An Exit Strategy for Resuming Nonemergency Neurosurgery after Severe Acute Respiratory Syndrome Coronavirus 2: A United Kingdom Perspective

INTRODUCTION: Substantial healthcare resources have been diverted to manage the effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and nonemergency neurosurgery has been effectively closed. As we begin to emerge from the crisis, we will need to manage the backlog of nonemergency neurosurgical patients whose treatment has been delayed and remain responsive to further possible surges of SARS-CoV-2 infections. METHODS: In the present study, we aimed to identify the core themes and challenges that will limit resumption of a normal neurosurgical service after the SARS-CoV-2 pandemic and to provide pragmatic advice and solutions that could be of utility to clinicians seeking to resume nonemergency neurosurgical care. We reviewed the relevant international policies, a wide range of journalistic and media sources, and expert opinion documents to address the stated aims. RESULTS: We have presented and discussed a range of factors that could become potential barriers to resuming full elective neurosurgical provision and important steps that must be completed to achieve pre-SARS-CoV-2 surgical capacity. We also explored how these challenges can be overcome and outlined the key requirements for a successful neurosurgical exit strategy from the pandemic. CONCLUSION: The performance of nonemergency neurosurgery can start once minimum criteria have been fulfilled: 1) a structured prioritization of surgical cases; 2) virus infection incidence decreased sufficiently to release previously diverted healthcare resources; 3) adequate safety criteria met for patients and staff, including sufficient personal protective equipment and robust testing availability; and 4) maintenance of systems for rapid communication at organizational and individual levels

Concepts, protocol, variations and current trends in surgery first orthognathic approach: A literature review

In the current era of expedited orthodontics, among many clinicians, tertiary care hospitals and patients, surgery first orthognathic approach (SFOA) has gained popularity. The advantages of SFOA (face first approach) are the reduced overall treatment duration and the early improvement in facial esthetics. In SFOA, the absence of a presurgical phase allows surgery to be performed first, followed by comprehensive orthodontic treatment to achieve the desired occlusion. The basic concepts of surgery early, surgery last, SFOA and Sendai SFOA technique along with its variations are reviewed in the present article. The recent advancement in SFOA in the context of preoperative preparation, surgical procedures and post-surgical orthodontics with pertinent literature survey are also discussed

Anatomical significance of a posterior horn of medial meniscus: the relationship between its radial tear and cartilage degradation of joint surface

<p>Abstract</p> <p>Background</p> <p>Traumatic injury and surgical meniscectomy of a medial meniscus are known to cause subsequent knee osteoarthritis. However, the difference in the prevalence of osteoarthritis caused by the individual type of the medial meniscal tear has not been elucidated. The aim of this study was to investigate what type of tear is predominantly responsible for the degradation of articular cartilage in the medial compartment of knee joints.</p> <p>Methods</p> <p>Five hundred and forty eight cadaveric knees (290 male and 258 female) were registered in this study. The average age of cadavers at death was 78.8 years old (range: 52-103 years). The knees were macroscopically examined and their medial menisci were classified into four groups according to types of tears: "no tear", "radial tear of posterior horn", "other types of tear" and "worn-out meniscus" groups. The severity of cartilage degradation in their medial compartment of knee joints was evaluated using the international cartilage repair society (ICRS) grading system. We statistically compared the ICRS grades among the groups using Mann-Whitney U test.</p> <p>Results</p> <p>The knees were assigned into the four groups: 416 "no tear" knees, 51 "radial tear of posterior horn" knees, 71 "other types of tear" knees, and 10 "worn-out meniscus" knees. The knees with substantial meniscal tears showed the severer ICRS grades of cartilage degradation than those without meniscal tears. In addition, the ICRS grades were significantly severer in the "radial tear of posterior horn" group than in the "other types of tear" group, suggesting that the radial tear of posterior horn in the medial meniscus is one of the risk factors for cartilage degradation of joint surface.</p> <p>Conclusions</p> <p>We have clarified the relationship between the radial tear of posterior horn in the medial meniscus and the severer grade of cartilage degradation. This study indicates that the efforts should be made to restore the anatomical role of the posterior horn in keeping the hoop strain, when patients' physical activity levels are high and the tear pattern is simple enough to be securely sutured.</p

Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence

A Comparative Plasmonic Study of Nanoporous and Evaporated Gold Films

Previously, we have reported that nanoporous gold (NPG) films prepared by a chemical dealloying method have distinctive plasmonic properties, i.e., they can simultaneously support localized and propagating surface plasmon resonance modes (l-SPR and p-SPR, respectively). In this study, the plasmonic properties of NPG are quantified through direct comparison with thermally evaporated gold (EG) films. Cyclic voltammetry and electrochemical impedance spectroscopy experiments reveal that the NPG films have 4–8.5 times more accessible surface area than EG films. Assemblies of streptavidin–latex beads generate p-SPR responses on both NPG and EG films that correlate well with the bead density obtained from scanning electron microscopy (SEM) images. A layer-by-layer assembly experiment on NPG involving biotinylated anti-avidin IgG and avidin, studied by l-SPR and SEM, shows that the l-SPR signal is directly linked to the accessibility of the interior of the NPG porosity, an adjustable experimental parameter that can be set by the dealloying condition and time

LsrR-Mediated Quorum Sensing Controls Invasiveness of Salmonella typhimurium by Regulating SPI-1 and Flagella Genes

Bacterial cell-to-cell communication, termed quorum sensing (QS), controls bacterial behavior by using various signal molecules. Despite the fact that the LuxS/autoinducer-2 (AI-2) QS system is necessary for normal expression of Salmonella pathogenicity island-1 (SPI-1), the mechanism remains unknown. Here, we report that the LsrR protein, a transcriptional regulator known to be involved in LuxS/AI-2-mediated QS, is also associated with the regulation of SPI-1-mediated Salmonella virulence. We determined that LsrR negatively controls SPI-1 and flagella gene expressions. As phosphorylated AI-2 binds to and inactivates LsrR, LsrR remains active and decreases expression of SPI-1 and flagella genes in the luxS mutant. The reduced expression of those genes resulted in impaired invasion of Salmonella into epithelial cells. Expression of SPI-1 and flagella genes was also reduced by overexpression of the LsrR regulator from a plasmid, but was relieved by exogenous AI-2, which binds to and inactivates LsrR. These results imply that LsrR plays an important role in selecting infectious niche of Salmonella in QS dependent mode

Identification of a novel functional deletion variant in the 5'-UTR of the DJ-1 gene

<p>Abstract</p> <p>Background</p> <p>DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD). Various mutations in the <it>DJ-1 </it>(<it>PARK7</it>) gene have been shown to cause the autosomal recessive form of PD. In the present study South African PD patients were screened for mutations in <it>DJ-1 </it>and we aimed to investigate the functional significance of a novel 16 bp deletion variant identified in one patient.</p> <p>Methods</p> <p>The possible effect of the deletion on promoter activity was investigated using a Dual-Luciferase Reporter assay. The <it>DJ-1 </it>5'-UTR region containing the sequence flanking the 16 bp deletion was cloned into a pGL4.10-Basic luciferase-reporter vector and transfected into HEK293 and BE(2)-M17 neuroblastoma cells. Promoter activity under hydrogen peroxide-induced oxidative stress conditions was also investigated. Computational (<it>in silico</it>) <it>cis</it>-regulatory analysis of <it>DJ-1 </it>promoter sequence was performed using the transcription factor-binding site database, TRANSFAC via the PATCH™ and rVISTA platforms.</p> <p>Results</p> <p>A novel 16 bp deletion variant (g.-6_+10del) was identified in <it>DJ-1 </it>which spans the transcription start site and is situated 93 bp 3' from a Sp1 site. The deletion caused a reduction in luciferase activity of approximately 47% in HEK293 cells and 60% in BE(2)-M17 cells compared to the wild-type (<it>P </it>< 0.0001), indicating the importance of the 16 bp sequence in transcription regulation. The activity of both constructs was up-regulated during oxidative stress. Bioinformatic analysis revealed putative binding sites for three transcription factors AhR, ARNT, HIF-1 within the 16 bp sequence. The frequency of the g.-6_+10del variant was determined to be 0.7% in South African PD patients (2 heterozygotes in 148 individuals).</p> <p>Conclusion</p> <p>This is the first report of a functional <it>DJ-1 </it>promoter variant, which has the potential to influence transcript stability or translation efficiency. Further work is necessary to determine the extent to which the g.-6_+10del variant affects the normal function of the <it>DJ-1 </it>promoter and whether this variant confers a risk for PD.</p

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against &gt;100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology