Higher 2-Year Cumulative Incidence of Mental Health Disorders Following Irrigation and Debridement in Primary Lumbar Fusion.

Introduction: Spinal fusion is an operation that is employed to treat spinal diseases. Surgical site infection (SSI) after lumbar fusion (LF) is a postoperative complication. SSI is treated with irrigation and debridement (I&D), which requires readmittance following discharge or prolonged hospital stays, which are deleterious to patients' mental health.

De Novo Human Angiotensin-Converting Enzyme 2 Decoy NL-CVX1 Protects Mice From Severe Disease After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection.

A Slow Dynamic RNA Switch Regulates Processing of microRNA-21.

The microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of many eukaryotic genes, and whose dysregulation is a driver of human disease. Here we report the discovery of a very slow (0.1 s) conformational rearrangement at the Dicer cleavage site of pre-miR-21, which regulates the relative concentration of readily- and inefficiently-processed RNA structural states.

How the onset of the Covid-19 pandemic impacted pro-social behaviour and individual preferences: Experimental evidence from China.

We present experimental evidence on how pro-sociality, trust and attitudes towards risk and ambiguity evolved over the six weeks following the imposition of stringent Covid-19 related lockdown measures in the Hubei province of China. We compare incentivized economic decision-making in a baseline sample, collected pre-epidemic, with a series of repeated cross-sectional samples drawn from the same population between January and March, 2020. We find high rates of altruism, cooperation and aversion to risk taking under ambiguity in the immediate aftermath of the lockdown, while trust is significantly below its baseline level.

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2.

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.

design of ACE2 protein decoys to neutralize SARS-CoV-2.

There is an urgent need for the ability to rapidly develop effective countermeasures for emerging biological threats, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a generalized computational design strategy to rapidly engineer proteins that precisely recapitulate the protein surface targeted by biological agents, like viruses, to gain entry into cells. The designed proteins act as decoys that block cellular entry and aim to be resilient to viral mutational escape.

Primordial emergence of a nucleic acid-binding protein via phase separation and statistical ornithine-to-arginine conversion.

De novo emergence demands a transition from disordered polypeptides into structured proteins with well-defined functions. However, can polypeptides confer functions of evolutionary relevance, and how might such polypeptides evolve into modern proteins? The earliest proteins present an even greater challenge, as they were likely based on abiotic, spontaneously synthesized amino acids. Here we asked whether a primordial function, such as nucleic acid binding, could emerge with ornithine, a basic amino acid that forms abiotically yet is absent in modern-day proteins.

Structure of the RNA Specialized Translation Initiation Element that Recruits eIF3 to the 5'-UTR of c-Jun.

Specialized translation initiation is a novel form of regulation of protein synthesis, whereby RNA structures within the 5'-UTR regulate translation rates of specific mRNAs. Similar to internal ribosome entry sites (IRESs), specialized translation initiation requires the recruitment of eukaryotic initiation factor 3 (eIF3), but also requires cap recognition by eIF3d, a new 5'-mGTP recognizing protein. How these RNA structures mediate eIF3 recruitment to affect translation of specific mRNAs remains unclear.

Design of RNA-targeting macrocyclic peptides.

RNA structures play a pivotal role in many biological processes and the progression of human disease, making them an attractive target for therapeutic development. Often RNA structures operate through the formation of complexes with RNA-binding proteins, however, much like protein-protein interactions, RNA-protein interactions span large surface areas and often lack traditional druggable properties, making it challenging to target them with small molecules. Peptides provide much greater surface areas and therefore greater potential for forming specific and high affinity interactions with RNA.

An Allosteric Switch Primes Sequence-Specific DNA Recognition.

Regulation of protein-DNA binding specificity occurs through myriad mechanisms. Boudet et al. discover yet a new form of specificity through allosteric regulation, an ATP-induced structural switch that mediates specific DNA recognition in an archaeoeukaryotic primase.

Standardised Warfarin Reversal Expedites Time to Theatre for Fractured Neck of Femur Surgery and Improves Mortality Rates: A Matched Cohort Study.

Background: This study aims to evaluate outcomes for warfarinised hip fracture patients and compare them with a matched nonwarfarinised group, before and after the introduction of national hip fracture guidelines in the United Kingdom.

Methods: A retrospective cohort study of 1743 hip fracture patients was undertaken. All patients admitted taking warfarin were identified.

A Macrocyclic Peptide Ligand Binds the Oncogenic MicroRNA-21 Precursor and Suppresses Dicer Processing.

MicroRNAs (miRNAs) help orchestrate cellular growth and survival through post-transcriptional mechanisms. The dysregulation of miRNA biogenesis can lead to cellular growth defects and chemotherapeutic resistance and plays a direct role in the development of many chronic diseases. Among these RNAs, miR-21 is consistently overexpressed in most human cancers, leading to the down-regulation of key tumor-suppressing and pro-apoptotic factors, suggesting that inhibition of miR-21 biogenesis could reverse these negative effects.

Automatic determination of differential coronary artery motion minima for cardiac computed tomography optimal phase selection.

Rationale And Objectives: Selecting the optimal phase for coronary artery evaluation can be challenging, especially at higher heart rates, given that the optimal phase may differ for each of the coronary arteries. This study aimed to evaluate a novel vessel-specific algorithm which automatically outputs the minimum motion phase per coronary artery.

Materials And Methods: The study included 44 patients who underwent 256-slice cardiac computed tomography for evaluation of chest pain.

Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle.

Airway smooth muscle (ASM) cellular and molecular biology is typically studied with single-cell cultures grown on flat 2D substrates. However, cells in vivo exist as part of complex 3D structures, and it is well established in other cell types that altering substrate geometry exerts potent effects on phenotype and function. These factors may be especially relevant to asthma, a disease characterized by structural remodeling of the airway wall, and highlights a need for more physiologically relevant models of ASM function.

Segmentation of the heart and great vessels in CT images using a model-based adaptation framework.

Recently, model-based methods for the automatic segmentation of the heart chambers have been proposed. An important application of these methods is the characterization of the heart function. Heart models are, however, increasingly used for interventional guidance making it necessary to also extract the attached great vessels.

Quantification of aortic valve area at 256-slice computed tomography: comparison with transesophageal echocardiography and cardiac catheterization in subjects with high-grade aortic valve stenosis prior to percutaneous valve replacement.

Purpose: The purpose of this study was to compare planimetric aortic valve area (AVA) measurements from 256-slice CT to those derived from transesophageal echocardiography (TEE) and cardiac catheterization in high-risk subjects with known high-grade calcified aortic stenosis.

Methods And Materials: The study included 26 subjects (10 males, mean age: 79±6; range, 61-88 years). All subjects were clinically referred for aortic valve imaging prior to percutaneous aortic valve replacement from April 2008 to March 2009.

Coronary plaque imaging with 256-slice multidetector computed tomography: interobserver variability of volumetric lesion parameters with semiautomatic plaque analysis software.

The purpose of this study was to evaluate the potential clinical value of coronary plaque imaging with a new generation CT scanner and the interobserver variability of coronary plaque assessment with a new semiautomatic plaque analysis application. Thirty-five isolated plaques of the left anterior descending coronary artery from 35 patients were evaluated with a new semiautomatic plaque analysis application. All patients were scanned with a 256-slice MDCT scanner (Brilliance iCT, Philips Healthcare, Cleveland OH, USA).

Quantitative right and left ventricular functional analysis during gated whole-chest MDCT: a feasibility study comparing automatic segmentation to semi-manual contouring.

Purpose: To evaluate the feasibility of an automatic, whole-heart segmentation algorithm for measuring global heart function from gated, whole-chest MDCT images.

Material And Methods: 15 patients with suspicion of PE underwent whole-chest contrast-enhanced MDCT with retrospective ECG synchronization. Two observers computed right and left ventricular functional indices using a semi-manual and an automatic whole-heart segmentation algorithm.

Prospectively gated axial CT coronary angiography: preliminary experiences with a novel low-dose technique.

To assess image quality and radiation exposure with prospectively gated axial CT coronary angiography (PGA) compared to retrospectively gated helical techniques (RGH). Forty patients with suspected coronary artery disease (CAD) and a stable heart rate below 65 bpm underwent CT coronary angiography (CTCA) using a 64-channel CT system. The patient cohort consisted of 20 consecutive patients examined using a PGA technique and 20 patients examined using a standard RGH technique.

Automatic model-based segmentation of the heart in CT images.

Automatic image processing methods are a prerequisite to efficiently analyze the large amount of image data produced by computed tomography (CT) scanners during cardiac exams. This paper introduces a model-based approach for the fully automatic segmentation of the whole heart (four chambers, myocardium, and great vessels) from 3-D CT images. Model adaptation is done by progressively increasing the degrees-of-freedom of the allowed deformations.

Empirical regioselectivity models for human cytochromes P450 3A4, 2D6, and 2C9.

Cytochromes P450 3A4, 2D6, and 2C9 metabolize a large fraction of drugs. Knowing where these enzymes will preferentially oxidize a molecule, the regioselectivity, allows medicinal chemists to plan how best to block its metabolism. We present QSAR-based regioselectivity models for these enzymes calibrated against compiled literature data of drugs and drug-like compounds.

Cardiac imaging using multislice computed tomography scanners: technical considerations.

Conventional coronary angiography is currently the gold standard in the detection and diagnosis of coronary artery disease. This modality, however, is invasive in nature. Hence, there is a need for noninvasive imaging techniques to provide comprehensive assessment of coronary artery disease, especially in stable patients at low to moderate risk of disease.

A model for predicting likely sites of CYP3A4-mediated metabolism on drug-like molecules.

We have developed a rapid semiquantitative model for evaluating the relative susceptibilities of different sites on drug molecules to metabolism by cytochrome P450 3A4. The model is based on the energy necessary to remove a hydrogen radical from each site, plus the surface area exposure of the hydrogen atom. The energy of hydrogen radical abstraction is conventionally measured by AM1 semiempirical molecular orbital calculations.

CKB - the compound knowledge base: a text based chemical search system.

The Compound Knowledge Base (CKB) was developed as a means of locating structures and additional relevant information from a given known structural identifier. Any of Chemical Abstracts Service Registry Number, company code (code number the producing company refers to the chemical entity internally), generic name (trivial or class name), or trade name (name under which the compound is marketed) can be provided as a query. CKB will provide the remaining available information as well as the corresponding structure for any matching compound in the database.