Individuals deal with dying and death differently and may not experience the same journey. We investigated Kübler-Ross’ Five Stages of Grief on terminally ill patients to review the current applicability of the model among this population. The aims of this paper is to share information regarding the Five Stages of Grief, the emotions associated with the stages, and the challenges that terminally ill patients, namely those diagnosed with cancer, experience. Methods: Non-structured interviews were conducted among terminally ill patients located at the palliative ward for two years. Results: We found that terminally ill patients at the palliative ward were undergoing the Five Stages of Grief, and that the emotions associated with the stages were reported to be similar to the emotions proposed in the model and among the patients. Conclusion: Kübler-Ross’ Five Stages of Grief is still applicable among terminally ill patients. The thoughts regarding dying and death still remain negative, therefore, the change in the myths of dying and death are required to help improve the journey towards death.

INTRODUCTIONInstitutional febrile neutropenia (FN) management protocols were changed following the finding of a high prevalence of ceftazidime-resistant Gram-negative bacteraemia (CR-GNB) among haematology patients with FN. Piperacillin/tazobactam replaced ceftazidime as the initial empirical antibiotic of choice, whereas carbapenems were prescribed empirically for patients with recent extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae colonisation/infection. An audit was conducted to determine the impact of these changes.

METHODSData from all FN episodes between October 2008 and December 2010 were collected prospectively, with mid-November 2009 demarking the transition between pre-intervention and intervention periods. Outcomes measured included 30-day mortality post-development of FN and the presence of CR-GNB.

RESULTSThere were 427 FN episodes (200 in the pre-intervention period) from 225 patients. The prevalence of CRGNB was 10.3%, while the 30-day mortality was 4.7%, with no difference between pre-intervention and intervention periods. Independent risk factors for 30-day mortality included the presence of active haematological disease, vancomycin prescription and older age. Independent factors associated with initial CR-GNB were profound neutropenia, the presence of severe sepsis and active haematological disease. Recent ESBL-producing Enterobacteriaceae colonisation/infection was not predictive of subsequent CR-GNB (positive predictive value 17.3%), whereas a model based on independent risk factors had better negative predictive value (95.4%) but similarly poor positive predictive value (21.4%), despite higher sensitivity.

CONCLUSIONA change in the FN protocol did not result in improved outcomes. Nonetheless, the audit highlighted that empirical carbapenem prescription may be unnecessary in FN episodes without evidence of severe sepsis or septic shock, regardless of previous microbiology results.

Academic Medical Centers ; Adult ; Bacteremia ; complications ; drug therapy ; Carbapenems ; therapeutic use ; Ceftazidime ; pharmacology ; Drug Resistance, Multiple ; Febrile Neutropenia ; complications ; drug therapy ; Female ; Gram-Negative Bacteria ; Humans ; Male ; Middle Aged ; Penicillanic Acid ; administration & dosage ; analogs & derivatives ; Piperacillin ; administration & dosage ; Prevalence ; Prospective Studies ; Risk Factors ; Sepsis ; Singapore ; Treatment Outcome ; Universities

Alzheimer’s disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7 ,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. T o expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/ apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) has immunostimulatory effects including macrophage activation. Analysis of infiltration of inflammatory cells into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages, lymphocytes, neutrophils, and monocytes into the peritoneal cavity. Treatment of spleen cells isolated from C57BL/6 mice with GDB significantly increased the proliferation of B cells and T cells induced by LPS and ConA, respectively. Treatment with GDB significantly increased the cytolytic capacity of NK cells and macrophages against YAC-1 and B16 cells, respectively. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including iNOS, IL-1beta, and TNF-alpha in mouse macrophage cell line, RAW 264.7 cells. RT-PCR and ELISA showed that GDB increased the expression of IL-1beta, and TNF-alpha, whereas iNOS was not induced by GDB. Collectively, this series of experiments indicates that GDB stimulates immune system including macrophage activation.
Animals ; B-Lymphocytes ; Cell Line ; Dioscorea ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins ; Immune System ; Killer Cells, Natural ; Lymphocytes ; Macrophage Activation ; Macrophages ; Mice ; Monocytes ; Neutrophils ; Peritoneal Cavity ; Spleen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha

BACKGROUND: Urinary trypsin inhibitor (UTI), which is speculated to have anti-inflammatory effects, is one of serine protease inhibitors found in human urine and blood. The present study was conducted to clarify the effect of urinary trypsin inhibitor (UTI) on human neutrophil activation and its intracellular signaling mechanism in vitro. METHODS: To assess the possible interactions between UTI and lipopolysaccharide (LPS) in neutrophil activation, neutrophils from human blood were incubated with varying concentrations of UTI (1, 10, 100, 1,000 and 10,000 U/ml) plus LPS (100 ng/ml) or LPS alone in 24-well plates (5 x 106 cells/well). We measured protein levels for interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) using enzyme-linked immunosorbent assay (ELISA) kits after 4 hours of incubation period. To elucidate the intracellular signaling pathway, we also measured the levels of phosphorylation of p38, ERK1/2 and JNK via Western blot analysis. Moreover, the nuclear levels of nuclear factor-kappa B (NF-kappaB) were determined with electrophoretic mobility shift assays (EMSA). RESULTS: UTI decreased the expression of inflammatory cytokines, including TNF-alpha and IL-6, and activation of intracellular signaling pathways, such as JNK, but not P38, ERK1/2 and nuclear translocation of NF-kappaB. CONCLUSIONS: UTI can attenuate LPS-induced neutrophil responses and may partially contribute to the treatment of neutrophil-mediated inflammatory diseases.
Blotting, Western ; Cytokines ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins ; Humans ; Interleukin-6 ; Interleukins ; Mitogen-Activated Protein Kinases ; Neutrophil Activation ; Neutrophils ; Phosphorylation ; Serine Proteinase Inhibitors ; Trypsin ; Tumor Necrosis Factor-alpha

PURPOSE: Techniques designed to identify differentially expressed genes (DEGs) in tumors have become important in modern pathology. Genefishing technique(TM) using the annealing control primer (ACP) system has recently been developed to screen for DEG transcripts. We tried to identify DEGs involved in papillary thyroid cancer (PTC) by using Genefishing technique(TM). MATERIALS AND METHODS: We utilized a new differential display method, designated with Genefishing technique(TM), to analyze DEGs in 21 cases of PTCs. RESULTS: Comparing the gene expression profiles between PTC and normal thyroid, we detected 17 genes that were differentially expressed in PTCs and performed cloning with sequencing in 10 genes. We confirmed the expression patterns of 2 DEGs by RT-PCR assay and identified the same results in 17 out of 21 (81%) PTCs. The 2 DEGs over-expressed in PTCs were identified as DC-STAMP and type I collagen A1. They are novel genes identified first in PTCs. CONCLUSION: We confirmed 2 DEGs in PTCs as DC-STAMP and type I collagen A1 by using Genefishing technique(TM). Although the detailed functions of those 2 genes and their products remain to be determined, the genes will provide insights into mechanisms of carcinogenesis or tumor progression in PTCs.
Adolescent ; Adult ; Aged ; Carcinoma, Papillary/*genetics ; Collagen Type I/*genetics ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Membrane Proteins/*genetics ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Thyroid Neoplasms/*genetics ; Young Adult

Background and Objectives: Pathophysiological changes of right ventricle (RV) after repair of tetralogy of Fallot (TOF) are coupled with a highly compliant low-pressure pulmonary artery (PA) system. This study aimed to determine whether pulmonary vascular function was associated with RV parameters and exercise capacity, and its impact on RV remodeling after pulmonary valve replacement. Methods: In a total of 48 patients over 18 years of age with repaired TOF, pulmonary arterial elastance (Ea), RV volume data, and RV-PA coupling ratio were calculated and analyzed in relation to exercise capacity. Results: Patients with a low Ea showed a more severe pulmonary regurgitation volume index, greater RV end-diastolic volume index, and greater effective RV stroke volume (p=0.039, p=0.013, and p=0.011, respectively). Patients with a high Ea had lower exercise capacity than those with a low Ea (peak oxygen consumption [peak VO2 ] rate: 25.8±7.7 vs. 34.3±5.5 mL/kg/min, respectively, p=0.003), while peak VO2 was inversely correlated with Ea and mean PA pressure (p=0.004 and p=0.004, respectively). In the univariate analysis, a higher preoperative RV end-diastolic volume index and RV end-systolic volume index, left ventricular end-systolic volume index, and higher RV-PA coupling ratio were risk factors for suboptimal outcomes. Preoperative RV volume and RV-PA coupling ratio reflecting the adaptive PA system response are important factors in optimal postoperative results. Conclusions We found that PA vascular dysfunction, presenting as elevated Ea in TOF, may contribute to exercise intolerance. However, Ea was inversely correlated with pulmonary regurgitation (PR) severity, which may prevent PR, RV dilatation, and left ventricular dilatation in the absence of significant pulmonary stenosis.

INTRODUCTIONFebrile neutropenia (FN) remains a major cause of morbidity and mortality in Oncology/Haematology units. We launched a new protocol for FN management that incorporates risk stratification at our institute from October 2008. An audit was performed concurrently to evaluate the protocol and to define the epidemiology of FN locally.

MATERIALS AND METHODSCase records of all inpatients with FN between October 2008 and June 2009 were reviewed prospectively. Clinical and microbiological characteristics were collated along with outcomes and programme adherence. Statistical testing was performed using Stata 10.1.

RESULTSThere were 178 FN episodes (50 in patients with solid cancers) from 131 patients. Forty-two (23.6%) episodes were classified as high-risk according to MASCC criteria. Initial blood cultures were positive in 49 (27.5%) episodes, of which gram-negative bacilli (GNB) predominated. Overall compliance to the protocol was 56.7%, with the main issue being disinclination to use oral antibiotics as fi rst-line empirical therapy for low-risk episodes. Overall mortality was 7.3% and infection-related mortality was 4.5%. High-risk FN and the presence of central venous catheters were independently associated with bacteraemia on multivariate analysis, but there were no independent predictors of infection-related mortality.

CONCLUSIONSGNB accounted for the majority of bloodstream infections at our institute, unlike data from developed countries. Uptake of the new FN protocol was satisfactory, although the use of oral antibiotics as fi rst-line empirical therapy can be improved. A better method for predicting infections caused by antibiotic-resistant GNB is urgently required, and antibiotic resistance trends should be monitored to enable the implementation of more appropriate antibiotic regimens over time.

Adult ; Aged ; Aged, 80 and over ; Drug Resistance, Microbial ; Female ; Fever ; drug therapy ; physiopathology ; Gram-Negative Bacteria ; Hospitals, University ; Humans ; Male ; Medical Audit ; Middle Aged ; Neutropenia ; drug therapy ; physiopathology ; Outcome Assessment (Health Care) ; Prospective Studies ; Severity of Illness Index ; Singapore ; Young Adult

OBJECTIVETo investigate the influence of the consistency of resin composite and insertion techniques on the homogeneity of the Class I restorations.

METHODSStandardized Class I cavities were prepared in polymethyl methyacrylate (PMMA) blocks and restored with three resin composites (Prodigy, Tetric EvoCeram and Tetric Ceram HB) using either a packing or an injection technique by six operators. Then the restorations were sectioned longitudinally and inspected for the presence of porosities and voids with microscope. The consistence of the three resins was tested using an area method.

RESULTSThere is little porosity in original resin. After insertion, large numbers of porosities were observed in restorations, with Tetric EvoCeram presented much more porosities (1137.1 +/- 365.0 for packing and 566.1 +/- 206.4 for injection) than Prodigy (241.0 +/- 116.1, 195.8 +/- 28.7) and Tetric Ceram HB (193.1 +/- 35.8, 156.3 +/- 33.0). Tetric Ceram HB showed the highest consistency, followed by Tetric EvoCeram and Prodigy. No linear correlation was found between the consistency of the composite and the porosity of their restorations. For Tetric EvoCeram, the restorations inserted with packing showed significant more porosity than that with injection. Contrastively, the restorations of Prodigy or Tetric Ceram HB presented no apparent difference for the two filling techniques.

CONCLUSIONSThe porosity in restoration was primarily created during the insertion. There was no linear correlation between the consistency of the composite and the porosity of their restorations. The porosity of composite resin is material-brand dependent. The influence of filling techniques on the porosity of restoration is depending on the composite used.

Composite Resins ; Dental Cavity Preparation ; methods ; Dental Restoration, Permanent ; methods ; Porosity

BACKGROUND: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). METHODS: The anti-inflammatory effects of IFE against nitric oxide (NO), PGE2, TNF-alpha, and IL-6 release, as well as NF-kappa B and MAP kinase activation were evaluated in RAW 264.7 cells. RESULTS: IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-alpha and IL-6. Furthermore, IFE inhibited the NF-kappa B activation induced by LPS, which was associated with the abrogation of I kappa B-alpha degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. CONCLUSION: These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-kappa B activation via suppression of I kappa B alpha and MAP kinase phosphorylation in macrophages.
Cytokines ; Dinoprostone ; Down-Regulation ; Flowers ; I-kappa B Proteins ; Interleukin-6 ; Inula ; Macrophages ; Medicine, Traditional ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Tumor Necrosis Factor-alpha