Prevalence and risk factors of post-traumatic stress disorder among elderly survivors six months after the 2008 Wenchuan earthquake in China.

BACKGROUND: Several studies indicate that older age is a risk factor for probable post-traumatic stress disorder (PTSD). However, evidence on the prevalence and risk factors for elderly disaster survivors is limited. METHODS: Multi-stage stratified sampling was applied in this cross-sectional study. The Revised Version of the Impact of Event Scale (IES-R) was used to evaluate symptoms of PTSD. Chi-squared test was used for univariable analysis of prevalence of probable PTSD by possible determinants. Multivariable logistic regression analysis was utilized to further explore risk factors for PTSD. RESULTS: 427 elderly survivors age 60 or older participated. The prevalence of probable PTSD was 40.5, 36.3, and 21.5% according to a cut off score of the IES-R of 33, 35, and 2 points on average across items, respectively. In multivariable logistic regression, elderly survivors with a higher number of diagnosed chronic illnesses were more likely to be screened positive for PTSD and those with a greater number of family members living in the same home were less likely to be classified as having probable PTSD for all cut off scores. Elderly survivors with improved economic status and those with primary school or lower education were more often estimated to have probable PTSD with a cut off score of 35 and 2 points on average. CONCLUSIONS: Elderly survivors in a high impact area following a major earthquake are at high risk for developing PTSD. Those who live alone and report pre-existing chronic illness are particularly vulnerable.

Improvement of a miRNA inhibitor by intracellular selection.

Sequences surrounding the miRNA binding domain of the miRNA inhibitor LidNA were selected intracellularly. The library was transfected into cells, and then, inhibitors that were associated with argonaute 2 were selected. The potent inhibitors were slowly degraded intracellularly, while the lower-activity inhibitors were rapidly degraded. A combination of the selected sequences surrounding the miRNA binding domain enhanced miRNA inhibitory activity. ABBREVIATIONS: LidNA: DNA that puts a lid on miRNA function; LNA: locked nucleic acid; Ago2: argonaute 2; LNA: locked nucleic acid.

Structural improvement of LidNA: delta-type LidNA is a potent miRNA inhibitor constructed with unmodified DNA.

Many miRNA inhibitors have been developed, including chemically modified oligonucleotides, such as 2'-O-methylated RNA and locked nucleic acid (LNA). Unmodified DNA has not yet been reported as a miRNA inhibitor due to relatively low DNA/miRNA binding affinity. We designed a structured DNA, LidNA, which was constructed with unmodified DNA, consisting of a complementary sequence to the target miRNA flanked by two structured DNA regions, such as double-stranded DNA. LidNA inhibited miRNA activity more potently than 2'-O-methylated RNA or LNA. To optimize LidNA, two double-stranded regions were joined, causing the molecule to assume a delta-like shape, which we termed delta-type LidNA. Delta-type LidNAs were developed to target endogenous and exogenous miRNAs, and exhibited potent miRNA inhibitory effects with a duration of at least 10 days. Delta-type LidNA-21, which targeted miR-21, inhibited the growth of cancer cell lines. This newly developed LidNA could contribute to miRNA studies across multiple fields.Abbreviations: LidNA: DNA that puts a lid on miRNA function; LNA: locked nucleic acid; 3'-UTR: 3'-untranslated regions; RISC: RNA-induced silencing complex; MBL: Molecular beacon-like LidNA; YMBL: Y-type molecular beacon-like LidNA; TDMD: target-directed microRNA degradation.

Examining patterns of cognitive impairment among homeless and precariously housed urban youth.

INTRODUCTION: Homeless and precariously housed young people are a complex, vulnerable population frequently perceived as being difficult to engage in health and social services. Although unrecognized deficits in cognitive functioning may adversely affect their ability to access assistance and meaningfully participate in programming, few researchers have examined these deficits. The purpose of this study was to examine the extent of global and domain-specific cognitive impairment of street involved young people. METHODS: A retrospective chart review was conducted using intake data from 494 clients (64% male; average age of 21 years) enrolled in a community-based inner city mental health program in Vancouver, Canada. Descriptive statistics were used to examine performance on six cognitive domains for a subsample (N = 44) referred for neuropsychological evaluation and bivariate statistics were used to compare youth who were and were not referred. RESULTS: Cognitive impairment was evident in 80% of referred clients, with the most frequent difficulties involving attention and processing speed. Approximately 51% of clients referred for testing did not have more than a grade ten education and only 5% received government support for those with significant disabilities. Apart from alcohol use disorder, no significant differences were identified on sociodemographic and mental health variables between groups of referred and non-referred clients. CONCLUSIONS: Significant cognitive impairment was found in 80% of the young people referred for neuropsychological evaluation. This level of impairment combined with high levels of early school exiting and low levels of government support highlight the need for targeted screening to facilitate early identification and intervention.

"I'm Just Forgetting and I Don't Know Why": Exploring How People Living With HIV-Associated Neurocognitive Disorder View, Manage, and Obtain Support for Their Cognitive Difficulties.

HIV-associated neurocognitive disorder (HAND) is common, but the lived experience of HAND is not well-understood. In this descriptive qualitative study, we explored how adults with HAND view, manage, and obtain support for cognitive difficulties. We interviewed 25 participants (20% female; median age = 51 years) who were diagnosed with HAND using neuropsychological assessment and a clinical interview. Semistructured interviews, co-developed with community members living with HIV, focused on how cognitive difficulties manifested and progressed, impacted well-being, and were discussed with others. We analyzed interview transcripts using a team-based, thematic approach. Participants described concentration, memory, and multitasking difficulties that fluctuated over time, as well as potential risk factors, management strategies, and psychosocial consequences. They reported they seldom discussed cognitive impairment with health care professionals, and that receiving a HAND diagnosis was validating, informative, yet somewhat disconcerting. Conversations between health care professionals and people living with HIV about HAND may provide opportunities for education, assessment, and support.

Probable Post-Traumatic Stress Disorder and Its Predictors in Disaster-Bereaved Survivors: A Longitudinal Study After the Sichuan Earthquake.

This study examined the trajectory of probable PTSD prevalence and severity, and analyzed the predictors for PTSD severity in bereaved survivors at 6 months and 18 months after the 2008 Sichuan earthquake. This was a longitudinal study with 226 bereaved survivors sampled at 6 months and 18 months post-earthquake. The instrument used in the study was the revised version of the Impact of Event Scale. The results showed that the prevalence of probable PTSD in bereaved survivors decreased significantly from 38.9% at 6 months to 16.8% at 18 months post-earthquake. Loss of a child, being directly exposed to the death of family members and property loss during the earthquake, and mental health services utilization after the earthquake were significant predictors for PTSD severity at both assessments. These findings can contribute to post-disaster psychological rescue work. The bereaved survivors at high risk for more severe PTSD should be particularly targeted.

What was the role of nurses during the 2011 great East earthquake of Japan? An integrative review of the Japanese literature.

BACKGROUND: An earthquake and tsunami hit the east coast of Japan on March 11, 2011. Nurses were actively involved in the health response to this disaster and, subsequently, many authors have reported on the role nurses played in these efforts in Japanese nursing professional journals. Aim To describe the role of nurses who assisted in the 2011 Great East Earthquake of Japan by reviewing Japanese literature and reporting the findings in English. METHOD: This research used an integrative literature review methodology. Manuscripts were obtained from the Japanese database Ichushi Ver. 5 (Japan Medical Abstracts Society, Tokyo, Japan). A total of 44 manuscripts were identified and included in a thematic analysis. RESULTS: Three main themes were identified: (1) nursing roles, (2) specialized nursing roles, and (3) preparedness education. Nurses fulfilled different roles in the period after the disaster (ie, as a clinician, a communicator, a leader, and a provider of psychosocial support). Additionally, the specialized nurse role was identified, along with the need for preparedness education to support the nurse's role in a disaster. CONCLUSION: The understanding of the role of nurses in disasters is expanding. There is a need to further explore the roles of specialized nurses in disasters. Further disaster education opportunities should be available as a part of continuing education for all nurses. Radiation aspects of disaster assistance should be included in disaster education programs where there are radio-nuclear hazards present in the environment.

Cognitive Impairment in Marginally Housed Youth: Prevalence and Risk Factors.

Objective: Homeless and marginally housed youth are particularly vulnerable members of society, and are known to experience numerous health problems, including psychiatric illness, substance use, and viral infection. Despite the presence of these risk factors for cognitive compromise, there is limited research on the cognitive functioning of homeless and marginally housed youth. The present study examines the degree and pattern of cognitive impairment and associations with key risk factors in a sample of marginally housed young adults. Method: Participants (N = 101) aged 20-29 years old were recruited from single-room occupancy hotels, and underwent cognitive, psychiatric, neurological, and serological assessments. Results: Forty percent of participants were identified as mildly cognitively impaired across multiple domains, and 16% were moderately-severely impaired. Deficits in memory and attention were most prevalent, while impairments in inhibitory control/processing speed and cognitive flexibility were also present but tended to be less severe. Developmental and historical factors (premorbid intellectual functioning, neurological soft signs, earlier exposure to and longer duration of homelessness or marginal housing), as well as current health risks (stimulant dependence and hepatitis C exposure), were associated with cognitive impairment. Conclusions: The strikingly high rate of cognitive impairment in marginally housed young adults represents a major public health concern and is likely to pose a significant barrier to treatment and rehabilitation. These results suggest that the pathway to cognitive impairment involves both developmental vulnerability and modifiable risk factors. This study highlights the need for early interventions that address cognitive impairment and risk factors in marginalized young people.

Education and research on disaster nursing in Japan.

The educational and research program "Disaster Nursing in a Ubiquitous Society in Japan" has facilitated the development of various networks for disaster nursing, disaster nursing care strategies, and disaster nursing education. Replication of these activities related to disaster nursing are encouraged globally to improve disaster outcomes.

Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation.

PURPOSE: We developed an effective immunotherapy, which could induce antitumor immune responses against shared and unique tumor antigens expressed in autologous tumors. EXPERIMENTAL DESIGN: Intratumoral administration of dendritic cells is one of the individualized immunotherapies; however, the antitumor activity is relatively weak. In this study, we attempted to enhance the antitumor efficacy of the i.t. dendritic cell administration by combining dendritic cells stimulated with Bacillus Calmette-Guerin cell wall skeleton (BCG-CWS) additionally with cryoablative pretreatment of tumors and analyzed the therapeutic mechanisms. RESULTS: These two modifications (cryoablation of tumors and BCG-CWS stimulation of dendritic cells) significantly increases the antitumor effect on both the treated tumor and the untreated tumor, which was distant at the opposite side, in a bilateral s.c. murine CT26 colon cancer model. Further analysis of the augmented antitumor effects revealed that the cryoablative pretreatment enhances the uptake of tumor antigens by the introduced dendritic cells, resulting in the induction of tumor-specific CD8(+) T cells responsible for the in vivo tumor regression of both treated and remote untreated tumors. This novel combination i.t. dendritic cell immunotherapy was effective against well-established large tumors. The antitumor efficacy was further enhanced by depletion of CD4(+)CD25(+)FoxP3(+) regulatory T cells. CONCLUSIONS: This novel dendritic cell immunotherapy with i.t. administration of BCG-CWS-treated dendritic cells following tumor cryoablation could be used for the therapy of cancer patients with multiple metastases.

Dietary fat content modulates the hypolipidemic effect of dietary inulin in rats.

SCOPE: Dietary fat content (low versus high fat) may modulate the serum lipid-lowering effect of high-performance (HP)-inulin. This study investigated the effect of dietary HP-inulin on metabolism in rats fed a low- or high-fat diet. METHODS AND RESULTS: Rats were fed a diet of 5% fat with 5% cellulose or 5% HP-inulin (average degree of polymerization = 24) (low-fat diet) or of 20% fat with 5% cellulose or 5% HP-inulin (high-fat diet) for 28 days. Total, HDL, and non-HDL cholesterols, and triglyceride concentrations in the serum were measured along with total lipid content of liver and feces. Hepatic triglyceride and cholesterol, and fecal neutral and acidic sterol concentrations in total lipid were assessed. In addition, cecum SCFA levels and bacterial profiles were determined. The hypolipidemic effect of HP-inulin differed depending on dietary fat content (5% versus 20%). Specifically, 5% inulin instead of cellulose in a semi-purified diet significantly reduced serum lipid levels in rats fed a high-fat diet, which was strongly associated with increased total lipid and neutral sterol excretion. CONCLUSION: Dietary fat content modulates the hypolipidemic effect of dietary inulin.

Development of disaster nursing in Japan, and trends of disaster nursing in the world.

AIM: The aims of this paper are to describe what Japanese nurses have learned and contributed to disaster nursing development, and to review trends of disaster nursing in the world. METHODS: The content of the paper is based on literature reviews. The description of the paper is also based on experiences by author. RESULTS: Through experiences among Japanese nurses related to Hanshin-Awaji Earthquake in Japan, development of nursing support network, academic societies of disaster nursing, nursing care provision system were accomplished. Disaster nursing education at undergraduate and graduate programs and continuing training have been started. Descriptive research and evaluation research have been conducted in the world. CONCLUSION: Disaster nursing is one domain of nursing discipline generated from demands in reality and society. More research and capacity building related to disaster nursing are needed while facilitating development of networking and collaboration among relevant organizations.

Crystallographic evidence that the dinuclear copper center of tyrosinase is flexible during catalysis.

At high resolution, we determined the crystal structures of copper-bound and metal-free tyrosinase in a complex with ORF378 designated as a "caddie" protein because it assists with transportation of two CuII ions into the tyrosinase catalytic center. These structures suggest that the caddie protein covers the hydrophobic molecular surface of tyrosinase and interferes with the binding of a substrate tyrosine to the catalytic site of tyrosinase. The caddie protein, which consists of one six-strandedbeta-sheet and one alpha-helix, has no similarity with all proteins deposited into the Protein Data Bank. Although tyrosinase and catechol oxidase are classified into the type 3 copper protein family, the latter enzyme lacks monooxygenase activity. The difference in catalytic activity is based on the structural observations that a large vacant space is present just above the active center of tyrosinase and that one of the six His ligands for the two copper ions is highly flexible. These structural characteristics of tyrosinase suggest that, in the reaction that catalyzes the ortho-hydroxylation of monophenol, one of the two Cu(II) ions is coordinated by the peroxide-originated oxygen bound to the substrate. Our crystallographic study shows evidence that the tyrosinase active center formed by dinuclear coppers is flexible during catalysis.

Memory interference in multiple sclerosis.

To explore verbal memory impairments associated with multiple sclerosis (MS), we compared proactive and retroactive interference effects on the California Verbal Learning Test (CVLT; Delis et al., 1987) in a sample of 83 community-residing individuals with MS and 80 healthy participants. Individuals with MS demonstrated normal accumulation of proactive interference (PI), but attenuated release from PI relative to healthy individuals. Furthermore, accumulation of retroactive interference (RI) at short-delay free recall (SDFR) was intensified for those with MS as compared to healthy participants. Interestingly, accumulation of RI predicted long-term memory (LTM) only for participants with MS. These findings suggest that individuals with MS may experience particular difficulty when required to use semantic properties of information flexibly to facilitate verbal LTM.

An efficient method for the overexpression and purification of active tyrosinase from Streptomyces castaneoglobisporus.

The melanin-synthesizing gene operon cloned from Streptomyces castaneoglobisporus HUT6202 consists of two genes, designated tyrC and orf378, which encode apotyrosinase (TYRC) and its activator protein (ORF378), respectively. We have suggested that ORF378 may facilitate the incorporation of Cu(II) into apotyrosinase to express tyrosinase activity. To overproduce ORF378 and TYRC in Escherichia coli BL21(DE3)-pLysS, tyrC, and orf378 were independently but not polycistronically placed under the control of a T7 promoter in a vector, pET-21a(+). His(6)-tagged TYRC and His(6)-tagged ORF378 were simultaneously overproduced in an E. coli strain harboring a plasmid, designated pET-mel2, and the two proteins were co-purified with a Ni(II)-bound affinity column. Gel filtration analysis revealed that the two proteins form a heterodimer complex. The complexed protein was retrieved at a high efficiency (11 mg/L). To obtain an active TYRC, which is a Cu(II)-bound form of tyrosinase, we constructed pET-mel3 that carries orf378 without His(6)-tag and His(6)-tagged tyrC. After the cell-free extract from E. coli harboring pET-mel3 was subjected to Cu(II)-bound affinity column chromatography, His(6)-tagged TYRC, eluted from the column, exhibited the tyrosinase activity. The k(cat) and K(m) values for l-3,4-dihydroxyphenylalanine (l-DOPA) of His(6)-tagged TYRC, which catalyzes the oxidation of l-DOPA to dopaquinone, were 880+/-80s(-1) and 8.1+/-0.9 mM, respectively.

Identification of bladder cancer antigens recognized by IgG antibodies of a patient with metastatic bladder cancer.

To identify tumor antigens useful for the diagnosis and treatment of patients with bladder cancer, a lambda phage cDNA library constructed from a high-grade bladder cancer cell line was screened with autologous serum from a patient with metastatic bladder cancer. Forty-eight distinct antigens were isolated. By evaluating the immunogenicity and the tissue-specific expression, KU-BL-1 and KU-BL-2 were identified as immunogenic antigens with restricted tissue expression. KU-BL-1 was found to be a putative human lipoic acid synthetase with a metal-binding site, CXXXCXXC, that was expressed in bladder cancer cell lines and most bladder cancer tissues, as well as normal bladder mucosa and testis tissues. Immunoglobulin (Ig)G antibody to KU-BL-1 was detected in 2 of 28 patients with bladder cancer, but not in 30 healthy individuals. KU-BL-2 was found to be a putative human kelch-like protein that was homologous to Drosophila kelch, with a BTB/POZ domain and kelch repeats. KU-BL-2 was expressed in bladder cancer cell lines, most bladder cancer tissues, testis and heart, but not in normal bladder mucosa. IgG antibody to KU-BL-2 was detected in 8 of 28 patients with bladder cancer, but not in 16 healthy individuals. Tumor reactive T cells were induced from peripheral blood mononuclear cells (PBMC) by stimulation with one of the HLA-A24 binding KU-BL-2 peptides. Therefore, KU-BL-1 and KU-BL-2, which showed preferential expression in bladder cancer with restricted expression in normal tissues, as well as immunogenicity in multiple patients with bladder cancer, may be useful for the development of diagnostic and therapeutic methods for patients with bladder cancer.