The Abbreviated Maslach Burnout Inventory Can Overestimate Burnout: A Study of Anesthesiology Residents.

The Maslach Burnout Inventory for healthcare professionals (MBI-HSS) and its abbreviated version (aMBI), are the most common tools to detect burnout in clinicians. A wide range in burnout prevalence is reported in anesthesiology, so this study aimed to ascertain which of these two tools most accurately detected burnout in our anesthesiology residents. The MBI-HSS and aMBI were distributed amongst 86 residents across three hospitals, with a total of 58 residents completing the survey (67.4% response rate; 17 male and 41 female). Maslach-recommended cut-offs for the MBI-HSS and the aMBI with standard cut-offs were used to estimate burnout prevalence, and actual prevalence was established clinically by a thorough review of multiple data sources. Burnout proportions reported by the MBI-HSS and aMBI were found to be significantly different; 22.4% vs. 62.1% respectively (p < 0.0001). Compared to the actual prevalence of burnout in our cohort, the MBI-HSS detected burnout most accurately; area under receiver operating characteristic of 0.99 (95% confidence interval (CI): 0.92-1.0). Although there was a good correlation between the MBI-HSS and aMBI subscale scores, the positive predictive value of the aMBI was poor; 33.3% (95% CI:27.5-39.8%), therefore caution and clinical correlation are advised when using the aMBI tool because of the high rates of false-positives

Burnout and work-related stressors in gastroenterology: a protocol for a multinational observational study in the ASEAN region.

BACKGROUND: Clinician burnout is an important occupational hazard that may be exacerbated by the novel COVID-19 pandemic. Within Southeast Asia, burnout in gastroenterology is understudied. The primary objective of this study is to estimate the prevalence of burnout symptoms within gastroenterology, in member states of the Associations of Southeast Asian Nations (ASEAN), during and after the COVID-19 pandemic. The secondary objective is to identify work-related stressors that contribute to burnout in ASEAN gastroenterologists. METHODS AND ANALYSIS: This is an observational study that will use anonymised online surveys to estimate the prevalence of burnout symptoms at two time points: during the COVID-19 pandemic in 2020 and in 2022 (assumed to be after the pandemic). Gastroenterologists from Singapore, Malaysia, Thailand, Indonesia, Philippines and Brunei will be invited to participate in the online survey through their national gastroenterology and endoscopy societies. Burnout will be assessed using the Maslach Burnout Inventory-Human Services Survey tool. Supplementary questions will collect demographic and qualitative data. Associations between demographic characteristics and burnout will be tested by multiple regression. RESULTS: The prevalence of burnout symptoms in gastroenterology during the COVID-19 pandemic, and the baseline prevalence after COVID-19, will be established in the above-mentioned countries. Work-related stressors commonly associated with burnout will be identified, allowing the introduction of preventative measures to reduce burnout in the future. ETHICS AND DISSEMINATION: Ethical approval was granted by the Singhealth Centralised Institutional Review Board (2020/2709). Results will be submitted for publication

D-Cbl Binding to Drk Leads to Dose-Dependent Down-Regulation of EGFR Signaling and Increases Receptor-Ligand Endocytosis

Proper control of Epidermal Growth Factor Receptor (EGFR) signaling is critical for normal development and regulated cell behaviors. Abnormal EGFR signaling is associated with tumorigenic process of various cancers. Complicated feedback networks control EGFR signaling through ligand production, and internalization-mediated destruction of ligand-receptor complexes. Previously, we found that two isoforms of D-Cbl, D-CblS and D-CblL, regulate EGFR signaling through distinct mechanisms. While D-CblL plays a crucial role in dose-dependent down-regulation of EGFR signaling, D-CblS acts in normal restriction of EGFR signaling and does not display dosage effect. Here, we determined the underlying molecular mechanism, and found that Drk facilitates the dose-dependent regulation of EGFR signaling through binding to the proline-rich motif of D-CblL, PR. Furthermore, the RING finger domain of D-CblL is essential for promoting endocytosis of the ligand-receptor complex. Interestingly, a fusion protein of the two essential domains of D-CblL, RING- PR, is sufficient to down-regulate EGFR signal in a dose-dependent manner by promoting internalization of the ligand, Gurken. Besides, RING-SH2Drk, a fusion protein of the RING finger domain of D-Cbl and the SH2 domain of Drk, also effectively down-regulates EGFR signaling in Drosophila follicle cells, and suppresses the effects of constitutively activated EGFR. The RING-SH2Drk suppresses EGFR signaling by promoting the endosomal trafficking of ligand-receptor complexes, suggesting that Drk plays a negative role in EGFR signaling by enhancing receptor endocytosis through cooperating with the RING domain of D-Cbl. Interfering the recruitment of signal transducer, Drk, to the receptor by the RING-SH2Drk might further reduces EGFR signaling. The fusion proteins we developed may provide alternative strategies for therapy of cancers caused by hyper-activation of EGFR signaling

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Respiratory viral pathogens among Singapore military servicemen 2009 - 2012: Epidemiology and clinical characteristics

10.1186/1471-2334-14-204BMC Infectious Diseases141-BIDM

Inhibition of Proliferation and Induction of Apoptosis in Multiple Myeloma Cell Lines by CD137 Ligand Signaling

BACKGROUND: Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells, and the second most prevalent blood cancer. At present there is no cure for MM, and the average prognosis is only three to five years. Current treatments such as chemotherapy are able to prolong a patient's life but rarely prevent relapse of the disease. Even hematopoietic stem cell transplants and novel drug combinations are often not curative, underscoring the need for a continued search for novel therapeutics. CD137 and its ligand are members of the Tumor Necrosis Factor (TNF) receptor and TNF superfamilies, respectively. Since CD137 ligand cross-linking enhances proliferation and survival of healthy B cells we hypothesized that it would also act as a growth stimulus for B cell cancers. METHODOLOGY/PRINCIPAL FINDINGS: Proliferation and survival of B cell lymphoma cell lines were not affected or slightly enhanced by CD137 ligand agonists in vitro. But surprisingly, they had the opposite effects on MM cells, where CD137 ligand signals inhibited proliferation and induced cell death by apoptosis. Furthermore, secretion of the pro-inflammatory cytokines, IL-6 and IL-8 were also enhanced in MM but not in non-MM cell lines in response to CD137 ligand agonists. The secretion of these cytokines in response to CD137 ligand signaling was consistent with the observed activation of the classical NF-kappaB pathway. We hypothesize that the induction of this pathway results in activation-induced cell death, and that this is the underlying mechanism of CD137-induced MM cell death and growth arrest. CONCLUSIONS/SIGNIFICANCE: These data point to a hitherto unrecognized role of CD137 and CD137 ligand in MM cell biology. The selective inhibition of proliferation and induction of cell death in MM cells by CD137 ligand agonists may also warrant a closer evaluation of their therapeutic potential

Land-use effects on local biodiversity in tropical forests vary between continents

The file attached is the Published/publisher’s pdf version of the article

Mitochondrial Pathway Mediates the Antileukemic Effects of Hemidesmus Indicus, a Promising Botanical Drug

Although cancers are characterized by the deregulation of multiple signalling pathways, most current anticancer therapies involve the modulation of a single target. Because of the enormous biological diversity of cancer, strategic combination of agents targeted against the most critical of those alterations is needed. Due to their complex nature, plant products interact with numerous targets and influence several biochemical and molecular cascades. The interest in further development of botanical drugs has been increasing steadily and the FDA recently approved the first new botanical prescription drug. The present study is designed to explore the potential antileukemic properties of Hemidesmus indicus with a view to contributing to further development of botanical drugs. Hemidesmus was submitted to an extensive in vitro preclinical evaluation.A variety of cellular assays and flow cytometry, as well as a phytochemical screening, were performed on different leukemic cell lines. We have demonstrated that Hemidesmus modulated many components of intracellular signaling pathways involved in cell viability and proliferation and altered the protein expression, eventually leading to tumor cell death, mediated by a loss of mitochondrial transmembrane potential and increased Bax/Bcl-2 ratio. ADP, adenine nucleotide translocator and mitochondrial permeability transition pore inhibitors did not reverse Hemidesmus-induced mitochondrial depolarization. Hemidesmus induced a significant [Ca(2+)](i) raise through the mobilization of intracellular Ca(2+) stores. Moreover, Hemidesmus significantly enhanced the antitumor activity of three commonly used chemotherapeutic drugs (methotrexate, 6-thioguanine, cytarabine). A clinically relevant observation is that its cytotoxic activity was also recorded in primary cells from acute myeloid leukemic patients.These results indicate the molecular basis of the antileukemic effects of Hemidesmus and identify the mitochondrial pathways and [Ca(2+)](i) as crucial actors in its anticancer activity. On these bases, we conclude that Hemidesmus can represent a valuable tool in the anticancer pharmacology, and should be considered for further investigations

Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore

10.1186/1471-2334-12-336BMC Infectious Diseases12-BIDM