Phytogalactolipid dLGG Inhibits Mouse Melanoma Brain Metastasis through Regulating Oxylipin Activity and Re-Programming Macrophage Polarity in the Tumor Microenvironment.

Current conventional cancer therapies for melanoma brain metastasis (MBM) remain ineffective. In this study, we demonstrated the bioefficacy of a phyto-glyceroglycolipid, 1,2-di-O-α-linolenoyl-3-O-ß-galactopyranosyl-sn-glycerol (dLGG) alone, or in combination with liposomal doxorubicin (Lip-DOX) or Avastin against MBM in a syngeneic B16BM4COX-2/Luc brain-seeking melanoma mouse model. Treatment with dLGG-10, dLGG-25, dLGG-10 + Avastin-5, Lipo-DOX-2, dLGG-10 + Lipo-DOX-2 or Lipo-DOX-2 + Avastin-5 suppressed, respectively, 17.9%, 59.1%, 55.7%, 16.2%, 44.5% and 72.4% of MBM in mice relative to the untreated tumor control. Metastatic PD-L1+ melanoma cells, infiltration of M2-like macrophages and CD31+ endothelial cells, and high expression levels of 15-LOX/CYP450 4A enzymes in the brain tumor microenvironment of the tumor control mice were significantly attenuated in dLGG-treated mice; conversely, M1-like resident microglia and cytotoxic T cells were increased. A lipidomics study showed that dLGG promoted B16BM4 cells to secrete oxylipins 9,10-/12,13-EpOMEs into the culture medium. Furthermore, the conditioned medium of B16BM4 cells pretreated with dLGG or 9,10-EpOMEs + 12,13-EpOMEs drove M2-like macrophages to polarize into M1-like macrophages in vitro. An ex vivo 3D-culture assay further demonstrated that dLGG, 9,10-EpOME or 9,10-EpOME + 12,13-EpOME pretreatment attenuated B16BM4 cells invading brain tissue, and prevented microglia/macrophages infiltrating into the interface of melanoma plug and brain organ/tissue. In summary, this report provides a novel therapeutic strategy and mechanistic insights into phytogalactolipid dLGG for combating MBM.

Do-not-attempt resuscitation independently predict in-hospital mortality in septic patients.

INTRODUCTION: Sepsis patients require timely and appropriate treatment in an intensive care setting. However, "do-not-attempt resuscitation" (DNAR) status may affect physicians' priorities and treatment preferences. The aim of this study was to evaluate whether DNAR status affects the outcomes of septic patients. METHODS: This was a retrospective cohort study included septic patients admitted to the emergency department intensive care unit (ED-ICU) in a university-based teaching hospital during April-November 2015. Septic patients admitted to the ED-ICU were included. RESULTS: Of the 132 eligible patients, 49.2% (65/132) had DNAR status (median age 80 years old, IQR, 73-86). The overall in-hospital mortality rate was 28.8% (38/132). Non-survivors had a higher percentage of receiving inotropes/vasopressors (52.6% vs 34.0%, p = 0.048), higher median Charlson comorbidity index scores [8.5 (IQR, 7-11.75) vs 8 (IQR, 6-9), p = 0.012], higher APACHE II score [25 (IQR, 20-30.25) vs 20 (IQR, 17-25), p = 0.002], and higher SOFA score [7 (IQR, 6-11) vs 6 (IQR,4-8), p = 0.012]. There was no significant difference in intubation among the two groups. In a multivariate logistic regression analysis, DNAR status was an independent predictor of in-hospital mortality (odds ratio = 6.22, 95% confidence interval (CI) = (2.71-17.88), p < 0.001). The area under the ROC curve for the logistic regression model was 0.84 [95% CI = (0.77-0.92), p < 0.001]. In subgroup analysis, DNAR status remained an independent predictor of mortality among age ≥65 years and ≥80 years. CONCLUSION: After adjusting for comorbidities, treatments, and illness severity, DNAR status was associated with in-hospital mortality of septic patients. Further studies should evaluate physicians' attitudes toward septic patients with DNAR status.

Characteristics and outcomes of "Do Not Resuscitate" patients admitted to the emergency department-Intensive care unit.

BACKGROUND: Appropriate utilization of intensive care unit (ICU) beds are essential. Patients with critical illness who have do not resuscitate (DNR) have a reduced priority of intensive care. However, the possibility of recovery/survival is ambiguous and multifactorial. OBJECTIVE: To deliberate the characteristics and outcomes of critical illness in patients with prior DNR who were admitted to the emergency department (ED)-ICU. METHOD: This was a retrospective cohort study conducted between April 2015 and November 2015 in a university-based hospital. Non-traumatic patients with DNR admitted to ED-ICU from ED were included. RESULTS: Seventy-eight non-trauma patients with prior DNR status were included in the final analysis. 51.3% (40/78) patients were male with median age 83 (IQR: 75-89) years. The median APACHE II score was 24.5 (IQR: 20-30). 50% (39/78) of the DNR patients survived to discharge. Patients who survived to discharge had lower APACHE II score (23 (IQR: 20-28) vs. 28 (18-38), p = 0.028). There was no significant difference in age, gender, and Charlson index. ROC curves were constructed, generating a cut-off of the APACHE II score at 29.5 for determining survival to discharge (AUC = 0.644, p = 0.028). In multivariate Cox proportional model, APACHE II score above 29.5 was an independent predictor for mortality. (Hazard ratio = 2.46; 95% confidence interval: 1.04-5.83, p = 0.042). CONCLUSION: Our study found that 50% of patients with prior DNR on ICU admission survived to discharge, indicating that aggressive care is not definitely futile. Further prospective studies are required to evaluate the cost-effectiveness and patients' and/or families' satisfaction of the ICU admission of DNR patients.

Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF-α-mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice.

This study demonstrates the bioefficacy and gives mechanistic insights into a plant galactolipid 1,2-di-O-linolenoyl-3-O-ß-galactopyranosyl-sn-glycerol (dLGG) against metastatic melanoma using a syngeneic mouse model implanted with B16COX-2/Luc melanoma. dLGG-20 (p.o. dLGG 20 mg/kg) and anti-cancer drug CP-2 (i.p. cisplatin 2 mg/kg) treatment significantly inhibited lung metastasis of melanoma in mice 91 and 57%, respectively, as determined by bioluminescence intensity. Moreover, dLGG-20 and CP-2 treatment prolonged mouse mean survival time. dLGG-20 treatment significantly inhibited the expression levels of several molecular markers, that is, PCNA, MMP2, COX-2, VEGF, vimentin, snail, TGF-ß, ß-catenin, TNF-α, PD-1 and PD-L1 in mouse lung tissues compared to tumor control mice. Significant inhibition of macrophage and neutrophil infiltration and promotion of CD8 + Tc cell recruitment in the lung microenvironment was observed in dLGG-20-treated mice. A LC/MS-based comparative oxylipin metabolomics study showed that dLGG-20 treatment significantly induced (5.0- to 12.8-fold) the 12/15-LOX catalyzed oxylipin products in mouse serum including 17-HDHA from DHA, 15-HEPE from EPA, 8- and 12-HETEs from AA, and CYP450-derived 20-HETE from AA. CP-2 treatment increased 12/15-LOX derived 8-, 11- and 12-HETEs from AA, and CYP450 derived 11,12-EET from AA ad 9,10-DHOME from LA by 5.3- to 8.1-fold. Of note, dLGG and 17-HDHA were more effective than CP in preventing B16 melanoma cell-induced pulmonary vascular permeability in mice through inhibition of TNF-α production, up-regulation of tight junction proteins claudin1 and ZO-2 and deregulation of Src activation. In conclusion, this study shows the novel therapeutic effect of phytoagent dLGG and suggests its potential as a therapeutic agent for metastatic melanoma.

miR-4725-3p targeting stromal interacting molecule 1 signaling is involved in xanthohumol inhibition of glioma cell invasion.

Glioblastoma multiforme is the most common brain tumor in adults. Because of its highly invasive nature, it is not easy to treat, resulting in high mortality rates. Stromal interacting molecule 1 (Stim1) plays important roles in regulating store-operated Ca2+ entry, and controls invasion by cancer cells. However, the mechanisms and functions of Stim1 in glioma progression are still unclear. In this study, we investigated the effects of targeting Stim1 expression on glioma cell invasion. By analyzing profiles of glioblastoma multiforme patients from RNA-sequencing data in The Cancer Genome Atlas, higher expression levels of STIM1 were correlated with the poor survival. Furthermore, signaling pathways associated with tumor malignancy, including the epithelial-to-mesenchymal transition (EMT), were activated in patients with high STIM1 expression according to gene set enrichment analyses. Higher Stim1 levels were found in glioma cells compared to human astrocytes, and these higher levels enhanced glioma cell invasion. Xanthohumol (XN), a prenylated flavonoid extracted from the hop plant Humulus lupulus L. (Cannabaceae), significantly reduced cell invasion through inhibiting Stim1 expression. From an micro(mi)RNA array analysis, miR-4725-3p was up-regulated by XN treatment. Over-expression of miR-4725-3p inhibited glioma cell invasion via directly targeting the 3'-untranslated region of STIM1. The extracellular signal-regulated kinase/c-Fos pathway was also validated to participate in XN-up-regulated miR-4725-3p expression according to promoter and chromatin immunoprecipitation assays. These results emphasize that miR-4725-3p-inhibited STIM1 signaling is involved in XN-attenuated glioma cell invasion. These findings may provide insights into novel therapeutic strategies for future glioblastoma therapy and drug development. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/.

Improved effects of honokiol on temozolomide-induced autophagy and apoptosis of drug-sensitive and -tolerant glioma cells.

BACKGROUND: Temozolomide (TMZ)-induced side effects and drug tolerance to human gliomas are still challenging issues now. Our previous studies showed that honokiol, a major bioactive constituent of Magnolia officinalis (Houpo), is safe for normal brain cells and can kill human glioma cells. This study was further aimed to evaluate the improved effects of honokiol and TMZ on drug-sensitive and -resistant glioma cells and the possible mechanisms. METHODS: TMZ-sensitive human U87-MG and murine GL261 glioma cells and TMZ-resistant human U87-MR-R9 glioma cells were exposed to honokiol and TMZ, and cell viability and LC50 of honokiol were assayed. To determine the death mechanisms, caspase-3 activity, DNA fragmentation, apoptotic cells, necrotic cells, cell cycle, and autophagic cells. The glioma cells were pretreated with 3-methyladenine (3-MA) and chloroquine (CLQ), two inhibitors of autophagy, and then exposed to honokiol or TMZ. RESULTS: Exposure of human U87-MG glioma cells to honokiol caused cell death and significantly enhanced TMZ-induced insults. As to the mechanism, combined treatment of human U87-MG cells with honokiol and TMZ induced greater caspase-3 activation, DNA fragmentation, cell apoptosis, and cell-cycle arrest at the G1 phase but did not affect cell necrosis. The improved effects of honokiol on TMZ-induced cell insults were further verified in mouse GL261 glioma cells. Moreover, exposure of drug-tolerant human U87-MG-R9 cells to honokiol induced autophagy and consequent apoptosis. Pretreatments with 3-MA and CLQ caused significant attenuations in honokiol- and TMZ-induced cell autophagy and apoptosis in human TMZ-sensitive and -tolerant glioma cells. CONCLUSIONS: Taken together, this study demonstrated the improved effects of honokiol with TMZ on autophagy and subsequent apoptosis of drug-sensitive and -tolerant glioma cells. Thus, honokiol has the potential to be a drug candidate for treating human gliomas.

Red blood cell distribution width is associated with mortality in elderly patients with sepsis.

INTRODUCTION: RDW is a prognostic biomarker and associated with mortality in cardiovascular disease, stroke and metabolic syndrome. For elderly patients, malnutrition and multiple comorbidities exist, which could affect the discrimination ability of RDW in sepsis. The main purpose of our study was to evaluate the prognostic value of RDW in sepsis among elderly patients. METHODS: This was a retrospective cohort study conducted in emergency department intensive care units (ED-ICU) between April 2015 and November 2015. Elderly patients (≥65years old) who were admitted to the ED-ICU with a diagnosis of severe sepsis and/or septic shock were included. The demographic data, biochemistry data, qSOFA, and APACHE II score were compared between survivors and nonsurvivors. RESULTS: A total of 117 patients was included with mean age 81.5±8.3years old. The mean APACHE II score was 21.9±7.1. In the multivariate Cox proportional hazards model, RDW level was an independent variable for mortality (hazard ratio: 1.18 [1.03-1.35] for each 1% increase in RDW, p=0.019), after adjusting for CCI, any diagnosed malignancy, and eGFR. The AUC of RDW in predicting mortality was 0.63 (95% confidence interval [CI]: 0.52-0.74, p=0.025). In subgroup analysis, for qSOFA <2, nonsurvivors had higher RDW levels than survivors (17.0±3.3 vs. 15.3±1.4%, p=0.044). CONCLUSIONS: In our study, RDW was an independent predictor of in-hospital mortality in elderly patients with sepsis. For qSOFA scores <2, higher RDW levels were associated with poor prognosis. RDW could be a potential parameter used alongside the clinical prediction rules.

The Inhibition of microRNA-128 on IGF-1-Activating mTOR Signaling Involves in Temozolomide-Induced Glioma Cell Apoptotic Death.

Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death. By performing miRNA microarray and bioinformatics analyses, we observed that expression of 248 miRNAs was altered, including five significantly upregulated and 17 significantly downregulated miRNAs, in TMZ-treated U87MG cells. miR-128 expression levels were lower in different glioma cells and strongly associated with poor survival. TMZ treatment significantly upregulated miR-128 expression. TMZ significantly enhanced miR-128-1 promoter activity and transcriptionally regulated miR-128 levels through c-Jun N-terminal kinase 2/c-Jun pathways. The overexpression and knockdown of miR-128 expression significantly affected TMZ-mediated cell viability and apoptosis-related protein expression. Furthermore, the overexpression of miR-128 alone enhanced apoptotic death of glioma cells through caspase-3/9 activation, poly(ADP ribose) polymerase degradation, reactive oxygen species generation, mitochondrial membrane potential loss, and non-protective autophagy formation. Finally, we identified that key members in mammalian target of rapamycin (mTOR) signaling including mTOR, rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR signaling through miR-128 regulation. These results indicate that miR-128-inhibited mTOR signaling is involved in TMZ-mediated cytotoxicity. Our findings may provide a better understanding of cytotoxic mechanisms of TMZ involved in glioblastoma development.

The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death.

Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development.

Preclinical effects of honokiol on treating glioblastoma multiforme via G1 phase arrest and cell apoptosis.

BACKGROUND: Our previous study showed that honokiol, a bioactive polyphenol, can traverse the blood-brain barrier and kills neuroblastoma cells. PURPOSE: In this study, we further evaluated the preclinical effects of honokiol on development of malignant glioma and the possible mechanisms. METHODS: Effects of honokiol on viability, caspase activities, apoptosis, and cell cycle arrest in human glioma U87 MG or U373MG cells were assayed. As to the mechanisms, levels of inactive or phosphorylated (p) p53, p21, CDK6, CDK4, cyclin D1, and E2F1 were immunodetected. Pifithrin-α (PFN-α), a p53 inhibitor, was pretreated into the cells. Finally, our in vitro findings were confirmed using intracranial nude mice implanted with U87 MG cells. RESULTS: Exposure of human U87 MG glioma cells to honokiol decreased the cell viability. In parallel, honokiol induced activations of caspase-8, -9, and -3, apoptosis, and G1 cell cycle arrest. Treatment of U87 MG cells with honokiol increased p53 phosphorylation and p21 levels. Honokiol provoked signal-transducing downregulation of CDK6, CDK4, cyclin D1, phosphorylated (p)RB, and E2F1. Pretreatment of U87 MG cells with PFN-α significantly reversed honokiol-induced p53 phosphorylation and p21 augmentation. Honokiol-induced alterations in levels of CDK6, CDK4, cyclin D1, p-RB, and E2F1 were attenuated by PFN-α. Furthermore, honokiol could induce apoptotic insults to human U373MG glioma cells. In our in vivo model, administration of honokiol prolonged the survival rate of nude mice implanted with U87 MG cells and induced caspase-3 activation and chronological changes in p53, p21, CDK6, CDK4, cyclin D1, p-RB, and E2F1. CONCLUSIONS: Honokiol can repress human glioma growth by inducing apoptosis and cell cycle arrest in tumor cells though activating a p53/cyclin D1/CDK6/CDK4/E2F1-dependent pathway. Our results suggest the potential of honokiol in therapies for human malignant gliomas.

Protecting against ischaemic stroke in rats by heat shock protein 20-mediated exercise.

BACKGROUND: Exercise preconditioning (EP(+) ) has been widely accepted as a being of safe and effective preventive measure for stroke. The purpose of this study was to investigate whether EP(+) improves outcomes of ischaemic stroke by promoting neuronal and glial expression of heat shock protein (HSP) 20. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (288 in number) were used to investigate the contribution of HSP20-containing neurons and HSP20-containing glial cells in the exercise-mediated neuroprotection in the stroke condition using middle cerebral artery occlusion. RESULTS: Exercise preconditioning, in addition to increasing the numbers of both the HSP20-containg neurons (88 ± 8 vs. 43 ± 4; n = 8 each group; P < 0·05) and the HSP20-containg astrocytes (102 ± 10 vs. 56 ± 5; n = 8; P < 0·05) significantly attenuated stroke-induced brain infarct (140 ± 9 vs. 341 ± 20 mm(3) ; n = 8 per group; P < 0·01), neuronal apoptosis (20 ± 5 vs. 87 ± 7; n = 8 per group; n = 8; P < 0·01), glial apoptosis (29 ± 5 vs. 101 ± 4; n = 8; P < 0·01), and neurological deficits (6·6 ± 0·3 vs. 11·7 ± 0·8; n = 8 per group; P < 0·01). Reducing the numbers of both HSP20-containing neurons and HSP20-contaiing glia by intracerebral injection of pSUPER small interfering RNAί expressing HSP20 significantly reversed the beneficial effects of EP(+) in attenuating stroke-induced cerebral infarct, neuronal and glial apoptosis, and neurological deficits. CONCLUSIONS: The numbers of both the HSP20-containing neurons and the HSP20-containing glia inversely correlated with the outcomes of ischaemic stroke. In addition, preischaemic treadmill exercise improves outcomes of ischaemic stroke by increasing the numbers of both the HSP20-containing neurons and the HSP20-containing glia.

A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management in Moderate and Severe Traumatic Brain Injury Patients.

The purpose of this study was to compare the effect of PbtO2-guided therapy with traditional intracranial pressure- (ICP-) guided treatment on the management of cerebral variables, therapeutic interventions, survival rates, and neurological outcomes of moderate and severe traumatic brain injury (TBI) patients. From 2009 to 2010, TBI patients with a Glasgow coma scale <12 were recruited from 6 collaborative hospitals in northern Taiwan, excluding patients with severe systemic injuries, fixed and dilated pupils, and other major diseases. In total, 23 patients were treated with PbtO2-guided management (PbtO2 > 20 mmHg), and 27 patients were treated with ICP-guided therapy (ICP < 20 mmHg and CPP > 60 mmHg) in the neurosurgical intensive care unit (NICU); demographic characteristics were similar across groups. The survival rate in the PbtO2-guided group was also significantly increased at 3 and 6 months after injury. Moreover, there was a significant correlation between the PbtO2 signal and Glasgow outcome scale-extended in patients from 1 to 6 months after injury. This finding demonstrates that therapy directed by PbtO2 monitoring is valuable for the treatment of patients with moderate and severe TBI and that increasing PaO2 to 150 mmHg may be efficacious for preventing cerebral hypoxic events after brain trauma.

Astragaloside improves outcomes of traumatic brain injury in rats by reducing microglia activation.

Astragaloside (AST) is traditionally prescribed for the prevention and treatment of cerebrovascular diseases. We directly tested the therapeutic effects of AST in a rat model of traumatic brain injury (TBI). One hour after the onset of TBI rats were given Saline (1 ml/kg) or AST (20-80 mg/kg) via i.p. injection. AST causes the attenuation of TBI-induced cerebral contusion, neuronal apoptosis, and neurological motor dysfunction. TBI-induced microglial activation evidenced by the morphological transformation of microglia (or ameboid microglia) and the microglial overexpression of tumor necrosis factor-alpha was reduced by AST. Our results indicate that AST may protect against brain contusion and neuronal apoptosis after TBI by attenuating microglia activation in male rats.

Exercise preconditioning protects against spinal cord injury in rats by upregulating neuronal and astroglial heat shock protein 72.

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI.

Early morning awakening and nonrestorative sleep are associated with increased minor non-fatal accidents during work and leisure time.

BACKGROUND: The relationship between a composite measure of insomnia and occupational or fatal accidents has been investigated previously; however, little is known regarding the effect of various insomnia symptoms on minor non-fatal accidents during work and leisure time. OBJECTIVE: We investigated the predicting role of insomnia symptoms on minor non-fatal accidents during work and leisure time. METHODS: Data from the 2005 Taiwan Social Development Trend Survey of 36,473 Taiwanese aged ≥18 years were analyzed in 2013. Insomnia symptoms, including difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), early morning awakening (EMA), and nonrestorative sleep (NRS) were investigated. A minor non-fatal accident was defined as any mishap such as forgetting to turn off the gas or faucets, accidental falls, and abrasions or cuts occurring during work and leisure time in the past month that do not require immediate medical attention. Multivariable logistic regression was performed to assess the odds ratios (ORs) and associated 95% confidence interval (CI) of minor non-fatal accidents (as a binary variable) for each insomnia symptom compared with those of people presenting no symptoms, while controlling for possible confounders. RESULTS: EMA and NRS increased the odds of minor non-fatal accidents occurring during work and leisure time (adjusted OR=1.19, 95% CI=1.08-1.32 and adjusted OR=1.27, 95% CI=1.17-1.37, respectively). CONCLUSION: EMA and NRS are two symptoms that are significantly associated with an increased likelihood of minor non-fatal accidents during work and leisure time after adjusting for of a range of covariates.

Brain-derived neurotrophic factor-transfected and nontransfected 3T3 fibroblasts enhance migratory neuroblasts and functional restoration in mice with intracerebral hemorrhage.

Neurogenesis via the activation of endogenous neural progenitor cells is a potential treatment strategy for brain injury, including intracerebral hemorrhage (ICH). We assessed the efficacy of combined cell and brain-derived neurotrophic factor (BDNF) treatment in a mouse model of ICH induced by intracerebral collagenase injection. Complementary DNAs of mouse BDNF were transfected into cell lines of 3T3 fibroblasts. The expression and bioactivity of BDNF were analyzed by immunocytochemistry, Western blot, ELISA, and functional assays. Hematoma area and brain tissue loss were assessed by magnetic resonance imaging. The BDNF-transfected or nontransfected 3T3 fibroblasts were implanted as a growth factor source in mice with ICH. Neurogenesis and functional recovery were evaluated 15 days after ICH. The BDNF-treated mice had the most doublecortin-positive cells near lesions and the least brain tissue loss in all groups. Both cell treatment groups had abundant newly proliferative glial fibrillary acidic protein-positive cells and better functional improvement than controls. These results indicate that fibroblast transplantation, together with recombinant BDNF treatment, after ICH is beneficial in mice. The early functional recovery may result from the growth factors that are provided or evoked by the implanted grafts. These results suggest a potential approach for combining gene and cell therapy for ICH treatment.

Brushing teeth with purified water to reduce ventilator-associated pneumonia.

BACKGROUND: Oral care may decrease the development of ventilator-associated pneumonia (VAP) and improve oral hygiene. However, little evidence is available to guide the development of oral care protocols. The practical effect of toothbrushing on VAP development and oral health and hygiene improvement is inconclusive. PURPOSE: This study evaluated the effects in postneurosurgical, intensive care unit patients of brushing teeth twice daily with purified water on VAP rates and oral health or hygiene. METHODS: This study conducted a randomized controlled pilot trial. Patients consecutively admitted to the surgical intensive care unit at a suburban hospital in 2007 were invited to participate if they met two inclusion criteria: (a) under ventilator support for at least 48 to 72 hours and (b) no current pneumonia. Upon obtaining informed consent, subjects were randomized into experimental and control groups. Both groups received usual hospital care, that is, daily oral care using cotton swabs. The experimental group additionally received a twice-daily oral care protocol of toothbrushing with purified water, elevating the head of the bed, and before-and-after hypopharyngeal suctioning. The control group also received twice-daily mock oral care (elevating the head of the bed, moisturizing the lips, and before-and-after hypopharyngeal suctioning). VAP was defined by a clinical pulmonary infection score of > 6. Oral hygiene and health was assessed after conclusion of the intervention. RESULTS: Patients (N = 53) were predominantly male (64.2%), mean age was 60.6 years old, and most had received emergency surgery (75.5%). After 7 days of toothbrushing with purified water, cumulative VAP rates were significantly lower in the experimental (17%) than in the control (71%; p <.05) group. The experimental group also had significantly better scores for oral health (p <.05) and plaque index (p <.01). CONCLUSION/IMPLICATION FOR PRACTICE: Findings suggest that, as an inexpensive alternative to existing protocols, toothbrushing twice daily with purified water reduces VAP and improves oral health and hygiene.

A retrospective survey of patients with malignant gliomas treated in the neuro-oncological care system under the Universal National Health Insurance program in Taiwan.

In 1995 a government-supported Universal National Health care system was implemented in Taiwan, which in 2008 was available to 98% of the population. This system offers affordable, rapid medical attention. A multi-center retrospective study was conducted to assess the prognosis of malignant glioma patients under this system. In 2005 and 2006, patients at 14 independent neuro-oncology centers with newly diagnosed malignant glioma were enrolled. The patient profile, pathology, treatment modalities, and prognosis were collected by questionnaire at each center. The Taiwan Neuro-Oncology Society was responsible for the data analysis. The overall median survival period, 1-year survival rate, and 2-year survival rate for patients with World Health Organization grade III glioma were 33.8 months, 81.4%, and 58.2%, respectively, and 15 months, 57.3%, and 33.9% in patients with grade IV glioma. The median survival period, 1-year survival rate, and 2-year-survival rate in patients receiving temozolomide adjuvant therapy was 36 months, 84.2%, and 61.8%, respectively, for patients with grade III glioma and 19.8 months, 73.1%, and 43.7%, for patients with grade IV glioma. The universal health care system in Taiwan offers a comparable prognosis with an affordable premium relative to other large series in developed countries.