Spiritual Care Guide in Hospice∙Palliative Care.

The Spiritual Care Guide in Hospice∙Palliative Care is evidence-based and focuses on the universal and integral aspects of human spirituality-such as meaning and purpose, interconnectedness, and transcendence-which go beyond any specific religion. This guide was crafted to improve the spiritual well-being of adult patients aged 19 and older, as well as their families, who are receiving end-of-life care. The provision of spiritual care in hospice and palliative settings aims to assist patients and their families in finding life's meaning and purpose, restoring love and relationships, and helping them come to terms with death while maintaining hope. It is recommended that spiritual needs and the interventions provided are periodically reassessed and evaluated, with the findings recorded. Additionally, hospice and palliative care teams are encouraged to pursue ongoing education and training in spiritual care. Although challenges exist in universally applying this guide across all hospice and palliative care organizations in Korea-due to varying resources and the specific environments of medical institutions-it is significant that the Korean Society for Hospice and Palliative Care has introduced a spiritual care guide poised to enhance the spiritual well-being and quality of care for hospice and palliative care patients.

Effects of a Meaning-Centered Spiritual Care Training Program for Hospice Palliative Care Teams in South Korea: A Nonrandomized Controlled Trial.

BACKGROUND: Spiritual care is an essential part and a core component of quality palliative care, as identified by the World Health Organization. However, spiritual care training for hospice palliative care teams (HPCTs) is infrequent. OBJECTIVE: The aim of this study was to investigate the effects of a meaning-centered spiritual care training program for HPCTs (McSCTP-HPCT). METHODS: This study used a nonrandomized controlled design. The McSCTP-HPCT comprised 5 modules. The participants were HPCTs working in 15 national hospice institutions and were allocated to either the experimental group (n = 33) or the control group (n = 27) based on the participating institutions' preference. Three outcome variables were tested: spiritual care competency, spiritual care therapeutics, and compassion fatigue. Data were analyzed using descriptive statistics, χ 2 test, 1-way analysis of variance, and repeated-measures analysis of variance. RESULTS: There was a significant difference in the interaction between measurement time and group assignment in spiritual care competency ( P = .002) and spiritual care therapeutics ( P = .038), whereas no significant difference was found for compassion fatigue ( P = .716). CONCLUSION: The McSCTP-HPCT conducted in this study shows effectiveness in increasing the spiritual care competency and spiritual care therapeutics of HPCTs and may support the importance of spiritual care training. IMPLICATIONS FOR PRACTICE: The McSCTP-HPCTs adds to the scientific evidence on spiritual care and has the capacity to improve the quality of care for patients with a life-threatening illness.

A meaning-centered spiritual care training program for hospice palliative care teams in South Korea: development and preliminary evaluation.

BACKGROUND: Spirituality is a fundamental, intrinsic aspect of human beings and should be a core component of quality palliative care. There is an urgent need to train hospice palliative care teams (HPCTs) to enhance their ability to provide spiritual care. This study aimed to develop and evaluate a meaning-centered, spiritual care training program (McSCTP) for HPCTs (McSCTP-HPCTs). METHODS: The modules' content was informed by Viktor Frankl's meaning-centered logotherapy with its emphasis on spiritual resources, as well as the spiritual care model of the Interprofessional Spiritual Care Education Curriculum (ISPEC). Following development, we conducted a pilot test with four nurses. We used the results to inform the final program, which we tested in an intervention involving 13 members of HPCTs. We took measurements using self-administered questionnaires at three points before and after the intervention. Using descriptive statistics, the Mann-Whitney U test, and the Kruskal-Wallis test, we analyzed the participants' demographic and career-related characteristics, as well as the degree of variance between three outcome variables: compassion fatigue (CF), spiritual care competencies (SCCs), and spiritual care therapeutics (SCT). RESULTS: We divided the McSCTP-HPCTs into five modules. Module I: The HPCTs' SCC evaluation, understanding the major concepts of spiritual care and logotherapy; Modules II-IV: Meaning-centered interventions (MCIs) related to spiritual needs (existential, relational, and transcendental/religious); Module V: The process of meaning-centered spiritual care. The preliminary evaluation revealed significant differences in all three outcome variables at the posttest point (CF, p = 0.037; SCCs, p = 0.005; SCT, p = 0.002). At the four-week follow-up test point, we only found statistical significance with the SCCs (p = 0.006). CONCLUSIONS: The McSCTP-HPCTs is suitable for use in clinical settings and provides evidence for assessing the SCCs of HPCTs.

The bacterial endoribonuclease RNase E can cleave RNA in the absence of the RNA chaperone Hfq.

RNase E is a component of the RNA degradosome complex and plays a key role in RNA degradation and maturation in Escherichia coli RNase E-mediated target RNA degradation typically involves the RNA chaperone Hfq and requires small guide RNAs (sRNAs) acting as a seed by binding to short (7-12-bp) complementary regions in target RNA sequences. Here, using recombinantly expressed and purified proteins, site-directed mutagenesis, and RNA cleavage and protein cross-linking assays, we investigated Hfq-independent RNA decay by RNase E. Exploring its RNA substrate preferences in the absence of Hfq, we observed that RNase E preferentially cleaves AU-rich sites of single-stranded regions of RNA substrates that are annealed to an sRNA that contains a monophosphate at its 5'-end. We further found that the quaternary structure of RNase E is also important for complete, Hfq-independent cleavage at sites both proximal and distal to the sRNA-binding site within target RNAs containing monophosphorylated 5'-ends. Of note, genetic RNase E variants with unstable quaternary structure exhibited decreased catalytic activity. In summary, our results show that RNase E can degrade its target RNAs in the absence of the RNA chaperone Hfq. We conclude that RNase E-mediated, Hfq-independent RNA decay in E. coli requires a cognate sRNA sequence for annealing to the target RNA, a 5'-monophosphate at the RNA 5'-end, and a stable RNase E quaternary structure.

Autophagy and KRT8/keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress.

Contribution of autophagy and regulation of related proteins to the degeneration of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD) remain unknown. We report that upregulation of KRT8 (keratin 8) as well as its phosphorylation are accompanied with autophagy and attenuated with the inhibition of autophagy in RPE cells under oxidative stress. KRT8 appears to have a dual role in RPE pathophysiology. While increased expression of KRT8 following autophagy provides a cytoprotective role in RPE, phosphorylation of KRT8 induces pathologic epithelial-mesenchymal transition (EMT) of RPE cells under oxidative stress, which is mediated by MAPK1/ERK2 (mitogen-activated protein kinase 1) and MAPK3/ERK1. Inhibition of autophagy further promotes EMT, which can be reversed by inhibition of MAPK. Thus, regulated enhancement of autophagy with concurrent increased expression of KRT8 and the inhibition of KRT8 phosphorylation serve to inhibit oxidative stress-induced EMT of RPE cells as well as to prevent cell death, suggesting that pharmacological manipulation of KRT8 upregulation through autophagy with combined inhibition of the MAPK1/3 pathway may be attractive therapeutic strategies for the treatment of AMD.

Dependence of RIG-I Nucleic Acid-Binding and ATP Hydrolysis on Activation of Type I Interferon Response.

Exogenous nucleic acids induce an innate immune response in mammalian host cells through activation of the retinoic acid-inducible gene I (RIG-I). We evaluated RIG-I protein for RNA binding and ATPase stimulation with RNA ligands to investigate the correlation with the extent of immune response through RIG-I activation in cells. RIG-I protein favored blunt-ended, double-stranded RNA (dsRNA) ligands over sticky-ended dsRNA. Moreover, the presence of the 5'-triphosphate (5'-ppp) moiety in dsRNA further enhanced binding affinity to RIG-I. Two structural motifs in RNA, blunt ends in dsRNA and 5'-ppp, stimulated the ATP hydrolysis activity of RIG-I. These structural motifs also strongly induced IFN expression as an innate immune response in cells. Therefore, we suggest that IFN induction through RIG-I activation is mainly determined by structural motifs in dsRNA that increase its affinity for RIG-I protein and stimulate ATPase activity in RIG-I.

Dual effects of duplex RNA harboring 5'-terminal triphosphate on gene silencing and RIG-I mediated innate immune response.

Duplex RNA harboring the 5'-terminal triphosphate RNA is hypothesized to not only execute selective gene silencing via RNA interference, but also induce type I interferon (IFN) through activation of the retinoic acid inducible gene I (RIG-I). We evaluated gene silencing efficacy of the shRNA containing 5'-triphosphate (3p-shRNA) targeting the hepatitis C virus (HCV) RNA genome in hepatic cells. Gene silencing efficacy of the 3p-shRNA was diminished due to the presence of the 5'-triphosphate moiety in shRNA, whereas the shRNA counterpart without 5'-triphosphate (HO-shRNA) showed a strong antiviral activity without significant induction of type I IFN in the cells. 3p-shRNA was observed to be a better activator of the RIG-I signaling than the HO-shRNA with an elevated induction of type I IFN in cells that express RIG-I. Taken together, we suggest that competition for the duplex RNA bearing 5'-triphosphate between RIG-I and RNA interference factors may compromise efficacy of selective gene silencing.

Ilimaquinone and ethylsmenoquinone, marine sponge metabolites, suppress the proliferation of multiple myeloma cells by down-regulating the level of ß-catenin.

Deregulation of Wnt/ß-catenin signaling promotes the development of a broad range of human cancers, including multiple myeloma, and is thus a potential target for the development of therapeutics for this disease. Here, we used a cell-based reporter system to demonstrate that ilimaquinone and ethylsmenoquinone (formerly smenorthoquinone), sesquiterpene-quinones from a marine sponge, inhibited ß-catenin response transcription induced with Wnt3a-conditioned medium, by down-regulating the level of intracellular ß-catenin. Pharmacological inhibition of glycogen synthase kinase-3ß did not abolish the ilimaquinone and ethylsmenoquinone-mediated ß-catenin down-regulation. Degradation of ß-catenin was consistently found in RPMI-8226 multiple myeloma cells after ilimaquinone and ethylsmenoquinone treatment. Ilimaquinone and ethylsmenoquinone repressed the expression of cyclin D1, c-myc, and axin-2, which are ß-catenin/T-cell factor-dependent genes, and inhibited the proliferation of multiple myeloma cells. In addition, ilimaquinone and ethylsmenoquinone significantly induced G0/G1 cell cycle arrest and apoptosis in RPMI-8266 cells. These findings suggest that ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by blocking the Wnt/ß-catenin pathway and have significant potential as therapies for multiple myeloma.

Detection and quantification of the Bcr/Abl chimeric protein on biochips using LDI-TOF MS.

The Bcr/Abl chimeric protein was captured by two antibodies, anti-Bcr on gold nanoparticles (AuNPs) and anti-Abl on a biochip, in a sandwich assay format. The presence of the Bcr/Abl in cells was then verified by amplified LDI-TOF MS signals, and relative amounts were quantified using AuNPs coated with deuterated alkanethiols as an internal standard.

Exosomal proteins in the aqueous humor as novel biomarkers in patients with neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) describes the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris and is the leading cause of blindness in people over 50. The molecular mechanisms underlying this multifactorial disease remain largely unknown. To uncover novel secretory biomarkers related to the pathogenesis of AMD, we adopted an integrated approach to compare the proteins identified in the conditioned medium (CM) of cultured RPE cells and the exosomes derived from CM and from the aqueous humor (AH) of AMD patients by LC-ESI-MS/MS. Finally, LC-MRM was performed on the AH from patients and controls, which revealed that cathepsin D, cytokeratin 8, and four other proteins increased in the AH of AMD patients. The present study has identified potential biomarkers and therapeutic targets for AMD treatment, such as proteins related to the autophagy-lysosomal pathway and epithelial-mesenchymal transition, and demonstrated a novel and effective approach to identifying AMD-associated proteins that might be secreted by RPE in vivo in the form of exosomes. The proteomics-based characterization of this multifactorial disease could help to match a particular marker to particular target-based therapy in AMD patients with various phenotypes.

Characterization of bacteriophage φPto-bp6g, a novel phage that lyses Pseudomonas tolaasii causing brown blotch disease in mushrooms.

The bacteriophage, φPto-bp6g, exhibited strong bactericidal activity against Pseudomonas tolaasii, the bacterium that causes brown blotch disease in cultivated mushrooms. Analysis of phage morphology with an electron microscope revealed that φPto-bp6g contains an icosahedral head and a long tail, which is classified as the family of Siphoviridae. The phage was observed to lyse P. tolaasii in the broth about 4h after inoculation, indicating a putative lytic pathway exists during bacterial growth. The whole genome of φPto-bp6g was completely sequenced, with a length of 26,499 bp and a G+C content of 42.7%. A total of 77 open reading frames (ORFs) as putative coding sequences were identified and annotated, whereas 43 ORFs possessed no homologs. Proteins of several ORFs showed similarity with proteins of a diverse group of phages, including Siphoviridae (5 ORFs), Myoviridae (11 ORFs), and Podoviridae (4 ORFs). Phage proteins were grouped into three categories based on their predicted functions: (i) DNA replication and nucleotide metabolism, (ii) phage particle formation, and (iii) host interaction. Since there is no identified gene encoding integrase and toxins in phage genome, phage φPto-bp6g could be potentially applicable as a safe biological control reagent against brown blotch disease in mushroom cultivation.

Site-specific cleavage of mutant ABL mRNA by DNAzyme is facilitated by peptide nucleic acid binding to RNA substrate.

RNA-cleaving DNAzymes were constructed to target the point mutation in the BCR-ABL transcript that causes imatinib resistance in leukemic cells. We examined the effect of 12mer peptide nucleic acids (PNAs) as facilitator oligonucleotides that bind to RNA substrate at the termini of the DNAzyme to improve DNAzyme-mediated cleavage of full-length RNA. When imatinib-resistant cells were transfected with the facilitator PNA and DNAzyme, DNAzyme activity was enhanced and the cells were sensitized to imatinib treatment. Thus, facilitator PNA may be used to enhance activity of antisense oligonucleotide targeting the full-length transcript.

Activation of mitogen activated protein kinase-Erk kinase (MEK) increases T cell immunoglobulin mucin domain-3 (TIM-3) transcription in human T lymphocytes and a human mast cell line.

The immune regulatory molecule T cell immunoglobulin mucin domain (TIM-3) is expressed in activated T cells and in mast cells treated with transforming growth factor (TGF)-ß, but underlying mechanisms for induction of TIM-3 transcription have not been well-explored. We studied the role of mitogen-activated protein kinase (MAPK) in TIM-3 transcription on the basis of the involvement of MAPK in T cell activation and TGF-ß signaling. Inhibitors of MAPK-Erk kinase (MEK) as well as p38 suppressed TIM-3 transcription in phorbol myristic acid (PMA)-stimulated T cells, but inhibitors of c-Jun NH2-terminal kinase (JNK) did not. MEK over-expression enhanced TIM-3 transcription in PMA-stimulated T cells. Furthermore, -1.5kb TIM-3 promoter was activated by PMA stimulation and repressed by MEK inhibitors in Jurkat T cells. Similarly, MEK activation enhanced TIM-3 transcription in TGF-ß-stimulated HMC-1 human mast cells, although MEK seemed not directly activated by TGF-ß. Concordantly, -1.5kb TIM-3 promoter activity was reduced by MEK inhibitors, but was not responsive to TGF-ß stimulation in HMC-1 cells. These results suggest the regulatory role of MEK in TIM-3 transcription by human CD4+ T cells and mast cells.

[Socioeconomic inequity in self-rated health status and contribution of health behavioral factors in Korea].

OBJECTIVES: The study is investigated socioeconomic variations in self-rated health status and contribution of health behavioral factors in Korea. METHODS: A nationally representative sample (2,800 men and 3,230 women aged 20-64 years) from the 2005 Korea National Health and Nutrition Surveys was analyzed using logistic regression. RESULTS: Self-rated health was lower among lower socioeconomic groups compared with higher socioeconomic groups, with gender being irrelevant. This association was attenuated when health behavioral and socio-demographic factors were adjusted. When each health behavioral factor was considered separately, mediators such as smoking in men, and stress or exercise in women explained a large part of the decreased socioeconomic health inequalities. CONCLUSIONS: In Korea, subjective health inequalities arise from different socioeconomic status, but this difference is decreased by health behavioral factors. Therefore, socioeconomic inequity in self-rated health status can be corrected more effectively by promotional health behaviors.

Hemodialysis using heparin-bound Hemophan in patients at risk of bleeding.

BACKGROUND/AIMS: Since heparin can bind to Hemophan, hemodialysis using heparin-bound Hemophan (HBH-HD) could be a useful modality in patients at risk of bleeding. We designed a simplified heparin binding technique and assessed the safety and efficiency of HBH-HD. METHODS: To bind heparin to Hemophan, heparin solution (1 liter, 20 IU/ml saline) was recirculated through Hemophan (GFS plus 11, Gambro) for 1 h while the saline solution (700 ml/h) was removed. In 28 maintenance dialysis patients at risk of bleeding, we evaluated the heparin concentration (HC) and activated partial thromboplastin time (aPTT) during HBH-HD to assess the increased risk of bleeding. We compared the safety and efficiency of HBH-HD with that of routine hemodialysis with low-dose heparinization (R-HD) in a prospective cross-over study, and then analyzed the outcomes of 1,057 HBH-HD in 159 patients. RESULTS: During HBH-HD, there was a slight increase in both HC (0.15 +/- 0.03 IU/ml, p < 0.01) and aPTT (43.7 +/- 5.7 s, p < 0.01) at 15 min after the initiation of dialysis compared to predialysis levels (0.11 +/- 0.03 IU/ml and 37.5 +/- 6.3 s). However, there was no increase in HC and aPTT at 60 min, 120 min and at the end of dialysis. In a cross-over study, aPTT during dialysis was markedly lower in HBH-HD than in R-HD (p < 0.01). The Kt/V (1.22 +/- 0.31, p > 0.05) and urea clearance (136 +/- 17 ml/min, p > 0.05) of HBH-HD did not significantly differ from those of R-HD (1.29 +/- 0.57 and 136 +/- 13 ml/min). However, the loss of total blood compartment volume of the dialyzer was greater in HBH-HD (17.5 +/- 9.2%, p < 0.01) than in R-HD (2.9 +/- 1.2%). Out of 1,057 HBH-HD, 982 HBH-HD (93%) were successfully completed while 75 HBH-HD (7%) resulted in severe clotting. CONCLUSION: We conclude that the HBH-HD could minimize the bleeding risk and be an efficient HD technique in patients at high risk of bleeding. Careful observation for extracorporeal clotting is, however, required during HBH-HD.