The risk of transmission of a viral haemorrhagic fever infection in a United Kingdom laboratory

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Are children and young people with additional learning needs at a systemic disadvantage regarding Welsh language opportunities?

This paper explores whether children and young people (CYP) with additional learning needs (ALN) are at a systemic disadvantage regarding Welsh language opportunities. Justification pertaining to why this should be on the radar of educational psychologists (EPs) in Wales is provided. Congruent with critical realism, quantitative and qualitative research is reviewed, examining micro, eco and macrosystems. A systemic lens illuminates the context and process factors that CYP with ALN and their families may encounter regarding Welsh language opportunities. This paper is informed by the bioecological Person Process Context Time (PPCT) model, and the Constructionist Model of Informed and Reasoned Action (COMOIRA). Limitations demarcating interpretation of identified issues are highlighted, without negating their significance. Implications for EPs are offered, contemplating their role in facilitating inclusion through supporting the development of greater cohesion between Welsh Government (WG) legislation (macrosystem), and the systemic realities of CYP with ALN in Wales

Evaluation of the Effectiveness of Common Hospital Hand Disinfectants Against Methicillin-Resistant Staphylococcus aureus, Glycopeptide-Intermediates, S aureus, and Heterogeneous Glycopeptide-Intermediate S. aureus

Background. The presence of methicillin‐resistant Staphylococcus aureus (MRSA) and glycopeptide‐intermediate S. aureus (GISA) in hospitals poses a significant challenge to hospital infection control teams. The use of disinfectants for both surface and hand cleaning is an essential part of the infection control measures. Objective. To evaluate the effectiveness of common hospital hand disinfectants against MRSA, GISA, and heterogeneous GISA (hGISA). Methods. For methicillin‐susceptible S. aureus (MSSA), MRSA, GISA, and hGISA, the levels of susceptibility to hand disinfectants and their active ingredients were determined. Suspension tests were performed on commercial handwashing products. Results. Minimum inhibitory concentrations (MICs) of 2‐propanol, chlorhexidine, and hexachlorophene were similar for all phenotypes. The MICs of cetrimide and triclosan were higher for the MRSA, GISA, and hGISA strains than for the MSSA strain. The MICs for the chlorhexidine‐containing agents Hibisol and Hibiscrub (AstraZeneca) and for the propanol‐containing agent Sterillium (Medline) were 1–2‐fold lower for the MSSA strains than for the MRSA, GISA, and hGISA strains. Suspension tests showed that the GISA and hGISA strains were less susceptible to the triclosan‐containing agent Aquasept (SSL) than were the MRSA and MSSA strains, with resistance increasing with glycopeptide resistance. Products containing Betadine (Purdue) were more effective against the GISA and hGISA strains than against the MRSA and MSSA strains, especially after the strain was exposed to the product for 30 seconds. Conclusions. Using the EN 1040 standard criteria for the performance of disinfectants, we determined that all agents, except 50% Aquasept for hGISA and 0.33% hexachlorophene for GISA, performed effectively. However, the GISA and hGISA strains were less susceptible to triclosan‐containing products, compared with the MRSA stains, but were more susceptible to products containing Betadine

Clinical significance of PD1 and PDL1 in human breast cancer

Background/Aim: Programmed death 1 (PD1) and its ligand programmed death ligand 1 (PDL1) form a pathway which when activated is thought to result in suppression of antitumor adaptive responses, influencing antitumor immunity. With potential targeted therapies emerging against PDL1, we investigated the clinical significance of mRNA expression levels of PD1 and PDL1 in our breast cancer cohort to explore its association with disease progression and prognosis. Previous studies evaluating the expression of PD1 and PDL1 (mRNA or protein) and its association with prognosis in breast cancer showed both positive and negative correlations and hence remain controversial. Materials and Methods: Quantitative polymerase chain reaction was used to determine transcript expression levels of PD1 and PDL1 in a cohort consisting of primary breast cancer tissues (n=127) and matching non-neoplastic background tissues (n=33) with available clinical and pathological information. Two-sample two-tailed t-test, Kaplan–Meier survival analysis and Wilcoxon tests were performed. Results: Significant PDL1 transcript level reductions were seen in patients who developed metastases, as well as those who had local recurrence, compared to patients who remained disease-free. Higher PDL1 transcript levels were also associated with better overall and disease-free survival. Significantly higher transcript expression levels of PD1 were found in tumor tissue, whilst a general increase in PDL1 expression was found in tumor tissues, although this did not reach statistical significance. Conclusion: Our study demonstrates higher levels of expression of PDL1 are associated with favorable clinical outcome

SIKs suppress tumor function and regulate drug resistance in breast cancer

Salt-inducible kinases (SIKs), belonging to an AMP-activated kinase (AMPK) family, have an evolving role in tumourigenesis and metastasis in many solid tumours. However, the function of SIKs in breast cancer is not fully established. Here, we systematically elucidated the function of SIK family members in breast cancer. In clinical cohort of breast cancer, the expression of SIK1, SIK2 and SIK3 increased expression of SIKs was associated with good clinical outcome in breast cancer cohort. In vitro, reduced expression of SIK2 and SIK3, by way of knockdown increased the proliferation of breast cancer cells. However, SIK2 and SIK3 had contrasting effects on adhesion in breast cancer cells. Knockdown of SIK2 only enhanced the adhesion of triple negative breast cancer cell, while knockdown of SIK3 can decrease the adhesion of both MDA-MB-231 and MCF-7 cells. Interestingly, knockdown of SIK1 and SIK3 was seen to increase the invasion of MDA-MB-231 cells. Furthermore, reduced SIKs, even triple knockdown of SIK1, SIK2 and SIK3 rendered the breast cancer cells to confer chemoresistance to paclitaxel and cisplatin. Collectively, the study reports that SIKs are actively involved in regulating the aggressive functions of breast cancer cells and influence the clinical course of the patients with breast cancer that they molecules are potential prognostic factors and chemotherapy biomarkers

Metagenomic next-generation sequencing aids the diagnosis of viral infections in febrile returning travellers

Objectives Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool. Methods Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays. Results In total, 11/40 patients were diagnosed with a viral infection. Standard of care diagnostics revealed 5 viral infections using plasma samples; dengue virus 1 (n = 2), hepatitis E (n = 1), Ebola virus (n = 1) and hepatitis A (n = 1), all of which were detected by MNGS. Three additional patients with Chikungunya virus (n = 2) and mumps virus were diagnosed by MNGS only. Respiratory infections detected by nasal/throat swabs only were not detected by MNGS of plasma. One patient had infection with malaria and mumps virus during the same admission. Conclusions MNGS analysis of plasma samples improves the sensitivity of diagnosis of viral infections and has potential as an all-in-one diagnostic test. It can be used to identify infections that have not been considered by the treating physician, co-infections and new or emerging pathogens. Summary Next generation sequencing (NGS) has potential as an all-in-one diagnostic test. In this study we used NGS to diagnose returning travellers with acute febrile illness in the UK, highlighting cases where the diagnosis was missed using standard methods

CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin

Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8− skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (programmed cell death protein 1+), senescent (CD57+, killer cell lectin-like receptor subfamily G member 1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput sequencing of expressed TCR β-chain (TRB) gene rearrangements showed that these CCR8-defined populations are clonotypically distinct, suggesting unique ontogenies in response to separate antigenic challenges and/or stimulatory conditions. Moreover, CCR8+ and CCR8− skin T cells were phenotypically stable in vitro and displayed similar levels of telomere erosion, further supporting the likelihood of a nonlinear differentiation pathway. On the basis of these results, we propose that long-lived memory T cells in human skin can be defined by the expression of CCR8

Expression of Claudin-9 (CLDN9) in breast cancer, the clinical significance in connection with its subcoat anchorage proteins ZO-1 and ZO-3 and impact on drug resistance

(1) Introduction: Claudin-9 (CLDN9) is a member of the claudin protein family, a critical transmembrane protein family for tight junctions that are implemented in the progression of numerous cancer types. The present study investigated the role that CLDN9, along with the subcoat proteins, Zonula Occludens (ZOs), plays in clinical breast cancer and subsequent impact on drug response of patients. (2) Methods: CLDN9 protein and CLDN9 transcript were determined and correlated with clinical and pathological indicators, together with the status of hormonal receptors. The levels of CLDN9 transcript were also assessed against the therapeutic responses of the patients to chemotherapies by using a dataset from the TCGA database. Breast cancer cell models, representing different molecular subtypes of breast cancer, with differential expression of CLDN9 were created and used to assess the biological impact and response to chemotherapeutic drugs. (3) Results: Breast cancer tissues expressed significantly higher levels of the CLDN9, with the high levels being associated with shorter survival. CLDN9 was significantly correlated with its anchorage proteins ZO-1 and ZO-3. Integrated expression of CLDN9, ZO-1 and ZO-3 formed a signature that was significantly linked to overall survival (OS) (p = 0.013) and relapse-free survival (RFS) (p = 0.024) in an independent matter. CLDN9 transcript was significantly higher in patients who were resistant to chemotherapies (p < 0.000001). CLDN9 connection to chemoresistance was particularly prominent in patients of ER-positive (ER(+)), Her-2-negative((Her-2(−)), ER(+)/Her-2(−) and triple-negative breast cancers (TNBCs), but not in patients with HER-2-positive tumors. In Her-2-negative MCF7 and MDA-MB-231 cancer cells, loss of CLDN9 significantly increased sensitivity to several chemotherapeutic drugs including paclitaxel, gemcitabine and methotrexate, which was not seen in Her-2(+) SKBR3 cells. However, suppressing Her-2 using neratinib, a permanent Her-2 inhibitor, sensitized cellular response to these chemodrugs in cells with CLDN9 knockdown. (4) Conclusions: CLDN9 is an important prognostic indicator for patients with breast cancer and also a pivotal factor in assessing patient responses to chemotherapies. Her-2 is a negating factor for the treatment response prediction value by CLDN9 and negating Her-2 and CLDN9 may enhance breast cancer cellular response to chemotherapeutic drugs

The effect of maternal smoking and alcohol consumption on lip morphology

Objective: To determine whether maternal smoking and/or alcohol consumption has an influence on lip morphology. Maternal smoking is a known risk factor for orofacial clefts; however, its influence on normal lip variation is unknown. Recent research regarding normal lip morphology has been contradictory. Design: Retrospective cohort study. Setting and participants: A total of 4747 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) who each had 3D facial scans carried out at 15 years of age were included in the study. Methods: Each of the participants was automatically categorised regarding predetermined lip morphological traits. Questionnaires completed by their mothers identified smoking and alcohol habits during pregnancy. Logistic regression analyses were applied to determine the effect of maternal smoking and alcohol consumption on lip morphology. Results: Maternal smoking has significant effects on upper and lower lip contours, Cupid’s bow, lower lip-chin shape and lower lip tone (all P 6 units of alcohol are consumed per week (P = 0.0149, 32 weeks). Overall results suggest a deeply grooved philtrum is more likely if alcohol is consumed. Investigating the combined effect of smoking and alcohol consumption, lower lip contour (P = 0.00923) and lower lip-chin shape (P = 0.0171) are statistically significant, with lower lip contour more likely to be narrow in the midline, and lower lip-chin shape more likely to be an angular concavity. Conclusion: Maternal smoking influences a number of lip traits, including a possible epigenetic effect on upper lip contour. Maternal alcohol consumption, particularly at a high level, influences philtrum shape. Maternal smoking and alcohol consumption have a combined effect on lower lip contour and lower lip-chin shape