PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer

Background: The sodium/iodide symporter (NIS) is a membrane glycoprotein mediating active iodide uptake in the thyroid gland and is the molecular basis for radioiodide imaging and therapeutic ablation of thyroid carcinomas. NIS is expressed in the lactating mammary gland and in many human breast tumors, raising interest in similar use for diagnosis and treatment. However, few human breast tumors have clinically evident iodide uptake ability. We previously identified PI3K signaling as important in NIS upregulation in transgenic mouse models of breast cancer, and the PI3K pathway is commonly activated in human breast cancer. Methods: NIS expression, subcellular localization, and function were analyzed in MCF-7 human breast cancer cells and MCF-7 cells stably or transiently expressing PI3K p110alpha subunit using Western blot of whole cell lysate, cell surface biotinylation Western blot and immunofluorescence, and radioiodide uptake assay, respectively. NIS localization was determined in a human breast cancer tissue microarray using immunohistochemical staining (IHC) and was correlated with preexisting pAkt IHC data. Statistical analysis consisted of Student's t-test (in vitro studies) or Fisher's Exact Test (in vivo correlational studies). Results: In this study, we demonstrate that PI3K activation in MCF-7 human mammary carcinoma cells leads to expression of underglycosylated NIS lacking cell surface trafficking necessary for iodide uptake ability. PI3K activation also appears to interfere with cell surface trafficking of exogenous NIS as well as all-trans retinoic acid-induced endogenous NIS. A correlation between NIS expression and upregulation of PI3K signaling was found in a human breast cancer tissue microarray. Conclusion: Thus, the PI3K pathway likely plays a major role in the discordance between NIS expression and iodide uptake in breast cancer patients. Further study is warranted to realize the application of NIS-mediated radioiodide ablation in breast cancer

Ketamine for the treatment of depression in patients receiving hospice care: a retrospective medical record review of thirty-one cases.

BACKGROUND: Depression is prevalent in patients receiving hospice care. Standard antidepressant medications do not work rapidly enough in this setting. Evidence suggests that ketamine rapidly treats treatment refractory depression in the general population. Ketamine׳s role for treating depression in the hospice population warrants further study. METHODS: A retrospective medical record review of 31 inpatients receiving hospice care who received ketamine for depression on a clinical basis was conducted. The primary outcome measure was the Clinical Global Impression Scale, which was used retrospectively to rate subjects׳ therapeutic improvement, global improvement, and side effects from ketamine over 21 days. Additionally, time to onset of therapeutic effect was analyzed. RESULTS: Using the Clinical Global Impression Scale, ketamine was found to be significantly therapeutically effective through the first week after ketamine dosing (p \u3c 0.05), with 93% of patients showing positive results for days 0-3 and 80% for days 4-7 following ketamine dosing. Patients experienced global improvement during all 4 studied time periods following ketamine dosing (p \u3c 0.05). Significantly more patients had either no side effects or side effects that did not significantly impair functioning at each of the 4 assessed time periods following ketamine dosing (p \u3c 0.05). Additionally, significantly more patients experienced their first therapeutic response during days 0-1 following ketamine dosing (p \u3c 0.001) than during any other time period. CONCLUSIONS: These data suggest that ketamine may be a safe, effective, and rapid treatment for clinical depression in patients receiving hospice care. Blinded, randomized, and controlled trials are required to substantiate these findings and support further clinical use of this medication in hospice settings

Patterns Of Intimate Partner Violence And Sexual Risk Behavior Among Young Heterosexually Active Men

Intimate partner violence (IPV) victimization is linked to sexual risk exposure among women. However, less is known about the intersection of IPV perpetration and sexual risk behavior among men. This study used data from a diverse, community sample of 334 heterosexually active young men, aged 18 to 25, across the United States to examine whether and how men with distinct IPV-related behavior patterns differed in sexual riskÃrelated behavior and attitudes. Participants were recruited and surveyed online, and grouped conceptually based on the types of IPV perpetration behavior(s) used in a current or recent romantic relationship. Groups were then compared on relevant sexual risk variables. Men reporting both physical abuse and sexual coercion against intimate partners reported significantly higher numbers of lifetime partners, higher rates of nonmonogamy, greater endorsement of nonmonogamy, and less frequent condom use relative to nonabusive men or those reporting controlling behavior only. This group also had higher sexually transmitted infection (STI) exposure compared to men who used controlling behavior only and men who used sexual coercion only. Findings suggest that interventions with men who use physical and sexual violence need to account for not only the physical and psychological harm of this behavior but also the sexual risk to which men may expose their partners

Experiences of learning through collaborative evaluation from a masters programme in professional education

This paper presents findings from a collaborative evaluation project within a masters programme in professional education. The project aimed to increase knowledge of research methodologies and methods through authentic learning where participants worked in partnership with the tutor to evaluate the module which they were studying. The project processes, areas of the course evaluated and the data collection methods are outlined. The findings focus on key themes from evaluating the effectiveness of using a collaborative evaluation approach, including: enhanced student engagement; creativity of the collaborative evaluation approach; equality between the tutor and students; and enhanced research skills. Discussion focuses on the outcomes and effectiveness of the project and tutor reflections on adopting a collaborative approach. This paper highlights lessons from the project relevant to those interested in staff-student partnership approaches and those facilitating postgraduate learning and teaching programmes and educational research courses

Cardiovascular Responses to Psychosocial Stress Reflect Motivation State in Adults Born at Extremely Low Birth Weight

Background. Adults born extremely preterm appear to have more difficulty managing the stresses of early adulthood than their term-born peers. Objective. To examine the effects of being born at extremely low birth weight (ELBW; birth weight < 1000 g) versus at full term on cardiovascular responses to stress. Method. Cardiovascular responses were elicited during administration of a widely used laboratory stressor, the Trier Social Stress Test (TSST). Results. Term-born adults exhibited a larger decrease in total peripheral resistance and larger increase in cardiac output for TSST performance, reflecting greater resilience, than did ELBW adults. Furthermore, in ELBW participants but not controls, cardiovascular responses were correlated with anxiety, suggesting that their responses reflected feelings of stress. Conclusions. Skills-training and practice with relevant stressors may be necessary to increase the personal resources of ELBW participants for managing stress as they transition to adulthood.Peer reviewe

Exploration of Burnout, Emotional Thriving, and Emotional Recovery in an Academic Medical Center: a Mixed Methods Quality Improvement Project

Introduction: Healthcare provider burnout, an indicator of wellbeing, impacts patient safety, provider distress, and employee turnover. In this mixed methods, multi-site quality improvement study conducted \u3c6 months prior to the start of the COVID-19 pandemic, we assessed employee wellbeing in a large clinical department. Methods: Wellbeing surveys were sent electronically to Department of Medicine clinicians, researchers, administrators, and staff from August-September 2019 assessing perceptions of Burnout, Emotional Thriving (ET), and Emotional Recovery (ER). Qualitative responses were reviewed for themes using mixed inductive-deductive analysis. The initial coding was done by small teams with consensus obtained through large group discussions. This study was IRB-approved as non-human subjects research. Results: Of the 671 respondents, 54% met criteria for burnout (Burnout+), 65% for ER (ER+), and 61% for ET (ET+). ER+ and ET+ were present in nearly half of Burnout+ respondents (53% and 43% respectively). Several themes emerged in the qualitative analysis: workload and expectations; tangible resources; work culture; and salary/benefits, with leadership influencing each of the domains. Conclusion: Burnout, ET, and ER can co-exist within the same individual. Employee wellbeing is not adequately reflected by the binary of whether or not an individual is experiencing burnout. All employees at academic medical centers, including staff, researchers, and clinicians, are vulnerable to the same workplace factors driving burnout. Our findings have been used to target areas of intervention during the COVID-19 pandemic at our institution. We propose that other academic medical centers may have similar workplace stressors that they could assess and target for improvement

A MAPK/c-Jun-mediated switch regulates the initial adaptive and cell death responses to mitochondrial damage in a neuronal cell model

Parkinson’s disease (PD) is defined by the progressive loss of dopaminergic neurons. Mitochondrial dysfunction and oxidative stress are associated with PD although it is not fully understood how neurons respond to these stresses. How adaptive and apoptotic neuronal stress response pathways are regulated and the thresholds at which they are activated remains ambiguous. Utilising SH-SY5Y neuroblastoma cells, we show that MAPK/AP-1 pathways are critical in regulating the response to mitochondrial uncoupling. Here we found the AP-1 transcription factor cJun can act in either a pro- or anti-apoptotic manner, depending on the level ofstress. JNK-mediated cell death in differentiated cells only occurred once a threshold of stress was surpassed. We also identified a novel feedback loop between Parkin activity and the c-Jun response, suggesting defective mitophagy may initiate MAPK/c-Jun-mediated neuronal loss observed in PD. Our data supports the hypothesis that blocking cell death pathways upstream of c-Jun as a therapeutic target in PD may not be appropriate due to crossover of the pro- and anti-apoptotic responses. Boosting adaptive responses or targeting specific aspects of the neuronal death response may therefore represent more viable therapeutic strategie

Bostonia: The Boston University Alumni Magazine. Volume 10

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Seasonal kinetic energy variability of near-inertial motions

Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 39 (2009): 1035-1049, doi:10.1175/2008JPO3920.1.Seasonal variability of near-inertial horizontal kinetic energy is examined using observations from a series of McLane Moored Profiler moorings located at 39°N, 69°W in the western North Atlantic Ocean in combination with a one-dimensional, depth-integrated kinetic energy model. The time-mean kinetic energy and shear vertical wavenumber spectra of the high-frequency motions at the mooring site are in reasonable agreement with the Garrett–Munk internal wave description. Time series of depth-dependent and depth-integrated near-inertial kinetic energy are calculated from available mooring data after filtering to isolate near-inertial-frequency motions. These data document a pronounced seasonal cycle featuring a wintertime maximum in the depth-integrated near-inertial kinetic energy deriving chiefly from the variability in the upper 500 m of the water column. The seasonal signal in the near-inertial kinetic energy is most prominent for motions with vertical wavelengths greater than 100 m but observable wintertime enhancement is seen down to wavelengths of the order of 10 m. Rotary vertical wavenumber spectra exhibit a dominance of clockwise-with-depth energy, indicative of downward energy propagation and implying a surface energy source. A simple depth-integrated near-inertial kinetic energy model consisting of a wind forcing term and a dissipation term captures the order of magnitude of the observed near-inertial kinetic energy as well as its seasonal cycle.Funding to initiate the McLane Moored Profiler observations at Line W were provided by grants from the G. Unger Vetlesen Foundation and the Comer Charitable Fund to the Woods Hole Oceanographic Institution’s Ocean and Climate Change Institute. Ongoing moored observations at Line W are supported by the National Science Foundation (NSF Grant OCE-0241354)