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59%) were VR-naïve, and 76 (52.41%) reported that they had previous VR experience. Results show that VR facilitated understanding of ophthalmological complications and was reasonably tolerated. Lastly, exposure to VR raised children and young people's awareness and interest in science.

The VR platform used was successfully utilized and was well accepted in children to display and interact with volume-rendered 3D ophthalmological data. Virtual reality (VR) is suitable as a novel image display platform in ophthalmology to engage children and young people.

The VR platform used was successfully utilized and was well accepted in children to display and interact with volume-rendered 3D ophthalmological data. Virtual reality (VR) is suitable as a novel image display platform in ophthalmology to engage children and young people.A simple and fast high-performance liquid chromatography with tandem mass spectrometry method for quantification of tazobactam, piperacillin, and meropenem in human plasma has been developed and validated. Simple sample preparation with a volume of 10 μL was done by protein precipitation with a mixture of methanol-acetonitrile-water (622, v/v/v). Chromatographic separation was achieved on a Luna column with a precolumn security guard by gradient elution using a mobile phase consisting of water with the addition of 0.1% formic acid (component A) and mixture methanol-acetonitrile (82, v/v) with the addition of 0.1% formic acid (component B). The run time was 2.7 min. The lower limits of detection and lower limits of quantification were for piperacillin 0.03 and 0.1 mg/L, for meropenem 0.04 and 0.2 mg/L and for tazobactam 0.16 and 0.5 mg/L. The validated method was used for therapeutic monitoring of tazobactam, piperacillin, and meropenem in samples of patients treated in the intensive care unit.

ZNF384 gene fusions resulting from translocations with several partner genes have been described in B cell acute lymphoblastic leukemia (B-ALL) with a characteristic immunophenotype (aberrant CD13 and or CD33 with dim CD10). The prognosis of patients with this rearrangement appears to depend on the fusion partner. ZNF384 rearrangements have been identified by high through put technologies such as RNA sequencing in most of the studies published. We tested the feasibility of using the characteristic immunophenotype as a tool to screen for patients with ZNF384 translocations which can be subsequently confirmed by cytogenetic / molecular methodologies.

ZNF384 rearrangements in B-ALL patients at diagnosis with CD10 <80% and were negative for the BCR-ABL1 fusion (n=109) were identified by fluorescence in situ hybridization followed by confirmation by reverse transcriptase-polymerase chain reaction and Sanger sequencing. The end of induction measurable residual disease evaluated by flow cytometry for these patients was obtained from patient records.

ZNF384 translocations were identified in 14 patients and were cytogenetically cryptic in 13. EP300-ZNF384 was the most common fusion partner (n=12), while TAF15-ZNF384 and TCF3-ZNF384 were identified in 1 patient each. End of induction MRD by flow cytometry was positive in 5 of 8 patients with the EP300-ZNF384 fusion treated at our center.

Our findings show a practical approach for the identification of ZNF384 gene rearrangements by widely available technologies and indicate that the response to therapy may be heterogeneous even in this subset, which has been reported as having a favorable prognosis.

Our findings show a practical approach for the identification of ZNF384 gene rearrangements by widely available technologies and indicate that the response to therapy may be heterogeneous even in this subset, which has been reported as having a favorable prognosis.

Cannabis-based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high-quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health-related quality of life and clinical safety.

A prospective case series was performed using the UK Medical Cannabis Registry. Primary outcomes were change in patient-reported outcomes measures (EQ-5D-5L, General Anxiety Disorder-7 (GAD-7) and Single-Item Sleep Quality Scale (SQS)) at 1 and 3months from baseline. The secondary outcome was the incidence of adverse events. Statistical significance was defined by a P-value <.050.

There were 129 patients included in the final analysis with a mean age of 46.23 (±14.51) years. The most common indication was chronic pain of undefined etiology (n=48; 37.2%). The median initial cannabidiol and (-)-trans-Δ⁹-tetrahydrocannabinol daily dose was 20.0mg (Range 0.0-768.0mg) andlimited scope of this initial analysis, with no placebo or an active comparator, with further research required.Immune checkpoint therapy, where CD8 tumor infiltrating T lymphocytes (TIL) are reactivated, is a promising anti-cancer treatment approach, yet with low response rates. The extracellular matrix, in particular tenascin-C, may generate barriers for TIL. To investigate this possibility, we used a MMTV-NeuNT and syngeneic mammary gland grafting model derived thereof with engineered tenascin-C levels and observed accumulation of CD8 TIL in tenascin-C-rich stroma. Inhibition studies revealed that tenascin-C induced CXCL12 through TLR4. By binding CXCL12, tenascin-C retained CD8 TIL in the stroma. Blockade of CXCR4, the receptor of CXCL12, enhanced macrophage and CD8 TIL infiltration and reduced tumor growth and subsequent metastasis. Retention of CD8 TIL by tenascin-C/CXCL12 was also observed in human breast cancer by tissue staining. Moreover, whereas high CD8 TIL numbers correlated with longer metastasis-free survival, this was not the case when also tenascin-C and CXCL12 levels were high. Altogether, these results may be useful for improving tumor immunity as diagnostic tool and to formulate a future "TIL-matrix-release-and-reactivate" strategy.

Adult T-Cell Leukemia/Lymphoma (ATLL) is an aggressive T-cell malignancy without known characteristic cytogenetic abnormalities. Recurrent mutations in TP53, APC, and epigenetic and histone-modifying genes have been identified in North American ATLL. Their roles in disease progression are not yet fully elucidated.

We studied the cytogenetic and Next-Generation Sequencing (NGS) findings of the North American ATLL cohort at our institution and compared the findings with Japanese and other North American cohorts. We also analyzed the genetic variants in TP53, APC, and histone-modifying genes and investigated the impact of their mutations on the number of mutations via NGS in ATLL.

Cases with more than 6 chromosomal breaks (n=13) had significantly shorter overall survival compared to cases with fewer chromosomal breaks (n=7) (P=.0007). Cases with breaks on chromosome 3q (n=4) exhibited worse survival compared to the rest of the cases (n=16) (P=.012). Chromosomal abnormalities on 3q, 14q, 1q, 1p, and 17q are likely primary changes in ATLL based on frequency and association with prognosis. The average number of mutations via NGS was significantly higher in cases with mutations in TP53 (n=8) (P=.020) as well as APC (n=6) (P=.024) compared to cases without mutations in these genes. All TP53 variants were pathogenic missense and truncating mutations in COSMIC database.

Cytogenetic and NGS methods are useful tools to monitor disease progression in indolent ATLL and assess prognosis in aggressive ATLL.

Cytogenetic and NGS methods are useful tools to monitor disease progression in indolent ATLL and assess prognosis in aggressive ATLL.In low- and middle-income countries (LMICs), access to water, sanitation and hygiene (WASH) is associated with nutritional status including stunting, which affects 144 million children under 5 globally. Despite the consistent epidemiological association between WASH indicators and nutritional status, the provision of WASH interventions alone has not been found to improve child growth in recent randomized control trials. We conducted a literature review to develop a new conceptual framework that highlights what is known about the WASH to nutrition pathways, the limitations of certain interventions and how future WASH could be leveraged to benefit nutritional status in populations. This new conceptual framework will provide policy makers, program implementors and researchers with a visual tool to bring into perspective multiple levels of WASH and how it may effectively influence nutrition while identifying existing gaps in implementation and research.

Residual disease (RD) detected using multiparametric flow cytometry (MFC) is an independent predictive variable of relapse in acute myeloid leukaemia (AML). WZ811 chemical structure However, RD thresholds and optimal assessment time points remain to be validated.

We investigated the significance of RD after induction therapy in paediatric AML with normal karyotype between June 2008 and June 2018. Bone marrow samples from 73 patients were collected at the end of the first (BMA-1) and second (BMA-2) induction courses to monitor RD using MFC.

Presence of RD after BMA-1 and/or BMA-2 correlated with poor relapse-free (RFS) and overall survival at 0.1% RD cutoff level. Receiver operating characteristic curve showed that RD cutoff levels of 1.3% and 0.5% after BMA-1 and BMA-2, respectively, predicted events with the highest sensitivity and specificity. In multivariable analysis, RD after BMA-2 was the strongest independent risk predictor for poor RFS (hazard ratio 2.934; 95% confidence interval 1.106-7.782; P=.031).

Our study therefore suggests that an RD level ≥0.5% after BMA-2 has a significant predictive impact on the prognosis of AML patients having normal karyotype and thus guide the stratification of treatment strategies.

Our study therefore suggests that an RD level ≥0.5% after BMA-2 has a significant predictive impact on the prognosis of AML patients having normal karyotype and thus guide the stratification of treatment strategies.Systemic problems of discrimination plague diversity and inclusion efforts in medical education globally. Medical educators need to acknowledge that learners are dealing with considerable emotional and perhaps social and economic stress and that this stress is likely worse for minoritized learners. In this milieu, what is the role of the medical educator? This article takes an inclusive approach to supporting students and explores various threads in the medical education literature to provide a roadmap for medical educators. This article traces the medical educator's journey with (1) understanding why medical students need educators to intervene, (2) exploring how to create a space for dialog, and (3) beginning the conversation with medical students. It ends with a series of concrete suggestions for medical educators.Thyroid-associated ophthalmopathy (TAO), the most common and severe manifestation of Graves' disease (GD), is a disfiguring and potentially blinding autoimmune disease. The high relapse rate (up to 20%) and substantial side effects of glucocorticoid treatment further decrease the life quality of TAO patients. To develop novel therapies, we amid to explore the immunopathogenesis of TAO. To identify the key immune-related genes (IRGs) in TAO, we integrated the IRG expression profiles in thyrocytes from a GD patient set (GD vs healthy control) and a TAO patient set (TAO vs GD). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and receiver operating characteristic (ROC) curve analyses identified the leptin receptor (LEPR) gene as the key IRG in TAO immunopathogenesis. Gene set enrichment analysis (GSEA) suggested enrichment of the antigen presentation pathway in TAO patients with higher LEPR. Increased LEPR expression was validated in TAO orbital tissues, and weighted gene co-expression network analysis (WGCNA) showed that cell adhesion processes were positively correlated with LEPR.