Intraoperative near-infrared fluorescent imaging during robotic operations.

PubMed

Macedo, Antonio Luiz de Vasconcellos; Schraibman, Vladimir

2016-01-01

The intraoperative identification of certain anatomical structures because they are small or visually occult may be challenging. The development of minimally invasive surgery brought additional difficulties to identify these structures due to the lack of complete tactile sensitivity. A number of different forms of intraoperative mapping have been tried. Recently, the near-infrared fluorescence imaging technology with indocyanine green has been added to robotic platforms. In addition, this technology has been tested in several types of operations, and has advantages such as safety, low cost and good results. Disadvantages are linked to contrast distribution in certain clinical scenarios. The intraoperative near-infrared fluorescent imaging is new and promising addition to robotic surgery. Several reports show the utility of this technology in several different procedures. The ideal dose, time and site for dye injection are not well defined. No high quality evidence-based comparative studies and long-term follow-up outcomes have been published so far. Initial results, however, are good and safe. RESUMO A identificação intraoperatória de certas estruturas anatômicas, por seu tamanho ou por elas serem ocultas à visão, pode ser desafiadora. O desenvolvimento da cirurgia minimamente invasiva trouxe dificuldades adicionais, pela falta da sensibilidade tátil completa. Diversas formas de detecção intraoperatória destas estruturas têm sido tentadas. Recentemente, a tecnologia de fluorescência infravermelha com verde de indocianina foi associada às plataformas robóticas. Além disso, essa tecnologia tem sido testada em uma variedade de cirurgias, e suas vantagens parecem estar ligadas a baixo custo, segurança e bons resultados. As desvantagens estão associadas à má distribuição do contraste em determinados cenários. A imagem intraoperatória por fluorescência infravermelha é uma nova e promissora adição à cirurgia robótica. Diversas séries mostram a utilidade da tecnologia em diferentes procedimentos. Dose ideal, local e tempo da injeção do corante ainda não estão bem estabelecidos. Estudos comparativos de alta qualidade epidemiológica baseados em evidência ainda não estão disponíveis. No entanto, os resultados iniciais são bons e seguros.

Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D.

PubMed

Abbink, Peter; Lemckert, Angelique A C; Ewald, Bonnie A; Lynch, Diana M; Denholtz, Matthew; Smits, Shirley; Holterman, Lennart; Damen, Irma; Vogels, Ronald; Thorner, Anna R; O'Brien, Kara L; Carville, Angela; Mansfield, Keith G; Goudsmit, Jaap; Havenga, Menzo J E; Barouch, Dan H

2007-05-01

Recombinant adenovirus serotype 5 (rAd5) vector-based vaccines are currently being developed for both human immunodeficiency virus type 1 and other pathogens. The potential limitations associated with rAd5 vectors, however, have led to the construction of novel rAd vectors derived from rare Ad serotypes. Several rare serotype rAd vectors have already been described, but a detailed comparison of multiple rAd vectors from subgroups B and D has not previously been reported. Such a comparison is critical for selecting optimal rAd vectors for advancement into clinical trials. Here we describe the construction of three novel rAd vector systems from Ad26, Ad48, and Ad50. We report comparative seroprevalence and immunogenicity studies involving rAd11, rAd35, and rAd50 vectors from subgroup B; rAd26, rAd48, and rAd49 vectors from subgroup D; and rAd5 vectors from subgroup C. All six rAd vectors from subgroups B and D exhibited low seroprevalence in a cohort of 200 individuals from sub-Saharan Africa, and they elicited Gag-specific cellular immune responses in mice both with and without preexisting anti-Ad5 immunity. The rAd vectors from subgroup D were also evaluated using rhesus monkeys and were shown to be immunogenic after a single injection. The rAd26 vectors proved the most immunogenic among the rare serotype rAd vectors studied, although all rare serotype rAd vectors were still less potent than rAd5 vectors in the absence of anti-Ad5 immunity. These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world.

Thermodynamic and classical instability of AdS black holes in fourth-order gravity

NASA Astrophysics Data System (ADS)

Myung, Yun Soo; Moon, Taeyoon

2014-04-01

We study thermodynamic and classical instability of AdS black holes in fourth-order gravity. These include the BTZ black hole in new massive gravity, Schwarzschild-AdS black hole, and higher-dimensional AdS black holes in fourth-order gravity. All thermo-dynamic quantities which are computed using the Abbot-Deser-Tekin method are used to study thermodynamic instability of AdS black holes. On the other hand, we investigate the s-mode Gregory-Laflamme instability of the massive graviton propagating around the AdS black holes. We establish the connection between the thermodynamic instability and the GL instability of AdS black holes in fourth-order gravity. This shows that the Gubser-Mitra conjecture holds for AdS black holes found from fourth-order gravity.

Emergence of a new human adenovirus type 4 (Ad4) genotype: identification of a novel inverted terminal repeated (ITR) sequence from majority of Ad4 isolates from US military recruits.

PubMed

Houng, Huo-Shu H; Clavio, Sarah; Graham, Katherine; Kuschner, Robert; Sun, Wellington; Russell, Kevin L; Binn, Leonard N

2006-04-01

Ad4 is the principal etiological agent of acute respiratory disease (ARD) in the US military. Discovery of the novel 208bp inverted terminal repeated (ITR) sequence from a recent Ad4 Jax78 field isolate was totally distinct from the analogous 116bp ITR of Ad4 prototype. To investigate the origin and distribution of the novel Ad4 ITR sequence from ARD infections. Direct sequencing of ligated Ad ITR termini. The new Ad4 ITR was highly homologous with the ITRs of human Ad subgroup B. The left post-ITR region of Ad4 Jax78 was found to be highly homologous to the corresponding region of subgroup B Ads: 81% for Ad11 and 98% for Ad3 and Ad7. The right post-ITR region of Ad4 Jax78 contained a truncated classic ITR of the Ad4 prototype. The Ad4 Jax78 ITR most likely evolved from Ad4 prototype by substituting the Ad4 prototype ITR with the subgroup B Ads ITR. The ITR-based PCR assays developed from this study can be used to distinguish the new Ad4 genotype from the classical Ad4 prototype. The new Ad4 genotype was first detected in 1976 from Georgia, USA, and is the main causative agent of ARD infections in US military population.

Angiolymphatic invasion as a prognostic fator in resected N0 pancreatic adenocarcinoma.

PubMed

Almeida, Ricardo Vitor Silva de; Pacheco, Adhemar Monteiro; Silva, Rodrigo Altenfelder; Moricz, André de; Campos, Tércio de

2017-01-01

Pancreatic adenocarcinoma remains one of the worst digestive cancers. Surgical resection is the main target when treating a patient with curative intent. To assess angiolymphatic invasion as a prognostic factor in resected pN0 pancreatic cancer. Thirty-eight patients were submitted to pancreatoduodenectomy due to head pancreatic cancer. Tumor size, margins, lymph nodes, pTNM staging, angiolymphatic and perineural invasion were described in the pathologists' reports. Most patients were female. Overall median survival was 13 months. Gemcitabine was the regimen of choice for chemotherapy in selected patients; however, it did not improve overall survival. pR0 resection had better survival compared with pR1. Within the pN0 group, survival was significantly better in patients without angiolymphatic invasion. Angiolymphatic invasion in N0 pancreatoduodenectomy can be demonstrated by the Hematoxylin-Eosin stain and may predict a poor prognosis factor for those patients. Adenocarcinoma pancreático continua sendo um dos piores cânceres do aparelho digestivo. A ressecção cirúrgica é o principal objetivo quando se trata de intenção curativa. Avaliar a invasão angiolinfática como um fator prognóstico no câncer da cabeça do pâncreas ressecado pN0. Trinta e oito pacientes foram submetidos a duodenopancreatectomia por câncer da cabeça do pâncreas. Tamanho do tumor, margens, linfonodos, estadiamento pTNM, invasão angiolinfática e perineural foram descritos nos laudos anatomopatológicos. A maioria foi de mulheres. A sobrevida mediana global foi de 13 meses. Gencitabina foi a droga de escolha para quimioterapia nos pacientes selecionados, entretanto não aumentou a sobrevida global. Pacientes com ressecção pR0 tiveram sobrevida global superior quando comparados com ressecção pR1. Dentro do grupo de pacientes com pN0, a sobrevida foi significativamente melhor no grupo de pacientes que não apresentavam invasão angiolinfática. A invasão angiolinfática da duodenopancreatectomia N0 pode ser demonstrada utilizando apenas a hematoxilina-eosina e pode predizer prognóstico ruim para estes pacientes.

Disrupted adenovirus-based vaccines against small addictive molecules circumvent anti-adenovirus immunity.

PubMed

De, Bishnu P; Pagovich, Odelya E; Hicks, Martin J; Rosenberg, Jonathan B; Moreno, Amira Y; Janda, Kim D; Koob, George F; Worgall, Stefan; Kaminsky, Stephen M; Sondhi, Dolan; Crystal, Ronald G

2013-01-01

Adenovirus (Ad) vaccine vectors have been used for many applications due to the capacity of the Ad capsid proteins to evoke potent immune responses, but these vectors are often ineffective in the context of pre-existing anti-Ad immunity. Leveraging the knowledge that E1(-)E3(-) Ad gene transfer vectors are potent immunogens, we have developed a vaccine platform against small molecules by covalently coupling analogs of small molecules to the capsid proteins of disrupted Ad (dAd5). We hypothesized that the dAd5 platform would maintain immunopotency even in the context of anti-Ad neutralizing antibodies. To test this hypothesis, we coupled cocaine and nicotine analogs, GNE and AM1, to dAd5 capsid proteins to generate dAd5GNE and dAd5AM1, respectively. Mice were pre-immunized with Ad5Null, resulting in high titer anti-Ad5 neutralizing antibodies comparable to those observed in the human population. The dAd5GNE and dAd5AM1 vaccines elicited high anti-cocaine and anti-nicotine antibody titers, respectively, in both naive and Ad5-immune mice, and both functioned to prevent cocaine or nicotine from reaching the brain of anti-Ad immune mice. Thus, disrupted Ad5 evokes potent humoral immunity that is effective in the context of pre-existing neutralizing anti-Ad immunity, overcoming a major limitation for current Ad-based vaccines.

Constructing the AdS dual of a Fermi liquid: AdS black holes with Dirac hair

NASA Astrophysics Data System (ADS)

Čubrović, Mihailo; Zaanen, Jan; Schalm, Koenraad

2011-10-01

We provide evidence that the holographic dual to a strongly coupled charged Fermi liquid has a non-zero fermion density in the bulk. We show that the pole-strength of the stable quasiparticle characterizing the Fermi surface is encoded in the AdS probability density of a single normalizable fermion wavefunction in AdS. Recalling Migdal's theorem which relates the pole strength to the Fermi-Dirac characteristic discontinuity in the number density at ω F , we conclude that the AdS dual of a Fermi liquid is described by occupied on-shell fermionic modes in AdS. Encoding the occupied levels in the total spatially averaged probability density of the fermion field directly, we show that an AdS Reissner-Nordström black holein a theory with charged fermions has a critical temperature, at which the system undergoes a first-order transition to a black hole with a non-vanishing profile for the bulk fermion field. Thermodynamics and spectral analysis support that the solution with non-zero AdS fermion-profile is the preferred ground state at low temperatures.

Localization of neutralization epitopes on adenovirus fiber knob from species C.

PubMed

Lang, Shuai; Wang, Lizheng; Wang, Zixuan; Zhu, Rui; Yan, Jingyi; Wang, Baoming; Wu, Jiaxin; Zhang, Haihong; Wu, Hui; Zhou, Yan; Kong, Wei; Yu, Bin; Yu, Xianghui

2016-04-01

Although potential neutralization epitopes on the fiber knob of adenovirus (AdV) serotype 2 (Ad2) and Ad5 have been revealed, few studies have been carried out to identify neutralization epitopes on the knob from a broader panel of AdV serotypes. In this study, based on sequence and structural analysis of knobs from Ad1, Ad2, Ad5 and Ad6 (all from species C), several trimeric chimeric knob proteins were expressed in Escherichia coli to identify the locations of neutralization epitopes on the knobs by analysing their reactivity with mouse and rabbit polyclonal sera raised against AdVs and human sera with natural AdV infection. The dominant neutralization epitopes were located mainly in the N-terminal part of knobs from Ad1, Ad2 and Ad5, but they seemed to be located in the C-terminal part of the Ad6 knob, with some individual differences in rabbit and human populations. Our study adds to our understanding of humoral immune responses to AdVs and will facilitate the construction of more desirable capsid-modified recombinant Ad5 vectors.

Disrupted Adenovirus-Based Vaccines Against Small Addictive Molecules Circumvent Anti-Adenovirus Immunity

PubMed Central

De, Bishnu P.; Pagovich, Odelya E.; Hicks, Martin J.; Rosenberg, Jonathan B.; Moreno, Amira Y.; Janda, Kim D.; Koob, George F.; Worgall, Stefan; Kaminsky, Stephen M.; Sondhi, Dolan

2013-01-01

Abstract Adenovirus (Ad) vaccine vectors have been used for many applications due to the capacity of the Ad capsid proteins to evoke potent immune responses, but these vectors are often ineffective in the context of pre-existing anti-Ad immunity. Leveraging the knowledge that E1−E3− Ad gene transfer vectors are potent immunogens, we have developed a vaccine platform against small molecules by covalently coupling analogs of small molecules to the capsid proteins of disrupted Ad (dAd5). We hypothesized that the dAd5 platform would maintain immunopotency even in the context of anti-Ad neutralizing antibodies. To test this hypothesis, we coupled cocaine and nicotine analogs, GNE and AM1, to dAd5 capsid proteins to generate dAd5GNE and dAd5AM1, respectively. Mice were pre-immunized with Ad5Null, resulting in high titer anti-Ad5 neutralizing antibodies comparable to those observed in the human population. The dAd5GNE and dAd5AM1 vaccines elicited high anti-cocaine and anti-nicotine antibody titers, respectively, in both naive and Ad5-immune mice, and both functioned to prevent cocaine or nicotine from reaching the brain of anti-Ad immune mice. Thus, disrupted Ad5 evokes potent humoral immunity that is effective in the context of pre-existing neutralizing anti-Ad immunity, overcoming a major limitation for current Ad-based vaccines. PMID:23140508

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

PubMed

Fuchs, Jonathan D; Bart, Pierre-Alexandre; Frahm, Nicole; Morgan, Cecilia; Gilbert, Peter B; Kochar, Nidhi; DeRosa, Stephen C; Tomaras, Georgia D; Wagner, Theresa M; Baden, Lindsey R; Koblin, Beryl A; Rouphael, Nadine G; Kalams, Spyros A; Keefer, Michael C; Goepfert, Paul A; Sobieszczyk, Magdalena E; Mayer, Kenneth H; Swann, Edith; Liao, Hua-Xin; Haynes, Barton F; Graham, Barney S; McElrath, M Juliana

2015-05-01

Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.

Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors.

PubMed

Crosby, Catherine M; Barry, Michael A

2017-02-18

Most adenovirus (Ad) vectors are E1 gene deleted replication defective (RD-Ad) vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad) vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed "single cycle" Ad (SC-Ad) vectors. SC-Ads amplify transgene expression and generated markedly stronger and more persistent immune responses than RD-Ad as expected. However, they also unexpectedly generated stronger immune responses than RC-Ad vectors. To explore the basis of this potency here, we compared gene expression and the cellular responses to infection to these vectors in vitro and in vivo. In vitro, in primary human lung epithelial cells, SC- and RC-Ad amplified their genomes more than 400-fold relative to RD-Ad with higher replication by SC-Ad. This replication translated into higher green fluorescent protein (GFP) expression for 48 h by SC- and RC-Ad than by RD-Ad. In vitro, in the absence of an immune system, RD-Ad expression became higher by 72 h coincident with cell death mediated by SC- and RC-Ad and release of transgene product from the dying cells. When the vectors were compared in human THP-1 Lucia- interferon-stimulated gene (ISG) cells, which are a human monocyte cell line that have been modified to quantify ISG activity, RC-Ad6 provoked significantly stronger ISG responses than RD- or SC-Ad. In mice, intravenous or intranasal injection produced up to 100-fold genome replication. Under these in vivo conditions in the presence of the immune system, luciferase expression by RC and SC-Ad was markedly higher than that by RD-Ad. In immunodeficient mice, SC-Ad drove stronger luciferase expression than RC- or RD-Ad. These data demonstrate better transgene expression by SC- and RC-Ad in vitro and in vivo than RD-Ad. This higher expression by the replicating vectors results in a peak of expression within 1 to 2 days followed by cell death of infected cells and release of transgene products. While SC- and RC-Ad expression were similar in mice and in Syrian hamsters, RC-Ad provoked much stronger ISG induction which may explain in part SC-Ad's ability to generate stronger and more persistent immune responses than RC-Ad in Ad permissive hamsters.

Evaluation of Biodistribution and Safety of Adenovirus Vectors Containing Group B Fibers after Intravenous Injection into Baboons

PubMed Central

NI, SHAOHENG; BERNT, KATHRIN; GAGGAR, ANUJ; LI, ZONG-YI; KIEM, HANS-PETER; LIEBER, ANDRÉ

2005-01-01

Vectors containing group B adenovirus (Ad) fibers are able to efficiently transduce gene therapy targets that are refractory to infection with standard Ad serotype 5 (Ad5) vectors, including malignant tumor cells, hematopoietic stem cells, and dendritic cells. Preliminary studies in mice indicate that, after intravenous injection, B-group fiber-containing Ads do not efficiently transduce most organs and cause less acute toxicity than Ad5 vectors. However, biodistribution and safety studies in mice are of limited value because the mouse analog of the B-group Ad receptor, CD46, is expressed only in the testis, whereas in humans, CD46 is expressed on all nucleated cells. Unlike mice, baboons have CD46 expression patterns and levels that closely mimic those in humans. We conducted a biodistribution and toxicity study of group B Ad fiber-containing vectors in baboons. Animals received phosphate-buffered saline, Ad5-bGal (a first-generation Ad5 vector), or B-group fiber-containing Ads (Ad5/35-bGal and Ad5/11-bGal) at a dose of 2 × 1012 VP/kg, and vector biodistribution and safety was analyzed over 3 days. The amount of Ad5/35-bGal and Ad5/11-bGal vector genomes was in most tissues one to three orders of magnitude below that of Ad5. Significant Ad5/35- and Ad5/11-mediated transgene (β-galactosidase) expression was seen only in the marginal zone of splenic follicles. Compared with the animal that received Ad5-bGal, all animals injected with B-group fiber-containing Ad vectors had lower elevations in serum proinflammatory cytokine levels. Gross and histopathology were normal in animals that received B-group Ad fiber-containing Ads, in contrast to the Ad5-infused animal, which showed widespread endothelial damage and inflammation. In a further study, a chimeric Ad5/35 vector carrying proapoptotic TRAIL and Ad E1A genes under tumor-specific regulation was well tolerated in a 30-day toxicity study. No major clinical, serologic, or pathologic abnormalities were noticed in this animal. OVERVIEW SUMMARY B-group Ad fiber-containing vectors are promising tools for gene therapy, for example, for the treatment of metastatic cancer or cardiovascular diseases, or for vaccination/immunotherapy. However, only a few studies of vectors containing B-group Ad fibers in mice have been conducted so far, and little is known about the mechanisms and effects of B-group Ad vector delivery in vivo. Before these vectors can be considered for clinical application, this knowledge gap must be filled. We performed biodistribution and safety studies after intravenous injection of chimeric Ad5 vectors containing Ad35 and Ad11 fibers into baboons. Our study suggests that Ad vectors possessing B-group Ad fibers have a better safety profile after intravenous injection than do conventional Ad5-based vectors. PMID:15960598

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses.

PubMed

Crosby, Catherine M; Matchett, William E; Anguiano-Zarate, Stephanie S; Parks, Christopher A; Weaver, Eric A; Pease, Larry R; Webby, Richard J; Barry, Michael A

2017-01-15

Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we developed "single-cycle" adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors in Syrian hamsters and rhesus macaques. To test them as potential vaccines, we engineered RD and SC versions of adenovirus serotype 6 (Ad6) to express the hemagglutinin (HA) gene from influenza A/PR/8/34 virus. We show here that it takes approximately 33 times less SC-Ad6 than RD-Ad6 to produce equal amounts of HA antigen in vitro SC-Ad produced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influenza titers than RD-Ad-vaccinated animals after challenge with influenza A/PR/8/34 virus. These data suggest that SC-Ads may be more potent vaccine platforms than conventional RD-Ad vectors and may have utility as "needle-free" mucosal vaccines. Most adenovirus vaccines that are being tested are replication-defective adenoviruses (RD-Ads). This work describes testing newer single-cycle adenovirus (SC-Ad) vectors that replicate transgenes to amplify protein production and immune responses. We show that SC-Ads generate markedly more influenza virus hemagglutinin protein and require substantially less vector to generate the same immune responses as RD-Ad vectors. SC-Ads therefore hold promise to be more potent vectors and vaccines than current RD-Ad vectors. Copyright © 2017 Crosby et al.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thoma, Clemens, E-mail: c.thoma@oxfordalumni.org; Bachy, Veronique; Seaton, Patricia

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5more » induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer.« less

High Energy Scattering in the AdS/CFT Correspondence

NASA Astrophysics Data System (ADS)

Penedones, Joao

2007-12-01

This work explores the celebrated AdS/CFT correspondence in the regime of high energy scattering in Anti--de Sitter (AdS) spacetime. In particular, we develop the eikonal approximation to high energy scattering in AdS and explore its consequences for the dual Conformal Field Theory (CFT). Using position space Feynman rules, we rederive the eikonal approximation for high energy scattering in flat space. Following this intuitive position space perspective, we then generalize the eikonal approximation for high energy scattering in AdS and other spacetimes. Remarkably, we are able to resum, in terms of a generalized phase shift, ladder and cross ladder Witten diagrams associated to the exchange of an AdS spin j field, to all orders in the coupling constant. By the AdS/CFT correspondence, the eikonal amplitude in AdS is related to the four point function of CFT primary operators in the regime of large 't Hooft coupling, including all terms of the 1/N expansion. We then show that the eikonal amplitude determines the behavior of the CFT four point function for small values of the cross ratios in a Lorentzian regime and that this controls its high spin and dimension conformal partial wave decomposition. These results allow us to determine the anomalous dimension of high spin and dimension double trace primary operators, by relating it to the AdS eikonal phase shift. Finally we find that, at large energies and large impact parameters in AdS, the gravitational interaction dominates all other interactions, as in flat space. Therefore, the anomalous dimension of double trace operators, associated to graviton exchange in AdS, yields a universal prediction for CFT's with AdS gravitational duals.

Combination recombinant simian or chimpanzee adenoviral vectors for vaccine development.

PubMed

Cheng, Cheng; Wang, Lingshu; Ko, Sung-Youl; Kong, Wing-Pui; Schmidt, Stephen D; Gall, Jason G D; Colloca, Stefano; Seder, Robert A; Mascola, John R; Nabel, Gary J

2015-12-16

Recombinant adenoviral vector (rAd)-based vaccines are currently being developed for several infectious diseases and cancer therapy, but pre-existing seroprevalence to such vectors may prevent their use in broad human populations. In this study, we investigated the potential of low seroprevalence non-human primate rAd vectors to stimulate cellular and humoral responses using HIV/SIV Env glycoprotein (gp) as the representative antigen. Mice were immunized with novel simian or chimpanzee rAd (rSAV or rChAd) vectors encoding HIV gp or SIV gp by single immunization or in heterologous prime/boost combinations (DNA/rAd; rAd/rAd; rAd/NYVAC or rAd/rLCM), and adaptive immunity was assessed. Among the rSAV and rChAd tested, rSAV16 or rChAd3 vector alone generated the most potent immune responses. The DNA/rSAV regimen also generated immune responses similar to the DNA/rAd5 regimen. rChAd63/rChAd3 and rChAd3 /NYVAC induced similar or even higher levels of CD4+ and CD8+ T-cell and IgG responses as compared to rAd28/rAd5, one of the most potent combinations of human rAds. The optimized vaccine regimen stimulated improved cellular immune responses and neutralizing antibodies against HIV compared to the DNA/rAd5 regimen. Based on these results, this type of novel rAd vector and its prime/boost combination regimens represent promising candidates for vaccine development. Published by Elsevier Ltd.

Antismoking Ads at the Point of Sale: The Influence of Ad Type and Context on Ad Reactions.

PubMed

Kim, Annice; Nonnemaker, James; Guillory, Jamie; Shafer, Paul; Parvanta, Sarah; Holloway, John; Farrelly, Matthew

2017-06-01

Efforts are underway to educate consumers about the dangers of smoking at the point of sale (POS). Research is limited about the efficacy of POS antismoking ads to guide campaign development. This study experimentally tests whether the type of antismoking ad and the context in which ads are viewed influence people's reactions to the ads. A national convenience sample of 7,812 adult current smokers and recent quitters was randomized to 1 of 39 conditions. Participants viewed one of the four types of antismoking ads (negative health consequences-graphic, negative social consequences-intended emotive, benefits of quitting-informational, benefits of quitting-graphic) in one of the three contexts (alone, next to a cigarette ad, POS tobacco display). We assessed participants' reactions to the ads, including perceived effectiveness, negative emotion, affective dissonance, and motivational reaction. Graphic ads elicited more negative emotion and affective dissonance than benefits of quitting ads. Graphic ads elicited higher perceived effectiveness and more affective dissonance than intended emotive ads. Antismoking ads fared best when viewed alone, and graphic ads were least influenced by the context in which they were viewed. These results suggest that in developing POS campaigns, it is important to consider the competitive pro-tobacco context in which antismoking ads will be viewed.

Segmented strings in AdS 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callebaut, Nele; Gubser, Steven S.; Samberg, Andreas

We study segmented strings in flat space and in AdS 3. In flat space, these well known classical motions describe strings which at any instant of time are piecewise linear. In AdS 3, the worldsheet is composed of faces each of which is a region bounded by null geodesics in an AdS 2 subspace of AdS 3. The time evolution can be described by specifying the null geodesic motion of kinks in the string at which two segments are joined. The outcome of collisions of kinks on the worldsheet can be worked out essentially using considerations of causality. We studymore » several examples of closed segmented strings in AdS 3 and find an unexpected quasi-periodic behavior. Here, we also work out a WKB analysis of quantum states of yo-yo strings in AdS 5 and find a logarithmic term reminiscent of the logarithmic twist of string states on the leading Regge trajectory.« less

Segmented strings in AdS 3

DOE PAGES

Callebaut, Nele; Gubser, Steven S.; Samberg, Andreas; ...

2015-11-17

We study segmented strings in flat space and in AdS 3. In flat space, these well known classical motions describe strings which at any instant of time are piecewise linear. In AdS 3, the worldsheet is composed of faces each of which is a region bounded by null geodesics in an AdS 2 subspace of AdS 3. The time evolution can be described by specifying the null geodesic motion of kinks in the string at which two segments are joined. The outcome of collisions of kinks on the worldsheet can be worked out essentially using considerations of causality. We studymore » several examples of closed segmented strings in AdS 3 and find an unexpected quasi-periodic behavior. Here, we also work out a WKB analysis of quantum states of yo-yo strings in AdS 5 and find a logarithmic term reminiscent of the logarithmic twist of string states on the leading Regge trajectory.« less

17 CFR 240.17Ad-4 - Applicability of §§ 240.17Ad-2, 240.17Ad-3 and 240.17Ad-6(a) (1) through (7) and (11).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Applicability of §§ 240.17Ad-2, 240.17Ad-3 and 240.17Ad-6(a) (1) through (7) and (11). 240.17Ad-4 Section 240.17Ad-4 Commodity... Commission or the Office of the Comptroller of the Currency, prepare and maintain in its possession a...

17 CFR 240.17Ad-4 - Applicability of §§ 240.17Ad-2, 240.17Ad-3 and 240.17Ad-6(a) (1) through (7) and (11).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Applicability of §§ 240.17Ad-2, 240.17Ad-3 and 240.17Ad-6(a) (1) through (7) and (11). 240.17Ad-4 Section 240.17Ad-4 Commodity... Commission or the Office of the Comptroller of the Currency, prepare and maintain in its possession a...

Asymptotic symmetries, holography and topological hair

NASA Astrophysics Data System (ADS)

Mishra, Rashmish K.; Sundrum, Raman

2018-01-01

Asymptotic symmetries of AdS4 quantum gravity and gauge theory are derived by coupling the holographically dual CFT3 to Chern-Simons gauge theory and 3D gravity in a "probe" (large-level) limit. Despite the fact that the three-dimensional AdS4 boundary as a whole is consistent with only finite-dimensional asymptotic symmetries, given by AdS isometries, infinite-dimensional symmetries are shown to arise in circumstances where one is restricted to boundary subspaces with effectively two-dimensional geometry. A canonical example of such a restriction occurs within the 4D subregion described by a Wheeler-DeWitt wavefunctional of AdS4 quantum gravity. An AdS4 analog of Minkowski "super-rotation" asymptotic symmetry is probed by 3D Einstein gravity, yielding CFT2 structure (in a large central charge limit), via AdS3 foliation of AdS4 and the AdS3/CFT2 correspondence. The maximal asymptotic symmetry is however probed by 3D conformal gravity. Both 3D gravities have Chern-Simons formulation, manifesting their topological character. Chern-Simons structure is also shown to be emergent in the Poincare patch of AdS4, as soft/boundary limits of 4D gauge theory, rather than "put in by hand" as an external probe. This results in a finite effective Chern-Simons level. Several of the considerations of asymptotic symmetry structure are found to be simpler for AdS4 than for Mink4, such as non-zero 4D particle masses, 4D non-perturbative "hard" effects, and consistency with unitarity. The last of these in particular is greatly simplified because in some set-ups the time dimension is explicitly shared by each level of description: Lorentzian AdS4, CFT3 and CFT2. Relatedly, the CFT2 structure clarifies the sense in which the infinite asymptotic charges constitute a useful form of "hair" for black holes and other complex 4D states. An AdS4 analog of Minkowski "memory" effects is derived, but with late-time memory of earlier events being replaced by (holographic) "shadow" effects. Lessons from AdS4 provide hints for better understanding Minkowski asymptotic symmetries, the 3D structure of its soft limits, and Minkowski holography.

Comparative Analysis of the Magnitude, Quality, Phenotype and Protective Capacity of SIV Gag-Specific CD8+ T Cells Following Human-, Simian- and Chimpanzee-Derived Recombinant Adenoviral Vector Immunisation

PubMed Central

Quinn, Kylie M.; Costa, Andreia Da; Yamamoto, Ayako; Berry, Dana; Lindsay, Ross W.B.; Darrah, Patricia A.; Wang, Lingshu; Cheng, Cheng; Kong, Wing-Pui; Gall, Jason G.D.; Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo; Gostick, Emma; Price, David A.; Gomez, Carmen E.; Esteban, Mariano; Wyatt, Linda S.; Moss, Bernard; Morgan, Cecilia; Roederer, Mario; Bailer, Robert T.; Nabel, Gary J.; Koup, Richard A.; Seder, Robert A.

2013-01-01

Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8+ T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. Here we show low seroreactivity in humans against simian- (sAd11, sAd16), or chimpanzee-derived (chAd3, chAd63) compared to human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype and protective capacity of CD8+ T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 × 107 to 109 PU), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8+ T cell responses, from most to least as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFNγ+TNFα+IL-2+ and KLRG1+CD127- CD8+ T cells, but strikingly ~30–80% of memory CD8+ T cells co-expressed CD127 and KLRG1. To further optimise CD8+ T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached ~60% of total CD8+ T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8+ T cell responses compared to prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8+ T cells for rapid effector function or robust long-term memory, respectively. PMID:23390298

Comment on ‘AdS nonlinear instability: moving beyond spherical symmetry’ (2016 Class. Quantum Grav. 33 23LT01)

NASA Astrophysics Data System (ADS)

Rostworowski, Andrzej

2017-06-01

We argue that if the degeneracy of the spectrum of linear perturbations of AdS is properly taken into account, there are globally regular, time-periodic, asymptotically AdS solutions (geons) bifurcating from each linear eigenfrequency of AdS.

A Claims-Based Examination of Health Care Costs Among Spouses of Patients With Alzheimer's Disease.

PubMed

Gilden, Daniel M; Kubisiak, Joanna M; Kahle-Wrobleski, Kristin; Ball, Daniel E; Bowman, Lee

2017-06-01

Spouses of Alzheimer's disease patients (AD spouses) may experience substantial health effects associated with their partner's chronic cognitive and behavioral dysfunction. Studies examining associations between the medical experiences of AD spouses in the period before and after their partner's AD diagnosis are limited, particularly those which measure health care resource use and cost. AD patients were identified through multiple Medicare claims containing an AD diagnostic code. Their spouses were identified through special coding in the Medicare eligibility records. The AD spouses were matched demographically to the spouses of Medicare beneficiaries without a history of AD. Longitudinal and annual cross-sectional Medicare cost comparisons utilized log-transformed linear regression. The longitudinal period of observation began 12 months before the AD patient's initial claim listing AD and continued for up to 38 months afterwards. The study identified 16,322 AD spouses. Total per person costs were 24% higher in AD spouses than in the controls ($694/month vs $561/month). AD spouses' excess costs began 3 months before their partners' AD diagnoses and continued for ≥30 months. Being an AD spouse predicted 29% higher Medicare costs after adjustment for chronic health status (P < .001). Increasing AD patient care complexity had a substantial impact on AD spouse Medicare costs (P < .001). This study documents a link between the health status of AD spouses and AD patients. Additional research is required to elicit the mechanism behind the association between AD spouse and AD patient diagnosis. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years.

PubMed

Ranginwala, Najeeb A; Hynan, Linda S; Weiner, Myron F; White, Charles L

2008-05-01

To examine the impact of newer neuropathological techniques on the power of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria for Alzheimer disease (AD) to detect AD at later postmortem study. We examined clinical and postmortem diagnoses of persons evaluated postmortem with thioflavin-S staining for plaques and tangles and immunohistochemical staining techniques for alpha synuclein, uhiquitin, and tau protein. Alzheimer Disease Center. Clinically evaluated persons for whom tissue diagnosis was available. Of 313 evaluees, 166 met criteria for probable AD. An additional 59 subjects had clinical diagnoses that included AD, e.g., possible AD, Lewy body variant of AD, AD and Parkinsonism, and mixed AD and vascular dementia. Of the 166 probable AD cases, 147 of 166 (88.6%) met pathologic criteria for AD. When all five AD groups were combined, 194 of 225 subjects (86.2%) met pathologic criteria for AD. There were five cases diagnosed pathologically as tangle-only dementia, which was considered a variant of AD. A pathologic diagnosis of Lewy body variant of AD was made in 56 (17.9%) of cases, including 44 of 313 (14.1%) cases diagnosed as probable or possible AD. Pure dementia with Lewy bodies was seen in 13 (4.2%). There were 9 (2.9%) cases of mixed AD and vascular dementia, and 37 (11.4%) cases of frontotemporal dementia. McKhann et al. criteria for probable and possible AD are valid for AD but do not exclude additional Lewy body pathology.

Image Ads and Issue Ads in U.S. Presidential Advertising: Using Videostyle To Explore Stylistic Differences in Televised Political Ads From 1952 to 2000.

ERIC Educational Resources Information Center

Johnston, Anne; Kaid, Lynda Lee

2002-01-01

Explores the differences in techniques, strategies, narratives, and symbols used in 1,213 television issue ads and image ads from 13 U.S. presidential campaigns. Concludes that although the majority of both types of ads were positive, negative appeals dominated a higher percentage of issue ads as compared with image ads. (SG)

Boundary stress tensor and asymptotically AdS3 non-Einstein spaces at the chiral point

NASA Astrophysics Data System (ADS)

Giribet, Gaston; Goya, Andrés; Leston, Mauricio

2011-09-01

Chiral gravity admits asymptotically AdS3 solutions that are not locally equivalent to AdS3; meaning that solutions do exist which, while obeying the strong boundary conditions usually imposed in general relativity, happen not to be Einstein spaces. In topologically massive gravity (TMG), the existence of non-Einstein solutions is particularly connected to the question about the role played by complex saddle points in the Euclidean path integral. Consequently, studying (the existence of) nonlocally AdS3 solutions to chiral gravity is relevant to understanding the quantum theory. Here, we discuss a special family of nonlocally AdS3 solutions to chiral gravity. In particular, we show that such solutions persist when one deforms the theory by adding the higher-curvature terms of the so-called new massive gravity. Moreover, the addition of higher-curvature terms to the gravity action introduces new nonlocally AdS3 solutions that have no analogues in TMG. Both stationary and time-dependent, axially symmetric solutions that asymptote AdS3 space without being locally equivalent to it appear. Defining the boundary stress tensor for the full theory, we show that these non-Einstein geometries have associated vanishing conserved charges.

Mucosal vaccination by adenoviruses displaying reovirus sigma 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaver, Eric A.; Camacho, Zenaido T.; Hillestad, Matthew L.

We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. Whenmore » wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.« less

SAO/NASA ADS at SAO: ADS Browse Service

Science.gov Websites

Sign on [SAO/NASA ADS] ADS Browse Service ADS Home | HELP | Sitemap ADS Services Search Browse myADS Mirrors Feedback FAQ What's new Site Map Help Other NASA Centers CXC HEASARC IRSA MAST NED NSSDC -Smithsonian Center for Astrophysics [ Smithsonian logo ] The NASA Astrophysics Data System provides different

An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ran-yi, E-mail: liuranyi@mail.sysu.edu.cn; Zhou, Ling; Zhang, Yan-ling

2013-12-13

Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endomore » via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.« less

Independent effects of adding weight and inertia on balance during quiet standing

PubMed Central

2012-01-01

Background Human balance during quiet standing is influenced by adding mass to the body with a backpack, with symmetrically-applied loads to the trunk, or with obesity. Adding mass to the body increases both the weight and inertia of the body, which theoretically could provide counteracting effects on body dynamics and balance. Understanding the independent effects of adding weight and inertia on balance may provide additional insight into human balance that could lead to novel advancements in balance training and rehabilitation. Therefore, the purpose of this study was to investigate the independent effects of adding weight and inertia on balance during quiet standing. Methods Sixteen normal-weight young adult participants stood as still as possible on a custom-built backboard apparatus under four experimental conditions: baseline, added inertia only, added weight only, and added inertia and weight. Results Adding inertia by itself had no measurable effect on center of pressure movement or backboard movement. Adding weight by itself increased center of pressure movement (indicated greater effort by the postural control system to stand as still as possible) and backboard movement (indicating a poorer ability of the body to stand as still as possible). Adding inertia and weight at the same time increased center of pressure movement but did not increase backboard movement compared to the baseline condition. Conclusions Adding inertia and adding weight had different effects on balance. Adding inertia by itself had no effect on balance. Adding weight by itself had a negative effect on balance. When adding inertia and weight at the same time, the added inertia appeared to lessen (but did not eliminate) the negative effect of adding weight on balance. These results improve our fundamental understanding of how added mass influences human balance. PMID:22507125

Independent effects of adding weight and inertia on balance during quiet standing.

PubMed

Costello, Kerry Elizabeth; Matrangola, Sara Louise; Madigan, Michael Lawrence

2012-04-16

Human balance during quiet standing is influenced by adding mass to the body with a backpack, with symmetrically-applied loads to the trunk, or with obesity. Adding mass to the body increases both the weight and inertia of the body, which theoretically could provide counteracting effects on body dynamics and balance. Understanding the independent effects of adding weight and inertia on balance may provide additional insight into human balance that could lead to novel advancements in balance training and rehabilitation. Therefore, the purpose of this study was to investigate the independent effects of adding weight and inertia on balance during quiet standing. Sixteen normal-weight young adult participants stood as still as possible on a custom-built backboard apparatus under four experimental conditions: baseline, added inertia only, added weight only, and added inertia and weight. Adding inertia by itself had no measurable effect on center of pressure movement or backboard movement. Adding weight by itself increased center of pressure movement (indicated greater effort by the postural control system to stand as still as possible) and backboard movement (indicating a poorer ability of the body to stand as still as possible). Adding inertia and weight at the same time increased center of pressure movement but did not increase backboard movement compared to the baseline condition. Adding inertia and adding weight had different effects on balance. Adding inertia by itself had no effect on balance. Adding weight by itself had a negative effect on balance. When adding inertia and weight at the same time, the added inertia appeared to lessen (but did not eliminate) the negative effect of adding weight on balance. These results improve our fundamental understanding of how added mass influences human balance.

AdDroid: Privilege Separation for Applications and Advertisers in Android

DTIC Science & Technology

2013-05-14

integrates these three components into the Android Open Source Project, version 2.3.3 (Ginger- bread ). 4.1 AdDroid Library API The AdDroid userspace...AdPropert ies IAB MRECT public stat ic int NO REFRESH stat ic enum AdPropert ies . Al ign BOTTOM TOP UNSET Class AdRequest public AdRequest ( ) public

The impact of salient advertisements on reading and attention on web pages.

PubMed

Simola, Jaana; Kuisma, Jarmo; Oörni, Anssi; Uusitalo, Liisa; Hyönä, Jukka

2011-06-01

Human vision is sensitive to salient features such as motion. Therefore, animation and onset of advertisements on Websites may attract visual attention and disrupt reading. We conducted three eye tracking experiments with authentic Web pages to assess whether (a) ads are efficiently ignored, (b) ads attract overt visual attention and disrupt reading, or (c) ads are covertly attended with distraction showing up indirectly in the reading performance. The Web pages contained an ad above a central text and another ad to the right of the text. In Experiments 1, 2, and 3A the task was to read for comprehension. Experiment 1 examined whether the degree of animation affects attention toward the ads. The results showed that ads were overtly attended during reading and that the dwell times on ads were the longest when the ad above was static and the other ad was animated. In Experiments 2 and 3, the ads appeared abruptly after a random time interval. The results showed that attention (i.e., the time when the eyes first entered an ad) was related to the ad onset time. This happened especially for the ad to the right, indicating that ads appearing close to the text region capture overt attention. In Experiment 3B the participants browsed the Web pages according to their own interest. The study demonstrated that salient ads attract overt visual attention and disrupt reading, but during free browsing, ads were viewed more frequently and for longer time than during reading.

What are the odds of anxiety disorders running in families? A family study of anxiety disorders in mothers, fathers, and siblings of children with anxiety disorders.

PubMed

Telman, Liesbeth G E; van Steensel, Francisca J A; Maric, Marija; Bögels, Susan M

2018-05-01

This family study investigated (1) the prevalence of anxiety disorders (ADs) in parents and siblings of children (n = 144) aged 8-18 years with ADs compared to control children (n = 49), and (2) the specificity of relationships between child-mother, child-father, and child-sibling ADs. Clinical interviews were used to assess current DSM-IV-TR ADs in children and siblings, and lifetime and current ADs in parents. Results showed that children with ADs were two to three times more likely to have at least one parent with current and lifetime ADs than the control children (odds ratio (OR) = 2.04 and 3.14). Children with ADs were more likely to have mothers with current ADs (OR = 2.51), fathers with lifetime ADs (OR = 2.84), but not siblings with ADs (OR = 0.75). Specific relationships between mother-child ADs were found for Social Anxiety Disorder (SAD, OR = 3.69) and Generalized Anxiety Disorder (OR = 3.47). Interestingly, all fathers and siblings with SAD came from families of children with SAD. Fathers of children with SAD were more likely to have lifetime ADs themselves (OR = 2.86). Findings indicate that children with ADs more often have parents with ADs, and specifically SAD is more prevalent in families of children with SAD. Influence of parent's (social) ADs should be considered when treating children with ADs.

Warped AdS3 black holes

NASA Astrophysics Data System (ADS)

Song, Wei; Anninos, Dionysios; Li, Wei; Padi, Megha; Strominger, Andrew

2009-03-01

Three dimensional topologically massive gravity (TMG) with a negative cosmological constant -ell-2 and positive Newton constant G admits an AdS3 vacuum solution for any value of the graviton mass μ. These are all known to be perturbatively unstable except at the recently explored chiral point μell = 1. However we show herein that for every value of μell ≠ 3 there are two other (potentially stable) vacuum solutions given by SL(2,Bbb R) × U(1)-invariant warped AdS3 geometries, with a timelike or spacelike U(1) isometry. Critical behavior occurs at μell = 3, where the warping transitions from a stretching to a squashing, and there are a pair of warped solutions with a null U(1) isometry. For μell > 3, there are known warped black hole solutions which are asymptotic to warped AdS3. We show that these black holes are discrete quotients of warped AdS3 just as BTZ black holes are discrete quotients of ordinary AdS3. Moreover new solutions of this type, relevant to any theory with warped AdS3 solutions, are exhibited. Finally we note that the black hole thermodynamics is consistent with the hypothesis that, for μell > 3, the warped AdS3 ground state of TMG is holographically dual to a 2D boundary CFT with central charges c_R-formula and c_L-formula.

Warped AdS3 black holes

NASA Astrophysics Data System (ADS)

Anninos, Dionysios; Li, Wei; Padi, Megha; Song, Wei; Strominger, Andrew

2009-03-01

Three dimensional topologically massive gravity (TMG) with a negative cosmological constant -l-2 and positive Newton constant G admits an AdS3 vacuum solution for any value of the graviton mass μ. These are all known to be perturbatively unstable except at the recently explored chiral point μl = 1. However we show herein that for every value of μl ≠ 3 there are two other (potentially stable) vacuum solutions given by SL(2,Bbb R) × U(1)-invariant warped AdS3 geometries, with a timelike or spacelike U(1) isometry. Critical behavior occurs at μl = 3, where the warping transitions from a stretching to a squashing, and there are a pair of warped solutions with a null U(1) isometry. For μl > 3, there are known warped black hole solutions which are asymptotic to warped AdS3. We show that these black holes are discrete quotients of warped AdS3 just as BTZ black holes are discrete quotients of ordinary AdS3. Moreover new solutions of this type, relevant to any theory with warped AdS3 solutions, are exhibited. Finally we note that the black hole thermodynamics is consistent with the hypothesis that, for μl > 3, the warped AdS3 ground state of TMG is holographically dual to a 2D boundary CFT with central charges c_R-formula and c_L-formula.

The Human Membrane Cofactor CD46 Is a Receptor for Species B Adenovirus Serotype 3

PubMed Central

Sirena, Dominique; Lilienfeld, Benjamin; Eisenhut, Markus; Kälin, Stefan; Boucke, Karin; Beerli, Roger R.; Vogt, Lorenz; Ruedl, Christiane; Bachmann, Martin F.; Greber, Urs F.; Hemmi, Silvio

2004-01-01

Many human adenovirus (Ad) serotypes use the coxsackie B virus-Ad receptor (CAR). Recently, CD46 was suggested to be a receptor of species B Ad serotype 11 (Ad11), Ad14, Ad16, Ad21, Ad35, and Ad50. Using Sindbis virus-mediated cDNA library expression, we identify here the membrane cofactor protein CD46 as a surface receptor of species B Ad3. All four major CD46 transcripts and one minor CD46 transcript expressed in nucleated human cells were isolated. Rodent BHK cells stably expressing the BC1 form of CD46 bound radiolabeled Ad3 with a dissociation constant of 0.3 nM, identical to that of CD46-positive HeLa cells expressing twice as many Ad3 binding sites. Pull-down experiments with recombinant Ad3 fibers and a soluble form of the CD46 extracellular domain linked to the Fc portion of human immunoglobulin G (CD46ex-Fc) indicated direct interactions of the Ad3 fiber knob with CD46ex-Fc but not CARex-Fc (Fc-linked extracellular domain of CAR). Ad3 colocalized with cell surface CD46 in both rodent and human cells at the light and electron microscopy levels. Anti-CD46 antibodies and CD46ex-Fc inhibited Ad3 binding to CD46-expressing BHK cells more than 10-fold and to human cells 2-fold. In CD46-expressing BHK cells, wild-type Ad3 and a chimeric Ad consisting of the Ad5 capsid and the Ad3 fiber elicited dose-dependent cytopathic effects and transgene expression, albeit less efficiently than in human cells. Together, our results show that all of the major splice forms of CD46 are predominant and functional binding sites of Ad3 on CD46-expressing rodent and human cells but may not be the sole receptor of species B Ads on human cells. These results have implications for understanding viral pathogenesis and therapeutic gene delivery. PMID:15078926

The human membrane cofactor CD46 is a receptor for species B adenovirus serotype 3.

PubMed

Sirena, Dominique; Lilienfeld, Benjamin; Eisenhut, Markus; Kälin, Stefan; Boucke, Karin; Beerli, Roger R; Vogt, Lorenz; Ruedl, Christiane; Bachmann, Martin F; Greber, Urs F; Hemmi, Silvio

2004-05-01

Many human adenovirus (Ad) serotypes use the coxsackie B virus-Ad receptor (CAR). Recently, CD46 was suggested to be a receptor of species B Ad serotype 11 (Ad11), Ad14, Ad16, Ad21, Ad35, and Ad50. Using Sindbis virus-mediated cDNA library expression, we identify here the membrane cofactor protein CD46 as a surface receptor of species B Ad3. All four major CD46 transcripts and one minor CD46 transcript expressed in nucleated human cells were isolated. Rodent BHK cells stably expressing the BC1 form of CD46 bound radiolabeled Ad3 with a dissociation constant of 0.3 nM, identical to that of CD46-positive HeLa cells expressing twice as many Ad3 binding sites. Pull-down experiments with recombinant Ad3 fibers and a soluble form of the CD46 extracellular domain linked to the Fc portion of human immunoglobulin G (CD46ex-Fc) indicated direct interactions of the Ad3 fiber knob with CD46ex-Fc but not CARex-Fc (Fc-linked extracellular domain of CAR). Ad3 colocalized with cell surface CD46 in both rodent and human cells at the light and electron microscopy levels. Anti-CD46 antibodies and CD46ex-Fc inhibited Ad3 binding to CD46-expressing BHK cells more than 10-fold and to human cells 2-fold. In CD46-expressing BHK cells, wild-type Ad3 and a chimeric Ad consisting of the Ad5 capsid and the Ad3 fiber elicited dose-dependent cytopathic effects and transgene expression, albeit less efficiently than in human cells. Together, our results show that all of the major splice forms of CD46 are predominant and functional binding sites of Ad3 on CD46-expressing rodent and human cells but may not be the sole receptor of species B Ads on human cells. These results have implications for understanding viral pathogenesis and therapeutic gene delivery.

Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain.

PubMed

Kobayashi, Eiji; Nakano, Masako; Kubota, Kenta; Himuro, Nobuaki; Mizoguchi, Shougo; Chikenji, Takako; Otani, Miho; Mizue, Yuka; Nagaishi, Kanna; Fujimiya, Mineko

2018-01-26

Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.

Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

PubMed

Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

2015-09-01

Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups, whereas during the second part it was suppressed in AD-G as much as Non-AD. In conclusion, central acylated ghrelin in rats prevented the deterioration of memory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment. Copyright © 2015 Elsevier Inc. All rights reserved.

Two Virasoro symmetries in stringy warped AdS 3

DOE PAGES

Compere, Geoffrey; Guica, Monica; Rodriguez, Maria J.

2014-12-02

We study three-dimensional consistent truncations of type IIB supergravity which admit warped AdS 3 solutions. These theories contain subsectors that have no bulk dynamics. We show that the symplectic form for these theories, when restricted to the non-dynamical subsectors, equals the symplectic form for pure Einstein gravity in AdS 3. Consequently, for each consistent choice of boundary conditions in AdS 3, we can define a consistent phase space in warped AdS 3 with identical conserved charges. This way, we easily obtain a Virasoro × Virasoro asymptotic symmetry algebra in warped AdS 3; two different types of Virasoro × Kač-Moody symmetriesmore » are also consistent alternatives. Next, we study the phase space of these theories when propagating modes are included. We show that, as long as one can define a conserved symplectic form without introducing instabilities, the Virasoro × Virasoro asymptotic symmetries can be extended to the entire (linearised) phase space. In conclusion, this implies that, at least at semi-classical level, consistent theories of gravity in warped AdS 3 are described by a two-dimensional conformal field theory, as long as stability is not an issue.« less

Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.

PubMed

Cho, Hanna; Jeon, Seun; Kim, Changsoo; Ye, Byoung Seok; Kim, Geon Ha; Noh, Young; Kim, Hee Jin; Yoon, Cindy W; Kim, Yeo Jin; Kim, Jung-Hyun; Park, Sang Eon; Kim, Sung Tae; Lee, Jong-Min; Kang, Sue J; Suh, Mee Kyung; Chin, Juhee; Na, Duk L; Kang, Dae Ryong; Seo, Sang Won

2015-01-01

Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years). As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.

Two Virasoro symmetries in stringy warped AdS 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Compere, Geoffrey; Guica, Monica; Rodriguez, Maria J.

We study three-dimensional consistent truncations of type IIB supergravity which admit warped AdS 3 solutions. These theories contain subsectors that have no bulk dynamics. We show that the symplectic form for these theories, when restricted to the non-dynamical subsectors, equals the symplectic form for pure Einstein gravity in AdS 3. Consequently, for each consistent choice of boundary conditions in AdS 3, we can define a consistent phase space in warped AdS 3 with identical conserved charges. This way, we easily obtain a Virasoro × Virasoro asymptotic symmetry algebra in warped AdS 3; two different types of Virasoro × Kač-Moody symmetriesmore » are also consistent alternatives. Next, we study the phase space of these theories when propagating modes are included. We show that, as long as one can define a conserved symplectic form without introducing instabilities, the Virasoro × Virasoro asymptotic symmetries can be extended to the entire (linearised) phase space. In conclusion, this implies that, at least at semi-classical level, consistent theories of gravity in warped AdS 3 are described by a two-dimensional conformal field theory, as long as stability is not an issue.« less

What makes an ad a cigarette ad? Commercial tobacco imagery in the lesbian, gay, and bisexual press

PubMed Central

Smith, E.; Offen, N.; Malone, R.

2005-01-01

Objectives: To determine the extent of commercial tobacco imagery in the lesbian, gay, and bisexual (LGB) press. Methods: Content analysis of all advertising containing tobacco related text or imagery in 20 LGB community periodicals, published between January 1990 and December 2000. Results: 3428 ads were found: 689 tobacco product ads, 1607 ads for cessation products or services, 99 ads with a political message about tobacco, and 1033 non-tobacco ads that showed tobacco (NAST). Although cessation ads were numerically dominant, tobacco product ads and NAST occupied more space and were more likely to use images. NAST almost never had an anti-tobacco message. Formal sponsorship between tobacco and other companies was very rare. Lesbian periodicals had proportionally more NAST and fewer cessation ads. Conclusions: Cigarette ads were outnumbered by NAST. Although these ads do not usually show brands, and are unlikely to be the result of formal sponsorship agreements, they may be "selling" smoking. Tobacco control advocates should persuade editors to refuse tobacco product ads and those with gratuitous tobacco imagery. PMID:16286500

Characteristics of Adenovirus Pneumonia in Korean Military Personnel, 2012–2016

PubMed Central

Yoon, Hee; Yoo, Hongseok; Park, Sung Bum

2017-01-01

Adenovirus (AdV) can cause severe pneumonia in non-immunocompromised host, but limited data exist on the distinctive characteristics of AdV pneumonia in non-immunocompromised patients. We evaluated distinctive clinico-laboratory and radiological characteristics and outcomes of AdV pneumonia (n = 179), compared with non-AdV pneumonia (n = 188) in Korean military personnel between 2012 and 2016. AdV pneumonia patients had a higher rate of consolidation with ground-glass opacity (101/152) in lobar distribution (89/152) on computed tomography (CT) (P < 0.001). Laboratory findings showed a higher incidence of unusual blood profiles such as leukopenia (55/179, P < 0.001) or thrombocytopenia (100/179, P < 0.001). The patients had more systemic symptoms such as myalgia (82/179, P = 0.001) or diarrhea (23/179, P < 0.001), compared with non-AdV pneumonia patients. Bacterial co-infection was identified in 28.5% of AdV pneumonia. Most of the AdV isolates typed (69/72, 95.8%) were AdV-55. Patients with a pneumonia severity index ≥ class III were more commonly observed in AdV pneumonia patients compared with non-AdV pneumonia patients (11.2% vs. 2.1%, P < 0.001), and time to clinical stabilization from admission was longer in the AdV pneumonia patients compared with the non-AdV pneumonia patients (3.8 vs. 2.6 days, P < 0.001). Mechanical ventilation (n = 6) was only required in AdV pneumonia patients, one of whom died due to AdV-55. Our data showed that AdV pneumonia in non-immunocompromised patients had distinct characteristics and most of the isolates typed in our study were AdV-55. It is suggested that AdV-55 is an important pathogen of pneumonia in Korean military personnel. PMID:28049240

Quantum spectral curve for the η-deformed AdS5 × S5 superstring

NASA Astrophysics Data System (ADS)

Klabbers, Rob; van Tongeren, Stijn J.

2017-12-01

The spectral problem for the AdS5 ×S5 superstring and its dual planar maximally supersymmetric Yang-Mills theory can be efficiently solved through a set of functional equations known as the quantum spectral curve. We discuss how the same concepts apply to the η-deformed AdS5 ×S5 superstring, an integrable deformation of the AdS5 ×S5 superstring with quantum group symmetry. This model can be viewed as a trigonometric version of the AdS5 ×S5 superstring, like the relation between the XXZ and XXX spin chains, or the sausage and the S2 sigma models for instance. We derive the quantum spectral curve for the η-deformed string by reformulating the corresponding ground-state thermodynamic Bethe ansatz equations as an analytic Y system, and map this to an analytic T system which upon suitable gauge fixing leads to a Pμ system - the quantum spectral curve. We then discuss constraints on the asymptotics of this system to single out particular excited states. At the spectral level the η-deformed string and its quantum spectral curve interpolate between the AdS5 ×S5 superstring and a superstring on "mirror" AdS5 ×S5, reflecting a more general relationship between the spectral and thermodynamic data of the η-deformed string. In particular, the spectral problem of the mirror AdS5 ×S5 string, and the thermodynamics of the undeformed AdS5 ×S5 string, are described by a second rational limit of our trigonometric quantum spectral curve, distinct from the regular undeformed limit.

Characteristics of Adenovirus Pneumonia in Korean Military Personnel, 2012-2016.

PubMed

Yoon, Hee; Jhun, Byung Woo; Kim, Hojoong; Yoo, Hongseok; Park, Sung Bum

2017-02-01

Adenovirus (AdV) can cause severe pneumonia in non-immunocompromised host, but limited data exist on the distinctive characteristics of AdV pneumonia in non-immunocompromised patients. We evaluated distinctive clinico-laboratory and radiological characteristics and outcomes of AdV pneumonia (n = 179), compared with non-AdV pneumonia (n = 188) in Korean military personnel between 2012 and 2016. AdV pneumonia patients had a higher rate of consolidation with ground-glass opacity (101/152) in lobar distribution (89/152) on computed tomography (CT) (P < 0.001). Laboratory findings showed a higher incidence of unusual blood profiles such as leukopenia (55/179, P < 0.001) or thrombocytopenia (100/179, P < 0.001). The patients had more systemic symptoms such as myalgia (82/179, P = 0.001) or diarrhea (23/179, P < 0.001), compared with non-AdV pneumonia patients. Bacterial co-infection was identified in 28.5% of AdV pneumonia. Most of the AdV isolates typed (69/72, 95.8%) were AdV-55. Patients with a pneumonia severity index ≥ class III were more commonly observed in AdV pneumonia patients compared with non-AdV pneumonia patients (11.2% vs. 2.1%, P < 0.001), and time to clinical stabilization from admission was longer in the AdV pneumonia patients compared with the non-AdV pneumonia patients (3.8 vs. 2.6 days, P < 0.001). Mechanical ventilation (n = 6) was only required in AdV pneumonia patients, one of whom died due to AdV-55. Our data showed that AdV pneumonia in non-immunocompromised patients had distinct characteristics and most of the isolates typed in our study were AdV-55. It is suggested that AdV-55 is an important pathogen of pneumonia in Korean military personnel.

Simulation of Black Hole Collisions in Asymptotically anti-de Sitter Spacetimes

NASA Astrophysics Data System (ADS)

Bantilan, Hans; Romatschke, Paul

2015-04-01

The main purpose of this talk is to describe, in detail, the necessary ingredients for achieving stable Cauchy evolution of black hole collisions in asymptotically anti-de Sitter (AdS) spacetimes. I will begin by motivating this program in terms of the heavy-ion physics it is intended to clarify. I will then give an overview of asymptotically AdS spacetimes, the mapping to the dual conformal field theory on the AdS boundary, and the method we use to numerically solve the fully non-linear Einstein field equations with AdS boundary conditions. As a concrete example of these ideas, I will describe the first proof of principle simulation of stable AdS black hole mergers in 5 dimensions.

Incidence and Duration of Cumulative Bisphosphonate Use among Community-Dwelling Persons with or without Alzheimer's Disease.

PubMed

Tiihonen, Miia; Taipale, Heidi; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa

2016-01-01

We studied the incidence and duration of cumulative bisphosphonate use among older Finnish women and men with or without Alzheimer's disease (AD). The MEDALZ-2005 cohort is a nationwide sample of all persons with clinically diagnosed AD on 31 December 2005 and their age-, gender-, and region of residence-matched control persons without AD. Information on bisphosphonate use by persons with an AD diagnosis and their controls without AD during 2002-2009 was obtained from the prescription register database containing reimbursed medications. A total of 6,041 (11.8%) persons used bisphosphonates during the 8-year follow-up. Bisphosphonates were more commonly used among persons without AD (n = 3121, 12.3%) than among persons with AD (n = 2,920, 11.2%) (p = 0.001). The median duration of bisphosphonate use was 743 days (IQR). Among persons with AD, the median duration of use was 777 days (IQR) and among persons without AD, 701 days (IQR) (p = 0.011). People without AD more often used bisphosphonate combination preparations including vitamin D than did people with AD (p <  0.0001). Bisphosphonate use was more common among people without AD who had comorbidities, asthma/COPD, or rheumatoid arthritis compared with users with AD. Short-term users were more likely to be male, at least 80 years old, and not having AD. Although the incidence of bisphosphonate use was slightly higher among persons without AD, the cumulative duration of bisphosphonate use was longer in persons with AD. Short-term use was associated with male gender, older age, and not having AD.

Differentiating the frontal variant of Alzheimer's disease.

PubMed

Woodward, Michael; Jacova, Claudia; Black, Sandra E; Kertesz, Andrew; Mackenzie, Ian R; Feldman, Howard

2010-07-01

Individuals with a clinical diagnosis of Alzheimer's disease (AD) may have prominent features of executive dysfunction and language impairment as well as behavioral abnormalities early in the disease ('high frontality'). When this occurs differentiation from frontotemporal dementia (FTD) is difficult. It is hypothesized that AD patients with high frontality may have clinical and pathological features that distinguish them from less frontal AD patients. In a well-characterized cohort of people with cognitive impairment, we used the Frontal Behavioral Inventory (FBI) in an attempt to identify AD patients with prominent frontal features (high-FBI AD) and distinguish them from the remainder of AD patients (low-FBI AD). The 18 high-FBI AD patients were compared with the 26 FTD patients who had an FBI performed and the 53 other low FBI AD patients. The individual FBI items did not differ significantly between the FTD and the high-FBI AD patients, and the high FBI AD patients were more like the FTD patients than the other AD patients with respect to presence of a family history of AD, proportion with homozygous apolipoprotein E(4) status, disability as measured by the Disability Assessment for Dementia (DAD) Scale and the Functional Rating Scale (FRS) and neuropsychiatric impairment as measured by the Neuropsychiatric Inventory (NPI). Memory symptom duration was similar in the high FBI AD group compared to the low FBI AD group. There is a subgroup of AD patients with high frontality that can be clinically distinguished from the remainder of AD patients but which requires pathological verification. (c) 2009 John Wiley & Sons, Ltd.

Anxiety Disorders and Rapid Cycling Data From a Cohort of 8129 Youths With Bipolar Disorder

PubMed Central

Castilla-Puentes, Ruby; Sala, Regina; Ng, Bernardo; Galvez, Juan; Camacho, Alvaro

2014-01-01

Anxiety disorders (ADs) are common in youths with bipolar disorder (BD). We examine psychiatric comorbidity, hospitalization, and treatment in youths with versus without AD and rapid cycling (four or more cycles per year). Data from the Integrated Healthcare Information Services cohort were used and included 8129 youths (ages ≤18 years). Prevalence of AD, demographic, type of AD, hospitalization, and use of psychotropics were compared between rapid and nonrapid cycling. Overall, 51% of the youths met criteria for at least one comorbid AD; they were predominantly female and were between 12 and 17 years of age. The most common comorbid ADs were generalized ADs and separation ADs. In the patients with rapid cycling, 65.5%met criteria for comorbid AD. The BD youths with AD were more likely to have major depressive disorders and other comorbid ADs, to be given more psychotropics, and to be hospitalized for depression and medical conditions more often than were those without AD. PMID:24284641

Gravity and large black holes in Randall-Sundrum II braneworlds.

PubMed

Figueras, Pau; Wiseman, Toby

2011-08-19

We show how to construct low energy solutions to the Randall-Sundrum II (RSII) model by using an associated five-dimensional anti-de Sitter space (AdS(5)) and/or four-dimensional conformal field theory (CFT(4)) problem. The RSII solution is given as a perturbation of the AdS(5)-CFT(4) solution, with the perturbation parameter being the radius of curvature of the brane metric compared to the AdS length ℓ. The brane metric is then a specific perturbation of the AdS(5)-CFT(4) boundary metric. For low curvatures the RSII solution reproduces 4D general relativity on the brane. Recently, AdS(5)-CFT(4) solutions with a 4D Schwarzschild boundary metric were numerically constructed. We modify the boundary conditions to numerically construct large RSII static black holes with radius up to ~20ℓ. For a large radius, the RSII solutions are indeed close to the associated AdS(5)-CFT(4) solution. © 2011 American Physical Society

Universal consistent truncation for 6d/7d gauge/gravity duals

NASA Astrophysics Data System (ADS)

Passias, Achilleas; Rota, Andrea; Tomasiello, Alessandro

2015-10-01

Recently, AdS7 solutions of IIA supergravity have been classified; there are infinitely many of them, whose expression is known analytically, and with internal space of S 3 topology. Their field theory duals are six-dimensional (1,0) SCFT's. In this paper we show that for each of these AdS7 solutions there exists a consistent truncation from massive IIA supergravity to minimal gauged supergravity in seven dimensions. This theory has an SU(2) gauge group, and a single scalar, whose value is related to a certain distortion of the internal S 3. This explains the universality observed in recent work on AdS5 and AdS4 solutions dual to compactifications of the (1, 0) SCFT6's. Thanks to previous work on the minimal gauged supergravity, the truncation also implies the existence of holographic RG-flows connecting those solutions to the AdS7 vacuum, as well as new classes of IIA AdS3 solutions.

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients

PubMed Central

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 (P < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group (P < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines. PMID:29563911

Malonyl-CoA decarboxylase (MCD) is differentially regulated in subcellular compartments by 5'AMP-activated protein kinase (AMPK). Studies using H9c2 cells overexpressing MCD and AMPK by adenoviral gene transfer technique.

PubMed

Sambandam, Nandakumar; Steinmetz, Michael; Chu, Angel; Altarejos, Judith Y; Dyck, Jason R B; Lopaschuk, Gary D

2004-07-01

Malonyl-CoA, a potent inhibitor of carnitine pamitoyl transferase-I (CPT-I), plays a pivotal role in fuel selection in cardiac muscle. Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, removes a potent allosteric inhibition on CPT-I and thereby increases fatty acid oxidation in the heart. Although MCD has several Ser/Thr phosphorylation sites, whether it is regulated by AMP-activated protein kinase (AMPK) has been controversial. We therefore overexpressed MCD (Ad.MCD) and constitutively active AMPK (Ad.CA-AMPK) in H9c2 cells, using an adenoviral gene delivery approach in order to examine if MCD is regulated by AMPK. Cells infected with Ad.CA-AMPK demonstrated a fourfold increase in AMPK activity as compared with control cells expressing green fluorescent protein (Ad.GFP). MCD activity increased 40- to 50-fold in Ad.MCD + Ad.GFP cells when compared with Ad.GFP control. Co-expressing AMPK with MCD further augmented MCD expression and activity in Ad.MCD + Ad.CA-AMPK cells compared with the Ad.MCD + Ad.GFP control. Subcellular fractionation further revealed that 54.7 kDa isoform of MCD expression was significantly higher in cytosolic fractions of Ad.MCD + Ad.CA-AMPK cells than of the Ad.MCD +Ad.GFP control. However, the MCD activities in cytosolic fractions were not different between the two groups. Interestingly, in the mitochondrial fractions, MCD activity significantly increased in Ad.MCD + Ad.CA-AMPK cells when compared with Ad.MCD + Ad.GFP cells. Using phosphoserine and phosphothreonine antibodies, no phosphorylation of MCD by AMPK was observed. The increase in MCD activity in mitochondria-rich fractions of Ad.MCD + Ad.CA-AMPK cells was accompanied by an increase in the level of the 50.7 kDa isoform of MCD protein in the mitochondria. This differential regulation of MCD expression and activity in the mitochondria by AMPK may potentially regulate malonyl-CoA levels at sites nearby CPT-I on the mitochondria.

Cognitively normal individuals with AD parents may be at risk for developing aging-related cortical thinning patterns characteristic of AD.

PubMed

Reiter, Katherine; Alpert, Kathryn I; Cobia, Derin J; Kwasny, Mary J; Morris, John C; Csernansky, John C; Wang, Lei

2012-07-02

Children of Alzheimer's disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p<0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female. Copyright © 2012 Elsevier Inc. All rights reserved.

COGNITIVELY NORMAL INDIVIDUALS WITH AD PARENTS MAY BE AT RISK FOR DEVELOPING AGING-RELATED CORTICAL THINNING PATTERNS CHARACTERISTIC OF AD

PubMed Central

Reiter, Katherine; Alpert, Kathryn I.; Cobia, Derin J.; Kwasny, Mary J.; Morris, John C.; Csernansky, John C.; Wang, Lei

2012-01-01

Children of Alzheimer's Disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p < 0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female. PMID:22503937

The clinical and economic burden of newly diagnosed Alzheimer's disease in a medicare advantage population.

PubMed

Suehs, Brandon T; Davis, Cralen D; Alvir, Jose; van Amerongen, Derek; Pharmd, Nick C Patel; Joshi, Ashish V; Faison, Warachal E; Shah, Sonali N

2013-06-01

Alzheimer's disease (AD) represents a serious public health issue affecting approximately 5.4 million individuals in the United States and is projected to affect up to 16 million by 2050. This study examined health care resource utilization (HCRU), costs, and comorbidity burden immediately preceding new diagnosis of AD and 2 years after diagnosis. This study utilized a claims-based, retrospective cohort design. Medicare Advantage members newly diagnosed with AD (n = 3374) were compared to matched non-AD controls (n = 6748). All patients with AD were required to have 12 months of continuous enrollment prior to AD diagnosis (International Classification of Diseases, Clinical Modification [ICD-9] 331.0), during which time no diagnosis of AD, a related dementia, or an AD medication was observed. Non-AD controls demonstrated no diagnosis of AD, a related dementia, or a prescription claim for an AD medication treatment during their health plan enrollment. Medical and pharmacy claims data were used to measure HCRU, costs, and comorbidity burden over a period of 36 months (12 months pre-diagnosis and 24 months post-diagnosis). The HCRU and costs were greater for AD members during the year prior to diagnosis and during postdiagnosis years 1 and 2 compared to controls. The AD members also displayed greater comorbidity than their non-AD counterparts during postdiagnosis years 1 and 2, as measured by 2 different comorbidity indices. Members newly diagnosed with AD demonstrated greater HCRU, health care costs, and comorbidity burden compared to matched non-AD controls.

Towards Linking Anonymous Authorship in Casual Sexual Encounter Ads

PubMed Central

Fries, Jason A.; Segre, Alberto M.; Polgreen, Philip M.

2013-01-01

Objective This paper constructs an authorship-linked collection or corpus of anonymous, sex-seeking ads found on the classifieds website Craigslist. This corpus is then used to validate an authorship attribution approach based on identifying near duplicate text in ad clusters, providing insight into how often anonymous individuals post sex-seeking ads and where they meet for encounters. Introduction The increasing use of the Internet to arrange sexual encounters presents challenges to public health agencies formulating STD interventions, particularly in the context of anonymous encounters. These encounters complicate or break traditional interventions. In previous work [1], we examined a corpus of anonymous personal ads seeking sexual encounters from the classifieds website Craigslist and presented a way of linking multiple ads posted across time to a single author. The key observation of our approach is that some ads are simply reposts of older ads, often updated with only minor textual changes. Under the presumption that these ads, when not spam, originate from the same author, we can use efficient near-duplicate detection techniques to cluster ads within some threshold similarity. Linking ads in this way allows us to preserve the anonymity of authors while still extracting useful information on the frequency with which authors post ads, as well as the geographic regions in which they seek encounters. While this process detects many clusters, the lack of a true corpus of authorship-linked ads makes it difficult to validate and tune the parameters of our system. Fortunately, many ad authors provide an obfuscated telephone number in ad text (e.g., 867–5309 becomes 8sixseven5three oh nine) to bypass Craigslist filters, which prohibit including phone numbers in personal ads. By matching phone numbers of this type across all ads, we can create a corpus of ad clusters known to be written by a single author. This authorship corpus can then be used to evaluate and tune our existing near-duplicate detection system, and in the future identify features for more robust authorship attribution techniques. Methods From 7-1-2009 until 7-1-2011, RSS feeds were collected daily for 8 personal ad categories from 414 sites across the United States, for a total of 67 million ads. To create an anonymous, author-linked corpus, we used a regular expression to identify obfuscated phone numbers in ad text. We measure the ability of near-duplicate detection to link clusters in two ways: 1) detecting all ads in a cluster; and 2) correctly detecting a subset of ads within a single cluster. Ads incorrectly assigned to more than 1 cluster are considered false positives. All results are reported in terms of precision, recall, and F-scores (common information retrieval metrics) across cluster size, expressed as number of ads. Results 652,014 ads contained phone numbers, producing a total of 46,079 authorship-linked ad clusters. For detecting all ads within a cluster, precision ranged from 0.05 to 0.0 and recall from 0.02 to 0.0 for all cluster sizes. For detecting partial clusters, see Figure 1. Conclusions We find that near-duplicate detection alone is insufficient to detect all ads within a cluster. However, we do find that the process can, with high precision and low recall, detect a subset of ads associated with a single author. This follows the intuition that an author’s total set of ads is itself comprised of multiple self-similar subsets. While a near-duplicate detection approach can correctly identify subsets of ads linked to a single author, this process alone cannot attribute multiple clusters to a single author. Future work will explore leveraging additional linguistic features to improve author attribution. (Top) Evaluations for partial cluster detection using the near-duplicate identification approach to linking anonymous authorship in Craigslist ads and (bottom) the distribution of ad cluster sizes.

Static Einstein-Maxwell Black Holes with No Spatial Isometries in AdS Space.

PubMed

Herdeiro, Carlos A R; Radu, Eugen

2016-11-25

We explicitly construct static black hole solutions to the fully nonlinear, D=4, Einstein-Maxwell-anti-de Sitter (AdS) equations that have no continuous spatial symmetries. These black holes have a smooth, topologically spherical horizon (section), but without isometries, and approach, asymptotically, global AdS spacetime. They are interpreted as bound states of a horizon with the Einstein-Maxwell-AdS solitons recently discovered, for appropriate boundary data. In sharp contrast to the uniqueness results for a Minkowski electrovacuum, the existence of these black holes shows that single, equilibrium, black hole solutions in an AdS electrovacuum admit an arbitrary multipole structure.

Risk of incident clinical diagnosis of AD-type dementia attributable to pathology-confirmed vascular disease

PubMed Central

Dodge, Hiroko H.; Zhu, Jian; Woltjer, Randy; Nelson, Peter T.; Bennett, David A.; Cairns, Nigel J.; Fardo, David W.; Kaye, Jeffrey A.; Lyons, Deniz-Erten; Mattek, Nora; Schneider, Julie A; Silbert, Lisa C.; Xiong, Chengjie; Yu, Lei; Schmitt, Frederick A.; Kryscio, Richard J.; Abner, Erin L.

2016-01-01

Introduction Presence of cerebrovascular pathology may increase the risk of clinical diagnosis of AD. Methods We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modelling of Aging and Risk of Transition (SMART) study, a consortium of longitudinal cohort studies with over 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts). Results The coexistence of lacunes and large infarcts results in higher likelihood of clinical diagnosis of AD only when AD pathology burden is low. Discussion Our results reinforce the diagnostic importance of AD pathology in clinical AD. Further harmonization of assessment approaches for vascular pathologies is required. PMID:28017827

Neurometabolic characteristics in the anterior cingulate gyrus of Alzheimer's disease patients with depression: a (1)H magnetic resonance spectroscopy study.

PubMed

Guo, Zhongwei; Zhang, Jiangtao; Liu, Xiaozheng; Hou, Hongtao; Cao, Yulin; Wei, Fuquan; Li, Japeng; Chen, Xingli; Shen, Yuedi; Chen, Wei

2015-12-02

Depression is a common comorbid psychiatric symptom in patients with Alzheimer's disease (AD), and the prevalence of depression is higher among people with AD compared with healthy older adults. Comorbid depression in AD may increase the risk of cognitive decline, impair patients' function, and reduce their quality of life. However, the mechanisms of depression in AD remain unclear. Here, our aim was to identify neurometabolic characteristics in the brain that are associated with depression in patients with mild AD. Thirty-seven patients were evaluated using the Neuropsychiatric Inventory (NPI) and Hamilton Depression Rating Scale (HAMD-17), and divided into two groups: 17 AD patients with depression (D-AD) and 20 non-depressed AD patients (nD-AD). Using proton magnetic resonance spectroscopy, we characterized neurometabolites in the anterior cingulate gyrus (ACG) of D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed lower N-acetylaspartate/creatine (NAA/Cr) and higher myo-inositol/creatine (mI/Cr) in the left ACG. NPI score correlated with NAA/Cr and mI/Cr in the left ACG, while HAMD correlated with NAA/Cr. Our findings show neurometabolic alterations in D-AD patients. Thus, D-AD pathogenesis may be attributed to abnormal activity of neurons and glial cells in the left ACG.

RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF

PubMed Central

Krause, A; Whu, W Z; Qiu, J; Wafadari, D; Hackett, N R; Sharma, A; Crystal, R G; Worgall, S

2013-01-01

Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine–glycine–aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8+ and interleukin (IL)-12 in CD4+], Th2 (IL-4, IL-5 and IL-13 in CD4+) and Th17 (IL-17 in CD4+). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P. aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity. PMID:23607394

SAO/NASA ADS at SAO: User Feedback

Science.gov Websites

Sign on [SAO/NASA ADS] User Feedback ADS Home | HELP | Sitemap ADS Services Search Browse myADS Mirrors Feedback FAQ What's new Site Map Help Other NASA Centers CXC HEASARC IRSA MAST NED NSSDC PDS [NASA] NASA ads at cfa.harvard.edu

A Comparison of the Behavioural and Emotional Characteristics of Alzheimer's Dementia in Individuals with and without Down Syndrome

ERIC Educational Resources Information Center

Temple, Valerie; Konstantareas, M. Mary

2005-01-01

The behavioural and emotional changes associated with Alzheimer's disease (AD) are compared for individuals with Down syndrome and AD and individuals with AD from the general population (AD-only). The primary caregivers of 30 people with Down syndrome and AD and 30 people with AD-only completed the BEHAVE-AD and the Apathy subscale of the CERAD.…

Next-Generation A/D Sampler ADS3000+ for VLBI2010

NASA Technical Reports Server (NTRS)

Takefuji, Kazuhiro; Takeuchi, Hiroshi; Tsutsumi, Masanori; Koyama, Yasuhiro

2010-01-01

A high-speed A/D sampler, called ADS3000+, has been developed in 2008, which can sample one analog signal up to 4 Gbps to versatile Linux PC. After A/D conversion, the ADS3000+ can perform digital signal processing such as real-time DBBC (Digital Base Band Conversion) and FIR filtering such as simple CW RFI filtering using the installed FPGAs. A 4 Gsps fringe test with the ADS3000+ has been successfully performed. The ADS3000+ will not exclusively be used for VLBI but will also be employed in other applications.

Amplified and persistent immune responses generated by single-cycle replicating adenovirus vaccines.

PubMed

Crosby, Catherine M; Nehete, Pramod; Sastry, K Jagannadha; Barry, Michael A

2015-01-01

Replication-competent adenoviral (RC-Ad) vectors generate exceptionally strong gene-based vaccine responses by amplifying the antigen transgenes they carry. While they are potent, they also risk causing adenovirus infections. More common replication-defective Ad (RD-Ad) vectors with deletions of E1 avoid this risk but do not replicate their transgene and generate markedly weaker vaccine responses. To amplify vaccine transgenes while avoiding production of infectious progeny viruses, we engineered "single-cycle" adenovirus (SC-Ad) vectors by deleting the gene for IIIa capsid cement protein of lower-seroprevalence adenovirus serotype 6. In mouse, human, hamster, and macaque cells, SC-Ad6 still replicated its genome but prevented genome packaging and virion maturation. When used for mucosal intranasal immunization of Syrian hamsters, both SC-Ad and RC-Ad expressed transgenes at levels hundreds of times higher than that of RD-Ad. Surprisingly, SC-Ad, but not RC-Ad, generated higher levels of transgene-specific antibody than RD-Ad, which notably climbed in serum and vaginal wash samples over 12 weeks after single mucosal immunization. When RD-Ad and SC-Ad were tested by single sublingual immunization in rhesus macaques, SC-Ad generated higher gamma interferon (IFN-γ) responses and higher transgene-specific serum antibody levels. These data suggest that SC-Ad vectors may have utility as mucosal vaccines. This work illustrates the utility of our recently developed single-cycle adenovirus (SC-Ad6) vector as a new vaccine platform. Replication-defective (RD-Ad6) vectors produce low levels of transgene protein, which leads to minimal antibody responses in vivo. This study shows that replicating SC-Ad6 produces higher levels of luciferase and induces higher levels of green fluorescent protein (GFP)-specific antibodies than RD in a permissive Syrian hamster model. Surprisingly, although a replication-competent (RC-Ad6) vector produces more luciferase than SC-Ad6, it does not elicit comparable levels of anti-GFP antibodies in permissive hamsters. When tested in the larger rhesus macaque model, SC-Ad6 induces higher transgene-specific antibody and T cell responses. Together, these data suggest that SC-Ad6 could be a more effective platform for developing vaccines against more relevant antigens. This could be especially beneficial for developing vaccines for pathogens for which traditional replication-defective adenovirus vectors have not been effective. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Abeta42 immunisation in Alzheimer's disease.

PubMed

Boche, Delphine; Donald, Jane; Love, Seth; Harris, Scott; Neal, James W; Holmes, Clive; Nicoll, James A R

2010-07-01

Alzheimer's disease (AD) pathology is characterised by aggregation in the brain of amyloid-beta (Abeta) peptide and hyperphosphorylated tau (phospho-tau), although how these proteins interact in disease pathogenesis is unclear. Abeta immunisation results in removal of Abeta from the brain but cognitive decline continues to progress, possibly due to persistent phospho-tau. We quantified phospho-tau and Abeta42 in the brains of 10 AD patients (iAD) who were actively immunised with Abeta42 (AN1792, Elan Pharmaceuticals) compared with 28 unimmunised AD cases (cAD). The phospho-tau load was lower in the iAD than the cAD group in the cerebral cortex (cAD 1.08% vs. iAD 0.72%, P = 0.048), CA1 hippocampus (cAD 2.26% vs. iAD 1.05%; P = 0.001), subiculum (cAD 1.60% vs. iAD 0.31%; P = 0.001) and entorhinal cortex (cAD 1.10% vs. iAD 0.18%; P < 0.001). Assessment of the localisation within neurons of phospho-tau indicated that the Abeta immunotherapy-associated reduction was confined to neuronal processes, i.e. neuropil threads and dystrophic neurites. However, the phospho-tau accumulation in the neuronal cell bodies, contributing to neurofibrillary tangles, appeared not to be affected. In showing that Abeta immunisation can influence phospho-tau pathology, we confirm the position of Abeta as a target for modifying tau accumulation in AD and demonstrate a link between these proteins. However, the continuing progression of cognitive decline in AD patients after Abeta immunisation may be explained by its lack of apparent effect on tangles.

Human adenovirus serotypes 4p and 11p are efficiently expressed in cell lines of neural tumour origin.

PubMed

Skog, Johan; Mei, Ya-Fang; Wadell, Göran

2002-06-01

Most currently used adenovirus vectors are based upon adenovirus serotypes 2 and 5 (Ad2 and Ad5), which have limited efficiencies for gene transfer to human neural cells. Both serotypes bind to the known adenovirus receptor, CAR (coxsackievirus and adenovirus receptor), and have restricted cell tropism. The purpose of this study was to find vector candidates that are superior to Ad5 in infecting human neural tumours. Using flow cytometry, the vector candidates Ad4p, Ad11p and Ad17p were compared to the commonly used adenovirus vector Ad5v for their binding capacity to neural cell lines derived from glioblastoma, medulloblastoma and neuroblastoma cell lines. The production of viral structural proteins and the CAR-binding properties of the different serotypes were also assessed in these cells. Computer-based models of the fibre knobs of Ad4p and Ad17 were created based upon the crystallized fibre knob structure of adenoviruses and analysed for putative receptor-interacting regions that differed from the fibre knob of Ad5. The non CAR-binding vector candidate Ad11p showed clearly the best binding capacity to all of the neural cell lines, binding more than 90% of cells of all of the neural cell lines tested, in contrast to 20% or less for the commonly used vector Ad5v. Ad4p and Ad11p were also internalized and produced viral proteins more successfully than Ad5. Ad4p showed a low binding ability but a very efficient capacity for infection in cell culture. Ad17p virions neither bound or efficiently infected any of the neural cell lines studied.

Association between Diabetes and Risk of Aortic Dissection: A Case-Control Study in a Chinese Population.

PubMed

He, Xingwei; Liu, Xintian; Liu, Wanjun; Wang, Bei; Liu, Yujian; Li, Zhuxi; Wang, Tao; Tan, Rong; Gao, Bo; Zeng, Hesong

2015-01-01

It is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD). The aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population. A hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk. The prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all P<0.001). Furthermore, in multivariate model, diabetes was found to be associated with lower AD risk, which not only applies to the overall AD (OR = 0.2, 95%CI: 0.15-0.26), but also type A AD (OR = 0.12, 95% CI: 0.07-0.20) and type B AD (OR = 0.25, 95%CI: 0.18-0.33). We observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends.

Atypical depression among psychiatric inpatients: clinical features and personality traits.

PubMed

Derecho, C N; Wetzler, S; McGinn, L K; Sanderson, W C; Asnis, G M

1996-06-20

This study investigates the frequency and characteristics of Atypical Depression (AD) among depressed inpatients. Twenty-one depressed inpatients received DSM-IV diagnoses, were rated on the Hamilton Depression Rating Scale (HAMD), and assessed for AD using the Atypical Depressive Disorder Scale. AD was defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. Mood reactivity was defined as the ability to reach 50% of a non-depressed mood. All subjects completed the SCL-90, MCMI-II, and a suicide survey. Seven patients (33%) met criteria for AD. AD and non-AD patients did not differ in terms of severity of depression, history of suicide attempts, levels of clinical symptomatology, age of onset of depression, prior hospitalizations, and most personality characteristics. However, AD patients scored significantly higher than non-AD patients on the SCL-90 Interpersonal Sensitivity and MCMI-II Avoidant scales, and were more likely to be single. AD is fairly prevalent on an inpatient service, comparable to the frequency found in outpatient settings. AD is not a milder form of depression. The only differences between AD and non-AD patients reflect the personality trait of rejection sensitivity which is a defining feature of AD.

Sense of coherence, depression, and anger among adults with atopic dermatitis.

PubMed

Takaki, Hiroko; Ishii, Yasutomo

2013-01-01

The prevalence of atopic disease (AD) in adults has significantly increased in industrialized countries. Psychological traits and lack of skills to cope with stress could be maintaining factors of AD. The first aim of the present study was to compare sense of coherence (SOC), depression, and anger among adult patients with AD, adults with remission from AD, and adults without AD. The second aim was to explore whether depression and anger have significant impacts on SOC. A cross-sectional survey was carried out from May to September of 2007. In total, 43 adult patients with AD, 32 adults with remission from AD, and 63 adults without AD participated. A one-way analysis of variance showed that adult patients with AD have significantly higher levels of depression than adults with remission from AD and adults without AD. Furthermore, structural equation modeling indicated a significant impact of depression on SOC across the three groups, along with a significant impact of anger suppression on depression, particularly in adult patients with AD. The findings of this study suggest that psychological traits have a negative impact on skills for coping with stress, and that this relationship might be a contributory factor for maintenance of AD.

Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43.

PubMed

Belousova, Natalya; Mikheeva, Galina; Xiong, Chiyi; Stagg, Loren J; Gagea, Mihai; Fox, Patricia S; Bassett, Roland L; Ladbury, John E; Braun, Michael B; Stehle, Thilo; Li, Chun; Krasnykh, Victor

2016-08-16

Unique molecular properties of species D adenoviruses (Ads)-the most diverse yet underexplored group of Ads-have been used to develop improved gene vectors. The low seroprevalence in humans of adenovirus serotype 43 (Ad43), an otherwise unstudied species D Ad, identified this rare serotype as an attractive new human gene therapy vector platform. Thus, in this study we wished to assess biological properties of Ad43 essential to its vectorization. We found that (1) Ad43 virions do not bind blood coagulation factor X and cause low random transduction upon vascular delivery; (2) they clear host tissues more quickly than do traditionally used Ad5 vectors; (3) Ad43 uses CD46 as primary receptor; (4) Ad43 can use integrins as alternative primary receptors. As the first step toward vectorization of Ad43, we demonstrated that the primary receptor specificity of the Ad43 fiber can be altered to achieve infection via Her2, an established oncotarget. Whereas this modification required use of the Ad5 fiber shaft, the presence of this domain in chimeric virions did not make them susceptible for neutralization by anti-Ad5 antibodies.

A content analysis of outdoor non-alcoholic beverage advertisements in Ghana.

PubMed

Bragg, Marie A; Hardoby, Tamara; Pandit, Natasha G; Raji, Yemi R; Ogedegbe, Gbenga

2017-06-06

This was a two-part descriptive study designed to (1) assess the marketing themes and sugar content of beverages promoted in outdoor advertisements (ads) within a portion of Accra, Ghana and (2) quantify the types of ads that appeared along the Accra-Cape Coast Highway. A 4.7 km 2 area of Accra, Ghana and a 151 km region along the highway represented the target areas for collecting photos of outdoor beverage ads. Number and types of beverage ads, sugar content of beverage products featured in ads and marketing themes used in ads. Two researchers photographed outdoor beverage ads in a 4.7 km 2 area of Accra and used content analysis to assess marketing themes of ads, including the portrayal of children, local culture, music, sports and health. Researchers also recorded the number and type of ads along a 151 km stretch of the Accra-Cape Coast Highway. Researchers assessed the added sugar content to determine which beverages were sugar-sweetened beverages (SSBs). Seventy-seven photographed ads were analysed. Seventy-three per cent (72.7%) of ads featured SSBs, and Coca-Cola accounted for 59.7% of ads. Sixty-five per cent (64.9%) of all ads featured sodas, while 35.1% advertised energy drinks, bottled or canned juice drinks and coffee-based, milk-based and water-based beverages. Thirteen per cent (13%) of ads featured children and 5.2% were located near schools or playgrounds. Nine per cent (9.1%) of ads contained a reference to health and 7.8% contained a reference to fitness/strength/sport. Along the Accra-Cape Coast Highway, Coca-Cola accounted for 60% of branded ads. This study demonstrates the frequency of outdoor SSB ads within a 4.7 km 2 area of Accra, Ghana. Coca-Cola was featured in the majority of ads, and the child-targeted nature of some ads indicates a need to expand the Children's Food and Beverage Advertising Initiative pledge to reduce child-targeted marketing on a global scale. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A content analysis of outdoor non-alcoholic beverage advertisements in Ghana

PubMed Central

Bragg, Marie A; Hardoby, Tamara; Pandit, Natasha G; Raji, Yemi R; Ogedegbe, Gbenga

2017-01-01

Objectives This was a two-part descriptive study designed to (1) assess the marketing themes and sugar content of beverages promoted in outdoor advertisements (ads) within a portion of Accra, Ghana and (2) quantify the types of ads that appeared along the Accra-Cape Coast Highway. Setting A 4.7 km2 area of Accra, Ghana and a 151 km region along the highway represented the target areas for collecting photos of outdoor beverage ads. Primary and secondary outcome measures Number and types of beverage ads, sugar content of beverage products featured in ads and marketing themes used in ads. Design Two researchers photographed outdoor beverage ads in a 4.7 km2 area of Accra and used content analysis to assess marketing themes of ads, including the portrayal of children, local culture, music, sports and health. Researchers also recorded the number and type of ads along a 151 km stretch of the Accra-Cape Coast Highway. Researchers assessed the added sugar content to determine which beverages were sugar-sweetened beverages (SSBs). Results Seventy-seven photographed ads were analysed. Seventy-three per cent (72.7%) of ads featured SSBs, and Coca-Cola accounted for 59.7% of ads. Sixty-five per cent (64.9%) of all ads featured sodas, while 35.1% advertised energy drinks, bottled or canned juice drinks and coffee-based, milk-based and water-based beverages. Thirteen per cent (13%) of ads featured children and 5.2% were located near schools or playgrounds. Nine per cent (9.1%) of ads contained a reference to health and 7.8% contained a reference to fitness/strength/sport. Along the Accra-Cape Coast Highway, Coca-Cola accounted for 60% of branded ads. Conclusion This study demonstrates the frequency of outdoor SSB ads within a 4.7 km2 area of Accra, Ghana. Coca-Cola was featured in the majority of ads, and the child-targeted nature of some ads indicates a need to expand the Children’s Food and Beverage Advertising Initiative pledge to reduce child-targeted marketing on a global scale. PMID:28588104

Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice.

PubMed

Baglietto-Vargas, David; Chen, Yuncai; Suh, Dongjin; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Myczek, Kristoffer; Green, Kim N; Baram, Tallie Z; LaFerla, Frank M

2015-09-01

Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD-related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short-term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short-term, multi-modal 'modern life-like' stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short-term stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. Epidemiological evidence indicates that life experiences, including chronic stress, are a risk for Alzheimer disease (AD). However, it is unknown if short stress in the range of hours influences the onset or progression of AD. Here, we determined the effect of short, multi-modal 'modern-lifelike'stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. © 2015 International Society for Neurochemistry.

Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.

PubMed

Struyfs, Hanne; Van Broeck, Bianca; Timmers, Maarten; Fransen, Erik; Sleegers, Kristel; Van Broeckhoven, Christine; De Deyn, Peter P; Streffer, Johannes R; Mercken, Marc; Engelborghs, Sebastiaan

2015-01-01

Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis. To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P). CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16). Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers. Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.

Testing messages to reduce smokers’ openness to using novel smokeless tobacco products

PubMed Central

Popova, Lucy; Neilands, Torsten B.; Ling, Pamela M.

2013-01-01

Introduction Tobacco manufacturers’ aggressive promotion of new smokeless tobacco products such as snus warrants a timely and effective public health response. This study tested potential counter-marketing messages to discourage current and former smokers from becoming dual users of smokeless tobacco and cigarettes. Methods In a pretest – post-test experiment, 1,836 adult current and recently former smokers from a national sample were randomized to view one of six anti-smokeless tobacco ads followed by a snus ad, to view a control ad followed by a snus ad; or to view two control ads. Perceived effectiveness of ads and actual changes in attitudes and openness to snus were compared across groups using analyses of variance. Results Some ads that were perceived as most effective did not change attitudes or openness to trying snus, and conversely, some ads not perceived as effective changed attitudes and openness to snus. Ads portraying the negative health effects of smokeless tobacco were perceived as most effective, but ads with anti-tobacco industry themes significantly decreased favorable attitudes toward snus. Responses to ads were different for smokers who had ever used smokeless tobacco: for this group health effects and humorous/testimonial ads were effective. Conclusions Measures of perceived effectiveness of anti-tobacco ads need to be augmented with measures of actual effectiveness to assess counter-marketing messages. Some of the developed ads, such as ads with anti-industry themes, were effective for the overall population of smokers whereas humorous/testimonial and health effects ads were particularly effective in changing attitudes of past users of smokeless tobacco. PMID:23467655

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

PubMed

Woodward, Matthew R; Hafeez, Muhammad Ubaid; Qi, Qianya; Riaz, Ahmed; Benedict, Ralph H B; Yan, Li; Szigeti, Kinga

2018-04-19

To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. Prospective multicenter cross-sectional study with a longitudinal arm. Outpatient memory diagnostic clinics in New York and Texas. Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients.

PubMed

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P  < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P  = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P  < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 ( P  < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group ( P  < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines.

The Knowing-Doing Gap in Advance Directives in Asian Americans: The Role of Education and Acculturation.

PubMed

Jang, Yuri; Park, Nan Sook; Chiriboga, David A; Radhakrishnan, Kavita; Kim, Miyong T

2017-11-01

The purposes of the present study were (1) to explore the completion rate of advance directives (ADs) in a sample of Asian Americans and (2) to examine the direct and moderating effects of knowledge of AD, education, and acculturation in predicting AD completion. Education and acculturation were conceptualized as moderators in the link between knowledge and completion of ADs. Using data from 2609 participants in the 2015 Asian American Quality of Life survey (aged 18-98), logistic regression analyses on AD completion were conducted, testing both direct and moderating effects. The overall AD completion rate in sample was about 12%. The AD knowledge and acculturation independently predicted AD completion. No direct effect of education was found; however, it interacted with AD knowledge. The AD knowledge was more likely to be translated into completion in the group with higher education. The AD completion rate observed in the present sample of Asian Americans was much lower than that of the US general population (26%-36%). The interactive role of education helps to explain the gap between AD knowledge and completion and suggests intervention strategies.

Genetics Home Reference: fibrodysplasia ossificans progressiva

MedlinePlus

... Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown ... added]; Morhart, Rolf [added]; Rogers, John G [added]; Smith, Roger [added]; Triffitt, James T [added]; Urtizberea, J ...

Structures and physical properties of the cocrystals of adefovir dipivoxil with dicarboxylic acids

NASA Astrophysics Data System (ADS)

Jung, Sungyup; Lee, Jonghwi; Kim, Il Won

2013-06-01

The cocrystallization of adefovir dipivoxil (AD) with suberic acid (SUB) or succinic acid (SUC) was examined. X-ray diffraction was used to determine the structures of AD/SUB and AD/SUC cocrystals. Both cocrystals were formed via multiple hydrogen bonds between the adenine part of AD and the carboxylic acid groups of SUB or SUC. Longer SUB effectively dispersed AD molecules, and AD hydrogen-bonded only to SUB. When shorter SUC was used, AD formed hydrogen bonding with both SUC and adjacent AD. As a result, the cocrystal compositions were AD/SUB=1:1 and AD/SUC=2:1. Both cocrystals displayed superior thermal stability and increased aqueous solubility. The present study demonstrated that the adenine and similar structures of active pharmaceutical ingredients could be used to produce cocrystals of improved physical properties.

Effects on asthma and induction of interleukin-8 caused by Asian dust particles collected in western Japan.

PubMed

Watanabe, Masanari; Kurai, Jun; Tomita, Katsuyuki; Sano, Hiroyuki; Abe, Satoshi; Saito, Rumiko; Minato, Sayaka; Igishi, Tadashi; Burioka, Naoto; Sako, Takanori; Yasuda, Kazuhito; Mikami, Masaaki; Kurita, Shinichi; Tokuyasu, Hirokazu; Ueda, Yasuto; Konishi, Tatsuya; Yamasaki, Akira; Aiba, Setsuya; Oshimura, Mitsuo; Shimizu, Eiji

2014-08-01

Asian dust storms (ADS) contain various airborne particles that may augment airway inflammation by increasing the level of interleukin-8. The objective of the study was to investigate the association of exposure to an ADS with worsening of symptoms of adult asthma and the effect of ADS particles on interleukin-8 transcriptional activity. The subjects were 112 patients with mild to moderate asthma who recorded scores for their daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF) from March to May 2011. Interleukin-8 transcriptional activity was assessed in THP-G8 cells that were exposed to airborne particles collected during days of ADS exposure. Of the 112 patients, 31 had comorbid allergic rhinitis (AR) and/or chronic sinusitis (CS), and had worsened scores for upper respiratory tract symptoms on ADS days compared to non-ADS days. Scores for lower respiratory tract symptoms during ADS days were higher than non-ADS days in all patients. Three patients also had unscheduled hospital visits for exacerbation of asthma on ADS days. However, there was no significant difference in daily morning PEF between ADS and non-ADS days. Airborne particles collected on ADS days induced interleukin-8 transcriptional activity in THP-G8 cells compared to the original soil of the ADS. Exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma. ADS airborne particles may increase airway inflammation through enhancement of interleukin-8 transcriptional activity.

Immunostimulatory activities of dendritic cells loaded with adenovirus vector carrying HBcAg/HBsAg

PubMed Central

Jia, Hongyu; Li, Chunling; Zhang, Yimin; Yu, Liang; Xiang, Dairong; Liu, Jun; Chen, Fengzhe; Han, Xiaochun

2015-01-01

Objective: This study is to investigate the immunostimulatory activities of dendritic cells (DCs) transfected with HBcAg and/or HBsAg recombinant adenovirus (rAd). Methods: DCs were transfected with rAd (DC/Ad-C+Ad-S, DC/Ad-C, and DC/Ad-S), or pulsed with HBcAg antigen (DC/HBcAg). Flow cytometry was used to detect the phenotype of DCs and the cytokine production of T lymphocytes. Mice were vaccinated with DCs transfected with rAd or pulsed with antigen, and DNA vaccine. Mixed lymphocyte reaction (MLR) was used to evaluate the T-cell stimulatory capacity, and HBcAg-specific cytotoxic T lymphocyte (CTL) activity was assessed. Results: Phenotypic analysis showed that DCs transfected with rAd or pulsed with HBcAg antigen exhibited mature phenotypes. MLR indicated no significant differences in stimulating T-cell proliferation between the DC/rAd and DC/HBcAg groups. When mixed with DCs, Th and Tc cells mainly secreted IFN-γ, indicating type I immune responses. In vaccinated mice, DCs transduced with rAd and pulsed with HBcAg induced significantly more IFN-γ secretion from Th cells, compared with DNA vaccine, indicating stronger Th1 response. Moreover, DCs transduced with rAd stimulated Tc cells to produce more IFN-γ, indicating stronger Tc1 response. In vaccinated mice, HBcAg-specific CTL activities were decreased in the following order: the DC/Ad-C+Ad-S, DC/Ad-C, DC/Ad-S, DC/HBcAg, and DNA vaccine groups. Conclusion: DCs transfected with rAd induce stronger Th1/Tc1 (type I) cell immune responses and specific CTL response than HBcAg-pulsed DCs or DNA vaccine. Our findings suggest that DCs transfected with rAd-C/rAd-S might provide an effective approach in the treatment of persistent hepatitis B virus infection. PMID:26064236

Profilaxia de tromboembolismo venoso na gestação

PubMed Central

de Oliveira, André Luiz Malavasi Longo; Marques, Marcos Arêas

2016-01-01

Resumo O tromboembolismo venoso é importante causa de morbidade e mortalidade obstétrica. Durante a gestação, o risco de sua ocorrência aumenta entre cinco e dez vezes quando comparado ao de mulheres não gestantes de mesma idade. Associado a esse fato, a gestante apresenta algumas limitações para o diagnóstico clínico (alta frequência de dor e edema nos membros inferiores), ecográfico (menor sensibilidade e especificidade no diagnóstico de trombose venosa de ilíaca com a evolução da gestação) e laboratorial (o D-dímero apresenta aumento progressivo no decorrer da gravidez). Uma estratificação criteriosa de risco de tromboembolismo venoso de cada mulher antes da gestação pode diminuir a incidência dessa doença, frequente e de difícil diagnóstico na gravidez, e suas complicações. PMID:29930607

Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.

PubMed

Leopold, Philip L; Wendland, Rebecca L; Vincent, Theresa; Crystal, Ronald G

2006-10-01

Neutralization of adenovirus (Ad) by anti-Ad neutralizing antibodies in serum involves formation of Ad-immune complexes that prevent the virus from interacting with target cells. We hypothesized that Ad-immune complexes likely contain viable Ad vectors which, although no longer capable of gaining access to receptors on target cells, may be able to express transgenes in cells bearing Fc receptors for immunoglobulins, i.e., that antibody-based "neutralization" of Ad vectors may be circumvented by the Fc receptor pathway. To test this hypothesis, we expressed the Fcgamma receptor IIA (FcgammaR) in A549 lung epithelial cells or human dermal fibroblasts and evaluated gene transfer in the presence of human neutralizing anti-Ad serum. FcgammaR-expressing cells bound and internalized copious amounts of Ad, with a distinct population of internalized Ad trafficking to the nucleus. The dose-response curves for inhibition of gene transfer revealed that FcgammaR-expressing cells required a more-than-10-fold higher concentration of anti-Ad serum to achieve 50% inhibition of Ad-encoded beta-galactosidase expression compared with non-FcgammaR-expressing cells. The discrepancy between neutralization of Ad during infection of FcgammaR-expressing cells and neutralization of Ad during infection of non-FcgammaR-expressing cells occurred with either heat-inactivated or non-heat-inactivated sera, was blocked by addition of purified Fc domain protein, and did not require the cytoplasmic domain of FcgammaR, suggesting that immune complex internalization proceeded via endocytosis rather than phagocytosis. FcgammaR-mediated infection by Ad-immune complexes did not require expression of the coxsackie virus-Ad receptor (CAR) since similar data were obtained when CAR-deficient human dermal fibroblasts were engineered to express FcgammaR. However, interaction of the Ad penton base with cell surface integrins contributed to the difference in neutralization between FcgammaR-expressing and non-FcgammaR-expressing cells. The data indicate that complexes formed from Ad and anti-Ad neutralizing antibodies, while compromised with respect to infection of non-FcgammaR-expressing target cells, maintain the potential to transfer genes to FcgammaR-expressing cells, with consequent expression of the transgene. The formation of Ad-immune complexes that can target viable virus to antigen-presenting cells may account for the success of Ad-based vaccines administered in the presence of low levels of neutralizing anti-Ad antibody.

A review on the applications of microbial electrolysis cells in anaerobic digestion.

PubMed

Yu, Zhengsheng; Leng, Xiaoyun; Zhao, Shuai; Ji, Jing; Zhou, Tuoyu; Khan, Aman; Kakde, Apurva; Liu, Pu; Li, Xiangkai

2018-05-01

Anaerobic digestion (AD) has been widely used for biogas or biofuel generation from waste treatment. Because a low production rate and instability of AD occur frequently, various technologies have been applied to improvement of AD. Microbial electrolysis cells (MECs), an emerging technology, can convert organic matter into hydrogen, methane, and other value-added products. Recent studies showed that application of MEC to AD (MEC-AD) can accelerate degradation of a substrate (including recalcitrant compounds) and alter AD microbial community by enriching exoelectrogens and methanogens thus increasing biogas production. With stable microbial communities established, improvement of MEC-AD for methane production was achieved. MEC-AD process can be monitored in real-time by detecting electric signals, which linearly correlate with substrate concentrations. This review attempts to evaluate interactions among the decomposition of substrates, MEC-AD system, and the microbial community. This analysis should provide useful insights into the improvement of methane production and the performance of MEC-AD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Abnormal baseline brain activity in Alzheimer's disease patients with depression: a resting-state functional magnetic resonance imaging study.

PubMed

Liu, Xiaozheng; Guo, Zhongwei; Ding, Yanping; Li, Jiapeng; Wang, Gang; Hou, Hongtao; Chen, Xingli; Yu, Enyan

2017-07-01

As one of the most common mental disorders and the most important precursor of suicide in Alzheimer's disease (AD), depression is associated with a decline in both well-being and daily functioning. At present, the diagnosis of AD patients with depression (D-AD) is largely dependent on clinical signs and symptoms, and the precise neural correlate underlying D-AD is still not fully understood. The current study sought to investigate low-frequency oscillations at the voxel level in D-AD patients based on the amplitude of low-frequency fluctuations (ALFF) measured using resting-state functional magnetic resonance imaging. We examined 22 D-AD patients and 21 non-depressed AD (nD-AD) patients. The results revealed that D-AD patients exhibited increased ALFF values in the left caudate and thalamus and decreased ALFF values in the left middle temporal pole compared with nD-AD patients. These findings may provide further insight into the underlying neuropathophysiology of AD with depression.

Depletion of coagulation factor XII ameliorates brain pathology and cognitive impairment in Alzheimer disease mice.

PubMed

Chen, Zu-Lin; Revenko, Alexey S; Singh, Pradeep; MacLeod, A Robert; Norris, Erin H; Strickland, Sidney

2017-05-04

Vascular abnormalities and inflammation are found in many Alzheimer disease (AD) patients, but whether these changes play a causative role in AD is not clear. The factor XII (FXII) -initiated contact system can trigger both vascular pathology and inflammation and is activated in AD patients and AD mice. We have investigated the role of the contact system in AD pathogenesis. Cleavage of high-molecular-weight kininogen (HK), a marker for activation of the inflammatory arm of the contact system, is increased in a mouse model of AD, and this cleavage is temporally correlated with the onset of brain inflammation. Depletion of FXII in AD mice inhibited HK cleavage in plasma and reduced neuroinflammation, fibrinogen deposition, and neurodegeneration in the brain. Moreover, FXII-depleted AD mice showed better cognitive function than untreated AD mice. These results indicate that FXII-mediated contact system activation contributes to AD pathogenesis, and therefore this system may offer novel targets for AD treatment. © 2017 by The American Society of Hematology.

Biogas energy production from tropical biomass wastes by anaerobic digestion.

PubMed

Ge, Xumeng; Matsumoto, Tracie; Keith, Lisa; Li, Yebo

2014-10-01

Anaerobic digestion (AD) is an attractive technology in tropical regions for converting locally abundant biomass wastes into biogas which can be used to produce heat, electricity, and transportation fuels. However, investigations on AD of tropical forestry wastes, such as albizia biomass and food wastes, such as taro, papaya, and sweet potato, are limited. In this study, these tropical biomass wastes were evaluated for biogas production by liquid AD (L-AD) and/or solid-state AD (SS-AD), depending on feedstock characteristics. When albizia leaves and chips were used as feedstocks, L-AD had greater methane yields (161 and 113 L kg(-1)VS, respectively) than SS-AD (156.8 and 59.6 L kg(-1)VS, respectively), while SS-AD achieved 5-fold higher volumetric methane productivity than L-AD. Mono-digestion and co-digestion of taro skin, taro flesh, papaya, and sweet potato achieved methane yields from 345 to 411 L kg(-1)VS, indicating the robustness of AD technology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preclinical Alzheimer's Disease: Implications for Refinement of the Concept.

PubMed

Vos, Stephanie J B; Visser, Pieter Jelle

2018-05-23

Increasing interest in clinical trials and clinical research settings to identify Alzheimer's disease (AD) in the earliest stages of the disease has led to the concept of preclinical AD. Individuals with preclinical AD have AD pathology without clinical symptoms yet. Accumulating evidence has shown that biomarkers can identify preclinical AD and that preclinical AD is associated with a poor clinical outcome. Little is known yet about the role of vascular and lifestyle risk factors in the development of preclinical AD. In order to better understand preclinical AD pathology and clinical progression rates, there is a need to refine the concept of preclinical AD. This will be of great value for advancements in future research, clinical trials, and eventually clinical practice.

Comparison of the Life Cycles of Genetically Distant Species C and Species D Human Adenoviruses Ad6 and Ad26 in Human Cells.

PubMed

Turner, Mallory A; Middha, Sumit; Hofherr, Sean E; Barry, Michael A

2015-12-01

Our understanding of adenovirus (Ad) biology is largely extrapolated from human species C Ad5. Most humans are immune to Ad5, so lower-seroprevalence viruses like human Ad6 and Ad26 are being tested as therapeutic vectors. Ad6 and Ad26 differ at the DNA level by 34%. To better understand how this might impact their biology, we examined the life cycle of the two viruses in human lung cells in vitro. Both viruses infected A549 cells with similar efficiencies, executed DNA replication with identical kinetics within 12 h, and began killing cells within 72 h. While Ad6-infected cells remained adherent until death, Ad26-infected cells detached within 12 h of infection but remained viable. Next-generation sequencing (NGS) of mRNA from infected cells demonstrated that viral transcripts constituted 1% of cellular mRNAs within 6 h and 8 to 16% within 12 h. Quantitative PCR and NGS revealed the activation of key early genes at 6 h and transition to late gene activation by 12 h by both viruses. There were marked differences in the balance of E1A and E1B activation by the two viruses and in the expression of E3 immune evasion mRNAs. Ad6 was markedly more effective at suppressing major histocompatibility complex class I (MHC I) display on the cell surface and in evading TRAIL-mediated apoptosis than was Ad26. These data demonstrate shared as well as divergent life cycles in these genetically distant human adenoviruses. An understanding of these differences expands the knowledge of alternative Ad species and may inform the selection of related Ads for therapeutic development. A burgeoning number of adenoviruses (Ads) are being harnessed as therapeutics, yet the biology of these viruses is generally extrapolated from Ad2 and Ad5. Here, we are the first to compare the transcriptional programs of two genetically distant Ads by mRNA next-generation sequencing (NGS). Species C Ad6 and Ad26 are being pursued as lower-seroprevalence Ad vectors but differ at the DNA level by 34%. Head-to-head comparison in human lung cells by NGS revealed that the two viruses generally conform to our general understanding of the Ad transcriptional program. However, fine mapping revealed subtle and strong differences in how these two viruses execute these programs, including differences in the balance of E1A and E1B mRNAs and in E3 immune evasion genes. This suggests that not all adenoviruses behave like Ad2 and Ad5 and that they may have unique strategies to infect cells and evade the immune system. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Determinants of completion of advance directives: a cross-sectional comparison of 649 outpatients from private practices versus 2158 outpatients from a university clinic

PubMed Central

Pfirstinger, Jochen; Bleyer, Bernhard; Blum, Christian; Rechenmacher, Michael; Wiese, Christoph H; Gruber, Hans

2017-01-01

Objectives To compare outpatients from private practices and outpatients from a university clinic regarding the determinants of completion of advance directives (AD) in order to generalise results of studies from one setting to the other. Five determinants of completion of AD were studied: familiarity with AD, source of information about AD, prior experiences with own life-threatening diseases or family members in need of care and motives in favour and against completion of AD. Design Observational cross-sectional study. Setting Private practices and a university clinic in Germany in 2012. Participants 649 outpatients from private practices and 2158 outpatients from 10 departments of a university clinic. Outcome measures Completion of AD, familiarity with AD, sources of information about AD (consultation), prior experiences (with own life-threatening disease and family members in need of care), motives in favour of or against completion of AD, sociodemographic data. Results Determinants of completion of AD did not differ between outpatients from private practices versus university clinic outpatients. Prior experience with severe disease led to a significantly higher rate of completion of AD (33%/36% with vs 24%/24% without prior experience). Participants with completion of AD had more often received legal than medical consultation before completion, but participants without completion of AD are rather aiming for medical consultation. The motives in favour of or against completion of AD indicated inconsistent patterns. Conclusions Determinants of completion of AD are comparable in outpatients from private practices and outpatients from a university clinic. Generalisations from university clinic samples towards a broader context thus seem to be legitimate. Only one-third of patients with prior experience with own life-threatening diseases or family members in need of care had completed an AD as expression of their autonomous volition. The participants’ motives for or against completion of AD indicate that ADs are considered a kind of ‘negative autonomy’ as instruments to prevent particular forms of therapy. Interactive, repeated and situation-based AD discussions might reach a higher percentage of patients and concurrently enable personal volitions and thereby strengthen individual ‘positive autonomy’. PMID:29273648

Confirmed recall and perceived effectiveness of tobacco countermarketing media in rural youth.

PubMed

Vogeltanz-Holm, Nancy; Holm, Jeffrey E; White Plume, Jessica; Poltavski, Dmitri

2009-12-01

This study was the first to examine rural youth's responses to ten television and radio tobacco countermarketing ads aired during a 13-week field campaign conducted in a U.S. Northern Plains state. A post-campaign survey of 391 girls and boys aged 12-17 years and including 58 American Indian youth provided information about their confirmed recall (CR) of the ads; and for recalled ads, their ratings of the ads' perceived effectiveness (PE). Results were that controlling for age and smoking risk, both American Indian and white girls and boys had the highest CR for the television ad Artery and for the radio ad ABC. Artery shows fatty deposits being squeezed from a deceased smoker's aorta, and ABC presents a former smoker speaking through his electro-larynx. Among the television ads, PE ratings were highest for the ad Artery in both boys and girls. Among the radio ads, boys rated ABC highest, whereas girls rated Joe DoBoer highest-an ad that discusses mouth lesions that developed from using smokeless tobacco. An analysis of race/ethnicity differences in PE for the ad Artery and ABC indicated American Indian and white youth considered these ads equally effective. These findings indicate certain TV and radio ads depicting graphic health harms from tobacco-especially the TV ad Artery and the radio ad ABC-are highly recalled and perceived as effective by both American Indian and white girls and boys from a rural region. Future research is needed to better understand which individual- and media-level factors increase the likelihood that anti-tobacco ads will be effective in reducing youth tobacco use.

Sexually Dimorphic Expression of Foxl2 and Ftz-F1 in Chinese Giant Salamander Andrias Davidianus.

PubMed

Hu, Qiaomu; Meng, Yan; Tian, Haifeng; Zhang, Y U; Xiao, Hanbing

2016-09-01

Foxl2 and FTZ-F1 play a crucial role in the regulation of gonad development in fish and mammals, but studies of their function in amphibians are scarce. We isolated the full length of Foxl2 (adFoxl2) and Ftz-F1 (adFtz-f1) cDNA from the Chinese giant salamander Andrias davidianus and quantified its expression in various tissues and developing gonads. The adFoxl2 gene encodes 301aa including a conserved forkhead box, and the adFtz-f1 gene encodes 467aa containing an Ftz-F1 box. The amino acid sequences showed high homology with other amphibians. adFoxl2 expression was high in ovary, whereas adFtz-f1 was higher in testis, moderate in pituitary, ovary, and kidney; and low in the remaining tested tissues. Expression of adFoxl2 gradually increased from 1Y to 5Y in ovary, whereas adFtz-f1 expression gradually decreased in testis. In addition, adFoxl2 and adFtz-f1 were detected in granulosa cell in ovary and in spermatocytes in testis. The adFoxl2 transcription was inhibited in brain and ovary after treatment with methyltestosterone and with letrozole, whereas adFtz-f1 expression was upregulated. High-temperature suppressed the expression of adFxl2 in ovary and enhanced the transcription of adFtz-f1. These results suggest that adFoxl2 functioned in ovary differentiation, whereas adFtz-f1 played a role in testis development, which lays a foundation for study of the sex differentiation mechanism in A. davidianus. © 2016 Wiley Periodicals, Inc.

Abnormal degree centrality in Alzheimer's disease patients with depression: A resting-state functional magnetic resonance imaging study.

PubMed

Guo, Zhongwei; Liu, Xiaozheng; Hou, Hongtao; Wei, Fuquan; Liu, Jian; Chen, Xingli

2016-06-15

Depression is common in Alzheimer's disease (AD) and occurs in AD patients with a prevalence of up to 40%. It reduces cognitive function and increases the burden on caregivers. Currently, there are very few medications that are useful for treating depression in AD patients. Therefore, understanding the brain abnormalities in AD patients with depression (D-AD) is crucial for developing effective interventions. The aim of this study was to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in D-AD patients based on degree centrality (DC) as measured by resting-state functional magnetic resonance imaging (R-fMRI). Our study included 32 AD patients. All patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale and further divided into two groups: 15 D-AD patients and 17 non-depressed AD (nD-AD) patients. R-fMRI datasets were acquired from these D-AD and nD-AD patients. First, we performed a DC analysis to identify voxels that showed altered whole brain functional connectivity (FC) with other voxels. We then further investigated FC using the abnormal DC regions to examine in more detail the connectivity patterns of the identified DC changes. D-AD patients had lower DC values in the right middle frontal, precentral, and postcentral gyrus than nD-AD patients. Seed-based analysis revealed decreased connectivity between the precentral and postcentral gyrus to the supplementary motor area and middle cingulum. FC also decreased in the right middle frontal, precentral, and postcentral gyrus. Thus, AD patients with depression fit a 'network dysfunction model' distinct from major depressive disorder and AD. Copyright © 2016. Published by Elsevier Inc.

Testing messages to reduce smokers' openness to using novel smokeless tobacco products.

PubMed

Popova, Lucy; Neilands, Torsten B; Ling, Pamela M

2014-07-01

Tobacco manufacturers' aggressive promotion of new smokeless tobacco products such as snus warrants a timely and effective public health response. This study tested potential countermarketing messages to discourage current and former smokers from becoming dual users of smokeless tobacco and cigarettes. In a pretest-post-test experiment, 1836 adult current and recently former smokers from a national sample were randomised to view one of six antismokeless tobacco ads followed by a snus ad, to view a control ad followed by a snus ad; or to view two control ads. Perceived effectiveness of ads and actual changes in attitudes and openness to snus were compared across groups using analyses of variance. Some ads that were perceived as most effective did not change attitudes or openness to trying snus, and conversely, some ads not perceived as effective changed attitudes and openness to snus. Ads portraying the negative health effects of smokeless tobacco were perceived as most effective, but ads with antitobacco industry themes significantly decreased favourable attitudes toward snus. Responses to ads were different for smokers who had ever used smokeless tobacco: for this group health effects and humorous/testimonial ads were effective. Measures of perceived effectiveness of antitobacco ads need to be augmented with measures of actual effectiveness to assess countermarketing messages. Some of the developed ads, such as ads with anti-industry themes, were effective for the overall population of smokers whereas humorous/testimonial and health effects ads were particularly effective in changing attitudes of past users of smokeless tobacco. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genome-wide association study of Alzheimer's disease with psychotic symptoms.

PubMed

Hollingworth, P; Sweet, R; Sims, R; Harold, D; Russo, G; Abraham, R; Stretton, A; Jones, N; Gerrish, A; Chapman, J; Ivanov, D; Moskvina, V; Lovestone, S; Priotsi, P; Lupton, M; Brayne, C; Gill, M; Lawlor, B; Lynch, A; Craig, D; McGuinness, B; Johnston, J; Holmes, C; Livingston, G; Bass, N J; Gurling, H; McQuillin, A; Holmans, P; Jones, L; Devlin, B; Klei, L; Barmada, M M; Demirci, F Y; DeKosky, S T; Lopez, O L; Passmore, P; Owen, M J; O'Donovan, M C; Mayeux, R; Kamboh, M I; Williams, J

2012-12-01

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.

The Effect of Comparatively-Framed versus Similarity-Framed E-Cigarette and Snus Print Ads on Young Adults’ Ad and Product Perceptions

PubMed Central

Banerjee, Smita C.; Greene, Kathryn; Li, Yuelin; Ostroff, Jamie S.

2016-01-01

Objectives This study examined the effects of comparative-framing [C-F; ads highlighting differences between the advertised product and conventional cigarettes and/or smokeless tobacco products] versus similarity-framing (S-F; ads highlighting congruence with conventional cigarettes and/or smokeless tobacco products) in e-cigarette and snus ads on young adult smokers’ and non-smokers’ ad- and product-related perceptions. Methods One thousand fifty one (1,051) young adults (18–24 years; 76% women; 50% smokers) from existing consumer panels were recruited in a within-subjects quasi-experiment. Each participant viewed 4 online advertisements, varied by tobacco product type (e-cigarette or snus) and ad framing (C-F or S-F). The dependent measures for this study were ad-related (ad perceptions, ad credibility) and product-related perceptions (absolute and comparative risk perceptions, product appeal, and product use intentions). Results Former and current smokers rated C-F ads as more persuasive than S-F ads, as evidenced by favorable ad perceptions and high product use intentions. Former and current smokers also rated e-cigarette ads with more favorable ad perceptions, low absolute and comparative risk perceptions, high product appeal, and high product use intentions as compared to snus ads. However, the effect sizes of the significant differences are less than.2, indicating small magnitude of difference between the study variables. Conclusions Unless FDA regulates e-cig and snus advertising, there is a potential of decreasing risk perceptions and increasing use of e-cigs among young adults. Further research on implicit/explicit comparative claims in e-cigarettes and snus advertisements that encourage risk misperceptions is recommended. PMID:28042597

The Effect of Comparatively-Framed versus Similarity-Framed E-Cigarette and Snus Print Ads on Young Adults' Ad and Product Perceptions.

PubMed

Banerjee, Smita C; Greene, Kathryn; Li, Yuelin; Ostroff, Jamie S

2016-07-01

This study examined the effects of comparative-framing [C-F; ads highlighting differences between the advertised product and conventional cigarettes and/or smokeless tobacco products] versus similarity-framing (S-F; ads highlighting congruence with conventional cigarettes and/or smokeless tobacco products) in e-cigarette and snus ads on young adult smokers' and non-smokers' ad- and product-related perceptions. One thousand fifty one (1,051) young adults (18-24 years; 76% women; 50% smokers) from existing consumer panels were recruited in a within-subjects quasi-experiment. Each participant viewed 4 online advertisements, varied by tobacco product type (e-cigarette or snus) and ad framing (C-F or S-F). The dependent measures for this study were ad-related (ad perceptions, ad credibility) and product-related perceptions (absolute and comparative risk perceptions, product appeal, and product use intentions). Former and current smokers rated C-F ads as more persuasive than S-F ads, as evidenced by favorable ad perceptions and high product use intentions. Former and current smokers also rated e-cigarette ads with more favorable ad perceptions, low absolute and comparative risk perceptions, high product appeal, and high product use intentions as compared to snus ads. However, the effect sizes of the significant differences are less than.2, indicating small magnitude of difference between the study variables. Unless FDA regulates e-cig and snus advertising, there is a potential of decreasing risk perceptions and increasing use of e-cigs among young adults. Further research on implicit/explicit comparative claims in e-cigarettes and snus advertisements that encourage risk misperceptions is recommended.

The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits.

PubMed

Kozlowski, Piotr; Montgomery, Scott; Befekadu, Rahel; Hahn-Strömberg, Victoria

2017-01-01

Light chain amyloidosis (AL) is a rare deposition disease and is present in 10-15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM). We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD. Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively). Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD.

Redirecting adenovirus tropism by genetic, chemical, and mechanical modification of the adenovirus surface for cancer gene therapy.

PubMed

Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

2016-06-01

Despite remarkable advancements, clinical evaluations of adenovirus (Ad)-mediated cancer gene therapies have highlighted the need for improved delivery and targeting. Genetic modification of Ad capsid proteins has been extensively attempted. Although genetic modification enhances the therapeutic potential of Ad, it is difficult to successfully incorporate extraneous moieties into the capsid and the engineering process is laborious. Recently, chemical modification of the Ad surface with nanomaterials and targeting moieties has been found to enhance Ad internalization into the target by both passive and active mechanisms. Alternatively, external stimulus-mediated targeting can result in selective accumulation of Ad in the tumor and prevent dissemination of Ad into surrounding nontarget tissues. In the present review, we discuss various genetic, chemical, and mechanical engineering strategies for overcoming the challenges that hinder the therapeutic efficacy of Ad-based approaches. Surface modification of Ad by genetic, chemical, or mechanical engineering strategies enables Ad to overcome the shortcomings of conventional Ad and enhances delivery efficiency through distinct and unique mechanisms that unmodified Ad cannot mimic. However, although the therapeutic potential of Ad-mediated gene therapy has been enhanced by various surface modification strategies, each strategy still possesses innate limitations that must be addressed, requiring innovative ideas and designs.

The burden of atopic dermatitis in US adults: Health care resource utilization data from the 2013 National Health and Wellness Survey.

PubMed

Eckert, Laurent; Gupta, Shaloo; Amand, Caroline; Gadkari, Abhijit; Mahajan, Puneet; Gelfand, Joel M

2018-01-01

There is a lack of data on the burden of atopic dermatitis (AD) in adults relative to the general population. To characterize the AD burden in adult patients relative to both matched non-AD controls and matched patients with psoriasis in terms of comorbidities, health care resource utilization (HCRU), and costs. Adults (≥18 years) who self-reported a diagnosis of AD or psoriasis and adult non-AD controls were identified from the 2013 US National Health and Wellness Survey. Patients with AD were propensity score-matched with non-AD controls and patients with psoriasis on demographic variables. Patient-reported outcomes were analyzed between matched cohorts. Patients with AD had a significantly greater risk for atopic comorbidities, as well as significantly greater HCRU and total cost compared with non-AD controls. The burden of AD was generally comparable to that of psoriasis, although patients with AD reported increased use of emergency room visits compared with patients with psoriasis. Patient-reported data are susceptible to recall bias and erroneous classification. Adult patients with AD reported a substantial disease burden, suggesting an unmet need for more effective AD treatment options. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Integrated Display and Simulation for Automatic Dependent Surveillance-Broadcast and Traffic Collision Avoidance System Data Fusion.

PubMed

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-11-13

Automatic Dependent Surveillance-Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications.

Collapse and Nonlinear Instability of AdS Space with Angular Momentum

NASA Astrophysics Data System (ADS)

Choptuik, Matthew W.; Dias, Óscar J. C.; Santos, Jorge E.; Way, Benson

2017-11-01

We present a numerical study of rotational dynamics in AdS5 with equal angular momenta in the presence of a complex doublet scalar field. We determine that the endpoint of gravitational collapse is a Myers-Perry black hole for high energies and a hairy black hole for low energies. We investigate the time scale for collapse at low energies E , keeping the angular momenta J ∝E in anti-de Sitter (AdS) length units. We find that the inclusion of angular momenta delays the collapse time, but retains a t ˜1 /E scaling. We perturb and evolve rotating boson stars, and find that boson stars near AdS space appear stable, but those sufficiently far from AdS space are unstable. We find that the dynamics of the boson star instability depend on the perturbation, resulting either in collapse to a Myers-Perry black hole, or development towards a stable oscillating solution.

Knowledge of Alzheimer's disease, feelings of shame, and awareness of services among Korean American elders.

PubMed

Yuri Jang; Kim, Giyeon; Chiriboga, David

2010-06-01

To explore predictors of knowledge of Alzheimer's disease (AD), feelings of shame if a family member were to have AD, and awareness of AD-related services among Korean American elders. Using data from 675 Korean American elders (mean age = 70.2, SD = 6.87), the study estimates hierarchical linear or logistic regression models. Greater knowledge of AD is predicted by higher levels of education and acculturation. Feelings of shame associated with family members having AD are more likely to be reported by individuals with lower levels of education, acculturation, and knowledge of AD. Those who are married have greater levels of education and acculturation, and those who have a family member with AD are more aware of AD-related services. The study findings underscore the pivotal role of education and acculturation in predicting knowledge of AD, feelings of shame, and awareness of AD-related services.

Holographic definition of points and distances

NASA Astrophysics Data System (ADS)

Czech, Bartłomiej; Lamprou, Lampros

2014-11-01

We discuss the way in which field theory quantities assemble the spatial geometry of three-dimensional anti-de Sitter space (AdS3). The field theory ingredients are the entanglement entropies of boundary intervals. A point in AdS3 corresponds to a collection of boundary intervals which is selected by a variational principle we discuss. Coordinates in AdS3 are integration constants of the resulting equation of motion. We propose a distance function for this collection of points, which obeys the triangle inequality as a consequence of the strong subadditivity of entropy. Our construction correctly reproduces the static slice of AdS3 and the Ryu-Takayanagi relation between geodesics and entanglement entropies. We discuss how these results extend to quotients of AdS3 —the conical defect and the BTZ geometries. In these cases, the set of entanglement entropies must be supplemented by other field theory quantities, which can carry the information about lengths of nonminimal geodesics.

A Model of Consumer Response to Over-the-Counter Drug Advertising: Antecedents and Influencing Factors.

PubMed

Huh, Jisu; Delorme, Denise E; Reid, Leonard N

2016-01-01

Given the importance of over-the-counter (OTC) drugs in the health care marketplace and lack of systematic research on OTC drug advertising (OTCA) effects, this study tested a theory-based, product category-specific OTCA effects model. Structural equation modeling analysis of data for 1 OTC drug category, analgesics, supported the proposed model, explaining the OTCA effect process from key consumer antecedents to ad involvement, from ad involvement to ad attention, from ad attention to cognitive responses, then to affective/evaluative responses, leading to the final behavioral outcome. Several noteworthy patterns also emerged: (a) Product involvement was directly linked to ad attention, rather than exerting an indirect influence through ad involvement; (b) ad attention was significantly related to both cognitive and affective/evaluative responses to different degrees, with stronger links to cognitive responses; and (c) ad-prompted actions were influenced by both ad trust and ad attitude.

Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease.

PubMed

Watabe-Rudolph, M; Song, Z; Lausser, L; Schnack, C; Begus-Nahrmann, Y; Scheithauer, M-O; Rettinger, G; Otto, M; Tumani, H; Thal, D R; Attems, J; Jellinger, K A; Kestler, H A; von Arnim, C A F; Rudolph, K L

2012-02-21

DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia. Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1α) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia. Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (β-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia. Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated.

Role of familial factors in late-onset Alzheimer disease as a function of age.

PubMed

Wu, Z; Kinslow, C; Pettigrew, K D; Rapoport, S I; Schapiro, M B

1998-09-01

Whereas early-onset Alzheimer disease (AD; usually onset at age < 50 years) has been defined with genetic mutation on chromosomes 1, 14, and 21, the degree of familial contribution to late-onset AD is unclear. Further, it is uncertain if subgroups of late-onset AD exist. To examine the influence of familial factors as a function of age in late-onset AD we investigated lifetime risks and age-specific hazard rates of AD-like illness among late-onset AD probands' and controls' first-degree relatives, using questionnaires and medical records. As part of a longitudinal study on aging and AD, we studied 78 AD probands with age of onset > or =50 years (28 "definite" and 50 "probable" AD according to NINCDS/ADRDA criteria) and 101 healthy old controls seen since 1981. Both probands and controls were screened rigorously with medical tests and brain imaging and seen regularly until autopsy. Multiple informants and medical records were used for first-degree relatives. Among first-degree relatives, 49 secondary cases of AD-like illness were found for the AD probands' relatives (391 relatives 40 years old or older) compared with 20 cases among controls' relatives (456 relatives 40 years old or older). Relatives of AD probands had a significantly increased lifetime risk of AD-like illness of 52.8+/-11.4% by age 94 years compared with a lifetime risk in relatives of controls of 22.1+/-5.8% by age 90 years. Age-specific hazard rates in relatives of AD probands increased until the 75-79-year age interval and then decreased; in contrast the age-specific hazard rates increased in relatives of controls after the 80-84-year age interval. To determine if a dividing line exist among late-onset AD, several cutoff ages were used in our study to compare cumulative risk curves of AD-like illness between relatives of late-onset probands and relatives of late-late-onset probands. Differences in the pattern of cumulative incidence of AD in relatives showed that 67-71 years is the range for a dividing line between late- and late-late-onset AD. Age-specific hazard rates of AD in relatives supported a difference between late- and late-late-onset. Whereas these rates increased until the 75-79-year age interval and then decreased in late-onset AD, the rates began increasing after the 65-69-year age interval and through the oldest age interval in both late-late-onset AD and control groups. Our results support the concept that familial factors exist in late-onset AD and that different familial factors may exist in late-onset AD subgroups.

78 FR 73739 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

...). SUMMARY: We propose to supersede Airworthiness Directives (ADs) 97-11- 07 and AD 99-18-23, which apply to all The Boeing Company Model MD-90- 30 airplanes. AD 97-11-07 and AD 99-18-23 currently require... for safe-life limited parts. Since we issued AD 97-11-07 and AD 99-18- 23, an analysis of data...

Antismoking advertisements for youths: an independent evaluation of health, counter-industry, and industry approaches.

PubMed

Pechmann, Cornelia; Reibling, Ellen T

2006-05-01

We used a validated copy test method to examine the effectiveness of 8 types of antismoking advertisements representing health, counterindustry, and industry approaches. We tested the hypothesis that health ads about tobacco victims can lower most adolescents' intent to smoke if the ads elicit disgust and anti-industry feelings rather than fear. We hypothesized null effects for adolescents with conduct disorder because of their abnormally low empathy. Ninth-grade students from 8 California public schools (n=1725) were randomly assigned to view 1 of 9 videotapes containing a TV show with ads that included either a set of antismoking ads or a set of control ads. Participants completed baseline measures assessing personality traits and postexposure measures assessing smoking intent, feelings, beliefs, and ad evaluations. Ads focusing on young victims suffering from serious tobacco-related diseases elicited disgust, enhanced anti-industry motivation, and reduced intent to smoke among all but conduct-disordered adolescents. Counterindustry and industry ads did not significantly lower smoking intention. Sponsors of tobacco use prevention ad campaigns should consider using ads showing tobacco-related disease and suffering, not just counterindustry ads. Ads should be copy tested before airing.

Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43

PubMed Central

Belousova, Natalya; Mikheeva, Galina; Xiong, Chiyi; Stagg, Loren J.; Gagea, Mihai; Fox, Patricia S.; Bassett, Roland L.; Ladbury, John E.; Braun, Michael B.; Stehle, Thilo; Li, Chun; Krasnykh, Victor

2016-01-01

Unique molecular properties of species D adenoviruses (Ads)—the most diverse yet underexplored group of Ads—have been used to develop improved gene vectors. The low seroprevalence in humans of adenovirus serotype 43 (Ad43), an otherwise unstudied species D Ad, identified this rare serotype as an attractive new human gene therapy vector platform. Thus, in this study we wished to assess biological properties of Ad43 essential to its vectorization. We found that (1) Ad43 virions do not bind blood coagulation factor X and cause low random transduction upon vascular delivery; (2) they clear host tissues more quickly than do traditionally used Ad5 vectors; (3) Ad43 uses CD46 as primary receptor; (4) Ad43 can use integrins as alternative primary receptors. As the first step toward vectorization of Ad43, we demonstrated that the primary receptor specificity of the Ad43 fiber can be altered to achieve infection via Her2, an established oncotarget. Whereas this modification required use of the Ad5 fiber shaft, the presence of this domain in chimeric virions did not make them susceptible for neutralization by anti-Ad5 antibodies. PMID:27462785

The portrayal of older people in television advertisements: a cross-cultural content analysis of the United States and South Korea.

PubMed

Lee, Oungkwan; Kim, Bong-Chul; Han, Sangpil

2006-01-01

A cross-cultural content analysis of 2295 prime-time television ads--859 ads from the United States and 1436 ads from South Korea-was conducted to examine the differences in the portrayal of older people between U.S. and Korean ads. In two countries, the underrepresentation of older people in ads was found in terms of proportions of the actual population. The findings also showed that older people are more likely to play major roles in Korean television ads than in U.S. ads. In terms of the attributes of older people depicted in ads, differences between U.S. and Korean ads were also found. The results showed that Korean television ads are likely to more positively depict older people than American television ads are. These findings supported the basic assumption of cross-cultural advertising, in which the differences in cultural values between the two cultures are related to the differences in the contents of their advertisements. However, the problems of underrepresentation and stereotypes in the portrayal of older people were still identified both in Korean and U.S. prime-time television ads.

The treatment of Alzheimer's disease using Chinese medicinal plants: from disease models to potential clinical applications.

PubMed

Su, Yang; Wang, Qiuhong; Wang, Changfu; Chan, Kelvin; Sun, Yanping; Kuang, Haixue

2014-03-28

Alzheimer's disease (AD) is characterized by the sustained higher nervous disorders of the activities and functions of the brain. Due to its heavy burden on society and the patients' families, it is urgent to review the treatments for AD to provide basic data for further research and new drug development. Among these treatments, Chinese Material Medica (CMM) has been traditionally clinical used in China to treat AD for a long time with obvious efficacy. With the further research reports of CMM, new therapeutic materials may be recovered from troves of CMM. However, So far, little or no review work has been reported to conclude anti-AD drugs from CMM in literature. Therefore, a systematic introduction of CMM anti-AD research progress is of great importance and necessity. This paper strives to systematically describe the progress of CMM in the treatment of AD, and lays a basis data for anti-AD drug development from CMM, and provides the essential theoretical support for the further development and utilization of CMM resources through a more comprehensive research of the variety of databases regarding CMM anti-AD effects reports. Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries. This review mainly introduces the current research on the Chinese Material Medica (CMM) theoretical research on Alzheimer's disease (AD), anti-AD active constituent of CMM, anti-AD effects on AD models, anti-AD mechanism of CMM, and anti-AD effect of CMM formula. Scholars around the world have made studies on the anti-AD molecular mechanism of CMM from different pathways, and have made substantial progress. The progress not only enriched the anti-AD theory of CMM, but also provided clinical practical significance and development prospects in using CMM to treat AD. Western pure drugs cannot replace the advantages of CMM in the anti-AD aspect. Therefore, in the near future, the development of CMM anti-AD drugs with a more clearly role and practical data will be a major trend in the field of AD drug development, and it will promote the use of CMM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cerebrospinal Fluid Aβ40 Improves the Interpretation of Aβ42 Concentration for Diagnosing Alzheimer’s Disease

PubMed Central

Dorey, Aline; Perret-Liaudet, Armand; Tholance, Yannick; Fourier, Anthony; Quadrio, Isabelle

2015-01-01

The combination of decreased amyloid β42 (Aβ42) and increased total tau proteins (T-Tau) and phosphorylated tau (P-Tau) in cerebrospinal fluid (CSF) has recently been considered as a biological diagnostic criterion of Alzheimer’s disease (AD). Previous studies showed significant heterogeneity in CSF Aβ42 levels to discriminate AD from non-AD patients. It was also suggested that the CSF amyloid peptide β42/β40 ratio has better diagnostic performance than Aβ42 alone. The objective of the present study was to investigate the potential added value of determining CSF amyloid β40 peptide (Aβ40) for biological diagnosis of AD when CSF Aβ42 levels failed. CSF AD biomarkers were run in 2,171 samples from 1,499 AD and 672 non-AD patients. The following pathologic thresholds were used to define an AD-positive CSF biomarker profile: T-Tau ≥ 400 ng/L, P-Tau181 ≥ 60 ng/L, and Aβ42 ≤ 700 ng/L. CSF Aβ40 was assayed in AD patients with CSF Aβ42 levels above 700 ng/L and non-AD patients with CSF Aβ42 levels below 700 ng/L. CSF Aβ40 levels were higher in AD than non-AD patients. The receiver operator characteristic curves of CSF Aβ40 and the Aβ42/Aβ40 ratio defined AD cut-off values at 12,644 ng/L and 0.06, respectively. In AD patients with non-pathological CSF Aβ42, CSF Aβ40 concentration was able to correct 76.2% of cases when expressed as CSF Aβ42/Aβ40 ratio and 94.7% of cases when used alone. Using CSF Aβ42 and then CSF Aβ40, the percentage of misinterpreted AD patients fell to 1.0%. CSF Aβ40 concentration improved interpretation of Aβ42 level for the diagnosis of AD. CSF Aβ40 alone showed better diagnostic performance than the amyloid peptide Aβ42/Aβ40 ratio. The added value of determining CSF Aβ40 in AD diagnosis now needs confirming in a cohort of definite AD patients and to be completed with novel amyloid cascade biomarkers. PMID:26640457

Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients.

PubMed

Vaitkevičius, Arūnas; Kaubrys, Gintaras; Audronytė, Eglė

2015-07-03

Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naïve and on stable donepezil treatment, matched by age, education, sex, and cognitive function. We recruited 22 consecutive treatment-naïve AD patients (AD-N group), 22 AD patients treated with a stable donepezil dose of 10 mg/day for at least 3 months (AD-T group), and 50 healthy controls were recruited. Neuropsychological testing (MMSE, ADAS-Cog, and additional tests) and ERP recording was performed and analyzed. All groups did not differ according to age, duration of education, or sex (p>0.05). AD-N and AD-T groups did not differ according to cognitive function. The AD-T group had longer duration of disease than the AD-N group (p<0.001). The AD-T and AD-N groups did not differ in P300 latencies (p=0.49). N200 latency was longer in the AD-T group (p<0.001). The general linear model showed that significant predictors of P300 latency were age (p=0.019) and AD treatment status (p<0.001). Duration of AD was a significant predictor of N200 latency (p=0.004). The response of N200 latency to donepezil treatment differs from the response of P300. P300 is a better marker of ChEI treatment-dependent cognitive functions. N200 is more dependent on the duration of AD.

Strong evidence for a genetic contribution to late-onset Alzheimer's disease mortality: a population-based study.

PubMed

Kauwe, John S K; Ridge, Perry G; Foster, Norman L; Cannon-Albright, Lisa A

2013-01-01

Alzheimer's disease (AD) is an international health concern that has a devastating effect on patients and families. While several genetic risk factors for AD have been identified much of the genetic variance in AD remains unexplained. There are limited published assessments of the familiality of Alzheimer's disease. Here we present the largest genealogy-based analysis of AD to date. We assessed the familiality of AD in The Utah Population Database (UPDB), a population-based resource linking electronic health data repositories for the state with the computerized genealogy of the Utah settlers and their descendants. We searched UPDB for significant familial clustering of AD to evaluate the genetic contribution to disease. We compared the Genealogical Index of Familiality (GIF) between AD individuals and randomly selected controls and estimated the Relative Risk (RR) for a range of family relationships. Finally, we identified pedigrees with a significant excess of AD deaths. The GIF analysis showed that pairs of individuals dying from AD were significantly more related than expected. This excess of relatedness was observed for both close and distant relationships. RRs for death from AD among relatives of individuals dying from AD were significantly increased for both close and more distant relatives. Multiple pedigrees had a significant excess of AD deaths. These data strongly support a genetic contribution to the observed clustering of individuals dying from AD. This report is the first large population-based assessment of the familiality of AD mortality and provides the only reported estimates of relative risk of AD mortality in extended relatives to date. The high-risk pedigrees identified show a true excess of AD mortality (not just multiple cases) and are greater in depth and width than published AD pedigrees. The presence of these high-risk pedigrees strongly supports the possibility of rare predisposition variants not yet identified.

Advertising Content, Platform Characteristics and the Appeal of Beer Advertising on a Social Networking Site.

PubMed

Noel, Jonathan K; Babor, Thomas F; Grady, James J

2018-03-15

The current study was conducted to investigate how changes in the content of a social media ad, user engagement values associated with the ad and user-generated comments (UGCs) associated with the ad can influence the appeal (i.e. source appeal, informational appeal and emotional appeal) of a social media ad. Facebook beer ads that violated the guidelines of a relevant marketing code were rated as more emotionally appealing compared to Facebook beer ads that did not violated the guidelines. Increased emotional appeal in beer advertising increases the probability that the ad will be remembered and influence future drinking occasions. A 2 (ad regulatory compliance: compliant vs. non-compliant) × 2 (user engagement: low vs. high) × 2 (UGC congruence: pro- vs anti-alcohol) mixed factorial experiment was conducted with 120 young adults, 21-24 years old. Each participant viewed four Facebook beer ads that were previously evaluated for thematic content and regulatory compliance. Participants were randomized to view either high or low user engagement values and either pro- or anti-drinking user-generated comments. After each ad exposure, ad appeal was assessed. Statistical analysis was conducted using hierarchical linear modeling. Models were adjusted for demographics, Alcohol Use Disorders Identification Test (AUDIT) scores and Facebook involvement. Source appeal (P = 0.034) and informational appeal (P < 0.001) were significantly higher among ads that were compliant with existing advertising regulations. Emotional appeal was significantly higher among ads that were non-compliant (P = 0.004). The effect of user engagement and UGCs were non-significant (p's > 0.05). Additionally, AUDIT scores (p's < 0.01) and Facebook involvement scores (p's < 0.01) were positively associated with all forms of ad appeal. The appeal of Facebook beer ads may be primarily determined by ad content. Increased emotional appeal in advertising caused by non-compliant advertising may increase the probability that the ad will be remembered and influence future drinking occasions.

Parental Meta-Emotion Philosophy and Emotion Coaching in Families of Children and Adolescents with an Anxiety Disorder.

PubMed

Hurrell, Katherine E; Houwing, Frances L; Hudson, Jennifer L

2017-04-01

Using a multi-method approach, this study examined differences in parental meta-emotional philosophy (including, parental emotional awareness and emotion coaching) for families with anxiety disordered (AD; n = 74) and non-AD (n = 35) children (aged 7 to 15). Further, it was investigated whether children's emotion regulation (ER) varied across the AD and non-AD groups. Parent(s) were interviewed about their awareness of emotions and emotion coaching; completed a battery of questionnaires that included a measure assessing children's emotion regulation; and engaged in a parent-child discussion task. Results indicated that compared to parents of non-AD youth, parents of AD youth were less aware of their own emotions and their children's emotions, and these results varied by emotion type. Parents of AD youth engaged in significantly less emotion coaching than parents of non-AD youth. AD youth were identified as having significantly greater difficulty regulating their emotions when compared to non-AD youth. Implications for the role of parental meta-emotional philosophy and AD youth's emotion regulation are discussed.

The search for adenovirus 14 in children in Houston, Texas.

PubMed

Laham, Federico R; Jewell, Alan M; Schoonover, Shauna L; Demmler, Gail J; Piedra, Pedro A

2008-07-01

Adenovirus (Ad)14 has recently emerged in the United States causing outbreaks of severe respiratory disease. To determine if Ad14 circulated in Houston, Texas, during the same time as an outbreak in military recruits in nearby San Antonio, 215 pediatric adenovirus isolates were serotyped using microneutralization. None were Ad14; Ad1, Ad2, and Ad3 were the most common identified serotypes.

Multimerization of Adenovirus Serotype 3 Fiber Knob Domains Is Required for Efficient Binding of Virus to Desmoglein 2 and Subsequent Opening of Epithelial Junctions▿

PubMed Central

Wang, Hongjie; Li, ZongYi; Yumul, Roma; Lara, Stephanie; Hemminki, Akseli; Fender, Pascal; Lieber, André

2011-01-01

Recently, we identified desmoglein 2 (DSG2) as the main receptor for a group of species B adenoviruses (Ads), including Ad3, a serotype that is widely distributed in the human population (H. Wang et al., Nat. Med. 17:96–104, 2011). In this study, we have attempted to delineate structural details of the Ad3 interaction with DSG2. For CAR- and CD46-interacting Ad serotypes, attachment to cells can be completely blocked by an excess of recombinant fiber knob protein, while soluble Ad3 fiber knob only inefficiently blocks Ad3 infection. We found that the DSG2-interacting domain(s) within Ad3 is formed by several fiber knob domains that have to be in the spatial constellation that is present in viral particles. Based on this finding, we generated a small recombinant, self-dimerizing protein containing the Ad3 fiber knob (Ad3-K/S/Kn). Ad3-K/S/Kn bound to DSG2 with high affinity and blocked Ad3 infection. We demonstrated by confocal immunofluorescence and transmission electron microscopy analyses that Ad3-K/S/Kn, through its binding to DSG2, triggered the transient opening of intercellular junctions in epithelial cells. The pretreatment of epithelial cells with Ad3-K/S/Kn resulted in increased access to receptors that are localized in or masked by epithelial junctions, e.g., CAR or Her2/neu. Ad3-K/S/Kn treatment released CAR from tight junctions and thus increased the transduction of epithelial cells by a serotype Ad5-based vector. Furthermore, the pretreatment of Her2/neu-positive breast cancer cells with Ad3-K/S/Kn increased the killing of cancer cells by the Her2/neu-targeting monoclonal antibody trastuzumab (Herceptin). This study widens our understanding of how Ads achieve high avidity to their receptors and the infection of epithelial tissue. The small recombinant protein Ad3-K/S/Kn has practical implications for the therapy of epithelial cancer and gene/drug delivery to normal epithelial tissues. PMID:21525338

Using Google AdWords for international multilingual recruitment to health research websites.

PubMed

Gross, Margaret S; Liu, Nancy H; Contreras, Omar; Muñoz, Ricardo F; Leykin, Yan

2014-01-20

Google AdWords, the placement of sponsored links in Google search results, is a potent method of recruitment to Internet-based health studies and interventions. However, the performance of Google AdWords varies considerably depending on the language and the location of the target audience. Our goal was to describe differences in AdWords performance when recruiting participants to the same study conducted in four languages and to determine whether AdWords campaigns can be optimized in order to increase recruitment while decreasing costs. Google AdWords were used to recruit participants to the Mood Screener, a multilingual online depression screening tool available in English, Russian, Spanish, and Chinese. Two distinct recruitment periods are described: (1) "Unmanaged", a 6-month period in which ads were allowed to run using only the AdWords tool itself, with no human intervention, and (2) "Managed", a separate 7-week period during which we systematically sought to optimize our recruitment campaigns. During 6 months of unmanaged recruitment, our ads were shown over 1.3 million times, resulting in over 60,000 site visits. The average click-through rate (ratio of ads clicked to ads displayed) varied from 1.86% for Chinese ads to 8.48% for Russian ads, as did the average cost-per-click (from US $0.20 for Chinese ads to US $0.50 for English ads). Although Chinese speakers' click-through rate was lowest, their rate of consenting to participate was the highest, at 3.62%, with English speakers exhibiting the lowest consent rate (0.97%). The conversion cost (cost to recruit a consenting participant) varied from US $10.80 for Russian speakers to US $51.88 for English speakers. During the 7 weeks of "managed" recruitment, we attempted to improve AdWords' performance in regards to the consent rate and cost by systematically deleting underperforming ads and adjusting keywords. We were able to increase the number of people who consent after coming to the site by 91.8% while also decreasing per-consent cost by 23.3%. Our results illustrate the need to linguistically and culturally adapt Google AdWords campaigns and to manage them carefully to ensure the most cost-effective results.

Plasma cortisol in Alzheimer’s disease with or without depressive symptoms

PubMed Central

Zvěřová, Martina; Fišar, Zdeněk; Jirák, Roman; Kitzlerová, Eva; Hroudová, Jana; Raboch, Jiří

2013-01-01

Background Cortisol is presumed to be a risk factor for stress- and age-related disorders, such as depressive disorder and Alzheimer’s disease (AD). The aim of this study was to investigate the association of plasma cortisol concentration with AD in presence or absence of comorbid depressive symptoms. Material/Methods Plasma cortisol concentration was measured in 80 AD patients (35 of them with depressive symptoms), 27 elderly depressive patients without AD, and 37 elderly controls. Results Compared to controls, a significant increase of mean plasma cortisol was found in AD patients but not in depressive patients. Plasma cortisol was positively correlated with cognitive impairment in AD patients. We confirmed a U-shaped association between plasma cortisol and major depression and a linear association between plasma cortisol and AD without depressive symptoms. Significantly increased relative risk of disease in people with high plasma cortisol was found for AD with depressive symptoms and for AD with mild dementia. Conclusions Plasma cortisol reflects the degree of cognitive impairment in AD rather than the severity of comorbid depression. We confirmed that both hypercortisolemia and hypocortisolemia are associated with depressive disorder. Significant association between high plasma cortisol and AD was found, supporting the use of high plasma cortisol as a component of a panel of biochemical markers for AD with depressive symptoms as well as AD in the early stage of dementia development. PMID:23955525

Chemokine RANTES in atopic dermatitis.

PubMed

Glück, J; Rogala, B

1999-01-01

Chemokines play a key role in inflammatory diseases. The aim of this study was to estimate chemokine RANTES in the sera of patients with atopic dermatitis (AD) and to analyze the correlation between RANTES serum level and the immunological and clinical parameters of the disease. Serum levels of RANTES (ELISA; R&D Systems), total IgE and specific IgE (FEIA; Pharmacia CAP System) were estimated in 24 patients with AD, 28 patients with pollinosis (PL) and 22 healthy nonatopic subjects (HC). The division of the AD group into a pure AD (pAD) subgroup, without a coexisting respiratory allergy, and a subgroup of patients with AD and a respiratory allergy (AD+AO) was done according to Wütrich. Levels of RANTES were higher in the AD group than in the HC group and the PL group. RANTES levels did not differ among subgroups with various clinical scores and between the pAD and AD+AO subgroups. There were no correlations between levels of RANTES and total IgE. Significant positive correlations between serum levels of RANTES and Dermatophagoides farinae and cat dander-specific IgE were found in the AD group. We conclude that the serum level of chemokine RANTES differs patients with AD from patients with PL. The increase of RANTES concentration in the serum of patients with AD depends neither on a clinical picture nor an IgE system.

Just a Spoonful of Sugar Will Land You Six Feet Underground: Should the Food and Drug Administration Revoke Added Sugar's GRAS Status?

PubMed

Card, Melissa Marie; Abela, John Francis

2015-01-01

This article assesses whether added sugar meets FDA's standard to be generally recognized as safe ("GRAS"). If added sugar is not GRAS, then manufacturers are subject to premarket approval prior to using added sugar in their products. This article advocates that FDA should issue a Federal Register notice determining that added sugar is not GRAS, allowing FDA to regulate the amount of added sugar used in processed foods, decreasing the health adversities that stem from added sugar consumption.

Throat quantization of the Schwarzschild-Tangherlini(-AdS) black hole

NASA Astrophysics Data System (ADS)

Maeda, Hideki

2018-01-01

By the throat quantization pioneered by Louko and Mäkelä, we derive the mass and area/entropy spectra for the Schwarzschild-Tangherlini-type asymptotically flat or AdS vacuum black hole in arbitrary dimensions. Using the WKB approximation for black holes with large mass, we show that area/entropy is equally spaced for asymptotically flat black holes, while mass is equally spaced for asymptotically AdS black holes. Exact spectra can be obtained for toroidal AdS black holes in arbitrary dimensions including the three-dimensional BTZ black hole.

An overview of the etiology, diagnosis, and treatment of Alzheimer disease.

PubMed

Forsyth, E; Ritzline, P D

1998-12-01

Alzheimer disease (AD) is the most common form of dementia affecting elderly people. It is the fourth leading cause of death among adults in the United States, following heart disease, cancer, and stroke. The prevalence of AD increases with increasing age. An estimated 10% of people aged 65 years have this progressive, degenerative disease, and this percentage increases to 47.2% for people aged 85 years and older. An early-onset form of AD can affect individuals who are middle-aged, with the youngest documented case being that of a 28-year-old. In the Framingham cohort, women with AD outnumbered men by a ratio of 2.8:1 for those aged 75 years or older. Undoubtedly, as our population continues to age, the increasing prevalence of AD will have an even greater impact on society than it does today. Approximately 4 million Americans have AD, and it is projected that the number will rise to 14 million by the middle of the next century. The financial impact of AD is staggering, with the average lifetime cost for an individual with AD exceeding $170,000. Although the majority of individuals with AD are cared for by family and friends at home, individuals with AD constitute half of all nursing home residents. The average cost of a year of nursing home care for an individual with AD is $42,000, and this cost can exceed $70,000. The purpose of this article is to provide an overview of the etiology of AD, the tools used in the diagnosis of AD, and the treatment of individuals with AD. In addition, the clinical presentation of the various stages of AD is described, and the psychosocial implications of this disease are discussed.

Effects of cognitive function and depressive mood on the quality of life in Chinese Alzheimer's disease patients in Hong Kong.

PubMed

Chan, Ivy Wai-Ping; Chu, Leung-Wing; Lee, Peter W H; Li, Siu-Wah; Yu, Ka-Kui

2011-01-01

In view of the paucity of data on the quality of life (QOL) in Chinese Alzheimer's disease (AD) patients, we investigated the effects of cognitive function and depressive mood on QOL among our Chinese AD patients in Hong Kong, using the Cantonese Chinese version of Quality of Life in Alzheimer's disease (QOL-AD). This was a cross-sectional study. The Cantonese Chinese version of QOL-AD was adapted from the Mandarin Chinese and English versions of QOL-AD, and was administered to 111 AD patients and their caregivers. The Cantonese Chinese version of QOL-AD showed good internal consistency, test-retest and inter-rater reliability. The patients' and caregivers' reports of QOL-AD were moderately correlated (r=0.516, P<0.001). Both QOL-AD scores from patient and caregiver reports varied significantly in relation to the severity of cognitive impairment, being lowest in the subgroup with Mini-Mental State Examination scores of 10 or less. The mean QOL-AD scores from both patient and caregiver reports were also significantly lower in the depressed (Geriatric Depression Scale [GDS] scores≥15) than non-depressed groups (GDS scores≤15) (QOL-AD patient report 23.8 and 34.2, respectively, P<0.001, Student's t-test; QOL-AD caregiver report 28.9 and 31.0, respectively, P<0.05, Student's t-test). General linear model analyses showed that only the MMSE and GDS scores were independent significant factors associated with the patient but not the caregiver reports of the QOL-AD. Among Chinese AD patients in Hong Kong, depressive mood and low MMSE score adversely affect the QOL-AD from the patient but not the caregiver perspectives. © 2010 Japan Geriatrics Society.

Genomic stability of adipogenic human adenovirus 36.

PubMed

Nam, J-H; Na, H-N; Atkinson, R L; Dhurandhar, N V

2014-02-01

Human adenovirus Ad36 increases adiposity in several animal models, including rodents and non-human primates. Importantly, Ad36 is associated with human obesity, which has prompted research to understand its epidemiology and to develop a vaccine to prevent a subgroup of obesity. For this purpose, understanding the genomic stability of Ad36 in vivo and in vitro infections is critical. Here, we examined whether in vitro cell passaging over a 14-year period introduced any genetic variation in Ad36. We sequenced the whole genome of Ad36-which was plaque purified in 1998 from the original strain obtained from American Type Culture Collection, and passaged approximately 12 times over the past 14 years (Ad36-2012). This DNA sequence was compared with a previously published sequence of Ad36 likely obtained from the same source (Ad36-1988). Compared with Ad36-1988, only two nucleotides were altered in Ad36-2012: a T insertion at nucleotide 1862, which may induce early termination of the E1B viral protein, and a T➝C transition at nucleotide 26 136. Virus with the T insertion (designated Ad36-2012-T6) was mixed with wild-type virus lacking the T insertion (designated Ad36-2012-T5) in the viral stock. The transition at nucleotide 26 136 does not change the encoded amino acid (aspartic acid) in the pVIII viral protein. The rate of genetic variation in Ad36 is ∼2.37 × 10(-6) mutations/nucleotide/passage. Of particular importance, there were no mutations in the E4orf1 gene, the critical gene for producing obesity. This very-low-variation rate should reduce concerns about genetic variability when developing Ad36 vaccines or developing assays for detecting Ad36 infection in populations.

Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy.

PubMed

Choi, Joung-Woo; Kim, Hyun Ah; Nam, Kihoon; Na, Youjin; Yun, Chae-Ok; Kim, SungWan

2015-12-28

Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ability of endosomal escape, efficient nuclear entry mechanism, and high transduction, and therapeutic efficacy, tumor specific targeting and antiviral immune response still remain as a critical challenge in clinical setting. To overcome these obstacles and achieve cancer-specific targeting, we constructed tumor targeting bioreducible polymer, an arginine grafted bio-reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1 peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG-HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG-HCBP1, showed a hepatoma cancer specific uptake and transduction compared to either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP-ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide rather than coxsackie and adenovirus receptor specific antibody. In addition, ABP-PEG-HCBP1 can protect biological activity of Ad against serum, and considerably reduced both innate and adaptive immune response against Ad. shMet-expressing oncolytic Ad (oAd; RdB/shMet) complexed with ABP-PEG-HCBP1 delivered oAd efficiently into hepatoma cancer cells. The oAd/ABP-PEG-HCBP1 demonstrated enhanced cancer cell killing efficacy in comparison to oAd/ABP complex. Furthermore, Huh7 and HT1080 cancer cells treated with oAd/shMet-ABP-PEG-HCBP1 complex had significantly decreased Met and VEGF expression in hepatoma cancer, but not in non-hepatoma cancer. In sum, these results suggest that HCBP1-conjugated bioreducible polymer could be used to deliver oncolytic Ad safely and efficiently to treat hepatoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy

PubMed Central

Choi, Joung-Woo; Kim, Hyun Ah; Nam, Kihoon; Na, Youjin; Yun, Chae-Ok; Kim, SungWan

2015-01-01

Despite adenovirus (Ad) vector’s numerous advantages for cancer gene therapy, such as high ability of endosomal escape, efficient nuclear entry mechanism, and high transduction, and therapeutic efficacy, tumor specific targeting and antiviral immune response still remain as a critical challenge in clinical setting. To overcome these obstacles and achieve cancer-specific targeting, we constructed tumor targeting bioreducible polymer, an arginine grafted bio-reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1 peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG-HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG-HCBP1, showed a hepatoma cancer specific uptake and transduction compared to either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP-ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide rather than coxsackie and adenovirus receptor specific antibody. In addition, ABP-PEG-HCBP1 can protect biological activity of Ad against serum, and considerably reduced both innate and adaptive immune response against Ad. shMet-expressing oncolytic Ad (oAd; RdB/shMet) complexed with ABP-PEG-HCBP1 delivered oAd efficiently into hepatoma cancer cells. The oAd/ABP-PEG-HCBP1 demonstrated enhanced cancer cell killing efficacy in comparison to oAd/ABP complex. Furthermore, Huh7 and HT1080 cancer cells treated with oAd/shMet-ABP-PEG-HCBP1 complex had significantly decreased Met and VEGF expression in hepatoma cancer, but not in non-hepatoma cancer. In sum, these results suggest that HCBP1-conjugated bioreducible polymer could be used to deliver oncolytic Ad safely and efficiently to treat hepatoma. PMID:26437261

Vacuum degeneracy and Conformal Mass in Lovelock AdS gravity

NASA Astrophysics Data System (ADS)

Arenas-Henriquez, Gabriel; Miskovic, Olivera; Olea, Rodrigo

2017-11-01

It is shown that the notion of Conformal Mass can be defined within a given anti-de Sitter (AdS) branch of a Lovelock gravity theory as long as the corresponding vacuum is not degenerate. Indeed, conserved charges obtained by the addition of Kounterterms to the bulk action turn out to be proportional to the electric part of the Weyl tensor, when the fall-off of a generic solution in that AdS branch is considered. The factor of proportionality is the degeneracy condition for the vacua in the particular Lovelock AdS theory under study. This last feature explains the obstruction to define Conformal Mass in the degenerate case.

Impacts of changing atmospheric deposition chemistry on nitrogen and phosphorus loading to Ganga River (India).

PubMed

Pandey, Jitendra; Singh, Anand V; Singh, Ashima; Singh, Rachna

2013-08-01

Investigations on atmospheric deposition (AD) and water chemistry along a 35 km stretch of Ganga River indicated that although N:P stoichiometry of AD did not change, there were over 1.4-2.0 fold increase in AD-NO₃⁻, AD-NH₄⁺ and AD-PO₄³⁻ overtime. Concentration of dissolved inorganic-N (DIN) in river showed significant positive correlations with AD-NO₃⁻ and runoff DIN. Similarly, dissolved reactive-P (DRP) in river showed significant positive correlation with AD-PO₄³⁻ and runoff DRP. The study shows that AD has become an important source of N and P input to Ganga River.

TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects.

PubMed

Kamer, Angela R; Craig, Ronald G; Pirraglia, Elizabeth; Dasanayake, Ananda P; Norman, Robert G; Boylan, Robert J; Nehorayoff, Andrea; Glodzik, Lidia; Brys, Miroslaw; de Leon, Mony J

2009-11-30

The associations of inflammation/immune responses with clinical presentations of Alzheimer's disease (AD) remain unclear. We hypothesized that TNF-alpha and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-alpha classification of clinical AD and NL. This study shows that TNF-alpha and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.

Um supressor de fundo térmico para a câmara infravermelha CamIV

NASA Astrophysics Data System (ADS)

Jablonski, F.; Laporte, R.

2003-08-01

O ângulo sólido subtendido pelos pixels na câmara infravermelha do NexGal (CamIV) que operamos no OPD/LNA contém contribuições provenientes do sistema de coleta de fluxo propriamente dito - sendo esta a parte que interessa para as medidas astronômicas - e contribuições da obstrução central, sistema de suporte do espelho secundário e região exterior à pupila de entrada do telescópio. Estas últimas contribuições são devi-das à emissão de corpo negro à temperatura ambiente e aumentam exponencialmente para comprimentos de onda maiores que 2 micra (banda K, no infravermelho próximo). Embora a resultante pode ser quantificada e subtraída dos sinais relevantes, sua variância se adiciona à variância do sinal, e pode ser facilmente a contribuição domi-nante para a incerteza final das medidas, tornando ineficiente o processo de extração de informação e degradando a sensibilidade da câmara. A maneira clássica de resolver esse problema em sistemas ópticos que operam no infravermelho, onde os efeitos da emissão térmica do ambiente são importantes, é restringir o ângulo sólido subtendido pelos pixels individuais exclusivamente aos raios provenientes do sistema óptico. Para tanto, projeta-se uma imagem real, bastante reduzida, da pupila de entrada do sistema óptico num anteparo que transmita para o sistema de imageamento só o que interessa, bloqueando as contribuições das bordas externas à pupila de entrada, obstrução central do telescópio e sistema de suporte. Como a projeção é realizada em ambiente criogênico, a contribuição térmica espúria é efetivamente eliminada. Nós optamos por um sistema do tipo Offner para implementar na prática esta função. Trata-se de um sistema baseado em espelhos esféricos, bastante compacto e ajustado por construção. A opção por espelhos do mesmo material que o sistema de suporte (Alumínio) minimiza a dilatação diferencial, crítica nesse tipo de aplicação. Apresentamos as soluções detalhadas do projeto óptico-mecânico, bem como uma análise de flexões e desempenho em termos de qualidade de imagem.

Prevalence of Comorbidity in Patients With Young-Onset Alzheimer Disease Compared With Late-Onset: A Comparative Cohort Study.

PubMed

Gerritsen, Adrie A J; Bakker, Christian; Verhey, Frans R J; de Vugt, Marjolein E; Melis, René J F; Koopmans, Raymond T C M

2016-04-01

With the lack of a cure for Alzheimer disease (AD), the identification of comorbidity is important to reduce the possibility of excess disability. Although comorbidity in patients with late-onset AD (LO-AD) is common, for people with young-onset AD (YO-AD), it is unclear how often comorbidity occurs. Furthermore, it is uncertain whether comorbidity in patients with YO-AD differs from that in patients with LO-AD. The aim of this study was to explore the prevalence, types of morbidity, and morbidity profiles in patients with YO-AD compared with those of patients with LO-AD. Explorative cohort study from 2 separate Dutch cohorts (Needs in Young-onset Dementia [NeedYD] and the Clinical Course of Cognition and Comorbidity-Dementia Study [4C-Dementia study]). Participants were recruited in 2007 and 2008 from (1) the memory clinics of 3 Dutch Alzheimer centers, (2) the memory clinics of general hospitals, (3) mental health services in the southern part of the Netherlands, and (4) young-onset dementia specialized day care facilities. A comparison group of community-dwelling, elderly patients with AD was selected from the 4C-Dementia study. Patients in this study were recruited in 2010 and 2011 from the aforementioned Alzheimer centers. The prevalence rates of comorbidity were compared between 177 patients with YO-AD and 155 patients with LO-AD. Comorbidity was classified using the International Classification of Diseases, 10th Revision (ICD-10). The total amount of comorbidity was established by counting the number of existing diseases (ICD categories or chapters) and comorbidity was also dichotomized as present or absent. Furthermore, a hierarchical cluster analysis was performed to study clusters of comorbidity. Compared with LO-AD, patients with YO-AD showed less (P < .001) overall comorbidity (58.2% vs 86.5%) and had lower prevalence rates of diabetes, obesity, and circulatory diseases; however, the prevalence rates of diseases of the nervous system in YO-AD (6.2%) were higher compared with those of patients with LO-AD (4.5%). The cluster analysis revealed a distinctive group of patients with YO-AD with either no comorbidity or with a disease of the nervous system. Endocrine, nutritional, and metabolic diseases and diseases of the circulatory system were present in 34% of the patients with YO-AD. Comorbidity is less common in YO-AD than in LO-AD. However, general practitioners should be aware that approximately one-third of the patients with YO-AD suffer from or have endocrine, nutritional, and metabolic diseases and/or diseases of the circulatory system. Treatment should therefore not only focus on dementia but also on comorbidity. This attention may slow the functional decline in AD. These exploratory analyses suggested a higher prevalence of nervous system diseases in YO-AD compared with LO-AD. However, the finding did not reach statistical significance and in combination with the exploratory nature of the analyses justifies further investigation. If verified, this finding may help to decrease the time to diagnosis of AD and, subsequently, support in young patients with a neurological disease. Further investigation is needed to gain more insight into the association between comorbidity and AD in younger people. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Current Advances and Future Challenges in Adenoviral Vector Biology and Targeting

PubMed Central

Campos, Samuel K.; Barry, Michael A.

2008-01-01

Gene delivery vectors based on Adenoviral (Ad) vectors have enormous potential for the treatment of both hereditary and acquired disease. Detailed structural analysis of the Ad virion, combined with functional studies has broadened our knowledge of the structure/function relationships between Ad vectors and host cells/tissues and substantial achievement has been made towards a thorough understanding of the biology of Ad vectors. The widespread use of Ad vectors for clinical gene therapy is compromised by their inherent immunogenicity. The generation of safer and more effective Ad vectors, targeted to the site of disease, has therefore become a great ambition in the field of Ad vector development. This review provides a synopsis of the structure/function relationships between Ad vectors and host systems and summarizes the many innovative approaches towards achieving Ad vector targeting. PMID:17584037

Adenovirus receptors and their implications in gene delivery

PubMed Central

Sharma, Anurag; Li, Xiaoxin; Bangari, Dinesh S.; Mittal, Suresh K.

2010-01-01

Adenoviruses (Ads) have gained popularity as gene delivery vectors for therapeutic and prophylactic applications. Ad entry into host cells involves specific interactions between cell surface receptors and viral capsid proteins. Several cell surface molecules have been identified as receptors for Ad attachment and entry. Tissue tropism of Ad vectors is greatly influenced by their receptor usage. A variety of strategies have been investigated to modify Ad vector tropism by manipulating the receptor-interacting moieties. Many such strategies are aimed at targeting and/or detargeting of Ad vectors. In this review, we discuss the various cell surface molecules that are implicated as receptors for virus attachment and internalization. Special emphasis is given to Ad types that are utilized as gene delivery vectors. Various strategies to modify Ad tropism using the knowledge of Ad receptors are also discussed. PMID:19647886

Modification to the Capsid of the Adenovirus Vector That Enhances Dendritic Cell Infection and Transgene-Specific Cellular Immune Responses

PubMed Central

Worgall, Stefan; Busch, Annette; Rivara, Michael; Bonnyay, David; Leopold, Philip L.; Merritt, Robert; Hackett, Neil R.; Rovelink, Peter W.; Bruder, Joseph T.; Wickham, Thomas J.; Kovesdi, Imi; Crystal, Ronald G.

2004-01-01

Adenovirus (Ad) gene transfer vectors can be used to transfer and express antigens and function as strong adjuvants and thus are useful platforms for the development of genetic vaccines. Based on the hypothesis that Ad vectors with enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced immune responses against antigens encoded by the vector in vivo, the present study analyzes the vaccine potential of an Ad vector expressing β-galactosidase as a model antigen and genetically modified with RGD on the fiber knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity against the β-galactosidase antigen. Infection of murine DC in vitro with AdZ.F(RGD) showed an eightfold-increased transgene expression following infection compared to AdZ (also expressing β-galactosidase, but with a wild-type capsid). Binding, cellular uptake, and trafficking in DC were also increased with AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced immune responses to β-galactosidase in vivo, C57BL/6 mice were immunized with AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both vectors were comparable, with similar anti-β-galactosidase antibody levels following vector administration. However, cellular responses to β-galactosidase were significantly enhanced, with the frequency of CD4+ as well as the CD8+ β-galactosidase-specific gamma interferon response in cells isolated from the draining lymph nodes increased following immunization with AdZ.F(RGD) compared to Ad.Z (P < 0.01). Importantly, this enhanced cellular immune response of the AdZ.F(RGD) vector was sufficient to evoke enhanced inhibition of the growth of preexisting tumors expressing β-galactosidase: BALB/c mice implanted with the CT26 syngeneic β-galactosidase-expressing colon carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased tumor growth and improved survival compared to mice immunized with AdZ. These data demonstrate that addition of an RGD motif to the Ad fiber knob increases the infectibility of DC and leads to enhanced cellular immune responses to the Ad-transferred transgene, suggesting that the RGD capsid modification may be useful in developing Ad-based vaccines. PMID:14963160

Determinants of completion of advance directives: a cross-sectional comparison of 649 outpatients from private practices versus 2158 outpatients from a university clinic.

PubMed

Pfirstinger, Jochen; Bleyer, Bernhard; Blum, Christian; Rechenmacher, Michael; Wiese, Christoph H; Gruber, Hans

2017-12-21

To compare outpatients from private practices and outpatients from a university clinic regarding the determinants of completion of advance directives (AD) in order to generalise results of studies from one setting to the other. Five determinants of completion of AD were studied: familiarity with AD, source of information about AD, prior experiences with own life-threatening diseases or family members in need of care and motives in favour and against completion of AD. Observational cross-sectional study. Private practices and a university clinic in Germany in 2012. 649 outpatients from private practices and 2158 outpatients from 10 departments of a university clinic. Completion of AD, familiarity with AD, sources of information about AD (consultation), prior experiences (with own life-threatening disease and family members in need of care), motives in favour of or against completion of AD, sociodemographic data. Determinants of completion of AD did not differ between outpatients from private practices versus university clinic outpatients. Prior experience with severe disease led to a significantly higher rate of completion of AD (33%/36% with vs 24%/24% without prior experience). Participants with completion of AD had more often received legal than medical consultation before completion, but participants without completion of AD are rather aiming for medical consultation. The motives in favour of or against completion of AD indicated inconsistent patterns. Determinants of completion of AD are comparable in outpatients from private practices and outpatients from a university clinic. Generalisations from university clinic samples towards a broader context thus seem to be legitimate. Only one-third of patients with prior experience with own life-threatening diseases or family members in need of care had completed an AD as expression of their autonomous volition. The participants' motives for or against completion of AD indicate that ADs are considered a kind of 'negative autonomy' as instruments to prevent particular forms of therapy. Interactive, repeated and situation-based AD discussions might reach a higher percentage of patients and concurrently enable personal volitions and thereby strengthen individual 'positive autonomy'. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Integrated Display and Simulation for Automatic Dependent Surveillance–Broadcast and Traffic Collision Avoidance System Data Fusion

PubMed Central

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-01-01

Automatic Dependent Surveillance–Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications. PMID:29137194

Adenoviral Vector Immunity: Its Implications and circumvention strategies

PubMed Central

Ahi, Yadvinder S.; Bangari, Dinesh S.; Mittal, Suresh K.

2014-01-01

Adenoviral (Ad) vectors have emerged as a promising gene delivery platform for a variety of therapeutic and vaccine purposes during last two decades. However, the presence of preexisting Ad immunity and the rapid development of Ad vector immunity still pose significant challenges to the clinical use of these vectors. Innate inflammatory response following Ad vector administration may lead to systemic toxicity, drastically limit vector transduction efficiency and significantly abbreviate the duration of transgene expression. Currently, a number of approaches are being extensively pursued to overcome these drawbacks by strategies that target either the host or the Ad vector. In addition, significant progress has been made in the development of novel Ad vectors based on less prevalent human Ad serotypes and nonhuman Ad. This review provides an update on our current understanding of immune responses to Ad vectors and delineates various approaches for eluding Ad vector immunity. Approaches targeting the host and those targeting the vector are discussed in light of their promises and limitations. PMID:21453277

A note on the entropy of rotating BPS AdS7 × S4 black holes

NASA Astrophysics Data System (ADS)

Hosseini, Seyed Morteza; Hristov, Kiril; Zaffaroni, Alberto

2018-05-01

In this note we show that the entropy of BPS, rotating, electrically charged AdS7 × S 4 black holes can be obtained by an extremization principle involving a particular combination of anomaly coefficients of the six-dimensional N=(2,0) theory. This result extends our previous finding for BPS, rotating AdS5 × S 5 black holes.

Factors influencing the intention to watch online video advertising.

PubMed

Lee, Joonghwa; Lee, Mira

2011-10-01

This study examines the factors influencing consumer intention to watch online video ads, by applying the theory of reasoned action. The attitude toward watching online video ads, the subjective norm, and prior frequency of watching online video ads positively influence the intention to watch online video ads. Further, beliefs held about entertainment and information outcomes from watching online video ads and subjective norm influence attitude toward watching these ads.

Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice

PubMed Central

Baglietto-Vargas, David; Chen, Yuncai; Suh, Dongjin; Ager, Rahasson R.; Rodriguez-Ortiz, Carlos J.; Mederios, Rodrigo; Myczek, Kristoffer; Green, Kim N.; Baram, Tallie Z.; LaFerla, Frank M.

2016-01-01

Alzheimer’s disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD-related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short-term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short-term, multi-modal ‘modern life-like’ stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short-term stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. PMID:26077803

The contribution of small vessel disease to subtypes of Alzheimer's disease: a study on cerebrospinal fluid and imaging biomarkers.

PubMed

Ferreira, Daniel; Shams, Sara; Cavallin, Lena; Viitanen, Matti; Martola, Juha; Granberg, Tobias; Shams, Mana; Aspelin, Peter; Kristoffersen-Wiberg, Maria; Nordberg, Agneta; Wahlund, Lars-Olof; Westman, Eric

2018-05-30

We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß 1-42 , total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD. Copyright © 2018 Elsevier Inc. All rights reserved.

Progressive aphasia secondary to Alzheimer disease pathology: A clinicopathologic and MRI study

PubMed Central

Josephs, Keith A.; Whitwell, Jennifer L.; Duffy, Joseph R.; Vanvoorst, Wendy A.; Strand, Edyth A.; Hu, William T.; Boeve, Bradley F.; Graff-Radford, Neill R.; Parisi, Joseph E.; Knopman, David S.; Dickson, Dennis W.; Jack, Clifford R.; Petersen, Ronald C.

2009-01-01

Background The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive-inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD). Objective To compare clinicopathological and MRI features of subjects with progressive aphasia and AD pathology, to subjects with aphasia and FTLD-U pathology, and subjects with typical AD. Methods We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathological re-analysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared to a normal control group. Results All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed grey matter atrophy predominantly in the temporoparietal cortices with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy. Conclusions A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying AD pathology rather than FTLD-U. PMID:18166704

Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies

PubMed Central

Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.

2011-01-01

Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

Trends in exposure to television food advertisements in South Korea.

PubMed

Han, Euna; Powell, Lisa M; Kim, Tae Hyun

2013-03-01

Given the increased concern about the impact of TV food advertisements (ads) on individual food choices, we provide important evidence on TV food ad exposure between 2004 and 2009 in South Korea. We used monthly targeted ratings data by age group as the number of ads seen daily from Korean Nielsen Media Research. We generated six food groups: beverages (milk, soda, fruit drinks, sports/energy drinks, water, coffee/tea products, and other); snacks/sweets (cookies/chips, candy, and chewing gum); fast food (Domino's pizza, Lotteria, McDonald's, Mr. Pizza, Pizza Hut, local chicken and pizza franchises, and other); instant noodle; full-service restaurants; and other. From 2004 to 2009, overall exposure to television food ads fell by 19.0% (from 6.8 to 5.5 ads daily), although exposure to full-service restaurant ads increased over that time period by 45.7%. While fast-food ad exposure fell overall, exposure to ads for local fried chicken franchises nearly doubled, making them the most commonly seen fast-food ads by 2009. Fast-food and instant noodle ads made up larger proportions of total ad exposure in 2009 than in 2004 in all age groups, with the largest increase among adolescents. Beverage ads continue to be the most prevalent food ads seen in South Korea. Differential trends found in exposure across and within food product categories and differences by age groups highlight the need for continued monitoring to help inform the regulatory policy debate on food advertising, particularly with regards to ads directed at children and adolescents. Copyright © 2012 Elsevier Ltd. All rights reserved.

Financial and health literacy predict incident AD dementia and AD pathology

PubMed Central

Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.; Boyle, Patricia A.

2017-01-01

Background Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. Objective We test the hypothesis that domain specific literacy is associated with AD dementia and AD pathology after controlling for cognition. Methods Participants were community based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined post-mortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. Results All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p<0.001), and the association persisted after controlling for cognition (Hazard Ratio=1.50, p=0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β=0.07, p=0.035). Conclusion Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition. PMID:28157101

Abnormal functional connectivity of the posterior cingulate cortex is associated with depressive symptoms in patients with Alzheimer’s disease

PubMed Central

Zhang, Jiangtao; Guo, Zhongwei; Liu, Xiaozheng; Jia, Xize; Li, Jiapeng; Li, Yaoyao; Lv, Danmei; Chen, Wei

2017-01-01

Background Depressive symptoms are significant and very common psychiatric complications in patients with Alzheimer’s disease (AD), which can aggravate the decline in social function. However, changes in the functional connectivity (FC) of the brain in AD patients with depressive symptoms (D-AD) remain unclear. Objective To investigate whether any differences exist in the FC of the posterior cingulate cortex (PCC) between D-AD patients and non-depressed AD patients (nD-AD). Materials and methods We recruited 15 D-AD patients and 17 age-, sex-, educational level-, and Mini-Mental State Examination (MMSE)-matched nD-AD patients to undergo tests using the Neuropsychiatric Inventory, Hamilton Depression Rating Scale, and 3.0T resting-state functional magnetic resonance imaging. Bilateral PCC were selected as the regions of interest and between-group differences in the PCC FC network were assessed using Student’s t-test. Results Compared with the nD-AD group, D-AD patients showed increased PCC FC in the right amygdala, right parahippocampus, right superior temporal pole, right middle temporal lobe, right middle temporal pole, and right hippocampus (AlphaSim correction; P<0.05). In the nD-AD group, MMSE scores were positively correlated with PCC FC in the right superior temporal pole and right hippocampus (false discovery rate corrected; P<0.05). Conclusion Differences were detected in PCC FC between nD-AD and D-AD patients, which may be related to depressive symptoms. Our study provides a significant enhancement to our understanding of the functional mechanisms underlying D-AD. PMID:29066900

Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer's Disease (sAD)-Like Pathology.

PubMed

Kamat, Pradip K; Kalani, Anuradha; Rai, Shivika; Tota, Santosh Kumar; Kumar, Ashok; Ahmad, Abdullah S

2016-09-01

Alzheimer's disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer's disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology.

Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in Combination with rAd5-EnvA in Healthy Adults (VRC 012).

PubMed

Crank, Michelle C; Wilson, Eleanor M P; Novik, Laura; Enama, Mary E; Hendel, Cynthia S; Gu, Wenjuan; Nason, Martha C; Bailer, Robert T; Nabel, Gary J; McDermott, Adrian B; Mascola, John R; Koup, Richard A; Ledgerwood, Julie E; Graham, Barney S

2016-01-01

VRC 012 was a Phase I study of a prototype recombinant adenoviral-vector serotype-35 (rAd35) HIV vaccine, the precursor to two recently published clinical trials, HVTN 077 and 083. On the basis of prior evaluation of multiclade rAd5 HIV vaccines, Envelope A (EnvA) was selected as the standard antigen for a series of prototype HIV vaccines to compare various vaccine platforms. In addition, prior studies of rAd5-vectored vaccines suggested pre-existing human immunity may be a confounding factor in vaccine efficacy. rAd35 is less seroprevalent across human populations and was chosen for testing alone and in combination with a rAd5-EnvA vaccine in the present two-part phase I study. First, five subjects each received a single injection of 109, 1010, or 1011 particle units (PU) of rAd35-EnvA in an open-label, dose-escalation study. Next, 20 Ad5/Ad35-seronegative subjects were randomized to blinded, heterologous prime-boost schedules combining rAd5-EnvA and rAd35-EnvA with a three month interval. rAd35-EnvA was given at 1010 or 1011 PU to ten subjects each; all rAd5-EnvA injections were 1010 PU. EnvA-specific immunogenicity was assessed four weeks post-injection. Solicited reactogenicity and clinical safety were followed after each injection. Vaccinations were well tolerated at all dosages. Antibody responses measured by ELISA were detected at 4 weeks in 30% and 50% of subjects after single doses of 1010 or 1011 PU rAd35, respectively, and in 89% after a single rAd5-EnvA 1010 PU injection. EnvA-specific IFN-γ ELISpot responses were detected at four weeks in 0%, 70%, and 50% of subjects after the respective rAd35-EnvA dosages compared to 89% of subjects after rAd5. T cell responses were higher after a single rAd5-EnvA 1010 PU injection than after a single rAd35-EnvA 1010 PU injection, and humoral responses were low after a single dose of either vector. Of those completing the vaccine schedule, 100% of rAd5-EnvA recipients and 90% of rAd35-EnvA recipients had both T cell and humoral responses after boosting with the heterologous vector. ELISpot response magnitude was similar in both regimens and comparable to a single dose of rAd5. A trend toward more robust CD8 T cell responses using rAd5-EnvA prime and rAd35-EnvA boost was observed. Humoral response magnitude was also similar after either heterologous regimen, but was several fold higher than after a single dose of rAd5. Adverse events (AEs) related to study vaccines were in general mild and limited to one episode of hematuria, Grade two. Activated partial thromboplastin time (aPTT) AEs were consistent with an in vitro effect on the laboratory assay for aPTT due to a transient induction of anti-phospholipid antibody, a phenomenon that has been reported in other adenoviral vector vaccine trials. Limitations of the rAd vaccine vectors, including the complex interactions among pre-existing adenoviral immunity and vaccine-induced immune responses, have prompted investigators to include less seroprevalent vectors such as rAd35-EnvA in prime-boost regimens. The rAd35-EnvA vaccine described here was well tolerated and immunogenic. While it effectively primed and boosted antibody responses when given in a reciprocal prime-boost regimen with rAd5-EnvA using a three-month interval, it did not significantly improve the frequency or magnitude of T cell responses above a single dose of rAd5. The humoral and cellular immunogenicity data reported here may inform future vaccine and study design. ClinicalTrials.gov NCT00479999.

Addison's disease: a survey on 633 patients in Padova.

PubMed

Betterle, Corrado; Scarpa, Riccardo; Garelli, Silvia; Morlin, Luca; Lazzarotto, Francesca; Presotto, Fabio; Coco, Graziella; Masiero, Stefano; Parolo, Anna; Albergoni, Maria Paola; Favero, Roberta; Barollo, Susi; Salvà, Monica; Basso, Daniela; Chen, Shu; Rees Smith, Bernard; Furmaniak, Jadwiga; Mantero, Franco

2013-12-01

Addison's disease (AD) is a rare endocrine condition. We aimed to evaluate clinical, immunologic, adrenal imaging, and genetic features in 633 Italian patients with AD followed up since 1967. Adrenal cortex autoantibodies, presence of other autoimmune and nonautoimmune diseases, nonadrenal autoantibodies, adrenal imaging, and genetic profile for HLA-DRB1 and AIRE were analyzed. A total of 492 (77.7%) patients were found to be affected by autoimmune AD (A-AD), 57 (9%) tuberculous AD, 29 (4.6%) genetic-associated AD, 10 (1.6%) adrenal cancer, six (0.94%) post-surgical AD, four (0.6%) vascular disorder-related AD, three (0.5%) post-infectious AD, and 32 (5.1%) were defined as idiopathic. Adrenal cortex antibodies were detected in the vast majority (88100%) of patients with recent onset A-AD, but in none of those with nonautoimmune AD. Adrenal imaging revealed normal/atrophic glands in all A-AD patients: 88% of patients with A-AD had other clinical or subclinical autoimmune diseases or were positive for nonadrenal autoantibodies. Based on the coexistence of other autoimmune disorders, 65.6% of patients with A-AD were found to have type 2 autoimmune polyendocrine syndrome (APS2), 14.4% have APS1, and 8.5% have APS4. Class II HLA alleles DRB1*03 and DRB1*04 were increased, and DRB1*01, DRB1*07, DRB1*013 were reduced in APS2 patients when compared with controls. Of the patients with APS1, 96% were revealed to have AIRE gene mutations. A-AD is the most prevalent form of adrenal insufficiency in Italy, and ∼90% of the patients are adrenal autoantibody-positive at the onset. Assessment of patients with A-AD for the presence of other autoimmune diseases should be helpful in monitoring and diagnosing APS types 1, 2, or 4 and improving patients' care.

In situ reprogramming to transdifferentiate fibroblasts into cardiomyocytes using adenoviral vectors: Implications for clinical myocardial regeneration.

PubMed

Mathison, Megumi; Singh, Vivek P; Chiuchiolo, Maria J; Sanagasetti, Deepthi; Mao, Yun; Patel, Vivekkumar B; Yang, Jianchang; Kaminsky, Stephen M; Crystal, Ronald G; Rosengart, Todd K

2017-02-01

The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors. Ad or lentivirus vectors encoding Gata4 (G), Mef2c (M), and Tbx5 (T) were validated in vitro. Sprague-Dawley rats then underwent coronary ligation and Ad-mediated administration of vascular endothelial growth factor to generate infarct prevascularization. Three weeks later, animals received Ad or lentivirus encoding G, M, or T (AdGMT or LentiGMT) or an equivalent dose of a null vector (n = 11, 10, and 10, respectively). Outcomes were analyzed by echocardiography, magnetic resonance imaging, and histology. Ad and lentivirus vectors provided equivalent G, M, and T expression in vitro. AdGMT and LentiGMT both likewise induced expression of the cardiomyocyte marker cardiac troponin T in approximately 6% of cardiac fibroblasts versus <1% cardiac troponin T expression in AdNull (adenoviral vector that does not encode a transgene)-treated cells. Infarcted myocardium that had been treated with AdGMT likewise demonstrated greater density of cells expressing the cardiomyocyte marker beta myosin heavy chain 7 compared with AdNull-treated animals. Echocardiography demonstrated that AdGMT and LentiGMT both increased ejection fraction compared with AdNull (AdGMT: 21% ± 3%, LentiGMT: 14% ± 5%, AdNull: -0.4% ± 2%; P < .05). Ad vectors are at least as effective as lentiviral vectors in inducing cardiac fibroblast transdifferentiation into induced cardiomyocyte-like cells and improving cardiac function in postinfarct rat hearts. Short-term expression Ad vectors may represent an important means to induce cardiac cellular reprogramming in humans. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Alzheimer disease with cerebrovascular disease and vascular dementia: clinical features and course compared with Alzheimer disease.

PubMed

Bruandet, A; Richard, F; Bombois, S; Maurage, C A; Deramecourt, V; Lebert, F; Amouyel, P; Pasquier, F

2009-02-01

Vascular dementia (VaD) and Alzheimer disease with cerebrovascular disease (AD+CVD) are the leading causes of dementia after Alzheimer disease alone (AD). Little is known about the progression of either VaD or AD+CVD. The aim of this study was to compare demographic features, cognitive decline and survival of patients with VaD, AD+CVD and AD alone attending a memory clinic. This study included 970 patients who were followed at the Lille-Bailleul memory clinic, France. Cognitive functions were measured with the Mini Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). Survival rate was analysed with a left-truncated Cox model. Analyses were adjusted for age, sex, education, hypertension, diabetes and baseline MMSE and DRS. Of 970 patients, 141 had VaD, 663 AD alone and 166 AD+CVD. The latter were significantly older than AD or VaD patients at onset (71 (SD 7) vs 69 (9) and 68 (9) years, p = 0.01) and at first visit (75 (6) vs 73 (8) and 72 (8) years, p = 0.0002). Baseline MMSE and DRS evaluations were highest for VaD compared with AD alone or AD+CVD patients (p<0.006). Cognitive decline during follow-up was slowest for VaD, intermediate for AD+CVD and fastest for AD alone (p = 0.03). After adjustment, compared with AD patients, mortality risk was similar for those with VaD (relative mortality risk (RR) = 0.7 (0.5 to 1.1)) and tended to be lower for AD+CVD (RR = 0.7 (0.5 to 1.0)). The shorter the delay between first symptoms and first visit, the longer patients survived. This clinical cohort study shows that patients with VaD, AD+CVD and AD present different characteristics at baseline and during follow-up, and underlines the need to distinguish between them.

[A model of world population growth as an experiment in systematic research].

PubMed

Kapitsa, S

1997-01-01

A mathematical model was developed for the estimation of global population growth, and the estimates were compared with those of the UN and covered the stretch of 4.4 million years B.C. to the years 2175 and 2500 A.D. The estimates were also broken down into human, geological, and technological historical periods. The model showed that human population would stabilize at the level of 14 billion around 2500 A.D. and 13 billion around 2200 A.D., in accordance with UN projections. It also revealed the history of human population growth through the following stages (UN figures are listed in parentheses): 100,000, about 1.6 million years ago; 5 (1-5) million, 35,000 B.C.; 21 (10-15) million, 7000 B.C.; 46 (47) million, 2000 B.C.; 93 (100-230) million, at the time of Christ; 185 (275-345) million, 1000 A.D.; 366 (450-540) million, 1500 A.D.; 887 (907) million, 1800 A.D.; 1158 (1170) million, 1850 A.D.; 1656 (1650-1710) million, 1900 A.D.; 2812 (2515) million, 1950 A.D.; 5253 (5328) million, 1990 A.D.; 6265 (6261) million, 2000 A.D.; 10,487 (10,019) million, 2050 A.D.; 12,034 (11,186) million, 2100 A.D.; 12,648 (11,543) million, 2150 A.D.; 12,946 (11,600) million, 2200 A.D.; and 13,536 million, 2500 A.D. The model advanced the investigation of phenomena by studying the interactions between economical, technological, social, cultural, and biological processes. The analysis showed that humanity has reached a critical phase in its growth and that development in each period depended on external, not internal, factors. This permits the formulation of the principle of demographic imperative (distinct from the Malthusian principle), which states that resources determine the speed and extent of the growth of population.

New massive gravity and AdS(4) counterterms.

PubMed

Jatkar, Dileep P; Sinha, Aninda

2011-04-29

We show that the recently proposed Dirac-Born-Infeld extension of new massive gravity emerges naturally as a counterterm in four-dimensional anti-de Sitter space (AdS(4)). The resulting on-shell Euclidean action is independent of the cutoff at zero temperature. We also find that the same choice of counterterm gives the usual area law for the AdS(4) Schwarzschild black hole entropy in a cutoff-independent manner. The parameter values of the resulting counterterm action correspond to a c=0 theory in the context of the duality between AdS(3) gravity and two-dimensional conformal field theory. We rewrite this theory in terms of the gauge field that is used to recast 3D gravity as a Chern-Simons theory.

Effects of message framing and visual-fear appeals on smoker responses to antismoking ads.

PubMed

Kang, Jungsuk; Lin, Carolyn A

2015-01-01

This study examined the effects of antismoking ads on Korean adult male smokers. An experiment was conducted to explore how message framing and visual-fear appeals embedded in antismoking ads may influence ad-evoked fear, threat appraisals, and intention to quit smoking. Results showed that (a) antismoking ad exposure increased ad-evoked fear and cessation intention; (b) optimistic bias was stronger when the visual-fear appeal was absent in antismoking ads; and (c) preexposure cessation intension as well as postexposure perceived severity and optimistic bias were positively predictive of smokers' postexposure cessation intention The study provided the first preliminary empirical evidence for validating the combined effects of message frames and visual-fear appeals in antismoking ads on facilitating cessation intention.

The genetics of Alzheimer disease.

PubMed

Tanzi, Rudolph E

2012-10-01

Family history is the second strongest risk factor for Alzheimer disease (AD) following advanced age. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 virtually guarantee early-onset (<60 years) familial AD, which represents ∼5% of AD. On the other hand, common gene polymorphisms, such as the ε4 and ε2 variants of the APOE gene, can influence susceptibility for ∼50% of the common late-onset AD. These four genes account for 30%-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of 11 additional AD candidate genes. This paper reviews the past, present, and future attempts to elucidate the complex and heterogeneous genetic underpinnings of AD.

AdS5×S(5) mirror model as a string sigma model.

PubMed

Arutyunov, Gleb; van Tongeren, Stijn J

2014-12-31

Doing a double Wick rotation in the world sheet theory of the light cone AdS5×S(5) superstring results in an inequivalent, so-called mirror theory that plays a central role in the field of integrability in the AdS-CFT correspondence. We show that this mirror theory can be interpreted as the light cone theory of a free string on a different background. This background is related to dS5×H(5) by a double T-duality, and has hidden supersymmetry. The geometry can also be extracted from an integrable deformation of the AdS5×S(5) sigma model, and we prove the observed mirror duality of these deformed models at the bosonic level as a byproduct. While we focus on AdS5×S(5), our results apply more generally.

Quantum criticality and duality in the Sachdev-Ye-Kitaev/AdS2 chain

NASA Astrophysics Data System (ADS)

Jian, Shao-Kai; Xian, Zhuo-Yu; Yao, Hong

2018-05-01

We show that the quantum critical point (QCP) between a diffusive metal and ferromagnetic (or antiferromagnetic) phases in the SYK chain has a gravitational description corresponding to the double-trace deformation in an AdS2 chain. Specifically, by studying a double-trace deformation of a Z2 scalar in an AdS2 chain where the Z2 scalar is dual to the order parameter in the SYK chain, we find that the susceptibility and renormalization group equation describing the QCP in the SYK chain can be exactly reproduced in the holographic model. Our results suggest that the infrared geometry in the gravity theory dual to the diffusive metal of the SYK chain is also an AdS2 chain. We further show that the transition in SYK model captures universal information about double-trace deformation in generic black holes with near horizon AdS2 space-time.

Secure ADS-B authentication system and method

NASA Technical Reports Server (NTRS)

Viggiano, Marc J (Inventor); Valovage, Edward M (Inventor); Samuelson, Kenneth B (Inventor); Hall, Dana L (Inventor)

2010-01-01

A secure system for authenticating the identity of ADS-B systems, including: an authenticator, including a unique id generator and a transmitter transmitting the unique id to one or more ADS-B transmitters; one or more ADS-B transmitters, including a receiver receiving the unique id, one or more secure processing stages merging the unique id with the ADS-B transmitter's identification, data and secret key and generating a secure code identification and a transmitter transmitting a response containing the secure code and ADSB transmitter's data to the authenticator; the authenticator including means for independently determining each ADS-B transmitter's secret key, a receiver receiving each ADS-B transmitter's response, one or more secure processing stages merging the unique id, ADS-B transmitter's identification and data and generating a secure code, and comparison processing comparing the authenticator-generated secure code and the ADS-B transmitter-generated secure code and providing an authentication signal based on the comparison result.

The Genetics of Alzheimer Disease

PubMed Central

Tanzi, Rudolph E.

2012-01-01

Family history is the second strongest risk factor for Alzheimer disease (AD) following advanced age. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 virtually guarantee early-onset (<60 years) familial AD, which represents ∼5% of AD. On the other hand, common gene polymorphisms, such as the ε4 and ε2 variants of the APOE gene, can influence susceptibility for ∼50% of the common late-onset AD. These four genes account for 30%–50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of 11 additional AD candidate genes. This paper reviews the past, present, and future attempts to elucidate the complex and heterogeneous genetic underpinnings of AD. PMID:23028126

Generation of a Kupffer Cell-evading Adenovirus for Systemic and Liver-directed Gene Transfer

PubMed Central

Khare, Reeti; May, Shannon M; Vetrini, Francesco; Weaver, Eric A; Palmer, Donna; Rosewell, Amanda; Grove, Nathan; Ng, Philip; Barry, Michael A

2011-01-01

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to escape Kupffer cell uptake as evidenced by producing no Kupffer cell death in vivo, not requiring predosing in vivo, and being phagocytosed less efficiently by macrophages in vitro compared to Ad5. When tested as a helper-dependent adenovirus (Ad) vector, Ad5/6 mediated higher luciferase and factor IX transgene expression than either helper-dependent adenoviral 5 (HD-Ad5) or HD-Ad6 vectors. These data suggest that the Ad5/6 hexon-chimera evades Kupffer cells and may have utility for systemic and liver-directed therapies. PMID:21505422

Generation of a Kupffer cell-evading adenovirus for systemic and liver-directed gene transfer.

PubMed

Khare, Reeti; May, Shannon M; Vetrini, Francesco; Weaver, Eric A; Palmer, Donna; Rosewell, Amanda; Grove, Nathan; Ng, Philip; Barry, Michael A

2011-07-01

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to escape Kupffer cell uptake as evidenced by producing no Kupffer cell death in vivo, not requiring predosing in vivo, and being phagocytosed less efficiently by macrophages in vitro compared to Ad5. When tested as a helper-dependent adenovirus (Ad) vector, Ad5/6 mediated higher luciferase and factor IX transgene expression than either helper-dependent adenoviral 5 (HD-Ad5) or HD-Ad6 vectors. These data suggest that the Ad5/6 hexon-chimera evades Kupffer cells and may have utility for systemic and liver-directed therapies.

Measurement and validation of the nature of salivary adiponectin.

PubMed

Akuailou, Eleonore-N; Vijayagopal, Parakat; Imrhan, Victorine; Prasad, Chandan

2013-10-01

Adiponectin (Ad) is an adipocyte-derived hormone that plays an essential role in regulating insulin sensitivity, inflammation, and atherogenesis. Levels of some hormones in saliva change in a fashion similar to that in plasma in response to a disease or physiological condition. Since saliva is an easy to obtain biological fluid, measurements of salivary hormonal changes are preferred in diagnoses and treatments. Therefore, it was of interest to examine the nature of salivary Ad. While there have been two publications in the literature reporting presence of Ad in human saliva, the nature of salivary Ad has not been characterized. To this end, we investigated the effect of sample dilution on the measurement of Ad in saliva. To our surprise, we observed an increase in measurable level of Ad in saliva on sample dilution. One explanation for this paradoxical observation may be the presence of inhibitor(s) of Ad/anti-Ad binding in saliva that following dilution relieves the inhibitory effect. Working with this hypothesis, we were able to demonstrate the presence of an inhibitor in saliva that co-eluted with the dimeric form of Ad and was capable of inhibiting Ad assay. The presence of such inhibitor(s) may lead to underestimation of Ad in saliva.

Utility of the AD8 as a self-rating tool for cognitive impairment in an Asian population.

PubMed

Chin, Rowena; Ng, Amanda; Narasimhalu, Kaavya; Kandiah, Nagaendran

2013-05-01

AD8 is a brief informant interview used to detect early cognitive change. This study evaluated the diagnostic performance of the participant-rated AD8 (p-AD8) in a predominantly Chinese population. Data on demographics, clinical, and cognitive features were collected from 73 participants with no cognitive impairment (NCI), 27 participants with mild cognitive impairments, and 78 participants with Alzheimer's disease-informant dyads. Agreement and discriminative properties of p-AD8 were assessed. AD8 scores were associated with dementia severity. Participant and informant AD8 scores were moderately correlated within dementia dyads. The p-AD8 showed good diagnostic performance in differentiating between participants with NCI and participants with cognitive impairment (sensitivity = 85.0%, specificity = 74.0%, and area under the curve = 0.80), with a cutoff score of ≥1. Combination of impairment in Mini-Mental State Examination and p-AD8 is more useful in detecting cognitive impairment than using the AD8 alone. Within a transcultural setting, the p-AD8 demonstrated good discriminative validity and can be used to gain a preliminary understanding of an individual's cognitive status.

A mitocentric view of Alzheimer's disease suggests multi-faceted treatments.

PubMed

Gibson, Gary E; Shi, Qingli

2010-01-01

Alzheimer's disease (AD) is defined by senile plaques made of amyloid-beta peptide (Abeta), neurofibrillary tangles made of hyperphosphorylated tau proteins, and memory deficits. Thus, the events initiating the cascade leading to these end points may be more effective therapeutic targets than treating each facet individually. In the small percentage of cases of AD that are genetic (or animal models that reflect this form of AD), the factor initiating AD is clear (e.g., genetic mutations lead to high Abeta1-42 or hyperphosphorylated tau proteins). In the vast majority of AD cases, the cause is unknown. Substantial evidence now suggests that abnormalities in glucose metabolism/mitochondrial function/oxidative stress (GMO) are an invariant feature of AD and occur at an early stage of the disease process in both genetic and non-genetic forms of AD. Indeed, decreases in brain glucose utilization are diagnostic for AD. Changes in calcium homeostasis also precede clinical manifestations of AD. Abnormal GMO can lead to plaques, tangles, and the calcium abnormalities that accompany AD. Abnormalities in GMO diminish the ability of the brain to adapt. Therapies targeting mitochondria may ameliorate abnormalities in plaques, tangles, calcium homeostasis, and cognition that comprise AD.

Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization

PubMed Central

Maxfield, Lori F.; Abbink, Peter; Stephenson, Kathryn E.; Borducchi, Erica N.; Ng'ang'a, David; Kirilova, Marinela M.; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank

2015-01-01

Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. PMID:26376928

Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization.

PubMed

Maxfield, Lori F; Abbink, Peter; Stephenson, Kathryn E; Borducchi, Erica N; Ng'ang'a, David; Kirilova, Marinela M; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank; Barouch, Dan H

2015-11-01

Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. Copyright © 2015, Maxfield et al.

Smoking, death, and Alzheimer disease: a case of competing risks.

PubMed

Chang, Chung-Chou H; Zhao, Yongyun; Lee, Ching-Wen; Ganguli, Mary

2012-01-01

If smoking is a risk factor for Alzheimer disease (AD) but a smoker dies of another cause before developing or manifesting AD, smoking-related mortality may mask the relationship between smoking and AD. This phenomenon, referred to as competing risk, complicates efforts to model the effect of smoking on AD. Typical survival regression models assume that censorship from analysis is unrelated to an individual's probability for developing AD (ie, censoring is noninformative). However, if individuals who die before developing AD are younger than those who survive long enough to develop AD, and if they include a higher percentage of smokers than nonsmokers, the incidence of AD will appear to be higher in older individuals and in nonsmokers. Further, age-specific mortality rates are higher in smokers because they die earlier than nonsmokers. Therefore, if we fail to take into account the competing risk of death when we estimate the effect of smoking on AD, we bias the results and are in fact only comparing the incidence of AD in nonsmokers with that in the healthiest smokers. In this study, we demonstrate that the effect of smoking on AD differs in models that are and are not adjusted for competing risks.

Bacterial pattern and antibiotic sensitivity in children and adolescents with infected atopic dermatitis

NASA Astrophysics Data System (ADS)

Samosir, C. T.; Ruslie, R. H.; Rusli, R. E.

2018-03-01

Atopic dermatitis (AD) is a pruritic and chronic inflammatory skin disease which affected approximately 20% in children. Bacterial infection is common in AD patients and correlates directly with AD severity. A cross-sectional study was conducted to evaluate the prevalence of bacterial skin infection in AD patients and its relation with severity of AD and also to study bacteria in the infected AD and its antibiotic sensitivity. Samples were 86 children and adolescents with an AD in Helvetia Community Health Center Medan from March 2016 until February 2017. Index of SCORing Atopic Dermatitis (SCORAD) was used to evaluate the severity of AD. Lesion and nonlesional skinwere swabbed to take sterile cultures. All bacteria noted and tested for antibiotic sensitivity. Datawere by using Chi-Square and Mann Whitney test with 95% CI and p-value<0.05 was considered statistically significant. Fifty-six AD patients (65.1%) were bacterial infected. There was a significant relationship between severity of AD and bacterial infection (p = 0.006). Staphylococcus aureus was the leading bacteria from all degrees of AD severity. Isolated Staphylococcus aureuswas sensitive to amoxicillin-clavulanate (93.3%), clindamycin (90%), erythromycin (90%), and gentamicin (90%), while sensitivity to tetracycline was low (20%).

Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up.

PubMed

Marden, Jessica R; Mayeda, Elizabeth R; Walter, Stefan; Vivot, Alexandre; Tchetgen Tchetgen, Eric J; Kawachi, Ichiro; Glymour, M Maria

2016-01-01

Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores measured 1 to 8 times between 1998 and 2012 (average baseline age=62), we calculated weighted polygenic risk scores [AD Genetic Risk Score (AD-GRS)] using the top 22 AD-associated loci, and an alternative score excluding apolipoprotein E (APOE) (AD-GRSexAPOE). We used generalized linear models with AD-GRS-by-age and AD-GRS-by-age interactions (age centered at 70) to predict memory decline. Average NHB decline was 26% faster than NHW decline (P<0.001). Among NHW, 10% higher AD-GRS predicted faster memory decline (linear β=-0.058 unit decrease over 10 y; 95% confidence interval,-0.074 to -0.043). AD-GRSexAPOE also predicted faster decline for NHW, although less strongly. Among NHB, AD-GRS predicted faster memory decline (linear β=-0.050; 95% confidence interval, -0.106 to 0.006), but AD-GRSexAPOE did not. Our nonsignificant estimate among NHB may reflect insufficient statistical power or a misspecified AD-GRS among NHB as an overwhelming majority of genome-wide association studies are conducted in NHW. A polygenic score based on previously identified AD loci predicts memory loss in US blacks and whites.

Novel Treatment Strategies Using TiO2-Nanowired Delivery of Histaminergic Drugs and Antibodies to Tau With Cerebrolysin for Superior Neuroprotection in the Pathophysiology of Alzheimer's Disease.

PubMed

Sharma, Aruna; Menon, Preeti K; Patnaik, Ranjana; Muresanu, Dafin F; Lafuente, José V; Tian, Z Ryan; Ozkizilcik, Asya; Castellani, Rudy J; Mössler, Herbert; Sharma, Hari S

2017-01-01

More than 5.5 million Americans of all ages are suffering from Alzheimer's disease (AD) till today for which no suitable therapy has been developed so far. Thus, there is an urgent need to explore novel therapeutic measures to contain brain pathology in AD. The hallmark of AD includes amyloid-beta peptide (AβP) deposition and phosphorylation of tau in AD brain. Recent evidences also suggest a marked decrease in neurotrophic factors in AD. Thus, exogenous supplement of neurotrophic factors could be one of the possible ways for AD therapy. Human postmortem brain in AD shows alterations in histamine receptors as well, indicating an involvement of the amine in AD-induced brain pathology. In this review, we focused on role of histamine 3 and 4 receptor-modulating drugs in the pathophysiology of AD. Moreover, antibodies to histamine and tau appear to be also beneficial in reducing brain pathology, blood-brain barrier breakdown, and edema formation in AD. Interestingly, TiO 2 -nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors attenuated AβP deposition and reduced tau phosphorylation in AD brain leading to neuroprotection. Coadministration of cerebrolysin with histamine antibodies or tau antibodies has further enhanced neuroprotection in AD. These novel observations strongly suggest a role of nanomedicine in AD that requires further investigation. © 2017 Elsevier Inc. All rights reserved.

The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis

PubMed Central

Park, Kyung-Duck; Pak, Sok Cheon; Park, Kwan-Kyu

2016-01-01

Atopic dermatitis (AD) is a common allergic skin disease that is associated with chronic, recurrent eczematous and pruritic lesions at the flexural folds caused by interacting factors related to environmental and immune system changes. AD results in dry skin, and immunoglobulin E-mediated allergic reactions to foods and environmental allergens. While steroids and anti-histamines temporarily relieve the symptoms of AD, the possibility of side effects from pharmacological interventions remains. Despite intensive research, the underlying mechanisms for AD have not been clarified. A study of Staphylococcus aureus (S. aureus) established the role of its toxins in the pathogenesis of AD. Approximately 90% of patients with AD experience S. aureus colonization and up to 50%–60% of the colonizing S. aureus is toxin-producing. Any damage to the protective skin barrier allows for the entry of invading allergens and pathogens that further drive the pathogenesis of AD. Some natural toxins (or their components) that have therapeutic effects on AD have been studied. In addition, recent studies on inflammasomes as one component of the innate immune system have been carried out. Additionally, studies on the close relationship between the activation of inflammasomes and toxins in AD have been reported. This review highlights the literature that discusses the pathogenesis of AD, the role of toxins in AD, and the positive and negative effects of toxins on AD. Lastly, suggestions are made regarding the role of inflammasomes in AD. PMID:28025545

Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease

PubMed Central

Price, Joseph L.; McKeel, Daniel W.; Buckles, Virginia D.; Roe, Catherine M.; Xiong, Chengjie; Grundman, Michael; Hansen, Lawrence A.; Petersen, Ronald C.; Parisi, Joseph E.; Dickson, Dennis W.; Smith, Charles D.; Davis, Daron G.; Schmitt, Frederick A.; Markesbery, William R.; Kaye, Jeffrey; Kurlan, Roger; Hulette, Christine; Kurland, Brenda F.; Higdon, Roger; Kukull, Walter; Morris, John C.

2009-01-01

Objective To determine the frequency and possible cognitive effect of histological Alzheimer’s disease (AD) in autopsied older nondemented individuals. Design Senile plaques (SPs) and neurofibrillary tangles (NFTs) were assessed quantitatively in 97 cases from 7 Alzheimer’s Disease Centers (ADCs). Neuropathological diagnoses of AD (npAD) were also made with four sets of criteria. Adjusted linear mixed models tested differences between participants with and without npAD on the quantitative neuropathology measures and psychometric test scores prior to death. Spearman rank-order correlations between AD lesions and psychometric scores at last assessment were calculated for cases with pathology in particular regions. Setting Washington University Alzheimer’s Disease Research Center. Participants Ninety-seven nondemented participants who were age 60 years or older at death (mean = 84 years). Results About 40% of nondemented individuals met at least some level of criteria for npAD; when strict criteria were used, about 20% of cases had npAD. Substantial overlap of Braak neurofibrillary stages occurred between npAD and no-npAD cases. Although there was no measurable cognitive impairment prior to death for either the no-npAD or npAD groups, cognitive function in nondemented aging appears to be degraded by the presence of NFTs and SPs. Conclusions Neuropathological processes related to AD in persons without dementia appear to be associated with subtle cognitive dysfunction and may represent a preclinical stage of the illness. By age 80–85 years, many nondemented older adults have substantial AD pathology. PMID:19376612

Chemical and neuropathological analyses of an Alzheimer’s disease patient treated with solanezumab

PubMed Central

Roher, Alex E; Maarouf, Chera L; Kokjohn, Tyler A; Belden, Christine; Serrano, Geidy; Sabbagh, Marwan S; Beach, Thomas G

2016-01-01

Introduction: Based on the amyloid cascade hypothesis of Alzheimer’s disease (AD) pathogenesis, a series of clinical trials involving immunotherapies have been undertaken including infusion with the IgG1 monoclonal anti-Aβ antibody solanezumab directed against the middle of the soluble Aβ peptide. In this report, we give an account of the clinical history, psychometric testing, gross and microscopic neuropathology as well as immunochemical quantitation of soluble and insoluble Aβ peptides and other proteins of interest related to AD pathophysiology in a patient treated with solanezumab. Materials and Methods: The solanezumab-treated AD case (SOLA-AD) was compared to non-demented control (NDC, n = 5) and non-immunized AD (NI-AD, n = 5) subjects. Brain sections were stained with H&E, Thioflavine-S, Campbell-Switzer and Gallyas methods. ELISA and Western blots were used for quantification of proteins of interest. Results: The SOLA-AD subject’s neuropathology and biochemistry differed sharply from the NDC and NI-AD groups. The SOLA-AD case had copious numbers of amyloid laden blood vessels in all areas of the cerebral cortex, from leptomeningeal perforating arteries to arteriolar deposits which attained the cerebral amyloid angiopathy (CAA) maximum score of 12. In contrast, the maximum CAA for the NI-AD cases averaged a total of 3.6, while the NDC cases only reached 0.75. The SOLA-AD subject had 4.4-fold more soluble Aβ40 and 5.6-fold more insoluble Aβ40 in the frontal lobe compared to NI-AD cases. In the temporal lobe of the SOLA-AD case, the soluble Aβ40 was 80-fold increased, and the insoluble Aβ40 was 13-fold more abundant compared to the non-immunized AD cases. Both soluble and insoluble Aβ42 levels were not dramatically different between the SOLA-AD and NI-AD cohort. Discussion: Solanezumab immunotherapy provided no apparent relief in the clinical evolution of dementia in this particular AD patient, since there was a continuous cognitive deterioration and full expression of amyloid deposition and neuropathology. PMID:27725918

A unique mitigator sequence determines the species specificity of the major late promoter in adenovirus type 12 DNA.

PubMed Central

Zock, C; Iselt, A; Doerfler, W

1993-01-01

Human adenovirus type 12 (Ad12) cannot replicate in hamster cells, whereas human cells are permissive for Ad12. Ad12 DNA replication and late-gene and virus-associated RNA expression are blocked in hamster cells. Early Ad12 genes are transcribed, and the viral DNA can be integrated into the host genome. Ad12 DNA replication and late-gene transcription can be complemented in hamster cells by E1 functions of Ad2 or Ad5, for which hamster cells are fully permissive (for a review, see W. Doerfler, Adv. Virus Res. 39:89-128, 1991). We have previously demonstrated that a 33-nucleotide mitigator sequence, which is located in the downstream region of the major late promoter (MLP) of Ad12 DNA, is responsible for the inactivity of the Ad12 MLP in hamster cells (C. Zock and W. Doerfler, EMBO J. 9:1615-1623, 1990). A similar negative regulator has not been found in the MLP of Ad2 DNA. We have now studied the mechanism of action of this mitigator element. The results of nuclear run-on experiments document the absence of MLP transcripts in the nuclei of Ad12-infected BHK21 hamster cells. Surprisingly, the mitigator element cannot elicit its function in in vitro transcription experiments with nuclear extracts from both hamster BHK21 and human HeLa cells. Intact nuclear topology and/or tightly bound nuclear elements that cannot be eluted in nuclear extracts are somehow required for recognition of the Ad12 mitigator. Electrophoretic mobility shift assays have not revealed significant differences in the binding of proteins from human HeLa or hamster BHK21 cells to the mitigator sequence in the MLP of Ad12 DNA or to the corresponding sequence in Ad2 DNA. We have converted the sequence of the mitigator in the MLP of Ad12 DNA to the equivalent sequence in the MLP of Ad2 DNA by site-directed mutagenesis. This construct was not active in hamster cells. When the Ad12 mitigator, on the other hand, was inserted into the Ad2 MLP, the latter's function in hamster cells was not compromised. Deletions in the 5' upstream region of the Ad12 MLP have provided evidence for the existence of additional sequences that codetermine the deficiency of the Ad12 MLP in hamster cells. The amphifunctional YY1 protein from HeLa cells can bind specifically to the mitigator and to upstream elements of the MLP of Ad12 DNA.(ABSTRACT TRUNCATED AT 400 WORDS) Images PMID:8419643

Multimodality Imaging of Gene Transfer with a Receptor-Based Reporter Gene

PubMed Central

Chen, Ron; Parry, Jesse J.; Akers, Walter J.; Berezin, Mikhail Y.; El Naqa, Issam M.; Achilefu, Samuel; Edwards, W. Barry; Rogers, Buck E.

2010-01-01

Gene therapy trials have traditionally used tumor and tissue biopsies for assessing the efficacy of gene transfer. Non-invasive imaging techniques offer a distinct advantage over tissue biopsies in that the magnitude and duration of gene transfer can be monitored repeatedly. Human somatostatin receptor subtype 2 (SSTR2) has been used for the nuclear imaging of gene transfer. To extend this concept, we have developed a somatostatin receptor–enhanced green fluorescent protein fusion construct (SSTR2-EGFP) for nuclear and fluorescent multimodality imaging. Methods An adenovirus containing SSTR2-EGFP (AdSSTR2-EGFP) was constructed and evaluated in vitro and in vivo. SCC-9 human squamous cell carcinoma cells were infected with AdEGFP, AdSSTR2, or AdSSTR2-EGFP for in vitro evaluation by saturation binding, internalization, and fluorescence spectroscopy assays. In vivo biodistribution and nano-SPECT imaging studies were conducted with mice bearing SCC-9 tumor xenografts directly injected with AdSSTR2-EGFP or AdSSTR2 to determine the tumor localization of 111In-diethylenetriaminepentaacetic acid (DTPA)-Tyr3-octreotate. Fluorescence imaging was conducted in vivo with mice receiving intratumoral injections of AdSSTR2, AdSSTR2-EGFP, or AdEGFP as well as ex vivo with tissues extracted from mice. Results The similarity between AdSSTR2-EGFP and wild-type AdSSTR2 was demonstrated in vitro by the saturation binding and internalization assays, and the fluorescence emission spectra of cells infected with AdSSTR2-EGFP was almost identical to the spectra of cells infected with wild-type AdEGFP. Biodistribution studies demonstrated that the tumor uptake of 111In-DTPA-Tyr3-octreotate was not significantly different (P > 0.05) when tumors (n = 5) were injected with AdSSTR2 or AdSSTR2-EGFP but was significantly greater than the uptake in control tumors. Fluorescence was observed in tumors injected with AdSSTR2-EGFP and AdEGFP in vivo and ex vivo but not in tumors injected with AdSSTR2. Although fluorescence was observed, there were discrepancies between in vivo imaging and ex vivo imaging as well as between nuclear imaging and fluorescent imaging. Conclusion These studies showed that the SSTR2-EGFP fusion construct can be used for in vivo nuclear and optical imaging of gene transfer. PMID:20720053

Using Google AdWords for International Multilingual Recruitment to Health Research Websites

PubMed Central

Gross, Margaret S; Liu, Nancy H; Contreras, Omar; Muñoz, Ricardo F

2014-01-01

Background Google AdWords, the placement of sponsored links in Google search results, is a potent method of recruitment to Internet-based health studies and interventions. However, the performance of Google AdWords varies considerably depending on the language and the location of the target audience. Objective Our goal was to describe differences in AdWords performance when recruiting participants to the same study conducted in four languages and to determine whether AdWords campaigns can be optimized in order to increase recruitment while decreasing costs. Methods Google AdWords were used to recruit participants to the Mood Screener, a multilingual online depression screening tool available in English, Russian, Spanish, and Chinese. Two distinct recruitment periods are described: (1) “Unmanaged”, a 6-month period in which ads were allowed to run using only the AdWords tool itself, with no human intervention, and (2) “Managed”, a separate 7-week period during which we systematically sought to optimize our recruitment campaigns. Results During 6 months of unmanaged recruitment, our ads were shown over 1.3 million times, resulting in over 60,000 site visits. The average click-through rate (ratio of ads clicked to ads displayed) varied from 1.86% for Chinese ads to 8.48% for Russian ads, as did the average cost-per-click (from US $0.20 for Chinese ads to US $0.50 for English ads). Although Chinese speakers’ click-through rate was lowest, their rate of consenting to participate was the highest, at 3.62%, with English speakers exhibiting the lowest consent rate (0.97%). The conversion cost (cost to recruit a consenting participant) varied from US $10.80 for Russian speakers to US $51.88 for English speakers. During the 7 weeks of “managed” recruitment, we attempted to improve AdWords’ performance in regards to the consent rate and cost by systematically deleting underperforming ads and adjusting keywords. We were able to increase the number of people who consent after coming to the site by 91.8% while also decreasing per-consent cost by 23.3%. Conclusions Our results illustrate the need to linguistically and culturally adapt Google AdWords campaigns and to manage them carefully to ensure the most cost-effective results. PMID:24446166

Effect of AHA dietary counselling on added sugar intake among participants with metabolic syndrome.

PubMed

Zhang, Lijuan; Pagoto, Sherry; May, Christine; Olendzki, Barbara; L Tucker, Katherine; Ruiz, Carolina; Cao, Yu; Ma, Yunsheng

2018-04-01

High added sugar consumption has been associated with the development of metabolic syndrome (MetS). The American Heart Association (AHA) diet is designed to prevent and treat MetS; however, it remains unclear whether the AHA diet is effective on decreasing added sugar consumption. The aim of our study was to evaluate the effect of the AHA dietary counselling on added sugar consumption among participants with MetS. The AHA dietary counselling was conducted among 119 participants with MetS from June 2009 to January 2014 (ClinicalTrials.gov: NCT00911885). Unannounced 24-hour recalls were collected at baseline, 3, 6 and 12 months. Added sugar consumption patterns over time were examined using linear mixed models. After 1-year dietary counselling, intake of added sugars decreased by 23.8 g/day (95% CI 15.1, 32.4 g/day); intake of nonalcoholic beverages dropped from the leading contributor of added sugar intake to number 7 (from 11.9 to 4.4%); the Alternative Healthy Eating Index (AHEI) score increased by 5.4 (95% CI 2.9, 8.0); however, added sugar intake for 48% participants still exceeded the recommendation. Added sugar intake per meal among different meal type was similar (24.2-25.8%) at baseline. After the 1-year dietary counselling, breakfast became the major resource of added sugar intake (33.3%); the proportion of added sugar intake from snacks decreased from 25.8% (CI 23.1, 28.5%) to 20.9% (CI 19.6, 22.3%). Although the consumption of added sugars in participants with MetS decreased after the 1-year AHA dietary counselling, added sugar intake from majority of participants still exceeds recommended limits. Actions of successful public health strategies that focus on reducing added sugar intake are needed.

2009 Alzheimer's disease facts and figures.

PubMed

2009-05-01

Alzheimer's disease (AD) is the sixth leading cause of all deaths in the United States, and the fifth leading cause of death in Americans aged 65 and older. Whereas other major causes of death have been on the decrease, deaths attributable to AD have been rising dramatically. Between 2000 and 2006, heart-disease deaths decreased nearly 12%, stroke deaths decreased 18%, and prostate cancer-related deaths decreased 14%, whereas deaths attributable to AD increased 47%. An estimated 5.3 million Americans have AD; the approximately 200,000 persons under age 65 years with AD comprise the younger-onset AD population. Every 70 seconds, someone in America develops AD; by 2050, this time is expected to decrease to every 33 seconds. Over the coming decades, the "baby-boom" population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million people. Significant cost implications related to AD and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (e.g., decreased business productivity) costs. Not included in these figures is the $94 billion in unpaid services to individuals with AD provided annually by an estimated 10 million caregivers. Mild cognitive impairment (MCI) is an important component in the continuum from healthy cognition to dementia. Understanding which individuals with MCI are at highest risk for eventually developing AD is key to our ultimate goal of preventing AD. This report provides information meant to increase an understanding of the public-health impact of AD, including incidence and prevalence, mortality, lifetime risks, costs, and impact on family caregivers. This report also sets the stage for a better understanding of the relationship between MCI and AD.

Melanopsin retinal ganglion cell loss in Alzheimer disease

PubMed Central

Ross‐Cisneros, Fred N.; Koronyo, Yosef; Hannibal, Jens; Gallassi, Roberto; Cantalupo, Gaetano; Sambati, Luisa; Pan, Billy X.; Tozer, Kevin R.; Barboni, Piero; Provini, Federica; Avanzini, Pietro; Carbonelli, Michele; Pelosi, Annalisa; Chui, Helena; Liguori, Rocco; Baruzzi, Agostino; Koronyo‐Hamaoui, Maya; Sadun, Alfredo A.; Carelli, Valerio

2015-01-01

Objective Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction. Methods We assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls. Results We demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs. Interpretation We show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109 PMID:26505992

Adenovirus Vector Pseudotyping in Fiber-Expressing Cell Lines: Improved Transduction of Epstein-Barr Virus-Transformed B Cells

PubMed Central

Von Seggern, Dan J.; Huang, Shuang; Fleck, Shonna Kaye; Stevenson, Susan C.; Nemerow, Glen R.

2000-01-01

While adenovirus (Ad) gene delivery vectors are useful in many gene therapy applications, their broad tropism means that they cannot be directed to a specific target cell. There are also a number of cell types involved in human disease which are not transducible with standard Ad vectors, such as Epstein-Barr virus (EBV)-transformed B lymphocytes. Adenovirus binds to host cells via the viral fiber protein, and Ad vectors have previously been retargeted by modifying the fiber gene on the viral chromosome. This requires that the modified fiber be able to bind to the cell in which the vector is grown, which prevents truly specific vector targeting. We previously reported a gene delivery system based on a fiber gene-deleted Ad type 5 (Ad5) vector (Ad5.βgal.ΔF) and packaging cells that express the viral fiber protein. Expression of different fibers in packaging cells will allow Ad retargeting without modifying the viral chromosome. Importantly, fiber proteins which can no longer bind to the producer cells can also be used. Using this approach, we generated for the first time pseudotyped Ad5.βgal.ΔF particles containing either the wild-type Ad5 fiber protein or a chimeric fiber with the receptor-binding knob domain of the Ad3 fiber. Particles equipped with the chimeric fiber bound to the Ad3 receptor rather than the coxsackievirus-adenovirus receptor protein used by Ad5. EBV-transformed B lymphocytes were infected efficiently by the Ad3-pseudotyped particles but poorly by virus containing the Ad5 fiber protein. The strategy described here represents a broadly applicable method for targeting gene delivery to specific cell types. PMID:10590124

Gender effects in alcohol dependence: an fMRI pilot study examining affective processing.

PubMed

Padula, Claudia B; Anthenelli, Robert M; Eliassen, James C; Nelson, Erik; Lisdahl, Krista M

2015-02-01

Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Fearful Condition-The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition-AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing. Copyright © 2015 by the Research Society on Alcoholism.

The Frequency of Unhealthy Food Advertising on Mainland Chinese Television (TV) and Children and Adolescents' Risk of Exposure to Them.

PubMed

Zhou, Zhenghua; Diao, Qinqin; Shao, Nan; Liang, Youke; Lin, Li; Lei, Yan; Zheng, Lingmei

2015-01-01

To conduct an analysis of the frequency of unhealthy food advertising on mainland Chinese television (TV) and children and adolescents' risk of exposure to them. The frequencies of all types of advertisements (ads) on forty TV channels in mainland China, the exact ad broadcast times, and the name and brand of all snacks and western fast foods advertised were recorded from 0800 hours to 2400 hours on both a weekday and a weekend day in a week. The difference in the frequencies of the diverse types of ads over eight time intervals (each time interval was 2 hours) were compared, and the trends in ad frequencies during the time intervals were described. The TV channels broadcast 155 (91-183) (expressed as median [P25-P75]) food ads, 87 (38-123) snack ads, 49 (11-85) beverage ads, and 58 (25-76) ads of snacks suitable for limited consumption (SSLCs) in a day. The proportion of snack ads among food ads (SPF%) was 55.5% (40.3%-71.0%), and the proportion of SSLC ads among snack ads (LPS%) was 67.4% (55.4%-79.3%). The ad frequencies for food, snacks, SSLCs, and beverages demonstrated significant differences among the eight time intervals (all P=0.000). TV channels broadcast the most frequent ads for food, snacks, SSLCs, and beverages during the time interval from 2000 hours to 2200 hours among the eight time intervals. Chinese children and adolescents may be at a high risk of exposure to unhealthy food advertising on TV. Reducing the exposure risk strongly requires multisectoral cooperation.

Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease.

PubMed

Cho, Jinkyung; Shin, Min-Kyoo; Kim, Donghyun; Lee, Inhwan; Kim, Shinuk; Kang, Hyunsik

2015-09-01

This study investigated the effect of treadmill running on cognitive declines in the early and advanced stages of Alzheimer disease (AD) in 3xTg-AD mice. At 4 months of age, 3xTg-AD mice (N = 24) were assigned to control (AD + CON, n = 12) or exercise (AD + EX, n = 12) group. At 24 months of age, 3xTg-AD mice (N = 16) were assigned to AD + CON (n = 8) or AD + EX (n = 8) group. The AD + EX mice were subjected to treadmill running for 12 wk. At each pathological stage, the background strain mice were included as wild-type control (WT + CON, n = 8-12). At the early stage of AD, 3xTg-AD mice had impaired short- and long-term memory based on Morris water maze along with higher cortical Aβ deposition, higher hippocampal and cortical tau pathology, and lower hippocampal and cortical PSD-95 and synaptophysin. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the tau pathology along with suppression of the decreased PSD-95 and synaptophysin in the hippocampus and cortex. At the advanced stage of AD, 3xTg-AD mice had impaired short- and long-term memory along with higher levels of Aβ deposition, soluble Aβ1-40 and Aβ1-42, tau pathology, and lower levels of brain-derived neurotrophic factor, PSD-95, and synaptophysin in the hippocampus and cortex. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the Aβ and tau pathology along with suppression of the decreased synaptic proteins and brain-derived neurotrophic factor in the hippocampus and cortex. The current findings suggest that treadmill running provides a nonpharmacological means to combat cognitive declines due to AD pathology.

Gender Effects in Alcohol Dependence: An fMRI Pilot Study Examining Affective Processing

PubMed Central

Padula, Claudia B.; Anthenelli, Robert M.; Eliassen, James C.; Nelson, Erik; Lisdahl, Krista M.

2017-01-01

Background Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Methods Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Results Fearful Condition—The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition—AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Conclusions Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing. PMID:25684049

The Frequency of Unhealthy Food Advertising on Mainland Chinese Television (TV) and Children and Adolescents’ Risk of Exposure to Them

PubMed Central

Zhou, Zhenghua; Diao, Qinqin; Shao, Nan; Liang, Youke; Lin, Li; Lei, Yan; Zheng, Lingmei

2015-01-01

Objective To conduct an analysis of the frequency of unhealthy food advertising on mainland Chinese television (TV) and children and adolescents’ risk of exposure to them. Methods The frequencies of all types of advertisements (ads) on forty TV channels in mainland China, the exact ad broadcast times, and the name and brand of all snacks and western fast foods advertised were recorded from 0800 hours to 2400 hours on both a weekday and a weekend day in a week. The difference in the frequencies of the diverse types of ads over eight time intervals (each time interval was 2 hours) were compared, and the trends in ad frequencies during the time intervals were described. Results The TV channels broadcast 155 (91-183) (expressed as median [P 25-P 75]) food ads, 87 (38-123) snack ads, 49 (11-85) beverage ads, and 58 (25-76) ads of snacks suitable for limited consumption (SSLCs) in a day. The proportion of snack ads among food ads (SPF%) was 55.5% (40.3%-71.0%), and the proportion of SSLC ads among snack ads (LPS%) was 67.4% (55.4%-79.3%). The ad frequencies for food, snacks, SSLCs, and beverages demonstrated significant differences among the eight time intervals (all P=0.000). TV channels broadcast the most frequent ads for food, snacks, SSLCs, and beverages during the time interval from 2000 hours to 2200 hours among the eight time intervals. Conclusions Chinese children and adolescents may be at a high risk of exposure to unhealthy food advertising on TV. Reducing the exposure risk strongly requires multisectoral cooperation. PMID:26133984

Sex and the development of Alzheimer’s disease

PubMed Central

Pike, Christian J.

2016-01-01

Men and women exhibit differences in the development and progression of Alzheimer’s disease (AD). The factors underlying the sex differences in AD are not well understood. This review emphasizes the contributions of sex steroid hormones to the relationship between sex and AD. In women, events that decrease lifetime exposure to estrogens are generally associated with increased AD risk, whereas estrogen-based hormone therapy administered near the time of menopause may reduce AD risk. In men, estrogens do not exhibit age-related reduction and are not significantly associated with AD risk. Rather, normal age-related depletions of testosterone in plasma and brain predict enhanced vulnerability to AD. Both estrogens and androgens exert numerous protective actions in the adult brain that increase neural functioning and resilience as well as specifically attenuate multiple aspects of AD-related neuropathology. Aging diminishes the activational effects of sex hormones in sex-specific manners, which is hypothesized to contribute to the relationship between aging and AD. Sex steroid hormones may also drive sex differences in AD through their organizational effects during developmental sexual differentiation of the brain. Specifically, sex hormone actions during early development may confer inherent vulnerability of the female brain to development of AD in advanced age. The combined effects of organizational and activational effects of sex steroids yield distinct sex differences in AD pathogenesis, a significant variable that must be more rigorously considered in future research. PMID:27870425

Motivations, aims and communication around advance directives: a mixed-methods study into the perspective of their owners and the influence of a current illness.

PubMed

van Wijmen, Matthijs P S; Pasman, H Roeline W; Widdershoven, Guy A M; Onwuteaka-Philipsen, Bregje D

2014-06-01

What are motivations of owners of an advance directive (AD) to draft an AD, what do they aim for with their AD and do they communicate about their AD? Written questionnaires were sent to a cohort of people owning different types of ADs (n=5768). A purposive sample of people suffering from an illness was selected from the cohort for an in-depth interview (n=29). About half of our population had no direct motivation to draft their AD. Most mentioned motivation for the other half was an illness of a family member or friend. Many different and specific aims for drafting an AD were mentioned. An often mentioned more general aim in people with different ADs was to prevent unnecessary lengthening of life or treatment (14-16%). Most respondents communicated about having an AD with close-ones (63-88%) and with their GP (65-79%). In the interviews people gave vivid examples of experiences of what they hoped to prevent at the end of life. Some mentioned difficulties foreseeing the future and gave examples of response shift. ADs can give directions to caregivers about what people want at the end of life. ADs have to be discussed in detail by their owners and caregivers, since owners often have specific aims with their AD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 109.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Added poisonous or deleterious substances. 109.6...-PACKAGING MATERIAL General Provisions § 109.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 109.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Added poisonous or deleterious substances. 109.6...-PACKAGING MATERIAL General Provisions § 109.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 509.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Added poisonous or deleterious substances. 509.6...-PACKAGING MATERIAL General Provisions § 509.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

21 CFR 109.6 - Added poisonous or deleterious substances.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Added poisonous or deleterious substances. 109.6...-PACKAGING MATERIAL General Provisions § 109.6 Added poisonous or deleterious substances. (a) Use of an added... approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance...

Multi-Skyrmions on AdS2 × S2, rational maps and popcorn transitions

NASA Astrophysics Data System (ADS)

Canfora, Fabrizio; Tallarita, Gianni

2017-08-01

By combining two different techniques to construct multi-soliton solutions of the (3 + 1)-dimensional Skyrme model, the generalized hedgehog and the rational map ansatz, we find multi-Skyrmion configurations in AdS2 ×S2. We construct Skyrmionic multi-layered configurations such that the total Baryon charge is the product of the number of kinks along the radial AdS2 direction and the degree of the rational map. We show that, for fixed total Baryon charge, as one increases the charge density on ∂ (AdS2 ×S2) , it becomes increasingly convenient energetically to have configurations with more peaks in the radial AdS2 direction but a lower degree of the rational map. This has a direct relation with the so-called holographic popcorn transitions in which, when the charge density is high, multi-layered configurations with low charge on each layer are favored over configurations with few layers but with higher charge on each layer. The case in which the geometry is M2 ×S2 can also be analyzed.

Topological terms, AdS2 n gravity, and renormalized entanglement entropy of holographic CFTs

NASA Astrophysics Data System (ADS)

Anastasiou, Giorgos; Araya, Ignacio J.; Olea, Rodrigo

2018-05-01

We extend our topological renormalization scheme for entanglement entropy to holographic CFTs of arbitrary odd dimensions in the context of the AdS /CFT correspondence. The procedure consists in adding the Chern form as a boundary term to the area functional of the Ryu-Takayanagi minimal surface. The renormalized entanglement entropy thus obtained can be rewritten in terms of the Euler characteristic and the AdS curvature of the minimal surface. This prescription considers the use of the replica trick to express the renormalized entanglement entropy in terms of the renormalized gravitational action evaluated on the conically singular replica manifold extended to the bulk. This renormalized action is obtained in turn by adding the Chern form as the counterterm at the boundary of the 2 n -dimensional asymptotically AdS bulk manifold. We explicitly show that, up to next-to-leading order in the holographic radial coordinate, the addition of this boundary term cancels the divergent part of the entanglement entropy. We discuss possible applications of the method for studying CFT parameters like central charges.

[Establishment of novel biomarkers for Personalized medication for atopic dermatitis].

PubMed

Ohta, Shoichiro; Taniguchi, Kazuto; Arima, Kazuhiko; Suzuki, Shoichi; Shiraishi, Hiroshi; Masuoka, Miho; Izuhara, Kenji

2013-03-01

To diagnose atopic dermatitis (AD), an appearance of eczema examined by experienced dermatologists is required. Therefore, biomarkers to diagnose AD or to reflect the severity of AD would be of a great use for non-specialists in the clinic or hospitals. We can apply such a biomarker for realization of personalized medicine for AD in the future. Interleukin-4 (IL-4) and IL-13 have been known to play important roles in the pathogenesis of allergic diseases including AD. In addition to these, we previously identified SCCA1, SCCA2, and periostin as IL-4/IL-13-inducible genes. We recently established ELISA systems to measure serum levels of SCCA1, SCCA2, and periostin and evaluated their usefulness in the treatment of AD patients. Serum SCCA1 and SCCA2 are up-regulated in AD patients and can distinguish AD patients from non-atopic controls, and their serum levels reflect eczema grades. Periostin concentration is also elevated in the serum of AD patients. These results demonstrate that SCCA1, SCCA2, and periostin might be promising biomarkers for personalized medicine in allergic diseases including AD.

The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3.

PubMed

Sirena, Dominique; Ruzsics, Zsolt; Schaffner, Walter; Greber, Urs F; Hemmi, Silvio

2005-12-20

Human adenovirus (Ad) serotype 3 causes respiratory infections. It is considered highly virulent, accounting for about 13% of all Ad isolates. We report here the complete Ad3 DNA sequence of 35,343 base pairs (GenBank accession DQ086466). Ad3 shares 96.43% nucleotide identity with Ad7, another virulent subspecies B1 serotype, and 82.56 and 62.75% identity with the less virulent species B2 Ad11 and species C Ad5, respectively. The genomic organization of Ad3 is similar to the other human Ads comprising five early transcription units, E1A, E1B, E2, E3, and E4, two delayed early units IX and IVa2, and the major late unit, in total 39 putative and 7 hypothetical open reading frames. A recombinant E1-deleted Ad3 was generated on a bacterial artificial chromosome. This prototypic virus efficiently transduced CD46-positive rodent and human cells. Our results will help in clarifying the biology and pathology of adenoviruses and enhance therapeutic applications of viral vectors in clinical settings.

Hairy black holes and the endpoint of AdS4 charged superradiance

NASA Astrophysics Data System (ADS)

Dias, Óscar J. C.; Masachs, Ramon

2017-02-01

We construct hairy black hole solutions that merge with the anti-de Sitter (AdS4) Reissner-Nordström black hole at the onset of superradiance. These hairy black holes have, for a given mass and charge, higher entropy than the corresponding AdS4-Reissner-Nordström black hole. Therefore, they are natural candidates for the endpoint of the charged superradiant instability. On the other hand, hairy black holes never dominate the canonical and grand-canonical ensembles. The zero-horizon radius of the hairy black holes is a soliton (i.e. a boson star under a gauge transformation). We construct our solutions perturbatively, for small mass and charge, so that the properties of hairy black holes can be used to testify and compare with the endpoint of initial value simulations. We further discuss the near-horizon scalar condensation instability which is also present in global AdS4-Reissner-Nordström black holes. We highlight the different nature of the near-horizon and superradiant instabilities and that hairy black holes ultimately exist because of the non-linear instability of AdS.

Geometry and supersymmetry of heterotic warped flux AdS backgrounds

NASA Astrophysics Data System (ADS)

Beck, S.; Gutowski, J.; Papadopoulos, G.

2015-07-01

We classify the geometries of the most general warped, flux AdS backgrounds of heterotic supergravity up to two loop order in sigma model perturbation theory. We show under some mild assumptions that there are no AdS n backgrounds with n ≠ 3. Moreover the warp factor of AdS3 backgrounds is constant, the geometry is a product AdS 3 × M 7 and such solutions preserve, 2, 4, 6 and 8 supersymmetries. The geometry of M 7 has been specified in all cases. For 2 supersymmetries, it has been found that M 7 admits a suitably restricted G 2 structure. For 4 supersymmetries, M 7 has an SU(3) structure and can be described locally as a circle fibration over a 6-dimensional KT manifold. For 6 and 8 supersymmetries, M 7 has an SU(2) structure and can be described locally as a S 3 fibration over a 4-dimensional manifold which either has an anti-self dual Weyl tensor or a hyper-Kähler structure, respectively. We also demonstrate a new Lichnerowicz type theorem in the presence of α' corrections.

Cellular, synaptic and biochemical features of resilient cognition in Alzheimer’s disease

PubMed Central

Arnold, Steven. E.; Louneva, Natalia; Cao, Kajia; Wang, Li-San; Han, Li-Ying; Wolk, David A.; Negash, Selamawit; Leurgans, Sue E.; Schneider, Julie A.; Buchman, Aron S.; Wilson, Robert S.; Bennett, David A.

2012-01-01

While neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect as some people exhibit normal cognition despite high levels of AD pathology. We compared the cellular, synaptic and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: 1) pathological AD with normal cognition (“AD-Resilient”), 2) pathological AD with AD-typical dementia (“AD-Dementia)” and 3) pathologically normal with normal cognition (“Normal Comparison”). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared to the AD-Dementia group, and increased densities of GFAP astrocytes compared to both the AD-Dementia and Normal Comparison group. Further, in a discovery antibody microarray protein analysis we identified a number of candidate protein abnormalities that were associated with diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD. PMID:22554416

String in AdS black hole: A thermo field dynamic approach

NASA Astrophysics Data System (ADS)

Cantcheff, M. Botta; Gadelha, Alexandre L.; Marchioro, Dáfni F. Z.; Nedel, Daniel Luiz

2012-10-01

Based on Maldacena’s description of an eternal anti-de Sitter (AdS) black hole, we reassess the thermo field dynamics (TFD) formalism in the context of the AdS/CFT correspondence. The model studied here involves the maximally extended AdS-Schwarschild solution and two (noninteracting) copies of the conformal field theory (CFT) associated to the global AdS spacetime, along with an extension of the string by imposing natural gluing conditions in the horizon. We show that the gluing conditions in the horizon define a string boundary state which is identified with the TFD thermal vacuum, globally defined in the Kruskal extension of the AdS black hole. We emphasize the connection of this picture with unitary SU(1,1) TFD formulation, and we show that information about the bulk and the conformal boundary is present in the SU(1,1) parameters. Using the unitary SU(1,1) TFD formulation, a canonical prescription for calculating the world sheet real time thermal Green’s function is made, and the entropy associated with the entanglement of the two CFT’s is calculated.

Genetic dissection of Alzheimer disease, a heterogeneous disorder.

PubMed

Schellenberg, G D

1995-09-12

The genetics of Alzheimer disease (AD) are complex and not completely understood. Mutations in the amyloid precursor protein gene (APP) can cause early-onset autosomal dominant AD. In vitro studies indicate that cells expressing mutant APPs overproduce pathogenic forms of the A beta peptide, the major component of AD amyloid. However, mutations in the APP gene are responsible for 5% or less of all early-onset familial AD. A locus on chromosome 14 is responsible for AD in other early-onset AD families and represents the most severe form of the disease in terms of age of onset and rate of decline. Attempts to identify the AD3 gene by positional cloning methods are underway. At least one additional early-onset AD locus remains to be located. In late-onset AD, the apolipoprotein E gene allele epsilon 4 is a risk factor for AD. This allele appears to act as a dose-dependent age-of-onset modifier. The epsilon 2 allele of this gene may be protective. Other late-onset susceptibility factors remain to be identified.

Cholesterol as a Causative Factor in Alzheimer Disease: A Debatable Hypothesis

PubMed Central

Wood, W. Gibson; Li, Ling; Müller, Walter E.; Eckert, Gunter P.

2014-01-01

High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD. Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only APP and Aβ. The purpose of this review, therefore, is to examine the above-mentioned issues and discuss the pros and cons of the cholesterol-AD hypothesis, and the involvement of other lipids in the mevalonate pathway, such as isoprenoids and oxysterols, in AD. PMID:24329875

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens1

PubMed Central

Tatsis, Nia; Lasaro, Marcio O.; Lin, Shih-Wen; Xiang, Zhi Q.; Zhou, Dongming; DiMenna, Lauren; Li, Hua; Bian, Ang; Abdulla, Sarah; Li, Yan; Giles-Davis, Wynetta; Engram, Jessica; Ratcliffe, Sarah J.; Silvestri, Guido; Ertl, Hildegund C.; Betts, Michael R.

2009-01-01

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with pre-existing neutralizing antibodies against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee derived Ad (AdC) vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the AdC vectors induced higher T and B cell responses than repeated immunizations with the AdHu5 vector especially in AdHu5-pre-exposed macaques. PMID:19414814

Clinical Features of Alzheimer Disease With and Without Lewy Bodies.

PubMed

Chung, Eun Joo; Babulal, Ganesh M; Monsell, Sarah E; Cairns, Nigel J; Roe, Catherine M; Morris, John C

2015-07-01

Lewy bodies are a frequent coexisting pathology in late-onset Alzheimer disease (AD). Previous studies have examined the contribution of Lewy bodies to the clinical phenotype of late-onset AD with variable findings. To determine whether the presence of Lewy body pathology influences the clinical phenotype and progression of symptoms in longitudinally assessed participants with AD. Retrospective clinical and pathological cohort study of 531 deceased participants who met the neuropathologic criteria for intermediate or high likelihood of AD according to the National Institute on Aging-Ronald Reagan Institute guidelines for the neuropathologic diagnosis of AD. All participants had a clinical assessment within 2 years of death. The data were obtained from 34 AD centers maintained by the National Alzheimer Coordinating Center and spanned from September 12, 2005, to April 30, 2013. Standardized neuropathologic assessment and then brain autopsy after death. Clinical and neuropsychiatric test scores. The mean (SD) age at death was statistically significantly younger for participants who had AD with Lewy bodies (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2 [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More men than women had AD with Lewy bodies (P = .01). The frequency of having at least 1 APOE ε4 allele was higher for participants who had AD with Lewy bodies than for participants who had AD without Lewy bodies (P = .03). After adjusting for age, sex, education, frequency of plaques (neuritic and diffuse), and tangle stage, we found that participants who had AD with Lewy bodies had a statistically significantly higher mean (SD) Neuropsychiatric Inventory Questionnaire score (6.59 [1.44] [95% CI, 3.75-9.42] vs 5.49 [1.39] [95% CI, 2.76-8.23]; P = .04) and a statistically significantly higher mean (SD) Unified Parkinson Disease Rating Scale motor score (0.81 [0.18] [95% CI, 0.45-1.17] vs 0.54 [0.18] [95% CI, 0.19-0.88]; P < .001) than did participants who had AD without Lewy bodies. Participants with both AD and Lewy body pathology have a clinical phenotype that may be distinguished from AD alone. The frequency of Lewy bodies in AD and the association of Lewy bodies with the APOE ε4 allele suggest potential common mechanisms for AD and Lewy body pathologies.

Brain aging, Alzheimer's disease, and mitochondria

PubMed Central

Swerdlow, Russell H.

2011-01-01

The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

Tensionless string spectra on AdS3

NASA Astrophysics Data System (ADS)

Gaberdiel, Matthias R.; Gopakumar, Rajesh

2018-05-01

The spectrum of superstrings on AdS3 × S3 × M 4 with pure NS-NS flux is analysed for the background where the radius of the AdS space takes the minimal value ( k = 1). Both for M 4 = S3 × S1 and M 4 = T 4 we show that there is a special set of physical states, coming from the bottom of the spectrally flowed continuous representations, which agree in precise detail with the single particle spectrum of a free symmetric product orbifold. For the case of AdS3 × S3 × T 4 this relies on making sense of the world-sheet theory at k = 1, for which we make a concrete proposal. We also comment on the implications of this striking result.

Features of alcohol harm reduction advertisements that most motivate reduced drinking among adults: an advertisement response study

PubMed Central

Wakefield, Melanie A; Dunstone, Kimberley; Durkin, Sarah J; Dixon, Helen G; Pettigrew, Simone; Slater, Michael D

2017-01-01

Objectives To improve the effectiveness of alcohol harm reduction mass media campaigns, this study aimed to (1) identify existing advertisements (ads) with greatest potential to motivate reduced alcohol consumption, (2) assess consistency across audience subgroups in ad effectiveness and (3) identify ad features associated with effectiveness. Design Cross-sectional online ad response study with random assignment to view ads. Participants 2174 Australian adult weekly drinkers recruited from an online panel. Procedure Participants were randomly assigned to view three of 83 English-language alcohol harm reduction ads. Each ad was viewed and rated by a mean of 79 participants. Outcome measure After viewing each ad, participants reported the extent to which they felt motivated to reduce their drinking. Ads were ranked from most to least motivating using predicted means adjusted for demographic characteristics and alcohol consumption. We compared the characteristics of the top-ranked 15% of ads (most motivating) with the middle 70% and bottom 15%. Results An ad about the link between alcohol and cancer (‘Spread’) was most motivating, whereas an ad that encouraged drinking water instead of beer (‘Add nothing’) was least motivating. Top-ranked ads were more likely than other ads to feature a ‘why change’ message and less likely to carry a ‘how to change’ message; more likely to address long-term harms; more likely to be aimed at the general adult drinking population and more likely to include drinking guidelines. There was substantial overlap in top-ranked ads for younger versus older adults, men versus women and high-risk versus low-risk drinker subgroups. Conclusions The effectiveness of alcohol harm reduction campaigns may be improved by directly communicating alcohol's long-term harms to the general adult population of drinkers along with drinking guidelines. By doing so, campaigns can also efficiently influence high-risk drinkers and key demographic subgroups. PMID:28428186

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

PubMed Central

2010-01-01

Background Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials. PMID:20433705

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

PubMed

Furiak, Nicolas M; Klein, Robert W; Kahle-Wrobleski, Kristin; Siemers, Eric R; Sarpong, Eric; Klein, Timothy M

2010-04-30

Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

Potential effectiveness of anti-smoking advertisement types in ten low and middle income countries: do demographics, smoking characteristics and cultural differences matter?

PubMed

Durkin, Sarah; Bayly, Megan; Cotter, Trish; Mullin, Sandra; Wakefield, Melanie

2013-12-01

Unlike high income countries, there is limited research to guide selection of anti-tobacco mass media campaigns in low and middle income countries, although some work suggests that messages emphasizing serious health harms perform better than other message types. This study aimed to determine whether certain types of anti-smoking advertisements are more likely to be accepted and perceived as effective across smokers in 10 low to middle income countries. 2399 18-34 year old smokers were recruited in Bangladesh, China, Egypt, India, Indonesia, Mexico, Philippines, Russia, Turkey and Vietnam to view and rate 10 anti-tobacco ads. Five ads were shown in all countries and five ads were chosen by country representatives, providing a total of 37 anti-smoking ads across all countries (10 graphic health effects ads, 6 simulated health effects, 8 emotional stories of health effects, 7 other health effects and 6 non-health effects). Smokers rated ads on a series of 5-point scales containing aggregated measures of Message Acceptance and Perceived Effectiveness. All ads and materials were translated into the local language of the testing regions. In multivariate analysis, graphic health effects ads were most likely to be accepted and perceived as effective, followed by simulated health effects ads, health effects stories, other health effects ads, and then non-health effects ads. Interaction analyses indicated that graphic health effects ads were less likely to differ in acceptance or perceived effectiveness across countries, gender, age, education, parental status and amount smoked, and were less likely to be affected by cultural differences between characters and contexts in ads and those within each country. Ads that did not emphasize the health effects of smoking were most prone to inconsistent impact across countries and population subgroups. Graphic ads about the negative health effects of smoking may be most suitable for wide population broadcast in low and middle income countries. Copyright © 2013 Elsevier Ltd. All rights reserved.

Features of alcohol harm reduction advertisements that most motivate reduced drinking among adults: an advertisement response study.

PubMed

Wakefield, Melanie A; Brennan, Emily; Dunstone, Kimberley; Durkin, Sarah J; Dixon, Helen G; Pettigrew, Simone; Slater, Michael D

2017-04-20

To improve the effectiveness of alcohol harm reduction mass media campaigns, this study aimed to (1) identify existing advertisements (ads) with greatest potential to motivate reduced alcohol consumption, (2) assess consistency across audience subgroups in ad effectiveness and (3) identify ad features associated with effectiveness. Cross-sectional online ad response study with random assignment to view ads. 2174 Australian adult weekly drinkers recruited from an online panel. Participants were randomly assigned to view three of 83 English-language alcohol harm reduction ads. Each ad was viewed and rated by a mean of 79 participants. After viewing each ad, participants reported the extent to which they felt motivated to reduce their drinking. Ads were ranked from most to least motivating using predicted means adjusted for demographic characteristics and alcohol consumption. We compared the characteristics of the top-ranked 15% of ads (most motivating) with the middle 70% and bottom 15%. An ad about the link between alcohol and cancer (' Spread ') was most motivating, whereas an ad that encouraged drinking water instead of beer (' Add nothing ') was least motivating. Top-ranked ads were more likely than other ads to feature a 'why change' message and less likely to carry a 'how to change' message; more likely to address long-term harms; more likely to be aimed at the general adult drinking population and more likely to include drinking guidelines. There was substantial overlap in top-ranked ads for younger versus older adults, men versus women and high-risk versus low-risk drinker subgroups. The effectiveness of alcohol harm reduction campaigns may be improved by directly communicating alcohol's long-term harms to the general adult population of drinkers along with drinking guidelines. By doing so, campaigns can also efficiently influence high-risk drinkers and key demographic subgroups. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Yuhua; Zhang, Bo; Hou, Weihong

Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstratedmore » cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca{sup 2+}]{sub i} signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. - Highlights: •Excessive production of structural proteins is common to viral infection, which may regulate the host-virus equilibrium and the spreading of viruses. •The adenovirus (Ad) structural proteins, fiber and penton base, are respectively important for Ad binding to its receptor and subsequent internalization in host cells. In Ad infected cells, these two structural proteins are excessively produced. •The mechanisms underlying the release of fiber and penton base molecules at the early phase of Ad infection is yet poorly understood. •Our studies show that in Ad5 or Ad2 infected A549 cells, fiber and penton base molecules are actively and separately secreted. •Fiber secretion is dependent on cytoskeleton-mediated protein traffic. •Inhibition of myosin II motor and Ca{sup 2+} signaling activity significantly diminishes fiber secretion. •These findings could contribute to our understanding of Ad spread in human populations.« less

The Tetrahedral Zamolodchikov Algebra and the {AdS_5× S^5} S-matrix

NASA Astrophysics Data System (ADS)

Mitev, Vladimir; Staudacher, Matthias; Tsuboi, Zengo

2017-08-01

The S-matrix of the {AdS_5× S^5} string theory is a tensor product of two centrally extended su{(2|2)\\ltimes R^2 S-matrices, each of which is related to the R-matrix of the Hubbard model. The R-matrix of the Hubbard model was first found by Shastry, who ingeniously exploited the fact that, for zero coupling, the Hubbard model can be decomposed into two XX models. In this article, we review and clarify this construction from the AdS/CFT perspective and investigate the implications this has for the {AdS_5× S^5} S-matrix.

Consumer perceptions of prescription and over-the-counter drug advertisements with promotional offers.

PubMed

Aikin, Kathryn J; Sullivan, Helen W; O'Donoghue, Amie C; Betts, Kevin R

2016-01-01

Information on the effects of promotional offers in direct-to-consumer prescription drug ads is limited. In two studies, we examined the effect of promotional offers (e.g., money-back guarantee) and ad type (creating prescription and over-the-counter drug ads by varying the presence of benefit and risk information). We found little effect of promotional offers. Adding benefit (risk) information to the ad increased consumers' knowledge of the benefit (risk) information and their efficacy (risk) perceptions. In most cases, adding risk information to an ad with benefit information increased risk knowledge and perceptions without decreasing benefit knowledge or perceptions.

Introducing auto-disable syringes to the national immunization programme in Madagascar.

PubMed Central

Drain, Paul K.; Ralaivao, Josoa S.; Rakotonandrasana, Alexander; Carnell, Mary A.

2003-01-01

OBJECTIVE: To evaluate the safety and coverage benefits of auto-disable (AD) syringes, weighed against the financial and logis- tical costs, and to create appropriate health policies in Madagascar. METHODS: Fifteen clinics in Madagascar, trained to use AD syringes, were randomized to implement an AD syringe only, mixed (AD syringes used only on non-routine immunization days), or sterilizable syringe only (control) programme. During a five-week period, data on administered vaccinations were collected, interviews were conducted, and observations were recorded. FINDINGS: The use of AD syringes improved coverage rates by significantly increasing the percentage of vaccines administered on non-routine immunization days (AD-only 4.3%, mixed 5.7%, control 1.1% (P<0.05)). AD-only clinics eliminated sterilization sessions for vaccinations, whereas mixed clinics reduced the number of sterilization sessions by 64%. AD syringes were five times more expensive than sterilizable syringes, which increased AD-only and mixed clinics' projected annual injection costs by 365% and 22%, respectively. However, introducing AD syringes for all vaccinations would only increase the national immunization budget by 2%. CONCLUSION: The use of AD syringes improved vaccination coverage rates by providing ready-to-use sterile syringes on non-routine immunization days and decreasing the number of sterilization sessions, thereby improving injection safety. The mixed programme was the most beneficial approach to phasing in AD syringes and diminishing logistical complications, and it had minimal costs. AD syringes, although more expensive, can feasibly be introduced into a developing country's immunization programme to improve vaccination safety and coverage. PMID:14576886

Added sugar in the packaged foods and beverages available at a major Canadian retailer in 2015: a descriptive analysis.

PubMed

Acton, Rachel B; Vanderlee, Lana; Hobin, Erin P; Hammond, David

2017-01-01

Excess consumption of added sugars has been associated with a variety of health problems, but there is little information available characterizing added sugar in the Canadian food supply. This study examined the presence and types of added sugars in the packaged food and beverage products available at a major Canadian grocery retailer. We searched the ingredients lists of over 40 000 packaged food products available for sale in March 2015 for a variety of added sugar terms. Proportions of food products containing added sugar were identified overall and within food product categories. Differences in total sugar content were identified between food products with and without added sugar. Overall, 66% of the packaged food products analyzed contained at least 1 added sugar. The added sugar term "sugar" (and its variations) appeared the most frequently, followed by "dextrose." Added sugar presence and total sugar content varied within many product categories but were consistently higher in expected categories such as "beverages." Mean total sugar content was significantly higher in products with added sugar than in those without, both overall ( p < 0.001) and within most product subcategories ( p < 0.02). About two-thirds of the packaged foods and beverages available at a major Canadian grocery retailer contain added sugar, similar to recent patterns estimated for the US food supply. The results provide an estimation of the baseline characterization of added sugar in the Canadian food supply, which can be used to assess outcomes of future changes to sugar labelling policies in Canada.

Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease

PubMed Central

Matthews, Qiana L.; Farrow, Anitra L.; Rachakonda, Girish; Gu, Linlin; Nde, Pius; Krendelchtchikov, Alexandre; Pratap, Siddharth; Sakhare, Shruti S.; Sabbaj, Steffanie; Lima, Maria F.; Villalta, Fernando

2016-01-01

Background Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of Trypanosoma cruzi (T. cruzi) trypomastigote gp83 (Ad5-gp83) provided immunoprotection against T. cruzi infection. The purpose of this work was to design an improved vaccine for T. cruzi using a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of the T. cruzi amastigote surface protein 2. Methods Protein IX (pIX)-modified Ad vector (Ad5-pIX-ASP-M) was generated, characterized, and validated. C3H/He mice were immunized with Ad5-pIX-ASP-M and Ad5-gp83 and the cell-mediated responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and intracellular staining. Immunized mice were challenged with T. cruzi to evaluate the vaccine efficacy. Results Our findings indicate that Ad5-pIX-ASP-M was viable. Specific CD8+ T-cell mediated responses prior to the challenge show an increase in IFNγ and TNFα production. A single immunization with Ad5-pIX-ASP-M provided protection from T. cruzi infection, but co-immunizations with Ad5-pIX-ASP-M and Ad5-gp83 provided a higher immunoprotection and increased survival rate of mice. Conclusions Overall, these results suggest that the combination of gp83 and ASP-M specific epitopes onto the capsid-incorporated adenoviruses would provide superior protection against Chagas disease as compared with Ad5-gp83 alone. PMID:27709126

Species B adenovirus serotypes 3, 7, 11 and 35 share similar binding sites on the membrane cofactor protein CD46 receptor.

PubMed

Fleischli, Christoph; Sirena, Dominique; Lesage, Guillaume; Havenga, Menzo J E; Cattaneo, Roberto; Greber, Urs F; Hemmi, Silvio

2007-11-01

We recently characterized the domains of the human cofactor protein CD46 involved in binding species B2 adenovirus (Ad) serotype 35. Here, the CD46 binding determinants are mapped for the species B1 Ad serotypes 3 and 7 and for the species B2 Ad11. Ad3, 7 and 11 bound and transduced CD46-positive rodent BHK cells at levels similar to Ad35. By using antibody-blocking experiments, hybrid CD46-CD4 receptor constructs and CD46 single point mutants, it is shown that Ad3, 7 and 11 share many of the Ad35-binding features on CD46. Both CD46 short consensus repeat domains SCR I and SCR II were necessary and sufficient for optimal binding and transgene expression, provided that they were positioned at an appropriate distance from the cell membrane. Similar to Ad35, most of the putative binding residues of Ad3, 7 and 11 were located on the same glycan-free, solvent-exposed face of the SCR I or SCR II domains, largely overlapping with the binding surface of the recently solved fiber knob Ad11-SCR I-II three-dimensional structure. Differences between species B1 and B2 Ads were documented with competition experiments based on anti-CD46 antibodies directed against epitopes flanking the putative Ad-binding sites, and with competition experiments based on soluble CD46 protein. It is concluded that the B1 and B2 species of Ad engage CD46 through similar binding surfaces.

INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies.

PubMed

Ying, B; Toth, K; Spencer, J F; Meyer, J; Tollefson, A E; Patra, D; Dhar, D; Shashkova, E V; Kuppuswamy, M; Doronin, K; Thomas, M A; Zumstein, L A; Wold, W S M; Lichtenstein, D L

2009-08-01

Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors.

Anxious distress in depressed outpatients: Prevalence, comorbidity, and incremental validity.

PubMed

Rosellini, Anthony J; Bourgeois, Michelle L; Correa, Jeannette; Tung, Esther S; Goncharenko, Svetlana; Brown, Timothy A

2018-05-08

The goals of this study were to estimate the prevalence of the DSM-5 anxious distress specifier (AD) among depressed outpatients, to examine associations of AD with comorbid diagnoses, and to test the incremental validity of AD over comorbidity in predicting functional impairment and severity of anxiety and depression symptoms. The sample was 237 outpatients diagnosed with major depressive disorder (MDD) or persistent depressive disorder (PDD), with and without AD, using the Anxiety and Related Disorders Interview Schedule for DSM-5. Outpatients also completed self-report questionnaires assessing functional impairment and anxiety, stress, and depression symptom severity. Two-by-two contingency tables were used to examine the associations of AD with comorbidity. Two-thirds (66.2%) of outpatients were assigned AD, with similar rates among those with MDD and PDD. Outpatients with AD were significantly more likely than those without AD to have a comorbid GAD diagnosis (OR = 2.47). Hierarchical multiple regressions were used to test the incremental validity of AD in predicting functional impairment and symptom outcomes beyond comorbid disorders. Controlling for comorbid disorders, AD was significantly associated with more severe functional impairment, autonomic arousal, stress, panic, generalized anxiety, and depression. The strongest incremental association were observed between AD and autonomic arousal (f 2  = 0.12-0.18) and generalized anxiety (f 2  = 0.17). These findings add to a growing literature that AD is common among outpatients and associated with important clinical outcomes, suggesting that AD should be routinely assessed in patients with mood disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Role of the Adenovirus DNA-Binding Protein in In Vitro Adeno-Associated Virus DNA Replication

PubMed Central

Ward, Peter; Dean, Frank B.; O’Donnell, Michael E.; Berns, Kenneth I.

1998-01-01

A basic question in adeno-associated virus (AAV) biology has been whether adenovirus (Ad) infection provided any function which directly promoted replication of AAV DNA. Previously in vitro assays for AAV DNA replication, using linear duplex AAV DNA as the template, uninfected or Ad-infected HeLa cell extracts, and exogenous AAV Rep protein, demonstrated that Ad infection provides a direct helper effect for AAV DNA replication. It was shown that the nature of this helper effect was to increase the processivity of AAV DNA replication. Left unanswered was the question of whether this effect was the result of cellular factors whose activity was enhanced by Ad infection or was the result of direct participation of Ad proteins in AAV DNA replication. In this report, we show that in the in vitro assay, enhancement of processivity occurs with the addition of either the Ad DNA-binding protein (Ad-DBP) or the human single-stranded DNA-binding protein (replication protein A [RPA]). Clearly Ad-DBP is present after Ad infection but not before, whereas the cellular level of RPA is not apparently affected by Ad infection. However, we have not measured possible modifications of RPA which might occur after Ad infection and affect AAV DNA replication. When the substrate for replication was an AAV genome inserted into a plasmid vector, RPA was not an effective substitute for Ad-DBP. Extracts supplemented with Ad-DBP preferentially replicated AAV sequences rather than adjacent vector sequences; in contrast, extracts supplemented with RPA preferentially replicated vector sequences. PMID:9420241

Managing emergency department overcrowding via ambulance diversion: a discrete event simulation model.

PubMed

Lin, Chih-Hao; Kao, Chung-Yao; Huang, Chong-Ye

2015-01-01

Ambulance diversion (AD) is considered one of the possible solutions to relieve emergency department (ED) overcrowding. Study of the effectiveness of various AD strategies is prerequisite for policy-making. Our aim is to develop a tool that quantitatively evaluates the effectiveness of various AD strategies. A simulation model and a computer simulation program were developed. Three sets of simulations were executed to evaluate AD initiating criteria, patient-blocking rules, and AD intervals, respectively. The crowdedness index, the patient waiting time for service, and the percentage of adverse patients were assessed to determine the effect of various AD policies. Simulation results suggest that, in a certain setting, the best timing for implementing AD is when the crowdedness index reaches the critical value, 1.0 - an indicator that ED is operating at its maximal capacity. The strategy to divert all patients transported by ambulance is more effective than to divert either high-acuity patients only or low-acuity patients only. Given a total allowable AD duration, implementing AD multiple times with short intervals generally has better effect than having a single AD with maximal allowable duration. An input-throughput-output simulation model is proposed for simulating ED operation. Effectiveness of several AD strategies on relieving ED overcrowding was assessed via computer simulations based on this model. By appropriate parameter settings, the model can represent medical resource providers of different scales. It is also feasible to expand the simulations to evaluate the effect of AD strategies on a community basis. The results may offer insights for making effective AD policies. Copyright © 2012. Published by Elsevier B.V.

Depression in dementia with Lewy bodies: A comparison with Alzheimer's disease

PubMed Central

Chiu, Pai-Yi; Wang, Chein-Wei; Tsai, Chun-Tang; Li, Shin-Hua; Lin, Chih-Li; Lai, Te-Jen

2017-01-01

Background Depression is highly associated with dementia, and this study will compare the frequencies, severity, and symptoms of depression between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). Methods Frequency of depression was determined according to the DSM-IV criteria for major depression or the National Institute of Mental Health criteria for depression in AD (NIMH-dAD). Severity of depression were assessed using the Hamilton Depression Rating Scale, the Cornell Scale for Depression in Dementia, and the depression subscale in Neuropsychiatric Inventory. The rates of depressive symptoms were compared between AD and DLB. Results A total of 312 patients were investigated (AD/DLB = 241/71). The frequency of major depression was significantly higher (p = 0.017) in DLB (19.7%) than in AD (8.7%). The higher frequency of depression in DLB was not reproduced by using the NIMH-dAD criteria (DLB: AD = 43.7%: 33.2%; p = 0.105). The severity of depression was higher in DLB than in AD according to the Hamilton Depression Rating Scale (p < 0.001) and the Cornell Scale for Depression in Dementia (p < 0.001). Among depressive symptoms, pervasive anhedonia had the highest odds ratio in DLB compared with AD. Conclusion This is the first study using the NIMH-dAD criteria to investigate the frequency of depression in DLB. Our study shows that co-morbid major depression is more frequent in DLB than in AD. Pervasive anhedonia had the greatest value for the differential diagnosis of depression between DLB and AD. PMID:28617831

Male adolescents' reactions to TV beer advertisements: the effects of sports content and programming context.

PubMed

Slater, M D; Rouner, D; Murphy, K; Beauvais, F; Van Leuven, J; Rodríguez, M D

1996-07-01

This study examines white male adolescent responses to TV beer advertisements with and without sports content and to nonbeer ads when embedded in sports and entertainment programming. A total of 72 advertisements and 24 television program excerpts were randomly sampled from national television programming. White male adolescents (N = 157) recruited in a public school system each viewed six ads (one of each of three types of ad embedded in each of two types of programming) comprising the 2 x 2 x 3 factorial, within-subjects, mixed-model (random and fixed effects) experimental design along with an age-level blocking factor and random factors for commercial and program stimuli. Cognitive responses to each ad were content-analyzed. Individual difference variables including alcohol use behavior, sensation-seeking, masculinity and sports involvement were also measured. Subjects showed a consistent preference for beer ads with sports content. A significant three-way interaction between ad type, programming type and junior versus senior high-school age level also indicated that sports programming had an inconsistent effect on responses to beer ads but that nonbeer ads were responded to more positively during sports than during entertainment programming. Other analyses showed that subjects were more cognitively resistant to beer ads than to nonbeer ads. These results support public and official concerns that sports content in beer ads increase the ads appeal to underage youth. They do not support hypothesized concerns that sports programming might prime adolescents to be more receptive to beer ads. Implications for alcohol education efforts are discussed.

The Use of Advance Directives Among Patients With Implantable Cardioverter Defibrillators

PubMed Central

Tajouri, Tanya H.; Ottenberg, Abigale L.; Hayes, David L.; Mueller, Paul S.

2013-01-01

Background We aimed to determine the prevalence of advance directives (ADs) among patients with implantable cardioverter defibrillators (ICDs) and of ADs that addressed ICD management at the end of life. Methods The medical records of all patients who underwent ICD implantation during 2007 at a single institution were reviewed retrospectively to determine the number of patients with an AD and the number of ADs mentioning the ICD specifically (ie, ICD management at end of life). Results During 2007, 420 patients (males, 71%) underwent ICD implantation at our institution (mean age [range] at implantation, 63 [1–90] years). Primary prevention was the most common indication for device therapy (254 patients [61%]). Overall, 127 patients (30%) had an AD, with 83 ADs (65%) completed more than 12 months before ICD implantation and 10 (8%) completed after it. Several life-sustaining treatments were mentioned in the ADs: tube feeding, 46 (37%); cardiopulmonary resuscitation, 25 (20%); mechanical ventilation, 22 (17%); and hemodialysis, 9 (7%). Pain control was mentioned in 58 ADs (46%) and comfort measures in 38 (30%). However, only 2 ADs (2%) mentioned the ICD or its deactivation at end of life. Conclusions About one-third of patients with ICDs had an AD, but only a couple ADs mentioned the ICD. These results suggest that clinicians should not only encourage patients with ICDs to complete an AD, but also encourage them to address ICD management specifically. Not addressing ICD management in an AD may result in ethical dilemmas during end-of- life care. PMID:22432897

Added sugar in the packaged foods and beverages available at a major Canadian retailer in 2015: a descriptive analysis

PubMed Central

Acton, Rachel B.; Vanderlee, Lana; Hobin, Erin P.; Hammond, David

2017-01-01

Background: Excess consumption of added sugars has been associated with a variety of health problems, but there is little information available characterizing added sugar in the Canadian food supply. This study examined the presence and types of added sugars in the packaged food and beverage products available at a major Canadian grocery retailer. Methods: We searched the ingredients lists of over 40 000 packaged food products available for sale in March 2015 for a variety of added sugar terms. Proportions of food products containing added sugar were identified overall and within food product categories. Differences in total sugar content were identified between food products with and without added sugar. Results: Overall, 66% of the packaged food products analyzed contained at least 1 added sugar. The added sugar term "sugar" (and its variations) appeared the most frequently, followed by "dextrose." Added sugar presence and total sugar content varied within many product categories but were consistently higher in expected categories such as "beverages." Mean total sugar content was significantly higher in products with added sugar than in those without, both overall (p < 0.001) and within most product subcategories (p < 0.02). Interpretation: About two-thirds of the packaged foods and beverages available at a major Canadian grocery retailer contain added sugar, similar to recent patterns estimated for the US food supply. The results provide an estimation of the baseline characterization of added sugar in the Canadian food supply, which can be used to assess outcomes of future changes to sugar labelling policies in Canada. PMID:28401111

Pediatric advance directives: parents' knowledge, experience, and preferences.

PubMed

Liberman, Danica B; Pham, Phung K; Nager, Alan L

2014-08-01

To explore parents' and caregivers' experience, knowledge, and preferences regarding advance directives (ADs) for children who have chronic illness. We conducted a prospective, cross-sectional survey of parents and caregivers of children who have chronic illness. During ambulatory medical visits, participants were asked about previous AD experience and knowledge, future preferences regarding AD discussions, their child's past and current health status, and family demographics. Among 307 participants surveyed, previous AD experience was low, with 117 (38.1%) having heard of an AD, 54 (17.6%) having discussed one, and 77 (25.1%) having known someone who had an AD. Furthermore, 27 (8.8%) participants had an AD or living will of their own, and 8 (2.6%) reported that their chronically ill child had an AD. Previous AD knowledge was significantly more likely among parents and caregivers who had a college degree than those who did not have a high school diploma, yet significantly less likely among primarily Spanish-speaking parents and caregivers than those primarily English-speaking. Interest in creating an AD for the child was reported by 151 (49.2%) participants, and was significantly more likely among families who had more frequent emergency department visits over the previous year. The limited AD experience and knowledge of parents and caregivers of children who have chronic illness and their interest in creating an AD suggest an unmet need among families of children who have chronic illness, and an opportunity to enhance communication between families and medical teams regarding ADs and end-of-life care. Copyright © 2014 by the American Academy of Pediatrics.

White Matter Hyperintensities and Changes in White Matter Integrity in Patients with Alzheimer’s Disease

PubMed Central

Wang, Liya; Goldstein, Felicia C.; Levey, Allan I.; Lah, James J.; Meltzer, Carolyn C.; Holder, Chad A.; Mao, Hui

2012-01-01

Purpose White matter hyperintensities (WMHs) are a risk factor for Alzheimer’s disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs. Subjects and Methods Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR) and axial diffusivity (DA) were analyzed using the region of interest and Tract-Based Spatial Statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated. Results AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and DR were more sensitive measurements than MD and DA in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs. Conclusions WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. DR may serve as an imaging marker of myelin deficits associated with AD. PMID:21152911

Thermodynamic Volume in AdS/CFT

NASA Astrophysics Data System (ADS)

Kim, Kyung Kiu; Ahn, Byoungjoon

2018-01-01

In this note, we study on extended thermodynamics of AdS black holes by varying cosmological constant. We found and discussed pressure and volume of both bulk and boundary physics through AdS/CFT correspondence. In particular, we derive the relation between thermodynamic volume and a chemical potential for M2 brane dual to four dimensional AdS space. In addition, we show that thermodynamic volume of hyperbolic black hole is related to `entanglement pressure' coming from a generalized first law of entanglement entropy.

Transformations of asymptotically AdS hyperbolic initial data and associated geometric inequalities

NASA Astrophysics Data System (ADS)

Cha, Ye Sle; Khuri, Marcus

2018-01-01

We construct transformations which take asymptotically AdS hyperbolic initial data into asymptotically flat initial data, and which preserve relevant physical quantities. This is used to derive geometric inequalities in the asymptotically AdS hyperbolic setting from counterparts in the asymptotically flat realm, whenever a geometrically motivated system of elliptic equations admits a solution. The inequalities treated here relate mass, angular momentum, charge, and horizon area. Furthermore, new mass-angular momentum inequalities in this setting are conjectured and discussed.

Holographic helical superconductor with higher curvature corrections

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Subir; Paul, Chandrima

2018-01-01

We study SU(2) × U(1) gauge theory with Chern-Simons term, coupled to scalar field in adjoint, in Einstein-Gauss-Bonnet gravity. We explore phases of holographic superconductor in terms of the condensates and free energies in the background of AdS black hole and AdS soliton. In the case of black hole, we find with increasing strength of higher curvature terms, transition temperature decreases. For AdS soliton, the critical value of chemical potential increases as the higher curvature terms dominate.

Kinetics of Bacterial Growth on Chlorinated Aliphatic Compounds

PubMed Central

van den Wijngaard, Arjan J.; Wind, Richèle D.; Janssen, Dick B.

1993-01-01

With the pure bacterial cultures Ancylobacter aquaticus AD20 and AD25, Xanthobacter autotrophicus GJ10, and Pseudomonas sp. strain AD1, Monod kinetics was observed during growth in chemostat cultures on 1,2-dichloroethane (AD20, AD25, and GJ10), 2-chloroethanol (AD20 and GJ10), and 1,3-dichloro-2-propanol (AD1). Both the Michaelis-Menten constants (Km) of the first catabolic (dehalogenating) enzyme and the Monod half-saturation constants (Ks) followed the order 2-chloroethanol, 1,3-dichloro-2-propanol, epichlorohydrin, and 1,2-dichloroethane. The Ks values of strains GJ10, AD20, and AD25 for 1,2-dichloroethane were 260, 222, and 24 μM, respectively. The low Ks value of strain AD25 was correlated with a higher haloalkane dehalogenase content of this bacterium. The growth rates of strains AD20 and GJ10 in continuous cultures on 1,2-dichloroethane were higher than the rates predicted from the kinetics of the haloalkane dehalogenase and the concentration of the enzyme in the cells. The results indicate that the efficiency of chlorinated compound removal is indeed influenced by the kinetic properties and cellular content of the first catabolic enzyme. The cell envelope did not seem to act as a barrier for permeation of 1,2-dichloroethane. PMID:16348981

Added sugars: consumption and associated factors among adults and the elderly. São Paulo, Brazil.

PubMed

Bueno, Milena Baptista; Marchioni, Dirce Maria Lobo; César, Chester Luis Galvão; Fisberg, Regina Mara

2012-06-01

To investigate added sugar intake, main dietary sources and factors associated with excessive intake of added sugar. A population-based household survey was carried out in São Paulo, the largest city in Brazil. Cluster sampling was performed and the study sample comprised 689 adults and 622 elderly individuals. Dietary intake was estimated based on a 24-hour food recall. Usual nutrient intake was estimated by correcting for the within-person variance of intake using the Iowa State University (ISU) method. Linear regression analysis was conducted to identify factors associated with added sugar intake. Average of energy intake (EI) from added sugars was 9.1% (95% CI: 8.9%; 9.4%) among adults and 8.4% (95% CI: 8.2%; 8.7%) among the elderly (p < 0.05). Average added sugar intake (% EI) was higher among women than among men (p < 0.05). Soft drink was the main source of added sugar among adults, while table sugar was the main source of added sugar among the elderly. Added sugar intake increased with age among adults. Moreover, higher socioeconomic level was associated with added sugar intake in the same group. Added sugar intake is higher among younger adults of higher socioeconomic level. Soft drink and table sugar accounted for more than 50% of the sugar consumed.

Targeting modulates audiences’ brain and behavioral responses to safe sex video ads

PubMed Central

Lowen, Steven B; Shi, Zhenhao; Bissey, Bryn; Metzger, David S.; Langleben, Daniel D.

2016-01-01

Video ads promoting condom use are a key component of media campaigns to stem the HIV epidemic. Recent neuroimaging studies in the context of smoking cessation, point to personal relevance as one of the key variables that determine the effectiveness of public health messages. While minority men who have sex with men (MSM) are at the highest risk of HIV infection, most safe-sex ads feature predominantly Caucasian actors in heterosexual scenarios. We compared brain respons of 45 African American MSM to safe sex ads that were matched (i.e. ‘Targeted’) to participants’ sexual orientation and race, and ‘Untargeted’ ads that were un matched for these characteristics. Ad recall, perceived ‘convincingness’ and attitudes towards condom use were also assessed. We found that Targeted ads were better remembered than the Untargeted ads but perceived as equally convincing. Targeted ads engaged brain regions involved in self-referential processing and memory, including the amygdala, hippocampus, temporal and medial prefrontal cortices (MPFC) and the precuneus. Connectivity between MPFC and precuneus and middle temporal gyrus was stronger when viewing Targeted ads. Our results suggest that targeting may increase cognitive processing of safe sex ads and justify further prospective studies linking brain response to media public health interventions and clinical outcomes. PMID:27217112

Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

PubMed Central

Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

2014-01-01

Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620

Distinct chronology of neuronal cell cycle re-entry and tau pathology in the 3xTg-AD mouse model and Alzheimer's disease patients.

PubMed

Hradek, Alex C; Lee, Hyun-Pil; Siedlak, Sandra L; Torres, Sandy L; Jung, Wooyoung; Han, Ashley H; Lee, Hyoung-gon

2015-01-01

Cell cycle re-entry in Alzheimer's disease (AD) has emerged as an important pathological mechanism in the progression of the disease. This appearance of cell cycle related proteins has been linked to tau pathology in AD, but the causal and temporal relationship between the two is not completely clear. In this study, we found that hyperphosphorylated retinoblastoma protein (ppRb), a key regulator for G1/S transition, is correlated with a late marker for hyperphosphorylation of tau but not with other early markers for tau alteration in the 3xTg-AD mouse model. However, in AD brains, ppRb can colocalize with both early and later markers for tau alterations, and can often be found singly in many degenerating neurons, indicating the distinct development of pathology between the 3xTg-AD mouse model and human AD patients. The conclusions of this study are two-fold. First, our findings clearly demonstrate the pathological link between the aberrant cell cycle re-entry and tau pathology. Second, the chronological pattern of cell cycle re-entry with tau pathology in the 3xTg-AD mouse is different compared to AD patients suggesting the distinct pathogenic mechanism between the animal AD model and human AD patients.

A Family-Engaged Educational Program for Atopic Dermatitis: A Seven-Year, Multicenter Experience in Daegu-Gyeongbuk, South Korea

PubMed Central

Jang, Yong Hyun; Lee, Jin Sub; Kim, Sang Lim; Song, Chang Hyun; Jung, Hong Dae; Shin, Dong Hoon; Cho, Jae We; Chung, Hyun; Suh, Moo Kyu

2015-01-01

Background It is important to educate families of pediatric patients with atopic dermatitis (AD) so that they have a correct understanding of AD. Objective The purpose of this study is to introduce, evaluate, and improve our family-engaged educational program. Methods Children suffering from AD and their families have participated in a half-day educational program called "AD school" with catchy slogans such as "Enjoy with AD Families!" every year since 2005. Educational lectures were conducted for parents. For children with AD, various entertaining programs were provided. A feedback survey about AD school was administered for the purpose of evaluation. Results A total of 827 people (376 patients and 451 family members) participated in this program over 7 years. On-site surveys showed a positive response (i.e., "excellent" or "good") for the prick test (95.1%), emollient education (78.4%), educational lecture (97.0%), drawing contest and games (90.2%), and recreation (magic show; 99.0%) respectively. Telephone surveys one year later also elicited a positive response. Conclusion We herein introduce the experience of a half-day, family-engaged educational program for AD. Family-engaged education programs for AD such as this AD school encourage and validate family participation in the treatment of their children's AD. PMID:26273152

A Family-Engaged Educational Program for Atopic Dermatitis: A Seven-Year, Multicenter Experience in Daegu-Gyeongbuk, South Korea.

PubMed

Jang, Yong Hyun; Lee, Jin Sub; Kim, Sang Lim; Song, Chang Hyun; Jung, Hong Dae; Shin, Dong Hoon; Cho, Jae We; Chung, Hyun; Suh, Moo Kyu; Kim, Do Won

2015-08-01

It is important to educate families of pediatric patients with atopic dermatitis (AD) so that they have a correct understanding of AD. The purpose of this study is to introduce, evaluate, and improve our family-engaged educational program. Children suffering from AD and their families have participated in a half-day educational program called "AD school" with catchy slogans such as "Enjoy with AD Families!" every year since 2005. Educational lectures were conducted for parents. For children with AD, various entertaining programs were provided. A feedback survey about AD school was administered for the purpose of evaluation. A total of 827 people (376 patients and 451 family members) participated in this program over 7 years. On-site surveys showed a positive response (i.e., "excellent" or "good") for the prick test (95.1%), emollient education (78.4%), educational lecture (97.0%), drawing contest and games (90.2%), and recreation (magic show; 99.0%) respectively. Telephone surveys one year later also elicited a positive response. We herein introduce the experience of a half-day, family-engaged educational program for AD. Family-engaged education programs for AD such as this AD school encourage and validate family participation in the treatment of their children's AD.

Performance-oriented mobility assessment (POMA) balance score indicates need for assistive device.

PubMed

Mitchell, Kathryn D; Newton, Roberta A

2006-06-01

To determine (1) if older adults using an assistive device (AD) score lower on the Performance-Oriented Mobility Assessment (POMA) balance subscale (B-subscale) than individuals not using an AD; and (2) if a cut-score of 12 would indicate the need to use an AD. Elderly persons (n = 82, mean age = 82.1 years) were surveyed about AD use, health status, activity level and fall history. A one-time assessment of balance was conducted using the B-subscale. The 'arising task' was repeated to evaluate performance on the sit-to-stand task without using hands. A significant difference in B-subscale scores was observed between the two groups (AD; no AD), (P < 0.001). AD use was associated with lower activity level and health status. A cut-score of 12 points indicated device use (P = 0.000). The repeated 'arising task' demonstrated that 76.8% performed the task without using hands for support. Older adults using an AD will score lower on the B-subscale and report lower activity level and health status. A score of less than 12 on the B-subscale is indicative of AD need. Older adults who use an AD and self-report a falls history will score lower on the B-subscale than individuals using an AD and no reported history of falls.

Comprehensive Review on Magnetic Resonance Imaging in Alzheimer's Disease.

PubMed

Dona, Olga; Thompson, Jeff; Druchok, Cheryl

2016-01-01

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. However, definitive diagnosis of AD is only achievable postmortem and currently relies on clinical neurological evaluation. Magnetic resonance imaging (MRI) can evaluate brain changes typical of AD, including brain atrophy, presence of amyloid β (Aβ) plaques, and functional and biochemical abnormalities. Structural MRI (sMRI) has historically been used to assess the inherent brain atrophy present in AD. However, new techniques have recently emerged that have refined sMRI into a more precise tool to quantify the thickness and volume of AD-sensitive cerebral structures. Aβ plaques, a defining pathology of AD, are widely believed to contribute to the progressive cognitive decline in AD, but accurate assessment is only possible on autopsy. In vivo MRI of plaques, although currently limited to mouse models of AD, is a very promising technique. Measuring changes in activation and connectivity in AD-specific regions of the brain can be performed with functional MRI (fMRI). To help distinguish AD from diseases with similar symptoms, magnetic resonance spectroscopy (MRS) can be used to look for differing metabolite concentrations in vivo. Together, these MR techniques, evaluating various brain changes typical of AD, may help to provide a more definitive diagnosis and ease the assessment of the disease over time, noninvasively.

Industry sponsored anti-smoking ads and adolescent reactance: test of a boomerang effect.

PubMed

Henriksen, L; Dauphinee, A L; Wang, Y; Fortmann, S P

2006-02-01

To examine whether adolescents' exposure to youth smoking prevention ads sponsored by tobacco companies promotes intentions to smoke, curiosity about smoking, and positive attitudes toward the tobacco industry. A randomised controlled experiment compared adolescents' responses to five smoking prevention ads sponsored by a tobacco company (Philip Morris or Lorillard), or to five smoking prevention ads sponsored by a non-profit organisation (the American Legacy Foundation), or to five ads about preventing drunk driving. A large public high school in California's central valley. A convenience sample of 9th and 10th graders (n = 832) ages 14-17 years. Perceptions of ad effectiveness, intention to smoke, and attitudes toward tobacco companies measured immediately after exposure. As predicted, adolescents rated Philip Morris and Lorillard ads less favourably than the other youth smoking prevention ads. Adolescents' intention to smoke did not differ as a function of ad exposure. However, exposure to Philip Morris and Lorillard ads engendered more favourable attitudes toward tobacco companies. This study demonstrates that industry sponsored anti-smoking ads do more to promote corporate image than to prevent youth smoking. By cultivating public opinion that is more sympathetic toward tobacco companies, the effect of such advertising is likely to be more harmful than helpful to youth.

Introduction to the AdS/CFT Correspondence

NASA Astrophysics Data System (ADS)

Nąstase, Horaǧiu

2015-09-01

Preface; Introduction; Part I. Background: 1. Elements of quantum field theory and gauge theory; 2. Basics of general relativity. Anti-de Sitter space; 3. Basics of supersymmetry; 4. Basics of supergravity; 5. Kaluza-Klein dimensional reduction; 6. Black holes and p-branes; 7. String theory actions and spectra; 8. Elements of conformal field theory; 9. D-branes; Part II. Basics of AdS/CFT for N = 4 SYM vs AdS5 × S5: 10. The AdS/CFT correspondence: motivation, definition and spectra; 11. Witten prescription and 3-point correlator calculations; 12. Holography in Lorentzian signature: Poincaré and global; 13. Solitonic objects in AdS/CFT; 14. Quarks and the Wilson loop; 15. Finite temperature and N = 4 SYM plasmas; 16. Scattering processes and gravitational shockwave limit; 17. The pp-wave correspondence; 18. Spin chains; Part III. AdS/CFT Developments and Gauge-Gravity Dualities: 19. Other conformal cases; 20. The 3 dimensional ABJM model vs. AdS4 × CP3; 21. Gravity duals; 22. Holographic renormalization; 23. RG flow between fixed points; 24. Phenomenological gauge-gravity duality I: AdS/QCD; 25. Phenomenological gauge-gravity duality II: AdS/CMT; 26. Gluon scattering: the Alday-Maldacena prescription; 27. Holographic entanglement entropy: the Ryu-Takayanagi prescription.

Development of Clinical Vignettes to Describe Alzheimer's Disease Health States: A Qualitative Study

PubMed Central

Oremus, Mark; Xie, Feng; Gaebel, Kathryn

2016-01-01

Aims To develop clinical descriptions (vignettes) of life with Alzheimer’s disease (AD), we conducted focus groups of persons with AD (n = 14), family caregivers of persons with AD (n = 20), and clinicians who see persons with AD in their practices (n = 5). Methods Group participants read existing descriptions of AD and commented on the realism and comprehensibility of the descriptions. We used thematic framework analysis to code the comments into themes and develop three new vignettes to describe mild, moderate, and severe AD. Results Themes included the types of symptoms to mention in the new vignettes, plus the manner in which the vignettes should be written. Since the vignette descriptions were based on focus group participants’ first-hand knowledge of AD, the descriptions can be said to demonstrate content validity. Conclusion Members of the general public can read the vignettes and estimate their health-related quality-of-life (HRQoL) as if they had AD based on the vignette descriptions. This is especially important for economic evaluations of new AD medications, which require HRQoL to be assessed in a manner that persons with AD often find difficult to undertake. The vignettes will allow the general public to serve as a proxy and provide HRQoL estimates in place of persons with AD. PMID:27589604

Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis.

PubMed

Suárez-Fariñas, Mayte; Dhingra, Nikhil; Gittler, Julia; Shemer, Avner; Cardinale, Irma; de Guzman Strong, Cristina; Krueger, James G; Guttman-Yassky, Emma

2013-08-01

Atopic dermatitis (AD) is classified as extrinsic and intrinsic, representing approximately 80% and 20% of patients with the disease, respectively. Although sharing a similar clinical phenotype, only extrinsic AD is characterized by high serum IgE levels. Because most patients with AD exhibit high IgE levels, an "allergic"/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly TH2/TH22 polarization, and epidermal barrier defects. We sought to define whether both variants share a common pathogenesis. We stratified 51 patients with severe AD into extrinsic AD (n = 42) and intrinsic AD (n = 9) groups (with similar mean disease activity/SCORAD scores) and analyzed the molecular and cellular skin pathology of lesional and nonlesional intrinsic AD and extrinsic AD by using gene expression (real-time PCR) and immunohistochemistry. A significant correlation between IgE levels and SCORAD scores (r = 0.76, P < 10(-5)) was found only in patients with extrinsic AD. Marked infiltrates of T cells and dendritic cells and corresponding epidermal alterations (keratin 16, Mki67, and S100A7/A8/A9) defined lesional skin of patients with both variants. However, higher activation of all inflammatory axes (including TH2) was detected in patients with intrinsic AD, particularly TH17 and TH22 cytokines. Positive correlations between TH17-related molecules and SCORAD scores were only found in patients with intrinsic AD, whereas only patients with extrinsic AD showed positive correlations between SCORAD scores and TH2 cytokine (IL-4 and IL-5) levels and negative correlations with differentiation products (loricrin and periplakin). Although differences in TH17 and TH22 activation exist between patients with intrinsic AD and those with extrinsic AD, we identified common disease-defining features of T-cell activation, production of polarized cytokines, and keratinocyte responses to immune products. Our data indicate that a TH2 bias is not the sole cause of high IgE levels in patients with extrinsic AD, with important implications for similar therapeutic interventions. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Immunogenicity of adenovirus vaccines expressing the PCV2 capsid protein in pigs.

PubMed

Li, Delong; Du, Qian; Wu, Bin; Li, Juejun; Chang, Lingling; Zhao, Xiaomin; Huang, Yong; Tong, Dewen

2017-08-24

Porcine circovirus type 2 (PCV2) is the main pathogen of porcine circovirus associated disease (PCVAD), causing great economic losses in pig industry. In previous study, we constructed adenovirus vector vaccines expressing PCV2 Cap either modified with Intron A and WPRE, or CD40L and GMCSF, and evaluated all of these vaccines in mice and in pigs. Although Ad-A-C-W and Ad-CD40L-Cap-GMCSF could induce stronger immune responses than Ad-Cap, neither of them was better than commercial inactivated vaccine PCV2 SH-strain. In this study, secretory recombinant adenoviruses (Ad-A-spCap-W and Ad-A-spCD40L-spCap-spGMCSF-W) and non-secretory recombinant adenovirus Ad-A-CD40L-Cap-GMCSF-W were constructed, and identified by western blot and confocal laser microscope observation. The results of ELISA and VN showed that humoral immune responses induced by Ad-A-spCap-W and Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH-strain, but Ad-A-spCD40L-spCap-spGMCSF-W could induce significantly higher humoral immune response than SH-strain. Lymphocytes proliferative and cytokines releasing levels of Ad-A-spCap-W and Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH-strain, but Ad-A-spCD40L-spCap-spGMCSF-W was significantly higher than SH-strain. PCV2-challenge experiment showed that virus loads were significantly reduced in Ad-A-spCD40L-spCap-spGMCSF-W vaccinated group, and no obviously clinical and microscopic lesions were observed in Ad-A-spCD40L-spCap-spGMCSF-W vaccinated group. Altogether, these results demonstrate that recombinant adenovirus vaccine Ad-A-spCD40L-spCap-spGMCSF-W induces stronger immune responses and provides better protection than commercial inactivated vaccine PCV2 SH-strain, and suggest that Ad-A-spCD40L-spCap-spGMCSF-W could be a potential vaccine candidate against PCVAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age-related changes in core body temperature and activity in triple-transgenic Alzheimer’s disease (3xTgAD) mice

PubMed Central

Knight, Elysse M.; Brown, Timothy M.; Gümüsgöz, Sarah; Smith, Jennifer C. M.; Waters, Elizabeth J.; Allan, Stuart M.; Lawrence, Catherine B.

2013-01-01

SUMMARY Alzheimer’s disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4–10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD. PMID:22864021

Age-related changes in core body temperature and activity in triple-transgenic Alzheimer's disease (3xTgAD) mice.

PubMed

Knight, Elysse M; Brown, Timothy M; Gümüsgöz, Sarah; Smith, Jennifer C M; Waters, Elizabeth J; Allan, Stuart M; Lawrence, Catherine B

2013-01-01

Alzheimer's disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4-10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.

Inhibition of (Na(+)/K(+))-ATPase by Cibacron Blue 3G-A and its analogues.

PubMed

Breier, A; Bohácová, V; Docolomanský, P

2006-12-01

A specific feature of anthraquinone dyes (AD) is to mimic the adenine nucleotides ATP, ADP, NAD and NADH, enabling them to act as ligands in interaction with nucleotide-binding sites of several enzymes and receptors. In the present study, the interactions and/or inhibitory effects of eight AD, including Cibacron Blue 3G-A (Reactive Blue 2), Procion Blue MX-R (Reactive Blue 4) and Remazol Brilliant Blue R (Reactive Blue 19) on the activity of (Na(+)/K(+))-ATPase were investigated. The AD used in this paper could be divided into two groups: i) AD1-AD4 that do not contain the triazine moiety; ii) AD5-AD8 that contain the triazine moiety. Interaction affinity between the respective dye and (Na+/K+)-ATPase was characterized by means of enzyme kinetics. All AD, excluding AD1 and AD2 (which were practically ineffective) exerted effective competitive inhibition to the (Na(+)/K(+))-ATPase activity. Present study is devoted to elucidation of relationship between the inhibitory efficacy of AD against (Na(+)/K(+))-ATPase activity, their acid-basic properties and their three dimensional structure. From the results obtained, the following conclusions could be driven: 1. Similarities in the mutual position of positively and negatively charged parts of ATP and AD are responsible for their interaction with ATP-binding site of (Na(+)/K(+))-ATPase. This may be documented by fact that mutual position of 1-aminogroup of anthraquinone and -SO3(-) group of benzenesulphonate part of respective AD plays crucial role for inhibition of this enzyme. Distances of these two groups on all effective AD were found to be similar as the distance of the 6-aminogroup of adenine and the second phosphate group on ATP molecule. This similarity could be responsible for biomimetic recognition of AD in ATP-binding loci of (Na(+)/K(+))-ATPase. 2. The affinity of AD to ATP binding site of (Na(+)/K(+))-ATPase increases with increasing values of molar refractivity, i. e., with increasing molecular volume and polarizability.

[Value-Added--Adding Economic Value in the Food Industry].

ERIC Educational Resources Information Center

Welch, Mary A., Ed.

1989-01-01

This booklet focuses on the economic concept of "value added" to goods and services. A student activity worksheet illustrates how the steps involved in processing food are examples of the concept of value added. The booklet further links food processing to the idea of value added to the Gross National Product (GNP). Discussion questions,…

Myths & Facts about Value-Added Analysis

ERIC Educational Resources Information Center

TNTP, 2011

2011-01-01

This paper presents myths as well as facts about value-added analysis. These myths include: (1) "Value-added isn't fair to teachers who work in high-need schools, where students tend to lag far behind academically"; (2) "Value-added scores are too volatile from year-to-year to be trusted"; (3) "There's no research behind value-added"; (4) "Using…

Using the Want Ads. A Janus Survival Guide.

ERIC Educational Resources Information Center

Jew, Wing; Tandy, Carol

Originally intended for students with reading problems, this booklet may also be helpful to anyone who wants to make use of newspaper want ads. The eight teaching units discuss the following topics: (1) purposes for want ads, (2) finding want ads, (3) letting the alphabet help in reading want ads, (4) looking for a job, (5) looking for an…

78 FR 76360 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

... December 2012 added TCV; and (ii) has an ``added liquidity'' to ``added plus removed liquidity'' ratio of... lower; and (2) Have an ``added liquidity'' to ``added plus removed liquidity'' ratio of at least 85...) Remove Flag RS, which routes to NASDAQ OMX PSX (``PSX'') and adds liquidity; (ii) make a non-substantive...

78 FR 52841 - Airworthiness Directives; Lockheed Martin Corporation/Lockheed Martin Aeronautics Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-27

...-1011 series airplanes. AD 2005-15-01 required repetitive inspections to detect corrosion or fatigue... threshold required by the AD 2005-15-01. We are issuing this AD to prevent corrosion or fatigue cracking of... threshold required by AD 2005-15-01. We are issuing this AD to prevent corrosion or fatigue cracking of...

A brief history of Alzheimer's disease gene discovery.

PubMed

Tanzi, Rudolph E

2013-01-01

The rich and colorful history of gene discovery in Alzheimer's disease (AD) over the past three decades is as complex and heterogeneous as the disease, itself. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations inAPP, PSEN1, and PSEN2 are fully penetrant for early-onset (<60 years) familial AD, which represents <5% of AD. On the other hand, common gene polymorphisms, such as the 4 and 2 variants of the APOE gene, influence susceptibility for common (>95%) late-onset AD. These four genes account for 30-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of additional highly confirmed AD candidate genes. Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible.

Evaporation of large black holes in AdS: coupling to the evaporon

NASA Astrophysics Data System (ADS)

Rocha, Jorge V.

2008-08-01

Large black holes in an asymptotically AdS spacetime have a dual description in terms of approximately thermal states in the boundary CFT. The reflecting boundary conditions of AdS prevent such black holes from evaporating completely. On the other hand, the formulation of the information paradox becomes more stringent when a black hole is allowed to evaporate. In order to address the information loss problem from the AdS/CFT perspective we then need the boundary to become partially absorptive. We present a simple model that produces the necessary changes on the boundary by coupling a bulk scalar field to the evaporon, an external field propagating in one extra spatial dimension. The interaction is localized at the boundary of AdS and leads to partial transmission into the additional space. The transmission coefficient is computed in the planar limit and perturbatively in the coupling constant. Evaporation of the large black hole corresponds to cooling down the CFT by transferring energy to an external sector.

Effect of exposure to an Asian dust storm on fractional exhaled nitric oxide in adult asthma patients in Western Japan.

PubMed

Watanabe, Masanari; Kurai, Jun; Sano, Hiroyuki; Shimizu, Eiji

2015-01-01

Epidemiological investigations indicate that an Asian dust storm (ADS) can aggravate respiratory disorders. However, the effects of ADS on airway inflammation remain unclear. The aim of this study was to investigate the association of exposure to ADS with airway inflammation. The subjects were 33 adult patients with asthma who measured daily peak flow expiratory (PEF) from March to May 2012. Fractional exhaled nitric oxide (FeNO) was measured before and after ADS. The FeNO values were 13.8±13.7 ppb before the ADS and 20.3±19.0 ppb after the ADS, with no significant difference. There was also no significant association of PEF with ADS exposure. However, the increase of FeNO after ADS exposure was proportional to the decrease of PEF (R=-0.78, P<0.0001). These results suggest that airway inflammation aggravated by ADS exposure may induce a decrease in pulmonary function in some adult patients with asthma.

Genetics of psychosis of Alzheimer disease.

PubMed

Shah, Chintan; DeMichele-Sweet, Mary Ann A; Sweet, Robert A

2017-01-01

Psychotic symptoms, comprised of delusions and hallucinations, occur in about half of individuals with Alzheimer disease (AD with psychosis, AD+P). These individuals have greater agitation, aggression, depression, functional impairment, and mortality than individuals without psychosis (AD-P). Although the exact etiopathogenesis of AD+P is unclear, the rapidly developing field of genomics continues to expand our understanding of this disease. Several independent studies have demonstrated familial aggregation and heritability of AD+P. Linkage studies have been suggestive of loci on several chromosomes associated with AD+P. Association studies examining apolipoprotein E gene, the best established genetic risk factor for late-onset AD, did not find any significant association of this gene with AD+P. Other candidate gene studies focusing on monoamine neurotransmitter systems have yielded equivocal results. A genome-wide association study and studies examining copy number variations recently have detected suggestive associations, but have been underpowered. Approaches to increase sizes of AD+P samples for genome wide association studies are discussed. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genetics of Psychosis in Alzheimer Disease.

PubMed

DeMichele-Sweet, Mary Ann A; Sweet, Robert A

2014-03-01

Psychosis occurs in approximately half of patients with Alzheimer disease (AD with psychosis, AD+P). AD+P patients have more rapid cognitive decline, greater behavioral symptoms, and higher mortality than do AD patients without psychosis. Studies in three independent cohorts have shown that psychosis in AD aggregates in families, with estimated heritability of 29.5 - 60.8%. These findings have motivated studies to investigate and uncover the genes responsible for the development of psychosis, with the ultimate goal of identifying potential biologic mechanisms that may serve as leads to specific therapies. Linkage analyses have implicated loci on chromosomes 2, 6, 7, 8, 15, and 21 with AD+P. Association studies of APOE do not support it as a risk gene for psychosis in AD. No other candidate genes, such as neurodegenerative and monoamine genes, show conclusive evidence of association with AD+P. However, a recent genome-side association study has produced some promising leads, including among them genes that have been associated with schizophrenia. This review summarizes the current knowledge of the genetic basis of AD+P.

A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease.

PubMed

Huang, Kuan-Lin; Marcora, Edoardo; Pimenova, Anna A; Di Narzo, Antonio F; Kapoor, Manav; Jin, Sheng Chih; Harari, Oscar; Bertelsen, Sarah; Fairfax, Benjamin P; Czajkowski, Jake; Chouraki, Vincent; Grenier-Boley, Benjamin; Bellenguez, Céline; Deming, Yuetiva; McKenzie, Andrew; Raj, Towfique; Renton, Alan E; Budde, John; Smith, Albert; Fitzpatrick, Annette; Bis, Joshua C; DeStefano, Anita; Adams, Hieab H H; Ikram, M Arfan; van der Lee, Sven; Del-Aguila, Jorge L; Fernandez, Maria Victoria; Ibañez, Laura; Sims, Rebecca; Escott-Price, Valentina; Mayeux, Richard; Haines, Jonathan L; Farrer, Lindsay A; Pericak-Vance, Margaret A; Lambert, Jean Charles; van Duijn, Cornelia; Launer, Lenore; Seshadri, Sudha; Williams, Julie; Amouyel, Philippe; Schellenberg, Gerard D; Zhang, Bin; Borecki, Ingrid; Kauwe, John S K; Cruchaga, Carlos; Hao, Ke; Goate, Alison M

2017-08-01

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function.

Automatic Prediction of Conversion from Mild Cognitive Impairment to Probable Alzheimer’s Disease using Structural Magnetic Resonance Imaging

PubMed Central

Nho, Kwangsik; Shen, Li; Kim, Sungeun; Risacher, Shannon L.; West, John D.; Foroud, Tatiana; Jack, Clifford R.; Weiner, Michael W.; Saykin, Andrew J.

2010-01-01

Mild Cognitive Impairment (MCI) is thought to be a precursor to the development of early Alzheimer’s disease (AD). For early diagnosis of AD, the development of a model that is able to predict the conversion of amnestic MCI to AD is challenging. Using automatic whole-brain MRI analysis techniques and pattern classification methods, we developed a model to differentiate AD from healthy controls (HC), and then applied it to the prediction of MCI conversion to AD. Classification was performed using support vector machines (SVMs) together with a SVM-based feature selection method, which selected a set of most discriminating predictors for optimizing prediction accuracy. We obtained 90.5% cross-validation accuracy for classifying AD and HC, and 72.3% accuracy for predicting MCI conversion to AD. These analyses suggest that a classifier trained to separate HC vs. AD has substantial potential for predicting MCI conversion to AD. PMID:21347037

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens.

PubMed

Tatsis, Nia; Lasaro, Marcio O; Lin, Shih-Wen; Haut, Larissa H; Xiang, Zhi Q; Zhou, Dongming; Dimenna, Lauren; Li, Hua; Bian, Ang; Abdulla, Sarah; Li, Yan; Giles-Davis, Wynetta; Engram, Jessica; Ratcliffe, Sarah J; Silvestri, Guido; Ertl, Hildegund C; Betts, Michael R

2009-05-15

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.

Aspects of AdS/CFT: Conformal Deformations and the Goldstone Equivalence Theorem

NASA Astrophysics Data System (ADS)

Cantrell, Sean Andrew

The AdS/CFT correspondence provides a map from the states of theories situated in AdSd+1 to those in dual conformal theories in a d-dimensional space. The correspondence can be used to establish certain universal properties of some theories in one space by examining the behave of general objects in the other. In this thesis, we develop various formal aspects of AdS/CFT. Conformal deformations manifest in the AdS/CFT correspondence as boundary conditions on the AdS field. Heretofore, double-trace deformations have been the primary focus in this context. To better understand multitrace deformations, we revisit the relationship between the generating AdS partition function for a free bulk theory and the boundary CFT partition function subject to arbitrary conformal deformations. The procedure leads us to a formalism that constructs bulk fields from boundary operators. We independently replicate the holographic RG flow narrative to go on to interpret the brane used to regulate the AdS theory as a renormalization scale. The scale-dependence of the dilatation spectrum of a boundary theory in the presence of general deformations can be thus understood on the AdS side using this formalism. The Goldstone equivalence theorem allows one to relate scattering amplitudes of massive gauge fields to those of scalar fields in the limit of large scattering energies. We generalize this theorem under the framework of the AdS/CFT correspondence. First, we obtain an expression of the equivalence theorem in terms of correlation functions of creation and annihilation operators by using an AdS wave function approach to the AdS/CFT dictionary. It is shown that the divergence of the non-conserved conformal current dual to the bulk gauge field is approximately primary when computing correlators for theories in which the masses of all the exchanged particles are sufficiently large. The results are then generalized to higher spin fields. We then go on to generalize the theorem using conformal blocks in two and four-dimensional CFTs. We show that when the scaling dimensions of the exchanged operators are large compared to both their spins and the dimension of the current, the conformal blocks satisfy an equivalence theorem.

Human adenovirus serotypes 3 and 5 bind to two different cellular receptors via the fiber head domain.

PubMed Central

Stevenson, S C; Rollence, M; White, B; Weaver, L; McClelland, A

1995-01-01

The adenovirus fiber protein is responsible for attachment of the virion to cell surface receptors. The identity of the cellular receptor which mediates binding is unknown, although there is evidence suggesting that two distinct adenovirus receptors interact with the group C (adenovirus type 5 [Ad5]) and the group B (Ad3) adenoviruses. In order to define the determinants of adenovirus receptor specificity, we have carried out a series of competition binding experiments using recombinant native fiber polypeptides from Ad5 and Ad3 and chimeric fiber proteins in which the head domains of Ad5 and Ad3 were exchanged. Specific binding of fiber to HeLa cell receptors was assessed with radiolabeled protein synthesized in vitro, and by competition analysis with baculovirus-expressed fiber protein. Fiber produced in vitro was found as both monomer and trimer, but only the assembled trimers had receptor binding activity. Competition data support the conclusion that Ad5 and Ad3 interact with different cellular receptors. The Ad5 receptor distribution on several cell lines was assessed with a fiber binding flow cytometric assay. HeLa cells were found to express high levels of receptor, while CHO and human diploid fibroblasts did not. A chimeric fiber containing the Ad5 fiber head domain blocked the binding of Ad5 fiber but not Ad3 fiber. Similarly, a chimeric fiber containing the Ad3 fiber head blocked the binding of labeled Ad3 fiber but not Ad5 fiber. In addition, the isolated Ad3 fiber head domain competed effectively with labeled Ad3 fiber for binding to HeLa cell receptors. These results demonstrate that the determinants of receptor binding are located in the head domain of the fiber and that the isolated head domain is capable of trimerization and binding to cellular receptors. Our results also show that it is possible to change the receptor specificity of the fiber protein by manipulation of sequences contained in the head domain. Modification or replacement of the fiber head domain with novel ligands may permit adenovirus vectors with new receptor specificities which could be useful for targeted gene delivery in vivo to be engineered. PMID:7707507

Factors that influence advance directives completion amongst terminally ill patients at a tertiary hospital in Kenya.

PubMed

Omondi, Stephen; Weru, John; Shaikh, Asim Jamal; Yonga, Gerald

2017-01-25

An advance directive (AD) is a written or verbal document that legally stipulates a person's health care preference while they are competent to make decisions for themselves and is used to guide decisions on life-sustaining treatment in the event that they become incapacitated. AD can take the form of a living will, a limitation of care document, a do-not-resuscitate order, or an appointment of a surrogate by durable power of attorney. The completion rate of AD varies from region to region, and it is influenced by multiple factors. The objectives of this study were to determine the proportion of terminally ill patients with AD and to identify the factors that influence the completion of AD amongst terminally ill patients at a tertiary hospital in Kenya. The study was a retrospective survey. All available records of terminally ill patients seen at Aga Khan University Hospital, Nairobi, between July 2010 and December 2015, and that met the inclusion criteria were included in the study. In total, 216 records of terminally ill patients were analyzed: 89 records were of patients that had AD and 127 records were of patients that did not have AD. The proportion of terminally ill patients that had completed AD was 41.2%. The factors that were associated with the completion of AD on bivariate analysis were history of ICU admission, history of endotracheal intubation, functional status of the patient, the medical specialty taking care of the patient, patient's caregiver discussing the AD with the patient, and a palliative specialist review. On multivariate regression analysis, discussion of AD with a caregiver and patient's functional impairment were the factors with statistically significant association with completion of AD. The proportion of terminally ill patients that had AD in their medical records was significant. However, most terminally ill patients did not have AD. Our data, perhaps the first on the subject in East Africa, suggest that most of the factors associated with AD completion mirrored those seen in other regions of the world. Discussion between patient and their physician and patient's functional impairment were the factors independently associated with completion of AD. Therefore, physicians need to be aware of the importance of discussions of AD with their patients.

Stability of warped AdS3 vacua of topologically massive gravity

NASA Astrophysics Data System (ADS)

Anninos, Dionysios; Esole, Mboyo; Guica, Monica

2009-10-01

AdS3 vacua of topologically massive gravity (TMG) have been shown to be perturbatively unstable for all values of the coupling constant except the chiral point μl = 1. We study the possibility that the warped vacua of TMG, which exist for all values of μ, are stable under linearized perturbations. In this paper, we show that spacelike warped AdS3 vacua with Compère-Detournay boundary conditions are indeed stable in the range μl>3. This is precisely the range in which black hole solutions arise as discrete identifications of the warped AdS3 vacuum. The situation somewhat resembles chiral gravity: although negative energy modes do exist, they are all excluded by the boundary conditions, and the perturbative spectrum solely consists of boundary (pure large gauge) gravitons.

A 900-year pollen-inferred temperature and effective moisture record from varved Lake Mina, west-central Minnesota, USA

NASA Astrophysics Data System (ADS)

St. Jacques, Jeannine-Marie; Cumming, Brian F.; Smol, John P.

2008-04-01

Drought is endemic to the North American Great Plains, causing severe economic consequences. However, instrumental climate data only exist from ca AD 1890, and limited tree-ring, paleolimnological, archeological and eolian records document the last two millennia. To address this lack of monitoring and paleoclimatic data, the pollen preserved in the varved sediments of Lake Mina, Minnesota, on the northeastern border of the Great Plains, were analyzed. May and February mean monthly temperatures and "annual precipitation minus potential evapotranspiration" were reconstructed at a 4-year resolution using a pre-settlement pollen-climate calibration set. The period of the so-called Little Ice Age (LIA) (AD 1500-1870) was colder than the Medieval Climate Anomaly (MCA) (AD 1100-1500) in west-central Minnesota. Winter temperatures in the LIA declined more than summer ones. The pollen record suggests that the LIA occurred in three phases: an initial cold phase from AD 1505 to AD 1575, a warmer phase, and then a very cold phase from AD 1625 to AD 1775. There were severe droughts detected in the Lake Mina record from AD 1660 to AD 1710 and AD 1300 to AD 1400, suggesting that high-resolution pollen records can detect events previously defined from the tree-ring records. This latter century-scale drought is concurrent with the widely reported "AD 1250-1400 mega-drought", which exceeds the severity of 20th century droughts.

Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein.

PubMed

Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro; Ogihara, Takuo

2016-08-05

P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. Copyright © 2016 Elsevier Inc. All rights reserved.

C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease

PubMed Central

Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; DeGrush, Elizabeth; Reilly, Lindsey A.

2012-01-01

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency ERP component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage Alzheimer's disease (AD). Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (Controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using Principal Components Analysis. C145 amplitudes and spatial distributions were compared among Controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, Control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals. PMID:22886016

Advancing Alzheimer's research: A review of big data promises.

PubMed

Zhang, Rui; Simon, Gyorgy; Yu, Fang

2017-10-01

To review the current state of science using big data to advance Alzheimer's disease (AD) research and practice. In particular, we analyzed the types of research foci addressed, corresponding methods employed and study findings reported using big data in AD. Systematic review was conducted for articles published in PubMed from January 1, 2010 through December 31, 2015. Keywords with AD and big data analytics were used for literature retrieval. Articles were reviewed and included if they met the eligibility criteria. Thirty-eight articles were included in this review. They can be categorized into seven research foci: diagnosing AD or mild cognitive impairment (MCI) (n=10), predicting MCI to AD conversion (n=13), stratifying risks for AD (n=5), mining the literature for knowledge discovery (n=4), predicting AD progression (n=2), describing clinical care for persons with AD (n=3), and understanding the relationship between cognition and AD (n=3). The most commonly used datasets are AD Neuroimaging Initiative (ADNI) (n=16), electronic health records (EHR) (n=11), MEDLINE (n=3), and other research datasets (n=8). Logistic regression (n=9) and support vector machine (n=8) are the most used methods for data analysis. Big data are increasingly used to address AD-related research questions. While existing research datasets are frequently used, other datasets such as EHR data provide a unique, yet under-utilized opportunity for advancing AD research. Copyright © 2017 Elsevier B.V. All rights reserved.

Added Sugars Intake Across the Distribution of US Children and Adult Consumers: 1977-2012.

PubMed

Powell, Elyse S; Smith-Taillie, Lindsey P; Popkin, Barry M

2016-10-01

Public health organizations in the United States have recently increased focus on reducing population consumption of added sugars. The objective of this study is to provide in-depth information on national trends in added sugars consumption and to examine both the mean and distribution of added sugars intake from 1977 to 2012. We conducted a descriptive study using six cross-sectional nationally representative surveys of food intake in the United States: the 1977-1978 National Food Consumption Survey (n=29,668), the 1989-1991 Continuing Survey of Food Intake by Individuals (n=14,827), the 1994-1998 Continuing Survey of Food Intake by Individuals (n=19,027), the 2003-2004 National Health and Nutrition Examination Survey (NHANES; n=8,273), the 2009-2010 NHANES (n=9,042), and the 2011-2012 NHANES (n=16,451). We examined the key dependent variables, calories from added sugars and percentage of total energy intake from added sugars, at the mean and by quintiles of added sugars consumption for children (2 to 18 years) and adults (19 years and older) across the survey years. We also examined trends in added sugars intakes from foods and beverages. We used ordinary least squares regression to examine linear trends between survey years and multinomial logistic regressions to examine sociodemographic characteristics by quintile of added sugars consumption. We adjusted estimates by race, income, sex, and education. The US mean adjusted intake of added sugars remains high. In 2011-2012, children and adults consumed 326 kcal/day and 308 kcal/day, respectively, of added sugars, or 14% and 17%, respectively, of total their energy. For both children and adults, there was a considerable increase in calories from added sugars from 1977 to 2003, followed by a substantial decline from 2003 to 2012. There was no decline in the percentage of total energy intake from added sugars from 2003 to 2012. Changes over time were consistent across each quintile of added sugars consumption. The highest quintile of consumption was more likely to be male and in children was more likely to be non-Hispanic white. Despite a decline in consumption of added sugars since 2003 in the United States, mean adjusted added sugars intakes continue to be above the recommended level of 10% of the total energy intake. Changes in added sugars consumption from 1977 through 2012 occurred evenly across the distribution of added sugars intakes. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice

PubMed Central

2014-01-01

Introduction Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. Methods The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse’s back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. Results We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15–17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs’ migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Conclusions Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans. PMID:24423450

Added sugars intake across the distribution of US children and adult consumers: 1977–2012

PubMed Central

Powell, Elyse S.; Smith-Taillie, Lindsey P.

2016-01-01

Background Public health organizations in the United States (US) have recently increased focus on reducing population consumption of added sugars. Objective The objective of this study is to provide in-depth information on national trends in added sugars consumption and examine both the mean and the distribution of added sugars intake from 1977 to 2012. Design We conducted a descriptive study using 6 cross-sectional nationally representative surveys of food intake in the United States: the 1977–1978 National Food Consumption Survey (NFCS; n = 29,668), the 1989–1991 Continuing Survey of Food Intake by Individuals (CSFII; n = 14,827), the 1994–1998 CSFII (n = 19,027), the 2003–2004 National Health and Nutrition Examination Survey (NHANES; n = 8,273), the 2009–2010 NHANES (n = 9,042), and the 2011–2012 NHANES (n = 16,451). Analysis We examined the key dependent variables calories from added sugars and percentage of total energy intake from added sugars at the mean and by quintiles of added sugars consumption for children (2–18 years) and adults (≥ 19 years) across the survey years. We also examined trends in added sugars intakes from foods and beverages. We used ordinary least squares regression to examine linear trends between survey years and multinomial logistic regressions to examine sociodemographics by quintile of added sugars consumption. We adjusted estimates by gender, race, income, and education. Results The US mean adjusted intake of added sugars remains high. In 2011–2012 children and adults consumed 326 kilocalories/day and 308 kilocalories/day, respectively, of added sugars, or 14% and 17%, respectively, of total their energy. For both children and adults, there was a significant increase in calories from added sugars from 1977 to 2003, followed by a significant decline from 2003 to 2012. There was no decline in the percentage of the total energy intake from added sugars from 2003 to 2012. Changes over time were consistent across each quintile of added sugars consumption. The highest quintile of consumption was more likely to be male and in children was more likely to be non-Hispanic white. Conclusion Despite a decline in consumption of added sugars since 2003 in the United States, mean adjusted added sugars intakes continue to be above the recommended level of 10% of the total energy intake. Changes in added sugars consumption from 1977 through 2012 occurred evenly across the distribution of added sugars intakes. PMID:27492320

Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice.

PubMed

Navone, Stefania Elena; Pascucci, Luisa; Dossena, Marta; Ferri, Anna; Invernici, Gloria; Acerbi, Francesco; Cristini, Silvia; Bedini, Gloria; Tosetti, Valentina; Ceserani, Valentina; Bonomi, Arianna; Pessina, Augusto; Freddi, Giuliano; Alessandrino, Antonio; Ceccarelli, Piero; Campanella, Rolando; Marfia, Giovanni; Alessandri, Giulio; Parati, Eugenio Agostino

2014-01-14

Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse's back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15-17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs' migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans.

The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy.

PubMed

Yu, Jin-Tai; Tan, Lan

2012-04-01

Genetic variation in clusterin gene, also known as apolipoprotein J, has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, and plasma clusterin levels are associated with brain atrophy, baseline prevalence and severity, and rapid clinical progression in patients with AD, highlighting the importance of clusterin in AD pathogenesis. Emerging data suggest that clusterin contributes to AD through various pathways, including amyloid-β aggregation and clearance, lipid metabolism, neuroinflammation, and neuronal cell cycle control and apoptosis. Moreover, epigenetic regulation of the clusterin expression also seems to play an important role in the pathogenesis of AD. Emerging knowledge of the contribution of clusterin to the pathogenesis of AD presents new opportunities for AD therapy.

Acute effect of infection by adipogenic human adenovirus Ad36

PubMed Central

Pasarica, Magdalena; Loiler, Scott; Dhurandhar, Nikhil V.

2009-01-01

Human adenovirus Ad36 is causally and correlatively associated in animals and humans, respectively, with increased adiposity and altered metabolic profile. We inoculated rats with Ad36, UV-inactivated Ad36 or mock-infected. Four-days later, Ad36-infected rats showed 23% greater epididymal fat pad weight and viral mRNA, the viral DNA could also be detected in tissues viz. the liver, brain, and adipose tissue. Intranasal or intra-peritoneal routes of viral inoculations showed similar tissue affinity. Serum cytokine response was remarkably down regulated. Ad36 acutely suppresses systemic immune response and spreads widely. This information will help to determine Ad36 tissue tropism and its metabolic consequences. PMID:18830560

Novel strategies for Alzheimer's disease treatment: An overview of anti-amyloid beta monoclonal antibodies.

PubMed

Rygiel, Katarzyna

2016-01-01

Alzheimer's disease (AD) is a multifactorial, progressive neurodegenerative disorder with a poor prognosis, and thus, novel therapies for AD are certainly needed in a growing population of elderly patients or asymptomatic individuals, who are at risk for AD, worldwide. It has been established that some AD biomarkers such as amyloid-beta load in the brain, precede the onset of the disease, by approximately 20 years. Therefore, the therapy to prevent or effectively treat AD has to be initiated before the emergence of symptoms. A goal of this review is to present the results of recent clinical trials on monoclonal antibodies against amyloid beta, used for the treatment of AD and also to address some of the current challenges and emerging strategies to prevent AD. In recent trials, a monoclonal antibody, i.e. solanezumab has shown some beneficial cognitive effects among mild AD patients. Ongoing studies with gantenerumab and crenezumab will examine when exactly the AD treatment, aimed at modifying the disease course has to be started. This review was based on Medline database search for trials on passive anti-AD immunotherapy, for which the main timeframe was set from 2012 to 2015.

Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease.

PubMed

Pérez, María J; Ponce, Daniela P; Osorio-Fuentealba, Cesar; Behrens, Maria I; Quintanilla, Rodrigo A

2017-01-01

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients.

Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease

PubMed Central

Pérez, María J.; Ponce, Daniela P.; Osorio-Fuentealba, Cesar; Behrens, Maria I.; Quintanilla, Rodrigo A.

2017-01-01

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients. PMID:29056898

Structure of a Reptilian Adenovirus Reveals a Phage Tailspike Fold Stabilizing a Vertebrate Virus Capsid.

PubMed

Menéndez-Conejero, Rosa; Nguyen, Thanh H; Singh, Abhimanyu K; Condezo, Gabriela N; Marschang, Rachel E; van Raaij, Mark J; San Martín, Carmen

2017-10-03

Although non-human adenoviruses (AdVs) might offer solutions to problems posed by human AdVs as therapeutic vectors, little is known about their basic biology. In particular, there are no structural studies on the complete virion of any AdV with a non-mammalian host. We combine mass spectrometry, cryo-electron microscopy, and protein crystallography to characterize the composition and structure of a snake AdV (SnAdV-1, Atadenovirus genus). SnAdV-1 particles contain the genus-specific proteins LH3, p32k, and LH2, a previously unrecognized structural component. Remarkably, the cementing protein LH3 has a trimeric β helix fold typical of bacteriophage host attachment proteins. The organization of minor coat proteins differs from that in human AdVs, correlating with higher thermostability in SnAdV-1. These findings add a new piece to the intriguing puzzle of virus evolution, hint at the use of cell entry pathways different from those in human AdVs, and will help development of new, thermostable SnAdV-1-based vectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface.

PubMed

Warfield, Linda; Tuttle, Lisa M; Pacheco, Derek; Klevit, Rachel E; Hahn, Steven

2014-08-26

Although many transcription activators contact the same set of coactivator complexes, the mechanism and specificity of these interactions have been unclear. For example, do intrinsically disordered transcription activation domains (ADs) use sequence-specific motifs, or do ADs of seemingly different sequence have common properties that encode activation function? We find that the central activation domain (cAD) of the yeast activator Gcn4 functions through a short, conserved sequence-specific motif. Optimizing the residues surrounding this short motif by inserting additional hydrophobic residues creates very powerful ADs that bind the Mediator subunit Gal11/Med15 with high affinity via a "fuzzy" protein interface. In contrast to Gcn4, the activity of these synthetic ADs is not strongly dependent on any one residue of the AD, and this redundancy is similar to that of some natural ADs in which few if any sequence-specific residues have been identified. The additional hydrophobic residues in the synthetic ADs likely allow multiple faces of the AD helix to interact with the Gal11 activator-binding domain, effectively forming a fuzzier interface than that of the wild-type cAD.

Psychiatry outpatient visits by atopic dermatitis patients varying in the complexity of their prescriptions

PubMed Central

Shin, Jaeyong; Choi, Young; Park, Eun-Cheol; Lee, Kwang Hoon; Hwang, Seo Young; Oh, Sang Ho; Lee, Sang Gyu

2016-01-01

Abstract The uncomfortable symptoms of atopic dermatitis (AD) often trigger psychological stress. We investigated the association between AD severity and outpatient visits to psychiatrists using Korean National Health Insurance claims data from 2004 to 2013. This was a retrospective cohort analysis; we estimated hazard ratios (HRs). Of the 266,182 subjects, 18,290 (6.9%) had a history of visiting a psychiatrist, and 25,419 (9.5%) were diagnosed with AD. Compared with the subjects without AD, subjects with AD had a higher HR for visiting a psychiatrist (3.70, 95% confidence interval [CI]:48 3.43–3.98), and this significantly increased as the complexity of the AD medications increased. Subjects who received topical treatments plus a systematic steroid (HR: 4.88, 95% CI: 4.51–5.27) and those who received topical treatments plus a systematic steroid plus a systematic calcineurin inhibitor (HR: 9.56, 95% CI: 4.29–21.28) had higher HRs compared with those without AD. Severe AD patients exhibited greater psychological stress than those without AD or with mild AD symptoms. Moreover, medication diversity may represent an efficient and low-cost method by which to identify a vulnerable population. PMID:27930517

Mutation analysis of the chromosome 14q24.3 dihydrolipoyl succinyltransferase (DLST) gene in patients with early-onset Alzheimer disease.

PubMed

Cruts, M; Backhovens, H; Van Gassen, G; Theuns, J; Wang, S Y; Wehnert, A; van Duijn, C M; Karlsson, T; Hofman, A; Adolfsson, R

1995-10-13

Linkage analysis studies have indicated that the chromosome band 14q24.3 harbours a major gene for familial early-onset Alzheimer's disease (AD). Recently we localized the chromosome 14 AD gene (AD3) in the 6.4 cM interval between the markers D14S289 and D14S61. We mapped the gene encoding dihydrolipoyl succinyltransferase (DLST), the E2k component of human alpha-ketoglutarate dehydrogenase complex (KGDHC), in the AD3 candidate region using yeast artificial chromosomes (YACs). The DLST gene is a candidate for the AD3 gene since deficiencies in KGDHC activity have been observed in brain tissue and fibroblasts of AD patients. The 15 exons and the promoter region of the DLST gene were analysed for mutations in chromosome 14 linked AD cases and in two series of unrelated early-onset AD cases (onset age < 55 years). Sequence variations in intronic sequences (introns 3, 5 and 10) or silent mutations in exonic sequences (exons 8 and 14) were identified. However, no AD related mutations were observed, suggesting that the DLST gene is not the chromosome 14 AD3 gene.

High blood pressure, Alzheimer disease and antihypertensive treatment.

PubMed

Marfany, Agustí; Sierra, Cristina; Camafort, Miguel; Doménech, Mónica; Coca, Antonio

2018-03-01

Alzheimer's disease (AD), the most common form of dementia, is a complex disease, the mechanisms of which are poorly understood. AD represents 70% of all dementia cases, affecting up to 50% of elderly persons aged 85 or older, with functional dependence, poor quality of life, institutionalization and mortality. Advanced age is the main risk factor of AD, that is why population ageing, due to life expectancy improvements, increases AD incidence and prevalence, as well as the economic, social, and emotional costs associated with this illness. Existing anti-AD drugs present some limitations, as they target specific downstream neurochemical abnormalities while the upstream underlying pathology continues unchecked. Chronic hypertension has been suggested as one of the largest modifiable risk factors for developing AD. At least 25% of all adults and more than 50% of those over 60 years of age have hypertension. Epidemiological studies have shown that hypertension is a risk factor for dementia and AD, but the association is complex. Some studies have demonstrated that antihypertensive drugs can reduce the risk of AD. This review focuses on current knowledge about the relationship between chronic hypertension and AD as well as antihypertensive treatment effect on AD pathogenesis and its clinical outcomes.

Outpatient screening of Japanese children with epilepsy for attention-deficit/hyperactivity disorder (AD/HD).

PubMed

Tanabe, Takuya; Kashiwagi, Mitsuru; Shimakawa, Shuichi; Tamai, Hiroshi; Wakamiya, Eiji

2014-04-01

The significance of the Strengths and Difficulties Questionnaire (SDQ) score for AD/HD (attention-deficit/hyperactivity disorder) screening was assessed in Japanese epileptic children. Sixty-eight epileptic children were enrolled in this study. Parents were asked to fill out both the SDQ and AD/HD-rating scale (AD/HD-RS) simultaneously. The SDQ subscale of hyperactivity showed the highest score. The AD/HD-RS showed higher scores for both inattention and hyperactivity-impulsivity. Twenty-two (32.4%) of these subjects were diagnosed as having AD/HD. The SDQ subscale for hyperactivity showed 86.4% sensitivity and 95% specificity, respectively, for detection of AD/HD. All SDQ subscales correlated significantly with inattention and hyperactivity-impulsivity scores of the AD/HD-RS. The SDQ is a good screening tool which can contribute to the detection of AD/HD, not only of the hyperactive/impulsive but also the inattentive subtype. Furthermore, the SDQ can elucidate more complicated behavioral problems than the core symptoms of AD/HD that are not noticed in the epilepsy clinic. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Commercial complementary food consumption is prospectively associated with added sugar intake in childhood.

PubMed

Foterek, Kristina; Buyken, Anette E; Bolzenius, Katja; Hilbig, Annett; Nöthlings, Ute; Alexy, Ute

2016-06-01

Given that commercial complementary food (CF) can contain high levels of added sugar, a high consumption may predispose to a preference for sweet taste later in life. This study examined cross-sectional associations between commercial CF consumption and added sugar intake in infancy as well as its prospective relation to added sugar intake in pre-school and primary-school age children. In all, 288 children of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study with 3-d weighed dietary records at 0·5 and 0·75 (infancy), 3 and 4 (pre-school age) and 6 and 7 years of age (primary-school age) were included in this analysis. Individual commercial CF consumption as percentage of total commercial CF (%cCF) was averaged at 0·5 and 0·75 years. Individual total added sugar intake (g/d, energy percentage/d) was averaged for all three age groups. Multivariable logistic and linear regression models were used to analyse associations between %cCF and added sugar intake. In infancy, a higher %cCF was associated with odds for high added sugar intake from CF and for high total added sugar intake (>75th percentile, P<0·033). Prospectively, a higher %cCF was related to higher added sugar intake in both pre-school (P<0·041) and primary-school age children (P<0·039), although these associations were attenuated in models adjusting for added sugar intake in infancy. A higher %cCF in infancy may predispose to higher added sugar intake in later childhood by virtue of its added sugar content. Therefore, offering home-made CF or carefully chosen commercial CF without added sugar might be one strategy to reduce sugar intake in infancy and later on.

Reaction mechanism of CO oxidation on Cu2O(111): A density functional study

NASA Astrophysics Data System (ADS)

Sun, Bao-Zhen; Chen, Wen-Kai; Xu, Yi-Jun

2010-10-01

The possible reaction mechanisms for CO oxidation on the perfect Cu2O(111) surface have been investigated by performing periodic density functional theoretical calculations. We find that Cu2O(111) is able to facilitate the CO oxidation with different mechanisms. Four possible mechanisms are explored (denoted as MER1, MER2, MLH1, and MLH2, respectively): MER1 is CO(gas)+O2(ads)-->CO2(gas) MER2 is CO(gas)+O2(ads)-->CO3(ads)-->O(ads)+CO2(gas) MLH1 refers to CO(ads)+O2(ads)-->O(ads)+CO2(ads) and MLH2 refers to CO(ads)+O2(ads)-->OOCO(ads)-->O(ads)+CO2(ads). Our transition state calculations clearly reveal that MER1 and MLH2 are both viable; but MER1 mechanism preferentially operates, in which only a moderate energy barrier (60.22 kJ/mol) needs to be overcome. When CO oxidation takes place along MER2 path, it is facile for CO3 formation, but is difficult for its decomposition, thereby CO3 species can stably exist on Cu2O(111). Of course, the reaction of CO with lattice O of Cu2O(111) is also considered. However, the calculated barrier is 600.00 kJ/mol, which is too large to make the path feasible. So, we believe that on Cu2O(111), CO reacts with adsorbed O, rather than lattice O, to form CO2. This is different from the usual Mars-van Krevene mechanism. The present results enrich our understanding of the catalytic oxidation of CO by copper-based and metal-oxide catalysts.

Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase.

PubMed

Onuk, Emre; Badger, John; Wang, Yu Jing; Bardhan, Jaydeep; Chishti, Yasmin; Akcakaya, Murat; Brooks, Dana H; Erdogmus, Deniz; Minh, David D L; Makowski, Lee

2017-08-29

Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two states: an "open" conformation (apo) obtained in the absence of ligands and a "closed" conformation in which ligands are bound. Other AdK crystal structures suggest intermediate conformations that may lie on the transition pathway between these two states. To characterize the transition from open to closed states in solution, X-ray solution scattering data were collected from AdK in the apo form and with progressively increasing concentrations of five different ligands. Scattering data from apo AdK are consistent with scattering predicted from the crystal structure of AdK in the open conformation. In contrast, data from AdK samples saturated with Ap5A do not agree with that calculated from AdK in the closed conformation. Using cluster analysis of available structures, we selected representative structures in five conformational states: open, partially open, intermediate, partially closed, and closed. We used these structures to estimate the relative abundances of these states for each experimental condition. X-ray solution scattering data obtained from AdK with AMP are dominated by scattering from AdK in the open conformation. For AdK in the presence of high concentrations of ATP and ADP, the conformational ensemble shifts to a mixture of partially open and closed states. Even when AdK is saturated with Ap5A, a significant proportion of AdK remains in a partially open conformation. These results are consistent with an induced-fit model in which the transition of AdK from an open state to a closed state is initiated by ATP binding.

Content analysis of targeted food and beverage advertisements in a Chinese-American neighbourhood

PubMed Central

Bragg, Marie A; Pageot, Yrvane K; Hernández-Villarreal, Olivia; Kaplan, Sue A; Kwon, Simona C

2017-01-01

Objectives The current descriptive study aimed to: (i) quantify the number and type of advertisements (ads) located in a Chinese-American neighbourhood in a large, urban city; and (ii) catalogue the targeted marketing themes used in the food/beverage ads. Design Ten pairs of trained research assistants photographed all outdoor ads in a 0.6 mile2 (1.6 km2) area where more than 60.0 % of residents identify as Chinese American. We used content analysis to assess the marketing themes of ads, including references to: Asian cultures; health; various languages; children; food or beverage type (e.g. sugar-sweetened soda). Setting Lower East Side, a neighbourhood located in the borough of Manhattan in New York City, USA. Subjects Ads (n 1366) in the designated neighbourhood. Results Food/beverage ads were the largest ad category (29.7 %, n 407), followed by services (e.g. mobile phone services; 21.0 %, n 288). Sixty-seven per cent (66.9 %) of beverages featured were sugar-sweetened, and 50.8 % of food ads promoted fast food. Fifty-five per cent (54.9 %) of food/beverage ads targeted Asian Americans through language, ethnicity of person(s) in the ad or inclusion of culturally relevant images. Fifty per cent (50.2 %) of ads were associated with local/small brands. Conclusions Food/beverage marketing practices are known to promote unhealthy food and beverage products. Research shows that increased exposure leads to excessive short-term consumption among consumers and influences children’s food preferences and purchase requests. Given the frequency of racially targeted ads for unhealthy products in the current study and increasing rates of obesity-related diseases among Asian Americans, research and policies should address the implications of food and beverage ads on health. PMID:28587693

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease.

PubMed

Megna, Matteo; Patruno, Cataldo; Balato, Anna; Rongioletti, Franco; Stingeni, Luca; Balato, Nicola

2017-08-01

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which predominantly affects children. However, AD may persist until adulthood (persistent AD), or directly start in adults (adult-onset AD). AD often shows a non-flexural rash distribution, and atypical morphologic variants in adults and specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well as detailed data which can characterize persistent vs adult-onset subtype are scant. The aim of this study was to investigate on the main features of adult AD particularly highlighting differences between persistent vs adult-onset form. An Italian multicentre observational study was conducted between April 2015-July 2016 through a study-specific digital database. 253 adult AD patients were enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative pattern was the most frequent clinical presentation (74.3%). Flexural surface of upper limbs was most commonly involved (47.8%), followed by eyelid/periocular area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis (4.3%) were the most frequent comorbidities. A subgroup analysis between persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results only regarding AD severity (severe disease was more common in persistent group, p < 0.05), itch intensity (higher in adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p < 0.01). Adult AD showed uncommon features such as significant association with negative AD family history and lacking of association with systemic comorbidities respect to general population. No significant differences among persistent vs adult-onset subgroup were registered except for hypertension, itch intensity, and disease severity.

Functional connectivity increase in the default-mode network of patients with Alzheimer's disease after long-term treatment with Galantamine.

PubMed

Blautzik, Janusch; Keeser, Daniel; Paolini, Marco; Kirsch, Valerie; Berman, Albert; Coates, Ute; Reiser, Maximilian; Teipel, Stefan J; Meindl, Thomas

2016-03-01

Acetylcholinesterase inhibitors (AChEIs) are efficacious for the treatment of mild to moderate forms of Alzheimer's dementia (AD). Default-mode network (DMN) connectivity is considered to be early impaired in AD. Long-term effects of AChEIs on the DMN in AD have not yet been investigated. Twenty-eight AD patients and 11 age-matched healthy volunteers (HC) participated in the prospective study. AD patients were randomly assigned to either a pharmacotherapy arm (Galantamine, AD G) or to a placebo arm (AD P+G) for the period of 6 months followed by open-label Galantamine therapy from month 7-12. All subjects underwent neuropsychological testing, resting-state functional and structural MRI at baseline and after 12 months, AD patients additionally in between after 6 months. Thirteen AD patients completed the treatment trial and underwent all functional MRI follow-up sequences of good quality. Functional connectivity significantly increased within the AD G group in the posterior cingulate cortex and in the Precuneus between baseline and 12 months follow-up (pcorr<0.05). Between-group analyses demonstrated that functional connectivity in the AD G group significantly increased in the posterior cingulate cortex as well as in the Precuneus compared to the HC group and in the anteromedial aspect of the temporal lobes compared to the AD P+G group, respectively, at 12 months follow-up (pcorr<0.05). Cognitive performance remained stable within groups over time indicating that resting-state fMRI may be sensitive for the detection of pharmacologically induced effects on brain function of AD patients. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

PubMed Central

Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

2015-01-01

Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

Content analysis of targeted food and beverage advertisements in a Chinese-American neighbourhood.

PubMed

Bragg, Marie A; Pageot, Yrvane K; Hernández-Villarreal, Olivia; Kaplan, Sue A; Kwon, Simona C

2017-08-01

The current descriptive study aimed to: (i) quantify the number and type of advertisements (ads) located in a Chinese-American neighbourhood in a large, urban city; and (ii) catalogue the targeted marketing themes used in the food/beverage ads. Ten pairs of trained research assistants photographed all outdoor ads in a 0·6 mile2 (1·6 km2) area where more than 60·0 % of residents identify as Chinese American. We used content analysis to assess the marketing themes of ads, including references to: Asian cultures; health; various languages; children; food or beverage type (e.g. sugar-sweetened soda). Lower East Side, a neighbourhood located in the borough of Manhattan in New York City, USA. Ads (n 1366) in the designated neighbourhood. Food/beverage ads were the largest ad category (29·7 %, n 407), followed by services (e.g. mobile phone services; 21·0 %, n 288). Sixty-seven per cent (66·9 %) of beverages featured were sugar-sweetened, and 50·8 % of food ads promoted fast food. Fifty-five per cent (54·9 %) of food/beverage ads targeted Asian Americans through language, ethnicity of person(s) in the ad or inclusion of culturally relevant images. Fifty per cent (50·2 %) of ads were associated with local/small brands. Food/beverage marketing practices are known to promote unhealthy food and beverage products. Research shows that increased exposure leads to excessive short-term consumption among consumers and influences children's food preferences and purchase requests. Given the frequency of racially targeted ads for unhealthy products in the current study and increasing rates of obesity-related diseases among Asian Americans, research and policies should address the implications of food and beverage ads on health.

Impact of an automated dispensing system in outpatient pharmacies.

PubMed

Humphries, Tammy L; Delate, Thomas; Helling, Dennis K; Richardson, Bruce

2008-01-01

To evaluate the impact of an automated dispensing system (ADS) on pharmacy staff work activities and job satisfaction. Cross-sectional, retrospective study. Kaiser Permanente Colorado (KPCO) outpatient pharmacies in September 2005. Pharmacists and technicians from 18 outpatient pharmacies. All KPCO outpatient pharmacists (n = 136) and technicians (n = 160) were surveyed regarding demographics and work activities and pharmacist job satisfaction. Work activities and job satisfaction were compared between pharmacies with and without ADS. Historical prescription purchase records from ADS pharmacies were assessed for pre-ADS to post-ADS changes in productivity. Self-reported pharmacy staff work activities and pharmacist job satisfaction. Pharmacists who responded to the demographic questionnaire (n = 74) were primarily women (60%), had a bachelor's degree in pharmacy (68%), and had been in practice for 10 years or more (53%). Responding technicians (n = 72) were predominantly women (80%) with no postsecondary degree (90%) and fewer than 10 years (68%) in practice. Pharmacists in ADS pharmacies who responded to the work activities questionnaire (n = 50) reported equivalent mean hours spent in patient care activities and filling medication orders compared with non-ADS pharmacists (n = 33; P > 0.05). Similarly, technicians in ADS pharmacies who responded to the work activities questionnaire (n = 64) reported equivalent mean hours spent in filling medication orders compared with non-ADS technicians (n = 38; P > 0.05). An equivalent proportion of ADS pharmacists reported satisfaction with their current job compared with non-ADS pharmacies (P > 0.05). Mean productivity did not increase appreciably after automation (P >0.05). By itself, installing an ADS does not appear to shift pharmacist work activities from dispensing to patient counseling or to increase job satisfaction. Shifting pharmacist work activities from dispensing to counseling and monitoring drug therapy outcomes may be warranted in ADS pharmacies.

Short-fiber protein of ad40 confers enteric tropism and protection against acidic gastrointestinal conditions.

PubMed

Rodríguez, Ester; Romero, Carolina; Río, Adolfo; Miralles, Marta; Raventós, Aida; Planells, Laura; Burgueño, Joan F; Hamada, Hirofumi; Perales, Jose Carlos; Bosch, Assumpció; Gassull, Miguel Angel; Fernández, Ester; Chillon, Miguel

2013-08-01

The lack of vectors for selective gene delivery to the intestine has hampered the development of gene therapy strategies for intestinal diseases. We hypothesized that chimeric adenoviruses of Ad5 (species C) displaying proteins of the naturally enteric Ad40 (species F) might hold the intestinal tropism of the species F and thus be useful for gene delivery to the intestine. As oral-fecal dissemination of enteric adenovirus must withstand the conditions encountered in the gastrointestinal tract, we studied the resistance of chimeric Ad5 carrying the short-fiber protein of Ad40 to acid milieu and proteases and found that the Ad40 short fiber confers resistance to inactivation in acidic conditions and that AdF/40S was further activated upon exposure to low pH. In contrast, the chimeric AdF/40S exhibited only a slightly higher protease resistance compared with Ad5 to proteases present in simulated gastric juice. Then, the biodistribution of different chimeric adenoviruses by oral, rectal, and intravenous routes was tested. Expression of reporter β-galactosidase was measured in extracts of 15 different organs 3 days after administration. Our results indicate that among the chimeric viruses, only intrarectally given AdF/40S infected the colon (preferentially enteroendocrine cells and macrophages) and to a lesser extent, the small intestine, whereas Ad5 infectivity was very poor in all tissues. Additional in vitro experiments showed improved infectivity of AdF/40S also in different human epithelial cell lines. Therefore, our results point at the chimeric adenovirus AdF/40S as an interesting vector for selective gene delivery to treat intestinal diseases.

Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.

PubMed

Hodgson, Susanne H; Ewer, Katie J; Bliss, Carly M; Edwards, Nick J; Rampling, Thomas; Anagnostou, Nicholas A; de Barra, Eoghan; Havelock, Tom; Bowyer, Georgina; Poulton, Ian D; de Cassan, Simone; Longley, Rhea; Illingworth, Joseph J; Douglas, Alexander D; Mange, Pooja B; Collins, Katharine A; Roberts, Rachel; Gerry, Stephen; Berrie, Eleanor; Moyle, Sarah; Colloca, Stefano; Cortese, Riccardo; Sinden, Robert E; Gilbert, Sarah C; Bejon, Philip; Lawrie, Alison M; Nicosia, Alfredo; Faust, Saul N; Hill, Adrian V S

2015-04-01

Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy. We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%-79%, compared with 79%-84% for ChAd63-MVA ME-TRAP. ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development. NCT01623557. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Combined Gene Therapy Using AdsVEGFR2 and AdsTie2 With Chemotherapy Reduces the Growth of Human Ovarian Cancer and Formation of Ascites in Mice.

PubMed

Tuppurainen, Laura; Sallinen, Hanna; Karvonen, Anni; Valkonen, Elina; Laakso, Hanne; Liimatainen, Timo; Hytönen, Elisa; Hämäläinen, Kirsi; Kosma, Veli-Matti; Anttila, Maarit; Ylä-Herttuala, Seppo

2017-06-01

Ovarian cancer is highly dependent on tumor microvessels and angiogenesis regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) and angiopoietins (Ang) and their Tie receptors. We studied the efficacy of adenoviral (Ad) gene therapy with soluble VEGFR2 and Tie2 combined with paclitaxel and carboplatin for the treatment of ovarian cancer. An intraperitoneal human ovarian cancer xenograft model in nude mice (n = 44) was used in this study. Gene therapy was given intravenously when the presence of sizable tumors was confirmed in magnetic resonance imaging. The study groups were as follows: AdCMV as a control (group I), AdCMV with chemotherapy (group II), AdsVEGFR2 and AdsTie2 (group III), and AdsVEGFR2 and AdsTie2 with chemotherapy (group IV). Antitumor effectiveness was assessed by overall tumor growth, ascites, immunohistochemistry, microvessel density, and sequential magnetic resonance imaging analyses. AdsVEGFR2 and AdsTie2 gene therapy (group III) significantly reduced tumor weights as compared with group II (P = 0.007). Accumulation of ascites was significantly reduced when the mice were treated with AdsVEGFR2 and AdsTie2 gene therapy or with combined gene therapy and chemotherapy as compared with controls (P = 0.029 and P = 0.010, respectively). Vascular endothelial growth factor and Ang2 levels in ascites fluid were elevated after the gene therapy. Combined inhibition of VEGF/VEGFR2 and Ang/Tie2 pathways provided efficient therapy for ovarian cancer in mice. In addition, antiangiogenic gene therapy has potential as a treatment for the accumulation of ascites.

INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies

PubMed Central

Ying, B; Toth, K; Spencer, JF; Meyer, J; Tollefson, AE; Patra, D; Dhar, D; Shashkova, EV; Kuppuswamy, M; Doronin, K; Thomas, MA; Zumstein, LA; Wold, WSM; Lichtenstein, DL

2012-01-01

Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors. PMID:19197322

Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome

PubMed Central

Tierney, Michael; Wassermann, Eric M.; Spina, Salvatore; Oblak, Adrian L.; Ghetti, Bernardino; Grafman, Jordan; Huey, Edward

2014-01-01

Objective: To use the Visual Object and Space Perception Battery (VOSP) to distinguish Alzheimer disease (AD) from non-AD pathology in corticobasal syndrome (CBS). Methods: This clinicopathologic study assessed 36 patients with CBS on the VOSP. All were autopsied. The primary dependent variable was a binary pathologic outcome: patients with CBS who had primary pathologic diagnosis of AD (CBS-AD, n = 10) vs patients with CBS without primary pathologic diagnosis of AD (CBS-nonAD, n = 26). We also determined sensitivity and specificity of individual VOSP subtests. Results: Patients with CBS-AD had younger onset (54.5 vs 63.6 years, p = 0.001) and lower memory scores on the Mattis Dementia Rating Scale–2 (16 vs 22 points, p = 0.003). Failure on the VOSP subtests Incomplete Letters (odds ratio [OR] 11.5, p = 0.006), Position Discrimination (OR 10.86, p = 0.008), Number Location (OR 12.27, p = 0.026), and Cube Analysis (OR 45.71 p = 0.0001) had significantly greater odds of CBS-AD than CBS-nonAD. These associations remained when adjusting for total Mattis Dementia Rating score, disease laterality, education, age, and sex. Receiver operating characteristic curves demonstrated significant accuracy for Incomplete Letters and all VOSP spatial subtests, with Cube Analysis performing best (area under the curve 0.91, p = 0.0004). Conclusions: In patients with CBS, failure on specific VOSP subtests is associated with greater odds of having underlying AD. There may be preferential involvement of the dorsal stream in CBS-AD. Classification of evidence: This study provides Class II evidence that some subtests of the VOSP accurately distinguish patients with CBS-AD from those without AD pathology (e.g., Cube Analysis sensitivity 100%, specificity 77%). PMID:24991033

Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis.

PubMed

Mori, T; Ishida, K; Mukumoto, S; Yamada, Y; Imokawa, G; Kabashima, K; Kobayashi, M; Bito, T; Nakamura, M; Ogasawara, K; Tokura, Y

2010-01-01

Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.

PubMed

Martel, Britta C; Litman, Thomas; Hald, Andreas; Norsgaard, Hanne; Lovato, Paola; Dyring-Andersen, Beatrice; Skov, Lone; Thestrup-Pedersen, Kristian; Skov, Søren; Skak, Kresten; Poulsen, Lars K

2016-06-01

Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The primary aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD. In contrast to severe AD, expression of the majority of genes associated with skin barrier formation was unchanged or upregulated in patients with mild AD compared to normal healthy skin. Among these, no significant differences in the expression of filaggrin (FLG) and loricrin at both mRNA and protein level were found in lesional skin from patients with mild AD, despite the presence of heterozygous FLG mutations in the majority of patients with mild extrinsic AD. Several inflammation-associated genes such as S100A9, MMP12, CXCL10 and CCL18 were highly expressed in lesional skin from patients with mild psoriasis and were also increased in patients with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Injury downregulates the expression of the human cathelicidin protein hCAP18/LL-37 in atopic dermatitis.

PubMed

Mallbris, Lotus; Carlén, Lina; Wei, Tianling; Heilborn, Johan; Nilsson, Margareta Frohm; Granath, Fredrik; Ståhle, Mona

2010-05-01

Reduced production of antimicrobial peptides was proposed to contribute to susceptibility for skin infections in atopic dermatitis (AD). Focusing on the human cathelicidin protein, hCAP18, the aim of the present study was to explore whether reduced hCAP18 expression is a constitutive trait in AD and if established inducers affect the expression of hCAP18 in the skin of AD. First, we compared levels of hCAP18 mRNA between lesional skin in AD and psoriasis and verified significantly lower expression of hCAP18 mRNA in AD. In non-lesional skin, however, there was no difference between AD, psoriasis and healthy, indicating that there is no constitutive defect in the production of hCAP18 in AD patients. In healthy skin, hCAP18 was reported to be rapidly induced following wounding and here we verified this pattern in healthy controls and in psoriasis. In AD lesions, however, the expression of hCAP18 mRNA was markedly suppressed following wounding. Obviously, the inflammation in AD lesions neutralizes the expected induction of hCAP18 and even induces suppression. Notably, the mechanism to upregulate hCAP18 following vitamin D treatment was functional in lesional as well as in non-lesional AD indicating that the CAMP gene is normally regulated in this respect. In addition, cultured primary keratinocytes from non-lesional skin of psoriasis, AD and healthy skin, upregulated hCAP18mRNA following treatment with vitamin D. Itching is a hallmark of AD and scratching inevitably injures the skin. Failure to upregulate hCAP18 in eczema following injury is likely to affect antimicrobial protection and tissue repair in AD.

Role of Pro-Inflammatory Cytokines and Vitamin D in Probable Alzheimer's Disease with Depression

PubMed Central

Banerjee, Anindita; Khemka, Vineet Kumar; Roy, Debashree; Dhar, Aparajita; Sinha Roy, Tapan Kumar; Biswas, Atanu; Mukhopadhyay, Barun; Chakrabarti, Sasanka

2017-01-01

Symptoms of depression are present in a significant proportion of Alzheimer's disease (AD) patients. While epidemiological studies have shown a strong association between depression and AD, it has not been established whether depression is a risk factor or merely a co-morbidity of AD. It is also uncertain if depression affects the pathogenesis of AD. In this paper, we address these questions by measuring the serum levels of two common metabolic risk factors of AD and depression, inflammatory cytokines (IL 6 and TNF alpha) and serum 25-hydroxyvitamin D, in a case-control study. We measured the serum levels of IL 6, TNF α and 25-hydroxyvitamin D in age-matched healthy controls (n= 60) and in AD patients without depression (n=26) or AD patients with depression (n=34), and statistically analyzed the changes in these parameters among different groups under this study. Our results show that in AD there is a significant increase in IL 6 and TNF α and a marked decrease in 25-hydroxyvitamin D in the peripheral circulation compared to age-matched healthy controls. Furthermore, AD patients with depression have even significantly higher levels of IL 6 or TNF α and a lower level of 25-hydroxyvitamin D in circulation than in AD patients without depression. We also found a strong statistical correlation between the disease severity and the serum levels of IL 6, TNF α and 25-hydroxyvitamin D in AD patients with depression. These results suggest that altered circulating levels of common metabolic risk factors lead to the co-existence of depression with AD in many patients, and when they co-exist, the depression presumably affects the severity of AD presentations through more aggravated changes in these risk factors. PMID:28580183

d-serine levels in Alzheimer's disease: implications for novel biomarker development

PubMed Central

Madeira, C; Lourenco, M V; Vargas-Lopes, C; Suemoto, C K; Brandão, C O; Reis, T; Leite, R E P; Laks, J; Jacob-Filho, W; Pasqualucci, C A; Grinberg, L T; Ferreira, S T; Panizzutti, R

2015-01-01

Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-β oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-β/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis. PMID:25942042

Structure/Function Relationships of Adipose Phospholipase A2 Containing a Cys-His-His Catalytic Triad*

PubMed Central

Pang, Xiao-Yan; Cao, Jian; Addington, Linsee; Lovell, Scott; Battaile, Kevin P.; Zhang, Na; Rao, J. L. Uma Maheswar; Dennis, Edward A.; Moise, Alexander R.

2012-01-01

Adipose phospholipase A2 (AdPLA or Group XVI PLA2) plays an important role in the onset of obesity by suppressing adipose tissue lipolysis. As a consequence, AdPLA-deficient mice are resistant to obesity induced by a high fat diet or leptin deficiency. It has been proposed that AdPLA mediates its antilipolytic effects by catalyzing the release of arachidonic acid. Based on sequence homology, AdPLA is part of a small family of acyltransferases and phospholipases related to lecithin:retinol acyltransferase (LRAT). To better understand the enzymatic mechanism of AdPLA and LRAT-related proteins, we solved the crystal structure of AdPLA. Our model indicates that AdPLA bears structural similarity to proteins from the NlpC/P60 family of cysteine proteases, having its secondary structure elements configured in a circular permutation of the classic papain fold. Using both structural and biochemical evidence, we demonstrate that the enzymatic activity of AdPLA is mediated by a distinctive Cys-His-His catalytic triad and that the C-terminal transmembrane domain of AdPLA is required for the interfacial catalysis. Analysis of the enzymatic activity of AdPLA toward synthetic and natural substrates indicates that AdPLA displays PLA1 in addition to PLA2 activity. Thus, our results provide insight into the enzymatic mechanism and biochemical properties of AdPLA and LRAT-related proteins and lead us to propose an alternate mechanism for AdPLA in promoting adipose tissue lipolysis that is not contingent on the release of arachidonic acid and that is compatible with its combined PLA1/A2 activity. PMID:22923616

Now you see it. Now you don't: fair balance and adequate provision in advertisements for drugs before and after the switch from prescription to over-the-counter.

PubMed

Faerber, Adrienne E; Kreling, David H

2012-01-01

The objective of this study was to measure differences in fair balance (benefit and risk statements) and adequate provision (toll-free numbers, Internet URLs, print ad references, and medical professional references) in advertising content for drugs that have switched from prescription to over-the-counter (OTC). The Vanderbilt TV News Archive was used to select products to study, to measure the frequency and placement of ads for those products, and to view advertising content for those products. Unique advertisements (n = 108) for loratadine (Claritin), citirizine (Zyrtec), and omeprazole (Prilosec) were analyzed for the presence of adequate provision statements and for the frequency of benefit, risk, and other statements. OTC ads were shorter than prescription ads by 10.6 seconds but contained the same total number of statements. Most prescription ads (n (RX) = 31) contained toll-free numbers (97%), Internet URLs (94%), medical professional references (100%) and print ad references (68%). Few OTC ads (n (OTC) = 77) contained adequate provision statements: 4% contained toll-free numbers and 10% contained Internet URLs. Prescription ads had similar numbers of benefits (1.5) and risks (1.8) per 30 seconds of ad time, and OTC ads had more benefits (6.6) than risks (1.2) per 30 seconds of ad time. Prescription drug ads contained risk statements that listed specific side effects and explicit harms from taking the product, but OTC ads contained nonspecific risk information and statements that implied risk rather than directly identifying risk. Differences in the Food and Drug Administration (FDA) and Federal Trade Commission (FTC) regulation of advertising affected the balance of risk and benefit information that appeared and the specificity of risk information available.

Online training improves paramedics' knowledge of autonomic dysreflexia management guidelines.

PubMed

Martin Ginis, K A; Tomasone, J R; Welsford, M; Ethans, K; Sinden, A R; Longeway, M; Krassioukov, A

2017-02-01

Single-group pre-/post-test with 3- and 6-month follow-ups. To test the effects of the 'ABCs of AD' educational module on immediate and longer-term changes in paramedics' knowledge and beliefs about using the autonomic dysreflexia clinical practice guidelines (AD-CPGs). Canada. A total of 119 paramedics completed an AD knowledge test and measures of attitudes, perceived control, self-efficacy, social pressure from patients and health-care professionals, and intentions to use the AD-CPGs before and 1 week, 3 months and 6 months after viewing 'ABCs of AD'. There were significant improvements in AD knowledge, attitudes and social pressure from patients to use the AD-CPGs from baseline to 1 week, 3 months and 6 months post viewing (all P<0.001). Self-efficacy and intentions increased 1 week post viewing (P<0.001), but returned to baseline levels at 3 and 6 months (P>0.05). There was no change in perceived control or social pressure from health-care professionals. AD knowledge and beliefs explained 50-61% of the variance in intentions to use the AD-CPGs. Attitudes, social pressure from patients and perceived behavioural control were significant unique predictors of intentions at all time points (P<0.05); AD knowledge was a significant predictor at 6 months only (P=0.048). No other predictors were significant. 'ABCs of AD' has immediate and sustained effects on paramedics' knowledge of attitudes toward and perceived pressure from patients to use the AD-CPGs. Updates to paramedic patient care guidelines and standards are needed to increase paramedics' perceived control and self-efficacy to implement the guidelines, and their intentions to use the AD-CPGs. Canadian Institutes of Health Research (2011-CIHR- 260877).

University education and cervical artery dissection.

PubMed

Kellert, Lars; Grau, Armin; Pezzini, Alessandro; Debette, Stéphanie; Leys, Didier; Caso, Valeria; Thijs, Vincent N; Bersano, Anna; Touzé, Emmanuel; Tatlisumak, Turgut; Traenka, Christopher; Lyrer, Philippe A; Engelter, Stefan T; Metso, Tiina M; Grond-Ginsbach, Caspar; Kloss, Manja

2018-05-01

We investigated whether university education is more likely in cervical artery dissection (CeAD)-patients than in age- and sex-matched patients with ischemic stroke (IS) due to other causes (non-CeAD-IS-patients). Patients from the Cervical Artery Dissection and Ischemic Stroke Patients study with documented self-reported profession before onset of IS due to CeAD (n = 715) or non-CeAD causes (n = 631) were analyzed. In the reported profession, the absence or presence of university education was assessed. Professions could be rated as academic or non-academic in 518 CeAD and 456 non-CeAD patients. Clinical outcome at 3 months was defined as excellent if modified Rankin Scale was 0-1. University education was more frequent in CeAD-patients (100 of 518, 19.3%) than in non-CeAD-IS-patients (61 of 456, 13.4%, p = 0.008). CeAD-patients with and without university education differed significantly with regard to smoking (39 vs. 57%, p = 0.001) and excellent outcome (80 vs. 66%, p = 0.004). In logistic regression analysis, university education was associated with excellent outcome in CeAD-patients (OR 2.44, 95% CI 1.37-5.38) independent of other outcome predictors such as age (OR 0.97, 95% CI 0.84-0.99), NIHSS (OR 0.80, 95% CI 0.76-0.84) and local signs (OR 2.77, 95% CI 1.37-5.57). We observed a higher rate of university education in patients with CeAD compared with non-CeAD patients in our study population. University education was associated with favorable outcome in CeAD-patients. The mechanism behind this association remains unclear.

Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments.

PubMed

Karschnia, P; Scheuer, C; Heß, A; Später, T; Menger, M D; Laschke, M W

2018-05-09

The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF) is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO). Ad-MVF were isolated from green fluorescent protein (GFP)+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL) or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

2015 Alzheimer's disease facts and figures.

PubMed

2015-03-01

This report discusses the public health impact of Alzheimer’s disease (AD), including incidence and prevalence, mortality rates, costs of care and the overall effect on caregivers and society. It also examines the challenges encountered by health care providers when disclosing an AD diagnosis to patients and caregivers. An estimated 5.3 million Americans have AD; 5.1 million are age 65 years, and approximately 200,000 are age <65 years and have younger onset AD. By mid-century, the number of people living with AD in the United States is projected to grow by nearly 10 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops AD every 67 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year, and the estimated prevalence is expected to range from 11 million to 16 million. In 2013, official death certificates recorded 84,767 deaths from AD, making AD the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years. Between 2000 and 2013, deaths resulting from heart disease, stroke and prostate cancer decreased 14%, 23% and 11%, respectively, whereas deaths from AD increased 71%. The actual number of deaths to which AD contributes (or deaths with AD) is likely much larger than the number of deaths from AD recorded on death certificates. In 2015, an estimated 700,000 Americans age 65 years will die with AD, and many of them will die from complications caused by AD. In 2014, more than 15 million family members and other unpaid caregivers provided an estimated 17.9 billion hours of care to people with AD and other dementias, a contribution valued at more than $217 billion. Average per-person Medicare payments for services to beneficiaries age 65 years with AD and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2015 for health care, long-term care and hospice services for people age 65 years with dementia are expected to be $226 billion. Among people with a diagnosis of AD or another dementia, fewer than half report having been told of the diagnosis by their health care provider. Though the benefits of a prompt, clear and accurate disclosure of an AD diagnosis are recognized by the medical profession, improvements to the disclosure process are needed. These improvements may require stronger support systems for health care providers and their patients.

Assessment of Subclinical Doxorubicin-induced Cardiotoxicity in a Rat Model by Speckle-Tracking Imaging.

PubMed

Kang, Yu; Wang, Wei; Zhao, Hang; Qiao, Zhiqing; Shen, Xuedong; He, Ben

2017-07-10

Despite their clear therapeutic benefits, anthracycline-induced cardiotoxicity is a major concern limiting the ability to reduce morbidity and mortality associated with cancers. The early identification of anthracycline-induced cardiotoxicity is of vital importance to assess the cardiac risk against the potential cancer treatment. To investigate whether speckle-tracking analysis can provide a sensitive and accurate measurement when detecting doxorubicin-induced left ventricular injury. Wistar rats were divided into 4 groups with 8 rats each, given doxorubicin intraperitoneally at weekly intervals for up to 4 weeks. Group 1: 2.5 mg/kg/week; group 2: 3 mg/kg/week; group 3: 3.5mg/kg/week; group 4: 4mg/kg/week. An additional 5 rats were used as controls. Echocardiographic images were obtained at baseline and 1 week after the last dose of treatment. Radial (Srad) and circumferential (Scirc) strains, radial (SRrad) and circumferential (SRcirc) strain rates were analyzed. After the experiment, cardiac troponin I (cTnI) was analyzed and the heart samples were histologically evaluated. After doxorubicin exposure, LVEF was significantly reduced in group 4 (p = 0.006), but remained stable in the other groups. However, after treatment, Srads were reduced in groups 2, 3 and 4 (p all < 0.05). The decrease in Srads was correlated with cTnI (rho = -0.736, p = 0.000) and cardiomyopathy scores (rho = -0.797, p = 0.000). Radial strain could provide a sensitive and noninvasive index in early detection of doxorubicin-induced myocardial injury. The changes in radial strain had a significant correlation with myocardial lesions and serum cardiac troponin I levels, indicating that this parameter could accurately evaluate cardiotoxicity severity. Apesar dos seus claros benefícios terapêuticos, a cardiotoxicidade induzida pela antraciclina é uma grande preocupação que limita a capacidade de reduzir a morbidade e mortalidade associadas com cânceres. A identificação precoce da cardiotoxicidade induzida por antraciclina é de vital importância para o equilíbrio entre o risco cardíaco e o potencial tratamento do câncer. Investigar se a análise por speckle-tracking pode fornecer uma medida sensível e precisa na detecção de lesão ventricular esquerda induzida por doxorrubicina. Ratos Wistar foram divididos em 4 grupos de 8 ratos cada, e doxorrubicina foi administrada intraperitonealmente em intervalos semanais de até 4 semanas. Grupo 1: 2,5 mg/kg/semana; Grupo 2: 3 mg/kg/semana; Grupo 3: 3,5 mg/kg/semana; Grupo 4: 4 mg/kg/semana. Foram utilizados 5 ratos adicionais como controles. As imagens ecocardiográficas foram obtidas na linha basal e 1 semana após a última dose do tratamento. Foram analisados o strain radial (Srad) e circunferencial (Scirc) e as taxas de strain radial (TSrad) e circunferencial (TScirc). Após o experimento, a troponina cardíaca I (cTnI) foi analisada e as amostras cardíacas foram avaliadas histologicamente. Após a exposição à doxorrubicina, a FEVE foi significativamente reduzida no grupo 4 (p = 0,006), mas permaneceu estável nos outros grupos. Entretanto, após o tratamento, os Srads foram reduzidos nos grupos 2, 3 e 4 (p < 0,05). A diminuição dos Srads foi correlacionada com cTnI (rho = -0,736, p = 0,000) e os escores de cardiomiopatia (rho = -0,797, p = 0,000). O strain radial pode fornecer um índice sensível e não-invasivo na detecção precoce da lesão miocárdica induzida pela doxorrubicina. As alterações do strain radial apresentaram correlação significativa com lesões miocárdicas e níveis séricos de troponina I cardíaca, indicando que esse parâmetro pode avaliar com precisão a gravidade da cardiotoxicidade.

FROM COMPLEX EVOLVING TO SIMPLE: CURRENT REVISIONAL AND ENDOSCOPIC PROCEDURES FOLLOWING BARIATRIC SURGERY.

PubMed

Zorron, Ricardo; Galvão-Neto, Manoel Passos; Campos, Josemberg; Branco, Alcides José; Sampaio, José; Junghans, Tido; Bothe, Claudia; Benzing, Christian; Krenzien, Felix

Roux-en-Y gastric bypass (RYGB) is a standard therapy in bariatric surgery. Sleeve gastrectomy and gastric banding, although with good results in the literature, are showing higher rates of treatment failure to reduce obesity-associated morbidity and body weight. Other problems after bariatric may occur, as band erosion, gastroesophageal reflux disease and might be refractory to medication. Therefore, a laparoscopic conversion to a RYGB can be an effective alternative, as long as specific indications for revision are fulfilled. The objective of this study was to analyse own and literature data on revisional bariatric procedures to evaluate best alternatives to current practice. Institutional experience and systematic review from the literature on revisional bariatric surgery. Endoscopic procedures are recently applied to ameliorate failure and complications of bariatric procedures. Therapy failure following RYGB occurs in up to 20%. Transoral outlet reduction is currently an alternative method to reduce the gastrojejunal anastomosis. The diameter and volume of sleeve gastrectomy can enlarge as well, which can be reduced by endoscopic full-thickness sutures longitudinally. Dumping syndrome and severe hypoglycemic episodes (neuroglycopenia) can be present in patients following RYGB. The hypoglycemic episodes have to be evaluated and usually can be treated conventionally. To avoid partial pancreatectomy or conversion to normal anatomy, a new laparoscopic approach with remnant gastric resection and jejunal interposition can be applied in non-responders alternatively. Hypoglycemic episodes are ameliorated while weight loss is sustained. Revisional and endoscopic procedures following bariatric surgery in patients with collateral symptomatic or treatment failure can be applied. Conventional non-surgical approaches should have been applied intensively before a revisional surgery will be indicated. Former complex surgical revisional procedures are evolving to less complicated endoscopic solutions. Bypass gástrico em Y-de-Roux (BGYR) é procedimento padrão em cirurgia bariátrica. Gastrectomia vertical e banda gástrica, embora com bons resultados na literatura, estão mostrando taxas mais elevadas de insucesso no tratamento para reduzir a morbidade associada à obesidade e peso corporal. Outros problemas pós-operatórios podem ocorrer, como a erosão da banda, e doença do refluxo gastroesofágico refratária à medicação. Portanto, conversão laparoscópica para BGYR pode ser alternativa eficaz, desde que indicações específicas para a revisão sejam cumpridas. Analisar os nossos dados e os da literatura sobre procedimentos bariátricos revisionais para avaliar melhores alternativas para a prática atual. Foram efetuados experiência institucional e revisão sistemática da literatura sobre cirurgia bariátrica revisional. Procedimentos endoscópicos estão sendo aplicados recentemente para melhorar a falha e complicações de procedimentos bariátricos. Falha terapêutica após BGYR ocorre em até 20%. A redução transoral é atualmente um método alternativo para reduzir a anastomose gastrojejunal. A gastrectomia vertical pode apresentar aumento de volume e do diâmetro do pouch , o qual podem ser reduzidos por meio de sutura total endoscópica longitudinal. Síndrome de dumping e episódios de hipoglicemia grave (neuroglicopenia) podem estar presentes nos pacientes com BGYR. Os episódios hipoglicêmicos devem ser avaliados e geralmente podem ser tratados convencionalmente. Para evitar pancreatectomia parcial ou conversão à anatomia normal, uma nova abordagem laparoscópica com ressecção do remanescente gástrico e interposição de jejuno, pode ser aplicada como alternativa em não-respondedores. Episódios de hipoglicemia melhoram, enquanto a perda de peso é mantida. Procedimentos revisionais endoscópicos podem ser aplicados após cirurgia bariátrica em pacientes com sintomas colaterais ou na falha do tratamento. Abordagens convencionais não-cirúrgicas devem ser aplicadas intensivamente antes que uma operação revisional seja indicada. Antigos procedimentos cirúrgicos revisionais complexos estão evoluindo para soluções endoscópicas menos complicadas.

Spinning AdS loop diagrams: two point functions

NASA Astrophysics Data System (ADS)

Giombi, Simone; Sleight, Charlotte; Taronna, Massimo

2018-06-01

We develop a systematic approach to evaluating AdS loop amplitudes with spinning legs based on the spectral (or "split") representation of bulk-to-bulk propagators, which re-expresses loop diagrams in terms of spectral integrals and higher-point tree diagrams. In this work we focus on 2pt one-loop Witten diagrams involving totally symmetric fields of arbitrary mass and integer spin. As an application of this framework, we study the contribution to the anomalous dimension of higher-spin currents generated by bubble diagrams in higher-spin gauge theories on AdS.

Diffusion and chaos from near AdS 2 horizons

DOE PAGES

Blake, Mike; Donos, Aristomenis

2017-02-03

We calculate the thermal diffusivity D =more » $$\\kappa/c_\\rho$$ and butterfy velocity $$\\upsilon_\\beta$$ in holographic models that flow to $$AdS_2$$ x $R^d$ fixed points in the infra-red. We show that both these quantities are governed by the same irrelevant deformation of $$AdS_2$$ and hence establish a simple relationship between them. When this deformation corresponds to a universal dilaton mode of dimension $$\\Delta$$ = 2 then this relationship is always given by D = $$\\upsilon_B^2$$/(2$$\\pi$$T).« less

Alternative detox.

PubMed

Ernst, E

2012-01-01

The concept that alternative therapies can eliminate toxins and toxicants from the body, i.e. 'alternative detox' (AD) is popular. Selected textbooks and articles on the subject of AD. The principles of AD make no sense from a scientific perspective and there is no clinical evidence to support them. The promotion of AD treatments provides income for some entrepreneurs but has the potential to cause harm to patients and consumers. In alternative medicine, simplistic but incorrect concepts such as AD abound. AREAS TIMELY FOR RESEARCH: All therapeutic claims should be scientifically tested before being advertised-and AD cannot be an exception.

Phases of global AdS black holes

NASA Astrophysics Data System (ADS)

Basu, Pallab; Krishnan, Chethan; Subramanian, P. N. Bala

2016-06-01

We study the phases of gravity coupled to a charged scalar and gauge field in an asymptotically Anti-de Sitter spacetime ( AdS 4) in the grand canonical ensemble. For the conformally coupled scalar, an intricate phase diagram is charted out between the four relevant solutions: global AdS, boson star, Reissner-Nordstrom black hole and the hairy black hole. The nature of the phase diagram undergoes qualitative changes as the charge of the scalar is changed, which we discuss. We also discuss the new features that arise in the extremal limit.

Divergences and boundary modes in $$ \\mathcal{N}=8 $$ supergravity

DOE PAGES

Larsen, Finn; Lisbao, Pedro

2016-01-07

We reconsider the one loop divergence ofmore » $$ \\mathcal{N}=8 $$ supergravity in four dimensions. We compute the finite effective potential of $$ \\mathcal{N}=8 $$ anti-deSitter supergravity and interpret it as logarithmic running of the cosmological constant. We show that quantum inequivalence between fields that are classically dual is due to boundary modes in AdS 4. In conclusion, the boundary modes are important in global AdS 4 but not in thermal AdS 4 since these geometries have different Euler characteristic.« less

Holography in Lovelock Chern-Simons AdS gravity

NASA Astrophysics Data System (ADS)

Cvetković, Branislav; Miskovic, Olivera; Simić, Dejan

2017-08-01

We analyze holographic field theory dual to Lovelock Chern-Simons anti-de Sitter (AdS) gravity in higher dimensions using first order formalism. We first find asymptotic symmetries in the AdS sector showing that they consist of local translations, local Lorentz rotations, dilatations and non-Abelian gauge transformations. Then, we compute 1-point functions of energy-momentum and spin currents in a dual conformal field theory and write Ward identities. We find that the holographic theory possesses Weyl anomaly and also breaks non-Abelian gauge symmetry at the quantum level.

Consumption of added sugar among U.S. children and adolescents, 2005-2008.

PubMed

Ervin, R Bethene; Kit, Brian K; Carroll, Margaret D; Ogden, Cynthia L

2012-03-01

Approximately 16% of children and adolescents’ total caloric intakes came from added sugars. Boys consumed more added sugars than girls. Preschool-aged children consumed the fewest calories from added sugars. Although girls consumed a smaller absolute amount of calories from added sugars than boys, their intakes were not that different from boys when the amounts are expressed as a percentage of total caloric intakes. Non-Hispanic white children and adolescents consumed a larger percentage of their calories from added sugars than Mexican-American children and adolescents. Also, Non-Hispanic black girls consumed a larger percentage of their calories from added sugars than Mexican-American girls. There was very little difference in added sugar consumption based on PIR. More of the added sugars calories came from foods as opposed to beverages. Previous research has demonstrated that sodas are the single leading food source of added sugars intakes among children, adolescents, and adults (2,4). Our results showed a little more than 40% of calories from added sugars came from beverages. Poti and Popkin (5) have suggested that eating location impacts daily energy intake in children and adolescents and that foods prepared away from home, are contributing to their increased total energy intake. Our results showed that more of the added sugars calories were consumed at home rather than away from home. A substantial percentage of calories in the diets of children and adolescents between 2005 and 2008 came from added sugars. According to the 2010 Dietary Guidelines "reducing the consumption of these sources of added sugars will lower the caloric content of the diet, without compromising its nutrient adequacy (3)." This strategy could play an important role in reducing the high prevalence of obesity in the United States (6) without compromising adequate nutrition. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

Non-Alzheimer's contributions to dementia and cognitive resilience in The 90+ Study.

PubMed

Robinson, John L; Corrada, Maria M; Kovacs, Gabor G; Dominique, Myrna; Caswell, Carrie; Xie, Sharon X; Lee, Virginia M-Y; Kawas, Claudia H; Trojanowski, John Q

2018-06-18

The diagnosis of Alzheimer's disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Logistic regression models-adjusting for age, sex and education-determined the association between each pathology and dementia or between subgroups. 53% had dementia, primarily AD or mixed AD; 23% had cognitive impairment without dementia (CIND); 23% were not impaired. Both AD and non-AD pathology was prevalent. 100% had tangles, 81% had plaques, and both tangles and plaques associated with dementia. ARTAG distributed across limbic (70%), brainstem (39%) and cortical regions (24%). 49% had possible CVD and 26% had definite CVD, while HS was noted in 15%. Cortical ARTAG, CVD and HS were each associated with dementia, but limbic and brainstem ARTAGs were not. TDP-43 and Lewy pathologies were found in 36 and 17% and both associated with dementia. No pathology distinguished CIND and the not impaired. By NIA-AA criteria and dementia status, the cohort was subdivided into four groups: those with minimal ADNPC included the not dementia (ND) and Not AD dementia groups; and those with significant ADNPC included the Resilient without dementia and AD dementia groups. Compared to the ND group, the Not AD dementia group had more HS, cortical ARTAG, TDP-43, and Lewy pathology. Compared to the AD dementia group, the Resilient group had less CVD, no HS and less cortical ARTAG, TDP-43 and Lewy pathology. Our findings imply that reductions in non-AD pathologies including CVD contribute to cognitive resilience in the oldest-old.

Alzheimer biomarkers and clinical Alzheimer disease were not associated with increased cerebrovascular disease in a memory clinic population.

PubMed

Spies, Petra E; Verbeek, Marcel M; Sjogren, Magnus J C; de Leeuw, Frank-Erik; Claassen, Jurgen A H R

2014-01-01

Preclinical and post-mortem studies suggest that Alzheimer disease (AD) causes cerebrovascular dysfunction, and therefore may enhance susceptibility to cerebrovascular disease (CVD). The objective of this study was to investigate this association in a memory clinic population. The AD biomarkers CSF amyloid β42, amyloid β40 and APOE-ε4 status have all been linked to increased CVD risk in AD, and therefore the first aim of this study was to analyze the association between these biomarkers and CVD. In 92 memory clinic patients the cross-sectional association between AD biomarkersand the severity of CVD was investigated with linear regression analysis. Additionally, we studied whether AD biomarkers modified the relation between vascular risk factors and CVD. CVD was assessed on MRI through a visual rating scale.Analyses were adjusted for age. The second aim of this study was to investigate the association between clinical AD and CVD, where 'clinical AD' was defined as follows: impairment in episodic memory, hippocampal atrophy and an aberrant concentration of cerebrospinal fluid (CSF) biomarkers. 47 of the 92 patients had AD. No association between CSF amyloid β42, amyloid β40 or APOE-ε4 status and CVD severity was found, nor did these AD biomarkers modify the relation between vascular risk factors and CVD. Clinical AD was not associated with CVD severity (p=0.83). Patients with more vascular risk factors had more CVD, but this relationship was not convincingly modified by AD (p=0.06). In this memory clinic population, CVD in patients with AD was related to vascular risk factors and age, comparable to patients without AD. Therefore, in our study, the preclinical and post-mortem evidence that AD would predispose to CVD could not be translated clinically. Further work, including replication of this work in a different and larger sample, is warranted.

Cost-effectiveness of cerebrospinal biomarkers for the diagnosis of Alzheimer's disease.

PubMed

Lee, Spencer A W; Sposato, Luciano A; Hachinski, Vladimir; Cipriano, Lauren E

2017-03-16

Accurate and timely diagnosis of Alzheimer's disease (AD) is important for prompt initiation of treatment in patients with AD and to avoid inappropriate treatment of patients with false-positive diagnoses. Using a Markov model, we estimated the lifetime costs and quality-adjusted life-years (QALYs) of cerebrospinal fluid biomarker analysis in a cohort of patients referred to a neurologist or memory clinic with suspected AD who remained without a definitive diagnosis of AD or another condition after neuroimaging. Parametric values were estimated from previous health economic models and the medical literature. Extensive deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results. At a 12.7% pretest probability of AD, biomarker analysis after normal neuroimaging findings has an incremental cost-effectiveness ratio (ICER) of $11,032 per QALY gained. Results were sensitive to the pretest prevalence of AD, and the ICER increased to over $50,000 per QALY when the prevalence of AD fell below 9%. Results were also sensitive to patient age (biomarkers are less cost-effective in older cohorts), treatment uptake and adherence, biomarker test characteristics, and the degree to which patients with suspected AD who do not have AD benefit from AD treatment when they are falsely diagnosed. The cost-effectiveness of biomarker analysis depends critically on the prevalence of AD in the tested population. In general practice, where the prevalence of AD after clinical assessment and normal neuroimaging findings may be low, biomarker analysis is unlikely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY gained. However, when at least 1 in 11 patients has AD after normal neuroimaging findings, biomarker analysis is likely cost-effective. Specifically, for patients referred to memory clinics with memory impairment who do not present neuroimaging evidence of medial temporal lobe atrophy, pretest prevalence of AD may exceed 15%. Biomarker analysis is a potentially cost-saving diagnostic method and should be considered for adoption in high-prevalence centers.

Should We Build “Obese” or “Lean” Anaerobic Digesters?

PubMed Central

Briones, Aurelio; Coats, Erik; Brinkman, Cynthia

2014-01-01

Conventional anaerobic digesters (ADs) treating dairy manure are fed with raw or fermented manure rich in volatile fatty acids (VFAs). In contrast, pre-fermented AD (PF-AD) is fed with the more recalcitrant, fiber-rich fraction of manure that has been pre-fermented and depleted of VFAs. Thus, the substrate of PF-AD may be likened to a lean diet rich in fibers while the pre-fermentation stage fermenter is fed a relatively rich diet containing labile organic substances. Previous results have shown that conventional and pre-fermented ADs fed with raw or pre-fermented manure, respectively, produced comparable methane yields. The primary objective of this study was to characterize, using next-generation DNA sequencing, the bacterial communities in various bioreactors (pre-fermentation stage fermenter; various operational arrangements PF-AD; conventional single-stage AD; and a full scale AD) and compare the Firmicutes to Bacteroidetes (F/B) ratios in these different systems. Firmicutes and Bacteroidetes constituted the two most abundant phyla in all AD samples analyzed, as well as most of the samples analyzed in the fermenters and manure samples. Higher relative abundance of Bacteroidetes, ranging from 26% to 51% of bacteria, tended to be associated with PF-AD samples, while the highest relative abundance of Firmicutes occurred in the fermenter (maximum of 76% of bacteria) and manure (maximum of 66% of bacteria) samples. On average, primary stage fermenters exhibited microbiological traits linked to obesity: higher F/B ratios and a ‘diet’ that is less fibrous and more labile compared to that fed to PF-AD. On the other hand, microbial characteristics associated with leanness (lower F/B ratios combined with fibrous substrate) were associated with PF-AD. We propose that bacterial communities in AD shift depending on the quality of substrate, which ultimately results in maintaining VFA yields in PF-AD, similar to the role of bacterial communities and a high fiber diet in lean mice. PMID:24831948

Improved therapeutic effectiveness by combining recombinant p14(ARF) with antisense complementary DNA of EGFR in laryngeal squamous cell carcinoma.

PubMed

Liu, Feng; Du, JinTao; Xian, Junming; Liu, Yafeng; Liu, Shixi; Lin, Yan

2015-01-01

The tumor suppressor p14(ARF) and proto-oncogene epidermal growth factor receptor (EGFR) play important roles in the development of laryngeal squamous cell carcinoma (LSCC). This study was aimed to determine whether combining recombinant p14(ARF) with antisense complementary DNA of EGFR could improve the therapeutic effectiveness in LSCC. After human larynx cancer cells (Hep-2) were infected with recombinant adenoviruses (Ad-p14(ARF) and Ad-antisense EGFR) together or alone in vitro, the proliferation and cell cycle distribution of Hep-2 cells were detected by MTT assay and flow cytometer analysis, respectively. Furthermore, the antitumor effects of recombinant adenoviruses together or alone on Hep-2 xenografts were examined in vivo. The levels of p14(ARF) and EGFR expressed in Hep-2 cells and xenografts were determined by western blot assay. Ad-p14(ARF) combining with Ad-antisense EGFR markedly inhibited the Hep-2 proliferation compared with alone (P=0.001, P=0.002 respectively). Combination of Ad-p14(ARF) and Ad-antisense EGFR led to the proportion of Hep-2 cells in G0/G1 phases increased by up to 86.9%. The down-expression of EGFR protein and overexpression of p14(ARF) protein were observed in vitro and in vivo, and this effect was preserved when Ad-p14(ARF) was combined with Ad-antisense EGFR. Besides, Ad-p14(ARF) plus Ad-antisense EGFR significantly (P<0.05) increased the antitumor activity against Hep-2 tumor xenografts comparing with Ad-p14(ARF) or Ad-antisense EGFR alone. Combination Ad-p14(ARF) with Ad-antisense EGFR significantly increased the antitumor responses in LSCC. An effectively potential gene therapy to prevent proliferation of LSCC was provided. Copyright © 2015 Elsevier Inc. All rights reserved.

Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations.

PubMed

Brunner, Patrick M; Israel, Ariel; Zhang, Ning; Leonard, Alexandra; Wen, Huei-Chi; Huynh, Thy; Tran, Gary; Lyon, Sarah; Rodriguez, Giselle; Immaneni, Supriya; Wagner, Annette; Zheng, Xiuzhong; Estrada, Yeriel D; Xu, Hui; Krueger, James G; Paller, Amy S; Guttman-Yassky, Emma

2018-06-01

Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments. We sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects. We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children (<5 years old) with early-onset AD (<6 months disease duration) compared with age-matched control subjects and adults with longstanding AD. Transcriptomic analyses revealed profound differences between pediatric patients with early-onset versus adult patients with longstanding AD in not only lesional but also nonlesional tissues. Although both patient populations harbored T H 2-centered inflammation, pediatric AD also showed significant T H 17/T H 22 skewing but lacked the T H 1 upregulation that characterizes adult AD. Pediatric AD exhibited relatively normal expression of epidermal differentiation and cornification products, which is downregulated in adults with AD. Defects in the lipid barrier (eg, ELOVL fatty acid elongase 3 [ELOVL3] and diacylglycerol o-acyltransferase 2 [DGAT2]) and tight junction regulation (eg, claudins 8 and 23) were evident in both groups. However, some lipid-associated mediators (eg, fatty acyl-CoA reductase 2 and fatty acid 2-hydroxylase) showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H and DGAT2) showed inverse correlations with transepidermal water loss, a functional measure of the epidermal barrier. Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Discrimination between stages of Alzheimer's disease with subsets of Mini-Mental State Examination items. An analysis of Consortium to Establish a Registry for Alzheimer's Disease data.

PubMed

Fillenbaum, G G; Wilkinson, W E; Welsh, K A; Mohs, R C

1994-09-01

To identify minimal sets of Mini-Mental State Examination (MMSE) items that can distinguish normal control subjects from patients with mild Alzheimer's disease (AD), patients with mild from those with moderate AD, and those with moderate from those with severe AD. Two randomly selected equivalent half samples. Results of logistic regression analysis from data from the first half of the sample were confirmed by receiver operating characteristic curves on the second half. Memory disorders clinics at major medical centers in the United States affiliated with the Consortium to establish a Registry for Alzheimer's Disease (CERAD). White, normal control subjects (n = 412) and patients with AD (n = 621) who met CERAD criteria; nonwhite subjects (n = 165) and persons with missing data (n = 27) were excluded. Three four-item sets of MMSE items that discriminate, respectively, (1) normal controls from patients with mild AD, (2) patients with mild from those with moderate AD, and (3) patients with moderate from those with severe AD. The MMSE items discriminating normal controls from patients with mild AD were day, date, recall of apple, and recall of penny; those discriminating patients with mild from those with moderate AD were month, city, spelling world backward, and county, and those discriminating patients with moderate from those with severe AD were floor of building, repeating the word table, naming watch, and folding paper in half. Performance on the first two four-item sets was comparable with that of the full MMSE; the third set distinguished patients with moderate from those with severe AD better than chance. A minimum set of MMSE items can effectively discriminate normal controls from patients with mild AD and between successive levels of severity of AD. Data apply only to white patients with AD. Performance in minorities, more heterogeneous groups, or normal subjects with questionable cognitive status has not been assessed.

Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer's disease.

PubMed

Silva, Aderbal R T; Santos, Ana Cecília Feio; Farfel, Jose M; Grinberg, Lea T; Ferretti, Renata E L; Campos, Antonio Hugo Jose Froes Marques; Cunha, Isabela Werneck; Begnami, Maria Dirlei; Rocha, Rafael M; Carraro, Dirce M; de Bragança Pereira, Carlos Alberto; Jacob-Filho, Wilson; Brentani, Helena

2014-01-01

Alzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) "clinical-pathological AD" (CP-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and clinical dementia (CDR ≥ 2, IQCODE>3.8); II) "pathological AD" (P-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE<3.2); and III) "normal aging" (N)--subjects without neuropathological AD (Braak ≤ II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.

Alzheimer's Prevention Education: If We Build It, Will They Come? www.AlzU.org.

PubMed

Isaacson, R S; Haynes, N; Seifan, A; Larsen, D; Christiansen, S; Berger, J C; Safdieh, J E; Lunde, A M; Luo, A; Kramps, M; McInnis, M; Ochner, C N

2014-01-01

Internet-based educational interventions may be useful for impacting knowledge and behavioral change. However, in AD prevention, little data exists about which educational tools work best in terms of learning and interest in participating in clinical trials. Primary: Assess effectiveness of interactive webinars vs. written blog-posts on AD prevention learning. Secondary: Evaluate the effect of AD prevention education on interest in participating in clinical trials; Assess usability of, and user perceptions about, an online AD education research platform; Classify target populations (demographics, learning needs, interests). Observational. Online. Men/Women, aged 25+, recruited via facebook.com. Alzheimer's Universe (www.AlzU.org) education research platform. Pre/post-test performance, self-reported Likert-scale ratings, completion rates. Over two-weeks, 4268 visits were generated. 503 signed-up for a user account (11.8% join rate), 196 participated in the lessons (39.0%) and 100 completed all beta-testing steps (19.9%). Users randomized to webinar instruction about AD prevention and the stages of AD demonstrated significant increases (p=0.01) in pre vs. post-testing scores compared to blog-post intervention. Upon joining, 42% were interested in participating in a clinical trial in AD prevention. After completing all beta-test activities, interest increased to 86%. Users were primarily women and the largest category was children of AD patients. 66.3% joined to learn more about AD prevention, 65.3% to learn more about AD treatment. Webinar-based education led to significant improvements in learning about AD prevention and the stages of AD. AlzU.org participation more than doubled interest in AD prevention clinical trial participation. Subjects were quickly and cost-effectively recruited, and highly satisfied with the AD education research platform. Based on these data, we will further refine AlzU.org prior to public launch and aim to study the effectiveness of 25 interactive webinar-based vs. blog-post style lessons on learning and patient outcomes, in a randomized, within-subjects design trial.

Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis.

PubMed

Zhang, Zenan; Zheng, Wenjiao; Xie, Hua; Chai, Ruonan; Wang, Junling; Zhang, Huiyun; He, Shaoheng

2017-05-01

Large numbers of CD8 + T cells were observed in atopic dermatitis (AD) skin, and monocytes from AD patients showed increased prostaglandin E2 production. However, little is known about the expression of substance P (SP) and its receptor NK1R in blood leukocytes of patients with AD. To explore the expression of SP and NK1R in leukocytes of AD and the influence of allergens on SP and NK1R expression. The expression levels of SP and NK1R in patients with AD were examined by flow cytometry, ELISA and a mouse AD model. The plasma SP level was 4.9-fold higher in patients with AD than in HC subjects. Both the percentage of SP expression in the population and mean fluorescence intensity (MFI) of SP expression were elevated in CD8 + T cells in the blood of AD patients. However, both the CD14 + NK1R + population and MFI of NK1R expression on CD14 + cells were enhanced in the blood of AD patients. Allergens ASWE, HDME and PPE failed to up-regulate SP expression in CD8 + T cells. However, allergens ASWE and HDME both enhanced NK1R expression on CD14 + blood leukocytes regardless of AD or HC subjects. OVA-sensitized AD mice showed an elevated proportion and MFI of SP-expressing CD8 + T cells in the blood, which agrees with the SP expression situation in human AD blood. Injection of SP into mouse skin did not up-regulate NK1R expression on monocytes. An elevated plasma SP level, up-regulated expression of SP and NK1R indicate that the SP/NK1R complex is important in the development of AD. Therefore, SP and NK1R antagonist or blocker agents may help to treat patients with AD. Trial registration Registration number: ChiCTR-BOC-16010279; Registration date: Dec., 28, 2016; retrospectively registered.

Tree-ring-width-based PDSI reconstruction for central Inner Mongolia, China over the past 333 years

NASA Astrophysics Data System (ADS)

Liu, Yu; Zhang, Xinjia; Song, Huiming; Cai, Qiufang; Li, Qiang; Zhao, Boyang; Liu, Han; Mei, Ruochen

2017-02-01

A tree-ring-width chronology was developed from Pinus tabulaeformis aged up to 333 years from central Inner Mongolia, China. The chronology was significantly correlated with the local Palmer Drought Severity Index (PDSI). We therefore reconstructed the first PDSI reconstruction from March to June based on the local tree ring data from 1680 to 2012 AD. The reconstruction explained 40.7 % of the variance (39.7 % after adjusted the degrees of freedom) of the actual PDSI during the calibration period (1951-2012 AD). The reconstructed PDSI series captured the severe drought event of the late 1920s, which occurred extensively in northern China. Running variance analyses indicated that the variability of drought increased sharply after 1960, indicating more drought years, which may imply anthropogenic related global warming effects in the region. In the entire reconstruction, there were five dry periods: 1730-1814 AD, 1849-1869 AD, 1886-1942 AD (including severe drought in late 1920s), 1963-1978 AD and 2004-2007 AD; and five wet periods: 1685-1729 AD, 1815-1848 AD, 1870-1885 AD, 1943-1962 AD and 1979-2003 AD. Conditions turned dry after 2003 AD, and the PDSI from March to June (PDSI36) captured many interannual extreme drought events since then, such as 2005-2008 AD. The reconstruction is comparable to other tree-ring-width-based PDSI series from the neighboring regions, indicating that our reconstruction has good regional representativeness. Significant relationships were found between our PDSI reconstruction and the solar radiation cycle and the sun spot cycle, North Atlantic Oscillation, the El Niño-Southern Oscillation, as well as the Pacific Decadal Oscillation. Power spectral analyses detected 147.0-, 128.2-, 46.5-, 6.5-, 6.3-, 2.6-, 2.2- and 2.0-year quasi-cycles in the reconstructed series.

Seed-competent HMW tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients

PubMed Central

Takeda, Shuko; Commins, Caitlin; DeVos, Sarah L.; Nobuhara, Chloe K.; Wegmann, Susanne; Roe, Allyson D.; Costantino, Isabel; Fan, Zhanyun; Nicholls, Samantha B.; Sherman, Alexis E.; Trisini Lipsanopoulos, Ana T.; Scherzer, Clemens R.; Carlson, George A.; Pitstick, Rose; Peskind, Elaine R.; Raskind, Murray A.; Li, Ge; Montine, Thomas J.; Frosch, Matthew P.; Hyman, Bradley T.

2016-01-01

Objective Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated tau in AD CSF is just a marker of neurodegeneration or in fact a part of the disease process is uncertain. Moreover, it is unknown how CSF tau relates to the recently described soluble high-molecular-weight (HMW) species that is found in postmortem AD brain and can be taken up by neurons and seed aggregates. Methods We have examined seeding and uptake properties of brain extracellular tau from various sources including: interstitial fluid (ISF) and CSF from an AD transgenic mouse model, and postmortem ventricular and antemortem lumbar CSF from AD patients. Results We found that brain ISF and CSF tau from the AD mouse model can be taken up by cells and induce intracellular aggregates. Ventricular CSF from AD patients contained a rare HMW tau species that exerted a higher seeding activity. Notably, the HMW tau species was also detected in lumbar CSF from AD patients and its levels were significantly elevated compared with control subjects. HMW tau derived from CSF of AD patients was seed-competent in vitro. Interpretation These findings suggest that CSF from an AD brain contains potentially bioactive HMW tau species giving new insights into the role of CSF tau and biomarker development for AD. PMID:27351289

Enhanced Prostate Cancer Gene Transfer and Therapy Using a Novel Serotype Chimera Cancer Terminator Virus (Ad.5/3-CTV)

PubMed Central

AZAB, BELAL M.; DASH, RUPESH; DAS, SWADESH K.; BHUTIA, SUJIT K.; SARKAR, SIDDIK; SHEN, XUE-NING; QUINN, BRIDGET A.; DENT, PAUL; DMITRIEV, IGOR P.; WANG, XIANG-YANG; CURIEL, DAVID T.; PELLECCHIA, MAURIZIO; REED, JOHN C.; SARKAR, DEVANAND; FISHER, PAUL B.

2015-01-01

Few options are available for treating patients with advanced prostate cancer (PC). As PC is a slow growing disease and accessible by ultrasound, gene therapy could provide a viable option for this neoplasm. Conditionally replication-competent adenoviruses (CRCAs) represent potentially useful reagents for treating PC. We previously constructed a CRCA, cancer terminator virus (CTV), which showed efficacy both in vitro and in vivo for PC. The CTV was generated on a serotype 5-background (Ad.5-CTV) with infectivity depending on Coxsackie-Adenovirus Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs thereby limiting effective Ad-mediated therapy. Using serotype chimerism, a novel CTV (Ad.5/3-CTV) was created by replacing the Ad.5 fiber knob with the Ad.3 fiber knob thereby facilitating infection in a CAR-independent manner. We evaluated Ad.5/3-CTV in comparison with Ad.5-CTV in low CAR human PC cells, demonstrating higher efficiency in inhibiting cell viability in vitro. Moreover, Ad.5/3-CTV potently suppressed in vivo tumor growth in a nude mouse xenograft model and in a spontaneously induced PC that develops in Hi-myc transgenic mice. Considering the significant responses in a Phase I clinical trial of a non-replicating Ad.5-mda-7 in advanced cancers, Ad.5/3-CTV may exert improved therapeutic benefit in a clinical setting. PMID:23868767

Sweat glucose and GLUT2 expression in atopic dermatitis: Implication for clinical manifestation and treatment

PubMed Central

Ono, Emi; Mori, Yuki; Yoshioka, Yoshichika; Nomura, Yuko; Munetsugu, Takichi; Yokozeki, Hiroo; Katayama, Ichiro

2018-01-01

Sweat includes active components and metabolites, which are needed to maintain skin homeostasis. Component changes in sweat derived from atopic dermatitis (AD) have been reported. To investigate the influence of sweat components on the pathogenesis of AD, we performed a multifaceted assessment, including nuclear magnetic resonance spectroscopy-based metabolomic analysis, and linked these features to clinical features of AD. Distinctive properties of AD sweat are the quite-variation in protein, anti-microbial peptides and glucose concentrations. pH, sodium, and other salt levels in sweat of AD were comparable to that of healthy subjects. Sweat from AD patients with acute inflammation had a more prominent increase in glucose concentration than sweat from healthy individuals or those with AD with chronic inflammation. Topical glucose application delayed recovery of transepidermal water loss in barrier-disrupted mice. Furthermore, the glucose transporter GLUT2 was highly expressed in the lumen of sweat glands from AD patients. AD patients with chronic inflammation had significantly increased GLUT2 mRNA expression and near normal sweat glucose levels. Despite the small sample size in our study, we speculate that the increased glucose levels might be affected by AD severity and phenotype. We hope that this report will bring novel insight into the impact of sweat components on the clinical manifestation of AD. PMID:29677207

Multicentered black holes with a negative cosmological constant

NASA Astrophysics Data System (ADS)

Chimento, Samuele; Klemm, Dietmar

2014-01-01

We present a recipe that allows us to construct multicentered black holes embedded in an arbitrary Friedmann-Lemaître-Robertson-Walker (FLRW) universe. These solutions are completely determined by a function satisfying the conformal Laplace equation on the spatial slices E3, S3, or H3. Since anti-de Sitter (AdS) space can be written in FLRW coordinates, this includes as a special case multicentered black holes in AdS, in the sense that, far away from the black holes, the energy density and the pressure approach the values given by a negative cosmological constant. We study in some detail the physical properties of the single-centered asymptotically AdS case, which does not coincide with the usual Reissner-Nordström-AdS black hole, but is highly dynamical. In particular, we determine the curvature singularities and trapping horizons of this solution, compute the surface gravity of the trapping horizons, and show that the generalized first law of black hole dynamics proposed by Hayward holds in this case. It turns out that the spurious big bang/big crunch singularities that appear when one writes AdS in FLRW form become real in the presence of these dynamical black holes. This implies that actually only one point of the usual conformal boundary of AdS survives in the solutions that we construct. Finally, a generalization to arbitrary dimension is also presented.

Targeting modulates audiences' brain and behavioral responses to safe sex video ads.

PubMed

Wang, An-Li; Lowen, Steven B; Shi, Zhenhao; Bissey, Bryn; Metzger, David S; Langleben, Daniel D

2016-10-01

Video ads promoting condom use are a key component of media campaigns to stem the HIV epidemic. Recent neuroimaging studies in the context of smoking cessation, point to personal relevance as one of the key variables that determine the effectiveness of public health messages. While minority men who have sex with men (MSM) are at the highest risk of HIV infection, most safe-sex ads feature predominantly Caucasian actors in heterosexual scenarios. We compared brain respons of 45 African American MSM to safe sex ads that were matched (i.e. 'Targeted') to participants' sexual orientation and race, and 'Untargeted' ads that were un matched for these characteristics. Ad recall, perceived 'convincingness' and attitudes towards condom use were also assessed. We found that Targeted ads were better remembered than the Untargeted ads but perceived as equally convincing. Targeted ads engaged brain regions involved in self-referential processing and memory, including the amygdala, hippocampus, temporal and medial prefrontal cortices (MPFC) and the precuneus. Connectivity between MPFC and precuneus and middle temporal gyrus was stronger when viewing Targeted ads. Our results suggest that targeting may increase cognitive processing of safe sex ads and justify further prospective studies linking brain response to media public health interventions and clinical outcomes. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Ad hoc vs. Non-ad hoc Percutaneous Coronary Intervention Strategies in Patients With Stable Coronary Artery Disease.

PubMed

Toyota, Toshiaki; Morimoto, Takeshi; Shiomi, Hiroki; Ando, Kenji; Ono, Koh; Shizuta, Satoshi; Kato, Takao; Saito, Naritatsu; Furukawa, Yutaka; Nakagawa, Yoshihisa; Horie, Minoru; Kimura, Takeshi

2017-03-24

Few studies have evaluated the prevalence and clinical outcomes of ad hoc percutaneous coronary intervention (PCI), performing diagnostic coronary angiography and PCI in the same session, in stable coronary artery disease (CAD) patients.Methods and Results:From the CREDO-Kyoto PCI/CABG registry cohort-2, 6,943 patients were analyzed as having stable CAD and undergoing first PCI. Ad hoc PCI and non-ad hoc PCI were performed in 1,722 (24.8%) and 5,221 (75.1%) patients, respectively. The cumulative 5-year incidence and adjusted risk for all-cause death were not significantly different between the 2 groups (15% vs. 15%, P=0.53; hazard ratio: 1.15, 95% confidence interval: 0.98-1.35, P=0.08). Ad hoc PCI relative to non-ad hoc PCI was associated with neutral risk for myocardial infarction, any coronary revascularization, and bleeding, but was associated with a trend towards lower risk for stroke (hazard ratio: 0.78, 95% confidence interval: 0.60-1.02, P=0.06). Ad hoc PCI in stable CAD patients was associated with at least comparable 5-year clinical outcomes as with non-ad hoc PCI. Considering patients' preference and the cost-saving, the ad hoc PCI strategy might be a safe and attractive option for patients with stable CAD, although the prevalence of ad hoc PCI was low in the current study population.

The effects of verbal reaction time in Alzheimer's disease.

PubMed

Midi, Ipek; Doǧan, Müzeyyen; Pata, Yavuz Selim; Kocak, Ismail; Mollahasanoglu, Aynur; Tuncer, Nese

2011-07-01

Verbal fluency deteriorates with normal aging, but is much more severe in Alzheimer's Disease (AD). Verbal functions were analyzed to find differences between normal aging subjects in patients with mild cognitive impairment (MCI), and in patients with early and moderate stages of AD. This study measured the verbal response time in patients with AD, MCI, and in control subjects This study measured the verbal response time in patients with AD, MCI, and in control subjects Fifteen patients with MCI, 15 patients with early AD, 8 patients with moderate AD, and 15 subjects for controls were included in the study. Word length in milliseconds, reaction time to a phoneme, word, or sentence and acoustic analysis of voice quality and speech diadochokinetic rate (DDK) were measured. Reaction time for a phoneme, word, or sentence especially the initiation period for them were longer in patients with early AD compared to patients with MCI (P < .001). The mean DDK rate was lower with increased severity of the disease, and was much more severe in patients with moderate AD. Clinical discrimination of the early stages of AD and MCI is challenging. Unfortunately, there are no laboratory markers present for the diagnosis of preclinical cases of AD. With the results of this study, the assessments of verbal reaction time may helpful for diagnosis of early AD. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Industry sponsored anti‐smoking ads and adolescent reactance: test of a boomerang effect

PubMed Central

Henriksen, L; Dauphinee, A L; Wang, Y; Fortmann, S P

2006-01-01

Objective To examine whether adolescents' exposure to youth smoking prevention ads sponsored by tobacco companies promotes intentions to smoke, curiosity about smoking, and positive attitudes toward the tobacco industry. Design A randomised controlled experiment compared adolescents' responses to five smoking prevention ads sponsored by a tobacco company (Philip Morris or Lorillard), or to five smoking prevention ads sponsored by a non‐profit organisation (the American Legacy Foundation), or to five ads about preventing drunk driving. Setting A large public high school in California's central valley. Subjects A convenience sample of 9th and 10th graders (n  =  832) ages 14–17 years. Main outcome measures Perceptions of ad effectiveness, intention to smoke, and attitudes toward tobacco companies measured immediately after exposure. Results As predicted, adolescents rated Philip Morris and Lorillard ads less favourably than the other youth smoking prevention ads. Adolescents' intention to smoke did not differ as a function of ad exposure. However, exposure to Philip Morris and Lorillard ads engendered more favourable attitudes toward tobacco companies. Conclusions This study demonstrates that industry sponsored anti‐smoking ads do more to promote corporate image than to prevent youth smoking. By cultivating public opinion that is more sympathetic toward tobacco companies, the effect of such advertising is likely to be more harmful than helpful to youth. PMID:16436398

Dependence as a unifying construct in defining Alzheimer’s disease severity

PubMed Central

McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J. Michael; Sullivan, Sean D.; Spackman, D. Eldon; Neumann, Peter J.; Cohen, Joshua; Stern, Yaakov

2012-01-01

This article reviews measures of Alzheimer’s disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient’s perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression. PMID:21044778

Thermodynamics and phase transition of charged AdS black holes with a global monopole

NASA Astrophysics Data System (ADS)

Deng, Gao-Ming; Fan, Jinbo; Li, Xinfei; Huang, Yong-Chang

2018-01-01

Thermodynamical properties of charged AdS black holes with a global monopole still remain obscure. In this paper, we investigate the thermodynamics and phase transition of the black holes in the extended phase space. It is shown that thermodynamical quantities of the black holes exhibit an interesting dependence on the internal global monopole, and they perfectly satisfy both the first law of thermodynamics and Smarr relation. Furthermore, analysis of the local and the global thermodynamical stability manifests that the charged AdS black hole undergoes an elegant phase transition at critical point. Of special interest, critical behaviors of the black holes resemble a Van der Waals liquid-gas system. Our results not only reveal the effect of a global monopole on thermodynamics of AdS black holes, but also further support that Van der Waals-like behavior of the black holes is a universal phenomenon.

QCD Condensates and Holographic Wilson Loops for Asymptotically AdS Spaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quevedo, R. Carcasses; Goity, Jose L.; Trinchero, Roberto C.

2014-02-01

The minimization of the Nambu-Goto (NG) action for a surface whose contour defines a circular Wilson loop of radius a placed at a finite value of the coordinate orthogonal to the border is considered. This is done for asymptotically AdS spaces. The condensates of dimension n = 2, 4, 6, 8, and 10 are calculated in terms of the coefficients in the expansion in powers of the radius a of the on-shell subtracted NG action for small a->0. The subtraction employed is such that it presents no conflict with conformal invariance in the AdS case and need not introduce anmore » additional infrared scale for the case of confining geometries. It is shown that the UV value of the gluon condensates is universal in the sense that it only depends on the first coefficients of the difference with the AdS case.« less

Worldsheet scattering in AdS3/CFT2

NASA Astrophysics Data System (ADS)

Sundin, Per; Wulff, Linus

2013-07-01

We confront the recently proposed exact S-matrices for AdS 3/ CFT 2 with direct worldsheet calculations. Utilizing the BMN and Near Flat Space (NFS) expansions for strings on AdS 3 × S 3 × S 3 × S 1 and AdS 3 × S 3 × T 4 we compute both tree-level and one-loop scattering amplitudes. Up to some minor issues we find nice agreement in the tree-level sector. At the one-loop level however we find that certain non-zero tree-level processes, which are not visible in the exact solution, contribute, via the optical theorem, and give an apparent mismatch for certain amplitudes. Furthermore we find that a proposed one-loop modification of the dressing phase correctly reproduces the worldsheet calculation while the standard Hernandez-Lopez phase does not. We also compute several massless to massless processes.

Hawking radiation power equations for black holes

NASA Astrophysics Data System (ADS)

Mistry, Ravi; Upadhyay, Sudhaker; Ali, Ahmed Farag; Faizal, Mir

2017-10-01

We derive the Hawking radiation power equations for black holes in asymptotically flat, asymptotically Anti-de Sitter (AdS) and asymptotically de Sitter (dS) black holes. This is done by using the greybody factor for these black holes. We observe that the radiation power equation for asymptotically flat black holes, corresponding to greybody factor at low frequency, depends on both the Hawking temperature and the horizon radius. However, for the greybody factors at asymptotic frequency, it only depends on the Hawking temperature. We also obtain the power equation for asymptotically AdS black holes both below and above the critical frequency. The radiation power equation for at asymptotic frequency is same for both Schwarzschild AdS and Reissner-Nordström AdS solutions and only depends on the Hawking temperature. We also discuss the power equation for asymptotically dS black holes at low frequency, for both even or odd dimensions.

Direct-to-Consumer Prescription Medicine Advertising and Seniors' Knowledge of Alzheimer's Disease.

PubMed

Park, Jin Seong

2016-02-01

This study examined whether seniors' exposure to direct-to-consumer advertising (DTCA) for Alzheimer's disease (AD) medicine contributes to his or her subjective and objective knowledge of AD. A self-administered survey was conducted with a sample of 626 US seniors who were registered for an online consumer research panel. The study found that (1) exposure to DTCA for AD medicine was positively related to seniors' subjective knowledge of AD, (2) DTCA exposure had no significant relationship with overall objective knowledge of AD, and (3) DTCA exposure might influence knowledge of specific features of AD. Although DTCA for AD medicine may induce people to "feel" knowledgeable about AD, it may not result in an equivalent increase in actual knowledge. Therefore, to enhance doctor-patient interactions, both patients and doctors should be aware that although DTCA delivers important and potentially useful health information, it does not necessarily enhance actual knowledge. © The Author(s) 2014.

Dependence as a unifying construct in defining Alzheimer's disease severity.

PubMed

McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J Michael; Sullivan, Sean D; Spackman, D Eldon; Neumann, Peter J; Cohen, Joshua; Stern, Yaakov

2010-11-01

This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression. Copyright © 2010. Published by Elsevier Inc.

Topologically massive gravity and Ricci-Cotton flow

NASA Astrophysics Data System (ADS)

Lashkari, Nima; Maloney, Alexander

2011-05-01

We consider topologically massive gravity (TMG), which is three-dimensional general relativity with a cosmological constant and a gravitational Chern-Simons term. When the cosmological constant is negative the theory has two potential vacuum solutions: anti-de Sitter space and warped anti-de Sitter space. The theory also contains a massive graviton state which renders these solutions unstable for certain values of the parameters and boundary conditions. We study the decay of these solutions due to the condensation of the massive graviton mode using Ricci-Cotton flow, which is the appropriate generalization of Ricci flow to TMG. When the Chern-Simons coupling is small the AdS solution flows to warped AdS by the condensation of the massive graviton mode. When the coupling is large the situation is reversed, and warped AdS flows to AdS. Minisuperspace models are constructed where these flows are studied explicitly.

Dissecting Alzheimer disease in Down syndrome using mouse models

PubMed Central

Choong, Xun Yu; Tosh, Justin L.; Pulford, Laura J.; Fisher, Elizabeth M. C.

2015-01-01

Down syndrome (DS) is a common genetic condition caused by the presence of three copies of chromosome 21 (trisomy 21). This greatly increases the risk of Alzheimer disease (AD), but although virtually all people with DS have AD neuropathology by 40 years of age, not all develop dementia. To dissect the genetic contribution of trisomy 21 to DS phenotypes including those relevant to AD, a range of DS mouse models has been generated which are trisomic for chromosome segments syntenic to human chromosome 21. Here, we consider key characteristics of human AD in DS (AD-DS), and our current state of knowledge on related phenotypes in AD and DS mouse models. We go on to review important features needed in future models of AD-DS, to understand this type of dementia and so highlight pathogenic mechanisms relevant to all populations at risk of AD. PMID:26528151

Dissecting Alzheimer disease in Down syndrome using mouse models.

PubMed

Choong, Xun Yu; Tosh, Justin L; Pulford, Laura J; Fisher, Elizabeth M C

2015-01-01

Down syndrome (DS) is a common genetic condition caused by the presence of three copies of chromosome 21 (trisomy 21). This greatly increases the risk of Alzheimer disease (AD), but although virtually all people with DS have AD neuropathology by 40 years of age, not all develop dementia. To dissect the genetic contribution of trisomy 21 to DS phenotypes including those relevant to AD, a range of DS mouse models has been generated which are trisomic for chromosome segments syntenic to human chromosome 21. Here, we consider key characteristics of human AD in DS (AD-DS), and our current state of knowledge on related phenotypes in AD and DS mouse models. We go on to review important features needed in future models of AD-DS, to understand this type of dementia and so highlight pathogenic mechanisms relevant to all populations at risk of AD.

Randomized study of placebo and framing information in direct-to-consumer print advertisements for prescription drugs.

PubMed

O'Donoghue, Amie C; Sullivan, Helen W; Aikin, Kathryn J

2014-12-01

Research suggests that quantitative information in direct-to-consumer (DTC) prescription drug ads may be helpful for consumers. The objective was to examine the effect of adding placebo rates and framing to DTC ads. In study 1, 2,000 Internet panel members with chronic pain participated in a randomized controlled experiment of DTC ads varying in placebo rate and framing. In study 2, 596 physicians ranked DTC ads varying in placebo rate and framing by how well they conveyed scientific information and their usefulness for patients. In study 1, participants who viewed placebo rates were able to recall them and use them to form certain perceptions. A mixed frame led to lower placebo rate recall and perceived efficacy. In study 2, overall, physicians preferred a placebo/single frame ad. Adding placebo rates to DTC ads may be useful for consumers. The evidence does not support using a mixed frame.

Kinetic, isotherm and thermodynamic studies of amaranth dye biosorption from aqueous solution onto water hyacinth leaves.

PubMed

Guerrero-Coronilla, Imelda; Morales-Barrera, Liliana; Cristiani-Urbina, Eliseo

2015-04-01

The present study explored the kinetics, equilibrium and thermodynamics of amaranth (acid red 27) anionic dye (AD) biosorption to water hyacinth leaves (LEC). The effect of LEC particle size, contact time, solution pH, initial AD concentration and temperature on AD biosorption was studied in batch experiments. AD biosorption increased with rising contact time and initial AD concentration, and with decreasing LEC particle size and solution pH. Pseudo-second-order chemical reaction kinetics provided the best correlation for the experimental data. Isotherm studies showed that the biosorption of AD onto LEC closely follows the Langmuir isotherm, with a maximum biosorption capacity of about 70 mg g(-1). The thermodynamic parameters confirm that AD biosorption by LEC is non-spontaneous and endothermic in nature. Results indicate that LEC is a strong biosorbent capable of effective detoxification of AD-laden wastewaters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integrally formed radio frequency quadrupole

DOEpatents

Abbott, Steven R.

1989-01-01

An improved radio frequency quadrupole (10) is provided having an elongate housing (11) with an elongate central axis (12) and top, bottom and two side walls (13a-d) symmetrically disposed about the axis, and vanes (14a-d) formed integrally with the walls (13a-d), the vanes (14a-d) each having a cross-section at right angles to the central axis (12) which tapers inwardly toward the axis to form electrode tips (15a-d) spaced from each other by predetermined distances. Each of the four walls (13a-d), and the vanes (14a-d) integral therewith, is a separate structural element having a central lengthwise plane (16) passing through the tip of the vane, the walls (13a-d) having flat mounting surfaces (17, 18) at right angles to and parallel to the control plane (16), respectively, which are butted together to position the walls and vane tips relative to each other.

Impact of 6-month aerobic exercise on Alzheimer's symptoms.

PubMed

Yu, Fang; Thomas, William; Nelson, Nathaniel W; Bronas, Ulf G; Dysken, Maurice; Wyman, Jean F

2015-06-01

Little is known about how aerobic exercise affects Alzheimer's disease (AD). The purpose of this pilot study was to test the impact of 6-month cycling on AD symptoms in community-dwelling older adults with mild-to-moderate AD, using a single-group, repeated-measures design (n = 26). AD symptoms were measured with the AD Assessment Scale-Cognitive (ADAS-Cog), Disability in AD (DAD), and Neuropsychiatric Inventory-Caregiver (NPI-Q) scales at baseline, 3 and 6 months. Data were analyzed using mixed linear models. The ADAS-Cog, DAD, and NPI-Q severity scores remained unchanged over the 6-month period, while caregiver distress decreased 40% (p < .05). We conclude that aerobic exercise may reduce AD symptoms and appears effective in decreasing caregiver distress. Further randomized controlled trials are needed to examine the effects of aerobic exercise in AD. © The Author(s) 2013.

Targeting adolescents? The content and frequency of alcoholic and nonalcoholic beverage ads in magazine and video formats November 1999-April 2000.

PubMed

Austin, Erica Weintraub; Hust, Stacey J T

2005-12-01

This study compared alcoholic and nonalcoholic beverage advertising to which adolescents are exposed. A census of beverage advertising (N = 757) in popular magazines and television during November 1999-April 2000 was analyzed. Most alcohol ads appeared in Sports Illustrated (110), Rolling Stone (98), and Playboy (75) and outnumbered nonalcoholic beverage advertising by 3 to 1. Alcohol was almost never associated with dining. Alcohol ads emphasized sexual and social stereotypes and lacked diversity. One of every 6 magazine alcohol ads, and 1 of every 14 video-based ads, appeared to target teenagers. Many similarities existed between alcohol and nonalcohol ads. We conclude that alcohol is advertised heavily to youth through placement and appeals. The fact that themes in alcohol ads frequently parallel those in nonalcoholic beverage ads may further increase youths' receptivity.

Maternal Emotions and Self-Efficacy Beliefs in Relation to Boys and Girls with AD/HD

ERIC Educational Resources Information Center

Maniadaki, Katerina; Sonuga-Barke, Edmund; Kakouros, Efthymios; Karaba, Rania

2005-01-01

This study examined the impact of child gender on mothers' emotional responses to AD/HD, self-efficacy beliefs and perceived severity of AD/HD. Mothers (N = 118) of pre-schoolers were presented with a vignette describing a typical boy or girl with AD/HD and then completed three scales relating to their emotional response to AD/HD behaviour, their…

Consumption of added sugars among US children and adults by food purchase location and food source.

PubMed

Drewnowski, Adam; Rehm, Colin D

2014-09-01

The proposed changes to the Nutrition Facts Label by the US Food and Drug Administration will include information on added sugars for the first time. The objective was to evaluate the sources of added sugars in the diets of a representative sample of US children and adults by food purchase location and food source (eg, food group). This cross-sectional study among 31,035 children, adolescents, and adults aged ≥6 y from the 2003-2004, 2005-2006, 2007-2008, and 2009-2010 NHANES used data from a 24-h dietary recall to evaluate consumption of added sugars. Food locations of origin were identified as stores (supermarket or grocery store), quick-service restaurants/pizza (QSRs), full-service restaurants (FSRs), schools, and others (eg, vending machines or gifts). Added sugars consumption by food purchase location was evaluated by age, family income-to-poverty ratio, and race-ethnicity. Food group sources of added sugars were identified by using the National Cancer Institute food categories. Added sugars accounted for ∼14.1% of total dietary energy. Between 65% and 76% of added sugars came from stores, 6% and 12% from QSRs, and 4% and 6% from FSRs, depending on age. Older adults (aged ≥51 y) obtained a significantly greater proportion of added sugars from stores than did younger adults. Lower-income adults obtained a significantly greater proportion of added sugars from stores than did higher-income adults. Intake of added sugars did not vary by family income among children/adolescents. Soda and energy and sports drinks were the largest food group sources of added sugars (34.4%), followed by grain desserts (12.7%), fruit drinks (8.0%), candy (6.7%), and dairy desserts (5.6%). Most added sugars came from foods obtained from stores. The proposed changes to the Nutrition Facts Label should capture the bulk of added sugars in the US food supply, which suggests that the recommended changes have the potential to reduce added sugars consumption. © 2014 American Society for Nutrition.

The Black Hole Firewall and Top-Down Constructions of AdS/CFT

NASA Astrophysics Data System (ADS)

Almheiri, Ahmed Eid Khamis Thani

In the first part of this dissertation we argue that the following statements cannot be all true: (i) Black hole formation and evaporation is a unitary process as viewed by external observers, (ii) Physics outside some microscopic distance away from the event horizon is described by local effective quantum field theory, (iii) A black hole is a quantum system with a finite number of states given by the exponential of the Bekenstein Hawking entropy, and (iv) An infalling observer's experience in the vicinity of the horizon is well described by local effective quantum field theory in the infalling reference frame. We argue that the most conservative resolution is that an infalling observer will see drastic violations of effective field theory far away from the singularity, and encounter high energy quanta, a firewall, just behind the black hole event horizon. We address counter proposals to the firewall which involve, in one way or another, radical modifications of quantum mechanics or locality, and argue that they are unsatisfactory in their current formulation. We conclude this part with an investigation into the existence of firewalls in the two dimensional Einstein-dilaton gravity model of CGHS. We find that black holes in such models do not develop firewalls, but rather evaporate down to form small mass remnants. We elaborate on why this is inevitable in two dimensions and argue against a similar conclusion in higher dimensions. In the second part of this dissertation we construct AdS2 and AdS3 magnetic brane solutions within the abelian truncations of AdS4 x orbifolded S7 and AdS5 x S5 supergravity. We find a class of supersymmetric solutions of the bulk theory to assure stability. We perform a preliminary analysis demonstrating the stability of some nonsupersymmetric embeddings. We identify the dual field theory and compare the thermal entropies across the duality. We end with an investigatation into the effects of backreaction on holography in AdS2. We study a classically solvable toy model that contains an IR AdS2 throat, and find that backreaction behaves as a strongly relevant perturbation deep in the AdS2 region.

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization.

PubMed

Noda, Shinji; Suárez-Fariñas, Mayte; Ungar, Benjamin; Kim, Soo Jung; de Guzman Strong, Cristina; Xu, Hui; Peng, Xiangyu; Estrada, Yeriel D; Nakajima, Saeko; Honda, Tetsuya; Shin, Jung U; Lee, Hemin; Krueger, James G; Lee, Kwang-Hoon; Kabashima, Kenji; Guttman-Yassky, Emma

2015-11-01

Atopic dermatitis (AD) shows very high prevalence in Asia, with a large unmet need for effective therapeutics. Direct comparisons between European American (EA) and Asian patients with AD are unavailable, but earlier blood studies detected increased IL-17(+)-producing cell counts in Asian patients with AD. We sought to characterize the Asian AD skin phenotype and compare it with the EA AD skin phenotype. We performed genomic profiling (real-time PCR) and immunohistochemistry on lesional and nonlesional biopsy specimens from 52 patients with AD (25 EAs and 27 Asians), 10 patients with psoriasis (all EAs), and 27 healthy subjects (12 EAs and 15 Asians). Although disease severity/SCORAD scores were similar between the AD groups (58.0 vs 56.7, P = .77), greater acanthosis, higher Ki67 counts, and frequent parakeratosis were characteristics of lesional epidermis from Asian patients with AD (P < .05). Most (24/27) Asian patients had high IgE levels. A principal component analysis using real-time PCR data clustered the Asian AD phenotype between the EA AD and psoriasis phenotypes. TH2 skewing characterized both Asian and EA patients with AD but not patients with psoriasis. Significantly higher TH17 and TH22 (IL17A, IL19, and S100A12 in lesional and IL-22 in nonlesional skin; P < .05) and lower TH1/interferon (CXCL9, CXCL10, MX1, and IFNG in nonlesional skin; P < .05) gene induction typified AD skin in Asian patients. The Asian AD phenotype presents (even in the presence of increased IgE levels) a blended phenotype between that of EA patients with AD and those with psoriasis, including increased hyperplasia, parakeratosis, higher TH17 activation, and a strong TH2 component. The relative pathogenic contributions of the TH17 and TH2 axes in creating the Asian AD phenotype need to be tested in future clinical trials with appropriate targeted therapeutics. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Sociodemographic and Behavioral Factors Associated with Added Sugars Intake among US Adults

PubMed Central

Park, Sohyun; Thompson, Frances E.; McGuire, Lisa C.; Pan, Liping; Galuska, Deborah A.; Blanck, Heidi M.

2016-01-01

Background Reducing added sugars intake is one of the Healthy People 2020 objectives. High added sugars intake may be associated with adverse health consequences. Objective This cross-sectional study identified sociodemographic and behavioral characteristics associated with added sugars intake among US adults (18 years and older) using the 2010 National Health Interview Survey data (n=24,967). Methods The outcome variable was added sugars intake from foods and beverages using scoring algorithms to convert dietary screener frequency responses on nine items to estimates of individual dietary intake of added sugars in teaspoons per day. Added sugars intake was categorized into tertiles (lowest, middle, highest) stratified by sex. The explanatory variables were sociodemographic and behavioral characteristics. Multinomial logistic regression was used to estimate the adjusted odds ratios for the highest and middle tertile added sugars intake groups as compared with the lowest tertile group. Results Estimated median added sugars intake was 17.6 tsp/d for men and 11.7 tsp/d for women. For men and women, those who had significantly greater odds for being in the highest tertile of added sugars intake (men: ≥22.0 tsp/d; women: ≥14.6 tsp/d) were younger, less educated, had lower income, were less physically active, were current smokers, and were former or current infrequent/light drinkers, whereas non-Hispanic other/multiracial and those living in the West had significantly lower odds for being in the highest tertile of added sugars intake. Different patterns were found by sex. Non-Hispanic black men had lower odds for being in the highest tertile of added sugars intake, whereas non-Hispanic black women had greater odds for being in the highest tertile. Conclusions One in three men consumed ≥22.0 tsp added sugars and one in three women consumed ≥14.6 tsp added sugars daily. Higher added sugars intake was associated with various sociodemographic and behavioral characteristics; this information can inform efforts to design programs and policies specific to high-intake populations. PMID:27236642

Incidence, prevalence and seasonal onset variation of Addison's disease among persons with type 1 diabetes mellitus: nationwide, matched cohort studies.

PubMed

Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Svensson, Ann-Marie; Johannsson, Gudmundur

2018-01-01

We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies. Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model. Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years ( P value = 0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1-16.5). The highest incidence of AD was observed during February-March and September-October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5). The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern. © 2018 European Society of Endocrinology.

Sociodemographic and Behavioral Factors Associated with Added Sugars Intake among US Adults.

PubMed

Park, Sohyun; Thompson, Frances E; McGuire, Lisa C; Pan, Liping; Galuska, Deborah A; Blanck, Heidi M

2016-10-01

Reducing added sugars intake is one of the Healthy People 2020 objectives. High added sugars intake may be associated with adverse health consequences. This cross-sectional study identified sociodemographic and behavioral characteristics associated with added sugars intake among US adults (18 years and older) using the 2010 National Health Interview Survey data (n=24,967). The outcome variable was added sugars intake from foods and beverages using scoring algorithms to convert dietary screener frequency responses on nine items to estimates of individual dietary intake of added sugars in teaspoons per day. Added sugars intake was categorized into tertiles (lowest, middle, highest) stratified by sex. The explanatory variables were sociodemographic and behavioral characteristics. Multinomial logistic regression was used to estimate the adjusted odds ratios for the highest and middle tertile added sugars intake groups as compared with the lowest tertile group. Estimated median added sugars intake was 17.6 tsp/d for men and 11.7 tsp/d for women. For men and women, those who had significantly greater odds for being in the highest tertile of added sugars intake (men: ≥22.0 tsp/d; women: ≥14.6 tsp/d) were younger, less educated, had lower income, were less physically active, were current smokers, and were former or current infrequent/light drinkers, whereas non-Hispanic other/multiracial and those living in the West had significantly lower odds for being in the highest tertile of added sugars intake. Different patterns were found by sex. Non-Hispanic black men had lower odds for being in the highest tertile of added sugars intake, whereas non-Hispanic black women had greater odds for being in the highest tertile. One in three men consumed ≥22.0 tsp added sugars and one in three women consumed ≥14.6 tsp added sugars daily. Higher added sugars intake was associated with various sociodemographic and behavioral characteristics; this information can inform efforts to design programs and policies specific to high-intake populations. Published by Elsevier Inc.

Consumption of added sugars among US children and adults by food purchase location and food source123

PubMed Central

Drewnowski, Adam; Rehm, Colin D

2014-01-01

Background: The proposed changes to the Nutrition Facts Label by the US Food and Drug Administration will include information on added sugars for the first time. Objective: The objective was to evaluate the sources of added sugars in the diets of a representative sample of US children and adults by food purchase location and food source (eg, food group). Design: This cross-sectional study among 31,035 children, adolescents, and adults aged ≥6 y from the 2003–2004, 2005–2006, 2007–2008, and 2009–2010 NHANES used data from a 24-h dietary recall to evaluate consumption of added sugars. Food locations of origin were identified as stores (supermarket or grocery store), quick-service restaurants/pizza (QSRs), full-service restaurants (FSRs), schools, and others (eg, vending machines or gifts). Added sugars consumption by food purchase location was evaluated by age, family income-to-poverty ratio, and race-ethnicity. Food group sources of added sugars were identified by using the National Cancer Institute food categories. Results: Added sugars accounted for ∼14.1% of total dietary energy. Between 65% and 76% of added sugars came from stores, 6% and 12% from QSRs, and 4% and 6% from FSRs, depending on age. Older adults (aged ≥51 y) obtained a significantly greater proportion of added sugars from stores than did younger adults. Lower-income adults obtained a significantly greater proportion of added sugars from stores than did higher-income adults. Intake of added sugars did not vary by family income among children/adolescents. Soda and energy and sports drinks were the largest food group sources of added sugars (34.4%), followed by grain desserts (12.7%), fruit drinks (8.0%), candy (6.7%), and dairy desserts (5.6%). Conclusions: Most added sugars came from foods obtained from stores. The proposed changes to the Nutrition Facts Label should capture the bulk of added sugars in the US food supply, which suggests that the recommended changes have the potential to reduce added sugars consumption. PMID:25030785

[Effects of chronic intermittent hypoxia on oxidative stress and inflammatory response and the interventional roles of adiponectin].

PubMed

Pan, Guoyu; Su, Mei; Ding, Wenxiao; Ding, Ning; Huang, Hanpeng; Zhang, Xilong

2015-04-28

To explore the effects of chronic intermittent hypoxia (CIH) on oxidative stress and inflammatory response and the interventional roles of adiponectin (Ad). A total of 45 male Wistar rats were randomly divided into three groups of control group, CIH and CIH+Ad (n = 15 each). The control group breathed room air while the CIH and CIH+Ad groups received CIH 8 h/d for 5 successive weeks. The CIH+Ad group Ad had an injection of 10 µg once a week through tail vein. At the end of experiment (Day 35), comparison was performed among three groups about Ad, tumor necrosis factor α (TNF-α), C-reactive protein (CRP) and interleukin (IL) 6 from serum as well as malondialdehyde, superoxide dismutase (SOD), myeloperoxidase (MPO), reactive oxygen spieces (ROS) and nuclear factor (NF) κB from genioglossus. Serum Ad level in CIH group was lower than those in control and CIH+Ad groups ((4 208 ± 2 239) vs (7 051 ± 2 432) and (6 405 ± 2 384) ng/ml, all P < 0.05) with no statistic difference between control and CIH+Ad groups. Both serum levels of TNF-α and CRP were higher in CIH group than those in control and CIH+Ad groups ((70.87 ± 35.16) vs (26.54 ± 20.32) and (29.50 ± 22.54) pg/ml, as well as (31.84 ± 11.48) vs (22.68 ± 9.63), (25.32 ± 8.34) mg/L, all P < 0.05)with no significant difference between control and CIH+Ad groups. Serum IL-6 levels were all higher in CIH group and CIH+Ad group than that in control group ((30.54 ± 12.25) and (23.04 ± 13.) vs (14.10 ± 8.83) pg/ml, all P < 0.05) with no significant difference between CIH and CIH+Ad groups. Genioglossal malondialdehyde level was significantly elevated in CIH group than those in control and CIH+Ad groups ((8.05 ± 4.53) vs (5.18 ± 3.03) and ((5.74 ± 3.06) nmol/mg, all P < 0.01) with no significant difference between control and CIH+Ad groups. Genioglossal SOD activity was lower in CIH+Ad group than that in CIH group but higher than that in control group ((42.42 ± 23.17) vs (61.77 ± 36.38) and (18.62 ± 11.67) U/mg, all P < 0.05). Genioglossal MPO levels were significantly higher in both CIH and CIH+Ad groups than that in control group ((0.40 ± 0.29) and (0.31 ± 0.17) vs (0.17 ± 0.08) µU/mg, all P < 0.01), with no significance between CIH and CIH+Ad groups. The relative level of total reactive oxygen species (ROS) in genioglossus of CIH+Ad group was significantly lower than that in CIH group but higher than that in control group (1.94 ± 1.01 vs 3.31 ± 1.56 and 1.08 ± 0.38 all P < 0.05). The transcription of NF-κB was significantly higher in CIH group than that in control and CIH+Ad groups (2.24 ± 0.34 vs 0.78 ± 0.21, P < 0.05), but there was no statistical difference with CIH+Ad group (1.04 ± 0.27). CIH may induce oxidative stress and inflammation possibly through NF κB pathway while a supplement of Ad attenuates the above CIH-induced responses.

[Construction of autocatalytic caspase-3 driven by amplified human telomerase reverse transcriptase promoter and its enhanced efficacy of inducing apoptosis in human ovarian carcinoma].

PubMed

Song, Yue; Shen, Keng; He, Chun-Xia

2007-09-01

To construct recombinant adenoviral vector expressing autocatalysis caspase-3 driven by human telomerase reverse transcriptase promoter amplified by two-step transcription amplification (hTERTp-TSTA), and investigate its antitumor effect in ovarian cancer in vitro and in vivo. Recombinant adenoviruses expressing autocatalytic caspase-3 (rev-caspase-3) driven by hTERTp-TSTA were prepared, which were named as AdHTVP2G5-rev-casp3. AdHT-rev-casp3, Ad-rev-casp3 and AdHTVP2G5-EGEP, which express rev-caspase-3 driven by hTERTp, cytomegalovirus promoter (CMVp) and enhanced green fluorescent protein (EGFP), respectively, were used as controls. Western blot, cell counting kit (CCK-8), flow cytometry (FCM) and TdT-mediated dUTP-biotin nick end labeling (TUNEL) were used to detect the expression of p17, active subunit of caspase-3, and p85, and to measure cell survival rates, apoptotic rates and cell cycle distribution in ovarian cell line AO and normal human umbilical vein endothelial cell line HUVEC, following treatments of AdHTVP2G5-rev-casp3. subcutaneous tumor models and abdominally spread tumor models of human ovarian carcinoma using AO cells in BALB/c nude mice were established. Following treatments of AdHTVP2G5-rev-casp3, western blot was used to detect the expression of active caspase-3 in abdominally spread tumors and liver tissues, respectively, and the mouse survival rates and the volume of tumor nodules were measured, and the serum level of alanine transaminase (ALT) and aspartate transaminase (AST) were analyzed to monitor liver damages and HE staining was used to detect the histopathological changes of various organs. The levels of p17 expression in AdHTVP2G5-rev-casp3-treated AO cells were significantly higher than that in Ad-rev-casp3 or AdHT-rev-casp3 treated AO cells, while no expression was observed in AdHTVP2G5-rev-casp3-treated HUVEC. There was strong cell killing of AdHTVP2G5-rev-casp3 of hTERT positive AO cells, but not of the hTERT-negative HUVEC cells. Cell survival rate and apoptotic rate of AO cells treated with AdHTVP2G5-rev-casp3 were 17.8% and 40.2%, respectively, significantly different from that treated with AdHT-rev-casp3 (75.2% and 16.1%) at the multiplicity of infection (MOI) of 70 (P < 0.01). There was no significant difference in HUVEC cell survival rate and apoptotic rate between AdHTVP2G5-rev-casp3 treatment (97.7% and 2.1%, respectively) and AdHT-rev-casp3 treatment (98.5% and 1.7%, respectively) at the same MOI (P > 0.05). Significant expressions of active caspase-3 were shown in AdHTVP2G5-rev-casp3-treated tumors, whereas no expression was shown in liver. In contrast, both tumors and liver tissues showed active caspase-3 expression following treatments of Ad-rev-casp3. AdHTVP2G5-rev-casp3 and Ad-rev-casp3 prolonged mouse survival [mean survival time of (259 +/- 14) d and (213 +/- 16) d], when compared with treatment with AdHT-rev-casp3 [(177 +/- 12) d] and AdHTVP2G5-EGFP [(109 +/- 7) d; P < 0.01]. The mean volume of AdHTVP2G5-rev-casp3-treated tumor was 406 mm(3), significantly less than those of AdHT-rev-casp3 treatment (990 mm(3)), Ad-rev-casp3 treatment (645 mm(3)) and AdHTVP2G5-EGFP treatment (1728 mm(3); P < 0.01). The serum ALT and AST levels were not significantly elevated in AdHTVP2G5-rev-casp3-treated mice, whereas significantly elevated in Ad-rev-casp3-treated mice. No obvious lesions were found in any organ in AdHTVP2G5-rev-casp-treated group. Recombinant adenovirus AdHTVP2G5-rev-casp3 expressing rev-caspase-3 driven by hTERTp-TSTA can result in marked cell apoptosis with significant tumor targeting, suppressing tumor growth and prolonging the mouse survival, meanwhile, it can prevent against the liver toxicity induced by rev-caspase-3.

Prevalence of Drug Combinations Increasing Bleeding Risk Among Warfarin Users With and Without Alzheimer's Disease.

PubMed

Taipale, Heidi; Vuorikari, Hanna; Tanskanen, Antti; Koponen, Marjaana; Tiihonen, Jari; Kettunen, Raimo; Hartikainen, Sirpa

2015-11-01

The aim of this study was to analyse the prevalence and predictors of drug combinations increasing bleeding risk among warfarin users with and without Alzheimer's disease (AD). This retrospective observational study utilised data from the Finnish MEDALZ-2005 cohort. The MEDALZ-2005 study included all community-dwelling persons with a clinically verified diagnosis of AD at the end of 2005, and one comparison person without AD for each case. Data on drug use was collected from the Prescription Register. We included persons who were warfarin users during the study period 2006-2009. Drug combinations increasing bleeding risk with warfarin included selective serotonin reuptake inhibitors (SSRIs), non-steroidal anti-inflammatory agents (NSAIDs), other antithrombotic drugs and tramadol. Factors associated with combination use were investigated with logistic regression. During the follow-up, 3385 persons with AD and 4830 persons without AD used warfarin. Drug combinations increasing bleeding risk were more common in warfarin users with AD than without AD [35.9 and 30.5%, respectively (p < 0.0001)]. The most common combination was SSRIs and warfarin, which was more common among persons with AD (23.8%) than among persons without AD (10.9%). NSAIDs and warfarin combination was more common among persons without AD. Combination use was associated with AD, female gender, younger age, diabetes mellitus, rheumatoid arthritis and asthma/chronic obstructive pulmonary disease (COPD). Use of drug combinations increasing bleeding risk was more common among warfarin users with AD. Special attention should be paid to minimise the duration of concomitant use and to find safer alternatives without increased bleeding risk.

Seroprevalence of neutralizing antibodies against adenovirus type 14 and 55 in healthy adults in Southern China

PubMed Central

Zheng, Xuehua; Rong, Xia; Feng, Ying; Sun, Xikui; Li, Liang; Wang, Qian; Wang, Min; Liu, Wenkuan; Li, Chufang; Yang, Yiyu; Zhou, Rong; Lu, Jiahai; Feng, Liqiang; Chen, Ling

2017-01-01

Re-emerging human adenovirus types 14 (Ad14) and 55 (Ad55) have caused severe respiratory diseases and even deaths during recent outbreaks. However, the seroprevalence of neutralizing antibodies (nAbs) in healthy adults, which may reflect previous circulation and help to predict potential outbreaks, remains unclear. In this study, we established micro-neutralizing (MN) assays on the basis of recombinant Ad14 and Ad55 reporter viruses, and we investigated serum nAbs in healthy blood donors from Southern China. We found that the overall seropositive rates were 24.8% and 22.4% for Ad14 and Ad55 nAbs, respectively. The seropositive rates were low in individuals younger than 20, and they gradually increased with age. Ad55-seropositive individuals tended to have high nAb titers (>1000), while low (72–200) and moderate (201–1000) nAb levels were frequently observed in Ad14-seropositive ones. Surprisingly, the seropositive rates and nAb levels were associated with the blood type but not the gender of the blood donors, with type AB individuals displaying higher seropositive rates and nAb levels. Interestingly, a significant positive correlation was observed between Ad14 and Ad55 seroprevalence, and higher titers of nAbs were detected in double-positive individuals compared to single-positive ones. These results clarified the human humoral immune responses against Ad14 and Ad55 and revealed a low level of herd immunity in some subpopulations, which emphasized the importance of monitoring these two highly virulent adenoviruses and reinforced the development of prophylactic vaccines. PMID:28588291

Atropinic burden of prescriptions forms in patients with Alzheimer disease: a cross-sectional study in a French PharmacoVigilance Database.

PubMed

Montastruc, François; Rouanet, Sarah; Gardette, Virginie; Rousseau, Vanessa; Bagheri, Haleh; Montastruc, Jean-Louis

2015-07-01

Atropinic drugs in patients with Alzheimer disease (AD) can decrease the effects of anticholinesterase drugs and/or induce adverse drug reactions (ADRs). Several atropinic risk scales defining an atropinic burden of drugs were proposed but were little used in AD patients. All ADRs' notifications of AD patients registered in the Midi-Pyrénées PharmacoVigilance Database between 1999 and 2013 were analyzed using Anticholinergic Drug Scale (ADS) and Anticholinergic Duran's list. The primary objective was to quantify atropinic burden in AD patients and the secondary one to investigate associated factors. Among the 475 notifications, at least one atropinic drug was found in 282 notifications (59.4%) according to ADS and 214 (45.1%) according to Duran. Mean number of atropinics per notifications was 0.9 ± 0.9 (ADS) and 0.7 ± 0.9 (Duran). Mean atropinic burden per notifications was 1.2 ± 1.5 (ADS) and 0.9 ± 1.3 (Duran). Atropinic burden ≥ 3 was found in 87 notifications (18.2%) according to ADS and 50 (10.5%) according to Duran. There was no association between atropinic burden and age of patients. The number of drugs is associated to a high atropinic burden. The present work found an association between an atropinic drug and an anticholinesterase agent in around 1 out of 2 AD patients and a clinically significant atropinic burden (≥ 3) in around 1 to 2 AD patients out of 10. The benefit harm balance of atropinic drugs must be discussed before each prescription in AD patients.

Financial and Health Literacy Predict Incident Alzheimer's Disease Dementia and Pathology.

PubMed

Yu, Lei; Wilson, Robert S; Schneider, Julie A; Bennett, David A; Boyle, Patricia A

2017-01-01

Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. We test the hypothesis that domain specific literacy is associated with Alzheimer's disease (AD) dementia and AD pathology after controlling for cognition. Participants were community-based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years, and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined postmortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p < 0.001), and the association persisted after controlling for cognition (hazard ratio = 1.50, p = 0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β= 0.07, p = 0.035). Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition.

Adenovirus vector covalently conjugated to polyethylene glycol with a cancer-specific promoter suppresses the tumor growth through systemic administration.

PubMed

Yao, Xinglei; Yoshioka, Yasuo; Morishige, Tomohiro; Eto, Yusuke; Narimatsu, Shogo; Mizuguchi, Hiroyuki; Mukai, Yohei; Okada, Naoki; Nakagawa, Shinsaku

2010-01-01

Cancer gene therapy with adenovirus vectors (Adv) is limited to local administration because systemic administration of Adv produces a weak therapeutic effect and severe side effects. Previously, we generated a dual cancer-specific Adv system by using Adv covalently conjugated to polyethylene glycol (PEG) for transductional targeting and the telomere reverse transcriptase (TERT) promoter as a cancer-specific promoter for transcriptional targeting (PEG-Ad-TERT). We demonstrated that systemic administration of PEG-Ad-TERT showed superior antitumor effects against lung metastatic cancer with negligible side effects. Here, we investigated the therapeutic efficacy of systemic administration of PEG-Ad-TERT for the treatment of primary tumors. We first evaluated the transgene expression of PEG-Ad-TERT containing the luciferase gene (PEG-Ad-TERT/Luc) in primary tumors. Systemic administration of PEG-Ad-TERT/Luc resulted high transgene expression, similar to that observed in tumors for the conventional cytomegalovirus (CMV) promoter-driven Adv containing the luciferase gene (Ad-CMV/Luc). By comparison, transgene expression was 2500-fold lower than that of Ad-CMV/Luc in liver. We then examined the therapeutic effect of systemic administration of PEG-Ad-TERT containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk) for the treatment of primary tumors. We showed that PEG-Ad-TERT/HSVtk produced a notable antitumor effect against primary tumors with negligible side effects. These results demonstrated that PEG-Ad-TERT can be regarded as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both metastatic and primary tumors.

Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer's Disease Development.

PubMed

Lövheim, Hugo; Olsson, Jan; Weidung, Bodil; Johansson, Anders; Eriksson, Sture; Hallmans, Göran; Elgh, Fredrik

2018-01-01

Several environmental factors, including infectious agents, have been suggested to cause Alzheimer's disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies. To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD. Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses. The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007). The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system.

3D culture models of Alzheimer's disease: a road map to a "cure-in-a-dish".

PubMed

Choi, Se Hoon; Kim, Young Hye; Quinti, Luisa; Tanzi, Rudolph E; Kim, Doo Yeon

2016-12-09

Alzheimer's disease (AD) transgenic mice have been used as a standard AD model for basic mechanistic studies and drug discovery. These mouse models showed symbolic AD pathologies including β-amyloid (Aβ) plaques, gliosis and memory deficits but failed to fully recapitulate AD pathogenic cascades including robust phospho tau (p-tau) accumulation, clear neurofibrillary tangles (NFTs) and neurodegeneration, solely driven by familial AD (FAD) mutation(s). Recent advances in human stem cell and three-dimensional (3D) culture technologies made it possible to generate novel 3D neural cell culture models that recapitulate AD pathologies including robust Aβ deposition and Aβ-driven NFT-like tau pathology. These new 3D human cell culture models of AD hold a promise for a novel platform that can be used for mechanism studies in human brain-like environment and high-throughput drug screening (HTS). In this review, we will summarize the current progress in recapitulating AD pathogenic cascades in human neural cell culture models using AD patient-derived induced pluripotent stem cells (iPSCs) or genetically modified human stem cell lines. We will also explain how new 3D culture technologies were applied to accelerate Aβ and p-tau pathologies in human neural cell cultures, as compared the standard two-dimensional (2D) culture conditions. Finally, we will discuss a potential impact of the human 3D human neural cell culture models on the AD drug-development process. These revolutionary 3D culture models of AD will contribute to accelerate the discovery of novel AD drugs.

Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease.

PubMed

Yu, Lei; Chibnik, Lori B; Srivastava, Gyan P; Pochet, Nathalie; Yang, Jingyun; Xu, Jishu; Kozubek, James; Obholzer, Nikolaus; Leurgans, Sue E; Schneider, Julie A; Meissner, Alexander; De Jager, Philip L; Bennett, David A

2015-01-01

Recent large-scale genome-wide association studies have discovered several genetic variants associated with Alzheimer disease (AD); however, the extent to which DNA methylation in these AD loci contributes to the disease susceptibility remains unknown. To examine the association of brain DNA methylation in 28 reported AD loci with AD pathologies. Ongoing community-based clinical pathological cohort studies of aging and dementia (the Religious Orders Study and the Rush Memory and Aging Project) among 740 autopsied participants 66.0 to 108.3 years old. DNA methylation levels at individual CpG sites generated from dorsolateral prefrontal cortex tissue using a bead assay. Pathological diagnosis of AD by National Institute on Aging-Reagan criteria following a standard postmortem examination. Overall, 447 participants (60.4%) met the criteria for pathological diagnosis of AD. Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 was associated with pathological AD. The association was robustly retained after replacing the binary trait of pathological AD with 2 quantitative and molecular specific hallmarks of AD, namely, Aβ load and paired helical filament tau tangle density. Furthermore, RNA expression of transcripts of SORL1 and ABCA7 was associated with paired helical filament tau tangle density, and the expression of BIN1 was associated with Aβ load. Brain DNA methylation in multiple AD loci is associated with AD pathologies. The results provide further evidence that disruption of DNA methylation is involved in the pathological process of AD.

Nanotechnology solutions for Alzheimer's disease: advances in research tools, diagnostic methods and therapeutic agents.

PubMed

Nazem, Amir; Mansoori, G Ali

2008-03-01

A century of research has passed since the discovery and definition of Alzheimer's disease (AD), the primary common dementing disorder worldwide. However, AD lacks definite diagnostic approaches and effective cure at the present. Moreover, the currently available diagnostic tools are not sufficient for an early screening of AD in order to start preventive approaches. Recently the emerging field of nanotechnology has promised new techniques to solve some of the AD challenges. Nanotechnology refers to the techniques of designing and manufacturing nanosize (1-100 nm) structures through controlled positional and/or self-assembly of atoms and molecules. In this report, we present the promises that nanotechnology brings in research on the AD diagnosis and therapy. They include its potential for the better understanding of the AD root cause molecular mechanisms, AD's early diagnoses, and effective treatment. The advances in AD research offered by the atomic force microscopy, single molecule fluorescence microscopy and NanoSIMS microscopy are examined here. In addition, the recently proposed applications of nanotechnology for the early diagnosis of AD including bio-barcode assay, localized surface plasmon resonance nanosensor, quantum dot and nanomechanical cantilever arrays are analyzed. Applications of nanotechnology in AD therapy including neuroprotections against oxidative stress and anti-amyloid therapeutics, neuroregeneration and drug delivery beyond the blood brain barrier (BBB) are discussed and analyzed. All of these applications could improve the treatment approach of AD and other neurodegenerative diseases. The complete cure of AD may become feasible by a combination of nanotechnology and some other novel approaches, like stem cell technology.

Efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus.

PubMed

Zhi, Yan; Figueredo, Joanita; Kobinger, Gary P; Hagan, Heather; Calcedo, Roberto; Miller, James R; Gao, Guangping; Wilson, James M

2006-05-01

Replication-deficient human adenovirus type 5 (AdH5) vectors can induce strong transgene product-specific cellular and humoral responses. However, many adult humans have neutralizing antibodies (NAbs) against AdH5 as a result of natural infection with this virus. Therefore, a chimpanzee adenovirus C7 (AdC7) vector was developed to circumvent interference by preexisting immunity to AdH5. This study evaluated the impact of preexisting immunity to human adenovirus on the efficacy of adenovirus-based vaccines against the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). Efficacy was assessed after intramuscular injection of the vector into mice and was measured as the frequency of SARS-CoV-specific T cells and NAbs against SARS-CoV. Immunogenicity of the AdH5-based vaccine was significantly attenuated or completely abolished when the preexisting anti-AdH5 NAb titer was higher than 40. Because 27% of human serum samples from the United States tested so far have an anti-AdH5 NAb titer higher than 40, our results suggested that a significant percentage of humans with preexisting anti-AdH5 immunity would not be candidates for vaccination with an AdH5-based genetic vaccine. In contrast, preexisting anti-AdH5 NAbs have a minimal effect on the potency of the AdC7-based genetic vaccine. Taken together, our studies warrant the further development of AdC7 as a vaccine carrier for human trials.

Biomarkers in Sporadic and Familial Alzheimer's Disease.

PubMed

Lista, Simone; O'Bryant, Sid E; Blennow, Kaj; Dubois, Bruno; Hugon, Jacques; Zetterberg, Henrik; Hampel, Harald

2015-01-01

Most forms of Alzheimer's disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the "exploratory biomarker discovery arena", proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD.

Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus

PubMed Central

Sakurai, Fuminori; Narii, Nobuhiro; Tomita, Kyoko; Togo, Shinsaku; Takahashi, Kazuhisa; Machitani, Mitsuhiro; Tachibana, Masashi; Ouchi, Masaaki; Katagiri, Nobuyoshi; Urata, Yasuo; Fujiwara, Toshiyoshi; Mizuguchi, Hiroyuki

2016-01-01

Circulating tumor cells (CTCs) are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP)–expressing conditionally replicating adenovirus (Ad) (rAd-GFP) was recently developed; however, there is concern about the production of false-positive cells (GFP-positive normal blood cells) when using rAd-GFP, particularly at high titers. In addition, CTCs lacking or expressing low levels of coxsackievirus–adenovirus receptor (CAR) cannot be detected by rAd-GFP, because rAd-GFP is constructed based on Ad serotype 5, which recognizes CAR. In order to suppress the production of false-positive cells, sequences perfectly complementary to blood cell–specific microRNA, miR-142-3p, were incorporated into the 3′-untranslated region of the E1B and GFP genes. In addition, the fiber protein was replaced with that of Ad serotype 35, which recognizes human CD46, creating rAdF35-142T-GFP. rAdF35-142T-GFP efficiently labeled not only CAR-positive tumor cells but also CAR-negative tumor cells with GFP. The numbers of false-positive cells were dramatically lower for rAdF35-142T-GFP than for rAd-GFP. CTCs in the blood of cancer patients were detected by rAdF35-142T-GFP with a large reduction in false-positive cells. PMID:26966699

Dual functional bioactive-peptide, AIMP1-derived peptide (AdP), for anti-aging.

PubMed

Kim, Jina; Kang, Sujin; Kwon, HanJin; Moon, HoSang; Park, Min Chul

2018-06-19

Human skin aging is caused by several factors, such as UV irradiation, stress, hormone, and pollution. Wrinkle formation and skin pigmentation are representative features of skin aging. Although EGF and arbutin are used as anti-wrinkle and skin whitening agents, respectively, they have adverse effects on skin. When more cosmeceutical ingredients are added to cosmetic product, adverse effects are also accumulated. For these reasons, multifunctional and safe cosmetic ingredients are in demand. The aim of the present study is to investigate the novel anti-aging agents, AIMP1-derived peptide (AdP, INCI name: sh-oligopeptide-5/sh-oligopeptide SP) for cosmetic products. To assess the anti-wrinkle effect of AdP, collagen type I synthesis and fibroblast proliferation were determined on human fibroblasts. The anti-wrinkle effect of AdP was examined by ELISA and cell titer glo assay. To assess the whitening, melanin content and tyrosinase activity were determined on melanocytes. The whitening effect of AdP was examined by melanin measurement and enzyme activity assay. The safety of AdP was determined by cytotoxicity and immunogenicity, CCK-8 and TNF-α ELISA assay, respectively. AdP treatment induced the collagen type I synthesis and fibroblast proliferation. Also, AdP treatment inhibited melanin synthesis by regulating tyrosinase activity. The anti-aging effect of AdP is more potent than EGF and albutin. AdP did not show adverse effects. These results show that AdP can be dual functional and safe cosmeceutical agent to prevent skin aging. © 2018 Wiley Periodicals, Inc.

Visual system manifestations of Alzheimer's disease.

PubMed

Kusne, Yael; Wolf, Andrew B; Townley, Kate; Conway, Mandi; Peyman, Gholam A

2017-12-01

Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

PubMed Central

Kim, Jung Eun; Kim, Jong Sic; Cho, Dae Ho; Park, Hyun Jeong

2016-01-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting from interactions between genetic susceptibility and environmental factors. The pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is still challenging. There is accumulating evidence for new gene polymorphisms related to the epidermal barrier function and innate and adaptive immunity in patients with AD. Newly-found T cells and dendritic cell subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism underlying AD. Genetic changes caused by environmental factors have been shown to contribute to the pathogenesis of AD. We herein present a review of the genetics, epigenetics, barrier dysfunction and immunological abnormalities in AD with a focus on updated molecular biology. PMID:27483258

Condition on Ramond-Ramond fluxes for factorization of worldsheet scattering in anti-de Sitter space

NASA Astrophysics Data System (ADS)

Wulff, Linus

2017-11-01

Factorization of scattering is the hallmark of integrable 1 +1 dimensional quantum field theories. For factorization of scattering to be possible the set of masses and momenta must be conserved in any two-to-two scattering process. We use this fact to constrain the form of the Ramond-Ramond fluxes for integrable supergravity anti-de Sitter (AdS) backgrounds by analyzing tree-level scattering of two AdS bosons into two fermions on the worldsheet of a Berenstein-Maldacena-Nastase string. We find a condition which can be efficiently used to rule out integrability of AdS strings and therefore of the corresponding AdS/conformal field theory dualities, as we demonstrate for some simple examples.

Methane production enhancement by an independent cathode in integrated anaerobic reactor with microbial electrolysis.

PubMed

Cai, Weiwei; Han, Tingting; Guo, Zechong; Varrone, Cristiano; Wang, Aijie; Liu, Wenzong

2016-05-01

Anaerobic digestion (AD) represents a potential way to achieve energy recovery from waste organics. In this study, a novel bioelectrochemically-assisted anaerobic reactor is assembled by two AD systems separated by anion exchange membrane, with the cathode placing in the inside cylinder (cathodic AD) and the anode on the outside cylinder (anodic AD). In cathodic AD, average methane production rate goes up to 0.070 mL CH4/mL reactor/day, which is 2.59 times higher than AD control reactor (0.027 m(3) CH4/m(3)/d). And COD removal is increased ∼15% over AD control. When changing to sludge fermentation liquid, methane production rate has been further increased to 0.247 mL CH4/mL reactor/day (increased by 51.53% comparing with AD control). Energy recovery efficiency presents profitable gains, and economic revenue from increased methane totally self-cover the cost of input electricity. The study indicates that cathodic AD could cost-effectively enhance methane production rate and degradation of glucose and fermentative liquid. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of solid-state to liquid anaerobic digestion of lignocellulosic feedstocks for biogas production.

PubMed

Brown, Dan; Shi, Jian; Li, Yebo

2012-11-01

Lignocellulosic biomass feedstocks (switchgrass, corn stover, wheat straw, yard waste, leaves, waste paper, maple, and pine) were evaluated for methane production under liquid anaerobic digestion (L-AD) and solid-state anaerobic digestion (SS-AD). No significant difference in methane yield between L-AD and SS-AD, except for waste paper and pine, were found. However, the volumetric productivity was 2- to 7-fold greater in the SS-AD system compared with the L-AD system, except for paper. Methane yields from corn stover, wheat straw, and switchgrass were 2-5 times higher than those from yard waste, maple, and pine biomass. Waste paper had a methane yield of only 15 L/kg VS caused by souring during SS-AD due to organic overloading. Pine also had very low biogas yield of 17 L/kg VS, indicating the need for pretreatment prior to SS-AD. The findings of this study can guide future studies to improve the efficiency and stability of SS-AD of lignocellulosic biomass. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease

PubMed Central

Swerdlow, Russell H.

2017-01-01

Decades of research indicate mitochondria from Alzheimer’s disease (AD) patients differ from those of non-AD individuals. Initial studies revealed structural differences, and subsequent studies showed functional deficits. Observations of structure and function changes prompted investigators to consider the consequences, significance, and causes of AD-related mitochondrial dysfunction. Currently, extensive research argues mitochondria may mediate, drive, or contribute to a variety of AD pathologies. The perceived significance of these mitochondrial changes continues to grow, and many currently believe AD mitochondrial dysfunction represents a reasonable therapeutic target. Debate continues over the origin of AD mitochondrial changes. Some argue amyloid-β (Aβ) induces AD mitochondrial dysfunction, a view that does not challenge the amyloid cascade hypothesis and that may in fact help explain that hypothesis. Alternatively, data indicate mitochondrial dysfunction exists independent of Aβ, potentially lies upstream of Aβ deposition, and suggest a primary mitochondrial cascade hypothesis that assumes mitochondrial pathology hierarchically supersedes Aβ pathology. Mitochondria, therefore, appear at least to mediate or possibly even initiate pathologic molecular cascades in AD. This review considers studies and data that inform this area of AD research. PMID:29036828

Integrability of the Ad{{S}_{5}}\\times {{S}^{5}} superstring and its deformations

NASA Astrophysics Data System (ADS)

van Tongeren, Stijn J.

2014-10-01

This article reviews the application of integrability to the spectral problem of strings on Ad{{S}5}× {{S}5} and its deformations. We begin with a pedagogical introduction to integrable field theories culminating in the description of their finite-volume spectra through the thermodynamic Bethe ansatz (TBA). Next, we apply these ideas to the Ad{{S}5}× {{S}5} string and in later sections discuss how to account for particular integrable deformations. Through the AdS/CFT correspondence this gives an exact description of anomalous scaling dimensions of single trace operators in planar N=4 supersymmetry Yang-Mills theory, its ‘orbifolds’, and β and γ-deformed supersymmetric Yang-Mills theory. We also touch upon some subtleties arising in these deformed theories. Furthermore, we consider complex excited states (bound states) in the su(2) sector and give their TBA description. Finally we discuss the TBA for a quantum deformation of the Ad{{S}5}× {{S}5} superstring S-matrix, with close relations to among others Pohlmeyer reduced string theory, and briefly indicate more recent developments in this area.

Linking vascular disorders and Alzheimer’s disease: Potential involvement of BACE1

PubMed Central

Cole, Sarah L.; Vassar, Robert

2012-01-01

The etiology of Alzheimer’s disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation. PMID:18289733

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients.

PubMed

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-19

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide.

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients

PubMed Central

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-01

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730

Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.

PubMed

Mehla, Jogender; Chauhan, Balwantsinh C; Chauhan, Neelima B

2014-01-01

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.

Osteoporosis in adult patients with atopic dermatitis: A nationwide population-based study

PubMed Central

Lu, Chun-Ching; Su, Yu-Feng; Tsai, Tai-Hsin; Wu, Chieh-Hsin

2017-01-01

The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. PMID:28207767

Abnormal Mitochondrial Dynamics and Synaptic Degeneration as Early Events in Alzheimer’s Disease: Implications to Mitochondria-Targeted Antioxidant Therapeutics

PubMed Central

Reddy, P. Hemachandra; Tripathy, Raghav; Troung, Quang; Thirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala P.; Mao, Peizhong; Manczak, Maria

2011-01-01

Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. PMID:22037588

Blood Ammonia as a Possible Etiological Agent for Alzheimer’s Disease

PubMed Central

Jin, Yan Yan; Singh, Parul; Chung, Hea-Jong; Hong, Seong-Tschool

2018-01-01

Alzheimer’s disease (AD), characterized by cognitive decline and devastating neurodegeneration, is the most common age-related dementia. Since AD is a typical example of a complex disease that is affected by various genetic and environmental factors, various factors could be involved in preventing and/or treating AD. Extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau undeniably play essential roles in the etiology of AD. However, interestingly enough, medications targeting Aβ or tau all failed and the only clinically efficient medications for AD are drugs targeting the cholinergic pathway. Also, a very intriguing discovery in AD is that the Mediterranean diet (MeDi), containing an unusually large quantity of Lactobacilli, is very effective in preventing AD. Based on recently emerging findings, it is our opinion that the reduction of blood ammonia levels by Lactobacilli in MeDi is the therapeutic agent of MeDi for AD. The recent evidence of Lactobacilli lowering blood ammonia level not only provides a link between AD and MeDi but also provides a foundation of pharmabiotics for hyperammonemia as well as various neurological diseases. PMID:29734664

Childrearing style in families of anxiety-disordered children: between-family and within-family differences.

PubMed

Lindhout, Ingeborg E; Markus, Monica Th; Borst, Sophie R; Hoogendijk, Thea H G; Dingemans, Peter M A J; Boer, Frits

2009-06-01

This study examined whether (1) parents of anxiety-disordered (AD) children differed from those of non-clinical controls in their childrearing style, and whether (2) the child-rearing style of parents towards AD children is different from that towards their siblings. A clinical sample of 25 AD children, age range 8-13 years, was compared with 25 siblings and a non-clinical control group (n = 25). Childrearing was assessed by means of parental self-report, child report and through an expressed emotion interview measure. AD children perceived more parental rejection than non-clinical control children or the AD children's siblings. High-expressed emotion was scored significantly more often towards AD children than non-clinical control children, or their siblings. On [Symbol: see text]care' and [Symbol: see text]control' parental self-report showed some differences regarding AD children on the one hand and non-clinical control children or siblings of AD children on the other. These results suggest that the rearing of AD children differs significantly both from the rearing of their siblings and that of non-clinical control children.

Holography for field theory solitons

NASA Astrophysics Data System (ADS)

Domokos, Sophia K.; Royston, Andrew B.

2017-07-01

We extend a well-known D-brane construction of the AdS/dCFT correspondence to non-abelian defects. We focus on the bulk side of the correspondence and show that there exists a regime of parameters in which the low-energy description consists of two approximately decoupled sectors. The two sectors are gravity in the ambient spacetime, and a six-dimensional supersymmetric Yang-Mills theory. The Yang-Mills theory is defined on a rigid AdS4 × S 2 background and admits sixteen supersymmetries. We also consider a one-parameter deformation that gives rise to a family of Yang-Mills theories on asymptotically AdS4 × S 2 spacetimes, which are invariant under eight supersymmetries. With future holographic applications in mind, we analyze the vacuum structure and perturbative spectrum of the Yang-Mills theory on AdS4 × S 2, as well as systems of BPS equations for finite-energy solitons. Finally, we demonstrate that the classical Yang-Mills theory has a consistent truncation on the two-sphere, resulting in maximally supersymmetric Yang-Mills on AdS4.

Blood Ammonia as a Possible Etiological Agent for Alzheimer's Disease.

PubMed

Jin, Yan Yan; Singh, Parul; Chung, Hea-Jong; Hong, Seong-Tschool

2018-05-04

Alzheimer’s disease (AD), characterized by cognitive decline and devastating neurodegeneration, is the most common age-related dementia. Since AD is a typical example of a complex disease that is affected by various genetic and environmental factors, various factors could be involved in preventing and/or treating AD. Extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau undeniably play essential roles in the etiology of AD. However, interestingly enough, medications targeting Aβ or tau all failed and the only clinically efficient medications for AD are drugs targeting the cholinergic pathway. Also, a very intriguing discovery in AD is that the Mediterranean diet (MeDi), containing an unusually large quantity of Lactobacilli, is very effective in preventing AD. Based on recently emerging findings, it is our opinion that the reduction of blood ammonia levels by Lactobacilli in MeDi is the therapeutic agent of MeDi for AD. The recent evidence of Lactobacilli lowering blood ammonia level not only provides a link between AD and MeDi but also provides a foundation of pharmabiotics for hyperammonemia as well as various neurological diseases.

[The efficacy of autocatalytic casapse-3 driven by human telomerase reverse transcriptase promoter on human ovarian carcinoma].

PubMed

Song, Yue; Shen, Keng; Yu, Jing-rong

2007-11-06

To construct recombinant adenoviral vector expressing autocatalysis caspase-3 driven by human telomerase reverse transcriptase promoter (hTERTp), and investigate its antitumor effect on ovarian cancer in vitro and in vivo. Recombinant adenovirus expressing autocatalytic caspase-3 (rev-csapase-3) driven by hTERTp, AdHT-rev-casp3, was constructed. Ad-rev-casp3 expressing rev-caspase-3 driven by cytomegalovirus promoter (CMVp) was used as a positive control. hTERT positive human ovarian cancer cells of the line AO and hTERT-negative human umbilical venous endothelial cells (HUVECs) were cultured and transfected with AdHT-rev-casp3, Ad-rev-casp3, or Ad-EGFG expressing enhanced green fluorescent protein as control group. Western blotting, Cell Counting Kit (CCK-8), flow cytometry, and TUNEL were used to detect the expression of p17, active subunit of caspase-3, and p85, a poly ADP-ribose polymerase (PARP) cleavage fragment, and they were also used to measure the cell survival rate and apoptotic rate. Western blotting was used to detect the expression of active caspase-3 and its substrate PARP in the AO cells and HUVECs. Twenty nude BALB/c mice were inoculated subcutaneously with AO cells to establish subcutaneous tumor models, when the tumor grew to the volume of 150 mm3 the rats were divided into 4 equal groups to undergo intra-tumor injection of AdHT-rev-casp3, Ad-rev-casp3, Ad-EGFG, and phosphate-buffered saline (PBS) respectively, the survival rate tumor inhibition rate was observed, 72 days later the mice were killed with their livers and tumors taken out, and Western blotting was used to detect the expression of active caspase-3. Another 40 mice underwent intraperitoneal injection of AO cells to establish intraperitoneal transplanted tumor models, 21 days later the rats were divided into 4 equal groups to be injected intraperitoneally with AdHT-rev-casp3, Ad-rev-casp3, Ad-EGFG, or PBS, the survival rate was observed, and the blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected. Following the administration of AdHT-rev-casp3, active caspase-3 protein was significantly expressed, and the levels of p17 and p85 expressions were significantly elevated in AO cells, while no expressions of p17 and p85 was observed in HUVEC. In contrast, both AO and HUVEC expressed high levels of p17 and p85 protein after administrations of Ad-rev-casp3. AdHT-rev-casp3 dose-dependently killed the hTERT positive AO cells, however, showed no killing effect on the hTERT-negative HUVEC cells; whereas Ad-rev-casp3 was cytotoxic independent of the hTERT status of the cells. The killing effect of Ad-rev-casp3 was stronger than that of AdHT-rev-casp3. Treated with AdHT-rev-cap3 the expression levels of the caspase-3 fragment p17 and PARP cleavage fragment p85 of the AO cells were significantly higher than those before the treatment, however, the expression levels of p17 and p85 were both weaker than those of the AO cells treated with Ad-rev-casp-3. Though treated with AdHT-rev-casp-3, there was still no remarkable expression of p17 and p85 in the HUVECs, however, rather high protein expression levels of p17 and p85 was shown. After treatment with AdHT-rev-casp3 remarkable expression of active caspase-3 was seen in the tumor collected from the mouse body, but not in the liver; however, high caspase-3 expression level was shown in both the liver and tumor after the treatment of Ad-rev-casp-3. 53 days after treatment the tumor suppression rate of the AdHT-rev-casp3 and ad-rev-casp-3 groups were 60% and 70% respectively, both significantly higher than that of the control group. The survival rates of the mice treated with AdHT-rev-casp3 and Ad-rev-casp-3 were both significantly longer than that of the PBS group; however the survival rate of the Ad-rev-casp-3 group was longer than that of the AdHT-rev-casp3 group. The serum ALT and AST levels were not significantly elevated in the AdHT-rev-casp3-treated mice, whereas 7-9-times that before treatment in the Ad-rev-casp3-treated mice. Recombinant adenovirus AdHT-rev-casp3 expressing rev-caspase-3 driven by hTERTp effectively causes cell apoptosis targeting tumor, significantly suppresses tumor growth and prolongs the mouse survival duration, with mild liver toxicity.

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

PubMed

Varma, Vijay R; Oommen, Anup M; Varma, Sudhir; Casanova, Ramon; An, Yang; Andrews, Ryan M; O'Brien, Richard; Pletnikova, Olga; Troncoso, Juan C; Toledo, Jon; Baillie, Rebecca; Arnold, Matthias; Kastenmueller, Gabi; Nho, Kwangsik; Doraiswamy, P Murali; Saykin, Andrew J; Kaddurah-Daouk, Rima; Legido-Quigley, Cristina; Thambisetty, Madhav

2018-01-01

The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of each metabolite to severity of AD pathology and disease progression (Endophenotype Association Score in Early Alzheimer's Disease [EASE-AD]). Finally, we mapped the main metabolite classes emerging from our analyses to key biological pathways implicated in AD pathogenesis. We found that distinct sphingolipid species including sphingomyelin (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were consistently associated with severity of AD pathology at autopsy and AD progression across prodromal and preclinical stages. Higher log-transformed blood concentrations of all four sphingolipids in cognitively normal individuals were significantly associated with increased risk of future conversion to incident AD: SM C16:0 (hazard ratio [HR] = 4.430, 95% confidence interval [CI] = 1.703-11.520, p = 0.002), SM C16:1 (HR = 3.455, 95% CI = 1.516-7.873, p = 0.003), SM (OH) C14:1 (HR = 3.539, 95% CI = 1.373-9.122, p = 0.009), and SM C18:1 (HR = 2.255, 95% CI = 1.047-4.855, p = 0.038). The sphingolipid species identified map to several biologically relevant pathways implicated in AD, including tau phosphorylation, amyloid-β (Aβ) metabolism, calcium homeostasis, acetylcholine biosynthesis, and apoptosis. Our study has limitations: the relatively small number of brain tissue samples may have limited our power to detect significant associations, control for heterogeneity between groups, and replicate our findings in independent, autopsy-derived brain samples. We present a novel framework to identify biologically relevant brain and blood metabolites associated with disease pathology and progression during the prodromal and preclinical stages of AD. Our results show that perturbations in sphingolipid metabolism are consistently associated with endophenotypes across preclinical and prodromal AD, as well as with AD pathology at autopsy. Sphingolipids may be biologically relevant biomarkers for the early detection of AD, and correcting perturbations in sphingolipid metabolism may be a plausible and novel therapeutic strategy in AD.

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study

PubMed Central

Oommen, Anup M.; Varma, Sudhir; Casanova, Ramon; An, Yang; O’Brien, Richard; Pletnikova, Olga; Kastenmueller, Gabi; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Thambisetty, Madhav

2018-01-01

Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Methods and findings Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and “asymptomatic Alzheimer’s disease” (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes—sphingolipids and glycerophospholipids—that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer’s Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of each metabolite to severity of AD pathology and disease progression (Endophenotype Association Score in Early Alzheimer’s Disease [EASE-AD]). Finally, we mapped the main metabolite classes emerging from our analyses to key biological pathways implicated in AD pathogenesis. We found that distinct sphingolipid species including sphingomyelin (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were consistently associated with severity of AD pathology at autopsy and AD progression across prodromal and preclinical stages. Higher log-transformed blood concentrations of all four sphingolipids in cognitively normal individuals were significantly associated with increased risk of future conversion to incident AD: SM C16:0 (hazard ratio [HR] = 4.430, 95% confidence interval [CI] = 1.703–11.520, p = 0.002), SM C16:1 (HR = 3.455, 95% CI = 1.516–7.873, p = 0.003), SM (OH) C14:1 (HR = 3.539, 95% CI = 1.373–9.122, p = 0.009), and SM C18:1 (HR = 2.255, 95% CI = 1.047–4.855, p = 0.038). The sphingolipid species identified map to several biologically relevant pathways implicated in AD, including tau phosphorylation, amyloid-β (Aβ) metabolism, calcium homeostasis, acetylcholine biosynthesis, and apoptosis. Our study has limitations: the relatively small number of brain tissue samples may have limited our power to detect significant associations, control for heterogeneity between groups, and replicate our findings in independent, autopsy-derived brain samples. Conclusions We present a novel framework to identify biologically relevant brain and blood metabolites associated with disease pathology and progression during the prodromal and preclinical stages of AD. Our results show that perturbations in sphingolipid metabolism are consistently associated with endophenotypes across preclinical and prodromal AD, as well as with AD pathology at autopsy. Sphingolipids may be biologically relevant biomarkers for the early detection of AD, and correcting perturbations in sphingolipid metabolism may be a plausible and novel therapeutic strategy in AD. PMID:29370177

Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

PubMed

Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

2015-06-01

The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI) and late stage of Alzheimer Disease. The progression of the disease is associated with a reduction in autophagy (Beclin-1 and LC-3) observed in Inferior parietal lobe of PCAD, MCI, and AD subjects (light red). Related to the autophagy impairment, the graph shows the impairment of PI3K/Akt/mTOR in MCI and AD subjects (dark red). © 2015 International Society for Neurochemistry.

Development and Operations of the Astrophysics Data System

NASA Technical Reports Server (NTRS)

Murray, Stephen S.; Oliversen, Ronald (Technical Monitor)

2003-01-01

The ADS was represented at the AAS meeting with 3 poster papers and a demonstration booth. We have setup a mirror site of the Vizier data base system at the CDS. functionality of the ADC at Goddard. This will replace the Preparations for the APS and LPSC meetings in March started. We will have demonstrations at both meetings. Preparations for the APS and LPSC meetings in March continued. We will have demonstrations at both meetings. The ADS was represented with a poster at the joint AGUEGU meeting in Nice, France. Discussions about the on-going collaboration between the ADS and the CDS in Strasbourg, France were held in Strasbourg. The ADS was invited to organize a session about the ADS and its mirror sites at the next United Nations Workshop on Basic Space Sciences in the Developing World. Efforts are under way to enter the tables of contents of all conference proceedings in the SA0 library into the ADS. This requires copying the tables of contents from all volumes in the library and have them typed in. This will greatly enhance the coverage of the literature in the ADS. We started the development of a search system for the full text of all scanned material in the ADS. This will eventually allow our users search capabilities that so far do not exist in any form. I order to enable the full text searching, we have purchased OCR software and are in the process of OCRing the scanned pages in the ADS. Efforts are in progress to handle the inclusion of data set identifiers in article manuscripts. The ADS will be the central system that will allow the journals to verify data set identifiers. The "master verifier" has been implemented in prototype form at the ADS. We started to include more journals in Geosciences/Geophysics in the ADS. The Royal astronomical Society has decided to archive their on-line journals in the ADS three years after publication. We have started to process these older on-line articles in order to archive them in the ADS. Our mirror site in Korea now has a full article mirror. We developed XML output capability in the ADS. This will make it easier to exchange data with other data systems. We started the development of new indexing software that will eventually reduce the indexing time for a database from days to hours or less. The ADS was represented at the IAU General Assembly with a poster. Discussions with the IAU management were held about extending the ADS IAU collaborations.

Prevalence and clinical features of adult atopic dermatitis in tertiary hospitals of China.

PubMed

Wang, Xin; Shi, Xiao-Dong; Li, Lin-Feng; Zhou, Ping; Shen, Yi-Wei; Song, Qing-Kun

2017-03-01

The prevalence of atopic dermatitis (AD) has increased substantially. Previous studies have focused mostly on pediatric patients, while epidemiological investigation on adult AD has been very limited.The aim of this study was to determine the prevalence and clinical features of adult AD in outpatients with dermatitis and eczema in China mainland.A multicenter cross-sectional study was conducted among outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in China from July 1 to September 30, 2014.Of 8758 patients, 407 were adult AD. Compared with adults with other types of dermatitis, the mean age (41.8 ± 14.3 vs 42.04 ± 15.38 years, P < 0.05) and onset age (35.2 ± 11.2 vs 39.2 ± 14.0 years, P < 0.001) of adult AD were younger, and mean disease duration was longer (5.3 ± 7.1 vs 2.8 ± 4.9 years, P < 0.001). About 53.3% adult AD involved 3 or more body locations, higher than adults with other types of dermatitis (34.4%, P < 0.001), but lower than those with pediatric and adolescent AD (73.8%, P < 0.001). History of asthma (19.2% vs 6.9%, P < 0.001) or allergic conjunctivitis (21.9% vs 14.9%, P < 0.05) was more common in adult AD than pediatric/adolescent AD. Suspected bacterial infection was more frequently in adult AD than adults with other types of dermatitis (24.3% vs 14.6%, P < 0.001) and pediatric/adolescent AD (24.3% vs 14.9%, P < 0.001). More severe itching was observed in 31.4% of adult AD, higher than that of adults with other types of dermatitis (15.4%, P < 0.001), whereas similar to that of pediatric/adolescent AD (28.7%, P > 0.05). The highest (8.7%) and lowest prevalence (3.7%) of adult AD were in 25°N to 30°N and 35°N to 40°N latitude region.A substantial part of adult outpatients with eczema or dermatitis is adult AD. Middle age, more body location involvement, more suspected bacterial infection, and severe itching are the main clinical feathers of adult AD. Geographical environment and economic situation work in synergy to adult AD.

Analysis Extract. AFSC 4D0X1 Diet Therapy (Active Duty)

DTIC Science & Technology

2002-07-01

Diet (s) exp-Lacto Vegetarian Active Active Active Active AD AD...3* 87* 22* V0143 Diet (s) exp-Lacto-Ovo Vegetarian Diet Active Active... Diet (s) exp-Ovo Vegetarian Active Active Active Active AD AD

Constant curvature black holes in Einstein AdS gravity: Euclidean action and thermodynamics

NASA Astrophysics Data System (ADS)

Guilleminot, Pablo; Olea, Rodrigo; Petrov, Alexander N.

2018-03-01

We compute the Euclidean action for constant curvature black holes (CCBHs), as an attempt to associate thermodynamic quantities to these solutions of Einstein anti-de Sitter (AdS) gravity. CCBHs are gravitational configurations obtained by identifications along isometries of a D -dimensional globally AdS space, such that the Riemann tensor remains constant. Here, these solutions are interpreted as extended objects, which contain a (D -2 )-dimensional de-Sitter brane as a subspace. Nevertheless, the computation of the free energy for these solutions shows that they do not obey standard thermodynamic relations.

Are restrictive guidelines for added sugars science based?

PubMed

Erickson, Jennifer; Slavin, Joanne

2015-12-12

Added sugar regulations and recommendations have been proposed by policy makers around the world. With no universal definition, limited access to added sugar values in food products and no analytical difference from intrinsic sugars, added sugar recommendations present a unique challenge. Average added sugar intake by American adults is approximately 13% of total energy intake, and recommendations have been made as low 5% of total energy intake. In addition to public health recommendations, the Food and Drug Administration has proposed the inclusion of added sugar data to the Nutrition and Supplemental Facts Panel. The adoption of such regulations would have implications for both consumers as well as the food industry. There are certainly advantages to including added sugar data to the Nutrition Facts Panel; however, consumer research does not consistently show the addition of this information to improve consumer knowledge. With excess calorie consumption resulting in weight gain and increased risk of obesity and obesity related co-morbidities, added sugar consumption should be minimized. However, there is currently no evidence stating that added sugar is more harmful than excess calories from any other food source. The addition of restrictive added sugar recommendations may not be the most effective intervention in the treatment and prevention of obesity and other health concerns.

78 FR 39633 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

...We propose to supersede three existing airworthiness directives (ADs) that apply to The Boeing Company Model 757-200, - 200PF, and -200CB series airplanes. The existing ADs currently require repetitive inspections and audible tap tests of the upper and lower skins of the trailing edge wedges on certain slats, and related investigative and corrective actions if necessary. Since we issued these ADs, we have received reports of slats disbonding on airplanes on which the terminating actions of the existing ADs were completed and also reports of slats disbonding on airplanes outside of the applicability of the existing ADs. This proposed AD would require a determination of the type of trailing edge wedges of the leading edge slats, repetitive inspections on certain trailing edge wedges for areas of skin-to-core disbonding, and corrective actions if necessary. This proposed AD would also provide an optional terminating action for the repetitive inspections. This AD would revise the applicability of the existing ADs to include additional airplanes. We are proposing this AD to prevent delamination of the trailing edge wedge of the leading edge slats, possible loss of pieces of the trailing edge wedge assembly during flight, reduction of the reduced maneuver and stall margins, and consequent reduced controllability of the airplane.

Auditory skills, language development, and adaptive behavior of children with cochlear implants and additional disabilities

PubMed Central

Beer, Jessica; Harris, Michael S.; Kronenberger, William G.; Holt, Rachael Frush; Pisoni, David B.

2012-01-01

Objective The objective of this study was to evaluate the development of functional auditory skills, language, and adaptive behavior in deaf children with cochlear implants (CI) who also have additional disabilities (AD). Design A two-group, pre-test versus post-test design was used. Study sample Comparisons were made between 23 children with CIs and ADs, and an age-matched comparison group of 23 children with CIs without ADs (No-AD). Assessments were obtained pre-CI and within 12 months post-CI. Results All but two deaf children with ADs improved in auditory skills using the IT-MAIS. Most deaf children in the AD group made progress in receptive but not expressive language using the Preschool Language Scale, but their language quotients were lower than the No-AD group. Five of eight children with ADs made progress in daily living skills and socialization skills; two made progress in motor skills. Children with ADs who did not make progress in language, did show progress in adaptive behavior. Conclusions Children with deafness and ADs made progress in functional auditory skills, receptive language, and adaptive behavior. Expanded assessment that includes adaptive functioning and multi-center collaboration is recommended to best determine benefits of implantation in areas of expected growth in this clinical population. PMID:22509948

Type IIB supergravity solution for the T-dual of the η-deformed AdS 5 × S 5 superstring

NASA Astrophysics Data System (ADS)

Hoare, B.; Tseytlin, A. A.

2015-10-01

We find an exact type IIB supergravity solution that represents a one-parameter deformation of the T-dual of the AdS 5 × S 5 background (with T-duality applied in all 6 abelian bosonic isometric directions). The non-trivial fields are the metric, dilaton and RR 5-form only. The latter has remarkably simple "undeformed" form when written in terms of a "deformation-rotated" vielbein basis. An unusual feature of this solution is that the dilaton contains a linear dependence on the isometric coordinates of the metric precluding a straightforward reversal of T-duality. If we still formally dualize back, we find exactly the metric, B-field and product of dilaton with RR field strengths as recently extracted from the η-deformed AdS 5 × S 5 superstring action in arXiv:1507.04239. We also discuss similar solutions for deformed AdS n × S n backgrounds with n = 2 , 3. In the η → i limit we demonstrate that all these backgrounds can be interpreted as special limits of gauged WZW models and are also related to (a limit of) the Pohlmeyer-reduced models of the AdS n × S n superstrings.

A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors

PubMed Central

Farrow, Anitra L.; Peng, Binghao J.; Gu, Linlin; Krendelchtchikov, Alexandre; Matthews, Qiana L.

2016-01-01

Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi’s amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the “Antigen Capsid-Incorporation” strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. PMID:26978385

The Impact of Alzheimer's Disease on the Chinese Economy.

PubMed

Keogh-Brown, Marcus R; Jensen, Henning Tarp; Arrighi, H Michael; Smith, Richard D

2016-02-01

Recent increases in life expectancy may greatly expand future Alzheimer's Disease (AD) burdens. China's demographic profile, aging workforce and predicted increasing burden of AD-related care make its economy vulnerable to AD impacts. Previous economic estimates of AD predominantly focus on health system burdens and omit wider whole-economy effects, potentially underestimating the full economic benefit of effective treatment. AD-related prevalence, morbidity and mortality for 2011-2050 were simulated and were, together with associated caregiver time and costs, imposed on a dynamic Computable General Equilibrium model of the Chinese economy. Both economic and non-economic outcomes were analyzed. Simulated Chinese AD prevalence quadrupled during 2011-50 from 6-28 million. The cumulative discounted value of eliminating AD equates to China's 2012 GDP (US$8 trillion), and the annual predicted real value approaches US AD cost-of-illness (COI) estimates, exceeding US$1 trillion by 2050 (2011-prices). Lost labor contributes 62% of macroeconomic impacts. Only 10% derives from informal care, challenging previous COI-estimates of 56%. Health and macroeconomic models predict an unfolding 2011-2050 Chinese AD epidemic with serious macroeconomic consequences. Significant investment in research and development (medical and non-medical) is warranted and international researchers and national authorities should therefore target development of effective AD treatment and prevention strategies.

The Impact of Alzheimer's Disease on the Chinese Economy

PubMed Central

Keogh-Brown, Marcus R.; Jensen, Henning Tarp; Arrighi, H. Michael; Smith, Richard D.

2015-01-01

Background Recent increases in life expectancy may greatly expand future Alzheimer's Disease (AD) burdens. China's demographic profile, aging workforce and predicted increasing burden of AD-related care make its economy vulnerable to AD impacts. Previous economic estimates of AD predominantly focus on health system burdens and omit wider whole-economy effects, potentially underestimating the full economic benefit of effective treatment. Methods AD-related prevalence, morbidity and mortality for 2011–2050 were simulated and were, together with associated caregiver time and costs, imposed on a dynamic Computable General Equilibrium model of the Chinese economy. Both economic and non-economic outcomes were analyzed. Findings Simulated Chinese AD prevalence quadrupled during 2011–50 from 6–28 million. The cumulative discounted value of eliminating AD equates to China's 2012 GDP (US$8 trillion), and the annual predicted real value approaches US AD cost-of-illness (COI) estimates, exceeding US$1 trillion by 2050 (2011-prices). Lost labor contributes 62% of macroeconomic impacts. Only 10% derives from informal care, challenging previous COI-estimates of 56%. Interpretation Health and macroeconomic models predict an unfolding 2011–2050 Chinese AD epidemic with serious macroeconomic consequences. Significant investment in research and development (medical and non-medical) is warranted and international researchers and national authorities should therefore target development of effective AD treatment and prevention strategies. PMID:26981556

Assessing the relationship between ad volume and awareness of a tobacco education media campaign

PubMed Central

Modayil, Mary V; Stevens, Colleen

2010-01-01

Background The relation between aided ad recall and level of television ad placement in a public health setting is not well established. We examine this association by looking back at 8 years of the California's Tobacco Control Program's (CTCP) media campaign. Methods Starting in July 2001, California's campaign was continuously monitored using five telephone series of surveys and six web-based series of surveys immediately following a media flight. We used population-based statewide surveys to measure aided recall for advertisements that were placed in each of these media flights. Targeted rating points (TRPs) were used to measure ad placement intensity throughout the state. Results Cumulative TRPs exhibited a stronger relation with aided ad recall than flight TRPs or TRP density. This association increased after log-transforming cumulative TRP values. We found that a one-unit increase in log-cumulative TRPs led to a 13.6% increase in aided ad recall using web-based survey data, compared to a 5.3% increase in aided ad recall using telephone survey data. Conclusions In California, the relation between aided ad recall and cumulative TRPs showed a diminishing return after a large volume of ad placements These findings may be useful in planning future ad placement for CTCP's media campaign. PMID:20382649

Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy.

PubMed

Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

2016-12-27

Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD.

Magnetic resonance imaging biomarkers for the early diagnosis of Alzheimer's disease: a machine learning approach.

PubMed

Salvatore, Christian; Cerasa, Antonio; Battista, Petronilla; Gilardi, Maria C; Quattrone, Aldo; Castiglioni, Isabella

2015-01-01

Determination of sensitive and specific markers of very early AD progression is intended to aid researchers and clinicians to develop new treatments and monitor their effectiveness, as well as to lessen the time and cost of clinical trials. Magnetic Resonance (MR)-related biomarkers have been recently identified by the use of machine learning methods for the in vivo differential diagnosis of AD. However, the vast majority of neuroimaging papers investigating this topic are focused on the difference between AD and patients with mild cognitive impairment (MCI), not considering the impact of MCI patients who will (MCIc) or not convert (MCInc) to AD. Morphological T1-weighted MRIs of 137 AD, 76 MCIc, 134 MCInc, and 162 healthy controls (CN) selected from the Alzheimer's disease neuroimaging initiative (ADNI) cohort, were used by an optimized machine learning algorithm. Voxels influencing the classification between these AD-related pre-clinical phases involved hippocampus, entorhinal cortex, basal ganglia, gyrus rectus, precuneus, and cerebellum, all critical regions known to be strongly involved in the pathophysiological mechanisms of AD. Classification accuracy was 76% AD vs. CN, 72% MCIc vs. CN, 66% MCIc vs. MCInc (nested 20-fold cross validation). Our data encourage the application of computer-based diagnosis in clinical practice of AD opening new prospective in the early management of AD patients.

Total, Added, and Free Sugars: Are Restrictive Guidelines Science-Based or Achievable?

PubMed Central

Erickson, Jennifer; Slavin, Joanne

2015-01-01

Sugar consumption, especially added sugars, is under attack. Various government and health authorities have suggested new sugar recommendations and guidelines as low as 5% of total calories from free sugars. Definitions for total sugars, free sugars, and added sugars are not standardized, nor are there accepted nutrient databases for this information. Our objective was to measure total sugars and added sugars in sample meal plans created by the United States Department of Agriculture (USDA) and the Academy of Nutrition and Dietetics (AND). Utilizing the Nutrition Data System for Research (NDSR) nutritional database, results found that plans created by the USDA and AND averaged 5.1% and 3.1% calories from added sugar, 8.7% and 3.1% from free sugar, and 23.3% and 21.1% as total sugars respectively. Compliance with proposed added sugar recommendations would require strict dietary compliance and may not be sustainable for many Americans. Without an accepted definition and equation for calculating added sugar, added sugar recommendations are arbitrary and may reduce intakes of nutrient-rich, recommended foods, such as yogurt, whole grains, and tart fruits including cranberries, cherries, and grapefruit. Added sugars are one part of excess calorie intake; however, compliance with low added sugar recommendations may not be achievable for the general public. PMID:25884659

Total, added, and free sugars: are restrictive guidelines science-based or achievable?

PubMed

Erickson, Jennifer; Slavin, Joanne

2015-04-15

Sugar consumption, especially added sugars, is under attack. Various government and health authorities have suggested new sugar recommendations and guidelines as low as 5% of total calories from free sugars. Definitions for total sugars, free sugars, and added sugars are not standardized, nor are there accepted nutrient databases for this information. Our objective was to measure total sugars and added sugars in sample meal plans created by the United States Department of Agriculture (USDA) and the Academy of Nutrition and Dietetics (AND). Utilizing the Nutrition Data System for Research (NDSR) nutritional database, results found that plans created by the USDA and AND averaged 5.1% and 3.1% calories from added sugar, 8.7% and 3.1% from free sugar, and 23.3% and 21.1% as total sugars respectively. Compliance with proposed added sugar recommendations would require strict dietary compliance and may not be sustainable for many Americans. Without an accepted definition and equation for calculating added sugar, added sugar recommendations are arbitrary and may reduce intakes of nutrient-rich, recommended foods, such as yogurt, whole grains, and tart fruits including cranberries, cherries, and grapefruit. Added sugars are one part of excess calorie intake; however, compliance with low added sugar recommendations may not be achievable for the general public.

The major types of added sugars and non-nutritive sweeteners in a sample of Australian packaged foods.

PubMed

Probst, Yasmine C; Dengate, Alexis; Jacobs, Jenny; Louie, Jimmy Cy; Dunford, Elizabeth K

2017-12-01

Limiting the intake of added sugars in the diet remains a key focus of global dietary recommendations. To date there has been no systematic monitoring of the major types of added sugars used in the Australian food supply. The present study aimed to identify the most common added sugars and non-nutritive sweeteners in the Australian packaged food supply. Secondary analysis of data from the Australian FoodSwitch database was undertaken. Forty-six added sugars and eight non-nutritive sweetener types were extracted from the ingredient lists of 5744 foods across seventeen food categories. Australia. Not applicable. Added sugar ingredients were found in 61 % of the sample of foods examined and non-nutritive sweetener ingredients were found in 69 %. Only 31 % of foods contained no added sugar or non-nutritive sweetener. Sugar (as an ingredient), glucose syrup, maple syrup, maltodextrin and glucose/dextrose were the most common sugar ingredient types identified. Most Australian packaged food products had at least one added sugar ingredient, the most common being 'sugar'. The study provides insight into the most common types of added sugars and non-nutritive sweeteners used in the Australian food supply and is a useful baseline to monitor changes in how added sugars are used in Australian packaged foods over time.

Gender's Effects to the Early Symptoms of Alzheimer's Disease in 5 Asian Countries.

PubMed

Yang, Yuan-Han; Meguro, Kenichi; Dominguez, Jacqueline; Chen, Christopher Li-Hsian; Wang, Huali; Ong, Paulus Anam

2017-06-01

Asia has the greatest population and more patients with dementia in the world. Early recognition of clinical symptoms of Alzheimer's disease (AD) is crucial for dementia care. In order to foster collaboration in AD care, a uniformed manner to report the early clinical symptoms of AD is necessary. We have recruited clinically diagnosed patients with AD at their very mild stage with Clinical Dementia Rating (CDR) 0.5 in Taiwan, Japan, China, Philippines, and Singapore. Demographic characteristics and psychometrics including Ascertain of Dementia-8 (AD8) questionnaire were administrated to collect and report the clinical presentation in these countries. In total, 713 clinically diagnosed patients with AD at very mild stage, CDR 0.5, have been recruited from these 5 countries. "Repeats questions, stories, or statements" were consistently the frequently reported symptom across these countries. Taiwan, China, and Singapore have the higher AD8 total score compared to that in Japan and Philippines. Japan and Philippines have the gender-related differences in clinical presentation of early AD. Difficulties in using small trouble appliance and in handling complicated financial affairs were frequently reported in Japan female, compared to male, patients with AD. Identifying the clinical symptom of AD and the gender-related issues would be crucial in the dementia care in Asia.

The dysregulation of intracellular calcium in Alzheimer disease.

PubMed

Supnet, Charlene; Bezprozvanny, Ilya

2010-02-01

Alzheimer disease (AD) is the most common neurodegenerative disorder worldwide and is at present, incurable. The accumulation of toxic amyloid-beta (Abeta) peptide aggregates in AD brain are thought to trigger the extensive synaptic loss and neurodegeneration linked to cognitive decline, an idea that underlies the 'amyloid hypothesis' of AD etiology in both the familal (FAD) and sporadic forms of the disease. Mutations causing FAD also result in the dysregulation of neuronal calcium (Ca2+) handling and may contribute to AD pathogenesis, an idea termed the 'calcium hypothesis' of AD. In particular, Ca2+ dysregulation by the endoplasmic reticulum (ER) in AD mouse models results in augmented cytosolic Ca2+ levels which can trigger signalling cascades that are detrimental to neuronal function and health. However, there is growing evidence to suggest that not all forms of Ca2+ dysregulation in AD neurons are harmful and some of them instead may be compensatory. These changes may help modulate neuronal excitability and slow AD pathology, especially in the early stages of the disease. Clearly, a better understanding of how dysregulation of neuronal Ca2+ handling contributes to neurodegeneration and neuroprotection in AD is needed as Ca2+ signalling modulators are targets of great interest as potential AD therapeutics. 2010 Elsevier Ltd. All rights reserved.

The dysregulation of intracellular calcium in Alzheimer disease

PubMed Central

Supnet, Charlene; Bezprozvanny, Ilya

2010-01-01

Alzheimer disease (AD) is the most common neurodegenerative disorder worldwide and is at present, incurable. The accumulation of toxic amyloid-beta (Aβ) peptide aggregates in AD brain are thought to trigger the extensive synaptic loss and neurodegeneration linked to cognitive decline, an idea that underlies the ‘amyloid hypothesis’ of AD etiology in both the familal (FAD) and sporadic forms of the disease. Mutations causing FAD also result in the dysregulation of neuronal calcium (Ca2+) handling and may contribute to AD pathogenesis, an idea termed the ‘calcium hypothesis’ of AD. In particular, Ca2+ dysregulation by the endoplasmic reticulum (ER) in AD mouse models results in augmented cytosolic Ca2+ levels which can trigger signaling cascades that are detrimental to neuronal function and health. However, there is growing evidence to suggest that not all forms of Ca2+ dysregulation in AD neurons are harmful and some of them instead may be compensatory. These changes may help modulate neuronal excitability and slow AD pathology, especially in the early stages of the disease. Clearly, a better understanding of how dysregulation of neuronal Ca2+ handling contributes to neurodegeneration and neuroprotection in AD is needed as Ca2+ signaling modulators are targets of great interest as potential AD therapeutics. PMID:20080301

Cardiovascular risk and blood pressure control in a Spanish hypertensive population attended in a Primary Care setting. Data from the PRESCAP 2006 study.

PubMed

Rodriguez-Roca, Gustavo C; Llisterri-Caro, Jose L; Barrios-Alonso, Vivencio; Alonso-Moreno, Francisco J; Lou-Arnal, Salvador; Prieto-Diaz, Miguel A; Sanchez-Ruiz, Tomas; Dura-Belinchon, Rafael; Santos-Rodriguez, Jose A; Divison-Garrote, Juan A; Gonzalez-Segura, Diego; Banegas-Banegas, Jose R

2009-01-01

To analyse the cardiovascular risk of a broad sample of hypertensive patients and to examine whether there are differences in blood pressure control and associated factors according to the different cardiovascular risk categories. A total of 10,520 patients > or = 18 years old were included (mean age 64.6+/-11.3 years; 53.7% women). In this cohort, 3.3% were average risk, 22.6% low added risk, 22.2% moderate added risk, 33.5% high added risk and 18.4% very high added risk. Blood pressure was controlled in 41.4% (95% CI 40.5-42.4) of the total population, in 91.7% of patients with low added risk, in 19.4% with moderate added risk, in 27.4% with high added risk and in 6.8% with very high added risk. Diabetes was the factor most strongly associated with poor blood pressure control in patients with high to very high added risk (OR=7.2; p<0.0001). More than half of the hypertensive patients treated in primary health care have a high or very high added cardiovascular risk. In these patients, blood pressure control is inadequate and diabetes is associated with a sevenfold increase in the likelihood of poor blood pressure control.

A Partial E3 Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products.

PubMed

Haut, Larissa H; Gill, Amanda L; Kurupati, Raj K; Bian, Ang; Li, Yan; Giles-Davis, Wynetta; Xiang, Zhiquan; Zhou, Xiang Yang; Ertl, Hildegund C J

2016-10-01

Adenovirus (Ad) is used extensively for construction of viral vectors, most commonly with deletion in its E1 and/or E3 genomic regions. Previously, our attempts to insert envelope proteins (Env) of HIV-1 into such vectors based on chimpanzee-derived Ad (AdC) viruses were thwarted. Here, we describe that genetic instability of an E1- and E3-deleted AdC vector of serotype C6 expressing Env of HIV-1 can be overcome by reinsertion of E3 sequences with anti-apoptotic activities. This partial E3 deletion presumably delays premature death of HEK-293 packaging cell lines due to Env-induced cell apoptosis. The same partial E3 deletion also allows for the generation of stable glycoprotein 140 (gp140)- and gp160-expressing Ad vectors based on AdC7, a distinct AdC serotype. Env-expressing AdC vectors containing the partial E3 deletion are genetically stable upon serial cell culture passaging, produce yields comparable to those of other AdC vectors, and induce transgene product-specific antibody responses in mice. A partial E3 deletion thereby allows expansion of the repertoire of transgenes that can be expressed by Ad vectors.

Induction of Shock After Intravenous Injection of Adenovirus Vectors: A Critical Role for Platelet-activating Factor

PubMed Central

Xu, Zhili; Smith, Jeffrey S.; Tian, Jie; Byrnes, Andrew P.

2009-01-01

Innate immune responses are a major barrier to safe systemic gene therapy with adenovirus (Ad) vectors. We show that intravenous (IV) injection of rats with Ad5 vectors causes a novel rapid shock reaction that involves hypotension, hemoconcentration, tissue edema, and vasocongestion, with notable pathology in the pancreas and the gastrointestinal system. We show for the first time that this reaction is dependent on platelet-activating factor (PAF), a lipid signaling molecule that is a known shock inducer. Ad upregulated PAF within 5 minutes in vivo, and antagonists of the PAF receptor were able to prevent Ad-induced shock. Ad upregulated PAF via the reticuloendothelial system (RES), because splenectomy or depletion of phagocytes blocked the ability of Ad to induce both PAF and shock. Rats were considerably more sensitive to Ad-induced shock than were mice, but PAF mediated shock in both species. Other Ad-induced innate immune responses such as cytokine induction and thrombocytopenia were not mediated by PAF. In summary, systemic IV injection of Ad stimulates the RES to upregulate PAF within a matter of minutes, which results in shock. The identification of this novel pathway suggests strategies to improve the safety of systemic gene therapy with Ad vectors. PMID:19953082

Disturbed Neurotransmitter Transporter Expression in Alzheimer Disease Brain

PubMed Central

Chen, Kevin H.; Reese, Edmund A.; Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.

2011-01-01

Alzheimer disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia. An imbalance of different neurotransmitters – glutamate, acetylcholine, dopamine, and serotonin - has been proposed as the neurobiological basis of behavioral symptoms in AD. The molecular changes associated with neurotransmission imbalance in AD are not clear. We hypothesized that altered reuptake of neurotransmitters by vesicular glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter (SERT), or the dopamine reuptake transporter (DAT)) are involved in the neurotransmission imbalance in AD. We tested this hypothesis by examining protein and mRNA levels of these transporters in postmortem prefrontal cortex from 10 AD patients and 10 matched non-AD controls. Compared with controls, protein and mRNA levels of VGLUTs, EAAT1–3, VAChT, and SERT were reduced significantly in AD. Expression of DAT and catechol O-methyltransferase (COMT) was unchanged. Reduced VGLUTs and EAATs may contribute to an alteration in glutamatergic recycling, and reduced SERT could exacerbate depressive symptoms in AD. The reduced VAChT expression could contribute to the recognized cholinergic deficit in AD. Altered neurotransmitter transporters could contribute to the pathophysiology of AD and are potential targets for therapy. PMID:21743130

Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad.5/3-CTV).

PubMed

Azab, Belal M; Dash, Rupesh; Das, Swadesh K; Bhutia, Sujit K; Sarkar, Siddik; Shen, Xue-Ning; Quinn, Bridget A; Dent, Paul; Dmitriev, Igor P; Wang, Xiang-Yang; Curiel, David T; Pellecchia, Maurizio; Reed, John C; Sarkar, Devanand; Fisher, Paul B

2014-01-01

Few options are available for treating patients with advanced prostate cancer (PC). As PC is a slow growing disease and accessible by ultrasound, gene therapy could provide a viable option for this neoplasm. Conditionally replication-competent adenoviruses (CRCAs) represent potentially useful reagents for treating PC. We previously constructed a CRCA, cancer terminator virus (CTV), which showed efficacy both in vitro and in vivo for PC. The CTV was generated on a serotype 5-background (Ad.5-CTV) with infectivity depending on Coxsackie-Adenovirus Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs thereby limiting effective Ad-mediated therapy. Using serotype chimerism, a novel CTV (Ad.5/3-CTV) was created by replacing the Ad.5 fiber knob with the Ad.3 fiber knob thereby facilitating infection in a CAR-independent manner. We evaluated Ad.5/3-CTV in comparison with Ad.5-CTV in low CAR human PC cells, demonstrating higher efficiency in inhibiting cell viability in vitro. Moreover, Ad.5/3-CTV potently suppressed in vivo tumor growth in a nude mouse xenograft model and in a spontaneously induced PC that develops in Hi-myc transgenic mice. Considering the significant responses in a Phase I clinical trial of a non-replicating Ad.5-mda-7 in advanced cancers, Ad.5/3-CTV may exert improved therapeutic benefit in a clinical setting. © 2013 Wiley Periodicals, Inc.

Recruitment techniques for alcohol pharmacotherapy clinical trials: A cost-benefit analysis.

PubMed

Tompkins, D Andrew; Sides, Jessica A; Harrison, Joseph A; Strain, Eric C

2015-12-01

Alcohol use disorders (AUDs) represent a large public health burden with relatively few efficacious pharmacotherapies. Randomized controlled trials (RCTs) for new AUD therapies can be hampered by ineffective recruitment, leading to increased trial costs. The current analyses examined the effectiveness of recruitment efforts during two consecutive outpatient RCTs of novel AUD pharmacotherapies conducted between 2009 and 2012. During an initial phone screen, participants identified an ad source for learning about the study. Qualified persons were then scheduled for in-person screens. The present analyses examined demographic differences amongst the eight ad sources utilized. Recruitment effectiveness was determined by dividing the number of persons meeting criteria for an in-person screen by the total number of callers from each ad source. Cost-effectiveness was determined by dividing total ad source cost by number of screens, participants randomized, and completers. 1,813 calls resulted in 1,005 completed phone screens. The most common ad source was TV (34%), followed by print (29%), word-of-mouth (11%), flyer (8%), internet (5%), radio (5%), bus ad (2%), and billboard (1%). Participants reporting bus ads (46%), billboard (44%), or print ads (34%) were significantly more likely than the other sources to meet criteria to be scheduled for in-person screens. The most cost-effective ad source was print ($2,506 per completer), while bus ad was the least cost-effective ($13,376 per completer). Recruitment in AUD RCTs can be successful using diverse advertising methods. The present analyses favored use of print ads as most cost-effective.

Loops in AdS from conformal field theory

DOE PAGES

Aharony, Ofer; Alday, Luis F.; Bissi, Agnese; ...

2017-07-10

We propose and demonstrate a new use for conformal field theory (CFT) crossing equations in the context of AdS/CFT: the computation of loop amplitudes in AdS, dual to non-planar correlators in holographic CFTs. Loops in AdS are largely unexplored, mostly due to technical difficulties in direct calculations. We revisit this problem, and the dual 1=N expansion of CFTs, in two independent ways. The first is to show how to explicitly solve the crossing equations to the first subleading order in 1=N 2, given a leading order solution. This is done as a systematic expansion in inverse powers of the spin, to all orders. These expansions can be resummed, leading to the CFT data for nite values of the spin. Our second approach involves Mellin space. We show how the polar part of the four-point, loop-level Mellin amplitudes can be fully reconstructed from the leading-order data. The anomalous dimensions computed with both methods agree. In the case ofmore » $$\\phi$$ 4 theory in AdS, our crossing solution reproduces a previous computation of the one-loop bubble diagram. We can go further, deriving the four-point scalar triangle diagram in AdS, which had never been computed. In the process, we show how to analytically derive anomalous dimensions from Mellin amplitudes with an in nite series of poles, and discuss applications to more complicated cases such as the N = 4 super-Yang-Mills theory.« less

Loops in AdS from conformal field theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aharony, Ofer; Alday, Luis F.; Bissi, Agnese

We propose and demonstrate a new use for conformal field theory (CFT) crossing equations in the context of AdS/CFT: the computation of loop amplitudes in AdS, dual to non-planar correlators in holographic CFTs. Loops in AdS are largely unexplored, mostly due to technical difficulties in direct calculations. We revisit this problem, and the dual 1=N expansion of CFTs, in two independent ways. The first is to show how to explicitly solve the crossing equations to the first subleading order in 1=N 2, given a leading order solution. This is done as a systematic expansion in inverse powers of the spin, to all orders. These expansions can be resummed, leading to the CFT data for nite values of the spin. Our second approach involves Mellin space. We show how the polar part of the four-point, loop-level Mellin amplitudes can be fully reconstructed from the leading-order data. The anomalous dimensions computed with both methods agree. In the case ofmore » $$\\phi$$ 4 theory in AdS, our crossing solution reproduces a previous computation of the one-loop bubble diagram. We can go further, deriving the four-point scalar triangle diagram in AdS, which had never been computed. In the process, we show how to analytically derive anomalous dimensions from Mellin amplitudes with an in nite series of poles, and discuss applications to more complicated cases such as the N = 4 super-Yang-Mills theory.« less

Clinical severity correlates with impaired barrier in filaggrin-related eczema.

PubMed

Nemoto-Hasebe, Ikue; Akiyama, Masashi; Nomura, Toshifumi; Sandilands, Aileen; McLean, W H Irwin; Shimizu, Hiroshi

2009-03-01

Mutations in the gene-encoding filaggrin (FLG), a key molecule involved in skin barrier function, have been shown to be a major predisposing factor for atopic dermatitis (AD; eczema). To elucidate the pathomechanisms underlying filaggrin-related AD, we investigated stratum corneum (SC) hydration and transepidermal water loss (TEWL) as parameters of barrier function in AD patients harboring FLG mutations compared to AD patients without any FLG mutation. In filaggrin-related AD, SC hydration was both significantly reduced (P<0.01-0.05) and thicker (P<0.01-0.05) than that in healthy controls. TEWL was demonstrably increased in non-filaggrin AD compared to healthy controls (P<0.01-0.05). The objective score of atopic dermatitis (OSCORAD), a disease clinical severity index, significantly correlated with TEWL (r=0.81, P<0.005), SC hydration (r=-0.65, P<0.05), and SC thickness (r=0.59, P<0.05) in filaggrin-related AD. On the contrary, there was no correlation between these parameters and the OSCORAD in non-filaggrin AD. Furthermore, a significant correlation was obtained between the OSCORAD and specific IgE for house dust (r=0.66, P<0.05), mite allergen (r=0.53, P<0.05), and cat dander (r=0.64, P<0.05) in filaggrin-related AD, but not in non-filaggrin AD. All these data suggest that experimentally demonstrable skin barrier defects due to FLG mutations may play a crucial role in the pathogenesis of AD.

Identification of pre-clinical Alzheimer’s disease by a profile of pathogenic proteins in neurally-derived blood exosomes: a case-control study

PubMed Central

Fiandaca, Massimo S.; Kapogiannis, Dimitrios; Mapstone, Mark; Boxer, Adam; Eitan, Erez; Schwartz, Janice B.; Abner, Erin L.; Petersen, Ronald C.; Federoff, Howard J.; Miller, Bruce L.; Goetzl, Edward J.

2014-01-01

Background Proteins pathogenic in Alzheimer’s disease (AD) were extracted from neurally-derived blood exosomes and quantified to develop biomarkers for staging of sporadic AD. Methods Blood exosomes obtained at one time-point from patients with AD (n=57) or frontotemporal dementia (FTD) (n=16), and at two time-points from others (n=24) when cognitively normal and one-ten years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by ELISAs. Results Mean exosomal levels of total Tau, P-T181-tau, P-S396-tau and Aβ1-42 for AD and levels of P-T181-tau and Aβ1-42 for FTD were significantly higher than for case-controls. Stepwise discriminant modeling incorporated P-T181-tau, P-S396-tau and Aβ1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau and Aβ1-42 were significantly higher than for controls both one to ten years before and when diagnosed with AD. Conclusions Levels of P-S396-tau, P-T181-tau and Aβ1-42 in extracts of neurally-derived blood exosomes predict development of AD up to 10 years prior to clinical onset. PMID:25130657

Loops in AdS from conformal field theory

NASA Astrophysics Data System (ADS)

Aharony, Ofer; Alday, Luis F.; Bissi, Agnese; Perlmutter, Eric

2017-07-01

We propose and demonstrate a new use for conformal field theory (CFT) crossing equations in the context of AdS/CFT: the computation of loop amplitudes in AdS, dual to non-planar correlators in holographic CFTs. Loops in AdS are largely unexplored, mostly due to technical difficulties in direct calculations. We revisit this problem, and the dual 1 /N expansion of CFTs, in two independent ways. The first is to show how to explicitly solve the crossing equations to the first subleading order in 1 /N 2, given a leading order solution. This is done as a systematic expansion in inverse powers of the spin, to all orders. These expansions can be resummed, leading to the CFT data for finite values of the spin. Our second approach involves Mellin space. We show how the polar part of the four-point, loop-level Mellin amplitudes can be fully reconstructed from the leading-order data. The anomalous dimensions computed with both methods agree. In the case of ϕ 4 theory in AdS, our crossing solution reproduces a previous computation of the one-loop bubble diagram. We can go further, deriving the four-point scalar triangle diagram in AdS, which had never been computed. In the process, we show how to analytically derive anomalous dimensions from Mellin amplitudes with an infinite series of poles, and discuss applications to more complicated cases such as the N = 4 super-Yang-Mills theory.

Monoaminergic Neuropathology in Alzheimer's disease

PubMed Central

Šimić, Goran; Leko, Mirjana Babić; Wray, Selina; Harrington, Charles; Delalle, Ivana; Jovanov-Milošević, Nataša; Bažadona, Danira; Buée, Luc; de Silva, Rohan; Di Giovanni, Giuseppe; Wischik, Claude; Hof, Patrick R.

2016-01-01

None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD. PMID:27084356

Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes.

PubMed

Saha, Sayoni; Hatch, Daniel J; Hayden, Kathleen M; Steffens, David C; Potter, Guy G

2016-10-01

Identify depression symptoms during active late-life depression (LLD) that predict conversion to dementia. The authors followed a cohort of 290 participants from the Neurocognitive Outcomes of Depression in the Elderly study. All participants were actively depressed and cognitively normal at enrollment. Depression symptom factors were derived from prior factor analysis: anhedonia and sadness, suicidality and guilt, appetite and weight loss, sleep disturbance, and anxiety and tension. Cox regression analysis modeled time to Alzheimer disease (AD) and non-AD dementia onset on depression symptom factors, along with age, education, sex, and race. Significant dementia predictors were tested for interaction with age at depression onset. Higher scores on the appetite and weight loss symptom factor were associated with an increased hazard of both AD and non-AD dementia. This factor was moderated by age at first depression onset, such that higher scores were associated with higher risk of non-AD dementia when depression first occurred earlier in life. Other depression symptom factors and overall depression severity were not related to risk of AD or non-AD dementia. Results suggest greater appetite/weight loss symptoms in active episodes of LLD are associated with increased likelihood of AD and non-AD dementia, but possibly via different pathways moderated by age at first depression onset. Results may help clinicians identify individuals with LLD at higher risk of developing AD and non-AD dementia and design interventions that reduce this risk. Copyright © 2016. Published by Elsevier Inc.

What's the point? Hole-ography in Poincaré AdS

NASA Astrophysics Data System (ADS)

Espíndola, Ricardo; Güijosa, Alberto; Landetta, Alberto; Pedraza, Juan F.

2018-01-01

In the context of the AdS/CFT correspondence, we study bulk reconstruction of the Poincaré wedge of AdS_3 via hole-ography, i.e., in terms of differential entropy of the dual CFT_2. Previous work had considered the reconstruction of closed or open spacelike curves in global AdS, and of infinitely extended spacelike curves in Poincaré AdS that are subject to a periodicity condition at infinity. Working first at constant time, we find that a closed curve in Poincaré is described in the CFT by a family of intervals that covers the spatial axis at least twice. We also show how to reconstruct open curves, points and distances, and obtain a CFT action whose extremization leads to bulk points. We then generalize all of these results to the case of curves that vary in time, and discover that generic curves have segments that cannot be reconstructed using the standard hole-ographic construction. This happens because, for the nonreconstructible segments, the tangent geodesics fail to be fully contained within the Poincaré wedge. We show that a previously discovered variant of the hole-ographic method allows us to overcome this challenge, by reorienting the geodesics touching the bulk curve to ensure that they all remain within the wedge. Our conclusion is that all spacelike curves in Poincaré AdS can be completely reconstructed with CFT data, and each curve has in fact an infinite number of representations within the CFT.

Cortical Iron Reflects Severity of Alzheimer’s Disease

PubMed Central

van Duijn, Sara; Bulk, Marjolein; van Duinen, Sjoerd G.; Nabuurs, Rob J.A.; van Buchem, Mark A.; van der Weerd, Louise; Natté, Remco

2017-01-01

Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer’s disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl’s histochemical procedure. AD and elderly subjects were not different with respect to age and sex distribution. Iron distribution in the frontal cortex was not affected by normal aging but was clearly different between AD and controls. AD showed accumulation of iron in plaques, activated microglia, and, in the most severe cases, in the mid-cortical layers along myelinated fibers. The degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology in the same block, as well as to Braak stage (p < 0.001). AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks. These findings may help the interpretation of high resolution in vivo MRI and suggest the potential of using changes in iron-based MRI contrast to indirectly determine the degree of AD pathology in the frontal cortex. PMID:29081415

The relationship of cardiovascular risk factors to Alzheimer disease in Choctaw Indians.

PubMed

Weiner, Myron F; Hynan, Linda S; Rossetti, Heidi; Womack, Kyle B; Rosenberg, Roger N; Gong, Yun-Hua; Qu, Bao-Xi

2011-05-01

To test the hypothesis that cardiovascular risk factors (CRFs) influence predisposition to and the clinical course of Alzheimer disease (AD), the authors compared Choctaw Indians, a group with known high CRF with white persons with AD. In addition to CRF history, the authors investigated the frequency of apolipoprotein E4 (apoE4) genotype andplasma homocysteine (HC) levels. The authors compared 39 Choctaw Indians with AD and 39 Choctaw Indians without AD to 39 white persons with AD with all groups similar in age. CRF history included diabetes, hypertension, high cholesterol or hypolipidemic agent use, or myocardial infarction. The authors also compared plasma HC concentration and apoE4 allele frequency. Choctaw persons with AD differed significantly from white persons with AD in history of hypertension, diabetes, and in HC values but not from Indians without AD. There was a significantly lower apoE4 allele frequency in Choctaw Indian AD than white persons with AD, and both AD groups had an affected first degree relative significantly more often than Indian controls. There was no relationship between the number of CRF and age at onset among Indians or whites, whereas HC concentration was associated with significantly earlier age of onset for Choctaw Indians but not for whites. This small study suggests that in Choctaw Indians modifiable risk factors may play more of a role in disease pathogenesis than in whites and that nonmodifiable risk factors such as apoE4 may play less of a role.

Implications of comorbidity on costs for patients with Alzheimer disease.

PubMed

Kuo, Tzu-Chun; Zhao, Yang; Weir, Sharada; Kramer, Marilyn Schlein; Ash, Arlene S

2008-08-01

No prior studies have used a comprehensive clinical classification system to examine the effect of differences in overall illness burden and the presence of other diseases on costs for patients with Alzheimer disease (AD) when compared with demographically matched nondemented controls. Of a total of 627,775 enrollees who were eligible for medical and pharmacy benefits for 2003 and 2004 in the MarketScan Medicare Supplemental and Coordination of Benefits Database, we found 25,109 AD patients. For each case, 3 demographically matched nondemented controls were selected using propensity scores. Applying the diagnostic cost groups (DCGs) model to all enrollees, 2003 diagnoses were used to estimate prospective relative risk scores (RRSs) that predict 2004 costs from all illness other than AD. RRSs were then used to control for illness burden to estimate AD's independent effect on costs. Compared with the control group, the AD cohort has more comorbid conditions (8.1 vs. 6.5) and higher illness burden (1.23 vs. 1.04). Individuals with AD are more likely to have mental health conditions, neurologic conditions, cognitive disorders, cerebrovascular disease, diabetes with acute complications, and injuries. Annual costs for AD patients are $3567 (34%) higher than for controls. Excess costs attributable to AD, after controlling for non-AD illness burden, are estimated at $2307 per year with outpatient pharmacy being the key driver ($1711 in excess costs). AD patients are sicker and more expensive than demographically matched controls. Even after adjusting for differences in illness burden, costs remain higher for AD patients.

Localized gravity in string theory.

PubMed

Karch, A; Randall, L

2001-08-06

We propose a string realization of the AdS4 brane in AdS5 that is known to localize gravity. Our theory is M D5 branes in the near horizon geometry of N D3 branes, where M and N are appropriately tuned.

Feedback Form for the ADS Abstract Service

Science.gov Websites

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Association of monoamine oxidase A gene polymorphism with Alzheimer's disease and Lewy body variant.

PubMed

Takehashi, Masanori; Tanaka, Seigo; Masliah, Eliezer; Ueda, Kunihiro

2002-07-19

The association between (GT)n dinucleotide repeats in monoamine oxidase gene loci, monoamine oxidase A (MAOA) and B (MAOB), and Parkinson's disease (PD), Alzheimer's disease (AD), and Lewy body variant (LBV) of AD were determined. MAOA-GT polymorphisms were significantly associated with pure AD and LBV. MAOA-GT allele 113 was excessively represented in pure AD and LBV compared with controls. Furthermore, the frequency of females homozygous for MAOA-GT allele 113 was higher in pure AD and LBV than controls by 2.79- and 2.77-fold, respectively. In contrast, there was no association between MAOA-GT or MAOB-GT polymorphisms and PD. These results suggest that polymorphisms within the MAOA gene may have implication in AD pathology shared by pure AD and LBV.

[Trend of sugar-sweetened beverage consumption and intake of added sugar in China nine provinces among adults].

PubMed

Li, Donghua; Yu, Dongmei; Zhao, Liyun

2014-01-01

To describe sugar-sweetened beverage ( SSB) consumption status and intake of added sugar in China nine provinces among adult from 2004 to 2009. Use of "U.S.D.A. Database for the Added Sugars Content of Selected Foods" to calculate the intake of added sugar from sugar-sweetened beverage. SSB consumption was basic on the rise. The daily average intake of added sugar from SSB was 13.4 g. Men were significantly higher than women, urban was higher than rural areas. Added sugar from soft drinks was higher than that from fruit juice. Added sugar intake level in our country is low relative to other developed countries, also did not exceed WHO and the AHA recommends. But it's on the rise in generally.

Mitochondrial abnormalities in Alzheimer’s disease: Possible targets for therapeutic intervention

PubMed Central

Silva, Diana F.; Selfridge, J. Eva; Lu, Jianghua; Lezi, E; Cardoso, Sandra M.; Swerdlow, Russell H.

2013-01-01

Mitochondria from persons with Alzheimer’s disease (AD) differ from those of age-matched, control subjects. Differences in mitochondrial morphology and function are well-documented, and are not brain-limited. Some of these differences are present during all stages of AD, and are even seen in individuals who are without AD symptoms and signs but who have an increased risk of developing AD. This chapter considers the status of mitochondria in AD subjects, the potential basis for AD subject mitochondrial perturbations, and the implications of these perturbations. Data from multiple lines of investigation, including epidemiologic, biochemical, molecular, and cytoplasmic hybrid studies are reviewed. The possibility that mitochondria could potentially constitute a reasonable AD therapeutic target is discussed, as are several potential mitochondrial medicine treatment strategies. PMID:22840745

Higher Spin Fields in Three-Dimensional Gravity

NASA Astrophysics Data System (ADS)

Lepage-Jutier, Arnaud

In this thesis, we study the effects of massless higher spin fields in three-dimensional gravity with a negative cosmological constant. First, we introduce gravity in Anti-de Sitter (AdS) space without the higher spin gauge symmetry. We recapitulate the semi-classical analysis that outlines the duality between quantum gravity in three dimensions with a negative cosmological constant and a conformal field theory on the asymptotic boundary of AdS 3. We review the statistical interpretation of the black hole entropy via the AdS/CFT correspondence and the modular invariance of the partition function of a CFT on a torus. For the case of higher spin theories in AdS 3 we use those modular properties to bound the amount of gauge symmetry present. We then discuss briefly cases that can evade this bound.

A safety review of the medications used to treat atopic dermatitis.

PubMed

Shukla, Shweta; Feldman, Steven R; Strowd, Lindsay C

2018-02-01

Atopic dermatitis (AD) is a common disease in children and adults which causes severe physical discomfort and psychosocial distress. Recently novel therapies for AD have been FDA approved for use which creates the need to review the safety surrounding current FDA approved AD medications. Areas covered: Published clinical studies involving topical and oral FDA approved medications for AD are included in this review. Authors used PubMed research database to search for clinical trials involving AD patients. Expert opinion: AD is a common disease which currently has limited FDA approved medications. Given the chronicity of this disease, medications are needed which control disease while minimizing side effects to allow for long term use. Newer approved medications show promise but safety data is limited given their relatively new utilization for AD.

Gauge boson exchange in AdS d+1

NASA Astrophysics Data System (ADS)

D'Hoker, Eric; Freedman, Daniel Z.

1999-04-01

We study the amplitude for exchange of massless gauge bosons between pairs of massive scalar fields in anti-de Sitter space. In the AdS/CFT correspondence this amplitude describes the contribution of conserved flavor symmetry currents to 4-point functions of scalar operators in the boundary conformal theory. A concise, covariant, Y2K compatible derivation of the gauge boson propagator in AdS d + 1 is given. Techniques are developed to calculate the two bulk integrals over AdS space leading to explicit expressions or convenient, simple integral representations for the amplitude. The amplitude contains leading power and sub-leading logarithmic singularities in the gauge boson channel and leading logarithms in the crossed channel. The new methods of this paper are expected to have other applications in the study of the Maldacena conjecture.

Skin reaction and regeneration after single sodium lauryl sulfate exposure stratified by filaggrin genotype and atopic dermatitis phenotype.

PubMed

Bandier, J; Carlsen, B C; Rasmussen, M A; Petersen, L J; Johansen, J D

2015-06-01

Filaggrin is key for the integrity of the stratum corneum. Mutations in the filaggrin gene (FLGnull) play a prominent role in atopic dermatitis (AD) pathogenesis. People with AD have increased susceptibility to irritants. However, little is known about the effect of filaggrin genotype and AD phenotype on irritant response and skin regeneration. To investigate the role of FLGnull and AD groups for skin reaction and recovery after sodium lauryl sulfate (SLS) irritation. This is a case-control study comprising 67 subjects, including healthy controls and patients with and without FLGnull and AD. Reactivity to different doses of SLS at 24, 48, 72 and 145 h after SLS application was measured by transepidermal water loss (TEWL) and laser Doppler flowmetry (LDF). Reactivity was assessed univariately and by pattern analysis. All patient groups showed a higher degree of skin-barrier disruption and inflammation than did controls in response to SLS. Assessing reactivity by the delta value of the area under the curve for both TEWL and LDF showed significant differences between healthy controls and those with the AD phenotype, irrespective of filaggrin mutation. The poorest regeneration was among those with the AD phenotype. The two AD phenotype groups were separated by multivariate technique, due to earlier inflammatory reactivity among subjects with FLGnullplus AD compared with the AD phenotype alone. Both skin reaction and regeneration were significantly different between the patient population and the healthy controls. Additionally, response severity and regeneration depended more on AD phenotype than on filaggrin genotype, whereas the response was more rapid among the FLGnullplus AD individuals. © 2015 British Association of Dermatologists.

Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kojis, T.L.; Heinzmann, C.; Ngo, J.T.

1996-02-01

In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yieldedmore » a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families. 39 refs., 4 figs., 3 tabs.« less

Estrogen receptor β in Alzheimer's disease: From mechanisms to therapeutics.

PubMed

Zhao, Liqin; Woody, Sarah K; Chhibber, Anindit

2015-11-01

Alzheimer's disease (AD) disproportionally affects women and men. The female susceptibility for AD has been largely associated with the loss of ovarian sex hormones during menopause. This review examines the current understanding of the role of estrogen receptor β (ERβ) in the regulation of neurological health and its implication in the development and intervention of AD. Since its discovery in 1996, research conducted over the last 15-20 years has documented a great deal of evidence indicating that ERβ plays a pivotal role in a broad spectrum of brain activities from development to aging. ERβ genetic polymorphisms have been associated with cognitive impairment and increased risk for AD predominantly in women. The role of ERβ in the intervention of AD has been demonstrated by the alteration of AD pathology in response to treatment with ERβ-selective modulators in transgenic models that display pronounced plaque and tangle histopathological presentations as well as learning and memory deficits. Future studies that explore the potential interactions between ERβ signaling and the genetic isoforms of human apolipoprotein E (APOE) in brain aging and development of AD-risk phenotype are critically needed. The current trend of lost-in-translation in AD drug development that has primarily been based on early-onset familial AD (FAD) models underscores the urgent need for novel models that recapitulate the etiology of late-onset sporadic AD (SAD), the most common form of AD representing more than 95% of the current human AD population. Combining the use of FAD-related models that generally have excellent face validity with SAD-related models that hold more reliable construct validity would together increase the predictive validity of preclinical findings for successful translation into humans. Copyright © 2015 Elsevier B.V. All rights reserved.

A recombinant chimeric Ad5/3 vector expressing a multi-stage Plasmodium antigen induces protective immunity in mice using heterologous prime-boost immunization regimens1

PubMed Central

Cabrera-Mora, Monica; Fonseca, Jairo Andres; Singh, Balwan; Zhao, Chunxia; Makarova, Natalia; Dmitriev, Igor; Curiel, David T.; Blackwell, Jerry; Moreno, Alberto

2016-01-01

An ideal malaria vaccine should target several stages of the parasite life cycle and induce anti-parasite and anti-disease immunity. We have reported a Plasmodium yoelii chimeric multi-stage recombinant protein (PyLPC/RMC), engineered to express several autologous T cell epitopes and sequences derived from the circumsporozoite protein (CSP) and the merozoite surface protein 1 (MSP-1). This chimeric protein elicits protective immunity, mediated by CD4+ T cells and neutralizing antibodies. However, experimental evidence from pre-erythrocytic vaccine candidates and irradiated sporozoites has shown that CD8+ T cells play a significant role in protection. Recombinant viral vectors have been used as a vaccine platform to elicit effective CD8+ T cell responses. The human adenovirus serotype 5 (Ad5) has been tested in malaria vaccine clinical trials with excellent safety profile. Nevertheless, a major concern for the use of Ad5 is the high prevalence of anti-vector neutralizing antibodies in humans, hampering its immunogenicity. To minimize the impact of anti-vector pre-existing immunity we developed a chimeric Ad5/3 vector in which the knob region of Ad5 was replaced with that of Ad3, conferring partial resistance to anti-Ad5 neutralizing antibodies. Furthermore, we implemented heterologous adenovirus/protein immunization regimens which include a single immunization with recombinant Ad vectors. Our data show that immunization with the recombinant Ad5/3 vector induces protective efficacy indistinguishable from that elicited by Ad5. Our study also demonstrate that the dose of the Ad vectors has an impact on the memory profile and protective efficacy. The results support further studies with Ad5/3 for malaria vaccine development. PMID:27574299

Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease.

PubMed

Merkulova-Rainon, Tatyana; Mantsounga, Chris S; Broquères-You, Dong; Pinto, Cristina; Vilar, José; Cifuentes, Diana; Bonnin, Philippe; Kubis, Nathalie; Henrion, Daniel; Silvestre, Jean-Sébastien; Lévy, Bernard I

2018-03-07

The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.

Production of first generation adenoviral vectors for preclinical protocols: amplification, purification and functional titration.

PubMed

Armendáriz-Borunda, Juan; Bastidas-Ramírez, Blanca Estela; Sandoval-Rodríguez, Ana; González-Cuevas, Jaime; Gómez-Meda, Belinda; García-Bañuelos, Jesús

2011-11-01

Gene therapy represents a promising approach in the treatment of several diseases. Currently, the ideal vector has yet to be designed; though, adenoviral vectors (Ad-v) have provided the most utilized tool for gene transfer due principally to their simple production, among other specific characteristics. Ad-v viability represents a critical variable that may be affected by storage or shipping conditions and therefore it is advisable to be assessed previously to protocol performance. The present work is unique in this matter, as the complete detailed process to obtain Ad-v of preclinical grade is explained. Amplification in permissive HEK-293 cells, purification in CsCl gradients in a period of 10 h, spectrophotometric titration of viral particles (VP) and titration of infectious units (IU), yielding batches of AdβGal, AdGFP, AdHuPA and AdMMP8, of approximately 10¹³-10¹⁴ VP and 10¹²-10¹³ IU were carried out. In vivo functionality of therapeutic AdHuPA and AdMMP8 was evidenced in rats presenting CCl₄-induced fibrosis, as more than 60% of fibrosis was eliminated in livers after systemic delivery through iliac vein in comparison with irrelevant AdβGal. Time required to accomplish the whole Ad-v production steps, including IU titration was 20 to 30 days. We conclude that production of Ad-v following standard operating procedures assuring vector functionality and the possibility to effectively evaluate experimental gene therapy results, leaving aside the use of high-cost commercial kits or sophisticated instrumentation, can be performed in a conventional laboratory of cell culture. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Sugar-Sweetened Beverages Are the Main Sources of Added Sugar Intake in the Mexican Population.

PubMed

Sánchez-Pimienta, Tania G; Batis, Carolina; Lutter, Chessa K; Rivera, Juan A

2016-09-01

Sugar intake has been associated with an increased prevalence of obesity, other noncommunicable diseases, and dental caries. The WHO recommends that free sugars should be <10% of total energy intake (TEI) and that additional health benefits could be obtained with a reduction below 5% of TEI. The objective of this study was to estimate the total, intrinsic, and added sugar intake in the Mexican diet and to identify the food groups that are the main sources of these sugars. We used data from a national probabilistic survey [ENSANUT (National Health and Nutrition Survey) 2012], which represents 3 geographic regions and urban and rural areas. Dietary information was obtained by administering a 24-h recall questionnaire to 10,096 participants. Total sugar intake was estimated by using the National Institute of Public Health (INSP) food-composition table and an established method to estimate added sugars. The mean intakes of total, intrinsic, and added sugars were 365, 127, and 238 kcal/d, respectively. Added sugars contributed 13% of TEI. Sugar-sweetened beverages (SSBs) were the main source of sugars, contributing 69% of added sugars. Food products high in saturated fat and/or added sugar (HSFAS) were the second main sources of added sugars, contributing 25% of added sugars. The average intake of added sugars in the Mexican diet is higher than WHO recommendations, which may partly explain the high prevalence of obesity and diabetes in Mexico. Because SSBs and HSFAS contribute >94% of total added sugars, strategies to reduce their intake should be strengthened. This includes stronger food labels to warn the consumer about the content of added sugars in foods and beverages. © 2016 American Society for Nutrition.

Advertisement scheduling on commercial radio station using genetics algorithm

NASA Astrophysics Data System (ADS)

Purnamawati, S.; Nababan, E. B.; Tsani, B.; Taqyuddin, R.; Rahmat, R. F.

2018-03-01

On the commercial radio station, the advertising schedule is done manually, which resulted in ineffectiveness of ads schedule. Playback time consists of two types such as prime time and regular time. Radio Ads scheduling will be discussed in this research is based on ad playback schedule between 5am until 12am which rules every 15 minutes. It provides 3 slots ads with playback duration per ads maximum is 1 minute. If the radio broadcast time per day is 12 hours, then the maximum number of ads per day which can be aired is 76 ads. The other is the enactment of rules of prime time, namely the hours where the common people (listeners) have the greatest opportunity to listen to the radio, namely between the hours and hours of 4 am - 8 am, 6 pm - 10 pm. The number of screenings of the same ads on one day are limited to prime time ie 5 times, while for regular time is 8 times. Radio scheduling process is done using genetic algorithms which are composed of processes initialization chromosomes, selection, crossover and mutation. Study on chromosome 3 genes, each chromosome will be evaluated based on the value of fitness calculated based on the number of infractions that occurred on each individual chromosome. Where rule 1 is the number of screenings per ads must not be more than 5 times per day and rule 2 is there should never be two or more scheduling ads delivered on the same day and time. After fitness value of each chromosome is acquired, then the do the selection, crossover and mutation. From this research result, the optimal advertising schedule with schedule a whole day and ads data playback time ads with this level of accuracy: the average percentage was 83.79%.

The "ABCs of AD": A pilot test of an online educational module to increase use of the autonomic dysreflexia clinical practice guidelines among paramedic and nurse trainees.

PubMed

Tomasone, Jennifer R; Martin Ginis, Kathleen A; Pulkkinen, Wayland; Krassioukov, Andrei

2014-09-01

Despite availability of clinical practice guidelines (CPGs), gaps in autonomic dysreflexia (AD) knowledge and practice persist. A free, online educational module, the "ABCs of AD", was developed to improve knowledge of the AD-CPGs among emergency healthcare personnel. We examine short-term changes in paramedic and nurse trainees' knowledge of, and social cognitions towards using, the AD-CPGs following module completion. Pre-post. Thirty-four paramedic and nurse trainees from two training programs in Canada completed measures immediately before and after viewing the online "ABCs of AD" module. AD knowledge test; Theory of Planned Behavior social cognition questionnaire; module feedback survey. Paired samples t-tests revealed significant increases in participants' AD knowledge test scores (M ± SDpre = 9.00 ± 2.46, M ± SDpost = 12.03 ± 4.07, P < 0.001; d = 0.84). Prior to viewing the module, participants reported positive social cognitions for using the AD-CPGs (all Ms ≥ 4.84 out of 7). From pre- to post-module, no significant changes were seen in participants' social cognitions for using the AD-CPGs. Participants' average module viewing time was 36.73 ± 24.17 minutes (range 8-90 minutes). There was a decline in viewing from the first to the last module sections, with only half of participants viewing all six sections. Knowledge alone is insufficient for clinical behavior change; as such, social cognitive determinants of behavior should be explicitly targeted in future iterations of the module to increase the likelihood of increased use of the AD-CPGs. To engage viewers across all module sections, the "ABCs of AD" module should include supplementary learning strategies, such as interactive quizzes and peer-to-peer interaction.

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies

PubMed Central

Yu, Lei; Buchman, Aron S.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

2016-01-01

Objective: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. Methods: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10−8) for pathologic AD for all variants. Results: APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67–5.46, p = 1.9 × 10−13), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30–0.61, p = 3.1 × 10−6). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Conclusions: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. PMID:27371493

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.

PubMed

Farfel, Jose M; Yu, Lei; Buchman, Aron S; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-08-02

To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10(-8)) for pathologic AD for all variants. APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 × 10(-13)), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 × 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. © 2016 American Academy of Neurology.

No added diagnostic value of non-phosphorylated tau fraction (p-taurel) in CSF as a biomarker for differential dementia diagnosis.

PubMed

Goossens, Joery; Bjerke, Maria; Struyfs, Hanne; Niemantsverdriet, Ellis; Somers, Charisse; Van den Bossche, Tobi; Van Mossevelde, Sara; De Vil, Bart; Sieben, Anne; Martin, Jean-Jacques; Cras, Patrick; Goeman, Johan; De Deyn, Peter Paul; Van Broeckhoven, Christine; van der Zee, Julie; Engelborghs, Sebastiaan

2017-07-14

The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1-42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1-42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests. The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls. The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.

A Content Analysis of Infant and Toddler Food Advertisements in Taiwanese Popular Pregnancy and Early Parenting Magazines.

PubMed

Chen, Yi-Chun; Chang, Jung-Su; Gong, Yu-Tang

2015-08-01

Mothers who are exposed to formula advertisements (ads) are less likely to initiate breastfeeding and more likely to breastfeed for a shorter duration than other mothers. The purpose of this study was to examine infant and toddler food ads in pregnancy and early parenting magazines. A content analysis of infant and toddler food ads printed in 12 issues of 4 magazines published in 2011 was performed. Coding categories of ads included product category, advertisement category, marketing information, and advertising appeal. The target age and health-related message of each product were coded. The researchers identified 756 infant and toddler food ads in the magazines. Compared with complementary food ads, formula product ads used more marketing strategies such as antenatal classes and baby contests to influence consumers and promote products. Nutritional quality and child health benefits were the two most frequently used advertising appeals. In addition, this study identified 794 formula products and 400 complementary food products; 42.8% of the complementary food products were intended for 4-month-old infants. Furthermore, 91.9% of the ads for formula products and 81% of the ads for complementary food products contained claims concerning health function or nutrient content. Taiwanese pregnancy and early parenting magazines contain numerous infant and toddler food ads. These ads generally use health-related claims regarding specific nutrient content and health functions to promote infant and toddler foods. Health professionals should provide more information to parents on the differences between breast milk and formula milk, and they should be aware of the potential effect of infant and toddler food ads on parents' infant feeding decisions. © The Author(s) 2015.

Clinical comparison of human and canine atopic dermatitis using human diagnostic criteria (Japanese Dermatological Association, 2009): proposal of provisional diagnostic criteria for canine atopic dermatitis.

PubMed

Terada, Yuri; Nagata, Masahiko; Murayama, Nobuo; Nanko, Hiroko; Furue, Masutaka

2011-08-01

Atopic dermatitis (AD) is a common skin disease encountered in both humans and dogs. Canine AD can be used in the analysis of naturally occurring AD; however, details of clinical comparison have been lacking. The purpose of this study is to compare those clinical features using the human diagnostic criteria (Japanese Dermatological Association, 2009). Fifty-one dogs with canine AD were evaluated by the human criteria. Prior to this study, canine AD was basically diagnosed by the fulfillment of two authentic canine AD criteria and a positive reaction against Dermatophagoides farinae in serum immunoglobulin E levels and/or in intradermal tests. Among the human AD criteria items, behavior corresponding to pruritus was observed in all 51 dogs. Skin lesions corresponding to eczematous dermatitis were seen in 50 dogs, and symmetrical distribution of skin lesions was noted in all 51 dogs. A chronic or chronically relapsing course was observed in 50 dogs. Based on these results, the concordance rate for the criteria was 96% (49/51). Differential diagnoses of AD were also investigated in the same manner. The concordance rate for the criteria was 0% (0/69) in scabies, 2% (1/50) in pyoderma, 0% (0/50) in demodicosis, 0% (0/9) in cutaneous lymphoma, 0% (0/2) in ichthyosis, 25% (2/7) in flea allergy, 48% (24/50) in seborrheic dermatitis and 75% (3/4) in food allergy. Canine AD is thus indicated as a valuable counterpart to human AD in clinical aspects. In addition, the human AD criteria could be applicable, with some modification, as provisional diagnostic criteria for canine AD. © 2011 Japanese Dermatological Association.

Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimer's disease.

PubMed

Kashani, Masoud Soheili; Tavirani, Mostafa Rezaei; Talaei, Sayyed Alireza; Salami, Mahmoud

2011-04-01

Alzheimer's disease (AD) is one of the most important neurodegenerative disorders. It is characterized by dementia including deficits in learning and memory. The present study aimed to evaluate the effects of aqueous extract of lavender (Lavandula angustifolia) on spatial performance of AD rats. Male Wistar rats were first divided into control and AD groups. Rat model of AD was established by intracerebroventricular injection of 10 μg Aβ1-42 20 d prior to administration of the lavender extract. Rats in both groups were then introduced to 2 stages of task learning (with an interval of 20 d) in Morris water maze, each followed by one probe test. After the first stage of spatial learning, control and AD animals received different doses (50, 100 and 200 mg/kg) of the lavender extract. In the first stage of experiment, the latency to locate the hidden platform in AD group was significantly higher than that in control group. However, in the second stage of experiment, control and AD rats that received distilled water (vehicle) showed similar performance, indicating that the maze navigation itself could improve the spatial learning of AD animals. Besides, in the second stage of experiment, control and AD rats that received lavender extract administration at different doses (50, 100, and 200 mg/ kg) spent less time locating the platform (except for the AD rats with 50 mg/kg extract treatment), as compared with their counterparts with vehicle treatment, respectively. In addition, lavender extract significantly improved the performance of control and AD rats in the probe test, only at the dose of 200 mg/kg, as compared with their counterparts with vehicle treatment. The lavender extract can effectively reverse spatial learning deficits in AD rats.

Environmental Stress and Atopic Dermatitis: Cure with Steroid-Free Treatment and Mutual Trust in a Good Life Style

NASA Astrophysics Data System (ADS)

Kimata, H.

Atopic Dermatitis (AD) is a chronic inflammatory skin diseasewith severe itching. The exact causes for AD still remain to be elucidated. However, there are at least following 3 causes: 1) allergy, 2) bacterial infection, and 3) environmental stress. These 3 causes are mixed in AD, and consequently symptoms of AD are very complex. In addition, patients with AD are reluctant to take steroid ointment treatment. This is due to the fact that steroid is an anti-inflammatory and immunosuppressive drug. Thus steroid ointment treatment only temporally improved AD by reduction of inflammation, while it failed to cure bacterial infection. Patients had to apply steroid ointment for long-term, which caused many side effects, including enhancement of IgE production, aggravation of skin infection, and rebound phenomenon. Rebound was aggravation of symptoms upon cessation of steroid ointment use. Enhancement of IgE production augmented allergic responses, while aggravation of skin infecti on worsened skin symptoms. Collectively, lone-term use of steroid ointment complicated AD instead of cure. Patients with AD suffered from these side effects, and they did not trust steroid treatment. Recently, tacrolimus ointment was widely used instead of steroid ointment. However, tacrolimus was more potent immunosuppressive drug, and US FDA warned cancer concern. Therefore, steroid- and tacrolimus-free treatment was considered safer and ideal. Patients with AD were susceptible to stress, which worsened symptoms. Recently, new environmental stress emerged, and patients with AD were suffering from them. In this article, I describe the effect of environmental stress on allergic responses, and explain the details of cases of AD with steroid-free treatment and mutual trust, which resulted in cure of AD.

Heme oxygenase-1 posttranslational modifications in the brain of subjects with Alzheimer disease and mild cognitive impairment.

PubMed

Barone, Eugenio; Di Domenico, Fabio; Sultana, Rukhsana; Coccia, Raffaella; Mancuso, Cesare; Perluigi, Marzia; Butterfield, D Allan

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Oxidative and nitrosative stress plays a principal role in the pathogenesis of AD. The induction of the heme oxygenase-1/biliverdin reductase-A (HO-1/BVR-A) system in the brain represents one of the earliest mechanisms activated by cells to counteract the noxious effects of increased reactive oxygen species and reactive nitrogen species. Although initially proposed as a neuroprotective system in AD brain, the HO-1/BVR-A pathophysiological features are under debate. We previously reported alterations in BVR activity along with decreased phosphorylation and increased oxidative/nitrosative posttranslational modifications in the brain of subjects with AD and those with mild cognitive impairment (MCI). Furthermore, other groups proposed the observed increase in HO-1 in AD brain as a possible neurotoxic mechanism. Here we provide new insights about HO-1 in the brain of subjects with AD and MCI, the latter condition being the transitional phase between normal aging and early AD. HO-1 protein levels were significantly increased in the hippocampus of AD subjects, whereas HO-2 protein levels were significantly decreased in both AD and MCI hippocampi. In addition, significant increases in Ser-residue phosphorylation together with increased oxidative posttranslational modifications were found in the hippocampus of AD subjects. Interestingly, despite the lack of oxidative stress-induced AD neuropathology in cerebellum, HO-1 demonstrated increased Ser-residue phosphorylation and oxidative posttranslational modifications in this brain area, suggesting HO-1 as a target of oxidative damage even in the cerebellum. The significance of these findings is profound and opens new avenues into the comprehension of the role of HO-1 in the pathogenesis of AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Consumer preferences and willingness to pay for value-added chicken product attributes.

PubMed

Martínez Michel, Lorelei; Anders, Sven; Wismer, Wendy V

2011-10-01

A growing demand for convenient and ready-to-eat products has increased poultry processors' interest in developing consumer-oriented value-added chicken products. In this study, a conjoint analysis survey of 276 chicken consumers in Edmonton was conducted during the summer of 2009 to assess the importance of the chicken part, production method, processing method, storage method, the presence of added flavor, and cooking method on consumer preferences for different value-added chicken product attributes. Estimates of consumer willingness to pay (WTP) premium prices for different combinations of value-added chicken attributes were also determined. Participants'"ideal" chicken product was a refrigerated product made with free-range chicken breast, produced with no additives or preservatives and no added flavor, which could be oven heated or pan heated. Half of all participants on average were willing to pay 30% more for a value-added chicken product over the price of a conventional product. Overall, young consumers, individuals who shop at Farmers' Markets and those who prefer free-range or organic products were more likely to pay a premium for value-added chicken products. As expected, consumers' WTP was affected negatively by product price. Combined knowledge of consumer product attribute preferences and consumer WTP for value-added chicken products can help the poultry industry design innovative value-added chicken products. Practical Application:  An optimum combination of product attributes desired by consumers for the development of a new value-added chicken product, as well as the WTP for this product, have been identified in this study. This information is relevant to the poultry industry to enhance consumer satisfaction of future value-added chicken products and provide the tools for future profit growth. © 2011 Institute of Food Technologists®

Conserved Sequences at the Origin of Adenovirus DNA Replication

PubMed Central

Stillman, Bruce W.; Topp, William C.; Engler, Jeffrey A.

1982-01-01

The origin of adenovirus DNA replication lies within an inverted sequence repetition at either end of the linear, double-stranded viral DNA. Initiation of DNA replication is primed by a deoxynucleoside that is covalently linked to a protein, which remains bound to the newly synthesized DNA. We demonstrate that virion-derived DNA-protein complexes from five human adenovirus serological subgroups (A to E) can act as a template for both the initiation and the elongation of DNA replication in vitro, using nuclear extracts from adenovirus type 2 (Ad2)-infected HeLa cells. The heterologous template DNA-protein complexes were not as active as the homologous Ad2 DNA, most probably due to inefficient initiation by Ad2 replication factors. In an attempt to identify common features which may permit this replication, we have also sequenced the inverted terminal repeated DNA from human adenovirus serotypes Ad4 (group E), Ad9 and Ad10 (group D), and Ad31 (group A), and we have compared these to previously determined sequences from Ad2 and Ad5 (group C), Ad7 (group B), and Ad12 and Ad18 (group A) DNA. In all cases, the sequence around the origin of DNA replication can be divided into two structural domains: a proximal A · T-rich region which is partially conserved among these serotypes, and a distal G · C-rich region which is less well conserved. The G · C-rich region contains sequences similar to sequences present in papovavirus replication origins. The two domains may reflect a dual mechanism for initiation of DNA replication: adenovirus-specific protein priming of replication, and subsequent utilization of this primer by host replication factors for completion of DNA synthesis. Images PMID:7143575

Which medical and social decision topics are important after early diagnosis of Alzheimer's Disease from the perspectives of people with Alzheimer's Disease, spouses and professionals?

PubMed

Bronner, Katharina; Perneczky, Robert; McCabe, Rose; Kurz, Alexander; Hamann, Johannes

2016-03-08

The relevance of early decision making will rise with increasing availability of early detection of Alzheimer's disease (AD) using brain imaging or biomarkers. Five people with mild AD, six relatives and 13 healthcare professionals with experience in the management of AD were interviewed in a qualitative study regarding medical and social decision topics that emerge after early diagnosis of Alzheimer's disease. Medical treatment, assistance in everyday life and legal issues emerged as the main decision topics after an early diagnosis of AD. People with AD mostly got in contact with the health and social care system through the initiative of their spouses. They were usually aware of their illness and most received antidementia drugs and/or behavioural interventions. Following diagnosis people with AD received support by their spouses. Healthcare professionals were aware of the risk of excessive demand on relatives due to supporting their family member with AD. In the opinion of healthcare professionals legal issues should be arranged in time before patients lose their decisional capacity. In addition, people with AD and spouses reported various coping strategies, in particular "carry on as normal" after diagnosis but mostly are reluctant to actively plan for future stages of the disease. Due to the common desire to "carry on as usual" after a diagnosis of AD, many people with AD and spouses may miss the opportunity to discuss and decide on important medical and social topics. A structured approach e.g. a decision aid might support people with AD and spouses in their decision making process and thereby preserve persons' with AD autonomy before they lose the capacity in decision-making.

Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis.

PubMed

Patel, Tejas K; Patel, Parvati B

2018-06-01

The aim of this study was to estimate the prevalence of mortality among patients due to adverse drug reactions that lead to hospitalisation (fatal ADR Ad ), to explore the heterogeneity in its estimation through subgroup analysis of study characteristics, and to identify system-organ classes involved and causative drugs for fatal ADR Ad . We identified prospective ADR Ad -related studies via screening of the PubMed and Google Scholar databases with appropriate key terms. We estimated the prevalence of fatal ADR Ad using a double arcsine method and explored heterogeneity using the following study characteristics: age groups, wards, study region, ADR definitions, ADR identification methods, study duration and sample size. We examined patterns of fatal ADR Ad and causative drugs. Among 312 full-text articles assessed, 49 studies satisfied the selection criteria and were included in the analysis. The mean prevalence of fatal ADR Ad was 0.20% (95% CI: 0.13-0.27%; I 2  = 93%). The age groups and study wards were the important heterogeneity modifiers. The mean fatal ADR Ad prevalence varied from 0.01% in paediatric patients to 0.44% in the elderly. Subgroup analysis showed a higher prevalence of fatal ADR Ad in intensive care units, emergency departments, multispecialty wards and whole hospitals. Computer-based monitoring systems in combination with other methods detected higher mortality. Intracranial haemorrhage, renal failure and gastrointestinal bleeding accounted for more than 50% of fatal ADR Ad cases. Warfarin, aspirin, renin-angiotensin system (RAS) inhibitors and digoxin accounted for 60% of fatal ADR Ad . ADR Ad is an important cause of mortality. Strategies targeting the safer use of warfarin, aspirin, RAS inhibitors and digoxin could reduce the large number of fatal ADR Ad cases.

Do Sex and Violence Sell? A Meta-Analytic Review of the Effects of Sexual and Violent Media and Ad Content on Memory, Attitudes, and Buying Intentions.

PubMed

Lull, Robert B; Bushman, Brad J

2015-09-01

It is commonly assumed that sex and violence sell. However, we predicted that sex and violence would have the opposite effect. We based our predictions on the evolution and emotional arousal theoretical framework, which states that people are evolutionarily predisposed to attend to emotionally arousing cues such as sex and violence. Thus, sexual and violent cues demand more cognitive resources than nonsexual and nonviolent cues. Using this framework, we meta-analyzed the effects of sexual media, violent media, sexual ads, and violent ads on the advertising outcomes of brand memory, brand attitudes, and buying intentions. The meta-analysis included 53 experiments involving 8,489 participants. Analyses found that brands advertised in violent media content were remembered less often, evaluated less favorably, and less likely to be purchased than brands advertised in nonviolent, nonsexual media. Brands advertised using sexual ads were evaluated less favorably than brands advertised using nonviolent, nonsexual ads. There were no significant effects of sexual media on memory or buying intentions. There were no significant effects of sexual or violent ads on memory or buying intentions. As intensity of sexual ad content increased, memory, attitudes, and buying intentions decreased. When media content and ad content were congruent (e.g., violent ad in a violent program), memory improved and buying intentions increased. Violence and sex never helped and often hurt ad effectiveness. These results support the evolution and emotional arousal framework. Thus, advertisers should consider the effects of media content, ad content, content intensity, and congruity to design and place more effective ads. (c) 2015 APA, all rights reserved).

An International Multi-center Study on Self-assessed and Family Quality of Life in Children with Atopic Dermatitis.

PubMed

Chernyshov, Pavel V; Ho, Roger C; Monti, Fiorella; Jirakova, Anna; Velitchko, Svitlana S; Hercogova, Jana; Neri, Erica

2015-01-01

Atopic dermatitis (AD) is a common childhood chronic inflammatory skin condition that greatly affects the quality of life (QoL) of affected children and their families. The aim of our study was to assess QoL and family QoL of children with AD from 4 different countries and then compare the data, evaluating the effects of AD severity and age of children. Data on the Children's Dermatology Life Quality Index (CDLQI) and the Dermatitis Family Impact (DFI) questionnaires and the SCORAD index of 167 AD children 5-16 years old from Ukraine, Czech Republic, Singapore, and Italy was used for the study. SCORAD correlated with the CDLQI in all 4 countries and with DFI in all countries except Singapore. Only in Czech children did the CDLQI correlate with their age. No significant correlations between age and DFI results were found. AD symptoms and expenditures related to AD were highly scored in all countries. Impact of AD on friendship and relations between family members were among the lower scored items, and family problems did not increase proportionately with duration of AD in any of the four countries. Self-assessed health-related QoL of children with AD in our study correlated better in most cases with disease severity than family QoL results. Parents of school children with AD were generally less stressed, tired, and exhausted than parents of preschool children. These data together with results showing that duration of AD in children does not affect relations between parents and other family members is optimistic news for families with children with AD who did not recover until adolescence.

Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro

P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNAmore » expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. -- Highlights: •Adenovirus vector infection induced P-gp mRNA expression in three NSCLC cell lines. •Adenovirus vector infection enhanced P-gp-mediated doxorubicin efflux from the cells. •The increase of P-gp was not mediated by nuclear receptors (PXR, CAR) or COX-2.« less

Vitamin B12 in Association with Antipsychotic Drugs Can Modulate the Expression of Pro-/Anti-Inflammatory Cytokines in Alzheimer Disease Patients.

PubMed

Vakilian, Alireza; Razavi-Nasab, Seyed Moein; Ravari, Ali; Mirzaei, Tayebeh; Moghadam-Ahmadi, Amir; Jalali, Nazanin; Bahramabadi, Reza; Rezayati, Mohammadtaghi; Yazdanpanah-Ravari, Amin; Bahmaniar, Farhad; Bagheri, Mohammad Reza; Sheikh Fathollahi, Mahmood; Asadikaram, Gholamreza; Kazemi Arababadi, Mohammad

2017-01-01

Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-β, tumor necrosis factor (TNF)-α, and endothelin (ET)-1). Serum levels of IL-6, IL-8, TGF-β, TNF-α, and ET-1 were evaluated in the following groups: healthy controls, nonpsychotic AD patients, psychotic AD patients, psychotic AD patients under treatment with risperidone, psychotic AD patients under treatment with risperidone plus vitamin B12, psychotic AD patients under treatment with quetiapine, and psychotic AD patients under treatment with quetiapine plus vitamin B12. Treatment with antipsychotic drugs plus vitamin B12 led to a decreased expression of IL-8 and TNF-α and an increased expression of TGF-β. Vitamin B12 in association with quetiapine reduced the pain in psychotic AD patients. Proinflammatory cytokines play important roles in the pathogenesis of psychosis in AD patients. Antipsychotic drugs plus vitamin B12 can reduce and induce the expression of proinflammatory and anti-inflammatory cytokines to improve psychotic symptoms in AD patients. © 2018 S. Karger AG, Basel.

Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer's disease.

PubMed

Grimm, Amandine; Friedland, Kristina; Eckert, Anne

2016-04-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease that represents the most common form of dementia among the elderly. Despite the fact that AD was studied for decades, the underlying mechanisms that trigger this neuropathology remain unresolved. Since the onset of cognitive deficits occurs generally within the 6th decade of life, except in rare familial case, advancing age is the greatest known risk factor for AD. To unravel the pathogenesis of the disease, numerous studies use cellular and animal models based on genetic mutations found in rare early onset familial AD (FAD) cases that represent less than 1 % of AD patients. However, the underlying process that leads to FAD appears to be distinct from that which results in late-onset AD. As a genetic disorder, FAD clearly is a consequence of malfunctioning/mutated genes, while late-onset AD is more likely due to a gradual accumulation of age-related malfunction. Normal aging and AD are both marked by defects in brain metabolism and increased oxidative stress, albeit to varying degrees. Mitochondria are involved in these two phenomena by controlling cellular bioenergetics and redox homeostasis. In the present review, we compare the common features observed in both brain aging and AD, placing mitochondrial in the center of pathological events that separate normal and pathological aging. We emphasize a bioenergetic model for AD including the inverse Warburg hypothesis which postulates that AD is a consequence of mitochondrial deregulation leading to metabolic reprogramming as an initial attempt to maintain neuronal integrity. After the failure of this compensatory mechanism, bioenergetic deficits may lead to neuronal death and dementia. Thus, mitochondrial dysfunction may represent the missing link between aging and sporadic AD, and represent attractive targets against neurodegeneration.

Alzheimer's disease and diet: a systematic review.

PubMed

Yusufov, Miryam; Weyandt, Lisa L; Piryatinsky, Irene

2017-02-01

Purpose/Aim: Approximately 44 million people worldwide have Alzheimer's disease (AD). Numerous claims have been made regarding the influence of diet on AD development. The aims of this systematic review were to summarize the evidence considering diet as a protective or risk factor for AD, identify methodological challenges and limitations, and provide future research directions. Medline, PsycINFO and PsycARTICLES were searched for articles that examined the relationship between diet and AD. On the basis of the inclusion and exclusion criteria, 64 studies were included, generating a total of 141 dietary patterns or "models". All studies were published between 1997 and 2015, with a total of 132 491 participants. Twelve studies examined the relationship between a Mediterranean (MeDi) diet and AD development, 10 of which revealed a significant association. Findings were inconsistent with respect to sample size, AD diagnosis and food measures. Further, the majority of studies (81.3%) included samples with mean baseline ages that were at risk for AD based on age (>65 years), ranging from 52.0 to 85.4 years. The range of follow-up periods was 1.5-32.0 years. The mean age of the samples poses a limitation in determining the influence of diet on AD; given that AD has a long prodromal phase prior to the manifestation of symptoms and decline. Further studies are necessary to determine whether diet is a risk or protective factor for AD, foster translation of research into clinical practice and elucidate dietary recommendations. Despite the methodological limitations, the finding that 50 of the 64 reviewed studies revealed an association between diet and AD incidence offers promising implications for diet as a modifiable risk factor for AD.