-bissilylsiloles suggesting enhanced conjugation between the silole π-system and the newly formed Si(II)-Si(IV)-Si(II) group. The bissilylene is easily oxidised by the elemental chalcogens S, Se, and Te and forms a bissilaimide by reaction with an arylazide.

Synthesis of Bisindole Alkaloids and Their Mode of Action against Methicillin-Resistant Staphylococcus Aureus.

About 100,000 deaths are attributed annually to infections with methicillin-resistant Staphylococcus aureus (MRSA) despite concerted efforts toward vaccine development and clinical trials involving several preclinically efficacious drug candidates. This necessitates the development of alternative therapeutic options against this drug-resistant bacterial pathogen. Using the Masuda borylation-Suzuki coupling (MBSC) sequence, we previously synthesized and modified naturally occurring bisindole alkaloids, alocasin A, hyrtinadine A and scalaradine A, resulting in derivatives showing potent in vitro and in vivo antibacterial efficacy. Here, we report on a modified one-pot MBSC protocol for the synthesis of previously reported and several undescribed N-tosyl-protected bisindoles with anti-MRSA activities and moderate cytotoxicity against human monocytic and kidney cell lines. In continuation of the mode of action investigation of the previously synthesized membrane-permeabilizing hit compounds, mechanistic studies reveal that bisindoles impact the cytoplasmic membrane of Gram-positive bacteria by promiscuously interacting with lipid II and membrane phospholipids while rapidly dissipating membrane potential. The bactericidal and lipid II-interacting lead compounds 5c and 5f might be interesting starting points for drug development in the fight against MRSA.

Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs).

A key feature of cancer is the disruption of cell cycle regulation, which is characterized by the selective and abnormal activation of cyclin-dependent kinases (CDKs). Consequently, targeting CDKs via meriolins represents an attractive therapeutic approach for cancer therapy. Meriolins represent a semisynthetic compound class derived from meridianins and variolins with a known CDK inhibitory potential. Here, we analyzed the two novel derivatives meriolin 16 and meriolin 36 in comparison to other potent CDK inhibitors and could show that they displayed a high cytotoxic potential in different lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells. In a kinome screen, we showed that meriolin 16 and 36 prevalently inhibited most of the CDKs (such as CDK1, 2, 3, 5, 7, 8, 9, 12, 13, 16, 17, 18, 19, 20). In drug-to-target modeling studies, we predicted a common binding mode of meriolin 16 and 36 to the ATP-pocket of CDK2 and an additional flipped binding for meriolin 36. We could show that cell cycle progression and proliferation were blocked by abolishing phosphorylation of retinoblastoma protein (a major target of CDK2) at Ser612 and Thr82. Moreover, meriolin 16 prevented the CDK9-mediated phosphorylation of RNA polymerase II at Ser2 which is crucial for transcription initiation. This renders both meriolin derivatives as valuable anticancer drugs as they target three different Achilles' heels of the tumor: (1) inhibition of cell cycle progression and proliferation, (2) prevention of transcription, and (3) induction of cell death.

Structural Characterization, and Antioxidative and Anti-inflammatory Activities of Phylloxanthobilins in Tropaeolum majus, a Plant with Relevance in Phytomedicine.

Tropaeolum majus (garden nasturtium) is a plant with relevance in phytomedicine, appreciated not only for its pharmaceutical activities, but also for its beautiful leaves and flowers. Here, we investigated the phytochemical composition of senescent nasturtium leaves. Indeed, we identified yellow chlorophyll catabolites, also termed phylloxanthobilins, which we show to contribute to the bright yellow color of the leaves in the autumn season. Moreover, we isolated and characterized the phylloxanthobilins from T. majus, and report the identification of a pyro-phylloxanthobilin, so far only accessible by chemical synthesis. We show that the phylloxanthobilins contribute to bioactivities of T. majus by displaying strong anti-oxidative effects in vitro and in cellulo, and anti-inflammatory effects as assessed by COX-1 and COX-2 enzyme inhibition, similar to other bioactive ingredients of T. majus, isoquercitrin, and chlorogenic acid. Hence, phylloxanthobilins could play a role in the efficacy of T. majus in the treatment of urinary tract infections, an established indication of T. majus. With the results shown in this study, we aid in the completion of the phytochemical profile of T. majus by identifying additional bioactive natural products as relevant components of this medicinal plant.

Natural Language Processing for Work-Related Stress Detection Among Health Professionals: Protocol for a Scoping Review.

BACKGROUND: There is an urgent need worldwide for qualified health professionals. High attrition rates among health professionals, combined with a predicted rise in life expectancy, further emphasize the need for additional health professionals. Work-related stress is a major concern among health professionals, affecting both the well-being of health professionals and the quality of patient care. OBJECTIVE: This scoping review aims to identify processes and methods for the automatic detection of work-related stress among health professionals using natural language processing (NLP) and text mining techniques. METHODS: This review follows Joanna Briggs Institute Methodology and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. The inclusion criteria for this scoping review encompass studies involving health professionals using NLP for work-related stress detection while excluding studies involving other professions or children. The review focuses on various aspects, including NLP applications for stress detection, criteria for stress identification, technical aspects of NLP, and implications of stress detection through NLP. Studies within health care settings using diverse NLP techniques are considered, including experimental and observational designs, aiming to provide a comprehensive understanding of NLP's role in detecting stress among health professionals. Studies published in English, German, or French from 2013 to present will be considered. The databases to be searched include MEDLINE (via PubMed), CINAHL, PubMed, Cochrane, ACM Digital Library, and IEEE Xplore. Sources of unpublished studies and gray literature to be searched will include ProQuest Dissertations & Theses and OpenGrey. Two reviewers will independently retrieve full-text studies and extract data. The collected data will be organized in tables, graphs, and a qualitative narrative summary. This review will use tables and graphs to present data on studies' distribution by year, country, activity field, and research methods. Results synthesis involves identifying, grouping, and categorizing. The final scoping review will include a narrative written report detailing the search and study selection process, a visual representation using a PRISMA-ScR flow diagram, and a discussion of implications for practice and research. RESULTS: We anticipate the outcomes will be presented in a systematic scoping review by June 2024. CONCLUSIONS: This review fills a literature gap by identifying automated work-related stress detection among health professionals using NLP and text mining, providing insights on an innovative approach, and identifying research needs for further systematic reviews. Despite promising outcomes, acknowledging limitations in the reviewed studies, including methodological constraints, sample biases, and potential oversight, is crucial to refining methodologies and advancing automatic stress detection among health professionals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56267.

The complexometric behavior of selected aroyl-S,N-ketene acetals shows that they are more than AIEgens.

Using the established synthetic methods, aroyl-S,N-ketene acetals and subsequent bi- and multichromophores can be readily synthesized. Aside from pronounced AIE (aggregation induced emission) properties, these selected examples possess distinct complexometric behavior for various metals purely based on the underlying structural motifs. This affects the fluorescence properties of the materials which can be readily exploited for metal ion detection and for the formation of different metal-aroyl-S,N-ketene acetal complexes that were confirmed by Job plot analysis. In particular, gold(I), iron(III), and ruthenium (III) ions reveal complexation enhanced or quenched emission. For most dyes, weakly coodinating complexes were observed, only in case of a phenanthroline aroyl-S,N-ketene acetal multichromophore, measurements indicate the formation of a strongly coordinating complex. For this multichromophore, the complexation results in a loss of fluorescence intensity whereas for dimethylamino-aroyl-S,N-ketene acetals and bipyridine bichromophores, the observed quantum yield is nearly tripled upon complexation. Even if no stable complexes are formed, changes in absorption and emission properties allow for a simple ion detection.

Synthesis, Electronic, and Antibacterial Properties of 3,7-Di(hetero)aryl-substituted Phenothiazinyl N-Propyl Trimethylammonium Salts.

In this study, a library of 3,7-di(hetero)aryl-substituted 10-(3-trimethylammoniumpropyl)10H-phenothiazine salts is prepared. These title compounds and their precursors are reversible redox systems with tunable potentials. The Hammett correlation gives a very good correlation of the first oxidation potentials with σp parameters. Furthermore, the title compounds and their precursors are blue to green-blue emissive. Screening of the salts reveals for some derivatives a distinct inhibition of several pathogenic bacterial strains (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Aconetobacter baumannii, and Klebsiella pneumoniae) in the lower micromolar range.

Private vs. public emergency visits for mental health due to heat: An indirect socioeconomic assessment of heat vulnerability and healthcare access, in Curitiba, Brazil.

Few studies have explored the influence of socioeconomic status (SES) on the heat vulnerability of mental health (MH) patients. As individual socioeconomic data was unavailable, we aimed to fill this gap by using the healthcare system type as a proxy for SES. Brazilian national statistics indicate that public patients have lower SES than private. Therefore, we compared the risk of emergency department visits (EDVs) for MH between patients from both healthcare types. EDVs for MH disorders from all nine public (101,452 visits) and one large private facility (154,954) in Curitiba were assessed (2017-2021). Daily mean temperature was gathered and weighed from 3 stations. Distributed-lag non-linear model with quasi-Poisson (maximum 10-lags) was used to assess the risk. We stratified by private and public, age, and gender under moderate and extreme heat. Additionally, we calculated the attributable fraction (AF), which translates individual risks into population-representative burdens - especially useful for public policies. Random-effects meta-regression pooled the risk estimates between healthcare systems. Public patients showed significant risks immediately as temperatures started to increase. Their cumulative relative risk (RR) of MH-EDV was 7.5 % higher than the private patients (Q-Test 26.2 %) under moderate heat, suggesting their particular heat vulnerability. Differently, private patients showed significant risks only under extreme heat, when their RR became 4.3 % higher than public (Q-Test 6.2 %). These findings suggest that private patients have a relatively greater adaptation capacity to heat. However, when faced with extreme heat, their current adaptation means were potentially insufficient, so they needed and could access healthcare freely, unlike their public counterparts. MH patients would benefit from measures to reduce heat vulnerability and access barriers, increasing equity between the healthcare systems in Brazil. AF of EDVs due to extreme heat was 0.33 % (95%CI 0.16;0.50) for the total sample (859 EDVs). This corroborates that such broad population-level policies are urgently needed as climate change progresses.

West Nile Virus Emergence in Germany 2019: Looking for Hidden Human West Nile Virus Infections.

Background: Autochthonous human West Nile virus (WNV) infections were notified in the infectious disease surveillance system in Germany in 2018 for the first time and every year since then. Since clinically apparent infections are infrequent, we conducted two studies to investigate subclinical infections of this emerging disease in Germany in 2019 to detect infections not visible to surveillance based on symptomatic infections: limited-scope blood donor testing and a serosurvey among employees at two Berlin zoos with a history of demonstrated WNV infections in animals. Methods: For the zoo study, employees of the two zoos in Berlin were invited to participate in the study in late 2019. Blood samples were drawn and tested for the presence of antibodies (immunoglobulin M [IgM] and immunoglobulin G [IgG]) against WNV, and two other flaviviruses present in Germany: Usutu virus and Tick-borne encephalitis virus (TBEV). For the study in blood donors, four blood establishments with collection sites in regions with documented WNV-infected animals in 2018 and 2019 participated in the study. All donations in these regions were tested for WNV genome from July to November 2019. Results: In the enzyme-linked immunosorbent assay, none of the 70 tested zoo employees were WNV IgM-positive, 8 were WNV IgG-positive, additional 2 participants had equivocal results. All 10 were negative in the virus neutralization test (VNT) for WNV, but positive in the VNT for TBEV. None of the 4273 samples from blood donors tested in areas with WNV-infected animals was positive for WNV-RNA. Conclusion: Our results indicate that WNV circulation in Germany, though clearly documented in animals in 2019, apparently affected very few humans. Still areas with WNV-positive animals remain risk areas for human infection as well.

Sugar beet PMT5a and STP13 carriers suitable for proton-driven plasma membrane sucrose and glucose import in taproots.

Sugar beet (Beta vulgaris) is the major sugar-producing crop in Europe and Northern America, as the taproot stores sucrose at a concentration of around 20%. Genome sequence analysis together with biochemical and electrophysiological approaches led to the identification and characterization of the TST sucrose transporter driving vacuolar sugar accumulation in the taproot. However, the sugar transporters mediating sucrose uptake across the plasma membrane of taproot parenchyma cells remained unknown. As with glucose, sucrose stimulation of taproot parenchyma cells caused inward proton fluxes and plasma membrane depolarization, indicating a sugar/proton symport mechanism. To decipher the nature of the corresponding proton-driven sugar transporters, we performed taproot transcriptomic profiling and identified the cold-induced PMT5a and STP13 transporters. When expressed in Xenopus laevis oocytes, BvPMT5a was characterized as a voltage- and H+-driven low-affinity glucose transporter, which does not transport sucrose. In contrast, BvSTP13 operated as a high-affinity H+/sugar symporter, transporting glucose better than sucrose, and being more cold-tolerant than BvPMT5a. Modeling of the BvSTP13 structure with bound mono- and disaccharides suggests plasticity of the binding cleft to accommodate the different saccharides. The identification of BvPMT5a and BvSTP13 as taproot sugar transporters could improve breeding of sugar beet to provide a sustainable energy crop.

Novel Types of Phyllobilins in a Fern - Molecular Reporters of the Evolution of Chlorophyll Breakdown in the Paleozoic Era.

Breakdown of chlorophyll (Chl), as studied in angiosperms, follows the pheophorbide a oxygenase/phyllobilin (PaO/PB) pathway, furnishing linear tetrapyrroles, named phyllobilins (PBs). In an investigation with fern leaves we have discovered iso-phyllobilanones (iPBs) with an intriguingly rearranged and oxidized carbon skeleton. We report here a key second group of iPBs from the fern and on their structure analysis. Previously, these additional Chl-catabolites escaped their characterization, since they exist in aqueous media as mixtures of equilibrating isomers. However, their chemical dehydration furnished stable iPB-derivatives that allowed the delineation of the enigmatic structures and chemistry of the original natural catabolites. The structures of all fern-iPBs reflect the early core steps of a PaO/PB-type pathway and the PB-to-iPB carbon skeleton rearrangement. A striking further degradative chemical ring-cleavage was observed, proposed to consume singlet molecular oxygen (1O2). Hence, Chl-catabolites may play a novel active role in detoxifying cellular 1O2. The critical deviations from the PaO/PB pathway, found in the fern, reflect evolutionary developments of Chl-breakdown in the green plants in the Paleozoic era.

Understanding the Dynamics of Polymer Extrusion: Simulation of Thermoplastics Processing with Planetary Roller Extruders.

Resource efficient processing of polymers is of paramount importance to minimize energy consumption, processing time, and material losses in the polymer industry. This study is concerned with polymer processing in planetary roller extruders. A three-dimensional numerical flow simulation was tailored to understand the polymer flow through the extruder in detail. Using the simulation software ANSYS Polyflow, we quantified both directly measurable process parameters, such as pressure build-up, and more intangible parameters, such as material shear. By varying operational and material parameters in a sensitivity analysis, we showed that the dynamics, material stress and pressure build-up are controlled primarily by the number of spindles and their rotational speed. Notably, this work provides the first successful validation of a 3D simulation of a polymer flow in a planetary roller extruder against actual experimental data. The simulation showed robust agreement between the simulated and experimental values, provided that a critical backpressure length is reached. This computational approach minimizes labor-intensive experimental testing in polymer processing.