Notes

Replaced 2-(2-hydroxyphenyl)-3H-quinazolin-4-ones along with their difluoroboron complexes: Functionality and photophysical qualities.
95--125) min for LLA and 125 (i.q.r. 110-145) min for TEP (P < 0.001). The median cost including all materials was 2433 (i.q.r. 2084-2734) Euros for LLA and 2395 (i.q.r. 2093-2784) Euro for TEP (P = 0.650). Mean sick leave was 4.2 days in the LLA group and 6.2 days in the TEP group (P = 0.830).

The overall cost to the hospital or length of sick leave did not differ between LLA and TEP.
The overall cost to the hospital or length of sick leave did not differ between LLA and TEP.
It is unclear how the length of prehospital transport time affects outcome in paediatric trauma. This study evaluated the association of transport time from alarm to arrival at hospital with adverse outcome in paediatric trauma patients in Sweden.

This was a retrospective study based on prospectively collected data from the Swedish trauma registry between 2012 and 2019 of children less than 18 years with major trauma (New Injury Severity Score (NISS) greater than 15). The primary outcome was 30-day mortality, and secondary outcomes were emergency interventions (e.g., chest tube or laparotomy) and low functional outcome (Glasgow Outcome Scale 2-3). Primary exposure was transport time from alarm to arrival at hospital. Co-variables in multivariable regressions were gender, age, ASA score before injury, injury intention, dominant injury type, NISS, Glasgow Coma Scale score, prehospital competence and hospital level.

Among 597 patients, 30-day mortality was 9.8 per cent, emergency interventions were performe an obstacle against centralization of paediatric trauma care. Further studies should focus on the role of prehospital competence and other transport-associated parameters and their association with adverse outcome.Although public voluntary health insurance (VHI) has been adopted in many low- and middle-income countries to improve access to care for the population, a common issue with VHI is its high dropout rate. Using the New Cooperative Medical Scheme (NCMS)-a public VHI in China-as a case study, this article employs a fixed-effects negative binomial regression model combining the difference-in-difference-in-differences approach and multivariate distance matching to examine the factors associated with dropping out and the impact of dropout on outpatient care utilization among middle-aged and older people in rural China. Drawing data from the China Health and Retirement Longitudinal Study, our results showed that healthy people, vulnerable people and people who use less healthcare tended to drop out. Dropout had a significant negative impact on outpatient care utilization, especially for those with worse health statuses and those living in poorer provinces. We also found that the impact of dropout on outpatient utilization was more pronounced at secondary and tertiary hospitals than at primary care clinics. We urge policymakers to rethink the design of the NCMS by waiving premiums for the most vulnerable people.
There are few data comparing the relative effectiveness of the individual β-lactams.

To quantify the reduced effectiveness, defined as switching to a different antibiotic being prescribed for the same indication, among new users of β-lactam antibiotics in primary care.

A retrospective cohort study was conducted using the Health Search Database, an Italian primary care data source. Patients newly prescribed with β-lactams for a specific indication between 1 January 2013 and 31 December 2017 were identified. A switch to a different antibiotic for the same indication occurring during a 30day follow-up was the study outcome. Cox regression was adopted to assess the risk of switching between the different β-lactams.

Among 178 256 patients newly treated with β-lactam antibiotics, 1172 (0.65%) switched to a different antibiotic. Amoxicillin/clavulanate (co-amoxiclav n = 104 891) and amoxicillin (n = 21 699) were the most frequently prescribed β-lactams. The other antibiotics showed significantly higher risk of switching when compared with co-amoxiclav for lower respiratory tract [e.g. ceftriaxone, hazard ratio (HR) 1.6, 95% CI 1.2-2.0], dental [e.g. amoxicillin, HR 4.2, 95% CI 2.9-5.9], and middle ear infections [e.g. amoxicillin, HR 1.8, 95% CI 1.1-2.7]. The same results were gathered when parenteral formulations were excluded.

The prevalence of reduced effectiveness of newly prescribed β-lactam antibiotics was lower than 1%. Specifically, the rate of switch to another antibiotic, when it was prescribed to treat low respiratory tract, dental, and middle ear infections, was lower among users of co-amoxiclav than those prescribed with other β-lactams.
The prevalence of reduced effectiveness of newly prescribed β-lactam antibiotics was lower than 1%. Specifically, the rate of switch to another antibiotic, when it was prescribed to treat low respiratory tract, dental, and middle ear infections, was lower among users of co-amoxiclav than those prescribed with other β-lactams.
The risk of brain injury following surgery for type A aortic dissection (TAAD) remains substantial and no consensus has still been reached on which neuroprotective technique should be preferred. We aimed to investigate the association between neuroprotective strategies and clinical outcomes following TAAD repair.

Using the UK National Adult Cardiac Surgical Audit, we identified 1929 patients undergoing surgery for TAAD (2011-2018). Deep hypothermic circulatory arrest (DHCA) only, unilateral (uACP), bilateral antegrade cerebral perfusion (bACP) and retrograde cerebral perfusion were used in 830, 117, 760 and 222 patients, respectively. The primary end point was a composite of death and/or cerebrovascular accident (CVA). Generalized linear mixed model was used to adjust the effect of neuroprotective strategies for other confounders.

The use of bACP was associated with longer circulatory arrest (CA) compared to other strategies. There was a trend towards lower incidence of death and/or CVA using uACP only for shorter CA. In particular, primary end point rate was 27.7% overall and 26.5%, 12.5%, 28.0% and 22.9% for CA <30 min and 28.6%, 30.4%, 33.3% and 33.0% for CA ≥30 min with DHCA only, uACP, bACP and retrograde cerebral perfusion, respectively. The use of DHCA only was associated with five-fold [odds ratio (OR) 5.35, 95% confidence interval (CI) 1.36-21.02] and two-fold (OR 1.77, 95% CI 1.01-3.09) increased risk of death and/or CVA compared to uACP and bACP, respectively, but the effect of uACP was significantly associated with CA duration (hazard ratio 0.97, 95% CI 0.94-0.99; P = 0.04).

In TAAD repair, the use of uACP and bACP was associated with a lower adjusted risk of death and/or CVA when compared to DHCA. uACP can offer some advantage but only for a shorter CA duration.
In TAAD repair, the use of uACP and bACP was associated with a lower adjusted risk of death and/or CVA when compared to DHCA. uACP can offer some advantage but only for a shorter CA duration.Cryo-electron microscopy (cryo-EM) is rapidly becoming an attractive method in the field of structural biology. With the exploding popularity of cryo-EM, sample preparation must evolve to prevent congestion in the workflow. The dire need for improved microscopy samples has led to a diversification of methods. This Review aims to categorize and explain the principles behind various techniques in the preparation of vitrified samples for the electron microscope. Various aspects and challenges in the workflow are discussed, from sample optimization and carriers to deposition and vitrification. Reliable and versatile specimen preparation remains a challenge, and we hope to give guidelines and posit future directions for improvement.RNA-binding proteins (RBPs) are critical regulators of gene expression and RNA processing that are required for gene function. Yet the dynamics of RBP regulation in single cells is unknown. To address this gap in understanding, we developed STAMP (Surveying Targets by APOBEC-Mediated Profiling), which efficiently detects RBP-RNA interactions. STAMP does not rely on ultraviolet cross-linking or immunoprecipitation and, when coupled with single-cell capture, can identify RBP-specific and cell-type-specific RNA-protein interactions for multiple RBPs and cell types in single, pooled experiments. Pairing STAMP with long-read sequencing yields RBP target sites in an isoform-specific manner. Finally, Ribo-STAMP leverages small ribosomal subunits to measure transcriptome-wide ribosome association in single cells. STAMP enables the study of RBP-RNA interactomes and translational landscapes with unprecedented cellular resolution.Hi-C, split-pool recognition of interactions by tag extension (SPRITE) and genome architecture mapping (GAM) are powerful technologies utilized to probe chromatin interactions genome wide, but how faithfully they capture three-dimensional (3D) contacts and how they perform relative to each other is unclear, as no benchmark exists. Here, we compare these methods in silico in a simplified, yet controlled, framework against known 3D structures of polymer models of murine and human loci, which can recapitulate Hi-C, GAM and SPRITE experiments and multiplexed fluorescence in situ hybridization (FISH) single-molecule conformations. We find that in silico Hi-C, GAM and SPRITE bulk data are faithful to the reference 3D structures whereas single-cell data reflect strong variability among single molecules. The minimal number of cells required in replicate experiments to return statistically similar contacts is different across the technologies, being lowest in SPRITE and highest in GAM under the same conditions. Noise-to-signal levels follow an inverse power law with detection efficiency and grow with genomic distance differently among the three methods, being lowest in GAM for genomic separations >1 Mb.Visualizing dynamic processes over large, three-dimensional fields of view at high speed is essential for many applications in the life sciences. Light-field microscopy (LFM) has emerged as a tool for fast volumetric image acquisition, but its effective throughput and widespread use in biology has been hampered by a computationally demanding and artifact-prone image reconstruction process. Here, we present a framework for artificial intelligence-enhanced microscopy, integrating a hybrid light-field light-sheet microscope and deep learning-based volume reconstruction. In our approach, concomitantly acquired, high-resolution two-dimensional light-sheet images continuously serve as training data and validation for the convolutional neural network reconstructing the raw LFM data during extended volumetric time-lapse imaging experiments. Our network delivers high-quality three-dimensional reconstructions at video-rate throughput, which can be further refined based on the high-resolution light-sheet images. We demonstrate the capabilities of our approach by imaging medaka heart dynamics and zebrafish neural activity with volumetric imaging rates up to 100 Hz.The innate immune response is critical for recognizing and controlling infections through the release of cytokines and chemokines. However, severe pathology during some infections, including SARS-CoV-2, is driven by hyperactive cytokine release, or a cytokine storm. The innate sensors that activate production of proinflammatory cytokines and chemokines during COVID-19 remain poorly characterized. In the present study, we show that both TLR2 and MYD88 expression were associated with COVID-19 disease severity. Mechanistically, TLR2 and Myd88 were required for β-coronavirus-induced inflammatory responses, and TLR2-dependent signaling induced the production of proinflammatory cytokines during coronavirus infection independent of viral entry. TLR2 sensed the SARS-CoV-2 envelope protein as its ligand. In addition, blocking TLR2 signaling in vivo provided protection against the pathogenesis of SARS-CoV-2 infection. Overall, our study provides a critical understanding of the molecular mechanism of β-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.
Read More: