The Effect of Acute Cocaine Exposure on NMDA Receptor Subunits in Pedunculopontine Nucleus to Substantia Nigra Pars Compacta Synapses

The substantia nigra pars compacta (SNc) is implicated in cocaine addiction due to increased NMDA receptor-mediated current found after acute cocaine exposure. The present study seeks to determine if this increase is driven by a subunit change that decreases magnesium blockage of the receptor and thus increases current. To test this, NMDA receptor-mediated current was isolated and recorded at holding voltages from -80 mV to +40 mV. It was found that at negative holding voltages, NMDA receptors conduct more current, potentially indicating that a subunit change occurs. However, more data collection will be needed to affirm these results. Continued support of a subunit change hypothesis would give researchers more knowledge on the cellular mechanisms of early-stage cocaine addiction, and provide guidance when investigating potential treatment options

Enterotoxigenic Escherichia coli Flagellin Inhibits TNF-Induced NF-κB Activation in Intestinal Epithelial Cells

Citation: Wang, G.; Geisbrecht, B.V.; Rueter, C.; Hardwidge, P.R. Enterotoxigenic Escherichia coli Flagellin Inhibits TNF-Induced NF-κB Activation in Intestinal Epithelial Cells. Pathogens 2017, 6, 18.Enterotoxigenic Escherichia coli (ETEC) causes childhood diarrhea in developing countries. ETEC strains produce the heat-labile enterotoxin (LT) and/or heat-stable enterotoxins (ST) and encode a diverse set of colonization factors used for adherence to intestinal epithelial cells. We previously found that ETEC secretes a heat-stable protein we designated as ETEC Secreted Factor (ESF) that inhibits the extent of NF-κB activation normally induced by tumor necrosis factor alpha (TNF). Here we fractionated ETEC supernatants using fast protein liquid chromatography (FPLC) and determined that ETEC flagellin was necessary and sufficient to protect IκBα from degradation in response to TNF stimulation. These data suggest a potentially novel mechanism by which ETEC may evade the host innate immune response by down-regulating NF-κB-dependent host responses

Physician-patient communication about genomic tumor testing: perceptions of oncology providers

Background: • Genomic tumor testing (GTT) is a new technology and a cornerstone of the “precision medicine” movement in cancer care. • GTT uses next-generation genome sequencing technology to identify somatic variants in tumor cells. • By identifying somatic variants that predict responses to cancer therapies, GTT can help tailor therapy to individual patients, making them more effective. • However, due to the fact that GTT also detects many variants of uncertain significance, its clinical value is currently unproven. • When using GTT, physicians counsel patients about both its benefits and its limitations, but the ideal goals and content of these physician-patient discussions have not been clearly defined

Community oncology clinicians’ knowledge, beliefs, and attitudes regarding genomic tumor testing

Introduction: Genomic tumor testing (GTT) is a new technology that promises to make cancer treatment more precise. However, little is known about clinicians’ knowledge, beliefs, and attitudes regarding GTT, particularly in community oncology settings

Genomic Profiling of Two Histologically Distinct Rare Urothelial Cancers in a Clinical Setting to Identify Potential Therapeutic Options for Treatment and Management of Disease.

Molecular profiling of urothelial cancers for therapeutic and prognostic potential has been very limited due to the absence of cancer-specific targeted therapies. We describe here 2 clinical cases with a histological diagnosis of an invasive sarcomatoid and a poorly differentiated carcinoma favoring urothelial with some neuroendocrine differentiation, two of the rarer types of urothelial cancers, which were evaluated for mutations in 212 genes for single-nucleotide variants and copy-number variants and 53 genes for fusions associated with solid tumors. In both cases, we identified variants in 2 genes, Case Rep Oncol 2018 Mar 27; 11(1):196-205

Community oncologists\u27 perceptions and utilization of large-panel genomic tumor testing.

PURPOSE: Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists\u27 perceptions and use of GTT, but little is known about community oncologists\u27 perceptions of GTT and how perceptions relate to clinicians\u27 intentions to use GTT. METHODS: Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs. Descriptive and multivariable regression analyses were conducted to characterize these perceptions and to explore the relationships between them. RESULTS: There was substantial variability in clinicians\u27 perceptions of GTT. Clinicians generally had moderate confidence in their ability to use GTT, but lower confidence in patients\u27 ability to understand test results and access targeted treatment. Clinicians had positive attitudes regarding the value of GTT. Clinicians\u27 future intentions to use GTT were associated with greater confidence in using GTT and greater perceived barriers to implementing GTT, but not with attitudes about the value of GTT. CONCLUSIONS: Community oncologists\u27 perceptions of large-panel genomic tumor testing are variable, and their future intentions to use GTT are associated with both their confidence in and perceived barriers to its use, but not with their attitudes towards GTT. More research is needed to understand other factors that determine how oncologists perceive and use GTT in clinical practice

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Impact of the COVID-19 pandemic on ongoing health research: an ad hoc survey among investigators in Germany

Objectives To gain insights into the impact of the COVID-19 pandemic on ongoing health research projects, using projects from a selected funding programme in Germany as an example. Design Online survey and validation workshop. Setting Lockdowns and social distancing policies impact on clinical and public health research in various forms, especially if unrelated to COVID-19. Research institutions have reduced onsite activities, data are often collected remotely, and during the height of the crisis, clinical researchers were partially forced to abandon their projects in favour of front-line care. Participants survey 120 investigators of health research projects across Germany, performed between 15 and 25 May 2020; workshop: 32 investigators, performed on 28 May 2020. Results The response rate (78%) showed that the survey generated significant interest among investigators. 85 responses were included for analysis, and the majority of investigators (93%) reported that their projects were affected by the pandemic, with many (80%) stating that data collection was not possible as planned, and they could not carry out interventions as intended (67%). Other impacts were caused by staff being unavailable, for example, through child or elder care commitments or because of COVID-19 quarantine or illness. Investigators also reported that publications were delayed or not feasible at all (56%), and some experienced problems with PhD or Masters theses (18%). The majority of investigators had mitigation strategies in place such as adjustment of data collection methods using digital tools (46%) or of project implementation in general (46%), others made changes in research design or research questions (27%). Conclusions The COVID-19 pandemic has severely impacted on health research projects. The main challenge is now to mitigate negative effects and to improve long-term resilience in health research. The pandemic has also acted as a driver of innovation and change, for example, by accelerating the use of digital methods.Peer Reviewe