Innovative design and construction solutions for improved therapeutic healing environments

Healthcare facilities need to be designed as innovative healing environments that improve quality of care, aid the recovery process, promote therapeutic goals and improve operational efficiency. A £5 billion hospital development programme has been designated to develop new healthcare infrastructure and upgrade existing hospital facilities to meet increasing demands of healthcare across the UK. This main aim of this paper is to collate information on current developments and practice in relation to therapeutic environments. An extensive review of literature relating to current practice has been undertaken. Relationships between the physical environment and patient recovery have been investigated in order to assess the potential impact of healthcare built environments on the healing process. Critical factors which impact on the performance of a healthcare facility, such as building layout and stakeholder participation have been examined. The benefits from innovative design and construction solutions, along with the barriers to innovation, have been highlighted to identify the opportunities for improving the quality of healthcare provision

Characterization of air-liquid interface culture of A549 alveolar epithelial cells

<div><p>Alveolar epithelia play an essential role in maintaining the integrity and homeostasis of lungs, in which alveolar epithelial type II cells (AECII) are a cell type with stem cell potential for epithelial injury repair and regeneration. However, mechanisms behind the physiological and pathological roles of alveolar epithelia in human lungs remain largely unknown, partially owing to the difficulty of isolation and culture of primary human AECII cells. In the present study, we aimed to characterize alveolar epithelia generated from A549 lung adenocarcinoma cells that were cultured in an air-liquid interface (ALI) state. Morphological analysis demonstrated that A549 cells could reconstitute epithelial layers in ALI cultures as evaluated by histochemistry staining and electronic microscopy. Immunofluorescent staining further revealed an expression of alveolar epithelial type I cell (AECI) markers aquaporin-5 protein (AQP-5), and AECII cell marker surfactant protein C (SPC) in subpopulations of ALI cultured cells. Importantly, molecular analysis further revealed the expression of AQP-5, SPC, thyroid transcription factor-1, zonula occludens-1 and Mucin 5B in A549 ALI cultures as determined by both immunoblotting and quantitative RT-PCR assay. These results suggest that the ALI culture of A549 cells can partially mimic the property of alveolar epithelia, which may be a feasible and alternative model for investigating roles and mechanisms of alveolar epithelia in vitro.</p></div

Mir-208 promotes cell proliferation by repressing SOX6 expression in human esophageal squamous cell carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in developing countries. The prognosis and survival rate of ESCC are very poor. Recently, microRNAs (miRNAs) have emerged as important regulators of cancer cell biological processes. To better understanding the molecular mechanisms by which they regulate the behavior of cancer cells is needed. Methods: The expression of miR-208 was examined in ESCC cell lines and tumor tissues by real-time PCR. Proliferation capability of ESCC cells upon regulation of miR-208 expression was detected by MTT assay, colony formation assay, anchorage-independent growth ability assay and flow cytometry analysis. The target of miR-208 was determined by western blotting analysis, luciferase reporter assay and real-time PCR. Results: miR-208 was upregulated in ESCC cell lines and tissues. Overexpression of miR-208 in ESCC cells increased cell proliferation, tumorigenicity and cell cycle progression, whereas inhibition of miR-208 reduced cells proliferation, tumorigenicity and cell cycle progression. Additionally, SOX6 was identified as a direct target of miR-208. Ectopic expression of miR-208 led to downregulation of SOX6 protein, which resulted in the downregulation of p21, upregulation of cyclin D1 and phosphorylation of Rb. Conclusions: These results suggest that miR-208 represents a potential onco-miR and participates in ESCC carcinogenesis by suppressing SOX6 expression

sj-docx-1-jdr-10.1177_00220345221114783 – Supplemental material for Mussel-Inspired Hydrogels for Fluoride Delivery and Caries Prevention

Supplemental material, sj-docx-1-jdr-10.1177_00220345221114783 for Mussel-Inspired Hydrogels for Fluoride Delivery and Caries Prevention by L. Zhen, K. Liang, J. Luo, X. Ke, S. Tao, M. Zhang, H. Yuan, L. He, F.B. Bidlack, J. Yang and J. Li in Journal of Dental Research</p

Using Atomic Force Microscopy to Predict Tumor Specificity of ICAM1 Antibody-Directed Nanomedicines

Atomic force microscopy (AFM) is a powerful tool to detect <i>in vitro</i> antibody–antigen interactions. To date, however, AFM-measured antibody–antigen interactions have yet to be exploited to predict <i>in vivo</i> tumor specificity of antibody-directed nanomedicines. In this study, we have utilized AFM to directly measure the biomechanical interaction between live triple negative breast cancer (TNBC) cells and an antibody against ICAM1, a recently identified TNBC target. For the first time, we provide proof-of-principle evidence that <i>in vitro</i> TNBC cell-ICAM1 antibody binding force measured by AFM on live cells more precisely correlates with <i>in vivo</i> tumor accumulation and therapeutic efficacy of ICAM1 antibody-directed liposomes than ICAM1 gene and surface protein overexpression levels. These studies demonstrate that live cell-antibody binding force measurements may be used as a novel <i>in vitro</i> metric for predicting the <i>in vivo</i> tumor recognition of antibody-directed nanomedicines

Functionalization of Azide-Terminated Silicon Surfaces with Glycans Using Click Chemistry: XPS and FTIR Study

Efficient functionalization of silicon substrates is important for the development of silicon-based sensors. Organic monolayers directly bonded to hydrogen-terminated silicon substrates via Si–C bonds display enhanced stability toward hydrolytic cleavage. Here, we show that monolayers presenting a high density of terminal azide groups are amenable to bioconjugation with alkynyl-derivatized glycans via a copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition. The prerequisite azide-functionalized silicon surface is fabricated via hydrosilylation of undecylenic acid with hydrogen-terminated silicon substrate followed by reaction of the thus formed monolayer of acid groups with short, bifunctional oligoethylene oxide chains carrying an amine function at one terminus and an azido group at the other. The possibility to functionalize these azido-surfaces with alkynyl-derivatized glycans such as propargyl mannose through a click protocol is demonstrated and evidenced using X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy. In addition, the interaction of these mannose-adorned silicon substrates with glycan binding proteins such as <i>Lens culinaris</i> lectin is investigated. The data establishes clearly the specificity of the interaction of this newly fabricated silicon surface for mannose-selective proteins as well as its reusability, thereby demonstrating its potential as a sensor

URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma cells in vitro via activation of the NF-κB signaling pathway

Background: Angiogenesis is essential for tumor growth. Hepatocellular carcinoma (HCC) is characterized by hypervascularity; high levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in HCC. Up-regulated gene-4 (URG4), also known as upregulator of cell proliferation (URGCP), is overexpressed in multiple tumor types and has been suggested to act as an oncogene. This study aimed to elucidate the effect of URG4/URGCP on the angiogenic capacity of HCC cells in vitro. Methods: Expression of URG4/URGCP in HCC cell lines and normal liver epithelial cell lines was examined by Western blotting and quantitative real-time PCR. URG4/URGCP was stably overexpressed or transiently knocked down using a shRNA in two HCC cell lines. The human umbilical vein endothelial cell (HUVEC) tubule formation and Transwell migration assays and chicken chorioallantoic membrane (CAM) assay were used to examine the angiogenic capacity of conditioned media from URG4/URGCP-overexpressing and knockdown cells. A luciferase reporter assay was used to examine the transcriptional activity of nuclear factor kappa – light – chain - enhancer of activated B cells (NF-κB). NF-κB was inhibited by overexpressing degradation-resistant mutant inhibitor of κB (IκB)-α. Expression of vascular endothelial growth factor C (VEGFC), tumor necrosis factor-α (TNFα), interleukin (IL)-6, IL-8 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) were examined by quantitative real-time PCR; VEGFC protein expression was analyzed using an ELISA. Results: URG4/URGCP protein and mRNA expression were significantly upregulated in HCC cell lines. Overexpressing URG4/URGCP enhanced - while silencing URG4/URGCP decreased - the capacity of HCC cell conditioned media to induce HUVEC tubule formation and migration and neovascularization in the CAM assay. Furthermore, overexpressing URG4/URGCP increased - whereas knockdown of URG4/URGCP decreased - VEGFC expression, NF-κB transcriptional activity, the levels of phosphorylated (but not total) IκB kinase (IKK) and IκB-α, and expression of TNFα, IL-6, IL-8 and MYC in HCC cells. Additionally, inhibition of NF-κB activity in HCC cells abrogated URG4/URGCP-induced NF-κB activation and angiogenic capacity. Conclusions: This study suggests that URG4/URGCP plays an important pro-angiogenic role in HCC via a mechanism linked to activation of the NF-κB pathway; URG4/URGCP may represent a potential target for anti-angiogenic therapy in HCC

Arabidopsis PCH2 mediates meiotic chromosome remodeling and maturation of crossovers

Meiotic chromosomes are organized into linear looped chromatin arrays by a protein axis localized along the loop-bases. Programmed remodelling of the axis occurs during prophase I of meiosis. Structured illumination microscopy (SIM) has revealed dynamic changes in the chromosome axis in Arabidopsis thaliana and Brassica oleracea. We show that the axis associated protein ASY1 is depleted during zygotene concomitant with synaptonemal complex (SC) formation. Study of an Atpch2 mutant demonstrates this requires the conserved AAA+ ATPase, PCH2, which localizes to the sites of axis remodelling. Loss of PCH2 leads to a failure to deplete ASY1 from the axes and compromizes SC polymerisation. Immunolocalization of recombination proteins in Atpch2 indicates that recombination initiation and CO designation during early prophase I occur normally. Evidence suggests that CO interference is initially functional in the mutant but there is a defect in CO maturation following designation. This leads to a reduction in COs and a failure to form COs between some homologous chromosome pairs leading to univalent chromosomes at metaphase I. Genetic analysis reveals that CO distribution is also affected in some chromosome regions. Together these data indicate that the axis remodelling defect in Atpch2 disrupts normal patterned formation of COs

Current status of intravenous tissue plasminogen activator dosage for acute ischaemic stroke: an updated systematic review.

The optimal dose of recombinant tissue plasminogen activator (rtPA) for acute ischaemic stroke (AIS) remains controversial, especially in Asian countries. We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA. We performed a systematic literature search across MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to 22 August 2016 to identify all related studies. The outcomes were death or disability (defined by modified Rankin Scale 2-6), death, and symptomatic intracerebral haemorrhage (sICH). Where possible, data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis. We included 26 observational studies and 1 randomised controlled trial with a total of 23 210 patients. Variable doses of rtPA were used for thrombolysis of AIS in Asia. Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability (OR 1.13, 95% CI 0.95 to 1.33), or death (OR 0.86, 95% CI 0.74 to 1.01), or decreased risk of sICH (OR 1.06, 95% CI 0.65 to 1.72). The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies. Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS. Low-dose rtPA was not associated with lower risk of death or disability, death alone, or sICH

Applicability of large-ion lithophile and high field strength element basalt discrimination diagrams

<p>Basalt discriminant diagrams have been used to identify the tectonic setting of basaltic magmatism since the 1970s and have played an important role in reconstructing paleotectonic environments. However, the significant increase in the availability of geochemical data has led to a reassessment of these diagrams, suggesting that some of the tectonic settings indicated by these diagrams are not accurate. Here, we use a database of global ocean island basalt (OIB), mid-ocean ridge basalt (MORB), and island arc basalt (IAB) geochemistry to propose a series of new tectonic discriminant diagrams based on the ratios of large-ion lithophile elements (LILEs) to high field strength elements (HFSEs). These new diagrams indicate that the LILE can be used to differentiate OIB, MORB, and IAB samples, meaning that LILE/HFSE ratios can discriminate between these basalts that form in different tectonic settings. Our new diagrams can correctly assign samples to OIB, MORB, and IAB categories more than 85% of the time, with the discrimination between OIB and MORB having an accuracy of slightly less than 85%.</p