Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells

What does the ‘chat’ tell us about participation and engagement in online video conferencing?

Although much is known about the experiential nature of online conferencing, we know less about actual participation and engagement. This paper investigates delegate interactions in the “parallel chat” function of a video platform during an online medical education conference. We collected 813 unique messages, posted while speakers presented on a digital stage. We used descriptive statistics to summarize message/chat content in terms of participant categories and topic. 23% of delegates posted in the chat. However, to go beyond these dimensions, we used conversation analytic methods to identify the actions accomplished in messages and their interconnectedness. We developed a coding scheme to report this analysis across the complete dataset. We found that messages mostly comprised positive assessments (“Wonderful talk!”) and appreciations (“Thank you!”). ‘Second’ messages were more common than initiations or ‘first’ messages, indicating extensive engagement between participants. Few messages received no response. Delegates also formulated what speakers said to develop ‘learning moments’ in the chat. Overall, we argue that a richer and more precise understanding of participation and engagement in video conferencing can be achieved by analysing actual participation and its content, rather than relying only on post-hoc reports and surveys. Data are in British English

Case Reports : Rheumatoid pleural effusions and trapped lung : An uncommon complication of rheumatoid arthritis

Rheumatoid arthritis (RA) is a disease affecting approximately 1[percent] of the population. It is familiarly defined as "chronic, symmetric, debilitating and destructive inflammatory polyarthritis characterized by proliferative synovial tissue (pannus) formation in affected joints" (1). Pain symptoms are typically worse in the morning, thedisease affects females more than males, and ulnar deviation and swan neck deformities are common. Perhaps less well known is the extensive list of extra-articular manifestations (EAMs) that can occur at any time duringthe course of the disease. EAMs affect an estimated 18-41[percent] of patients with RA (1). Renal, pulmonary cardiovascular, nervous, and integumentary system manifestations have all been described. Our case is that of anRA patient with shortness of breath and pleural effusions

CO2 Emissions, Energy Consumption and Economic Growth In Malaysia : A Cointegration Approach

This paper investigates the short run and long run relationships between energy consumption, economic growth and carbon emission in Malaysia using annual data from 1982 to 2011. For better understanding of the dynamism, the study first examines the dynamics between energy consumption, economic growth and capital formation. The results indicate that unidirectional causality runs from economic growth to capital formation in the short run. The result also shows that Malaysia is an energy dependent country as evident from the bidirectional causality between economic growth and energy consumption in both the short and long run. The study continues to study the dynamics between energy consumption, economic growth and carbon emissions. With carbon emissions added into the framework, there is evidence of a bidirectional relationship between GDP and EC and EC with CO2. One interesting result to note the existence of a unidirectional relationship running from CO2 and GDP in the long run. With the country’s goal to reduce carbon emissions, reduction in CO2 emission will have an adverse impact on the country’s economic growth. However, the study found that the current recommended policies might mitigated the problem

Reaching everyone in general practice?:Feasibility of an integrated domestic violence training and support intervention in primary care

Background Primary care needs to respond effectively to patients experiencing or perpetrating domestic violence and abuse (DVA) and their children, but there is uncertainty about the value of integrated programmes. The aim of the study was to develop and test the feasibility of an integrated primary care system-level training and support intervention, called IRIS+ (Enhanced Identification and Referral to Improve Safety), for all patients affected by DVA. IRIS+ was an adaptation of the original IRIS (Identification and Referral to Improve Safety) model designed to reach female survivors of DVA. Methods Observation of training; pre/post intervention questionnaires with clinicians and patients; data extracted from medical records and DVA agency; semi-structured interviews with clinicians, service providers and referred adults and children. Data collection took place between May 2017 and April 2018. Mixed method analysis was undertaken to triangulate data from various sources to assess the feasibility and acceptability of the intervention. Results Clinicians and service providers believed that the IRIS+ intervention had filled a service gap and was a valuable resource in identifying and referring women, men and children affected by DVA. Despite increased levels of preparedness reported by clinicians after training in managing the complexity of DVA in their practice, the intervention proved to be insufficient to catalyse identification and specialist referral of men and direct identification and referral (without their non-abusive parents) of children and young people. The study also revealed that reports provided to general practice by other agencies are important sources of information about adult and children patients affected by DVA. However, in the absence of guidance about how to use this information in patient care, there are uncertainties and variation in practice. Conclusions The study demonstrates that the IRIS+ intervention is not feasible in the form and timeframe we evaluated. Further adaptation is required to achieve identification and referral of men and children in primary care: an enhanced focus on engagement with men, direct engagement with children, and improved guidance and training on responding to reports of DVA received from other agencies

‘It felt like there was always someone there for us’:supporting children affected by domestic violence and abuse who are identified by general practice

One in five children in the UK are affected by domestic violence and abuse. However, primary care clinicians (GPs and nurses) struggle to effectively identify and support children and young people living in homes where it is present. The IRIS+ (Enhanced Identification and Referral to Improve Safety) training and advocacy support intervention aimed to improve how clinicians respond to children and young people affected by domestic violence and abuse. IRIS+ training was delivered as part of a feasibility study to four general practices in an urban area in England (UK). Our mixed method design included interviews and questionnaires about the IRIS+ intervention with general practice patients, including children and young people as well as with clinicians and advocacy service providers. We collected the number of identifications and referrals by clinicians of children experiencing domestic violence and abuse through a retrospective search of medical and agency records 10 months after the intervention. Forty-nine children exposed to domestic violence and abuse were recorded in medical records. Thirty-five children were referred to a specialist domestic violence and abuse support service over a period of 10 months. Of these, 22 received direct or indirect support. The qualitative findings indicated that children benefitted from being referred by clinicians to the service. However, several barriers at the patient and professional level prevented children and young people from being identified and supported. Some of these barriers can be addressed through modifications to professional training and guidance, but others require systematic and structural changes to the way health and social care services work with children affected by domestic violence and abuse