Clinical Outcomes of Operating an Acute Palliative Care Unit at a Comprehensive Cancer Center.

PURPOSE: Acute palliative care units (APCUs) are inpatient services in tertiary hospitals that provide intensive symptom management and assist in hospital discharge for transitions to hospice care. We aimed to analyze the clinical outcomes of operating an APCU at a comprehensive cancer center. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1,440 consecutive patients admitted to the APCU and analyzed demographic and clinical information, discharge outcomes, symptom assessments using the Edmonton Symptom Assessment System, spiritual distress, and financial distress. RESULTS: The median age of patients was 67.0 (range, 23-97) years, and 41% were female. The most common primary cancer types were lung (21.9%), hepatopancreatobiliary (14.1%), and colorectal cancers (12.9%). The median length of stay was 8.0 days (range, 1-60 days), and 31.0% of patients died in the APCU. Death in the APCU showed a significant decrease over time, and overall inpatient death in oncology wards did not increase after APCU opening. In total, 44.7% of patients were discharged to government-certified hospice centers. The proportion of patients discharged to certified hospice centers increased from 32.2% in 2015 to 62.4% in 2018. Among 715 patients with a follow-up evaluation 1 week after admission, Edmonton Symptom Assessment System symptom scores, spiritual distress, and financial distress showed statistically significant improvements compared with the baseline symptom scores (P < .001). This improvement was limited to patients who did not die in the APCU. CONCLUSION: Patients with advanced cancer admitted to the APCU may experience significant improvements in distressing symptoms. The majority of patients requiring transition to hospice were successfully transferred to certified hospice centers. The percentage discharged alive improved over time.

Direct Patterned Zinc-Tin-Oxide for Solution-Processed Thin-Film Transistors and Complementary Inverter through Electrohydrodynamic Jet Printing.

The solution-processed deposition of metal-oxide semiconducting materials enables the fabrication of large-area and low-cost electronic devices by using printing technologies. Additionally, the simple patterning process of these types of materials become an important issue, as it can simplify the cost and process of fabricating electronics such as thin-film transistors (TFTs). In this study, using the electrohydrodynamic (EHD) jet printing technique, we fabricated directly patterned zinc-tin-oxide (ZTO) semiconductors as the active layers of TFTs. The straight lines of ZTO semiconductors were successfully drawn using a highly soluble and homogeneous solution that comprises zinc acrylate and tin-chloride precursors. Besides, we found the optimum condition for the fabrication of ZTO oxide layers by analyzing the thermal effect in processing. Using the optimized condition, the resulting devices exhibited satisfactory TFT characteristics with conventional electrodes and conducting materials. Furthermore, these metal-oxide TFTs were successfully applied to complementary inverter with conventional p-type organic semiconductor-based TFT, showing high quality of voltage transfer characteristics. Thus, these printed ZTO TFT results demonstrated that solution processable metal-oxide transistors are promising for the realization of a more sustainable and printable next-generation industrial technology.

Comparison of the Protective Effects of Bee Venom Extracts with Varying PLA2 Compositions in a Mouse Model of Parkinson's Disease.

Bee venom contains a number of pharmacologically active components, including enzymes and polypeptides such as phospholipase A2 (PLA2) and melittin, which have been shown to exhibit therapeutic benefits, mainly via attenuation of inflammation, neurotoxicity, and nociception. The individual components of bee venom may manifest distinct biological actions and therapeutic potential. In this study, the potential mechanisms of action of PLA2 and melittin, among different compounds purified from honey bee venom, were evaluated against Parkinson's disease (PD). Notably, bee venom PLA2 (bvPLA2), but not melittin, exhibited neuroprotective activity against PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP-induced behavioral deficits were also abolished after bvPLA2 treatment, depending on the PLA2 content. Further, bvPLA2 administration activated regulatory T cells (Tregs) while inhibiting inflammatory T helper (Th) 1 and Th17 cells in the MPTP mouse model of PD. These results indicate that bvPLA2, but not melittin, protected against MPTP and alleviated inflammation in PD. Thus, bvPLA2 is a promising and effective therapeutic agent in Parkinson's disease.

Anomalous Ambipolar Transport of Organic Semiconducting Crystals via Control of Molecular Packing Structures.

Organic crystals deposited on 2-dimensional (2D) van der Waals substrates have been widely investigated due to their unprecedented crystal structures and electrical properties. van der Waals interaction between organic molecules and the substrate induces epitaxial growth of high quality organic crystals and their anomalous crystal morphologies. Here, we report on unique ambipolar charge transport of a "lying-down" pentacene crystal grown on a 2D hexagonal boron nitride van der Waals substrate. From in-depth analysis on crystal growth behavior and ultraviolet photoemission spectroscopy measurement, it is revealed that the pentacene crystal at the initial growth stage have a lattice-strained packing structure and unique energy band structure with a deep highest occupied molecular orbital level compared to conventional "standing-up" crystals. The lattice-strained pentacene few layers enable ambipolar charge transport in field-effect transistors with balanced hole and electron field-effect mobilities. Complementary logic circuits composed of the two identical transistors show clear inverting functionality with a high gain up to 15. The interesting crystal morphology of organic crystals on van der Waals substrates is expected to attract broad attentions on organic/2D interfaces for their electronic applications.

Photo-Patternable ZnO Thin Films Based on Cross-Linked Zinc Acrylate for Organic/Inorganic Hybrid Complementary Inverters.

Complementary inverters consisting of p-type organic and n-type metal oxide semiconductors have received considerable attention as key elements for realizing low-cost and large-area future electronics. Solution-processed ZnO thin-film transistors (TFTs) have great potential for use in hybrid complementary inverters as n-type load transistors because of the low cost of their fabrication process and natural abundance of active materials. The integration of a single ZnO TFT into an inverter requires the development of a simple patterning method as an alternative to conventional time-consuming and complicated photolithography techniques. In this study, we used a photocurable polymer precursor, zinc acrylate (or zinc diacrylate, ZDA), to conveniently fabricate photopatternable ZnO thin films for use as the active layers of n-type ZnO TFTs. UV-irradiated ZDA thin films became insoluble in developing solvent as the acrylate moiety photo-cross-linked; therefore, we were able to successfully photopattern solution-processed ZDA thin films using UV light. We studied the effects of addition of a tiny amount of indium dopant on the transistor characteristics of the photopatterned ZnO thin films and demonstrated low-voltage operation of the ZnO TFTs within ±3 V by utilizing Al2O3/TiO2 laminate thin films or ion-gels as gate dielectrics. By combining the ZnO TFTs with p-type pentacene TFTs, we successfully fabricated organic/inorganic hybrid complementary inverters using solution-processed and photopatterned ZnO TFTs.

A neurostimulant para-chloroamphetamine inhibits the arginylation branch of the N-end rule pathway.

In the arginylation branch of the N-end rule pathway, unacetylated N-terminal destabilizing residues function as essential determinants of protein degradation signals (N-degron). Here, we show that a neurostimulant, para-chloroamphetamine (PCA), specifically inhibits the Arg/N-end rule pathway, delaying the degradation of its artificial and physiological substrates, including regulators of G protein signaling 4 (RGS4), in vitro and in cultured cells. In silico computational analysis indicated that PCA strongly interacts with both UBR box and ClpS box, which bind to type 1 and type 2 N-degrons, respectively. Moreover, intraperitoneal injection of PCA significantly stabilized endogenous RGS4 proteins in the whole mouse brain and, particularly, in the frontal cortex and hippocampus. Consistent with the role of RGS4 in G protein signaling, treatment with PCA impaired the activations of GPCR downstream effectors in N2A cells, phenocopying ATE1-null mutants. In addition, levels of pathological C-terminal fragments of TDP43 bearing N-degrons (Arg208-TDP25) were significantly elevated in the presence of PCA. Thus, our study identifies PCA as a potential tool to understand and modulate various pathological processes regulated by the Arg/N-end rule pathway, including neurodegenerative processes in FTLD-U and ALS.

Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex.

The enzymatic activity of histone deacetylases (HDACs) leads to a histone deacetylation-mediated condensed chromatic structure, resulting in transcriptional repression, which has been implicated in the modifications of neural circuits and behaviors. Repeated treatment with electroconvulsive seizure (ECS) induces changes in histone acetylation, expression of various genes, and intrabrain cellular changes, including neurogenesis. In this study, we examined the effects of repeated ECS on the expression of class I HDACs and related changes in histone modifications and gene expression in the rat frontal cortex. Ten days of repeated ECS treatments (E10X) up-regulated HDAC2 expression at the mRNA and protein levels in the rat frontal cortex compared with sham-treated controls; this was evident in the nuclei of neuronal cells in the prefrontal, cingulate, orbital, and insular cortices. Among the known HDAC2 target genes, mRNA expression of N-methyl-d-aspartate (NMDA) receptor signaling-related genes, including early growth response-1 (Egr1), c-Fos, glutamate receptor, ionotropic, N-methyl d-aspartate 2A (Nr2a), Nr2b, neuritin1 (Nrn1), and calcium/calmodulin-dependent protein kinase II alpha (Camk2α), were decreased, and the histone acetylation of H3 and/or H4 proteins was also reduced by E10X. Chromatin immunoprecipitation analysis revealed that HDAC2 occupancy in the promoters of down-regulated genes was increased significantly. Moreover, administration of sodium butyrate, a HDAC inhibitor, during the course of E10X ameliorated the ECS-induced down-regulation of genes in the rat frontal cortex. These findings suggest that induction of HDAC2 by repeated ECS treatment could play an important role in the down-regulation of NMDA receptor signaling-related genes in the rat frontal cortex through histone modification.

Prognostic value of mucinous histology depends on microsatellite instability status in patients with stage III colon cancer treated with adjuvant FOLFOX chemotherapy: a retrospective cohort study.

BACKGROUND: The close association between mucinous histology and microsatellite instability (MSI) may have hindered the evaluation of prognostic significance of mucinous histology. The aim of this retrospective study was to investigate whether mucinous histology was associated with a worse prognosis, independent of MSI status, compared to nonmucinous histology in patients with stage III colon cancer. METHODS: This study enrolled 394 consecutive patients with stage III colorectal cancer treated with adjuvant FOLFOX after curative resection (R0). Clinicopathological information was retrospectively reviewed. Tumors were analyzed for MSI by polymerase chain reaction to determine MSI status. Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models were used. RESULTS: The estimated rate of 3-year disease-free survival (DFS) in patients with nonmucinous adenocarcinoma (NMA 79.2 %) was significantly greater than that in patients with mucinous adenocarcinoma (MA) and adenocarcinoma with mucinous component (MC) (56.9 %; log-rank, P = 0.002). In univariate analysis, histology (NMA vs. MA/MC), American Joint Committee on Cancer stage (IIIA, IIIB, and IIIC), and lymphovascular invasion (present vs. absent) were significantly associated with DFS. In multivariate analysis, mucinous histology (MA/MC) was associated with decreased DFS in all patients (hazard ratio 1.82, 95 % confidence interval 1.03-3.23, P = 0.0403). In patients with MA/MC, no difference in DFS was observed between MSI and microsatellite stability (log-rank, P = 0.732). CONCLUSIONS: Mucinous histology is an independent poor prognostic factor for DFS in patients with stage III colon cancer after adjuvant FOLFOX chemotherapy.

Intracerebroventricular administration of ouabain, a Na/K-ATPase inhibitor, activates mTOR signal pathways and protein translation in the rat frontal cortex.

Intracerebroventricular (ICV) injection of ouabain, a specific Na/K-ATPase inhibitor, induces behavioral changes in rats in a putative animal model of mania. The binding of ouabain to Na/K-ATPase affects signaling molecules in vitro, including ERK1/2 and Akt, which promote protein translation. We have also reported that ERK1/2 and Akt in the brain are involved in the ouabain-induced hyperactivity of rats. In this study, rats were given an ICV injection of ouabain, and then their frontal cortices were examined to determine the effects of ouabain on the mTOR/p70S6K/S6 signaling pathway and protein translation, which are important in modifications of neural circuits and behavior. Rats showed ouabain-induced hyperactivity up to 8h following injection, and increased phosphorylation levels of mTOR, p70S6K, S6, eIF4B, and 4E-BP at 1, 2, 4, and 8h following ouabain injection. Immunohistochemical analyses revealed that increased p-S6 immunoreactivity in the cytoplasm of neurons by ouabain was evident in the prefrontal, cingulate, and orbital cortex. These findings suggested increased translation initiation in response to ouabain. The rate of protein synthesis was measured as the amount of [(3)H]-leucine incorporation in the cell-free extracts of frontal cortical tissues, and showed a significant increase at 8h after ouabain injection. These results suggest that ICV injection of ouabain induced activation of the protein translation initiation pathway regulated by ERK1/2 and Akt, and prolonged hyperactivity in rats. In conclusion, protein translation pathway could play an important role in ouabain-induced hyperactivity in a rodent model of mania.

Development of a Korean version of the Cancer Therapy Satisfaction Questionnaire (CTSQ): cross-cultural adaptation, reliability, and validity.

PURPOSE: (1) To translate original English Cancer Therapy Satisfaction Questionnaire (CTSQ) into Korean and perform validation, (2) to compare CTSQ domains of expectations of therapy (ET), feelings about side effects (FSE), and satisfaction with therapy (SWT) by cancer therapy type. METHODS: Cross-cultural adaptation was performed according to guidelines: translation, back translation, focus-group, and field test. We performed validation with internal consistency by Cronbach's alpha and construct validity by exploratory factor analysis (EFA) with varimax rotation method. We compared each CTSQ domain between traditional Korean Medicine (TKM) and integrative cancer therapy (ICT) of combining western and TKM by two-sample t test. RESULTS: Cross-cultural adaptation produced no major modifications in the items and domains. A total of 102 outpatients were participated. Mean age was 51.9 ± 12.4. Most were stage 4 (74.4 %) cancer. Mean scores of ET, FSE, and SWT were 81.2 ± 15.7, 79.5 ± 22.9, and 75.7 ± 14.8, respectively. Cronbach's alpha of ET, FSE, and SWT were 0.86, 0.78, and 0.74, respectively. EFA loaded items on the three domains, which is very close to that of the original CTSQ. ET and SWT was similar, but FSE was significantly higher in TKM than ICT (87.5 ± 19.3 vs. 74.9 ± 23.5; p = 0.0054). CONCLUSIONS: Cross-cultural adaptation was successful, and the adapted Korean CTSQ demonstrated good internal consistency and construct validity. Similar expectation and satisfaction was shown between the two types of therapy, but patient's reported feelings about side effects was significantly lower in patients receiving TKM than receiving ICT. Korean version of CTSQ can be used to evaluate Korean cancer patient's experiences receiving various cancer therapy types.

Inpatient Course and Length of Hospital Stay in Patients with Brain Disorders in South Korea: A Population-based Registry Study.

OBJECTIVE: To describe inpatient course and length of hospital stay (LOS) for people who sustain brain disorders nationwide. METHOD: We interviewed 1,903 randomly selected community-dwelling patients registered as 'disabled by brain disorders' in 28 regions of South Korea. RESULTS: Seventy-seven percent were initially admitted to a Western medicine hospital, and 18% were admitted to a traditional Oriental medicine hospital. Forty-three percent were admitted to two or more hospitals. Mean LOS was 192 days. Most patients stayed in one hospital for more than 4 weeks. The transfer rate to other hospitals was 30-40%. Repeated admissions and increased LOS were related to younger onset age, higher education, non-family caregiver employment, smaller families, and more severe disability. CONCLUSION: Korean patients with brain disorders showed significantly prolonged LOS and repeated admissions. Factors increasing burden of care influenced LOS significantly.

Acupuncture for hot flashes in postmenopausal hemodialysis-dependent women: two case reports.

OBJECTIVE: This study aimed to observe the effects of acupuncture for hot flashes in postmenopausal hemodialysis-dependent women. METHODS: Two postmenopausal hemodialysis-dependent women were treated with individualized manual acupuncture for 1 and 3 months to reduce the occurrence of hot flashes and were observed through 7 and 11 months, respectively, from baseline. RESULTS: Hot flashes were significantly improved after acupuncture treatment in both of the patients, and the effects persisted through the final observation period (hot flash scores decreased from 57 to 33 and 22 at 1 and 11 months from baseline in patient 1, and from 14 to 6 and zero at 1 and 7 months from baseline in patient 2). The beneficial effects of acupuncture on quality of life were partially observed in these 2 patients. No acupuncture-related serious adverse events occurred during the study. CONCLUSIONS: Further controlled studies need to be conducted among larger samples to determine whether acupuncture is an effective and safe treatment for hot flashes in postmenopausal hemodialysis-dependent women.

Assessment of prescribed herbal medicine on liver function in Korea: a prospective observational study.

OBJECTIVE: The aim of this study was to investigate the influence of herbal medicine (HM) prescribed by doctors of Korean medicine (KMD) on liver function in Korea. DESIGN AND INTERVENTIONS: For this multicenter, prospective, observational study, we enrolled patients who wished to take HM prescribed by KMD for various medical purposes in Korea. One hundred and twenty-two (122) patients took HM for an average of 20.6 +/- 8.4 (mean +/- standard deviation) days, and completed questionnaires. OUTCOME MEASURES: Liver function tests (LFTs) were performed before (first test) and after each HM treatment (second test). For LFT, aspartate aminotransferase, alanine aminotransferase, total bilirubin (t-Bil), direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase were measured. RESULTS: There were no significant changes in LFT data between the first and second tests, except in the t-Bil level. However, all data of total bilirubin level in second test were within normal range, except only one patient. Multivariate analysis did not identify any herb that significantly increased t-Bil; hence no hepatotoxic herb was found. Twenty-one (21) of the 122 patients were abnormal on first testing, and 10 at the second testing. Of the patients taking herbs, 4 changed from normal to abnormal and 15 from abnormal to normal (p = 0.019). CONCLUSION: The current study showed that ingestion of HM prescribed by KMD did not increase the frequency of abnormal LFTs, at least in the short term.