The effect of needle tip displacement in co-axial electrohydrodynamic processing

Co-axial electrospraying and electrospinning are versatile electrohydrodynamic (EHD) techniques that can be used to encapsulate a variety of materials in the form of polymeric particles and fibres via a one step process. The successful production of uniform encapsulated products in co-axial EHD (CEHD) processing depends on multiple parameters including solution concentration, applied voltage and needle capillary diameter. Although many studies have been conducted to investigate the effects of these parameters, there has been very limited research on how the axial displacement between the two needle tips affects the final products formed. Hence the purpose of this study was to adjust the positioning of the inner needle such that its tip extends beyond, is level with or resides inside that of the outer needle and to thus determine the most effective arrangement for controlling product size, uniformity and/or yield. Core–shell particles were prepared using two polymers, poly(lactic-co-glycolic)acid (PLGA) as the shell and polymethylsilsesquioxane (PMSQ) as the core and core–shell fibres using PMSQ as the shell and a volatile liquid, perfluorohexane (PFH) as the core. The products formed were analyzed by optical microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). After analysis, it was concluded that the most effective arrangement for generating both particles and fibres with the optimal combination of size, uniformity and yield was to have the inner needle 2 mm inside the outer needle. This allows for formation of a stable cone–jet and successful encapsulation of the inner liquid within the outer liquid, before the outer stable cone–jet forms. The corresponding collected product diameter and percentage of products in which material was successfully encapsulated were found to be 0.6 ± 0.1 μm and 85 ± 3% respectively for particles and 9 ± 1 μm and 92 ± 2% for fibres

Generating Antibacterial Microporous Structures Using Microfluidic Processing

The aim of this study is to investigate the potential of microfluidic techniques to generate microporous structures, with potential utility as scaffolds, with a highly uniform architecture, possessing an antibacterial activity. Scaffolds were prepared by introducing N2 gas to gelatin (GE)-water or gelatin/hyaluronic acid (GE/HA)-water mixtures to form microbubbles at the interface. The effect of solution temperature on microbubble stability and their structural integrity were studied. A solution temperature of 40 °C produced the best results due to the higher solution viscosity. The effect of different cross-linking concentrations on scaffold swelling ratio was investigated. A concentration of 5% glutaraldehyde was found to be optimal and was chosen to cross-link structure and conduct subsequent degradation and antibacterial experiments. HA was incorporated into the scaffolds owing to its ability to make stable and highly absorbent scaffolds. This led to a decrease in the degradation rate and the introduction of an antibacterial effect. This effect could be further enhanced with the inclusion of lactoferrin. This work is the first reported attempt for making antibacterial GE/HA scaffolds by using microfluidics

Starting a movement: An epidemiological audit into the distribution and determinants of Clostridium Difficele infection at an Australian tertiary hospital site

BackgroundThe emergence of hypervirulent strains of Clostridioides (Clostridium) difficile over the past few decades has cemented C. difficile infection (CDI) as the most common cause of nosocomial infectious diarrhoea within Australia. This report was initiated to better understand the burden of disease at the Bankstown-Lidcombe Hospital through analysis of CDI incidence, risk factors, and treatment.AimsThe specific objectives of this study were two-fold; 1) to determine the prevalence of hospitalised patients affected with CDI and 2) to identify risk factors for CDI in hospitalised patients.Methods A retrospective review of all consecutive CDI cases at the Bankstown-Lidcombe Hospital between 1 July 2014 and 31 December 2018 was performed. CDI incidence was calculated based on the number of CDI cases observed per 10,000 patient days. Annual incidence and predisposing antibiotics to CDI were compared via univariate analysis and Student t-tests. Treatment for CDI was compared using contingency analysis via Pearson’s chi-squared analysis. Results The CDI diagnoses ranged from 3.2–4.6 (as a proportion of 10,000 occupied bed days) throughout 2014 and 2018. There was a significant decrease in CDI associated with Macrolides between 2017 and 2018 (p=0.03). There was a significant rise in CDI associated with Beta lactamase inhibitors and Penicillins (e.g., Tazobactam/Piperacillin). The majority of CDI patients were treated with single therapy metronidazole during their hospital stays.ConclusionCDI risk minimisation presents a significant challenge to all hospital departments. This audit highlights the importance of antibiotic usage influencing in-patient CDI cases and the vital role of multidisciplinary teams (microbiologists, pathologists, physicians, surgeons and pharmacists) in managing and monitoring these patients

Monoclonal antibodies and Fc-fusion protein biologic medicines: A multinational cross-sectional investigation of accessibility and affordability in Asia Pacific regions between 2010 and 2020

Background: Monoclonal antibody (mAb) and Fc-fusion protein (FcP) are highly effective therapeutic biologics. We aimed to analyse consumption and expenditure trends in 14 Asia-Pacific countries/regions (APAC) and three benchmark countries (the UK, Canada, and the US). Methods: We analysed 440 mAb and FcP biological products using the IQVIA-MIDAS global sales database. For each year between 2010 and 2020 inclusive, we used standard units (SU) sold per 1000 population and manufacture level price (standardised in 2019 US dollars) to evaluate consumption (accessibility) and expenditure (affordability). Changes of consumption and expenditure were estimated using compound annual growth rate (CAGR). Correlations between consumption, country's economic and health performance indicators were measured using Spearman correlation coefficient. Findings: Between 2010 and 2020, CAGRs of consumption in each region ranged from 7% to 34% and the CAGRs of expenditure ranged from 9% to 31%. The median consumption of biologics was extremely low in lower-middle-income economies (0·29 SU/1000 population) compared with upper-middle-income economies (1·20), high-income economies (40·94) and benchmark countries (109·55), although the median CAGRs of biologics consumption in lower-middle-income economies (31%) was greater than upper-middle-income (14%), high-income economies (13%) and benchmark countries (9%). Consumption was correlated with GDP per capita [Spearman's rank correlation coefficient (r) = 0·75, p < 0·001], health expenditure as a percentage of total (r = 0·83, p < 0·001) and medical doctors’ density (r = 0·85, p < 0·001). Interpretation: There have been significant increases in mAb and FcP biologics consumption and expenditure, however accessibility of biological medicines remains unequal and is largely correlated with country's income level. Funding: This research was funded by NHMRC Project Grant GNT1157506 and GNT1196900; Enhanced Start-up Fund for new academic staff and Internal Research Fund, Department of Medicine, LKS Faculty of Medicine, University of Hong Kong

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Hsa-miRNA-765 as a key mediator for inhibiting growth, migration and invasion in fulvestrant-treated prostate cancer

Fulvestrant (ICI-182,780) has recently been shown to effectively suppress prostate cancer cell growth in vitro and in vivo. But it is unclear whether microRNAs play a role in regulating oncogene expression in fulvestrant-treated prostate cancer. Here, this study reports hsa-miR-765 as the first fulvestrant-driven, ERβ-regulated miRNA exhibiting significant tumor suppressor activities like fulvestrant, against prostate cancer cell growth via blockage of cell-cycle progression at the G2/M transition, and cell migration and invasion possibly via reduction of filopodia/intense stress-fiber formation. Fulvestrant was shown to upregulate hsa-miR-765 expression through recruitment of ERβ to the 5′-regulatory-region of hsa-miR-765. HMGA1, an oncogenic protein in prostate cancer, was identified as a downstream target of hsa-miR-765 and fulvestrant in cell-based experiments and a clinical study. Both the antiestrogen and the hsa-miR-765 mimic suppressed HMGA1 protein expression. In a neo-adjuvant study, levels of hsa-miR-765 were increased and HMGA1 expression was almost completely lost in prostate cancer specimens from patients treated with a single dose (250 mg) of fulvestrant 28 days before prostatectomy. These findings reveal a novel fulvestrant signaling cascade involving ERβ-mediated transcriptional upregulation of hsa-miR-765 that suppresses HMGA1 protein expression as part of the mechanism underlying the tumor suppressor action of fulvestrant in prostate cancer. © 2014 Leung et al

High-Level Expression of Notch1 Increased the Risk of Metastasis in T1 Stage Clear Cell Renal Cell Carcinoma

Background: Although metastasis of clear cell renal cell carcinoma (ccRCC) is basically observed in late stage tumors, T1 stage metastasis of ccRCC can also be found with no definite molecular cause resulting inappropriate selection of surgery method and poor prognosis. Notch signaling is a conserved, widely expressed signal pathway that mediates various cellular processes in normal development and tumorigenesis. This study aims to explore the potential role and mechanism of Notch signaling in the metastasis of T1 stage ccRCC. Methodology/Principal Findings: The expression of Notch1 and Jagged1 were analyzed in tumor tissues and matched normal adjacent tissues obtained from 51 ccRCC patients. Compared to non-tumor tissues, Notch1 and Jagged1 expression was significantly elevated both in mRNA and protein levels in tumors. Tissue samples of localized and metastatic tumors were divided into three groups based on their tumor stages and the relative mRNA expression of Notch1 and Jagged1 were analyzed. Compared to localized tumors, Notch1 expression was significantly elevated in metastatic tumors in T1 stage while Jagged1 expression was not statistically different between localized and metastatic tumors of all stages. The average size of metastatic tumors was significantly larger than localized tumors in T1 stage ccRCC and the elevated expression of Notch1 was significantly positive correlated with the tumor diameter. The functional significance of Notch signaling was studied by transfection of 786-O, Caki-1 and HKC cell lines with full-length expression plasmids of Notch1 and Jagged1

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal