The Role of Postoperative Radiation Therapy for pN2 Non–small-cell Lung Cancer

BackgroundThe role for postoperative radiation therapy (PORT) for patients with non–small-cell lung cancer (NSCLC) with mediastinal lymph node (LN) involvement (pN2 disease) is controversial. We compared surgery alone with PORT among patients with pN2 NSCLC. We then performed subset analyses to better delineate patients that might benefit from PORT.Patients and MethodsWe conducted a propensity score (PS)-matched, inverse probability of treatment weighting (IPTW) Surveillance, Epidemiology, and End Results (SEER) analysis of patients with pN2 disease from 1989 to 2016 with surgery alone or PORT. Multiple imputation with chained equations was used for missing LN data.ResultsA total of 8631 patients were included in this analysis; 4579 underwent surgery alone, and 4052 underwent PORT. Following PS matching and IPTW, there was no difference in overall survival (OS) (hazard ratio [HR], 0.99; P = .76). However, PORT improved OS among a subset of patients with a LN positive to sampled ratio ≥ 50% (HR, 0.90; P = .01). Moreover, there was a trend towards improved OS among this subset, even with chemotherapy (HR, 0.91; P = .09).ConclusionPORT is not associated with an improvement or detriment in OS for all patients with pN2 NSCLC. However, patients with a positive to sampled LN ratio ≥ 50% may benefit, regardless of chemotherapy status. Nevertheless, PORT will remain the standard of care as we await the results of the ongoing LUNG ART trial.     

Oxidative modifications of proteins by sodium arsenite in human umbilical vein endothelial cells

Epidemiologic studies have demonstrated that chronic arsenic exposure is associated with the incidence of chronic diseases. This association is partly related to the increase in reactive oxygen species (ROS) overload and protein oxidation that result from arsenic exposure. In this study, we intended to identify proteins susceptible to oxidative carbonylation by sodium arsenite and the impact of carbonylation on the function of these proteins in human umbilical vein endothelial cells (HUVECs). The 2,4‐dinitrophenylhydrazine (DNPH) dot‐blot assay revealed that arsenite (0–50 μM) dose‐dependently increased protein carbonylation. Consistent with these findings, the cellular ROS level as measured by 2′,7′‐dichlorofluorescein diacetate (DCHF‐DA) assay was increased in cells exposed to arsenite. By two‐dimensional gel electrophoresis and matrix assist laser desorption ionization time of flight mass spectrometry (MALDI‐TOF/MS), one glycolytic enzyme, enolase‐α, two cytoskeleton proteins, fascin (F‐actin associated protein) and vimentin, and two protein quality control proteins, HSC70 (heat‐shock cognate protein 70), and PDIA3 (protein disulfide isomerase family A, member 3) were identified to be arsenic‐sensitive carbonlyated proteins. Accompanied by carbonylation, enolase‐α activity was dose‐dependently decreased and the F‐actin filament network was disturbed. Taken together, our results suggest that arsenite exposure results in the generation of carbonylated proteins, and the resultant changes in energy metabolism and in the cytoskeletal network may partly lead to cell damage. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Concurrent upregulation of postsynaptic L-type Ca(2+) channel function and protein kinase A signaling is required for the periadolescent facilitation of Ca(2+) plateau potentials and dopamine D1 receptor modulation in the prefrontal cortex

Further understanding of how prefrontal cortex (PFC) circuit change during postnatal development is of great interest due to its role in working memory and decision-making, two cognitive abilities that are refined late in adolescence and become altered in schizophrenia. While it is evident that dopamine facilitation of glutamate responses occurs during adolescence in the PFC, little is known about the cellular mechanisms that support these changes. Among them, a developmental facilitation of postsynaptic Ca²⁺ function is of particular interest given its role in coordinating neuronal ensembles, a process thought to contribute to maturation of PFC function. Here we conducted whole-cell patch clamp recordings of deep-layer pyramidal neurons in PFC brain slices and determined how somatic-evoked Ca²⁺-mediated plateau depolarizations change throughout postnatal day (PD) 25 (juvenile) to adulthood (PD 80). Postsynaptic Ca²⁺ potentials in the PFC increase in duration throughout postnatal development. A remarkable shift from short to prolonged depolarizations was observed after PD 40. This change is reflected by an enhancement of L-type Ca²⁺ channel function and postsynaptic PKA signaling. We speculate that such a protracted developmental facilitation of Ca²⁺ response in the PFC may contribute to improvement of working memory performance through adolescence.     

Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A‐induced hepatitis

We previously demonstrated the immunosuppressive activity of anti‐histone H1 autoantibody induced in experimental and clinical liver allograft tolerance. This study aimed to explore the immunological aspects of anti‐histone H1 autoantibody in liver injury induced by concanavalin A (Con A). To establish a Con A‐hepatitis model, 20 mg/kg Con A was intravenously injected into rats, after which liver function and histopathological analyses were performed. In this model, anti‐histone H1 autoantibody was transiently induced in the sera during the natural recovery stage, 3–7 days after Con A injection. To evaluate the therapeutic significance of anti‐histone H1 autoantibody, a polyclonal antibody against histone H1 was intraperitoneally injected immediately after Con A injection. We found that injection of anti‐histone H1 antibody could reduce Con A‐induced liver damage. Further mechanical analyses revealed that anti‐histone H1 antibody altered the intracellular activation of mitogen‐activated protein kinase, nuclear factor‐κB and calcineurin via T‐cell receptor signalling, suggesting that anti‐histone H1 antibody may protect the liver from Con A‐induced injury by inhibiting activation of effector T cells. These findings suggest that anti‐histone H1 autoantibody may be a natural immune regulatory factor that protects inflamed livers suffering from autoimmune hepatitis and may lead to T‐cell unresponsiveness through the selective regulation of mitogen‐activated protein kinase/nuclear factor‐κB and calcineurin signalling.     

Excitatory response of prefrontal cortical fast-spiking interneurons to ventral tegmental area stimulation in vivo

Prefrontal cortical (PFC) pyramidal neurons (PN) and fast spiking interneurons (FSI) receive dopaminergic (DA) and non-DA inputs from the ventral tegmental area (VTA). Although the responses of PN to VTA stimulation and DA administration have been extensively studied, little is known about the response of FSI to mesocortical activation. We explored this issue using single and double in vivo juxtacellular recordings of medial PFC PN and FSI with chemical VTA stimulation. Electrophysiological characteristics combined with Neurobiotin staining and parvalbumin immunohistochemistry allowed identification of recorded cells as FSI or PN. NMDA injection into the VTA increased firing in all FSI tested (n = 7), whereas most PN (7/11) responded with an inhibition. Furthermore, FSI excitation matching the temporal course of PN inhibition was observed with FSI-PN paired recordings (n = 5). These divergent electrophysiological responses to mesocortical activation could reflect PFC GABAergic interneurons contributing to silencing PN. Thus, the mesocortical system could provide a critical control of PFC circuits by simultaneously affecting FSI and PN firing.     

Laparoscopic Management of an Isolated Ovarian Metastasis on a Transposed Ovary in a Patient Treated for Stage IB1 Adenocarcinoma of the Cervix

Transposition of the ovaries is performed frequently in young women with early-stage cervical cancer. This procedure is performed to preserve their quality of life. However, this must be balanced with the risks of ovarian metastases especially in patients with adenocarcinomas. We report the first case of laparoscopic management of an isolated metastasis to a transposed ovary that occurred 2 years after primary laparoscopic treatment of a stage IB1 adenocarcinoma of the cervix.     

Construct validity of four exercise stage of change measures in adults

Measuring readiness to exercise, or exercise stage of change (ESOC), is an important first step when counseling adults about exercise. However, minimal construct validity testing of ESOC measures has been reported. With a sample of 95 adults, we estimated the construct validity of four ESOC measures with commonly used response formats (true/false, ladder, 5 choice, interview). Participants completed all four ESOC measures in random order as well as six validation measures: physical activity performed, exercise self‐efficacy, decisional balance pros and cons, and behavioral and experiential processes of change. Few participants were in the earliest stage of change. The true/false measure demonstrated the strongest validity. Further studies are needed in diverse samples with more representation across the stages of change. © 2010 Wiley Periodicals, Inc. Res Nurs Health 33:254–264, 2010