Case Report: Multiple Sclerosis Presenting as Unilateral Gaze-evoked Nystagmus.

SIGNIFICANCE: Unilateral gaze-evoked nystagmus is a rare neurologic finding that is largely diagnosed in connection with ischemic stroke. Gazed-evoked nystagmus is also a rare initial presentation of multiple sclerosis. PURPOSE: This study aimed to report a rare presentation of gaze-evoked nystagmus in a patient with multiple sclerosis and review the mechanism underlying the gaze-evoked nystagmus. CASE REPORT: A 32-year-old man presented with a 1-week history of diplopia. Neurologic examination revealed right-sided gaze-evoked nystagmus and right-sided ataxia. Laboratory test revealed a positive result for oligoclonal bands. Contrast brain MRI revealed multiple hyperintense T2 lesions including a hyperintense patch at the right inferior cerebellar peduncle. A diagnosis of multiple sclerosis was made. The patient received methylprednisolone 500 mg intravenously for 14 days. The diplopia and gaze-evoked nystagmus resolved and remained stable 2 months later. CONCLUSIONS: Our case demonstrates that damage to the inferior cerebellar peduncle may result in ipsilesional gaze-evoked nystagmus and ipsilesional ataxia, in contrast to ipsilesional gaze-evoked nystagmus and contralesional ataxia.

Polycyclic aromatic hydrocarbon metabolites and mortality risk in an adult population.

Occupational polycyclic aromatic hydrocarbons (PAHs) exposure has been shown to increase the risk of various cancers and may be associated with carcinogenic mortality. However, no study has explored the relationship between environmental PAH exposure and mortality in general population. The aim of our study was to explore the association between PAH exposure and all-cause, cardiovascular, and cancer mortality in a general US adult population. We analyzed data from the National Health and Nutrition Examination Survey (NHANES 2001-2006) based on the information in this dataset on 692 males and 717 females. PAH exposure was detected using biomarkers from urine samples. Follow-up data on mortality were derived from initial examination of the subjects until death or 31 December 2006 in the NHANES database. We calculated hazard ratios (HRs) of PAH metabolites among all-cause, cardiovascular, and cancer mortality using the multivariate Cox proportional hazards regression model after adjusting for covariates. Among males, 3-phenanthrene was positively associated with increased risk of all-cause mortality (HR 1.043, 95%CI 1.019-1.066). Female participants with higher 2-napthol (HR 1.043, 95%CI 1.014-1.072), 3-fluorene (HR 2.159, 95%CI 1.233-3.779), and 1-phenanthrene (HR = 1.259, 95%CI 1.070-1.481) levels had increased all-cause mortality. In addition, high 3-phenanthrene (HR 1.333, 95%CI 1.008-1.763) and 1-phenanthrene (HR 1.463, 95%CI 1.126-1.900) levels increased the risk of cardiovascular mortality. However, there were no significant findings for cancer mortality in both genders. Environmental PAH exposure among the adult population is associated with non-carcinogenic but not cancer mortality. Future studies are warranted to determine the underlying mechanisms related to these findings.

Impact of periodontal disease and chewing ability on the quality of life of the elderly in an affluent community.

BACKGROUND/PURPOSE: Improvement of the medical and social environment is an important aspect of government policies in assuring the quality of life (QoL) of older adults. However, few studies have appraised the impact and relationship of QoL with clinical factors among elderly individuals in affluent residential areas. METHODS: A total of 166 older adults from Chang Gung Health and Culture Village were enrolled. Oral health-related QoL was measured using the Geriatric Oral Health Assessment Index. Self-assessed chewing abilities and demographic characteristics were collected by questionnaire. Physical health was scored by activities of daily living (ADL) and instrumental ADL. Mini nutrition assessment questionnaire was used to evaluate the nutritional intake. Multiple linear regression was used to predict risk factors affecting QoL and to examine whether chewing ability was a mediator of oral health-related QoL. RESULTS: Poor chewing ability was associated with older age (OR = 1.82 for 76-85 years and 3.58 for 86-95 years), sufficient economic status (OR = 5.55) and removable denture-wearing (OR = 7.52). On the other hand, poor chewing ability (OR = 0.11), removable denture-wearing (OR = 0.48), periodontal disease (OR = 0.38) had lower likelihood of good oral health-related QoL. Mediator analyses showed that chewing ability was a mediator for the association between oral health-related QoL and economic status or removable denture-wearing or having more than 20 teeth. Periodontal disease was an independent factor for oral health-related QoL. CONCLUSION: Among older adults in an affluent community, periodontal disease is an independent risk factor directly related to oral health-related QoL, whereas chewing ability is a mediator between QoL and removable denture-wearing.

Characteristics of CD133-Sustained Chemoresistant Cancer Stem-Like Cells in Human Ovarian Carcinoma.

Cancer stem cells (CSCs) are considered to be the origin of ovarian cancer (OC) development, recurrence, and chemoresistance. We investigated changes in expression levels of the CSC biomarker, cluster of differentiation 133 (CD133), from primary OC cell lines to induction of CSC-spheres in an attempt to explore the mechanisms related to modulation of stemness, drug resistance, and tumorigenesis in CSCs, thus facilitating the search for new therapeutics for OC. The effect of CD133 overexpression on the induction of CSC properties was evaluated by sphere-forming assays, RT-qPCR, flow cytometry, cell viability assays, and in vivo xenograft experiments. Moreover, the potential signaling molecules that participate in CD133 maintenance of stemness were screened by RNA-sequencing. CD133 expression was upregulated during OCSC induction and chemotherapeutic drug treatment over time, which increased the expressions of stemness-related markers (SOX2, OCT4, and Nanog). CD133 overexpression also promoted tumorigenesis in NOD/SCID mice. Several signalings were controlled by CD133 spheres, including extracellular matrix receptor interactions, chemokine signaling, and Wnt signaling, all of which promote cell survival and cell cycle progression. Our findings suggest that CD133 possesses the ability to maintain functional stemness and tumorigenesis of OCSCs by promoting cell survival signaling and may serve as a potential target for stem cell-targeted therapy of OC.

Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol.

Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen.

Glucosamine impedes transforming growth factor ß1-mediated corneal fibroblast differentiation by targeting Krüppel-like factor 4.

BACKGROUND: Transforming growth factor (TGF) family members play important roles in the regulation of corneal integrity, and the pathogenesis of corneal fibrosis. Currently, there are no effective agents targeting TGF-ß signaling to diminish corneal fibrosis. Glucosamine (GlcN), which is widely used in the treatment of osteoarthritis, abrogates the morphologic effects of TGF-ß2 on retinal pigmented epithelial cells in a mouse disease model. Here, we sought to determine whether GlcN would exert beneficial effects against TGF-ß1-induced corneal fibrosis. METHODS: In human corneal fibroblasts (HCFs) treated with GlcN, the expression of Krüppel-like factor 4 (KLF4) and its downstream signaling effects were determined in the presence and absence of TGF-ß1 using immunoblot analysis. We further explored GlcN inhibition of fibroblast-to-myofibroblast differentiation via KLF4 siRNA. The effect of cycloheximide on KLF4 protein levels with or without GlcN administration was assessed to determine whether GlcN affects the stability of the KLF4 protein. RESULTS: In HCFs, GlcN induced the expression of KLF4, which regulated the maturation and maintenance of the ocular surface. GlcN partially suppressed the TGF-ß1-induced expression of alpha-smooth muscle actin (α-SMA) and reduced the collagen contraction capacity in HCFs, suggesting a decrease in fibroblast-to-myofibroblast differentiation. This effect appeared to be mediated through suppression of Smad2 phosphorylation and ERK-dependent signaling. The levels of KLF4 mRNA were increased by GlcN and decreased by TGF-ß1 and the TGF-ß1-induced α-SMA mRNA expression was upregulated when the KLF4 gene was silenced. GlcN also appeared to stabilize the KLF4 protein, reducing its turnover in corneal fibroblasts. CONCLUSION: These findings shed light on a novel mechanism by which GlcN suppresses TGF-ß1-induced fibroblast-to-myofibroblast differentiation through the upregulation of KLF4 expression. Current strategies for treating corneal fibrosis were not effective. Elevating KLF4 levels through the use of GlcN might provide an effective alternative to alleviate the development and progression of corneal fibrosis.

Ex Vivo Expanded Human Vγ9Vδ2 T-Cells Can Suppress Epithelial Ovarian Cancer Cell Growth.

γδ-T-cells have attracted attention because of their potent cytotoxicity towards tumors. Most γδ-T-cells become activated via a major histocompatibility complex (MHC)-independent pathway by the interaction of their receptor, Natural Killer Group 2 Member D (NKG2D) with the tumor-specific NKG2D ligands, including MHC class I-related chain A/B (MICA/B) and UL16-binding proteins (ULBPs), to kill tumor cells. However, despite their potent antitumor effects, the treatment protocols specifically targeting ovarian tumors require further improvements. Ovarian cancer is one of the most lethal and challenging female malignancies worldwide because of delayed diagnoses and resistance to traditional chemotherapy. In this study, we successfully enriched and expanded γδ-T-cells up to ~78% from peripheral blood mononuclear cells (PBMCs) with mostly the Vγ9Vδ2-T-cell subtype in the circulation. We showed that expanded γδ-T-cells alone exerted significant cytotoxic activities towards specific epithelial-type OVCAR3 and HTB75 cells, whereas the combination of γδ-T cells and pamidronate (PAM), a kind of aminobisphosphonates (NBPs), showed significantly enhanced cytotoxic activities towards all types of ovarian cancer cells in vitro. Furthermore, in tumor xenografts of immunodeficient NSG mice, γδ-T-cells not only suppressed tumor growth but also completely eradicated preexisting tumors with an initial size of ~5 mm. Thus, we concluded that γδ-T-cells alone possess dramatic cytotoxic activities towards epithelial ovarian cancers both in vitro and in vivo. These results strongly support the potential of clinical immunotherapeutic application of γδ-T-cells to treat this serious female malignancy.

Combining Whispering-Gallery Mode Optical Biosensors with Microfluidics for Real-Time Detection of Protein Secretion from Living Cells in Complex Media.

The noninvasive monitoring of protein secretion of cells responding to drug treatment is an effective and essential tool in latest drug development and for cytotoxicity assays. In this work, a surface functionalization method is demonstrated for specific detection of protein released from cells and a platform that integrates highly sensitive optical devices, called whispering-gallery mode biosensors, with precise microfluidics control to achieve label-free and real-time detection. Cell biomarker release is measured in real time and with nanomolar sensitivity. The surface functionalization method allows for antibodies to be immobilized on the surface for specific detection, while the microfluidics system enables detection in a continuous flow with a negligible compromise between sensitivity and flow control over stabilization and mixing. Cytochrome c detection is used to illustrate the merits of the system. Jurkat cells are treated with the toxin staurosporine to trigger cell apoptosis and cytochrome c released into the cell culture medium is monitored via the newly invented optical microfluidic platform.

Proteomic investigating the cooperative lethal effect of EGFR and MDM2 inhibitors on ovarian carcinoma.

With the concept of precision medicine, combining multiple molecular-targeting therapies has brought new approaches to current cancer treatments. Malfunction of the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under normal conditions, p53 is degraded through an ubiquitin-proteosome pathway regulated by its negative regulator, MDM2. In contrast, cellular stress such as DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2 overexpression rate. We assessed the effects of combined inhibition by MDM2 (JNJ-26854165) and EGFR (gefitinib) inhibitors on various ovarian cell lines to determine the importance of these two molecular targets on cell proliferation. We then used a proteomic strategy to investigate the relationship between MDM2 and EGFR inhibition to explore the underlying mechanisms of how their combined signaling blockades work together to exert cooperative inhibition. Our results demonstrated that all four cell lines were sensitive to both individual and combined, MDM2 and EGFR inhibition. The proteomic analysis also showed that gefitinib/JNJ-treated CAOV3 cells exhibited downregulation of proteins involved in nucleotide biosynthesis such as nucleoside diphosphate kinase B (NME2). In conclusion, our study showed that the combined treatment with JNJ and gefitinib exerted synergistic inhibition on cell proliferation, thereby suggesting the potential application of combining MDM2 inhibitors with EGFR inhibitors for enhancing efficacy in ovarian cancer treatment.

Mediating effects of burden on quality of life for caregivers of first-time stroke patients discharged from the hospital within one year.

BACKGROUND: Caregiver burden may be either a predictor or an outcome of caregiver quality of life (QoL). Patient or caregiver factors that directly affect caregiver QoL, predictors that are simultaneously shared with caregiver burden and QoL, and factors that affect caregiver QoL through caregiver burden are not well understood. This study explored predictors of caregiver QoL and identified whether caregiver burden is a mediator for caregivers of first-time stroke patients. METHODS: This is a cross-sectional study. We recruited first-time stroke patients who had been discharged from the hospital within 1 year. We screened caregivers with two major inclusion criteria: age > 20 years old and being the family member who provides the most patient-care hours out of all family caregivers. Caregiver burden (Caregiver Strain Index, CSI), QoL (Caregiver Quality of Life Index, CQLI), and patient and caregiver characteristics were assessed with structured questionnaires. Multiple-regression and bootstrap analysis were conducted for data analysis. RESULTS: A total of 126 caregivers completed the questionnaires. Higher caregiver burdens, lower caregiver education level, lower self-rated health, lower monthly family income, and spouses who were responsible for medical fees were significant predictors of lower caregiver QoL. Poor self-rated health and monthly family income of $ 666 USD or below were the strongest predictors of caregiver QoL. Spouses who were responsible for medical fees and lower monthly family income had direct negative effects on caregiver QoL, but these factors exhibited no indirect mediating effect between caregiver characteristics and QoL through caregiver burden as a mediator. Caregiver education level at or below elementary school and poor or fair self-rated-health had direct negative effects on caregiver QoL, which were mediated by caregiver burden. CONCLUSIONS: Our study indicated predictors of caregiver QoL and the relationships with caregiver burden among first-time stroke survivors in the early stage. Caregivers' financial factors affected caregiver QoL directly. Caregivers' poor self-rated health and lower education level negatively affected caregiver QoL indirectly through caregiver burden as a mediator. Interventions to make appropriate policies for financial subsidies, to enhance caregivers' health and to provide tailored stroke-related education through multidisciplinary cooperation may effectively promote caregiver QoL.

Benefit of hyperbaric oxygen therapy treatment in direct traumatic optic neuropathy: case report.

Direct traumatic optic neuropathy (TON) is a devastating condition and clinical challenge. Its adequate treatment remains controversial. Hyperbaric oxygen (HBO2) therapy has been proposed as an adjunctive treatment for eye disease but has rarely been used in optic neuropathy. The patient was a 57-year-old woman who had direct TON and brain injury after contusion injury. After receiving delayed HBO2 therapy her visual acuity got better - from hand motion to 6/60 - along with improvement of visual field and color vision. She was treated at 2.5 atmospheres absolute for 100 minutes, five times a week, for a total of 61 sessions. Our case highlights that HBO2 may be beneficial as an alternative treatment for direct TON, particularly when combined with brain injury. Although this entity is promising, further randomized controlled trials will be needed to clarify the efficacy of HBO2 in the treatment of direct TON.

Development and psychometric testing of the triggers of Suicidal Ideation Inventory for assessing older outpatients in primary care settings.

OBJECTIVE: The purpose of this study was to develop an instrument for assessing triggers of suicidal ideation among older outpatients and determine its psychometrics. METHOD: Participants were recruited from older outpatients of two hospitals in northern Taiwan. The 34-item Triggers of Suicidal Ideation Inventory (TSII) was developed, and its items were validated by experts in two runs of Delphi technique survey. Pre-testing this TSII in 200 older outpatients resulted in a 12-item TSII, with three items not considered triggers but suggesting the need for further psychiatric assessment. The 9-item TSII was examined by criterion validity, construct validity, internal consistency reliability, and test-retest reliability. RESULTS: Factor analysis of the final version of TSII yielded a three-factor solution, accounting for 68.75% of the variance. Participants with depressive tendency tended to have higher TSII scores than participants with no depressive tendency (t = 8.62, p < 0.01), indicating good construct validity. TSII scores were significantly and positively correlated with Beck Scale for Suicide Ideation (r = 0.45, p < 0.01) and UCLA Loneliness (r = 0.55, p < 0.01) scores, indicating satisfactory criterion validity. The TSII had Cronbach's α and intraclass correlation coefficient of 0.70 and 0.99, respectively, indicating acceptable internal consistency reliability and excellent test-retest reliability. Receiver operating characteristic analysis revealed an area under the curve of 0.82, indicating excellent ability to detect triggers of suicidal ideation. With a cutoff point of 2, the sensitivity and specificity were 0.76 and 0.69, respectively. CONCLUSIONS: The TSII can be completed in 5 min, is perceived as easy to complete, and yielded highly acceptable parameters of validity and reliability. Copyright © 2016 John Wiley & Sons, Ltd.

Proteomic Analysis of Various Rat Ocular Tissues after Ischemia-Reperfusion Injury and Possible Relevance to Acute Glaucoma.

Glaucoma is a group of eye diseases that can cause vision loss and optical nerve damage. To investigate the protein expression alterations in various intraocular tissues (i.e., the cornea, conjunctiva, uvea, retina, and sclera) during ischemia-reperfusion (IR) injury, this study performed a proteomic analysis to qualitatively investigate such alterations resulting from acute glaucoma. The IR injury model combined with the proteomic analysis approach of two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to monitor the protein expression alterations in two groups of specimens (an IR injury group and a control group). The analysis results revealed 221 unique differentially expressed proteins of a total of 1481 proteins in the cornea between the two groups. In addition, 97 of 1206 conjunctival proteins, 90 of 1354 uveal proteins, 61 of 1180 scleral proteins, and 37 of 1204 retinal proteins were differentially expressed. These findings imply that different ocular tissues have different tolerances against IR injury. To sum up, this study utilized the acute glaucoma model combined with 2D-DIGE and MALDI-TOF MS to investigate the IR injury affected protein expression on various ocular tissues, and based on the ratio of protein expression alterations, the alterations in the ocular tissues were in the following order: the cornea, conjunctiva, uvea, sclera, and retina.

Tracking micro-optical resonances for identifying and sensing novel procaspase-3 protein marker released from cell cultures in response to toxins.

The response of cells to toxins is commonly investigated by detecting intracellular markers for cell death, such as caspase proteins. This requires the introduction of labels by the permeabilization or complete lysis of cells. Here we introduce a non-invasive tool for monitoring a caspase protein in the extracellular medium. The tool is based on highly sensitive optical micro-devices, referred to as whispering-gallery mode biosensors (WGMBs). WGMBs are functionalized with antibodies for the specific and label-free detection of procaspase-3 released from human embryonic kidney HEK293 and neuroglioma H4 cells after introducing staurosporine and rotenone toxins, respectively. Additional tests show that the extracellular accumulation of procaspase-3 is concomitant with a decrease in cell viability. The hitherto unknown release of procaspase-3 from cells in response to toxins and its accumulation in the medium is further investigated by Western blot, showing that the extracellular detection of procaspase-3 is interrelated with cytotoxicity of alpha-synuclein protein (aSyn) overexpressed in H4 cells. These studies provide evidence for procaspase-3 as a novel extracellular biomarker for cell death, with applications in cytotoxicity tests. Such WGMBs could be applied to further identify as-yet unknown extracellular biomarkers using established antibodies against intracellular antigens.

Development and psychometric testing of the Protective Reasons Against Suicide Inventory for assessing older Chinese-speaking outpatients in primary care settings.

AIM: To develop and psychometrically test the Protective Reasons against Suicide Inventory among older Chinese-speaking outpatients. BACKGROUND: Tools currently exist to test reasons for living among individuals of all ages in western countries, but few are available to assess older adults' protective reasons against suicide in Asia. DESIGN: A cross-sectional survey to investigate protective reasons against suicide among older Chinese-speaking outpatients. METHODS: The Protective Reasons against Suicide Inventory was developed based on individual interviews with 83 older outpatients in Taiwan, the literature and the authors' clinical experiences. The resulting Inventory was examined in 2013 for content validity, face validity, construct validity, criterion-related validity, internal consistency reliability and test-retest reliability. RESULTS: The Inventory had excellent content validity and face validity. Factor analysis yielded a seven-factor solution, accounting for 87·7% of the variance. Scores on the global Inventory and its subscales tended to be higher in outpatients diagnosed without suicidal ideation than in outpatients diagnosed with suicidal ideation, indicating good criterion validity. Inventory reliability and the intraclass correlation coefficient were satisfactory. CONCLUSIONS: The Protective Reasons against Suicide Inventory can be completed in 5 minutes and is perceived as easy to complete. Moreover, the Inventory yielded highly acceptable parameters for validity and reliability. The Protective Reasons against Suicide Inventory can be used to assess older Chinese-speaking outpatients for factors that protect them from attempting suicide.

Proteinuria can predict prognosis after liver transplantation.

BACKGROUND: Proteinuria is a manifestation of renal dysfunction and it has been demonstrated to be a significant prognostic factor in various clinical situations. The study was designed to analyze prognosis of patients receiving liver transplantation as well as to determine predictive performance of perioperative proteinuria. METHODS: We retrospectively reviewed data of patients who had received a liver transplant in a medical center between 2002 and 2010. Demographic information and clinical characteristic parameters were recorded on the day of intensive care unit admission before operation and on postoperative days 1, 7, and 14. RESULTS: Among a total of 323 patients, in-hospital mortality and 90-day mortality rates were 13.0 % (42/323) and 14.2 % (46/323), respectively. Patients with proteinuria on admission had higher rates of acute kidney injury (26.8 % vs. 8.8 %, p < 0.001), severe infection episodes (48.8 % vs. 30.7 %, p = 0.023), hospital death (31.1 % vs. 10.1 %, p < 0.001), and 90-day mortality (37.7 % vs. 10.9 %, p < 0.001). Multivariate analysis showed that proteinuria on admission and Sequential Organ Failure Assessment (SOFA) score were independent predictors of in-hospital mortality. The discriminatory ability of proteinuria plus SOFA was even better than that of SOFA alone, especially on postoperative day 1. CONCLUSIONS: The presence of proteinuria before liver transplantation is supposed to be recognized as a negative predictor for in-hospital survival. Moreover, the presence of proteinuria after liver transplantation can assist in the early prediction of poor short-term prognosis for patients receiving liver transplantation.

Identification of Up- and Down-Regulated Proteins in Pemetrexed-Resistant Human Lung Adenocarcinoma: Flavin Reductase and Calreticulin Play Key Roles in the Development of Pemetrexed-Associated Resistance.

Drug resistance is one of the major causes of cancer chemotherapy failure. In the current study, we used a pair of lung adenocarcinoma cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a model to monitor resistance-dependent cellular responses and identify potential therapeutic targets. By means of 2D differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we investigated the global protein expression alterations induced by pemetrexed treatment and resistance. The proteomic result revealed that pemetrexed exposure obviously altered the expression of 81 proteins in the A549 cells, whereas no significant response was observed in the similarly treated A549/PEM cells, hence implying an association between these proteins and the drug-specific response. Moreover, 72 proteins including flavin reductase and calreticulin demonstrated differential expression between the A549 and A549/PEM cells, indicating baseline resistance. Additional tests employed siRNA silencing, protein overexpression, cell viability analysis, and analysis of apoptosis to examine and confirm the potency of flavin reductase and calreticulin proteins in the development of pemetrexed resistance. In summary, by using a proteomic approach, we identified numerous proteins, including flavin reductase and calreticulin, involved in pemetrexed drug resistance-developing mechanisms. Our results provide useful diagnostic markers and therapeutic candidates for pemetrexed-resistant lung cancer treatment.

Protective factors against suicide among young-old Chinese outpatients.

BACKGROUND: Suicide is common among the elderly worldwide. However, no literature could be found on the beliefs/expectations that protect young-old people from attempting suicide. The purpose of this study was to explore young-old outpatients' reasons for not killing themselves in Taiwan. METHOD: Data for this qualitative descriptive study were extracted from a large research series. From the 83 elderly outpatients in the original sample, 31 were chosen for this study because they were young-old (65-74 years old) and from two randomly selected medical centers in northern Taiwan. Data on participants' reasons for not killing themselves in unhappy situations were collected in individual interviews using a semi-structured guide and analyzed by content analysis. RESULTS: Analysis of interview data identified six major themes: satisfied with one's life, suicide cannot resolve problems, fear of humiliating one's children, religious beliefs, never thought about suicide, and living in harmony with nature. CONCLUSION: These identified protective factors (reasons for living) could be added to suicide-prevention programs for the elderly. Our findings may also serve as a reference for geriatric researchers in western countries with increasing numbers of elderly ethnic minority immigrants.

Perceived reasons for, opinions about, and suggestions for elders considering suicide: elderly outpatients' perspectives.

OBJECTIVES: The purposes of this study were to explore elderly outpatients' perceived reasons for, opinions of, and suggestions for elderly people considering suicide in Taiwan. METHOD: Elderly outpatients (N = 83) were recruited in 2011-2012 by convenience sampling from three randomly selected medical centers in Taiwan. Data were collected in individual interviews using a semi-structured guide and analyzed by content analysis. RESULTS: Findings revealed that most participants had heard of elderly suicide, with television news as the main source for their information. Their opinions about elderly suicide reflected judgmental attitudes, negative emotional reactions, expectations of social welfare, and could happen after losing one's meaning in life. Their suggestions for elderly people considering suicide fell into four major themes: give up suicidal ideas, seek help, enhance social welfare, and attend religious activities. CONCLUSION: Since television news was the main source for participants' information about elderly suicide, this mass medium should be used in suicide prevention to disseminate suicide knowledge, increase access to help, and strengthen suicide-protective factors among the elderly. Furthermore, no participants mentioned depression as a reason for attempted or completed suicide among older people despite depression being a well-known suicide-risk factor. Future suicide-prevention programs should emphasize the role of depression in suicide among older people. Participants also did not suggest that older people considering suicide seek help from the health system. Thus, older people should be educated about the role of the health system in suicide prevention and trained as gatekeepers to recognize signs of suicide ideation and respond appropriately.