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Sample records for early infection stages

  1. HMGCR inhibits the early stage of PCV2 infection, while PKC enhances the infection at the late stage.

    PubMed

    Ma, Teng; Chen, Xinrong; Ouyang, Hongsheng; Liu, Xiaohui; Ouyang, Ting; Peng, Zhiyuan; Yang, Xin; Chen, Fuwang; Pang, Daxin; Bai, Jieying; Ren, Linzhu

    2017-02-02

    Porcine circovirus type 2 (PCV2) is the smallest DNA virus, which causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD). Due the small size of viral genomic DNA, PCV2 replication predominantly relies on the host factors. In this study, effects of PKC and HMGCR on PCV2 infection were evaluated using real time PCR and western blot. We found that PKC and HMGCR participated in different stages of PCV2 infection. HMGCR works on the early stage of the infection to inhibit the virus infection, while PKC enhances the infection at the late stage. Furthermore, PKC enhances PCV2 replication by activating JNK1/2 and inactivating HMGCR via regulating phosphorylation of these two proteins, while HMGCR can suppress phosphorylation of JNK1/2. The results in the present study will provide new sights in the pathogenesis of PCV2 infection, as well as interactions between host factors during PCV2 infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Early infection risk with primary versus staged Hemodialysis Reliable Outflow (HeRO) graft implantation.

    PubMed

    Griffin, Andrew S; Gage, Shawn M; Lawson, Jeffrey H; Kim, Charles Y

    2017-01-01

    This study evaluated whether the use of a staged Hemodialysis Reliable Outflow (HeRO; Merit Medical, South Jordan, Utah) implantation strategy incurs increased early infection risk compared with conventional primary HeRO implantation. A retrospective review was performed of 192 hemodialysis patients who underwent HeRO graft implantation: 105 patients underwent primary HeRO implantation in the operating room, and 87 underwent a staged implantation where a previously inserted tunneled central venous catheter was used for guidewire access for the venous outflow component. Within the staged implantation group, 32 were performed via an existing tunneled hemodialysis catheter (incidentally staged), and 55 were performed via a tunneled catheter inserted across a central venous occlusion in an interventional radiology suite specifically for HeRO implantation (intentionally staged). Early infection was defined as episodes of bacteremia or HeRO infection requiring resection ≤30 days of HeRO implantation. For staged HeRO implantations, the median interval between tunneled catheter insertion and conversion to a HeRO graft was 42 days. The overall HeRO-related infection rate ≤30 days of implantation was 8.6% for primary HeRO implantation and 2.3% for staged implantations (P = .12). The rates of early bacteremia and HeRO resection requiring surgical resection were not significantly different between groups (P = .19 and P = .065, respectively), nor were age, gender, laterality, anastomosis to an existing arteriovenous access, human immunodeficiency virus status, diabetes, steroids, chemotherapy, body mass index, or graft location. None of the patient variables, techniques, or graft-related variables correlated significantly with the early infection rate. The staged HeRO implantation strategy did not result in an increased early infection risk compared with conventional primary implantation and is thus a reasonable strategy for HeRO insertion in hemodialysis patients

  3. Microaspiration of Solanum tuberosum root cells at early stages of infection by Globodera pallida.

    PubMed

    Kooliyottil, Rinu; Dandurand, Louise-Marie; Kuhl, Joseph C; Caplan, Allan; Xiao, Fangming

    2017-01-01

    Sedentary endoparasitic cyst nematodes form a feeding structure in plant roots, called a syncytium. Syncytium formation involves extensive transcriptional modifications, which leads to cell modifications such as increased cytoplasmic streaming, enlarged nuclei, increased numbers of organelles, and replacement of a central vacuole by many small vacuoles. When whole root RNA is isolated and analyzed, transcript changes manifested in the infected plant cells are overshadowed by gene expression from cells of the entire root system. Use of microaspiration allows isolation of the content of nematode infected cells from a heterogeneous cell population. However, one challenge with this method is identifying the nematode infected cells under the microscope at early stages of infection. This problem was addressed by staining nematode juveniles with a fluorescent dye prior to infection so that the infected cells could be located and microaspirated. In the present study, we used the fluorescent vital stain PKH26 coupled with a micro-rhizosphere chamber to locate the infected nematode Globodera pallida in Solanum tuberosum root cells. This enabled microaspiration of nematode-infected root cells during the early stages of parasitism. To study the transcriptional events occurring in these cells, an RNA isolation method from microaspirated samples was optimized, and subsequently the RNA was purified using magnetic beads. With this method, we obtained an RNA quality number of 7.8. For transcriptome studies, cDNA was synthesized from the isolated RNA and assessed by successfully amplifying several pathogenesis related protein coding genes. The use of PKH26 stained nematode juveniles enabled early detection of nematode infected cells for microaspiration. To investigate transcriptional changes in low yielding RNA samples, bead-based RNA extraction procedures minimized RNA degradation and provided high quality RNA. This protocol provides a robust procedure to analyze gene expression in

  4. Repression of inflammasome by Francisella tularensis during early stages of infection.

    PubMed

    Dotson, Rachel J; Rabadi, Seham M; Westcott, Elizabeth L; Bradley, Stephen; Catlett, Sally V; Banik, Sukalyani; Harton, Jonathan A; Bakshi, Chandra Shekhar; Malik, Meenakshi

    2013-08-16

    Francisella tularensis is an important human pathogen responsible for causing tularemia. F. tularensis has long been developed as a biological weapon and is now classified as a category A agent by the Centers for Disease Control because of its possible use as a bioterror agent. F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18. However, the Francisella factors and the mechanisms through which F. tularensis mediates these suppressive effects remain relatively unknown. Utilizing a mutant of F. tularensis in FTL_0325 gene, this study investigated the mechanisms of inflammasome repression by F. tularensis. We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1. Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion. An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3. Furthermore, F. tularensis LVS delayed pyroptotic cell death of the infected macrophages in an FTL_0325-dependent manner during the early stages of infection. In vivo studies in mice revealed that suppression of IL-1β by FTL_0325 early during infection facilitates the establishment of a fulminate infection by F. tularensis. Collectively, this study provides evidence that F. tularensis LVS represses inflammasome activation and that F. tularensis-encoded FTL_0325 mediates this effect.

  5. Repression of Inflammasome by Francisella tularensis during Early Stages of Infection*

    PubMed Central

    Dotson, Rachel J.; Rabadi, Seham M.; Westcott, Elizabeth L.; Bradley, Stephen; Catlett, Sally V.; Banik, Sukalyani; Harton, Jonathan A.; Bakshi, Chandra Shekhar; Malik, Meenakshi

    2013-01-01

    Francisella tularensis is an important human pathogen responsible for causing tularemia. F. tularensis has long been developed as a biological weapon and is now classified as a category A agent by the Centers for Disease Control because of its possible use as a bioterror agent. F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18. However, the Francisella factors and the mechanisms through which F. tularensis mediates these suppressive effects remain relatively unknown. Utilizing a mutant of F. tularensis in FTL_0325 gene, this study investigated the mechanisms of inflammasome repression by F. tularensis. We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1. Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion. An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3. Furthermore, F. tularensis LVS delayed pyroptotic cell death of the infected macrophages in an FTL_0325-dependent manner during the early stages of infection. In vivo studies in mice revealed that suppression of IL-1β by FTL_0325 early during infection facilitates the establishment of a fulminate infection by F. tularensis. Collectively, this study provides evidence that F. tularensis LVS represses inflammasome activation and that F. tularensis-encoded FTL_0325 mediates this effect. PMID:23821549

  6. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-04-01

    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775-875 cm-1, lectins at 1003, 1238, 1340, 1449 and 1672 cm-1, DNA in the region 1040-1140 cm-1 and alpha and beta structures of proteins in the region 933-967 cm-1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  7. Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection

    PubMed Central

    Lee, Chia Min; Weight, Alisha K.; Haldar, Jayanta; Wang, Ling; Klibanov, Alexander M.; Chen, Jianzhu

    2012-01-01

    Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance. PMID:23185023

  8. CHANGES IN HUMORAL IMMUNITY OCCURRING DURING THE EARLY STAGES OF EXPERIMENTAL PNEUMOCOCCUS INFECTION

    PubMed Central

    Terrell, Edward E.

    1930-01-01

    A study was made of the changes in humoral immunity occurring during the early phases of experimental pneumococcus infection in the dog and cat. The methods devised by Robertson and Sia were employed to demonstrate the presence of anti-pneumococcus properties in the serum of animals naturally resistant to this micro-organism. It was found that with a generalized and overwhelming infection accompanied by early blood invasion, there was a prompt and rapid decrease in the concentration of natural humoral immune bodies which frequently disappeared entirely by the time of death. This same early diminution of humoral immune substances, opsonins, agglutinins, and pneumococcidal-promoting bodies was observed in animals that survived a moderately severe generalized infection but the concentration of immune bodies rose again with the onset of recovery. The decrease in concentration of humoral immune substances during a severe generalized infection appeared to be due to the combination of "S" substance with the normal immune bodies. When the pneumococcus infection was more localized as in the case of true lobar pneumonia a quite different sequence of events was observed to occur. Several animals, in which extensive lobar pneumonia was produced, showed the presence in quantity of humoral immune bodies in the blood throughout the course of an infection terminating fatally. These findings suggest that after the inception of pneumococcus infection in the dog and cat the chief function of natural anti-pneurnococcus substances in the blood is to limit or prevent blood invasion. When pneumococcic infection is localized these circulating antibodies appear to have little effect either in preventing the spread of the process or determining the outcome of the disease. PMID:19869701

  9. [Surgical treatment for incisions fat colliquation or infections at early stage after operation of lumbar disc herniation].

    PubMed

    Guan, Ting-Jin; Zheng, Liang-Guo; Sun, Peng; Li, Xing-Xue

    2014-05-01

    To explore the reason, key diagnosic point and therapeutic method of the incisions fat colliquation or infections at early stage after operation of lumbar disc herniation. From July 2007 to May 2012, clinical data of 11 patients with incision fat liquefaction or early infection after lumbar discectomy were retrospectively analyzed. There were 5 males and 6 females with an average age of 43.1 years, and the mean time of incisions fat colliquation or infection was 5 days and a half after operation. The main clinical features included local wound pain aggravating, fervescence, fresh seepage in the wound, and blood inflammatory index increased, etc. The wound could heal at the first treatment stage or not was an evaluation standard of curative effect. All patients were followed up with an average period of 21 months. The wounds of 10 cases healed at the first stage without recurrence and complications. In 1 case infected by staphylococcus aureus, distal part of the wound present local red, swelling and with wave motion at 2 months after operation, staphylococcus aureus infection was confirmed after puncture and bacterial culture, and 1 thrum was found after local incision. The wound healed after change dressings for 1 week, without recurrence after followed up for 13 months. Preventing the risk factors before operation, minimizing invasive technique during operation reasonable antibiotics application for the lumbar operation reguiring placement objects, and correctly handling with wound after operation could prevent and reduce the incidence of incisions fat liquefaction or infection after operation of lumbar disc herniation. For incision fat liquefaction or infection, early diagnosis, debridement, VSD negative pressure irrigation and drainage, to choosing sensitive antibiotics according to the results of drug sensitivity, may contribute to wound early healing and decrease complication.

  10. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    NASA Astrophysics Data System (ADS)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  11. Host and bacterial factors that regulate LC3 recruitment to Listeria monocytogenes during the early stages of macrophage infection.

    PubMed

    Lam, Grace Y; Cemma, Marija; Muise, Aleixo M; Higgins, Darren E; Brumell, John H

    2013-07-01

    Listeria monocytogenes is a bacterial pathogen that can escape the phagosome and replicate in the cytosol of host cells during infection. We previously observed that a population (up to 35%) of L. monocytogenes strain 10403S colocalize with the macroautophagy marker LC3 at 1 h postinfection. This is thought to give rise to spacious Listeria-containing phagosomes (SLAPs), a membrane-bound compartment harboring slow-growing bacteria that is associated with persistent infection. Here, we examined the host and bacterial factors that mediate LC3 recruitment to bacteria at 1 h postinfection. At this early time point, LC3(+) bacteria were present within single-membrane phagosomes that are LAMP1(+). Protein ubiquitination is known to play a role in targeting cytosolic L. monocytogenes to macroautophagy. However, we found that neither protein ubiquitination nor the ubiquitin-binding adaptor SQSTM1/p62 are associated with LC3(+) bacteria at 1 h postinfection. Reactive oxygen species (ROS) production by the CYBB/NOX2 NADPH oxidase was also required for LC3 recruitment to bacteria at 1 h postinfection and for subsequent SLAP formation. Diacylglycerol is an upstream activator of the CYBB/NOX2 NADPH oxidase, and its production by both bacterial and host phospholipases was required for LC3 recruitment to bacteria. Our data suggest that the LC3-associated phagocytosis (LAP) pathway, which is distinct from macroautophagy, targets L. monocytogenes during the early stage of infection within host macrophages and allows establishment of an intracellular niche (SLAPs) associated with persistent infection.

  12. HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians

    PubMed Central

    Cook, R.; Jones, D. L.; Nehra, R.; Kumar, A. M.; Prabhakar, S.; Waldrop-Valverde, D.; Sharma, S.; Kumar, M.

    2017-01-01

    HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm3) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. PMID:23722088

  13. HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians.

    PubMed

    Cook, R; Jones, D L; Nehra, R; Kumar, A M; Prabhakar, S; Waldrop-Valverde, D; Sharma, S; Kumar, M

    2016-07-01

    HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm(3)) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. © The Author(s) 2013.

  14. [Preclinical study of AV0012 early stage inhibitor of hepatitis C virus infection: I. In vitro ADME and pharmacokinetics].

    PubMed

    Ivashchenko, A V; Iamanushkin, P M; Mit'kin, O D; Ezhova, E V; Korzinov, O M; Shevkun, N A; Koriakova, A G; Karapetian, R N; Bychko, V V; Ivashchenko, A A; Agrba, V Z; Lapin, B A; Orlov, S V

    2014-01-01

    In vitro immunohistochemical investigations on the human hepatoma cell line (Huh7) infected with hepatitis C virus (HCV) strain JFH-1 showed that AV0012 compound blocks the early stages of viral infection. AV0012 also blocked viral infection spread in tissue culture through the secreted virus and through tight cell-to-cell contact. AV0012 is a specific inhibitor of HCV but not of related pestivirus, flaviviruses and other RNA-containing viruses such as bovine diarrhea (BVDV), Venezuelan equine encephalitis (strain TC-83), dengue type 2 (New Guinea), yellow fever (strain 17D), west Nile fever, parainfluenza (type 3) virus, RSV (strain A2), and Rhinovirus (type 2 strain HGP). It is established that human serum does not significantly affect the antiviral activity of AV0012 in vitro. The drug combination studies with AV0012 and interferon alpha 2a in vitro showed that the two inhibitors act additively, which makes possible the use of this combination in clinical tests. AV0012 is highly soluble and stable in aqueous solutions and murine blood plasma, has limited metabolic stability, low binding to human plasma proteins, high permeability through biological membranes, and only interacts with isoenzymes 2D6 and 3A4 of human cytochrome P450. In animal pharmacokinetic studies, AV0012 was rapidly absorbed into the blood stream upon oral administration, showed sufficiently long half-elimination times, and had high oral bioavailability that reached 92% in monkeys. Further preclinical development of AV0012 is in progress.

  15. Serologic markers in early stages of African horse sickness virus infection.

    PubMed

    Martínez-Torrecuadrada, J L; Díaz-Laviada, M; Roy, P; Sánchez, C; Vela, C; Sánchez-Vizcaíno, J M; Casal, J I

    1997-02-01

    Fifteen horses were experimentally infected with African horse sickness virus (AHSV) serotype 4. To learn more about the time course of production and specificity of AHSV-specific antibodies, sera were analyzed by immunoblot analysis. Only animals that survived for more than 9 days were able to develop a humoral immune response detectable by immunoblotting. The earliest serological markers corresponded mainly to VP5, VP6, and NS2 and to a lesser extent to VP3, NS1, and NS3. Neutralizing antibodies to VP2 were not detected by immunoblotting, suggesting that they are mostly conformation dependent. VP7-specific antibodies were detected later in infection. These results make NS2 and VP6 the most attractive candidates for the rapid diagnosis of the infection.

  16. Serologic markers in early stages of African horse sickness virus infection.

    PubMed Central

    Martínez-Torrecuadrada, J L; Díaz-Laviada, M; Roy, P; Sánchez, C; Vela, C; Sánchez-Vizcaíno, J M; Casal, J I

    1997-01-01

    Fifteen horses were experimentally infected with African horse sickness virus (AHSV) serotype 4. To learn more about the time course of production and specificity of AHSV-specific antibodies, sera were analyzed by immunoblot analysis. Only animals that survived for more than 9 days were able to develop a humoral immune response detectable by immunoblotting. The earliest serological markers corresponded mainly to VP5, VP6, and NS2 and to a lesser extent to VP3, NS1, and NS3. Neutralizing antibodies to VP2 were not detected by immunoblotting, suggesting that they are mostly conformation dependent. VP7-specific antibodies were detected later in infection. These results make NS2 and VP6 the most attractive candidates for the rapid diagnosis of the infection. PMID:9003637

  17. Metabolic profiles of soybean roots during early stages of Fusarium tucumaniae infection

    Soybean germplasm exhibits various levels of resistance to Fusarium tucumaniae, the main causal agent of sudden death syndrome (SDS) of soybean in Argentina. In this study, two soybean genotypes, one susceptible (NA 4613) and one partially resistant (DM 4670) to SDS infection, were inoculated with F...

  18. Parasite distribution and early-stage encephalitis in Sarcocystis calchasi infections in domestic pigeons (Columba livia f. domestica).

    PubMed

    Maier, Kristina; Olias, Philipp; Enderlein, Dirk; Klopfleisch, Robert; Mayr, Sylvia L; Gruber, Achim D; Lierz, Michael

    2015-01-01

    Pigeon protozoal encephalitis is a biphasic, neurologic disease of domestic pigeons (Columba livia f. domestica) caused by the apicomplexan parasite Sarcocystis calchasi. Despite severe inflammatory lesions of the brain, associated parasitic stages have only rarely been identified and the cause of the lesions is still unclear. The aim of this study was therefore to characterize the tissue distribution of S. calchasi within pigeons between the two clinical phases and during the occurrence of neurological signs. For this purpose, a semi-quantitative real-time polymerase chain reaction (PCR) was developed. Forty-five domestic pigeons were infected orally (via a cannula into the crop) with 200 S. calchasi sporocysts and euthanized in groups of three pigeons at intervals of 2 to 10 days over a period of 61 days. Tissue samples including brain and skeletal muscle were examined by histology, immunohistochemistry, and PCR. Schizonts were detected in the liver of one pigeon at day 10 post infection. A mild encephalitis was detected at day 20 post infection, around 4 weeks before the onset of neurological signs. At the same time, immature sarcocysts were present in the skeletal muscle. In seven pigeons a few sarcocysts were identified in the brain, but not associated with any lesion. These results suggest that the encephalitis is induced at a very early stage of the S. calchasi lifecycle rather than in the chronic phase of pigeon protozoal encephalitis. Despite the increasing severity of lesions in the central nervous system, the amount of sarcocysts did not increase. This supports the hypothesis of a delayed-type hypersensitivity response as the cause of the encephalitis. The study also demonstrated that S. calchasi DNA is detectable in tissues negative by histological methods, indicating a higher sensitivity of the real-time PCR.

  19. Using NanoSIMS coupled with microfluidics to visualize the early stages of coral infection by Vibrio coralliilyticus.

    PubMed

    Gibbin, E; Gavish, A; Domart-Coulon, I; Kramarsky-Winter, E; Shapiro, O; Meibom, A; Vardi, A

    2018-04-20

    Global warming has triggered an increase in the prevalence and severity of coral disease, yet little is known about coral/pathogen interactions in the early stages of infection. The point of entry of the pathogen and the route that they take once inside the polyp is currently unknown, as is the coral's capacity to respond to infection. To address these questions, we developed a novel method that combines stable isotope labelling and microfluidics with transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS), to monitor the infection process between Pocillopora damicornis and Vibrio coralliilyticus under elevated temperature. Three coral fragments were inoculated with 15 N-labeled V. coralliilyticus and then fixed at 2.5, 6 and 22 h post-inoculation (hpi) according to the virulence of the infection. Correlative TEM/NanoSIMS imaging was subsequently used to visualize the penetration and dispersal of V. coralliilyticus and their degradation or secretion products. Most of the V. coralliilyticus cells we observed were located in the oral epidermis of the fragment that experienced the most virulent infection (2.5 hpi). In some cases, these bacteria were enclosed within electron dense host-derived intracellular vesicles. 15 N-enriched pathogen-derived breakdown products were visible in all tissue layers of the coral polyp (oral epidermis, oral gastrodermis, aboral gastrodermis), at all time points, although the relative 15 N-enrichment depended on the time at which the corals were fixed. Tissues in the mesentery filaments had the highest density of 15 N-enriched hotspots, suggesting these tissues act as a "collection and digestion" site for pathogenic bacteria. Closer examination of the sub-cellular structures associated with these 15 N-hotspots revealed these to be host phagosomal and secretory cells/vesicles. This study provides a novel method for tracking bacterial infection dynamics at the levels of the tissue and single cell

  20. Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-{alpha} gene at an early stage of infection

    SciT

    Shimizu, Yuya; Miyazaki, Yasuyuki; Ibuki, Kentaro

    2005-12-20

    TNF-{alpha} has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-{alpha} against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-{alpha} gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4{sup +} T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES andmore » by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-{alpha} contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection.« less

  1. Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection

    PubMed Central

    Raaben, Matthijs; Einerhand, Alexandra WC; Taminiau, Lucas JA; van Houdt, Michel; Bouma, Janneke; Raatgeep, Rolien H; Büller, Hans A; de Haan, Cornelis AM; Rossen, John WA

    2007-01-01

    Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy. PMID:17555580

  2. Evaluation of the therapeutic effect of potassium permanganate at early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus)

    The efficacy of potassium permanganate (KMnO4) against early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus) was evaluated. Fish were experimentally challenged, by waterborne exposure for 2 h to F. columnare after cutaneous abrasion, an...

  3. Early Life Stages

    EPA Pesticide Factsheets

    Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

  4. Examination of the early infection stages of koi herpesvirus (KHV) in experimentally infected carp, Cyprinus carpio L. using in situ hybridization.

    PubMed

    Monaghan, S J; Thompson, K D; Adams, A; Kempter, J; Bergmann, S M

    2015-05-01

    Koi herpesvirus (KHV) causes a highly infectious disease afflicting common carp and koi, Cyprinus carpio L. Various molecular and antibody-based detection methods have been used to elucidate the rapid attachment and dissemination of the virus throughout carp tissues, facilitating ongoing development of effective diagnostic approaches. In situ hybridization (ISH) was used here to determine the target tissues of KHV during very early infection, after infecting carp with a highly virulent KHV isolate. Analysis of paraffin-embedded tissues (i.e. gills, skin, spleen, kidney, gut, liver and brain) during the first 8 h and following 10 days post-infection (hpi; dpi) revealed positive signals in skin mucus, gills and gut sections after only 1 hpi. Respiratory epithelial cells were positive as early as 2 hpi. Viral DNA was also detected within blood vessels of various tissues early in the infection. Notable increases in signal abundance were observed in the gills and kidney between 5 and 10 dpi, and viral DNA was detected in all tissues except brain. This study suggests that the gills and gut play an important role in the early pathogenesis of this Alloherpesvirus, in addition to skin, and demonstrates ISH as a useful diagnostic tool for confirmation of acutely infected carp. © 2014 John Wiley & Sons Ltd.

  5. Respiratory syncytial virus (RSV) entry is inhibited by serine protease inhibitor AEBSF when present during an early stage of infection.

    PubMed

    Van der Gucht, Winke; Leemans, Annelies; De Schryver, Marjorie; Heykers, Annick; Caljon, Guy; Maes, Louis; Cos, Paul; Delputte, Peter L

    2017-08-17

    Host proteases have been shown to play important roles in many viral activities such as entry, uncoating, viral protein production and disease induction. Therefore, these cellular proteases are putative targets for the development of antivirals that inhibit their activity. Host proteases have been described to play essential roles in Ebola, HCV, HIV and influenza, such that specific protease inhibitors are able to reduce infection. RSV utilizes a host protease in its replication cycle but its potential as antiviral target is unknown. Therefore, we evaluated the effect of protease inhibitors on RSV infection. To measure the sensitivity of RSV infection to protease inhibitors, cells were infected with RSV and incubated for 18 h in the presence or absence of the inhibitors. Cells were fixed, stained and studied using fluorescence microscopy. Several protease inhibitors, representing different classes of proteases (AEBSF, Pepstatin A, E-64, TPCK, PMSF and aprotinin), were tested for inhibitory effects on an RSV A2 infection of HEp-2 cells. Different treatment durations, ranging from 1 h prior to inoculation and continuing for 18 h during the assay, were evaluated. Of all the inhibitors tested, AEBSF and TPCK significantly decreased RSV infection. To ascertain that the observed effect of AEBSF was not a specific feature related to HEp-2 cells, A549 and BEAS-2B cells were also used. Similar to HEp-2, an almost complete block in the number of RSV infected cells after 18 h of incubation was observed and the effect was dose-dependent. To gain insight into the mechanism of this inhibition, AEBSF treatment was applied during different phases of an infection cycle (pre-, peri- and post-inoculation treatment). The results from these experiments indicate that AEBSF is mainly active during the early entry phase of RSV. The inhibitory effect was also observed with other RSV isolates A1998/3-2 and A2000/3-4, suggesting that this is a general feature of RSV. RSV infection can be

  6. Interleukin-10 production at the early stage of infection with foot-and-mouth disease virus related to the likelihood of persistent infection in cattle.

    PubMed

    Zhang, Zhidong; Doel, Claudia; Bashiruddin, John B

    2015-11-19

    The factors leading to persistent infection of foot-and-mouth disease (FMD) virus in ruminants are not well defined. This paper provides evidence of the presence of interleukin-10 (IL-10) early in the course of infection (1-4 days) as a factor in the development of persistence of FMD virus in cattle. Results showed that serum IL-10 in carrier cattle infected with FMD virus type O (n = 4) was detected and peaked at 1 or 2 days post infection and rapidly declined thereafter. In contract, serum IL-10 levels in non-carrier cattle (n = 21) were very low or undetectable during the same period.

  7. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    PubMed

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  8. Immune reactivity in early life stages of sea-cage cultured Pacific bluefin tuna naturally infected with blood flukes from genus Cardicola (Trematoda: Aporocotylidae).

    PubMed

    Pennacchi, Ylenia; Shirakashi, Sho; Nowak, Barbara F; Bridle, Andrew R

    2016-11-01

    Pacific bluefin tuna (PBT), Thunnus orientalis, due to its high average price on the market is an economically valuable fish species. Infections by blood flukes from the genus Cardicola (Trematoda: Aporocotylidae) represent a growing concern for the cage culture of bluefin tuna in Japan, Australia and Southern Europe. The accumulation of numerous Cardicola eggs in the fish gills causes severe pathology that has been linked to mortality in PBT juveniles up to one year old. The only effective treatment used to mitigate the infection is the oral administration of the antihelminthic drug praziquantel (PZQ) to the affected fish. However, with the need to minimise therapeutic drug use in aquaculture it is hoped that immunoprophylaxis can provide a future alternative to protect the PBT juveniles against Cardicola infection. Currently, little is known of the host immune response to these parasites and of their infection dynamics. In this study, using real-time qPCR we aimed to quantitatively detect C. orientalis and C. opisthorchis DNA within the gills and heart of cultured PBT juveniles and to investigate the host immune response at the transcriptional level in the gills. The research focused mainly during early stages of infection soon after young PBT were transferred to culture cages (from 14 to 77 days post-transfer). An increase (up to 11-fold) of immune-related genes, namely IgM, MHC-I, TCR-β and IL-1β was observed in the PBT gills infected with Cardicola spp. (28-77 days post-transfer). Furthermore, IgM (19-fold increase) and MHC-I (11.5-fold increase) transcription was strongly up-regulated in gill samples of PBT infected with C. orientalis relative to uninfected fish but not in fish infected with C. opisthorchis. Cardicola-specific DNA was first detected in the host 14 days post-transfer (DPT) to sea-cages which was 55 days earlier than the first detection of parasite eggs and adults by microscopy. Oral administration of PZQ did not have an immediate effect

  9. Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.

    PubMed

    Porotto, Matteo; Rockx, Barry; Yokoyama, Christine C; Talekar, Aparna; Devito, Ilaria; Palermo, Laura M; Liu, Jie; Cortese, Riccardo; Lu, Min; Feldmann, Heinz; Pessi, Antonello; Moscona, Anne

    2010-10-28

    In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.

  10. Morphogenesis of early stage melanoma

    NASA Astrophysics Data System (ADS)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  11. Identification of immunodominant Leishmania major antigenic markers of the early C57BL/6 and BALB/c mice infection stages.

    PubMed

    Sassi, Atfa; Kaak, Olfa; Elgaaied, Amel Benammar

    2015-08-24

    The C57BL/6 mouse strain is resistant to Leishmania (L.) major infection and, unlike susceptible BALB/c, develops small self healing cutaneous lesions. The specific antibody responses of C57BL/6 and BALB/c mice were previously characterized by the predominance of IgG2a ("resistant" isotype associated with Th1) and IgG1 ("pathogenic" isotype associated with Th2) antibodies, respectively. In this study, we looked for the presence of antigens able to elicit an exclusive or predominant IgG1 production during the early stages of C57BL/6 lesion development and checked whether they are recognized or not by BALB/c mice. We demonstrate first that IgG2a predominance in C57BL/6 sera occurs only late after infection whereas in BALB/c, IgG1 antibodies dominate mostly in the early stages. Interestingly, soon after inoculation of live amastigotes, C57BL/6 displayed an exclusive IgG1 reactivity against particular L. major antigens but with MWs different from those identified in BALB/c. Furthermore, mice immunized with killed amastigotes displayed striking differences in their immunodetection profiles, particularly for the IgG1 isotype. Taken together, the observed differences in the specific antibody repertoires between infected mice resulted, at least in part, from immunological events independent from those triggered by the replicating parasite, and bring new insights into the selection of future vaccine candidates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. TREM-1 signaling promotes host defense during the early stage of infection with highly pathogenic Streptococcus suis.

    PubMed

    Yang, Chao; Chen, Bo; Zhao, Jianqing; Lin, Lan; Han, Li; Pan, Shan; Fu, Lei; Jin, Meilin; Chen, Huanchun; Zhang, Anding

    2015-08-01

    Infection with highly pathogenic Streptococcus suis can cause septic shock, which is characterized by high levels of inflammatory cytokines and a high mortality rate. Our previous study indicated that TREM-1 (triggering receptor expressed on myeloid cells 1) was upregulated in swine spleen cells in response to S. suis infection. The role of TREM-1 signaling in enhancement of the proinflammatory response promoted us to examine its effect on the outcome of S. suis infection. In the present study, the recombinant extracellular domain of TREM-1 (rTREM-1) and an agonistic TREM-1 antibody were used to inhibit and activate TREM-1 signaling to evaluate its role in neutrophil activation, pathogen clearance, proinflammatory cytokine response, and the outcome of highly pathogenic S. suis infection in a mouse model. Blockage of TREM-1 signaling caused a more severe proinflammatory response to S. suis infection and increased the mortality rate, while its activation had the opposite effect. Blockage or activation of TREM-1 signaling lowered or raised the number of neutrophils in the blood, which correlated well with host clearance of S. suis. In conclusion, the TREM-1-mediated innate immune response played an essential role in the activation of neutrophils and S. suis clearance, which further reduced severe inflammation and finally benefited the outcome of the infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Early stages of soldering reactions

    SciT

    Lord, R.A.; Umantsev, A.

    2005-09-15

    An experiment on the early stages of intermetallic compound layer growth during soldering and its theoretical analysis were conducted with the intent to study the controlling factors of the process. An experimental technique based on fast dipping and pulling of a copper coupon in liquid solder followed by optical microscopy allowed the authors to study the temporal behavior of the sample on a single micrograph. The technique should be of value for different areas of metallurgy because many experiments on crystallization may be described as the growth of a layer of intermediate phase. Comparison of the experimental results with themore » theoretical calculations allowed one to identify the kinetics of dissolution as the rate-controlling mechanism on the early stages and measure the kinetic coefficient of dissolution. A popular model of intermetallic compound layer structure coarsening is discussed.« less

  14. Cytoskeleton remodling and alterations in smooth muscle contractility in the bovine jejunum during the early stage of Cooperia oncophora infection

    Gastrointestinal nematodes of the genus Cooperia are arguably the most important parasites of cattle. We characterized the bovine jejunal transcriptome in response to C. oncophora infection using RNA-seq technology. Approximately 71% of the 25,670 bovine genes were detected in the jejunal transcript...

  15. The early stages of the immune response of the European abalone Haliotis tuberculata to a Vibrio harveyi infection.

    PubMed

    Cardinaud, Marion; Dheilly, Nolwenn M; Huchette, Sylvain; Moraga, Dario; Paillard, Christine

    2015-08-01

    Vibrio harveyi is a marine bacterial pathogen responsible for episodic abalone mortalities in France, Japan and Australia. In the European abalone, V. harveyi invades the circulatory system in a few hours after exposure and is lethal after 2 days of infection. In this study, we investigated the responses of European abalone immune cells over the first 24 h of infection. Results revealed an initial induction of immune gene expression including Rel/NF-kB, Mpeg and Clathrin. It is rapidly followed by a significant immuno-suppression characterized by reduced cellular hemocyte parameters, immune response gene expressions and enzymatic activities. Interestingly, Ferritin was overexpressed after 24 h of infection suggesting that abalone attempt to counter V. harveyi infection using soluble effectors. Immune function alteration was positively correlated with V. harveyi concentration. This study provides the evidence that V. harveyi has a hemolytic activity and an immuno-suppressive effect in the European abalone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Pathological analysis of the Candida albicans-infected tongue tissues of a murine oral candidiasis model in the early infection stage.

    PubMed

    Okada, Masashi; Hisajima, Tatsuya; Ishibashi, Hiroko; Miyasaka, Takahiro; Abe, Shigeru; Satoh, Tazuko

    2013-04-01

    The early pathological process of Candida infection and immunological responses in tongues of the mice with experimental oral candidiasis was analysed. CD-1 mice, pretreated by prednisolone were orally inoculated with Candida albicans. Symptoms were monitored by measuring the area of white tongue coating and number of viable Candida cells in oral cavity. The histopathological analysis was carried by PAS-stain and immunofluorescent staining. IL-4, IL-12p70, IFN-γ, TNF-α in recovered from the homogenates of the tongues were measured by ELISA. The fungus invaded the tongue surface of the mice and white patches developed within 24h after inoculation. Histopathological examination indicated the presence of local acute inflammation in superficial tissues of tongues covered by mycelium of C. albicans. Pathological exacerbation was observed from 24 to 48 h after the inoculation and from then the symptoms of oral candidiasis appeared to move into the recovery phase. Inflammatory cells mainly consisting of neutrophils was accumulated and located under the lesions covered by Candida-hyphae. An increase in IL-12p70 and IFN-γ in tongue homogenates was observed at 48 h after inoculation. The worst condition in the pathological process in experimental oral candidiasis was found 48 h after C. albicans inoculation. When the surface of the Candida-inoculated tongues was covered with Candida-hyphae, a dense accumulation of neutrophils was observed under the lesions and homogenates of the tongues contained increased levels of IL-12p70 and IFN-γ. These suggested that local pathological condition of Candida-infected tongues may be affected by neutrophils accumulation and increased levels of some cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Transcriptomic analysis of two Beauveria bassiana strains grown on cuticle extracts of the silkworm uncovers their different metabolic response at early infection stage.

    PubMed

    Wang, Jing-Jie; Bai, Wen-Wen; Zhou, Wei; Liu, Jing; Chen, Jie; Liu, Xiao-Yuan; Xiang, Ting-Ting; Liu, Ren-Hua; Wang, Wen-Hui; Zhang, Bao-Ling; Wan, Yong-Ji

    2017-05-01

    Beauveria bassiana is an important entomopathogenic fungus which not only widely distributes in the environment but also shows phenotypic diversity. However, the mechanism of pathogenic differences among natural B. bassiana strains has not been revealed at transcriptome-wide level. In the present study, in order to explore the mechanism, two B. bassiana strains with different pathogenicity were isolated from silkworms (Bombyx mori L.) and selected to analyze the gene expression of early stage by culturing on cuticle extracts of the silkworm and using RNA-sequencing technique. A total of 2108 up-regulated and 1115 down-regulated genes were identified in B. bassiana strain GXsk1011 (hyper-virulent strain) compared with B. bassiana strain GXtr1009 (hypo-virulent strain), respectively. The function categorization of differential expressed genes (DEGs) showed that most of them involved in metabolic process, biosynthesis of secondary metabolites, catalytic activity, and some involved in nutrition uptake, adhesion and host defense were also noted. Based on our data, distinct pathogenicity among different strains of B. bassiana may largely attribute to unique gene expression pattern which differed at very early infection process. Most of the genes involved in conidia adhesion, cuticle degradation and fungal growth were up-regulated in hyper-virulent B. bassiana strain GXsk1011. Furthermore, in combination with fungal growth analysis, our research provided a clue that fungal growth may also play an important role during early infection process. The results will help to explain why different B. bassiana strains show distinct pathogenicity on the same host even under same condition. Moreover, the transcriptome data were also useful for screening potential virulence factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Plum Pox Virus 6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection.

    PubMed

    Cui, Hongguang; Wang, Aiming

    2016-05-15

    The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian Plum pox virus (PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The trans expression of 6K1 or the cis expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage. Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically processed into 11 mature

  19. Plum Pox Virus 6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection

    PubMed Central

    Cui, Hongguang

    2016-01-01

    ABSTRACT The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian Plum pox virus (PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The trans expression of 6K1 or the cis expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage. IMPORTANCE Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically

  20. Biophysical Properties of Frog Virus and Its Deoxyribonucleic Acid: Fate of Radioactive Virus in the Early Stage of Infection 1

    PubMed Central

    Smith, William R.; McAuslan, Brian R.

    1969-01-01

    Frog virus (FV-3) was banded by isopycnic centrifugation in cesium chloride, sucrose, or potassium tartrate. Two bands of infectivity were regularly found at positions in cesium chloride corresponding to densities of 1.26 and 1.30 g/cm3, respectively. Deoxyribonucleic acid from either band had the following characteristics: double-stranded; a Tm of 76.3 C in 0.1 SSC (0.015 m NaCl plus 0.015 m sodium citrate) and a buoyant density of 1.720 g/cm3 in cesium chloride, corresponding to a guanine plus cytosine content of 56 to 58% and a molecular weight of 130 × 106 daltons, determined by velocity sedimentation. These data, together with electron micrographs of sections of cells infected with material from either band suggest that two types of infectious frog virus particles exists, rather than a second virus in the frog virus stocks. The composition of frog virus was determined. It was found that highly purified preparations of frog virus were composed of 55.8% protein, 30.1% deoxyribonucleic acid, and 14.2% lipid. The kinetics of adsorption and uncoating of FV-3 was studied with radioactive virus. Uncoating is comparatively rapid and in contrast to poxvirus is unaffected by inhibitors of protein synthesis. Images PMID:4980848

  1. Antibody responses and viral load in patients with Crimean-Congo hemorrhagic fever: a comprehensive analysis during the early stages of the infection.

    PubMed

    Ergunay, Koray; Kocak Tufan, Zeliha; Bulut, Cemal; Kinikli, Sami; Demiroz, Ali Pekcan; Ozkul, Aykut

    2014-05-01

    This study was performed to assess viral load, viral nucleocapsid (N), and glycoprotein precursor (GPC) antibodies in consecutive samples obtained from Crimean-Congo hemorrhagic fever patients to reveal viral replication kinetics and antiviral immune responses during the early stages of the infection. Among 116 samples from 20 individuals, 43.9% and 76.7% were positive for viral RNA and IgM/IgG antibodies, respectively, whereas both markers could be detected in 22.4%. Mean duration of viremia was 3 days (range: 1-6 days). N-IgM antibodies were identified as the initial serological marker during the infection, becoming detectable in a median of 2-3 days after disease onset, followed by GPC-IgM (4-6 days) and IgG antibodies (5-6 days). Clearance of viremia followed or coincided N-IgM response. Partial S gene sequences amplified in viremic patients were identical or closely related to previously characterized strains and grouped within European lineage I group II viruses via neighbor-joining analysis without significant amino acid substitutions. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Dynamics and functions of CD4⁺CD25 (high) regulatory T lymphocytes in Chinese rhesus macaques during the early stage of infection with SIVmac239.

    PubMed

    Li, Shao-You; Xia, Hou-Jun; Dai, Zheng-Xi; Zhang, Gao-Hong; Fan, Bo; Li, Ming-Hua; Wang, Rui-Rui; Zheng, Yong-Tang

    2012-05-01

    CD4(+)CD25(high) regulatory T cells (Treg), which are a specialized subset of T cells, play an important role in the prevention of autoimmune diseases, maintenance of immune system homeostasis and tolerance to self-antigens. Chinese rhesus macaques (CRMs) are widely used in preclinical research on potential therapeutic drugs, vaccines and mechanisms of human diseases. However, the basic immunological characterization of Treg cells of CRMs has not been well established. To characterize Treg cells, peripheral blood of 43 adult CRMs was analyzed for CD4+ T lymphocytes by flow cytometry. It was found that Treg cells ranged from 1.52% to 11.1% of CD4+ T cells, and the average value was 5.7%. With our SIV-infected CRM model, through further studies, it was found that Treg cells in peripheral blood increased both in relative and absolute quantities. Moreover, Treg cells maintained their functions by suppressing Th1 cytokine secretion of their target cells. The results show that Treg cells might render cellular immunity against SIV viruses dysfunctional during the early stage after infection.

  3. Early stages of Ostwald ripening

    NASA Astrophysics Data System (ADS)

    Shneidman, Vitaly A.

    2013-07-01

    The Becker-Döring (BD) nucleation equation is known to predict a narrow double-exponential front (DEF) in the distribution of growing particles over sizes, which is due to early transient effects. When mass conservation is included, nucleation is eventually exhausted while independent growth is replaced by ripening. Despite the enormous difference in the associated time scales, and the resulting demand on numerics, within the generalized BD model the early DEF is shown to be crucial for the selection of the unique self-similar Lifshitz-Slyozov-Wagner asymptotic regime. Being preserved till the latest stages of growth, the DEF provides a universal part of the initial conditions for the ripening problem, regardless of the mass exchange mechanism between the nucleus and the matrix.

  4. Identification of plant genes regulated in resistant potato Solanum sparsipilum during the early stages of infection by Globodera pallida.

    PubMed

    Jolivet, Katell; Grenier, Eric; Bouchet, Jean-Paul; Esquibet, Magali; Kerlan, Marie-Claire; Caromel, Bernard; Mugniéry, Didier; Lefebvre, Véronique

    2007-04-01

    Using a complementary (c)DNA-amplified fragment length polymorphism (AFLP) approach, we investigated differential gene expression linked to resistance mechanisms during the incompatible potato - Globodera pallida interaction. Expression was compared between a resistant and a susceptible potato clone, inoculated or not inoculated with G. pallida. These clones were issued from a cross between the resistant Solanum sparsipilum spl329.18 accession and the susceptible dihaploid S. tuberosum Caspar H3, and carried, respectively, resistant and susceptible alleles at the resistance quantitative trait loci (QTLs). Analysis was done on root fragments picked up at 4 time points, during a period of 6 days after infection, from penetration of the nematode in the root to degradation of the feeding site in resistant plants. A total of 2560 transcript-derived fragments (TDFs) were analyzed, resulting in the detection of 46 TDFs that were up- or downregulated. The number of TDFs that were up- or downregulated increased with time after inoculation. The majority of TDFs were upregulated at only 1 or 2 time points in response to infection. After isolation and sequencing of the TDFs of interest, a subset of 36 sequences were identified, among which 22 matched plant sequences and 2 matched nematode sequences. Some of the TDFs that matched plant genes showed clear homologies to genes involved in cell-cycle regulation, transcription regulation, resistance downstream signalling pathways, and defense mechanisms. Other sequences with homologies to plant genes of unknown function or without any significant similarity to known proteins were also found. Although not exhaustive, these results represent the most extensive list of genes with altered RNA levels after the incompatible G. pallida-potato interaction that has been published to date. The function of these genes could provide insight into resistance or plant defense mechanisms during incompatible potato-cyst nematode interactions.

  5. β-HPV Infection Correlates with Early Stages of Carcinogenesis in Skin Tumors and Patient-Derived Xenografts from a Kidney Transplant Recipient Cohort.

    PubMed

    Borgogna, Cinzia; Olivero, Carlotta; Lanfredini, Simone; Calati, Federica; De Andrea, Marco; Zavattaro, Elisa; Savoia, Paola; Trisolini, Elena; Boldorini, Renzo; Patel, Girish K; Gariglio, Marisa

    2018-01-01

    Many malignancies that occur in high excess in kidney transplant recipients (KTRs) are due to viruses that thrive in the setting of immunosuppression. Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR, has been associated with skin infection by human papillomavirus (HPV) from the beta genus. In this report, we extend our previous investigation aimed at identifying the presence of active β-HPV infection in skin tumors from KTRs through detection of viral protein expression. Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize infection in five tumors [one keratoacanthoma (KA), three actinic keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from two patients who had been both transplanted twice, had developed multiple KCs, and presented with a long history of immunosuppression (>30 years). These infected tissues displayed intraepidermal hyperplasia and increased expression of the ΔNp63 protein, which extended into the upper epithelial layers. In addition, using a xenograft model system in nude mice displaying a humanized stromal bed in the site of grafting, we successfully engrafted three AKs, two of which were derived from the aforementioned KTRs and displayed β-HPV infection in the original tumor. Of note, one AK-derived xenograft, along with its ensuing lymph node metastasis, was diagnosed as squamous cell carcinoma (SCC). In the latter, both β-HPV infection and ΔNp63 expression were no longer detectable. Although the overall success rate of engrafting was very low, the results of this study show for the first time that β-HPV + and ΔNp63 + intraepidermal hyperplasia can indeed progress to an aggressive SCC able to metastasize. Consistent with a series of reports attributing a causative role of β-HPV at early stages of skin carcinogenesis through ΔNp63 induction and increased keratinocytes stemness, here we provide in vivo evidence that

  6. β-HPV Infection Correlates with Early Stages of Carcinogenesis in Skin Tumors and Patient-Derived Xenografts from a Kidney Transplant Recipient Cohort

    PubMed Central

    Borgogna, Cinzia; Olivero, Carlotta; Lanfredini, Simone; Calati, Federica; De Andrea, Marco; Zavattaro, Elisa; Savoia, Paola; Trisolini, Elena; Boldorini, Renzo; Patel, Girish K.; Gariglio, Marisa

    2018-01-01

    Many malignancies that occur in high excess in kidney transplant recipients (KTRs) are due to viruses that thrive in the setting of immunosuppression. Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR, has been associated with skin infection by human papillomavirus (HPV) from the beta genus. In this report, we extend our previous investigation aimed at identifying the presence of active β-HPV infection in skin tumors from KTRs through detection of viral protein expression. Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize infection in five tumors [one keratoacanthoma (KA), three actinic keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from two patients who had been both transplanted twice, had developed multiple KCs, and presented with a long history of immunosuppression (>30 years). These infected tissues displayed intraepidermal hyperplasia and increased expression of the ΔNp63 protein, which extended into the upper epithelial layers. In addition, using a xenograft model system in nude mice displaying a humanized stromal bed in the site of grafting, we successfully engrafted three AKs, two of which were derived from the aforementioned KTRs and displayed β-HPV infection in the original tumor. Of note, one AK-derived xenograft, along with its ensuing lymph node metastasis, was diagnosed as squamous cell carcinoma (SCC). In the latter, both β-HPV infection and ΔNp63 expression were no longer detectable. Although the overall success rate of engrafting was very low, the results of this study show for the first time that β-HPV+ and ΔNp63+ intraepidermal hyperplasia can indeed progress to an aggressive SCC able to metastasize. Consistent with a series of reports attributing a causative role of β-HPV at early stages of skin carcinogenesis through ΔNp63 induction and increased keratinocytes stemness, here we provide in vivo evidence that

  7. Drought increases cowpea (Vigna unguiculata [L.] Walp.) susceptibility to cowpea severe mosaic virus (CPSMV) at early stage of infection.

    PubMed

    Silva, Rodolpho G G; Vasconcelos, Ilka M; Martins, Thiago F; Varela, Anna L N; Souza, Pedro F N; Lobo, Ana K M; Silva, Fredy D A; Silveira, Joaquim A G; Oliveira, Jose T A

    2016-12-01

    The physiological and biochemical responses of a drought tolerant, virus-susceptible cowpea genotype exposed to drought stress (D), infected by Cowpea severe mosaic virus (CPSMV) (V), and to these two combined stresses (DV), at 2 and 6 days post viral inoculation (DPI), were evaluated. Gas exchange parameters (net photosynthesis, transpiration rate, stomatal conductance, and internal CO 2 partial pressure) were reduced in D and DV at 2 and 6 DPI compared to control plants (C). Photosynthesis was reduced by stomatal and biochemical limitations. Water use efficiency increased at 2 DPI in D, DV, and V, but at 6 DPI only in D and DV compared to C. Photochemical parameters (effective quantum efficiency of photosystem II and electron transport rate) decreased in D and DV compared to C, especially at 6 DPI. The potential quantum efficiency of photosystem II did not change, indicating reversible photoinhibition of photosystem II. In DV, catalase decreased at 2 and 6 DPI, ascorbate peroxidase increased at 2 DPI, but decreased at 6 DPI. Hydrogen peroxide increased at 2 and 6 DPI. Peroxidase increased at 6 DPI and chitinase at 2 and 6 DPI. β-1,3-glucanase decreased in DV at 6 DPI compared to V. Drought increased cowpea susceptibility to CPSMV at 2 DPI, as verified by RT-PCR. However, at 6 DPI, the cowpea plants overcome this effect. Likewise, CPSMV increased the negative effects of drought at 2 DPI, but not at 6 DPI. It was concluded that the responses to combined stresses are not additive and cannot be extrapolated from the study of individual stresses. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Infection control measures on ships and in ports during the early stage of pandemic influenza A (H1N1) 2009.

    PubMed

    Schlaich, Clara; Gau, Bettina; Cohen, Nicole J; Kojima, Kazunobu; Marano, Nina; Menucci, Daniel

    2012-01-01

    Shipping companies were surveyed to evaluate the effect of public health measures during the influenza A (H1N1) pandemic of 2009 on ship and port operations. Of 31 companies that operated 960 cruise, cargo, and other ships, 32% experienced health-screening measures by port health authorities. Approximately a quarter of ports (26%) performed screening at embarkation and 77% of shipping companies changed procedures during the early stage of the pandemic. Four companies reported outbreaks of pandemic influenza A (H1N1) 2009 on ships, which were ultimately stopped through infection control practices. Public health measures did not interfere substantially with port and ship operations with the exception of some port authorities that delayed embarking and disembarking procedures in a few ships. However, in the shipping companies' experience, measures were inconsistent between port health authorities. Access to antiviral drugs and pandemic vaccine was not provided in all ports. Current guidelines on medical care, hygiene, and emergency procedures on ships need to address pandemic influenza preparedness in future revisions.

  9. A glass fiber-reinforced composite - bioactive glass cranioplasty implant: A case study of an early development stage implant removed due to a late infection.

    PubMed

    Posti, Jussi P; Piitulainen, Jaakko M; Hupa, Leena; Fagerlund, Susanne; Frantzén, Janek; Aitasalo, Kalle M J; Vuorinen, Ville; Serlo, Willy; Syrjänen, Stina; Vallittu, Pekka K

    2015-03-01

    This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial

  10. Early stages of zeolite growth

    NASA Astrophysics Data System (ADS)

    Kumar, Sandeep

    Zeolites are crystalline nonporous aluminosilicates with important applications in separation, purification, and adsorption of liquid and gaseous molecules. However, an ability to tailor the zeolite microstructure, such as particle size/shape and pore-size, to make it benign for specific application requires control over nucleation and particle growth processes. But, the nucleation and crystallization mechanisms of zeolites are not fully understood. In this context, the synthesis of an all-silica zeolite with MFI-type framework has been studied extensively as a model system. Throughout chapters 2, 4 and 5, MFI growth process has been investigated by small-angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Of fundamental importance is the role of nanoparticles (~5 nm), which are present in the precursor sol, in MFI nucleation and crystallization. Formation of amorphous aggregates and their internal restructuring are concluded as essential steps in MFI nucleation. Early stage zeolite particles have disordered and less crystalline regions within, which indicates the role of structurally distributed population of nanoparticles in growth. Faceting occurs after the depletion of nanoparticles. The chapter 6 presents growth studies in silica sols prepared by using a dimer of tertaprpylammonium (TPA) and reports that MFI nucleation and crystallization are delayed with a more pronounced delay in crystal growth.

  11. In vivo whole animal body imaging reveals colonization of Chlamydia muridarum to the lower genital tract at early stages of infection.

    PubMed

    Gupta, Rishein; Wali, Shradha; Yu, Jieh-Juen; Chambers, James P; Zhong, Guangming; Murthy, Ashlesh K; Bakar, Sazaly Abu; Guentzel, M N; Arulanandam, Bernard P

    2014-10-01

    The leading cause of sexually transmitted bacterial infection is Chlamydia trachomatis. The aim of this study is to investigate the early events in colonization of this bacterium within the murine genital tract. An in vivo animal body imaging technology was used to track fluorophore labeled C. muridarum elementary bodies (EBs) inoculated intravaginally in C57BL/6 mice during the first 24 h of infection. Ascension of viable EBs was observed (1) to be localized to the lower regions of the murine genital tract within the first 24 h post challenge and (2) was dose independent during this early exposure period. Molecular detection revealed enhanced bacterial load in lower regions of the genital tract with increasing bacterial load in the upper region beginning 12 h post inoculation. This study provides additional insight into chlamydial colonization in the murine genital tract during the first 12-24 h following inoculation.

  12. Host-cell interaction of attenuated and wild-type strains of yellow fever virus can be differentiated at early stages of hepatocyte infection.

    PubMed

    Lefeuvre, Anabelle; Contamin, Hugues; Decelle, Thierry; Fournier, Christophe; Lang, Jean; Deubel, Vincent; Marianneau, Philippe

    2006-05-01

    Yellow fever (YF) virus is currently found in tropical Africa and South America, and is responsible for a febrile to severe illness characterized by organ failure and shock. The attenuated YF 17D strain, used in YF vaccine, was derived from the wild-type strain Asibi. Although studies have been done on genetic markers of YF virulence, differentiation of the two strains in terms of host-cell interaction during infection remains elusive. As YF wild-type strains are hepatotropic, we chose a hepatic cell line (HepG2) to study YF virus-host cell interaction. HepG2 cells rapidly produced high titres of infectious viral particles for 17D and Asibi YF strains. However, HepG2 cells were more susceptible to the attenuated 17D virus infection, and only this virus strain induced early apoptosis in these cells. Molecular markers specific for the 17D virus were identified by microarray analysis and confirmed by quantitative RT-PCR analysis. As early as 1h postinfection, three genes, (IEX-1, IRF-1, DEC-1) all implicated in apoptosis pathways, were upregulated. Later in infection (48 h) two other genes (HSP70-1A and 1B), expressed in cases of cellular stress, were highly upregulated in 17D-infected HepG2 cells. The early specific upregulation of these cellular genes in HepG2 cells may be considered markers of the 17D virus. This study on the YF attenuated strain gives a new approach to the analysis of the factors involved in virus attenuation.

  13. SipA Activation of Caspase-3 Is a Decisive Mediator of Host Cell Survival at Early Stages of Salmonella enterica Serovar Typhimurium Infection

    PubMed Central

    McIntosh, Anne; Meikle, Lynsey M.; Ormsby, Michael J.; McCormick, Beth A.; Christie, John M.; Brewer, James M.; Roberts, Mark

    2017-01-01

    ABSTRACT Salmonella invasion protein A (SipA) is a dual-function effector protein that plays roles in both actin polymerization and caspase-3 activation in intestinal epithelial cells. To date its function in other cell types has remained largely unknown despite its expression in multiple cell types and its extracellular secretion during infection. Here we show that in macrophages SipA induces increased caspase-3 activation early in infection. This activation required a threshold level of SipA linked to multiplicity of infection and may be a limiting factor controlling bacterial numbers in infected macrophages. In polymorphonuclear leukocytes, SipA or other Salmonella pathogenicity island 1 effectors had no effect on induction of caspase-3 activation either alone or in the presence of whole bacteria. Tagging of SipA with the small fluorescent phiLOV tag, which can pass through the type three secretion system, allowed visualization and quantification of caspase-3 activation by SipA-phiLOV in macrophages. Additionally, SipA-phiLOV activation of caspase-3 could be tracked in the intestine through multiphoton laser scanning microscopy in an ex vivo intestinal model. This allowed visualization of areas where the intestinal epithelium had been compromised and demonstrated the potential use of this fluorescent tag for in vivo tracking of individual effectors. PMID:28630067

  14. PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells▿

    PubMed Central

    Paquet, Sophie; Daude, Nathalie; Courageot, Marie-Pierre; Chapuis, Jérôme; Laude, Hubert; Vilette, Didier

    2007-01-01

    We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface. PMID:17626095

  15. Cognitive function in early HIV infection.

    PubMed

    Prakash, Aanchal; Hou, Jue; Liu, Lei; Gao, Yi; Kettering, Casey; Ragin, Ann B

    2017-04-01

    This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

  16. The stochastic dance of early HIV infection

    NASA Astrophysics Data System (ADS)

    Merrill, Stephen J.

    2005-12-01

    The stochastic nature of early HIV infection is described in a series of models, each of which captures aspects of the dance of HIV during the early stages of infection. It is to this highly variable target that the immune response must respond. The adaptability of the various components of the immune response is an important aspect of the system's operation, as the nature of the pathogens that the response will be required to respond to and the order in which those responses must be made cannot be known beforehand. As HIV infection has direct influence over cells responsible for the immune response, the dance predicts that the immune response will be also in a variable state of readiness and capability for this task of adaptation. The description of the stochastic dance of HIV here will use the tools of stochastic models, and for the most part, simulation. The justification for this approach is that the early stages and the development of HIV diversity require that the model to be able to describe both individual sample path and patient-to-patient variability. In addition, as early viral dynamics are best described using branching processes, the explosive growth of these models both predicts high variability and rapid response of HIV to changes in system parameters.In this paper, a basic viral growth model based on a time dependent continuous-time branching process is used to describe the growth of HIV infected cells in the macrophage and lymphocyte populations. Immigration from the reservoir population is added to the basic model to describe the incubation time distribution. This distribution is deduced directly from the modeling assumptions and the model of viral growth. A system of two branching processes, one in the infected macrophage population and one in the infected lymphocyte population is used to provide a description of the relationship between the development of HIV diversity as it relates to tropism (host cell preference). The role of the immune

  17. A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.

    PubMed

    McCarthy, James S; Rückle, Thomas; Djeriou, Elhadj; Cantalloube, Cathy; Ter-Minassian, Daniel; Baker, Mark; O'Rourke, Peter; Griffin, Paul; Marquart, Louise; Hooft van Huijsduijnen, Rob; Möhrle, Jörg J

    2016-09-13

    Ferroquine (SSR97193) is a candidate anti-malarial currently undergoing clinical trials for malaria. To better understand its pharmacokinetic (PK) and pharmacodynamic (PD) parameters the compound was tested in the experimentally induced blood stage malaria infection model in volunteers. Male and non-pregnant female aged 18-50 years were screened for this phase II, controlled, single-centre clinical trial. Subjects were inoculated with ~1800 viable Plasmodium falciparum 3D7A-infected human erythrocytes, and treated with a single-dose of 800 mg ferroquine. Blood samples were taken at defined time-points to measure PK and PD parameters. The blood concentration of ferroquine and its active metabolite, SSR97213, were measured on dry blood spot samples by ultra-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Parasitaemia and emergence of gametocytes were monitored by quantitative PCR. Safety was determined by recording adverse events and monitoring clinical laboratory assessments during the course of the study. Eight subjects were enrolled into the study, inoculated with infected erythrocytes and treated with 800 mg ferroquine. Ferroquine was rapidly absorbed with maximal exposure after 4-8 and 4-12 h exposure for SSR97213. Non-compartmental PK analysis resulted in estimates for half-lives of 10.9 and 23.8 days for ferroquine and SSR97213, respectively. Parasite clearance as reported by parasite reduction ratio was 162.9 (95 % CI 141-188) corresponding to a parasite clearance half-life of 6.5 h (95 % CI: 6.4-6.7 h). PK/PD modelling resulted in a predicted minimal parasiticidal concentration of 20 ng/mL, and the single dosing tested in this study was predicted to maintain an exposure above this threshold for 454 h (37.8 days). Although ferroquine was overall well tolerated, transient elevated transaminase levels were observed in three subjects. Paracetamol was the only concomitant treatment among the two out of these three subjects

  18. The early stages of duplicate gene evolution

    PubMed Central

    Moore, Richard C.; Purugganan, Michael D.

    2003-01-01

    Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8–20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes. PMID:14671323

  19. Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection.

    PubMed

    Xu, Jinxian; Mo, Juan; Liu, Xinglou; Marshall, Brendan; Atherton, Sally S; Dong, Zheng; Smith, Sylvia; Zhang, Ming

    2018-05-01

    The purpose of this study was to determine if the receptor-interacting protein kinase 3 (RIP3) plays a significant role in innate immune responses and death of bystander retinal neurons during murine cytomegalovirus (MCMV) retinal infection, by comparing the innate immune response and cell death in RIP3-depleted mice (Rip3-/-) and Rip3+/+ control mice. Rip3-/- and Rip3+/+ mice were immunosuppressed (IS) and inoculated with MCMV via the supraciliary route. Virus-injected and mock-injected control eyes were removed at days 4, 7, and 10 post infection (p.i.) and markers of innate immunity and cell death were analyzed. Compared to Rip3+/+ mice, significantly more MCMV was recovered and more MCMV-infected RPE cells were observed in injected eyes of Rip3-/- mice at days 4 and 7 p.i. In contrast, fewer TUNEL-stained photoreceptors were observed in Rip3-/- eyes than in Rip3+/+ eyes at these times. Electron microscopy showed that significantly more apoptotic photoreceptor cells were present in Rip3+/+ mice than in Rip3-/- mice. Immunohistochemistry showed that the majority of TUNEL-stained photoreceptors died via mitochondrial flavoprotein apoptosis-inducing factor (AIF)-mediated, caspase 3-independent apoptosis. The majority of RIP3-expressing cells in infected eyes were RPE cells, microglia/macrophages, and glia, whereas retinal neurons contained much lower amounts of RIP3. Western blots showed significantly higher levels of activated nuclear factor-κB and caspase 1 were present in Rip3+/+ eyes compared to Rip3-/- eyes. Our results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor-κB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.

  20. Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection

    PubMed Central

    Xu, Jinxian; Mo, Juan; Liu, Xinglou; Marshall, Brendan; Atherton, Sally S.; Dong, Zheng; Smith, Sylvia

    2018-01-01

    Purpose The purpose of this study was to determine if the receptor-interacting protein kinase 3 (RIP3) plays a significant role in innate immune responses and death of bystander retinal neurons during murine cytomegalovirus (MCMV) retinal infection, by comparing the innate immune response and cell death in RIP3-depleted mice (Rip3−/−) and Rip3+/+ control mice. Methods Rip3−/− and Rip3+/+ mice were immunosuppressed (IS) and inoculated with MCMV via the supraciliary route. Virus-injected and mock-injected control eyes were removed at days 4, 7, and 10 post infection (p.i.) and markers of innate immunity and cell death were analyzed. Results Compared to Rip3+/+ mice, significantly more MCMV was recovered and more MCMV-infected RPE cells were observed in injected eyes of Rip3−/− mice at days 4 and 7 p.i. In contrast, fewer TUNEL-stained photoreceptors were observed in Rip3−/− eyes than in Rip3+/+ eyes at these times. Electron microscopy showed that significantly more apoptotic photoreceptor cells were present in Rip3+/+ mice than in Rip3−/− mice. Immunohistochemistry showed that the majority of TUNEL-stained photoreceptors died via mitochondrial flavoprotein apoptosis-inducing factor (AIF)-mediated, caspase 3–independent apoptosis. The majority of RIP3-expressing cells in infected eyes were RPE cells, microglia/macrophages, and glia, whereas retinal neurons contained much lower amounts of RIP3. Western blots showed significantly higher levels of activated nuclear factor–κB and caspase 1 were present in Rip3+/+ eyes compared to Rip3−/− eyes. Conclusions Our results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor–κB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.

  1. Liquid biopsy for early stage lung cancer.

    PubMed

    Liang, Wenhua; Zhao, Yi; Huang, Weizhe; Liang, Hengrui; Zeng, Haikang; He, Jianxing

    2018-04-01

    Liquid biopsy, which analyzes biological fluids especially blood specimen to detect and quantify circulating cancer biomarkers, have been rapidly introduced and represents a promising potency in clinical practice of lung cancer diagnosis and prognosis. Unlike conventional tissue biopsy, liquid biopsy is non-invasive, safe, simple in procedure, and is not influenced by manipulators' skills. Notably, some circulating cancer biomarkers are already detectable in disease with low-burden, making liquid biopsy feasible in detecting early stage lung cancer. In this review, we described a landscape of different liquid biopsy methods by highlighting the rationale and advantages, accessing the value of various circulating biomarkers and discussing their possible future development in the detection of early lung cancer.

  2. Hepatocellular carcinoma: early-stage management challenges

    PubMed Central

    Erstad, Derek J; Tanabe, Kenneth K

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. PMID:28721349

  3. RNA-Seq analysis of Citrus reticulata in the early stages of Xylella fastidiosa infection reveals auxin-related genes as a defense response.

    PubMed

    Rodrigues, Carolina M; de Souza, Alessandra A; Takita, Marco A; Kishi, Luciano T; Machado, Marcos A

    2013-10-03

    Citrus variegated chlorosis (CVC), caused by Xylella fastidiosa, is one the most important citrus diseases, and affects all varieties of sweet orange (Citrus sinensis L. Osb). On the other hand, among the Citrus genus there are different sources of resistance against X. fastidiosa. For these species identifying these defense genes could be an important step towards obtaining sweet orange resistant varieties through breeding or genetic engineering. To assess these genes we made use of mandarin (C. reticulata Blanco) that is known to be resistant to CVC and shares agronomical characteristics with sweet orange. Thus, we investigated the gene expression in Ponkan mandarin at one day after infection with X. fastidiosa, using RNA-seq. A set of genes considered key elements in the resistance was used to confirm its regulation in mandarin compared with the susceptible sweet orange. Gene expression analysis of mock inoculated and infected tissues of Ponkan mandarin identified 667 transcripts repressed and 724 significantly induced in the later. Among the induced transcripts, we identified genes encoding proteins similar to Pattern Recognition Receptors. Furthermore, many genes involved in secondary metabolism, biosynthesis and cell wall modification were upregulated as well as in synthesis of abscisic acid, jasmonic acid and auxin. This work demonstrated that the defense response to the perception of bacteria involves cell wall modification and activation of hormone pathways, which probably lead to the induction of other defense-related genes. We also hypothesized the induction of auxin-related genes indicates that resistant plants initially recognize X. fastidiosa as a necrotrophic pathogen.

  4. RNA-Seq analysis of Citrus reticulata in the early stages of Xylella fastidiosa infection reveals auxin-related genes as a defense response

    PubMed Central

    2013-01-01

    Background Citrus variegated chlorosis (CVC), caused by Xylella fastidiosa, is one the most important citrus diseases, and affects all varieties of sweet orange (Citrus sinensis L. Osb). On the other hand, among the Citrus genus there are different sources of resistance against X. fastidiosa. For these species identifying these defense genes could be an important step towards obtaining sweet orange resistant varieties through breeding or genetic engineering. To assess these genes we made use of mandarin (C. reticulata Blanco) that is known to be resistant to CVC and shares agronomical characteristics with sweet orange. Thus, we investigated the gene expression in Ponkan mandarin at one day after infection with X. fastidiosa, using RNA-seq. A set of genes considered key elements in the resistance was used to confirm its regulation in mandarin compared with the susceptible sweet orange. Results Gene expression analysis of mock inoculated and infected tissues of Ponkan mandarin identified 667 transcripts repressed and 724 significantly induced in the later. Among the induced transcripts, we identified genes encoding proteins similar to Pattern Recognition Receptors. Furthermore, many genes involved in secondary metabolism, biosynthesis and cell wall modification were upregulated as well as in synthesis of abscisic acid, jasmonic acid and auxin. Conclusions This work demonstrated that the defense response to the perception of bacteria involves cell wall modification and activation of hormone pathways, which probably lead to the induction of other defense-related genes. We also hypothesized the induction of auxin-related genes indicates that resistant plants initially recognize X. fastidiosa as a necrotrophic pathogen. PMID:24090429

  5. Late stage infection in sleeping sickness.

    PubMed

    Wolburg, Hartwig; Mogk, Stefan; Acker, Sven; Frey, Claudia; Meinert, Monika; Schönfeld, Caroline; Lazarus, Michael; Urade, Yoshihiro; Kubata, Bruno Kilunga; Duszenko, Michael

    2012-01-01

    At the turn of the 19(th) century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles.

  6. Multiple Circulating Infections Can Mimic the Early Stages of Viral Hemorrhagic Fevers and Possible Human Exposure to Filoviruses in Sierra Leone Prior to the 2014 Outbreak

    PubMed Central

    Boisen, Matthew L.; Schieffelin, John S.; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B.; Shaffer, Jeffrey G.; Hastie, Kathryn M.; Hartnett, Jessica N.; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K.; Andersen, Kristian G.; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W.; Geisbert, Joan B.; Pitts, Kelly R.; Geisbert, Thomas W.; Kulakoski, Peter; Wilson, Russell B.; Henderson, Lee; Sabeti, Pardis C.; Grant, Donald S.; Garry, Robert F.; Saphire, Erica O.; Khan, Sheik Humarr

    2015-01-01

    Abstract Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction–based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak. PMID:25531344

  7. Urinary Biomarkers at Early ADPKD Disease Stage

    PubMed Central

    Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

    2015-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

  8. Virtual exploration of early stage atherosclerosis.

    PubMed

    Olivares, Andy L; González Ballester, Miguel A; Noailly, Jérôme

    2016-12-15

    Biological mechanisms contributing to atherogenesis are multiple and complex. The early stage of atherosclerosis (AS) is characterized by the accumulation of low-density lipoprotein (LDL) droplets, leading to the creation of foam cells (FC). To address the difficulty to explore the dynamics of interactions that controls this process, this study aimed to develop a model of agents and infer on the most influential cell- and molecule-related parameters. FC started to accumulate after six to eight months of simulated hypercholesterolemia. A sensitivity analysis revealed the strong influence of LDL oxidation rate on the risk of FC creation, which was exploited to model the antioxidant effect of statins. Combined with an empirical simulation of the drug ability to decrease the level of LDL, the virtual statins treatment led to reductions of oxidized LDL levels similar to reductions measured in vivo. An Open source software was used to develop the agent-based model of early AS. Two different concentrations of LDL agents were imposed in the intima layer to simulate healthy and hypercholesterolemia groups of 'virtual patients'. The interactions programmed between molecules and cells were based on experiments and models reported in the literature. A factorial sensitivity analysis explored the respective effects of the less documented model parameters as (i) agent migration speed, (ii) LDL oxidation rate and (iii) concentration of autoantibody agents. Finally, the response of the model to known perturbations was assessed by introducing statins agents, able to reduce the oxidation rate of LDL agents and the LDL boundary concentrations. jerome.noailly@upf.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

    PubMed Central

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

    2013-01-01

    The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

  10. Is Single-stage Revision Safe Following Infected Total Knee Arthroplasty? A Critical Review.

    PubMed

    Vaishya, Raju; Agarwal, Amit Kumar; Rawat, Sudheer K; Singh, Harsh; Vijay, Vipul

    2017-08-30

    With the improvement in outcomes and modern prosthesis design, total knee arthroplasty (TKA) has now become a commonly performed surgery. It is postulated that a total of 2-5% of the primary and revision TKA becomes infected every year, requiring a revision procedure which to date is the conventional two-stage revision. The diagnosis and treatment of these periprosthetic infections is a major and challenging task, as it requires precise identification of the pathogen, meticulous debridement, and postoperative rehabilitation. To date, there have been very few studies in existing literature comparing the outcomes of single-stage versus two-stage procedure in infected TKA. The aim of the review was to provide the clinicians an insight into the outcome of the single-stage procedure compared to two-stage procedures and to suggest ways to improve the results further. In the following critical review, a total of 669 cases that underwent either a single or two-stage revision for infected TKA were studied. The postoperative functional scores were comparable in most studies during the early postoperative period. Our data supports the use of a single-stage revision surgery in infected TKA as an alternative to a conventional two-stage procedure. However, larger prospective and multicentric trials are required to validate our findings.

  11. Comparative performances of staging systems for early hepatocellular carcinoma.

    PubMed

    Nathan, Hari; Mentha, Gilles; Marques, Hugo P; Capussotti, Lorenzo; Majno, Pietro; Aldrighetti, Luca; Pulitano, Carlo; Rubbia-Brandt, Laura; Russolillo, Nadia; Philosophe, Benjamin; Barroso, Eduardo; Ferrero, Alessandro; Schulick, Richard D; Choti, Michael A; Pawlik, Timothy M

    2009-08-01

    Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c approximately 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c = 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c = 0.60) and identified three distinct prognostic groups. The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.

  12. Development of an early-stage toll revenue estimation model.

    DOT National Transportation Integrated Search

    2012-05-01

    With agencies and states increasingly considering tolls as a means to finance transportation infrastructure, : there is an increasing need to quickly assess the feasibility of potential tolling projects. In the early stages : of a project when an age...

  13. Characteristics of Early Stages of Corrosion Fatigue in Aircraft Skin

    DOT National Transportation Integrated Search

    1996-02-01

    SRI International is conducting research to characterize and quantitatively describe the early stages of corrosion fatigue in the fuselage skin of commercial aircraft. Specific objectives are to gain an improved deterministic understanding of the tra...

  14. Chemical defense of early life stages of benthic marine invertebrates.

    PubMed

    Lindquist, Niels

    2002-10-01

    Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

  15. A Four Stage Approach to Early Childhood Intervention.

    ERIC Educational Resources Information Center

    Haber, Julian S.

    This paper describes a model for the involvement of primary health care personnel in the identification and treatment of developmental disabilities as a part of early childhood intervention programs. The integrated multidisciplinary model is divided into four stages. During the first stage an assignment of prenatal, perinatal, and postnatal risk…

  16. [Experience of the three-stage strategy for intestinal fistula complicated with complex abdominal infection].

    PubMed

    Zhao, Qingchuan; Li, Xuzhao; Li, Xiaohua; Wang, Juan

    2017-03-25

    Intestinal fistula, as a serious complication after abdominal surgery, not only leads to a series of pathophysiological changes such as fluid loss, malnutrition and organ dysfunction, but also causes the severe abdominal infection, which often threatens the life of patients. How to make the diagnosis and give the treatment of intestinal fistula is the key to save the lives of high-risk patients. In our hospital, during the past course of diagnosis and treatment for intestinal fistula complicated with severe abdominal infection, based on the combination of literatures at home and abroad with our clinical experiences for many years, an effective three-stage prevention and treatment strategy was formed gradually, which included early diagnosis, effective treatment of infection source, open drainage of abdominal infection and early enteral nutrition support. This strategy subverts the traditional concept of surgery alone, and becomes an effective means to save patients with severe abdominal infection.

  17. Two-stage reimplantation for treating prosthetic shoulder infections.

    PubMed

    Sabesan, Vani J; Ho, Jason C; Kovacevic, David; Iannotti, Joseph P

    2011-09-01

    Two-stage reimplantation for prosthetic joint infection reportedly has the lowest risk for recurrent infection. Most studies to date have evaluated revision surgery for infection using an anatomic prosthetic. As compared with anatomic prostheses, reverse total shoulder arthroplasty is reported to have a higher rate of infection. We determined reinfection rates, functional improvement, types and rates of complications, and influence of rotator cuff tissue on function for two-stage reimplantation for prosthetic joint infection treated with reverse shoulder arthroplasty. We retrospectively reviewed 27 patients treated with a two-stage reimplantation for prosthetic shoulder infection using a uniform protocol for management of infection; of these, 17 had reverse shoulder arthroplasty at second-stage surgery. Types of organisms cultured, recurrence rates, complications, function, and radiographic followup were reviewed for all patients. One of the 17 patients had recurrence of infection. The mean (± SD) Penn shoulder scores for patients treated with reverse shoulder arthroplasty improved from 24.9 ± 22.3 to 66.4 ± 20.8. The average motion at last followup was 123° ± 33° of forward flexion and 26° ± 8° of external rotation in patients treated with a reverse shoulder arthroplasty. The major complication rate was 35% in reverse shoulder arthroplasty, with five dislocations and one reinfection. There was no difference in final Penn score between patients with and without external rotation weakness. Shoulder function and pain improved in patients treated with a second-stage reimplantation of a reverse prosthesis and the reinfection rate was low. Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.

  18. [Cognitive rehabilitation in early stage Alzheimer's disease].

    PubMed

    Kasper, E; Thöne-Otto, A; Bürger, K; Schröder, S G; Hoffmann, W; Schneider, W; Teipel, S

    2016-07-01

    Dementia impairs the coping with routine daily tasks and social relationships due to an increasing degeneration of cognitive abilities. An appropriate treatment must adequately consider the effects of declined cognitive abilities on patients and their environment. Therefore, in recent times, integrative procedures for cognitive rehabilitation (CR) have become increasingly important for the therapy of patients with mild cognitive impairment (MCI) and mild dementia (MD). CR approaches provide compensatory possibilities for clearly defined routine challenges and the individual needs of those affected. This overview article in the form of a selective review elaborates factors for the effectiveness of CR on the basis of the currently available literature: 1) individuality - consideration of personal needs and targets, 2) compensation - mediation of skills and strategies to compensate for cognitive impairments, 3) interaction - inclusion of relatives and environmental conditions and 4) integration - integration of various therapeutic disciplines and methods. On the basis of this assessment with regards to the content, a critical analysis of the methods of short and long-term therapeutic effects on MCD and MD was carried out. Although the resulting factors were of high long-term relevance for the improvement of depression and quality of life, effects on cognition were more pronounced for MCI than for MD, which emphasizes the importance of beginning therapy as early as possible. The results show that future studies on effectiveness must employ endpoints relevant for routine daily life, and that the possibility of an implementation of therapeutic concepts in a healthcare system should be considered as an essential criterion.

  19. SEOM clinical guidelines in early-stage breast cancer 2015.

    PubMed

    Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

    2015-12-01

    Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

  20. Surgical treatment for apparent early stage endometrial cancer

    PubMed Central

    2014-01-01

    Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

  1. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR Staging

    Cancer.gov

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective. For some time, the national lab’s Nanotechno

  2. CMV colitis in early HIV infection.

    PubMed

    Smith, P R; Glynn, M; Sheaff, M; Aitken, C

    2000-11-01

    Cytomegalovirus (CMV) colitis is a well recognized complication of advanced HIV disease and is only rarely diagnosed in patients with normal immune function. A case of CMV colitis occurring in early HIV infection is described. Although CMV infection is normally confined to patients with advanced HIV disease, it is possible that a number of contributing factors may have led to clinical disease in this patient. CMV colitis is an important diagnosis to consider in all patients who present with a diarrhoeal illness associated with systemic features, regardless of underlying immunosuppression.

  3. Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

    PubMed

    Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

    2016-12-29

    The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH 4 /H 2 S/H 2 O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

  4. Spiritual Diversity and Living with Early-Stage Dementia.

    PubMed

    McGee, Jocelyn Shealy; Zhao, Holly Carlson; Myers, Dennis R; Seela Eaton, Hannah

    2018-01-01

    Attention to spiritual diversity is necessary for the provision of culturally informed clinical care for people with early-stage dementia and their family members. In this article, an evidence-based theoretical framework for conceptualizing spiritual diversity is described in detail (Pargament, 2011). The framework is then applied to two clinical case studies of people living with early-stage dementia to elucidate the multilayered components of spiritual diversity in this population. The case studies were selected from a larger mixed-methods study on spirituality, positive psychological factors, health, and well-being in people living with early-stage dementia and their family members. To our knowledge this is the first systematic attempt to apply a theoretical framework for understanding spiritual diversity in this population. Implications for clinical practice are provided.

  5. Minimally invasive transcanal myringotomy for pediatric early stage congenital cholesteatoma.

    PubMed

    Jang, Chul Ho; Jung, Eun Kyung; Sung, Chung Man; Kim, Seung Beom; Kim, Young Yoon; Seong, Jong Yuap; Kang, Sung Hoon; Cho, Yong Beom

    2016-11-01

    Recently, minimally invasive transcanal myringotomy (MITM), which is a useful surgical technique for early stage congenital cholesteatoma (CC) in children, was introduced. The purpose of this study is to evaluate the short-term surgical results of MITM in pediatric early stage CC. We retrospectively reviewed the charts of 24 patients who underwent MITM between January 2013 and October 2015. The patients' ages ranged from 1 to 16 years (mean, 2.6 years). There were 17 male and 7 female patients. The right side (n = 13) was affected twice as often as the left side (n = 11). The most common site was the anterosuperior quadrant (15 cases). The diameter of the CC on axial computed tomography images ranged from 2.8 to 5.7 mm (mean, 3.9 mm). CCs were graded according to Potsic's system: 18 cases were classified as stage I, 3 case as stage II, and 3 cases as stage III. AllCCs except 1 were closed type. In21 patients, the tympanic membrane closed naturally without recurrence. Three patients showed small persistent dry perforation. Natural closure occurred in these patients, who were treated with paper patches. MITM is a simple, effective technique for removing an early stage CC from the middle ear, and it can minimize operative time, length of hospitalization, and postoperative morbidity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Early Stages of the Evolution of Life: a Cybernetic Approach

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.; Seleznev, Vladimir D.

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  7. Early stages of the evolution of life: a cybernetic approach.

    PubMed

    Melkikh, Alexey V; Seleznev, Vladimir D

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  8. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  9. Signatures of unfolding in the early stages of protein denaturation

    NASA Astrophysics Data System (ADS)

    Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

    2012-04-01

    A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.

  10. Bioaccumulation of lipophilic substances in fish early life stages

    SciT

    Petersen, G.I.; Kristensen, P.

    1998-07-01

    Accumulation of {sup 14}C-labeled polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, pyrene, and benzo(a)pyrene and polychlorinated biphenyl (PCB) congeners PCB 31 and PCB 105 with a log octanol/water partition coefficient (K{sub ow}) range from 3.37 to 6.5 was investigated in eggs and larvae of zebra fish (Brachydanio rerio), and in larvae of cod (Gadus morhua), herring (Clupea harengus), and turbot (Scophthalmus maximus). Significant differences in the uptake and elimination rate constants between eggs and larvae of zebra fish were seen. The low rate of uptake and the lower elimination rate of eggs did, however, lead to bioconcentration factors (BCFs) comparable to thosemore » for larvae. As biotransformation of xenobiotics in embryonic and larval stages was indicated to be insignificant compared to juvenile/adult stages, body burdens of readily biotransformed chemicals may be higher in fish early life stages. Because weight and lipid content did not differ much between the investigated species, the main reason for the variability in BCFs between marine species and freshwater species was considered to be caused by differences in exposure temperatures that affect the degree of biotransformation. Due to the smaller size of larvae and thus an increased total surface of the membranes per unit fish weight, steady-state conditions were reached at a faster r/ate in early life stages than in juvenile/adult life stages. The lipid-normalized bioconcentration factors (BCF{sub L}) were linearly related to K{sub ow} but BCF{sub L} was, in general, higher than K{sub ow}, indicating that octanol is not a suitable surrogate for fish lipids. Differences in bioconcentration kinetics between larvae and juvenile/adult life stages are considered to be the main reason for the higher sensitivity, with respect to external effect concentrations, generally obtained for early life stages of fish.« less

  11. 76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... SMALL BUSINESS ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage... Webinars regarding its proposed Early Stage Small Business Investment Companies (Early Stage SBIC) rule. The proposed Early Stage SBIC rule defines a new sub-category of small business investment companies...

  12. Folding of Polymer Chains in Early Stage of Crystallization

    NASA Astrophysics Data System (ADS)

    Yuan, Shichen; Miyoshi, Toshikazu

    Understanding the structural formation of long polymer chains in the early stage of crystallization is one of the long-standing problems in polymer science. Using solid state NMR, we investigated chain trajectory of isotactic polypropylene in the mesomorphic nano-domains formed via rapid and deep quenching. Comparison of experimental and simulated 13C-13C Double Quantum (DQ) buildup curves demonstrated that instead of random re-entry models and solidification models, individual chains in the mesomorphic form iPP adopt adjacent reentry sequences with an average folding number of = 3-4 (assuming an adjacent re-entry fraction of of 100%) during mesomorphic formation process via nucleation and growth in the early stage. This work was financially supported by the National Science Foundation (Grant DMR-1105829 and 1408855) and startup funds from the UA.

  13. Flavivirus Infection Impairs Peroxisome Biogenesis and Early Antiviral Signaling

    PubMed Central

    You, Jaehwan; Hou, Shangmei; Malik-Soni, Natasha; Xu, Zaikun; Kumar, Anil; Rachubinski, Richard A.; Frappier, Lori

    2015-01-01

    ABSTRACT Flaviviruses are significant human pathogens that have an enormous impact on the global health burden. Currently, there are very few vaccines against or therapeutic treatments for flaviviruses, and our understanding of how these viruses cause disease is limited. Evidence suggests that the capsid proteins of flaviviruses play critical nonstructural roles during infection, and therefore, elucidating how these viral proteins affect cellular signaling pathways could lead to novel targets for antiviral therapy. We used affinity purification to identify host cell proteins that interact with the capsid proteins of West Nile and dengue viruses. One of the cellular proteins that formed a stable complex with flavivirus capsid proteins is the peroxisome biogenesis factor Pex19. Intriguingly, flavivirus infection resulted in a significant loss of peroxisomes, an effect that may be due in part to capsid expression. We posited that capsid protein-mediated sequestration and/or degradation of Pex19 results in loss of peroxisomes, a situation that could result in reduced early antiviral signaling. In support of this hypothesis, we observed that induction of the lambda interferon mRNA in response to a viral RNA mimic was reduced by more than 80%. Together, our findings indicate that inhibition of peroxisome biogenesis may be a novel mechanism by which flaviviruses evade the innate immune system during early stages of infection. IMPORTANCE RNA viruses infect hundreds of millions of people each year, causing significant morbidity and mortality. Chief among these pathogens are the flaviviruses, which include dengue virus and West Nile virus. Despite their medical importance, there are very few prophylactic or therapeutic treatments for these viruses. Moreover, the manner in which they subvert the innate immune response in order to establish infection in mammalian cells is not well understood. Recently, peroxisomes were reported to function in early antiviral signaling, but

  14. Dyslipidogenic microangiopathy in guinea pigs at early stages of atherogenesis.

    PubMed

    Bersenev, A V; Klimenko, E D; Kobozeva, L P; Michunskaya, A B; Onishchenko, N A; Pozdnyakov, O M

    2003-08-01

    We studied the effect of dyslipidemia on lipid metabolism, state of microcirculatory system, and morphological alterations in the aorta and liver of guinea pigs at the early stages of experimental atherogenesis. The important role of microcirculatory disorders in the development of regional pathology and atherosclerosis is confirmed. The proposed alimentary model can be used in the development of novel methods for prevention and treatment of atherosclerosis.

  15. Multimodal imaging findings in 'hyper-early' stage MEWDS.

    PubMed

    Cahuzac, Armelle; Wolff, Benjamin; Mathis, Thibaud; Errera, Marie-Hélène; Sahel, José-Alain; Mauget-Faÿsse, Martine

    2017-10-01

    To describe a new stage of multiple evanescent white dot syndrome (MEWDS), occurring at a very early phase of the disease. Retrospective analysis of clinical, angiographic and tomographic findings in four patients with 'hyper-early' stage MEWDS. In four patients seen within 1 week of the onset of symptoms, fundus analysis revealed macular granity and the classic yellow-white dots, some having no corresponding hyperautofluorescent pattern. Spectral-domain optical coherence tomography (SD-OCT) showed central foveal disruption of the ellipsoid zone (EZ) and interdigitation layer with a hyper-reflective dome-shaped lesion. In two patients, fluorescein angiography (FA) revealed an intermediate hypofluorescent perimacular halo, whereas late indocyanine green angiography (ICGA) showed a hyperfluorescent halo as well as the classic MEWDS features. After a few days, the EZ disruption appeared complete on OCT and fundus autofluorescence (FAF) in all patients. Visual acuity, OCT and FAF findings had fully recovered within 3 months. We have shown a new feature of MEWDS on FAF, OCT, FA and ICGA, corresponding to a very early stage of the disease. 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/.

  16. Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

    PubMed

    Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

    2018-04-01

    Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

  17. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    PubMed

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Radiation therapy in early-stage invasive breast cancer.

    PubMed

    Lin, Ray; Tripuraneni, Prabhakar

    2011-06-01

    The treatment of breast cancer involves a multi-disciplinary approach with radiation therapy playing a key role. Breast-conserving surgery has been an option for women with early-stage breast cancer for over two decades now. Multiple randomized trials now have demonstrated the efficacy of breast-conserving surgery followed by radiation therapy. With the advancements in breast imaging and the successful campaign for early detection of breast cancer, more women today are found to have early-stage small breast cancers. Patient factors (breast size, tumor location, history of prior radiation therapy, preexisting conditions such as collagen vascular disease, age, having prosthetically augmented breasts), pathological factors (margin status, tumor size, presence of extensive intraductal component requiring multiple surgical excisions), as well as patient preference are all taken into consideration prior to surgical management of breast cancer. Whole-breast fractionated radiation therapy between 5 and 7 weeks is considered as the standard of care treatment following breast-conserving surgery. However, new radiation treatment strategies have been developed in recent years to provide alternatives to the conventional 5-7 week whole-breast radiation therapy for some patients. Accelerated partial breast radiation therapy (APBI) was introduced because the frequency of breast recurrences outside of the surgical cavity has been shown to be low. This technique allows treatments to be delivered quicker (usually 1 week, twice daily) to a limited volume. Often times, this treatment involves the use of a brachytherapy applicator to be placed into the surgical cavity following breast-conserving surgery. Accelerated hypofractionated whole-breast irradiation may be another faster way to deliver radiation therapy following breast-conserving surgery. This journal article reviews the role of radiation therapy in women with early-stage breast cancer addressing patient selection in breast

  19. Fertility sparing surgery in early stage epithelial ovarian cancer

    PubMed Central

    Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

    2014-01-01

    Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

  20. The effects of parasites on the early life stages of a damselfish

    NASA Astrophysics Data System (ADS)

    Sun, D.; Blomberg, S. P.; Cribb, T. H.; McCormick, M. I.; Grutter, A. S.

    2012-12-01

    Early life history traits, such as larval growth, influence the success of coral reef fish in the transition from the larval to the juvenile life phase. Few studies, however, have examined the relationship between parasites and growth in the early life history stages of such fishes. This study examined how parasite prevalence (% infected) and load, and the relationship between parasite presence and fish growth, differed among life stages of the damselfish Pomacentrus amboinensis. Parasite prevalence decreased significantly between the larval stage, which was sampled immediately before settlement on the reef (97 %) and recently settled juveniles (60 %); prevalence was also high for 4-month-old juveniles (90 %), 7-month-old juveniles (100 %) and adult fish (100 %). Total numbers of parasites per fish decreased dramatically (fourfold) between larval and recently settled fish, and then increased in the older stages to levels similar to those observed in larvae, but they did so more gradually than did prevalence. One explanation for these patterns is that heavily infected larvae were preferentially removed from the population during or soon after settlement. Daily fish growth, determined from otolith increments, revealed that growth did not differ between parasitised and non-parasitised larval fish, whereas recently settled fish that were parasitised had faster growth; these parasitised recently settled fish also displayed faster growth prior to settlement. These data provide evidence that parasites may explain some of the variation in growth and survival observed among coral reef fishes after settlement and thereby have a greater impact on population dynamics than previously understood.

  1. Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection

    PubMed Central

    Khoury, David S.; Cromer, Deborah; Akter, Jasmin; Sebina, Ismail; Elliott, Trish; Thomas, Bryce S.; Soon, Megan S. F.; James, Kylie R.; Best, Shannon E.; Haque, Ashraful; Davenport, Miles P.

    2017-01-01

    Severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to Plasmodium falciparum. Nevertheless, the host may partly control blood-stage parasite numbers while adaptive immunity is gradually established. Parasite control has typically been attributed to enhanced removal of parasites by the host, although in vivo quantification of this phenomenon remains challenging. We used a unique in vivo approach to determine the fate of a single cohort of semisynchronous, Plasmodium berghei ANKA- or Plasmodium yoelii 17XNL-parasitized red blood cells (pRBCs) after transfusion into naive or acutely infected mice. As previously shown, acutely infected mice, with ongoing splenic and systemic inflammatory responses, controlled parasite population growth more effectively than naive controls. Surprisingly, however, this was not associated with accelerated removal of pRBCs from circulation. Instead, transfused pRBCs remained in circulation longer in acutely infected mice. Flow cytometric assessment and mathematical modeling of intraerythrocytic parasite development revealed an unexpected and substantial slowing of parasite maturation in acutely infected mice, extending the life cycle from 24 h to 40 h. Importantly, impaired parasite maturation was the major contributor to control of parasite growth in acutely infected mice. Moreover, by performing the same experiments in rag1−/− mice, which lack T and B cells and mount weak inflammatory responses, we revealed that impaired parasite maturation is largely dependent upon the host response to infection. Thus, impairment of parasite maturation represents a host-mediated, immune system-dependent mechanism for limiting parasite population growth during the early stages of an acute blood-stage Plasmodium infection. PMID:28673996

  2. Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro.

    PubMed

    Zhao, Fu-Rong; Xie, Yin-Li; Liu, Ze-Zhong; Shao, Jun-Jun; Li, Shi-Fang; Zhang, Yong-Guang; Chang, Hui-Yun

    2017-11-01

    Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK-21 cell was dose-dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID 50 ) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT-qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti-FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in-depth research in vivo. © 2017 Wiley Periodicals, Inc.

  3. Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

    PubMed Central

    Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

    2016-01-01

    The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

  4. Frustration Sculpts the Early Stages of Protein Folding.

    PubMed

    Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano

    2015-09-07

    The funneled energy landscape theory implies that protein structures are minimally frustrated. Yet, because of the divergent demands between folding and function, regions of frustrated patterns are present at the active site of proteins. To understand the effects of such local frustration in dictating the energy landscape of proteins, here we compare the folding mechanisms of the two alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly identical sequence and structure, while displaying different frustration patterns. The analysis, based on the kinetic characterization of a large number of site-directed mutants, reveals that although the late stages for folding are very robust and biased by native topology, the early stages are more malleable and dominated by local frustration. The results are briefly discussed in the context of the energy-landscape theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The impact of p53 on the early stage replication of retrovirus.

    PubMed

    Kinnetz, Michaela; Alghamdi, Faris; Racz, Michael; Hu, Wenwei; Shi, Binshan

    2017-08-09

    The function of p53 in cancer biology has been studied extensively, but its role in anti-retrovirus infection has been elusive for many years. The restriction of retrovirus early stage replication by p53 was investigated in this study. VSV-G pseudotyped retrovirus with GFP reporter gene was used to infect both HCT116 p53 +/+ cells and its isogenic p53 knockout HCT116 p53 -/- cells. The infection was detected by flow cytometry. Reverse transcription products were quantified by real time PCR. Mutation analysis was performed after 1-LTR cycle and 2-LTR cycle DNA were amplified and PCR products were sequenced. Transcription and translation of cyclin-dependent kinase inhibitor 1 (p21 Cip1 ) and SAM domain and HD domain-containing protein 1 (SAMHD1) were analyzed by TaqMan PCR and Western blot experiments. siRNA experiment was applied to study the role of p53 downstream gene p21 Cip1 in the restriction of retrovirus infection. It was found that the block of retrovirus infection in non-cycling cells was significantly attenuated in HCT116 p53 -/- cells when compared to HCT116 p53 +/+ cells. It was found that both late reverse transcription products and viral 2-LTR cycle DNA were significantly increased in infected non-cycling HCT116 p53 -/- cells. Furthermore, the mutation frequency detected in 1-LTR DNA from HCT116 p53 +/+ cells were significantly decreased in comparison to HCT116 p53 -/- cells. A higher number of insertion and deletion mutations were detected in the joint region of 2-LTR cycle DNA in infected p53 +/+ cells. Cell cycle analysis showed retrovirus infection promoted host cell replication. Higher levels of mRNA and protein of p21 Cip1 were found in HCT116 p53 +/+ cells in comparison to the HCT116 p53 -/- cells. Furthermore, knockdown of p21 Cip1 in non-cycling HCT116 p53 +/+ cells significantly increased the infection. The results of this study showed that p53 is an important restriction factor that interferes with retrovirus infection in its early stage of

  6. Metabolomic Markers of Altered Nucleotide Metabolism in Early Stage Adenocarcinoma

    PubMed Central

    Wikoff, William R.; Grapov, Dmitry; Fahrmann, Johannes F.; DeFelice, Brian; Rom, William; Pass, Harvey; Kim, Kyoungmi; Nguyen, UyenThao; Taylor, Sandra L.; Kelly, Karen; Fiehn, Oliver; Miyamoto, Suzanne

    2015-01-01

    Adenocarcinoma, a type of non-small-cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and non-malignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and non-malignant lung tissue pairs from current or former smokers with early stage (Stage IA–IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared to non-malignant tissue. Cancer-associated biochemical alterations were characterized by: 1) decreased glucose levels, consistent with the Warburg effect, 2) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, 3) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, 4) increased 5'-deoxy-5'-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis and 5) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring. PMID:25657018

  7. Effects of genistein on early-stage cutaneous wound healing

    SciT

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These

  8. Reproductive and early life stages pathology - Histopathology workshop report

    Bruno, D.W.; Nowak, B.; Elliott, Diane G.

    2006-01-01

    Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

  9. Histopathological diagnosis of acral lentiginous melanoma in early stages.

    PubMed

    Fernandez-Flores, Angel; Cassarino, David S

    2017-02-01

    Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Late stages of accumulation and early evolution of the planets

    NASA Technical Reports Server (NTRS)

    Vityazev, Andrey V.; Perchernikova, G. V.

    1991-01-01

    Recently developed solutions of problems are discussed that were traditionally considered fundamental in classical solar system cosmogony: determination of planetary orbit distribution patterns, values for mean eccentricity and orbital inclinations of the planets, and rotation periods and rotation axis inclinations of the planets. Two important cosmochemical aspects of accumulation are examined: the time scale for gas loss from the terrestrial planet zone, and the composition of the planets in terms of isotope data. It was concluded that the early beginning of planet differentiation is a function of the heating of protoplanets during collisions with large (thousands of kilometers) bodies. Energetics, heat mass transfer processes, and characteristic time scales of these processes at the early stages of planet evolution are considered.

  11. Surgical Staging of Early Stage Endometrial Cancer: Comparison Between Laparotomy and Laparoscopy

    PubMed Central

    Api, Murat; Kayatas, Semra; Boza, Aysen Telce; Nazik, Hakan; Adiguzel, Cevdet; Guzin, Kadir; Eroglu, Mustafa

    2013-01-01

    Background The aim of the present study was to compare the laparotomy (LT) and laparoscopy (LS) in patients who undergone surgical staging for early stage endometrium cancer. Methods Retrospective data were collected and analyzed for amount of intraoperative bleeding, complication rates, total resected and laterality specific number of lymph nodes and duration of operation in patients operated with either LT or LS. Results Seventy-nine stage I endometrium cancer patients were found to be eligible for the trial purposes: 58 (73.4%) treated by LT and 21 (26.6%) treated by LS. The number of lymph nodes was similar in LT (8.9 ± 5.3) and LS (9.2 ± 4.8) (P = 0.8). In LT group, there was no difference in the number of lymph nodes between the right and left sides (10 ± 5.8 and 8.7 ± 4.8 respectively, P = 0.19); in LS group, the number of lymph nodes resected from the right side was higher than the left side (9.8 ± 5 and 7 ± 3.5 respectively, P = 0.039). The amount of intraoperative bleeding and hospitalization period were significantly higher in LT group. Seventy-nine patients had a median follow-up of 30 months. The two groups were similar for disease-free survival (P = 0.46, log rank test). Conclusions There was no significant difference between the two methods in terms of number of total resected lymph nodes. In early stage endometrial carcinoma, LS has provided adequate staging and similar survival rates with LT. PMID:29147363

  12. Ammonia and urea handling by early life stages of fishes.

    PubMed

    Zimmer, Alex M; Wright, Patricia A; Wood, Chris M

    2017-11-01

    Nitrogen metabolism in fishes has been a focus of comparative physiologists for nearly a century. In this Review, we focus specifically on early life stages of fishes, which have received considerable attention in more recent work. Nitrogen metabolism and excretion in early life differs fundamentally from that of juvenile and adult fishes because of (1) the presence of a chorion capsule in embryos that imposes a limitation on effective ammonia excretion, (2) an amino acid-based metabolism that generates a substantial ammonia load, and (3) the lack of a functional gill, which is the primary site of nitrogen excretion in juvenile and adult fishes. Recent findings have shed considerable light on the mechanisms by which these constraints are overcome in early life. Perhaps most importantly, the discovery of Rhesus (Rh) glycoproteins as ammonia transporters and their expression in ion-transporting cells on the skin of larval fishes has transformed our understanding of ammonia excretion by fishes in general. The emergence of larval zebrafish as a model species, together with genetic knockdown techniques, has similarly advanced our understanding of ammonia and urea metabolism and excretion by larval fishes. It has also now been demonstrated that ammonia excretion is one of the primary functions of the developing gill in rainbow trout larvae, leading to new hypotheses regarding the physiological demands driving gill development in larval fishes. Here, we highlight and discuss the dramatic changes in nitrogen handling that occur over early life development in fishes. © 2017. Published by The Company of Biologists Ltd.

  13. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  14. Loss of corticospinal tract integrity in early MS disease stages

    PubMed Central

    Neumann, Jens; Kaufmann, Jörn; Heidel, Jan; Stadler, Erhard; Sweeney-Reed, Catherine; Sailer, Michael; Schreiber, Stefanie

    2017-01-01

    Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages. Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study. Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified. Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy. PMID:28959706

  15. Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.

    PubMed

    Caballero, Ignacio S; Yen, Judy Y; Hensley, Lisa E; Honko, Anna N; Goff, Arthur J; Connor, John H

    2014-11-06

    Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods. In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR. These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.

  16. Metamorphic density controls on early-stage subduction dynamics

    NASA Astrophysics Data System (ADS)

    Duesterhoeft, Erik; Oberhänsli, Roland; Bousquet, Romain

    2013-04-01

    Subduction is primarily driven by the densification of the downgoing oceanic slab, due to dynamic P-T-fields in subduction zones. It is crucial to unravel slab densification induced by metamorphic reactions to understand the influence on plate dynamics. By analyzing the density and metamorphic structure of subduction zones, we may gain knowledge about the driving, metamorphic processes in a subduction zone like the eclogitization (i.e., the transformation of a MORB to an eclogite), the breakdown of hydrous minerals and the release of fluid or the generation of partial melts. We have therefore developed a 2D subduction zone model down to 250 km that is based on thermodynamic equilibrium assemblage computations. Our model computes the "metamorphic density" of rocks as a function of pressure, temperature and chemical composition using the Theriak-Domino software package at different time stages. We have used this model to investigate how the hydration, dehydration, partial melting and fractionation processes of rocks all influence the metamorphic density and greatly depend on the temperature field within subduction systems. These processes are commonly neglected by other approaches (e.g., gravitational or thermomechanical in nature) reproducing the density distribution within this tectonic setting. The process of eclogitization is assumed as being important to subduction dynamics, based on the very high density (3.6 g/cm3) of eclogitic rocks. The eclogitization in a MORB-type crust is possible only if the rock reaches the garnet phase stability field. This process is primarily temperature driven. Our model demonstrates that the initiation of eclogitization of the slab is not the only significant process that makes the descending slab denser and is responsible for the slab pull force. Indeed, our results show that the densification of the downgoing lithospheric mantle (due to an increase of pressure) starts in the early subduction stage and makes a significant

  17. HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling

    PubMed Central

    Dirk, Brennan S.; Pawlak, Emily N.; Johnson, Aaron L.; Van Nynatten, Logan R.; Jacob, Rajesh A.; Heit, Bryan; Dikeakos, Jimmy D.

    2016-01-01

    A defining characteristic of HIV-1 infection is the ability of the virus to persist within the host. Specifically, MHC-I downregulation by the HIV-1 accessory protein Nef is of critical importance in preventing infected cells from cytotoxic T-cell mediated killing. Nef downregulates MHC-I by modulating the host membrane trafficking machinery, resulting in the endocytosis and eventual sequestration of MHC-I within the cell. In the current report, we utilized the intracellular protein-protein interaction reporter system, bimolecular fluorescence complementation (BiFC), in combination with super-resolution microscopy, to track the Nef/MHC-I interaction and determine its subcellular localization in cells. We demonstrate that this interaction occurs upon Nef binding the MHC-I cytoplasmic tail early during endocytosis in a Rab5-positive endosome. Disruption of early endosome regulation inhibited Nef-dependent MHC-I downregulation, demonstrating that Nef hijacks the early endosome to sequester MHC-I within the cell. Furthermore, super-resolution imaging identified that the Nef:MHC-I BiFC complex transits through both early and late endosomes before ultimately residing at the trans-Golgi network. Together we demonstrate the importance of the early stages of the endocytic network in the removal of MHC-I from the cell surface and its re-localization within the cell, which allows HIV-1 to optimally evade host immune responses. PMID:27841315

  18. Early-stage aeolian protodune development and migration

    NASA Astrophysics Data System (ADS)

    Nield, J. M.; Baddock, M. C.; Wiggs, G.

    2017-12-01

    Early-stage bedforms, or protodunes, can be observed to form on sandy beaches, desert gravels or superimposed on the surfaces of larger dunes and can develop topography of 0.1 m or more over several hours. These protodunes are the precursors to embryo and eventually mature dunes, and so it is important to understand how feedbacks between flow, transport and form contribute to this development sequence. Whilst theory and conceptual models have offered some explanation for protodune existence and development, we know surprisingly little about how these bedforms initiate and migrate because it is difficult to measure small changes in form (millimetres; seconds) on highly active surfaces of limited topographic expression. Here, we employ terrestrial laser scanning (TLS) to measure morphological change at the high frequency and spatial resolution (sub-millimetre) required to gain new insights into protodune behaviour. Along with TLS derived saltation and surface moisture, additional sediment flux and windspeed measurements help to elucidate how the protodune topography interacts with airflow and sand transport. We focus on a number of coastal bedforms in various development stages including a 0.06 m high protodune which grew vertically by 0.005 m in two hours with the switch from erosion to deposition identified to occur at a point 0.07 m upwind of the crest. This growth was associated with a reduction in time-averaged sediment flux of 18% over the crestal region. We also observed a decline in lower stoss slope steepness (by 3°) and a steepening of the lee slope, indicating a reshaping of initial protodune form towards the morphology of a more mature dune. Our findings highlight the crucial role of form-flow feedbacks, even on very small bedforms, in driving early-stage bedform growth and development, and show how the use of high resolution TLS to measure both surface topography and grains moving above the surface, can offer new insights into a long standing deficiency

  19. Early-\\x90stage Electrical Breakdown involving Tunneling

    NASA Astrophysics Data System (ADS)

    Hjalmarson, Harold; Moore, Chris; Schultz, Peter; Bussman, Ezra; Scrymgeour, David; Hopkins, Matt

    The early stage of electrical breakdown from a surface is assumed to involve field emission. In real-world applications, the electrical field is often assumed to be increased by geometrical effects. In addition to these enhancement effects, contamination by adsorbates can lead to reductions in the effective work functions. To develop a physics-based understanding beyond the use of these empirical effects, the field emission currents at early times are being computed and measured. The calculations involve a solution of the Boltzmann equation, and the measurements involve a scanning tunneling microscope. Early results from this collaborative theoretical-experimental project will be described in this presentation. The presentation will focus on results for an ideal system with an absence of geometrical effects. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  20. Transcriptomic Analysis of Calonectria pseudoreteaudii during Various Stages of Eucalyptus Infection

    PubMed Central

    Ye, Xiaozhen; Liu, Hongyi; Jin, Yajie; Guo, Mengmeng; Huang, Aizhen; Chen, Quanzhu; Guo, Wenshuo; Zhang, Feiping; Feng, Lizhen

    2017-01-01

    Eucalyptus leaf blight caused by Calonectria spp. is a serious disease in Eucalyptus seedling and plantations. However, the molecular mechanisms of the infection process and pathogenesis of Calonectria to Eucalyptus is not well-studied. In this study, we analyzed the transcriptomes of C. pseudoreteaudii at three stages of Eucalyptus leaf infection, and in mycelium grown in potato dextrose broth using Illumina RNA-Seq technology. We identified 161 differentially expressed genes between C. pseudoreteaudii from leaf and mycelium grown in potato dextrose broth. GO and KEGG enrichment analyses of these genes suggested that they were mainly involved in oxidoreductase activity, hydrolase activity, and transmembrane transporter activity. Most of the differentially expressed genes at the early infection stage were upregulated. These upregulated genes were mainly involved in cell wall hydrolysis and toxin synthesis, suggesting a role for toxin and cell wall hydrolases in the establishment of Calonectria leaf blight. Genes related to detoxification of phytoalexins were continually upregulated during infection. The candidate effectors and putative pathogenicity determinants identified in this study will help in the functional analysis of C. pseudoreteaudii virulence and pathogenicity. PMID:28072879

  1. Transcriptomic Analysis of Calonectria pseudoreteaudii during Various Stages of Eucalyptus Infection.

    PubMed

    Ye, Xiaozhen; Liu, Hongyi; Jin, Yajie; Guo, Mengmeng; Huang, Aizhen; Chen, Quanzhu; Guo, Wenshuo; Zhang, Feiping; Feng, Lizhen

    2017-01-01

    Eucalyptus leaf blight caused by Calonectria spp. is a serious disease in Eucalyptus seedling and plantations. However, the molecular mechanisms of the infection process and pathogenesis of Calonectria to Eucalyptus is not well-studied. In this study, we analyzed the transcriptomes of C. pseudoreteaudii at three stages of Eucalyptus leaf infection, and in mycelium grown in potato dextrose broth using Illumina RNA-Seq technology. We identified 161 differentially expressed genes between C. pseudoreteaudii from leaf and mycelium grown in potato dextrose broth. GO and KEGG enrichment analyses of these genes suggested that they were mainly involved in oxidoreductase activity, hydrolase activity, and transmembrane transporter activity. Most of the differentially expressed genes at the early infection stage were upregulated. These upregulated genes were mainly involved in cell wall hydrolysis and toxin synthesis, suggesting a role for toxin and cell wall hydrolases in the establishment of Calonectria leaf blight. Genes related to detoxification of phytoalexins were continually upregulated during infection. The candidate effectors and putative pathogenicity determinants identified in this study will help in the functional analysis of C. pseudoreteaudii virulence and pathogenicity.

  2. Infection of Semen-Producing Organs by SIV during the Acute and Chronic Stages of the Disease

    PubMed Central

    Le Tortorec, Anna; Le Grand, Roger; Denis, Hélène; Satie, Anne-Pascale; Mannioui, Karim; Roques, Pierre; Maillard, Anne; Daniels, Sylvanne; Jégou, Bernard; Dejucq-Rainsford, Nathalie

    2008-01-01

    Background Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals. Methodology/Principal Findings Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected. Conclusions/Significance The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen. PMID:18347738

  3. Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

    PubMed Central

    Meyerson, Nicholas R.; Sharma, Amit; Wilkerson, Gregory K.

    2015-01-01

    ABSTRACT Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCE Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals

  4. Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

    PubMed

    García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

    2016-01-01

    Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Early stage response problem for post-disaster incidents

    NASA Astrophysics Data System (ADS)

    Kim, Sungwoo; Shin, Youngchul; Lee, Gyu M.; Moon, Ilkyeong

    2018-07-01

    Research on evacuation plans for reducing damages and casualties has been conducted to advise defenders against threats. However, despite the attention given to the research in the past, emergency response management, designed to neutralize hazards, has been undermined since planners frequently fail to apprehend the complexities and contexts of the emergency situation. Therefore, this study considers a response problem with unique characteristics for the duration of the emergency. An early stage response problem is identified to find the optimal routing and scheduling plan for responders to prevent further hazards. Due to the complexity of the proposed mathematical model, two algorithms are developed. Data from a high-rise building, called Central City in Seoul, Korea, are used to evaluate the algorithms. Results show that the proposed algorithms can procure near-optimal solutions within a reasonable time.

  6. Controversies in the Treatment of Early Stage Endometrial Carcinoma

    PubMed Central

    Press, Joshua Z.; Gotlieb, Walter H.

    2012-01-01

    Despite the publication of numerous studies, including some multicentered randomized controlled trials, there continues to be vigorous debate regarding the optimal management of early stage endometrial cancer, including the extent of surgery and the role of adjuvant chemotherapy and radiation. Resolving these questions has become increasingly important in view of the increase of endometrial cancer, related to the aging population and the alarming incidence of obesity. Furthermore, there are more surgical challenges encountered when operating on elderly patients or on patients with increased BMI and the associated comorbidities, such as diabetes, hypertension, heart disease, and pulmonary dysfunction. This paper will focus on the advantages of minimally invasive surgery, the value of lymphadenectomy including sentinel lymph node mapping, and some of the current controversies surrounding adjuvant chemotherapy and radiation. PMID:22685466

  7. Contingency Table Browser - prediction of early stage protein structure.

    PubMed

    Kalinowska, Barbara; Krzykalski, Artur; Roterman, Irena

    2015-01-01

    The Early Stage (ES) intermediate represents the starting structure in protein folding simulations based on the Fuzzy Oil Drop (FOD) model. The accuracy of FOD predictions is greatly dependent on the accuracy of the chosen intermediate. A suitable intermediate can be constructed using the sequence-structure relationship information contained in the so-called contingency table - this table expresses the likelihood of encountering various structural motifs for each tetrapeptide fragment in the amino acid sequence. The limited accuracy with which such structures could previously be predicted provided the motivation for a more indepth study of the contingency table itself. The Contingency Table Browser is a tool which can visualize, search and analyze the table. Our work presents possible applications of Contingency Table Browser, among them - analysis of specific protein sequences from the point of view of their structural ambiguity.

  8. Early stage of plastic deformation in thin films undergoing electromigration

    NASA Astrophysics Data System (ADS)

    Valek, B. C.; Tamura, N.; Spolenak, R.; Caldwell, W. A.; MacDowell, A. A.; Celestre, R. S.; Padmore, H. A.; Bravman, J. C.; Batterman, B. W.; Nix, W. D.; Patel, J. R.

    2003-09-01

    Electromigration occurs when a high current density drives atomic motion from the cathode to the anode end of a conductor, such as a metal interconnect line in an integrated circuit. While electromigration eventually causes macroscopic damage, in the form of voids and hillocks, the earliest stage of the process when the stress in individual micron-sized grains is still building up is largely unexplored. Using synchrotron-based x-ray microdiffraction during an in-situ electromigration experiment, we have discovered an early prefailure mode of plastic deformation involving preferential dislocation generation and motion and the formation of a subgrain structure within individual grains of a passivated Al (Cu) interconnect. This behavior occurs long before macroscopic damage (hillocks and voids) is observed.

  9. Infrared coagulation versus rubber band ligation in early stage hemorrhoids.

    PubMed

    Gupta, P J

    2003-10-01

    The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54) or infrared coagulation (N = 46). Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years). The mean duration of disease was 17.5 months (range 12 to 34 months). The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale). Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059). The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03), but also had a higher recurrence or failure rate (P = 0.03). Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.

  10. Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography.

    PubMed

    Zhao, Jingxin; Zhai, Fei; Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

    2017-01-01

    Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis.

  11. Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography

    PubMed Central

    Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

    2017-01-01

    Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis. PMID:28107385

  12. Repair of Craniomaxillofacial Traumatic Soft Tissue Defects With Tissue Expansion in the Early Stage.

    PubMed

    Han, Yan; Zhao, Jianhui; Tao, Ran; Guo, Lingli; Yang, Hongyan; Zeng, Wei; Song, Baoqiang; Xia, Wensen

    2017-09-01

    Craniomaxillofacial traumatic soft tissue defects severely affect the function and appearance of the patients. The traditional skin grafting or free flap transplantation can only close the defects in the early stage of operation but cannot ensure similar color, texture, and relative aesthetic contour. In the present study, the authors have explored a novel strategy to repair craniomaxillofacial traumatic soft tissue defects by tissue expansion in the early stage and have obtained satisfactory results. Eighteen patients suffering large craniomaxillofacial traumatic soft tissue defects were treated by thorough debridement leaving the wounds unclosed or simply closed with thin split-thickness scalp grafts, adjacent expander implantation in the first stage, and expanded flap transposition in the second stage. There were 11 male patients and 7 female patients ranging in age from 3.5 to 40 years (mean, 19.4 ± 12.2 years), with average 15 months follow-up (range, 3-67 months). The average expansion time was 74.3 days (range, 53-96 days). The 18 patients with a total of 22 expanders were treated with satisfactory results. All the flaps survived and the skin color, texture, and contour well matched those of the peripheral tissue. Only 1 complication of infection happened in the 18 cases (5.56%) and the 22 expanders (4.55%), which was similar to the rate reported in the literature. No other complications related to the expanders occurred. Debridement and tissue expansion in the early stage has been proved to be a more effective strategy to repair craniomaxillofacial traumatic soft tissue defects. This strategy can not only achieve satisfactory color, unbulky and well-matched texture similar to normal, but also avoid unnecessary donor site injuries.

  13. Sentinel lymph node navigation surgery for early stage gastric cancer.

    PubMed

    Mitsumori, Norio; Nimura, Hiroshi; Takahashi, Naoto; Kawamura, Masahiko; Aoki, Hiroaki; Shida, Atsuo; Omura, Nobuo; Yanaga, Katsuhiko

    2014-05-21

    We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient's quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.

  14. Sentinel lymph node navigation surgery for early stage gastric cancer

    PubMed Central

    Mitsumori, Norio; Nimura, Hiroshi; Takahashi, Naoto; Kawamura, Masahiko; Aoki, Hiroaki; Shida, Atsuo; Omura, Nobuo; Yanaga, Katsuhiko

    2014-01-01

    We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient’s quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation. PMID:24914329

  15. Treatment of early-stage Hodgkin lymphoma.

    PubMed

    Engert, Andreas; Raemaekers, John

    2016-07-01

    Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Presence of early stage cancer does not impair the early protein metabolic response to major surgery

    PubMed Central

    Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

    2017-01-01

    Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

  17. Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

    PubMed

    Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

    2017-06-01

    Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

  18. Emergency department presentations in early stage breast cancer patients receiving adjuvant and neoadjuvant chemotherapy.

    PubMed

    Tang, Monica; Horsley, Patrick; Lewis, Craig R

    2018-05-01

    (Neo)adjuvant chemotherapy for early stage breast cancer is associated with side-effects, resulting in increased emergency department (ED) presentations. Treatment-related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non-neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel-containing regimen (P = 0.018). © 2018 Royal Australasian College of Physicians.

  19. Generic Difference Between Early and Late Stages of BATSE Gamma-Ray Bursts

    NASA Technical Reports Server (NTRS)

    Mitrofanov, Igor G.; Litvak, Maxim L.; Anfimov, Dimitrij S.; Sanin, Anton B.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey N.; Preece, Robert D.; Meegan, Charles A.

    2001-01-01

    The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

  20. General Differences between Early and Late Stages of BATSE Gamma-Ray Bursts

    NASA Technical Reports Server (NTRS)

    Mitrofanov, I. G.; Litvak, M. L.; Anfimov, D. S.; Sanin, A. B.; Briggs, M. S.; Paciesas, W. S.; Pendleton, G. N.; Preece, R. D.; Meegan, C. A.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

  1. Association of Marital Status With T Stage at Presentation and Management of Early-Stage Melanoma.

    PubMed

    Sharon, Cimarron E; Sinnamon, Andrew J; Ming, Michael E; Chu, Emily Y; Fraker, Douglas L; Karakousis, Giorgos C

    2018-05-01

    Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients. This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017. Marital status, categorized as married, never married, divorced, or widowed. Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm. A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married

  2. Does cemented or cementless single-stage exchange arthroplasty of chronic periprosthetic hip infections provide similar infection rates to a two-stage? A systematic review.

    PubMed

    George, D A; Logoluso, N; Castellini, G; Gianola, S; Scarponi, S; Haddad, F S; Drago, L; Romano, C L

    2016-10-10

    The best surgical modality for treating chronic periprosthetic hip infections remains controversial, with a lack of randomised controlled studies. The aim of this systematic review is to compare the infection recurrence rate after a single-stage versus a two-stage exchange arthroplasty, and the rate of cemented versus cementless single-stage exchange arthroplasty for chronic periprosthetic hip infections. We searched for eligible studies published up to December 2015. Full text or abstract in English were reviewed. We included studies reporting the infection recurrence rate as the outcome of interest following single- or two-stage exchange arthroplasty, or both, with a minimum follow-up of 12 months. Two reviewers independently abstracted data and appraised quality assessment. After study selection, 90 observational studies were included. The majority of studies were focused on a two-stage hip exchange arthroplasty (65 %), 18 % on a single-stage exchange, and only a 17 % were comparative studies. There was no statistically significant difference between a single-stage versus a two-stage exchange in terms of recurrence of infection in controlled studies (pooled odds ratio of 1.37 [95 % CI = 0.68-2.74, I 2  = 45.5 %]). Similarly, the recurrence infection rate in cementless versus cemented single-stage hip exchanges failed to demonstrate a significant difference, due to the substantial heterogeneity among the studies. Despite the methodological limitations and the heterogeneity between single cohorts studies, if we considered only the available controlled studies no superiority was demonstrated between a single- and two-stage exchange at a minimum of 12 months follow-up. The overalapping of confidence intervals related to single-stage cementless and cemented hip exchanges, showed no superiority of either technique.

  3. Prediction of invasion from the early stage of an epidemic

    PubMed Central

    Pérez-Reche, Francisco J.; Neri, Franco M.; Taraskin, Sergei N.; Gilligan, Christopher A.

    2012-01-01

    Predictability of undesired events is a question of great interest in many scientific disciplines including seismology, economy and epidemiology. Here, we focus on the predictability of invasion of a broad class of epidemics caused by diseases that lead to permanent immunity of infected hosts after recovery or death. We approach the problem from the perspective of the science of complexity by proposing and testing several strategies for the estimation of important characteristics of epidemics, such as the probability of invasion. Our results suggest that parsimonious approximate methodologies may lead to the most reliable and robust predictions. The proposed methodologies are first applied to analysis of experimentally observed epidemics: invasion of the fungal plant pathogen Rhizoctonia solani in replicated host microcosms. We then consider numerical experiments of the susceptible–infected–removed model to investigate the performance of the proposed methods in further detail. The suggested framework can be used as a valuable tool for quick assessment of epidemic threat at the stage when epidemics only start developing. Moreover, our work amplifies the significance of the small-scale and finite-time microcosm realizations of epidemics revealing their predictive power. PMID:22513723

  4. Native language change during early stages of second language learning.

    PubMed

    Bice, Kinsey; Kroll, Judith F

    2015-11-11

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill.

  5. Affective motives for smoking among early stage smokers.

    PubMed

    Mathew, Amanda R; Wahlquist, Amy E; Garrett-Mayer, Elizabeth; Gray, Kevin M; Saladin, Michael E; Carpenter, Matthew J

    2014-10-01

    As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR - NR), such that higher dependence was associated with more prominent NR motives for smoking. Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Affective Motives for Smoking Among Early Stage Smokers

    PubMed Central

    Wahlquist, Amy E.; Garrett-Mayer, Elizabeth; Gray, Kevin M.; Saladin, Michael E.; Carpenter, Matthew J.

    2014-01-01

    Background: As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Methods: Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16–20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Results: Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR − NR), such that higher dependence was associated with more prominent NR motives for smoking. Conclusions: Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. PMID:24924155

  7. A microengineered pathophysiological model of early-stage breast cancer.

    PubMed

    Choi, Yoonseok; Hyun, Eunjeh; Seo, Jeongyun; Blundell, Cassidy; Kim, Hee Chan; Lee, Eunhee; Lee, Su Hyun; Moon, Aree; Moon, Woo Kyung; Huh, Dongeun

    2015-08-21

    A mounting body of evidence in cancer research suggests that the local microenvironment of tumor cells has a profound influence on cancer progression and metastasis. In vitro studies on the tumor microenvironment and its pharmacological modulation, however, are often hampered by the technical challenges associated with creating physiological cell culture environments that integrate cancer cells with the key components of their native niche such as neighboring cells and extracellular matrix (ECM) to mimic complex microarchitecture of cancerous tissue. Using early-stage breast cancer as a model disease, here we describe a biomimetic microengineering strategy to reconstitute three-dimensional (3D) structural organization and microenvironment of breast tumors in human cell-based in vitro models. Specifically, we developed a microsystem that enabled co-culture of breast tumor spheroids with human mammary ductal epithelial cells and mammary fibroblasts in a compartmentalized 3D microfluidic device to replicate microarchitecture of breast ductal carcinoma in situ (DCIS). We also explored the potential of this breast cancer-on-a-chip system as a drug screening platform by evaluating the efficacy and toxicity of an anticancer drug (paclitaxel). Our microengineered disease model represents the first critical step towards recapitulating pathophysiological complexity of breast cancer, and may serve as an enabling tool to systematically examine the contribution of the breast cancer microenvironment to the progression of DCIS to an invasive form of the disease.

  8. Multiscale Investigations of the Early Stage Oxidation on Cu Surfaces

    NASA Astrophysics Data System (ADS)

    Zhu, Qing; Xiao, Penghao; Lian, Xin; Yang, Shen-Che; Henkelman, Grame; Saidi, Wissam; Yang, Judith; University of Pittsburgh Team; University of Texas at Austin Team

    Previous in situ TEM experiments have shown that the oxidation of the three low index Cu surfaces (100), (110) and (111) exhibit different oxide nucleation rates, and the resulting oxides have 3-dimensional (3D) island shapes or 2D rafts under different conditions. In order to better understand these results, we have investigated the early stages of Cu oxidation using a multiscale computational approach that employs density functional theory (DFT), reactive force field (ReaxFF), and kinetic Mote Carlo (KMC). With DFT calculation, we have compared O2 dissociation barriers on Cu (100), (110) and (111) surfaces at high oxygen coverage to evaluate the kinetic barrier of sublayer oxidization. We found that O2 dissociation barriers on Cu(111) surface are all lower than those on (110) and (100) surfaces. This trend agrees with experimental observations that (111) surface is easier to oxidize. These DFT calculated energy barriers are then incorporated into KMC simulations. The large scale ReaxFF molecular dynamics and KMC simulations detail the oxidation dynamics of the different Cu surfaces, and show the formation of various oxide morphologies that are consistent with experimental observations.

  9. Life satisfaction of women in early stages of fertility treatment.

    PubMed

    Ben Shlomo, Shirley; Pascal, Mor; Taubman Ben-Ari, Orit; Azuri, Yoseph; Horowtz, Eran

    2017-01-01

    As many women perceive motherhood to be a central component of identity that enhances life satisfaction, difficulties conceiving may lead to stress. This study examined women in the early stages of fertility treatment to ascertain the relations of perceived stress, cognitive appraisal, and self-mastery to the life satisfaction of women embarking on fertility treatment and whether the associations were the same for women who were already mothers versus those who were not. Women were recruited for the study over a period of 18 months, from January 2013 to June 2014. The final sample was composed of 145 women; of these, 67 had 1 or 2 children and 78 had no children. No significant differences were found in perceived stress and life satisfaction between women with and without children. However, in the sample as a whole, higher levels of self-mastery and lower levels of stress were associated with greater life satisfaction. Moreover, the associations between self-mastery and cognitive appraisals of threat and self-efficacy were mediated by perceived stress. The findings highlight the importance of developing interventions at fertility clinics that begin at the very first point of contact to promote the psychological well-being of women being treated for infertility.

  10. Nanoparticles target early-stage breast cancer metastasis in vivo

    NASA Astrophysics Data System (ADS)

    Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E.; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

    2017-10-01

    Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

  11. Visual Contrast Sensitivity in Early-Stage Parkinson's Disease.

    PubMed

    Ming, Wendy; Palidis, Dimitrios J; Spering, Miriam; McKeown, Martin J

    2016-10-01

    Visual impairments are frequent in Parkinson's disease (PD) and impact normal functioning in daily activities. Visual contrast sensitivity is a powerful nonmotor sign for discriminating PD patients from controls. However, it is usually assessed with static visual stimuli. Here we examined the interaction between perception and eye movements in static and dynamic contrast sensitivity tasks in a cohort of mildly impaired, early-stage PD patients. Patients (n = 13) and healthy age-matched controls (n = 12) viewed stimuli of various spatial frequencies (0-8 cyc/deg) and speeds (0°/s, 10°/s, 30°/s) on a computer monitor. Detection thresholds were determined by asking participants to adjust luminance contrast until they could just barely see the stimulus. Eye position was recorded with a video-based eye tracker. Patients' static contrast sensitivity was impaired in the intermediate spatial-frequency range and this impairment correlated with fixational instability. However, dynamic contrast sensitivity and patients' smooth pursuit were relatively normal. An independent component analysis revealed contrast sensitivity profiles differentiating patients and controls. Our study simultaneously assesses perceptual contrast sensitivity and eye movements in PD, revealing a possible link between fixational instability and perceptual deficits. Spatiotemporal contrast sensitivity profiles may represent an easily measurable metric as a component of a broader combined biometric for nonmotor features observed in PD.

  12. Partial breast radiation for early-stage breast cancer.

    PubMed

    McCormick, Beryl

    2012-02-01

    This review is to provide an update on the current status of partial breast irradiation (PBI) for women presenting with early-stage breast cancer, as an alternate radiation technique to fractionated, whole breast radiation, following conservation surgery. As more women are asking for and receiving this treatment, both on and off protocols, understanding recent additions to the literature is important to physicians caring for this patient population. Newly published retrospective studies, with follow-up times out to 10 years and the status of both recently completed and still open large prospective phase III trials will be covered, with emphasis on unexpected side effects reported, and some hypothesis-generating radiobiology observations. A recent consensus treatment guideline for PBI use is also discussed. Selected retrospective studies continue to report outcomes matching those achieved with whole breast radiation; however, results from large prospective randomized trials comparing PBI to whole breast radiation have been reported only with short follow-up times, or in two studies, are still pending. A recent consensus guideline is useful at present in selecting patients for discussion of this treatment.

  13. Metformin inhibits early stage diethylnitrosamine-induced hepatocarcinogenesis in rats

    PubMed Central

    JO, WOORI; YU, EUN-SIL; CHANG, MINSUN; PARK, HYUN-KYU; CHOI, HYUN-JI; RYU, JAE-EUN; JANG, SUNGWOONG; LEE, HYO-JU; JANG, JA-JUNE; SON, WOO-CHAN

    2016-01-01

    Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)-induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma-specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S-transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK-dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high-risk patients, including chronic hepatitis and cirrhosis. PMID:26548419

  14. Early-Stage Aggregation of Human Islet Amyloid Polypeptide

    NASA Astrophysics Data System (ADS)

    Guo, Ashley; de Pablo, Juan

    Human islet amyloid polypeptide (hIAPP, or human amylin) is implicated in the development of type II diabetes. hIAPP is known to aggregate into amyloid fibrils; however, it is prefibrillar oligomeric species, rather than mature fibrils, that are proposed to be cytotoxic. In order to better understand the role of hIAPP aggregation in the onset of disease, as well as to design effective diagnostics and therapeutics, it is crucial to understand the mechanism of early-stage hIAPP aggregation. In this work, we use atomistic molecular dynamics simulations combined with multiple advanced sampling techniques to examine the formation of the hIAPP dimer and trimer. Metadynamics calculations reveal a free energy landscape for the hIAPP dimer, which suggest multiple possible transition pathways. We employ finite temperature string method calculations to identify favorable pathways for dimer and trimer formation, along with relevant free energy barriers and intermediate structures. Results provide valuable insights into the mechanisms and energetics of hIAPP aggregation. In addition, this work demonstrates that the finite temperature string method is an effective tool in the study of protein aggregation. Funded by National Institute of Standards and Technology.

  15. Toxicity of TFM lampricide to early life stages of walleye

    Seelye, J.G.; Marking, L.L.; King, E.L.; Hanson, L.H.; Bills, T.D.

    1987-01-01

    The authors studied the effects of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) on gametes, newly fertilized eggs, eyed eggs, larvae, and swim-up fry of the walleye Stizostedion vitreum . When gametes from sexually mature walleyes were stripped into solutions of TFM, no effects were observed during the fertilization process at concentrations up to 3.0 mg/L - three times the concentration lethal to 99.9% of larval sea lampreys Petromyzon marinus held 12 h (LC99.9) under the same test conditions. Newly fertilized eggs likewise were unaffected during water hardening by concentrations of TFM that were lethal to sea lamprey ammocoetes. Eyed eggs, sac fry, and swim-up fry yielded LC25 values that were 2.5 to 5 times greater than the 12-h LC99.9 for sea lamprey ammocoetes. The data thus indicated that all of the early life stages of walleyes tested were considerably more resistant than sea lamprey ammocoetes to TFM, and that it is unlikely they would be adversely affected by standard stream treatments to kill sea lamprey ammocoetes.

  16. 76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... respect to geographic location. SBA's primary concern in terms of geography is to ensure that the Early... SBICs is the primary source of cash used to service their SBA debt. SBA expects that some Early Stage...--Early Stage SBICs AGENCY: U.S. Small Business Administration. ACTION: Proposed rule. SUMMARY: In this...

  17. Chorioamnionitis and Culture-Confirmed, Early-Onset Neonatal Infections

    PubMed Central

    Hansen, Nellie I.; Schrag, Stephanie J.; Hale, Ellen; Van Meurs, Krisa; Sánchez, Pablo J.; Cantey, Joseph B.; Faix, Roger; Poindexter, Brenda; Goldberg, Ronald; Bizzarro, Matthew; Frantz, Ivan; Das, Abhik; Benitz, William E.; Shane, Andi L.; Higgins, Rosemary; Stoll, Barbara J.

    2016-01-01

    BACKGROUND: Current guidelines for prevention of neonatal group B streptococcal disease recommend diagnostic evaluations and empirical antibiotic therapy for well-appearing, chorioamnionitis-exposed newborns. Some clinicians question these recommendations, citing the decline in early-onset group B streptococcal disease rates since widespread intrapartum antibiotic prophylaxis implementation and potential antibiotic risks. We aimed to determine whether chorioamnionitis-exposed newborns with culture-confirmed, early-onset infections can be asymptomatic at birth. METHODS: Multicenter, prospective surveillance for early-onset neonatal infections was conducted during 2006–2009. Early-onset infection was defined as isolation of a pathogen from blood or cerebrospinal fluid collected ≤72 hours after birth. Maternal chorioamnionitis was defined by clinical diagnosis in the medical record or by histologic diagnosis by placental pathology. Hospital records of newborns with early-onset infections born to mothers with chorioamnionitis were reviewed retrospectively to determine symptom onset. RESULTS: Early-onset infections were diagnosed in 389 of 396 586 live births, including 232 (60%) chorioamnionitis-exposed newborns. Records for 229 were reviewed; 29 (13%) had no documented symptoms within 6 hours of birth, including 21 (9%) who remained asymptomatic at 72 hours. Intrapartum antibiotic prophylaxis exposure did not differ significantly between asymptomatic and symptomatic infants (76% vs 69%; P = .52). Assuming complete guideline implementation, we estimated that 60 to 1400 newborns would receive diagnostic evaluations and antibiotics for each infected asymptomatic newborn, depending on chorioamnionitis prevalence. CONCLUSIONS: Some infants born to mothers with chorioamnionitis may have no signs of sepsis at birth despite having culture-confirmed infections. Implementation of current clinical guidelines may result in early diagnosis, but large numbers of uninfected

  18. One-stage versus two-stage exchange arthroplasty for infected total knee arthroplasty: a systematic review.

    PubMed

    Nagra, Navraj S; Hamilton, Thomas W; Ganatra, Sameer; Murray, David W; Pandit, Hemant

    2016-10-01

    Infection complicating total knee arthroplasty (TKA) has serious implications. Traditionally the debate on whether one- or two-stage exchange arthroplasty is the optimum management of infected TKA has favoured two-stage procedures; however, a paradigm shift in opinion is emerging. This study aimed to establish whether current evidence supports one-stage revision for managing infected TKA based on reinfection rates and functional outcomes post-surgery. MEDLINE/PubMed and CENTRAL databases were reviewed for studies that compared one- and two-stage exchange arthroplasty TKA in more than ten patients with a minimum 2-year follow-up. From an initial sample of 796, five cohort studies with a total of 231 patients (46 single-stage/185 two-stage; median patient age 66 years, range 61-71 years) met inclusion criteria. Overall, there were no significant differences in risk of reinfection following one- or two-stage exchange arthroplasty (OR -0.06, 95 % confidence interval -0.13, 0.01). Subgroup analysis revealed that in studies published since 2000, one-stage procedures have a significantly lower reinfection rate. One study investigated functional outcomes and reported that one-stage surgery was associated with superior functional outcomes. Scarcity of data, inconsistent study designs, surgical technique and antibiotic regime disparities limit recommendations that can be made. Recent studies suggest one-stage exchange arthroplasty may provide superior outcomes, including lower reinfection rates and superior function, in select patients. Clinically, for some patients, one-stage exchange arthroplasty may represent optimum treatment; however, patient selection criteria and key components of surgical and post-operative anti-microbial management remain to be defined. III.

  19. Preventing urinary tract infections in early childhood.

    PubMed

    Williams, Gabrielle J; Craig, Jonathan C; Carapetis, Jonathan R

    2013-01-01

    Urinary tract infection (UTI) is common in children, causes them considerable discomfort, as well as distress to parents and has a tendency to recur. Approximately 20% of those children who experience one infection will have a repeat episode. Since 1975, 11 trials of long-term antibiotics compared with placebo or no treatment in 1,550 children have been published. Results have been heterogeneous, but the largest trial demonstrated a small reduction (6% absolute risk reduction, risk ratio 0.65) in the risk of repeat symptomatic UTI over 12 months of treatment. This effect was consistent across sub groups of children based upon age, gender, vesicoureteric reflux status and number of prior infections. Trials involving re-implantation surgery (and antibiotics compared with antibiotics alone) for the sub-group of children with vesicoureteric reflux have not shown a reduction in repeat UTI, with the possible exception of a very small benefit for febrile UTI. Systematic reviews have shown that circumcision reduces the risk of repeat infection but 111 circumcisions would need to be performed to prevent one UTI in unpredisposed boys. Given the need for anaesthesia and the risk of surgical complication, net clinical benefit is probably restricted to those who are predisposed (such as those with recurrent infection). Many small trials in complementary therapies have been published and many suggest some benefit, however inclusion of children is limited. Only three trials involving 394 children for cranberry products, two trials with a total of 252 children for probiotics and one trial with 24 children for vitamin A are published. Estimates of efficacy vary widely and imprecision is evident. Multiple interventions to prevent UTI in children exist. Of those, long-term low dose antibiotics has the strongest evidence base, but the benefit is small. Circumcision in boys reduces the risk substantially, but should be restricted to those at risk. There is little evidence of benefit of

  20. Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

    PubMed

    Shemenski, Justin

    2016-04-09

    potential immunomodulator. CIM therapy has been shown to increase levels of the TH1 associated cytokines IL-12, TNF-α, and IFN-γ while decreasing levels of the TH2 associated cytokine IL-10. The author proposes a novel theory that CIM therapy during early Bb infection may promote a more appropriate immune response and increase the utility of antibiotic therapy during early stage Lyme disease, thus improving clinical outcomes of the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Dream features in the early stages of Parkinson's disease.

    PubMed

    Bugalho, Paulo; Paiva, Teresa

    2011-11-01

    Few studies have investigated the relation between dream features and cognition in Parkinson's disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients' dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient's dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.

  2. Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication

    PubMed Central

    König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.

    2008-01-01

    Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154

  3. A systematic review of the evidence for single stage and two stage revision of infected knee replacement

    PubMed Central

    2013-01-01

    Background Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. Methods A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. Results 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. Conclusions Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority. PMID:23895421

  4. Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL.

    PubMed

    Blanco, Gonzalo; Vardi, Anna; Puiggros, Anna; Gómez-Llonín, Andrea; Muro, Manuel; Rodríguez-Rivera, María; Stalika, Evangelia; Abella, Eugenia; Gimeno, Eva; López-Sánchez, Manuela; Senín, Alicia; Calvo, Xavier; Abrisqueta, Pau; Bosch, Francesc; Ferrer, Ana; Stamatopoulos, Kostas; Espinet, Blanca

    2018-01-01

    Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4 + and CD8 + T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4 + T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

  5. Early detection of Trichinella spiralis DNA in the feces of experimentally infected mice by using PCR.

    PubMed

    Liu, Xiao Lin; Ren, Hua Nan; Shi, Ya Li; Hu, Chen Xi; Song, Yan Yan; Duan, Jiang Yang; Zhang, Hui Ping; Du, Xin Rui; Liu, Ruo Dan; Jiang, Peng; Wang, Zhong Quan; Cui, Jing

    2017-02-01

    The aim of this study was to detect Trichinella spiralis DNA in mouse feces during the early stages of infection using PCR. The target gene fragment, a 1.6kb repetitive sequence of T. spiralis genome, was amplified by PCR from feces of mice infected with 100 or 300 larvae at 3-24h post infection (hpi) and 2-28dpi. The sensitivity of PCR was 0.016 larvae in feces. The primers used were highly specific for T. spiralis. No cross-reactivity was observed with the DNA of other intestinal helminths. T. spiralis DNA was detected in 100% (12/12) of feces of mice infected with 100 or 300 larvae as early as 3hpi, with the peak detection lasting to 12-24hpi, and then fluctuating before declining gradually. By 28dpi, the detection rate of T. spiralis DNA in feces of the two groups of infected mice decreased to 8.33% and 25%, respectively. PCR detection of T. spiralis DNA in feces is simple and specific; it might be useful for the early diagnosis of Trichinella infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Experimental constrain of hydrogen production during early serpentinization stages

    NASA Astrophysics Data System (ADS)

    Clément, M.; Munoz, M.; Vidal, O.; Parra, T.

    2009-04-01

    Hydrothermal alteration of mantellic peridotites and ultramafic rocks along axial valleys of low spread oceanic ridges plays a key role in different fundamental domains like, 1) energetic gaz production (H2 and hydrocarbons) representing a potential source of energy for future generations, 2) formation of organic pre-biotic molecules in potential relation with the origin of life. Moreover, such complex volcanic-related alteration processes play fundamental role in economic geology, being widely associated to important polymetallic sulphides ore deposits. Recent researches proposed an initial hydrogen production due to the integration of ferric iron in Fe,Mg-serpentine. To better understand the early stages of hydrogen production, a series of natural peridotite rocks have been experimentally exposed to hydrothermal conditions, up to 300°C, 300 bars during different time scales. Experiments have been performed in using autoclaves with a sampling gas system. A systematic mineralogical characterization of the new products was carried out using classical spectroscopic tools. In particular, we focused on the iron behaviour using a redox and structural micro-XANES investigation. Redox information has been accurately derived from the pre-peak features previously calibrated from model compounds, while structural information about short and medium range order around iron has been extracted from the XANES region of the spectra, based both on experimental standards and ab-initio theoretical calculations. Two processes of oxidation emerged. Before two month experiment duration, serpentine displays a not negligible oxidation of ferrous iron in his structure (up to 60%), while after two months, iron oxides and hydroxides appear in the system. These results seem to correspond to natural observations. The iron coordination decreases linearly with time. It means that iron also integrates the serpentine tetrahedral sites. Moreover, high resolution µ-XAS maps on experimental samples

  7. Susceptibility of early life stages of Xenopus laevis to cadmium

    SciT

    Herkovits, J.; Perez-Coll, C.S.; Cardellini, P.

    1997-02-01

    The susceptibility of Xenopus laevis to cadmium during different stages of development was evaluated by exposing embryos to cadmium concentrations ranging from 0.1 to 10 mg Cd{sup 2+}/L for 24, 48, and 72 h and assessing lethality and malformations. Susceptibility increased from the two blastomeres stage (stage 2) to stage 40, in which the 24-h LC100 was 1.13 mg Cd{sup 2+}/L, and resistance increased from this stage onward. Malformations occurred at all developmental stages evaluated, the most common being reduced size, incurvated axis, underdeveloped or abnormally developed fin, microcephaly, and microphtalmy. Scanning electron microscopy revealed changes in the ectodermal surfacemore » ranging from slightly vaulted cells to a severe reduction in the number of ciliated cells as the concentration of cadmium increased. The intraspecific variation evaluated in embryos (from four sets of parents) at seven developmental stages, expressed as the coefficient of variation of the LC100, ranged from 10 to 112% and reflects the capacity of Xenopus laevis to adapt to changing environmental conditions at different embryonic stages.« less

  8. Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

    PubMed

    Han, Dolly; Hogeveen, Sophie; Sweet Goldstein, Miriam; George, Ralph; Brezden-Masley, Christine; Hoch, Jeffrey; Haq, Rashida; Simmons, Christine E

    2012-02-01

    After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase

  9. Prediction of early postoperative infections in pediatric liver transplantation by logistic regression

    NASA Astrophysics Data System (ADS)

    Uzunova, Yordanka; Prodanova, Krasimira; Spassov, Lubomir

    2016-12-01

    Orthotopic liver transplantation (OLT) is the only curative treatment for end-stage liver disease. Early diagnosis and treatment of infections after OLT are usually associated with improved outcomes. This study's objective is to identify reliable factors that can predict postoperative infectious morbidity. 27 children were included in the analysis. They underwent liver transplantation in our department. The correlation between two parameters (the level of blood glucose at 5th postoperative day and the duration of the anhepatic phase) and postoperative infections was analyzed, using univariate analysis. In this analysis, an independent predictive factor was derived which adequately identifies patients at risk of infectious complications after a liver transplantation.

  10. Single-stage Acetabular Revision During Two-stage THA Revision for Infection is Effective in Selected Patients.

    PubMed

    Fink, Bernd; Schlumberger, Michael; Oremek, Damian

    2017-08-01

    The treatment of periprosthetic infections of hip arthroplasties typically involves use of either a single- or two-stage (with implantation of a temporary spacer) revision surgery. In patients with severe acetabular bone deficiencies, either already present or after component removal, spacers cannot be safely implanted. In such hips where it is impossible to use spacers and yet a two-stage revision of the prosthetic stem is recommended, we have combined a two-stage revision of the stem with a single revision of the cup. To our knowledge, this approach has not been reported before. (1) What proportion of patients treated with single-stage acetabular reconstruction as part of a two-stage revision for an infected THA remain free from infection at 2 or more years? (2) What are the Harris hip scores after the first stage and at 2 years or more after the definitive reimplantation? Between June 2009 and June 2014, we treated all patients undergoing surgical treatment for an infected THA using a single-stage acetabular revision as part of a two-stage THA exchange if the acetabular defect classification was Paprosky Types 2B, 2C, 3A, 3B, or pelvic discontinuity and a two-stage procedure was preferred for the femur. The procedure included removal of all components, joint débridement, definitive acetabular reconstruction (with a cage to bridge the defect, and a cemented socket), and a temporary cemented femoral component at the first stage; the second stage consisted of repeat joint and femoral débridement and exchange of the femoral component to a cementless device. During the period noted, 35 patients met those definitions and were treated with this approach. No patients were lost to followup before 2 years; mean followup was 42 months (range, 24-84 months). The clinical evaluation was performed with the Harris hip scores and resolution of infection was assessed by the absence of clinical signs of infection and a C-reactive protein level less than 10 mg/L. All

  11. 40 CFR 797.1600 - Fish early life stage toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

  12. 40 CFR 797.1600 - Fish early life stage toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

  13. Three-peat NREL Intern Pushes Boundaries of Early-Stage Fuels Research on

    Early-Stage Fuels Research on Way to Master's Degree Three-peat NREL Intern Pushes Boundaries of Early -Stage Fuels Research on Way to Master's Degree January 4, 2018 Woman preparing a fuel evaluation in a constant volume combustion vessel Drew Cameron, Research Participant Program Intern, prepares a test for

  14. To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia

    ERIC Educational Resources Information Center

    Wöhrer, Veronika

    2014-01-01

    Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…

  15. Management of Early Stage, High-Risk Endometrial Carcinoma: Preoperative and Surgical Considerations

    PubMed Central

    Pettigrew, Gaetan

    2013-01-01

    Endometrial cancer is the most common gynecologic malignancy in the developed world. Most cases are diagnosed at an early stage and have low-grade histology, portending an overall excellent prognosis. There exists a subgroup of patients with early, high-risk disease, whose management remains controversial, as current data is clouded by inclusion of early stage tumors with different high-risk features for recurrence, unstandardized protocols for surgical staging, and an evolving staging system by which we are grouping these patients. Here, we present preoperative and intraoperative considerations that should be taken into account when planning surgical management for this population of patients. PMID:23878545

  16. Early physiological abnormalities after simian immunodeficiency virus infection.

    PubMed

    Horn, T F; Huitron-Resendiz, S; Weed, M R; Henriksen, S J; Fox, H S

    1998-12-08

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

  17. Early physiological abnormalities after simian immunodeficiency virus infection

    PubMed Central

    Horn, Thomas F. W.; Huitron-Resendiz, Salvador; Weed, Michael R.; Henriksen, Steven J.; Fox, Howard S.

    1998-01-01

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction. PMID:9844017

  18. Arthroscopic Synovectomy Combined with Autologous Fat Grafting in Early Stages of CMC Osteoarthritis of the Thumb.

    PubMed

    Kemper, Robert; Wirth, Johanna; Baur, Eva-Maria

    2018-04-01

    Background  Minimal invasive treatments such as arthroscopic techniques may be adequate to restore the anatomy and functional integrity of the thumb CMC (carpometacarpal) joint. In this paper, we reported the interposition of autologous fat tissue in combination with arthroscopic synovectomy/debridement for early stage of the thumb CMC joint osteoarthritis. Patients and Methods  Twelve patients with a mean age of 46 years with early radiological stages of thumb CMC joint osteoarthritis were included. Evaluation of outcome was measured prior and 3, 12, and 24 months after surgery including, Visual Analog Scale (VAS), QuickDASH, grip and pinch strength, range of motion (ROM), and patient satisfaction. Results  Pain at rest (or with load) was reduced from preoperative 4,7 (8,7) to 2 (5,9) at 3 to 6 months; 1,4 (4,3) at 12 months; and 0,75 (2,7) at 2 years after the surgery. Initial preoperative QuickDASH value of 52 points reduced to 33 (17-65) at 6 months, 23 (2-70) at 12 months, and 20 (11-29) at 24 months after the surgery. Grip strength and thumb pinch with respect to the contralateral untreated thumb was reduced in the first 12 months but recovered subsequently. ROM was equal to the contralateral thumb. Three patients suffered from tendinitis and required surgical treatment. One patient indicated prolonged pain symptoms. No infections were noted and no donor-site morbidity or side effects were detected. Conclusion  Arthroscopic synovectomy combined with autologous fat graft is a reliable surgical option for early thumb CMC joint osteoarthritis and that effect continues for more than 24 months.

  19. A Four-Stage Method for Developing Early Interventions for Alcohol among Aboriginal Adolescents

    ERIC Educational Resources Information Center

    Mushquash, Christopher J.; Comeau, M. Nancy; McLeod, Brian D.; Stewart, Sherry H.

    2010-01-01

    This paper details a four-stage methodology for developing early alcohol interventions for at-risk Aboriginal youth. Stage 1 was an integrative approach to Aboriginal education that upholds Aboriginal traditional wisdom supporting respectful relationships to the Creator, to the land and to each other. Stage 2 used quantitative methods to…

  20. May one-stage exchange for Candida albicans peri-prosthetic infection be successful?

    PubMed

    Jenny, J-Y; Goukodadja, O; Boeri, C; Gaudias, J

    2016-02-01

    Fungal infection of a total joint arthroplasty has a low incidence but is generally considered as more difficult to cure than bacterial infection. As for bacterial infection, two-stage exchange is considered as the gold standard of treatment. We report two cases of one-stage total joint exchange for fungal peri-prosthetic infection with Candida albicans, where the responsible pathogens was only identified on intraoperative samples. This situation can be considered as a one-stage exchange for fungal peri-prosthetic infection without preoperative identification of the responsible organism, which is considered as having a poor prognosis. Both cases were free of infection after two years. One-stage revision has several potential advantages over two-stage revision, including shorter hospital stay and rehabilitation, no interim period with significant functional impairment, shorter antibiotic treatment, better functional outcome and probably lower costs. We suggest that one-stage revision for C. albicans peri-prosthetic infection may be successful even without preoperative fungal identification. Level IV-Historical cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Early Weight Development of Goats Experimentally Infected with Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Malone, Alyssa N.; Fletcher, Darcy M.; Vogt, Megan B.; Meyer, Stephen K.; Hess, Ann M.; Eckstein, Torsten M.

    2013-01-01

    Johne’s disease is an infectious chronic inflammatory bowel disease in ruminants. The key factor for the management of this disease is an early positive diagnosis. Unfortunately, most diagnostics detect animals with Johne’s disease in the clinical stage with positive serology and/or positive fecal cultures. However, for effective management of the disease within herds, it is important to detect infected animals as early as possible. This might only be possible with the help of parameters not specific for Johne’s disease but that give an early indication for chronic infections such as weight development. Here we report our findings on the development of total body weight and weight gain during the first six months of goats experimentally infected to induce Johne’s disease. Twenty dairy goat kids age 2 to 5 days were included in this study. Goats were divided into two groups: a negative control group and a positive infected group. The weight was obtained weekly throughout the study. Goats of the positive group were infected at the age of seven weeks. We detected significant changes in weight gain and total body weight as early as one week after infection. Differences are significant throughout the six month time period. Weight as a non-specific parameter should be used to monitor infection especially in studies on Johne’s disease using the goat model. Our study suggests that goats with Johne’s disease have a reduced weight gain and reduced weight when compared with healthy goats of the same age. PMID:24349564

  2. Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

    PubMed Central

    2014-01-01

    Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

  3. Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia.

    PubMed

    Yuan, Cun-Quan; Sun, Yu-Han; Li, Yun-Fei; Zhao, Ke-Qi; Hu, Rui-Yang; Li, Yun

    2014-03-21

    Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low seed set in R. pseudoacacia.

  4. Early feeding: setting the stage for healthy eating habits.

    PubMed

    Mennella, Julie A; Ventura, Alison K

    2011-01-01

    Food habits, an integral part of all cultures, have their beginnings during early life. This chapter reviews the development of the senses of taste and smell, which provide information on the flavor of foods, and discusses how children's innate predispositions interact with early-life feeding experiences to form dietary preferences and habits. Young children show heightened preferences for foods that taste sweet and salty and rejection of that which tastes bitter. These innate responses are salient during development since they likely evolved to encourage children to ingest that which is beneficial, containing needed calories or minerals, and to reject that which is harmful. Early childhood is also characterized by plasticity, partially evidenced by a sensitive period during early life when infants exhibit heightened acceptance of the flavors experienced in amniotic fluid and breast milk. While learning also occurs with flavors found in formulae, it is likely that this sensitive period formed to facilitate acceptance of and attraction to the flavors of foods eaten by the mother. A basic understanding of the development and functioning of the chemical senses during early childhood may assist in forming evidence-based strategies to improve children's diets. Copyright © 2011 S. Karger AG, Basel.

  5. POLLUTION PREVENTION IN THE EARLY STAGES OF HIERARCHICAL PROCESS DESIGN

    EPA Science Inventory

    Hierarchical methods are often used in the conceptual stages of process design to synthesize and evaluate process alternatives. In this work, the methods of hierarchical process design will be focused on environmental aspects. In particular, the design methods will be coupled to ...

  6. Using Motivational Interviewing within the Early Stages of Group Development

    ERIC Educational Resources Information Center

    Young, Tabitha L.

    2013-01-01

    This article presents developmentally appropriate applications of Motivational Interviewing (MI; Miller & Rollnick, 2002) for use in preparing group members for the working stages of group. Practical strategies are offered for using MI to facilitate an atmosphere of trust, recognize member readiness for change, identify and resolve members'…

  7. Cancer stage at diagnosis in patients infected with the human immunodeficiency virus and transplant recipients.

    PubMed

    Shiels, Meredith S; Copeland, Glenn; Goodman, Marc T; Harrell, Janna; Lynch, Charles F; Pawlish, Karen; Pfeiffer, Ruth M; Engels, Eric A

    2015-06-15

    It is unknown whether immunosuppression results in more aggressive, advanced stage cancers. Because cancer stage is influenced both by tumor biology and medical surveillance, the authors assessed cancer stage in individuals infected with the human immunodeficiency virus (HIV) and solid organ transplant recipients, 2 immunosuppressed groups with differences in their health care use. The authors used data on all cases of 15 cancer types diagnosed during 1996 through 2010 in 2 studies that linked US cancer registries with HIV and transplant registries. Odds ratios (ORs) for advanced (vs local) disease were estimated comparing HIV and transplant populations with immunocompetent individuals in polytomous logistic regression models adjusted for age, sex, race, registry, and year. A total of 8411 of 4.5 million cancer cases occurred in HIV-infected individuals and 7322 of 6.4 million cancer cases occurred in transplant recipients. Compared with immunocompetent patients with cancer, those infected with HIV were more likely to be diagnosed with distant stage lung (OR, 1.13), female breast (OR, 1.99), and prostate (OR, 1.57) cancers, whereas transplant recipients had fewer distant stage lung (OR, 0.54), female breast (OR, 0.75), and prostate (OR, 0.72) cancers. Both immunosuppressed populations had a shift toward advanced stage melanoma (ORs of 1.97 for HIV-infected individuals and 1.82 for transplant recipients) and bladder cancer (ORs of 1.42 for HIV-infected individuals and 1.54 for transplant recipients). Bladder cancer and melanoma were more likely to be diagnosed at a nonlocal stage in both HIV-infected individuals and transplant recipients, suggesting a role for immunosuppression in their progression. In addition, we observed a shift for some common cancers toward later stages in HIV-infected individuals and toward earlier stages in transplant recipients, which is consistent with differential access to medical care or surveillance. © 2015 American Cancer Society.

  8. Physical labeling of papillomavirus-infected, immortal, and cancerous cervical epithelial cells reveal surface changes at immortal stage.

    PubMed

    Swaminathan Iyer, K; Gaikwad, R M; Woodworth, C D; Volkov, D O; Sokolov, Igor

    2012-06-01

    A significant change of surface features of malignant cervical epithelial cells compared to normal cells has been previously reported. Here, we are studying the question at which progressive stage leading to cervical cancer the surface alteration happens. A non-traditional method to identify malignant cervical epithelial cells in vitro, which is based on physical (in contrast to specific biochemical) labelling of cells with fluorescent silica micron-size beads, is used here to examine cells at progressive stages leading to cervical cancer which include normal epithelial cells, cells infected with human papillomavirus type-16 (HPV-16), cells immortalized by HPV-16, and carcinoma cells. The study shows a statistically significant (at p < 0.01) difference between both immortal and cancer cells and a group consisting of normal and infected. There is no significant difference between normal and infected cells. Immortal cells demonstrate the signal which is closer to cancer cells than to either normal or infected cells. This implies that the cell surface, surface cellular brush changes substantially when cells become immortal. Physical labeling of the cell surface represents a substantial departure from the traditional biochemical labeling methods. The results presented show the potential significance of physical properties of the cell surface for development of clinical methods for early detection of cervical cancer, even at the stage of immortalized, premalignant cells.

  9. Physical Labeling of Papillomavirus-Infected, Immortal, and Cancerous Cervical Epithelial Cells Reveal Surface Changes at Immortal Stage

    PubMed Central

    Iyer, K. Swaminathan; Gaikwad, R. M.; Woodworth, C. D.; Volkov, D. O.

    2013-01-01

    A significant change of surface features of malignant cervical epithelial cells compared to normal cells has been previously reported. Here, we are studying the question at which progressive stage leading to cervical cancer the surface alteration happens. A non-traditional method to identify malignant cervical epithelial cells in vitro, which is based on physical (in contrast to specific biochemical) labelling of cells with fluorescent silica micron-size beads, is used here to examine cells at progressive stages leading to cervical cancer which include normal epithelial cells, cells infected with human papillomavirus type-16 (HPV-16), cells immortalized by HPV-16, and carcinoma cells. The study shows a statistically significant (at p <0.01) difference between both immortal and cancer cells and a group consisting of normal and infected. There is no significant difference between normal and infected cells. Immortal cells demonstrate the signal which is closer to cancer cells than to either normal or infected cells. This implies that the cell surface, surface cellular brush changes substantially when cells become immortal. Physical labeling of the cell surface represents a substantial departure from the traditional biochemical labeling methods. The results presented show the potential significance of physical properties of the cell surface for development of clinical methods for early detection of cervical cancer, even at the stage of immortalized, pre-malignant cells. PMID:22351422

  10. The neutralizing role of IgM during early Chikungunya virus infection

    PubMed Central

    Chua, Chong-Long; Chiam, Chun-Wei; Chan, Yoke-Fun

    2017-01-01

    The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays. PMID:28182795

  11. Efficient embryonic culture method for the Japanese striped snake, Elaphe quadrivirgata, and its early developmental stages.

    PubMed

    Matsubara, Yoshiyuki; Sakai, Atsushi; Kuroiwa, Atsushi; Suzuki, Takayuki

    2014-10-01

    The morphogenesis of snake embryos is an elusive yet fascinating research target for developmental biologists. However, few data exist on development of early snake embryo due to limited availability of pregnant snakes, and the need to harvest early stage embryos directly from pregnant snakes before oviposition without knowing the date of fertilization. We established an ex vivo culture method for early snake embryos using the Japanese striped snake, Elaphe quadrivirgata. This method, which we named "sausage-style (SS) culture", allows us to harvest snake embryos at specific stages for each experiment. Using this SS culture system, we calculated somite formation rate at early stages before oviposition. The average somite formation rate between 6/7 and 12/13 somite stages was 145.9 min, between 60/70 and 80/91 somite stages 42.4 min, and between 113-115 and 126/127 somite stages 71 min. Thus, somite formation rate that we observed during early snake embryogenesis was changed over time. We also describe a developmental staging series for E. quadrivirgata. This is the first report of a developmental series of early snake embryogenesis prior to oviposition by full-color images with high-resolution. We propose that the SS culture system is an easy method for treating early snake embryos ex vivo. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

  12. Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

    PubMed

    Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. ERP Evidence of Visualization at Early Stages of Visual Processing

    ERIC Educational Resources Information Center

    Page, Jonathan W.; Duhamel, Paul; Crognale, Michael A.

    2011-01-01

    Recent neuroimaging research suggests that early visual processing circuits are activated similarly during visualization and perception but have not demonstrated that the cortical activity is similar in character. We found functional equivalency in cortical activity by recording evoked potentials while color and luminance patterns were viewed and…

  14. Impact of pretransplant rifaximin therapy on early post-liver transplant infections.

    PubMed

    Esfeh, Jamak Modaresi; Hanouneh, Ibrahim A; Koval, Christine E; Kovacs, Christopher; Dalal, Deepan S; Ansari-Gilani, Kianoush; Confer, Bradley D; Eghtesad, Bijan; Zein, Nizar N; Menon, K V Narayanan

    2014-05-01

    Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period. © 2014 American Association for the Study of Liver Diseases.

  15. Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

    DTIC Science & Technology

    2012-03-01

    patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

  16. DNA Copy Number Signature to Predict Recurrence in Early Stage Ovarian Cancer

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-14-1-0194 TITLE: DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer 5b. GRANT NUMBER W81XWH-14-1-0194 5c. PROGRAM...determine the copy number gain and loss for early stage high grade ovarian cancers through IlluminaHumanOmniExpress-FFPE BeadChip system • Subtask 1 DNA

  17. [Two-stage revision of infected total knee arthroplasty using antibiotic-impregnated articulating cement spacer].

    PubMed

    Cai, Pengde; Hu, Yihe; Xie, Lie; Wang, Long

    2012-10-01

    To investigate the effectiveness of two-stage revision of infected total knee arthroplasty (TKA) using an antibiotic-impregnated articulating cement spacer. The clinical data were analyzed from 23 patients (23 knees) undergoing two-stage revision for late infection after primary TKA between January 2007 and December 2009. There were 15 males and 8 females, aged from 43 to 75 years (mean, 65.2 years). Infection occurred at 13-52 months (mean, 17.3 months) after TKA. The time interval between infection and admission ranged from 15 days to 7 months (mean, 2.1 months). One-stage operation included surgical debridement and removal of all knee prosthesis and cement, then an antibiotic-impregnated articulating cement spacer was implanted. The re-implantation of prosthesis was performed after 8-10 weeks when infections were controlled. The American Hospital for Special Surgery (HSS) score and Knee Society Score (KSS) were used to compare the function of the knee between pre- and post-revision. The rate of infection control and complication were analyzed. All incisions healed primarily. Re-infection occurred in 2 cases after two-stage revision, and infection was controlled in the other 21 cases, with an infection control rate of 91.3%. The patients were followed up 2-5 years (mean, 3.6 years). The HSS score was increased from 60.6 +/- 9.8 at pre-revision to 82.3 +/- 7.4 at last follow-up, the KSS score was increased from 110.7 +/- 9.6 at pre-revision to 134.0 +/- 10.5 at last follow-up, all showing significant differences (P < 0.01). Radiographs showed that prosthesis had good position with no loosening, fracture, or periprosthetic radiolucent. Two-stage revision using an antibiotic-impregnated articulating cement spacer is an effective method to control infected TKA and to restore the function of affected knee.

  18. [Anxiety-phobic disorders in the early childhood stage].

    PubMed

    Volkova, O M; Kozlovskaia, G V; Proselkova, M O

    2012-01-01

    The complex of such phenomena as anxiety and fear in children of the early age and their relationship with risk factors for psychic pathology were investigated. Eighty cases of anxiety-phobic disorders in children of the first five years of life were studied. The types of behavioral and somatic reactions that allowed to reveal not only the clinically expressed phenomena of anxiety and fear but the higher readiness to them were described. The first anxiety-phobic reactions appeared at the age when emotional functions were not completely formed and might be considered as the presentations of emotional dysontogenesis. The authors assume that characteristics of fear expression in the early age allow to suspect a mental disease which might be timely diagnosed in case of its manifestation. The conclusions made in the paper may be useful for clinical practice of pediatricians, children neurologists, psychologists and psychiatrists.

  19. Can early host responses to mycobacterial infection predict eventual disease outcomes?

    PubMed

    de Silva, Kumudika; Begg, Douglas J; Plain, Karren M; Purdie, Auriol C; Kawaji, Satoko; Dhand, Navneet K; Whittington, Richard J

    2013-11-01

    Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Reorganization of Nuclear Pore Complexes and the Lamina in Late-Stage Parvovirus Infection.

    PubMed

    Mäntylä, Elina; Niskanen, Einari A; Ihalainen, Teemu O; Vihinen-Ranta, Maija

    2015-11-01

    Canine parvovirus (CPV) infection induces reorganization of nuclear structures. Our studies indicated that late-stage infection induces accumulation of nuclear pore complexes (NPCs) and lamin B1 concomitantly with a decrease of lamin A/C levels on the apical side of the nucleus. Newly formed CPV capsids are located in close proximity to NPCs on the apical side. These results suggest that parvoviruses cause apical enrichment of NPCs and reorganization of nuclear lamina, presumably to facilitate the late-stage infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Clusterin immunoexpression is associated with early stage endometrial carcinomas.

    PubMed

    Al-Maghrabi, Jaudah Ahmed; Butt, Nadeem Shafique; Anfinan, Nisrin; Sait, Khalid; Sait, Hesham; Bajouh, Osama; Khabaz, Mohamad Nidal

    2016-05-01

    Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184-15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Signs of Early-stage Disk Growth Revealed with ALMA

    NASA Astrophysics Data System (ADS)

    Yen, Hsi-Wei; Koch, Patrick M.; Takakuwa, Shigehisa; Krasnopolsky, Ruben; Ohashi, Nagayoshi; Aso, Yusuke

    2017-01-01

    We present ALMA 1.3 mm continuum, 12CO, C18O, and SO data for the Class 0 protostars Lupus 3 MMS, IRAS 15398-3559, and IRAS 16253-2429 at resolutions of ˜100 au. By measuring a rotational profile in C18O, a 100 au Keplerian disk around a 0.3 M⊙ protostar is observed in Lupus 3 MMS. No 100 au Keplerian disks are observed in IRAS 15398-3559 and IRAS 16253-2429. Nevertheless, embedded compact (<30 au) continuum components are detected. The C18O emission in IRAS 15398-3559 shows signatures of infall with a constant angular momentum. IRAS 16253-2429 exhibits signatures of infall and rotation, but its rotational profile is unresolved. By fitting the C18O data with our kinematic models, the protostellar masses and the disk radii are inferred to be 0.01 M⊙ and 20 au in IRAS 15398-3559, and 0.03 M⊙ and 6 au in IRAS 16253-2429. By comparing the specific angular momentum profiles from 10,000 au to 100 au in eight Class 0 and I protostars, we find that the evolution of envelope rotation can be described with conventional inside-out collapse models. In comparison with a sample of 18 protostars with known disk radii, our results reveal signs of disk growth, with the disk radius increasing as {{M}* }0.8+/- 0.14 or {t}1.09+/- 0.37 in the Class 0 stage, where M* is the protostellar mass and t is the age. The disk growth rate slows down in the Class I stage. In addition, we find a hint that the mass accretion rate declines as {t}-0.26+/- 0.04 from the Class 0 to the Class I stages.

  3. [Feedback of ultrasound and RMI in the staging of endometrial carcinoma in early stage].

    PubMed

    Buhler, J; Routiot, T; Polet-Lefebvre, K; Morel, O

    2015-04-01

    Endometrial cancer is the most common gynecological cancer in France. The therapeutic management is based on preoperative staging. The recommended imaging examination remains the MRI. This is to evaluate ultrasound and MRI in the staging for localized cancers. This is a retrospective observational study, conducted from July 2012 to July 2014, at the University Hospital of Nancy, on all patients care for endometrial cancer stage I, who underwent a pelvic ultrasound and MRI for the assessment of myometrial infiltration. Twenty-nine patients were included with a mean age of 69 years and a BMI of 30 kg/m(2). Using ultrasound, we have a sensitivity of 58%, a specificity of 100%, a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of 70% and an accuracy of 75%. Using MRI, we have a sensitivity of 83%, a specificity of 100%, a PPV of 83%, a VPN of 88%, and an accuracy of 86%. Transvaginal sonography should be performed before post-menopausal bleeding. It remains possible in the staging of localized cancers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Expression signatures of early-stage and advanced medaka melanomas.

    PubMed

    Klotz, Barbara; Kneitz, Susanne; Regensburger, Martina; Hahn, Lena; Dannemann, Michael; Kelso, Janet; Nickel, Birgit; Lu, Yuan; Boswell, William; Postlethwait, John; Warren, Wesley; Kunz, Manfred; Walter, Ronald B; Schartl, Manfred

    2018-06-01

    Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown. To contribute to a better understanding of the molecular processes of melanoma formation, we use a transgenic medaka melanoma model that is well suited for the investigation of melanoma tumor development because fish and human melanocytes are both localized in the epidermis. The purpose of our study was to gain insights into melanoma development from the first steps of tumor formation up to melanoma progression and to identify gene expression patterns that will be useful for monitoring treatment effects in drug screening approaches. Comparing transcriptomes from juvenile fish at the tumor initiating stage with nevi and advanced melanoma of adults, we identified stage specific expression signatures and pathways that are characteristic for the development of medaka melanoma, and are also found in human malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. One Stage Conversion of an Infected Fused Knee to Total Knee Replacement - A Surgical Challenge

    PubMed Central

    Ravikumar, Mukartihal; Kendoff, Daniel; Citak, Mustafa; Luck, Stefan; Gehrke, Thorsten; Zahar, Akos

    2013-01-01

    Background and Purpose: Two-stage revision arthroplasty is a common technique for the treatment of infected total knee replacement. Few reports have addressed the conversion of a fused knee into a total knee replacement. However, there is no case reported of converting an infected fused knee into a hinge knee using a one-stage procedure. Methods: We report on a 51-year old male patient with an infected fused knee after multiple surgeries. Results and Interpretation: A one-stage conversion of septic fused knee into total knee arthroplasty by a rotational hinge prosthesis was performed. The case highlights that with profound preoperative assessment, meticulous surgical technique, combined antibiotic treatment and the right implant, one-stage revision in a surgical challenge may have a role as a treatment option with good functional outcome. PMID:23526706

  6. Fully compressible solutions for early stage Richtmyer–Meshkov instability

    DOE PAGES

    Margolin, Len G.; Reisner, Jon Michael

    2016-10-27

    Here, we will consider the effects of compressibility and viscosity on the early dynamics of the Richtmyer–Meshkov instability (RMI). In particular, we will combine theory, scaling, and high resolution simulation of RMI to probe the details of the initial compression and the subsequent viscous damping as a shock interacts with a density discontinuity. We will propose a refinement of the classic 1D model for the linear regime of RMI that, for small initial perturbation wavelengths, more accurately reproduces the 2D dynamics of a fully resolved numerical simulation.

  7. Formal Verification Toolkit for Requirements and Early Design Stages

    NASA Technical Reports Server (NTRS)

    Badger, Julia M.; Miller, Sheena Judson

    2011-01-01

    Efficient flight software development from natural language requirements needs an effective way to test designs earlier in the software design cycle. A method to automatically derive logical safety constraints and the design state space from natural language requirements is described. The constraints can then be checked using a logical consistency checker and also be used in a symbolic model checker to verify the early design of the system. This method was used to verify a hybrid control design for the suit ports on NASA Johnson Space Center's Space Exploration Vehicle against safety requirements.

  8. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

    Cancer.gov

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

  9. Macular micropseudocysts in early stages of diabetic retinopathy.

    PubMed

    Tremolada, Gemma; Pierro, Luisa; de Benedetto, Umberto; Margari, Sergio; Gagliardi, Marco; Maestranzi, Gisella; Calori, Giliola; Lorenzi, Mara; Lattanzio, Rosangela

    2011-01-01

    To identify by noninvasive means early retinal abnormalities that may predict diabetic macular edema. The authors analyzed retrospectively data from consecutive patients with Type 1 (n = 16) or Type 2 (n = 23) diabetes who presented for routine follow-up of early retinopathy, had no clinical signs or symptoms of diabetic macular edema, and were evaluated with spectral-domain optical coherence tomography. Age- and gender-matched nondiabetic subjects provided normative data. Spectral-domain optical coherence tomography revealed in the macular region of diabetic patients small hyporeflective areas (median diameter, 55 μm) contained within discrete retinal layers that we named micropseudocysts (MPCs). Micropseudocysts are associated with vascular leakage. The patients showing MPCs had more frequently systemic hypertension and increased central foveal thickness than those without MPCs. The association with increased central foveal thickness was only in the patients with Type 2 diabetes. Macular MPCs in patients with mild diabetic retinopathy appear to reflect leakage and can precede macular thickening. The association of MPCs with increased central foveal thickness in patients with Type 2 diabetes, but not in patients with Type 1 diabetes, points to a greater tendency to retinal fluid accumulation in patients with Type 2 diabetes. Studies in larger cohorts will determine the usefulness of MPCs in strategies to abort diabetic macular edema.

  10. Staging Life in an Early Warm ‘Seltzer’ Ocean

    DOE PAGES

    Schoonen, Martin; Smirnov, Alexander

    2016-12-01

    A period as short as 20 million years within the first 100 million years after the formation of the Moon may have set the stage for the origin of life. This atmosphere contained more carbon dioxide than any other period afterwards. The carbon dioxide sustained greenhouse conditions, accelerated the weathering of a primitive crust and may have led to conditions conducive to the formation of the building blocks of life. The conversion of CO 2 as well as N 2 may have been facilitated by clays, zeolites, sulfides and metal alloys formed as the crust reacted with a warm ‘seltzer’more » ocean. We used geochemical modeling to constrain the conditions favorable for the formation of these potential mineral catalysts.« less

  11. Staging Life in an Early Warm ‘Seltzer’ Ocean

    SciT

    Schoonen, Martin; Smirnov, Alexander

    A period as short as 20 million years within the first 100 million years after the formation of the Moon may have set the stage for the origin of life. This atmosphere contained more carbon dioxide than any other period afterwards. The carbon dioxide sustained greenhouse conditions, accelerated the weathering of a primitive crust and may have led to conditions conducive to the formation of the building blocks of life. The conversion of CO 2 as well as N 2 may have been facilitated by clays, zeolites, sulfides and metal alloys formed as the crust reacted with a warm ‘seltzer’more » ocean. We used geochemical modeling to constrain the conditions favorable for the formation of these potential mineral catalysts.« less

  12. Upper thermal tolerances of early life stages of freshwater mussels

    Pandolfo, Tamara J.; Cope, W. Gregory; Arellano, Consuelo; Bringolf, Robert B.; Barnhart, M. Christopher; Hammer, E

    2010-01-01

    Freshwater mussels (order Unioniformes) fulfill an essential role in benthic aquatic communities, but also are among the most sensitive and rapidly declining faunal groups in North America. Rising water temperatures, caused by global climate change, industrial discharges, drought, or land development, could further challenge imperiled unionid communities. The aim of our study was to determine the upper thermal tolerances of the larval (glochidia) and juvenile life stages of freshwater mussels. Glochidia of 8 species of mussels were tested: Lampsilis siliquoidea, Potamilus alatus, Ligumia recta, Ellipsaria lineolata,Lasmigona complanata, Megalonaias nervosa, Alasmidonta varicosa, and Villosa delumbis. Seven of these species also were tested as juveniles. Survival trends were monitored while mussels held at 3 acclimation temperatures (17, 22, and 27°C) were exposed to a range of common and extreme water temperatures (20–42°C) in standard acute laboratory tests. The average median lethal temperature (LT50) among species in 24-h tests with glochidia was 31.6°C and ranged from 21.4 to 42.7°C. The mean LT50 in 96-h juvenile tests was 34.7°C and ranged from 32.5 to 38.8°C. Based on comparisons of LT50s, thermal tolerances differed among species for glochidia, but not for juveniles. Acclimation temperature did not affect thermal tolerance for either life stage. Our results indicate that freshwater mussels already might be living close to their upper thermal tolerances in some systems and, thus, might be at risk from rising environmental temperatures.

  13. Cancer Stage at Diagnosis in HIV-infected People and Transplant Recipients

    PubMed Central

    Shiels, Meredith S.; Copeland, Glenn; Goodman, Marc T.; Harrell, Janna; Lynch, Charles F.; Pawlish, Karen; Pfeiffer, Ruth M.; Engels, Eric A.

    2015-01-01

    Background It is unknown whether immunosuppression results in more aggressive, advanced stage cancers. As cancer stage is influenced both by tumor biology and medical surveillance, we assessed cancer stage in HIV-infected individuals and solid organ transplant recipients, two immunosuppressed groups with differences in healthcare utilization. Methods We used data on all cases of 15 cancer types, diagnosed during 1996–2010 in two studies that linked U.S. cancer registries to HIV and transplant registries. Odds ratios (ORs) for advanced (vs. local) disease were estimated comparing HIV and transplant populations to immunocompetent people in polytomous logistic regression models, adjusted for age, sex, race, registry and year. Results A total of 8,411 of 4.5 million cancer cases occurred in HIV-infected people, and 7,322 of 6.4 million cancer cases occurred in transplant recipients. Compared to immunocompetent people with cancer, HIV-infected people were more likely to be diagnosed with distant stage lung (OR=1.13), female breast (OR=1.99), and prostate cancers (OR=1.57), while transplant recipients had fewer distant stage lung (OR=0.54), female breast (OR=0.75) and prostate cancers (OR=0.72). Both immunosuppressed populations had a shift toward advanced stage melanoma (ORs: HIV=1.97; transplant=1.82) and bladder cancer (ORs: HIV=1.42; transplant=1.54). Conclusions Bladder cancer and melanoma were more likely to be diagnosed at non-local stage in both HIV-infected people and transplant recipients, suggesting a role of immunosuppression in their progression. Additionally, we observed a shift for some common cancers toward later stages in HIV-infected individuals and toward earlier stages in transplant recipients, consistent with differential access to medical care or surveillance. PMID:25739496

  14. Flexibility in Early Stage Design of U. S. Navy Ships: An Analysis of Options

    DTIC Science & Technology

    2011-01-01

    Flexibility in Early Stage Design of US Navy Ships: An Analysis of Options by Jonathan Page B.S., Systems Engineering, US Naval Academy, 2002...8217C/ v = (;!;!: ;: Pat Hale Director, Systems Design and Ma~ement Fellows Program E~i_yfering.S~~pivi~i~ Acceptedby...2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Flexibility in Early Stage Design of U. S. Navy Ships: An

  15. Development of an in vitro model of the early-stage bovine tuberculous granuloma using Mycobacterium bovis-BCG.

    PubMed

    Garza-Cuartero, Laura; McCarthy, Elaine; Brady, Joseph; Cassidy, Joseph; Hamilton, Clare; Sekiya, Mary; NcNair, Jim; Mulcahy, Grace

    2015-12-15

    Mycobacterium bovis causes 3.1% of human tuberculosis cases, as described by the World Health Organisation. In cattle, this organism causes bovine tuberculosis (BTB) which can have a prevalence of up to 39.5% in some developing countries. In developed countries, although the prevalence of BTB has been reduced through eradication programmes, complete eradication has in some cases proved elusive, with prevalences in cattle of 0.5% in the Republic of Ireland and of 4.3% in the UK. As the tuberculous granuloma is the fundamental lesion that reflects the pathogenesis, immune control and progression of BTB, we aimed to develop an in vitro model of the early-stage bovine tuberculous granuloma, in order to model the early stages of BTB, while also reducing the use of experimentally infected animals. In vitro models of human and ovine mycobacterial granulomas have previously been developed; however, so far, there is no model for the BTB granuloma. As the disease in cattle differs in a number of ways from that in other species, we consider this to be a significant gap in the tools available to study the pathogenesis of BTB. By combining bovine monocyte-derived macrophages infected with M. bovis-BCG and autologous lymphocytes we have developed an early-stage tuberculous bovine granuloma model. In the model, 3D cell aggregations formed a spherical-shape that grew for up to 11 days post-infection. This bovine tuberculous granuloma model can aid in the study of such lesion development, and in comparative studies of pathogenesis, such as, for example, the question of mycobacterial latency in bovine tuberculosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. The fourfold Democritus on the stage of early modern science.

    PubMed

    Lüthy, C

    2000-09-01

    The renewed success of ancient atomism in the seventeenth century has baffled historians not only because of the lack of empirical evidence in its favor but also because of the exotic heterogeneity of the models that were proposed under its name. This essay argues that one of the more intriguing reasons for the motley appearance of early modern atomism is that Democritus, with whose name this doctrine was most commonly associated, was a figure of similar incoherence. There existed in fact no fewer than four quite different Democriti of Abdera and as many literary traditions: the atomist, the "laughing philosopher," the moralizing anatomist, and the alchemist. Around the year 1600 the doctrines of these literary figures, three of whom had no tangible connection with atomism, began to merge into further hybrid personae, some of whom possessed notable scientific potential. This essay offers the story of how these Democriti contributed to the rise of incompatible "atomisms."

  17. Developmental rate and behavior of early life stages of bighead carp and silver carp

    Chapman, Duane C.; George, Amy E.

    2011-01-01

    The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.

  18. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

    PubMed

    Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  19. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection

    PubMed Central

    O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  20. Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.

    PubMed

    Zhou, Yumin; Zhong, Nan-Shan; Li, Xiaochen; Chen, Shuyun; Zheng, Jinping; Zhao, Dongxing; Yao, Weimin; Zhi, Rongchang; Wei, Liping; He, Bingwen; Zhang, Xiangyan; Yang, Changli; Li, Ying; Li, Fenglei; Du, Juan; Gui, Jianping; Hu, Bin; Bai, Chunxue; Huang, Ping; Chen, Gang; Xu, Yongjian; Wang, Changzheng; Liang, Biao; Li, Yinhuan; Hu, Guoping; Tan, Hui; Ye, Xianwei; Ma, Xitao; Chen, Yan; Hu, Xiwei; Tian, Jia; Zhu, Xiaodan; Shi, Zhe; Du, Xiufang; Li, Minjing; Liu, Shengming; Yu, Ronghuan; Zhao, Jianping; Ma, Qianli; Xie, Canmao; Li, Xiongbin; Chen, Tao; Lin, Yingxiang; Zeng, Lizhen; Ye, Changxiu; Ye, Weishu; Luo, Xiangwen; Zeng, Lingshan; Yu, Shuqing; Guan, Wei-Jie; Ran, Pixin

    2017-09-07

    Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 μg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV 1 ) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV 1 after bronchodilator use and the between-group difference in the annual decline in the FEV 1 before and after bronchodilator use from day 30 to month 24. Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV 1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV 1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV 1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22

  1. Current developments in the treatment of early-stage classical Hodgkin lymphoma.

    PubMed

    Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas

    2016-09-01

    After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.

  2. Significance of mediastinal involvement in early stage Hodgkin's disease

    SciT

    Mauch, P.; Goodman, R.; Hellman, S.

    1978-09-01

    Between April 1969 and December 1974, 111 consecutive surgically staged I A and II A patients with supradiaphragmatic Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Patients received 3600 to 4400 rad to mantle and para-aortic--splenic pedicle regions. Median follow-up was 56 months. Fourteen patients developed relapsing Hodgkin's disease and three patients died of possible treatment-related causes, two with acute myocardial infarctions and one with radiation pneumonitis. Patients with mediastinal enlargement greater than one third of the chest diameter have a significantly higher risk (p < 0.01) of developing relapse (9 of 18) than patients with lessermore » or no mediastinal disease (5 of 93). Of the 18 patients with large mediastinal disease, six relapsed in the mediastinum and two in the lung. There continue to be no pelvic extensions in the entire group. There is a 92% relapse-free and 97% overall survival in the 93 patients without extensive mediastinal disease. We continue to recommend mantle and para-aortic--splenic pedicle irradiation for these patients. In view of the large number of relapses in patients with extensive mediastinal disease, we are now treating this subgroup of patients with MOPP chemotherapy in addition to mantle and para-aortic irradiation.« less

  3. Slowdown of surface diffusion during early stages of bacterial colonization

    NASA Astrophysics Data System (ADS)

    Vourc'h, T.; Peerhossaini, H.; Léopoldès, J.; Méjean, A.; Chauvat, F.; Cassier-Chauvat, C.

    2018-03-01

    We study the surface diffusion of the model cyanobacterium Synechocystis sp. PCC6803 during the incipient stages of cell contact with a glass surface in the dilute regime. We observe a twitching motility with alternating immobile tumble and mobile run periods, resulting in a normal diffusion described by a continuous-time random walk with a coefficient of diffusion D . Surprisingly, D is found to decrease with time down to a plateau. This is observed only when the cyanobacterial cells are able to produce released extracellular polysaccharides, as shown by a comparative study between the wild-type strain and various polysaccharides-depleted mutants. The analysis of the trajectories taken by the bacterial cells shows that the temporal characteristics of their intermittent motion depend on the instantaneous fraction of visited sites during diffusion. This describes quantitatively the time dependence of D , related to the progressive surface coverage by the polysaccharides. The observed slowdown of the surface diffusion may constitute a basic precursor mechanism for microcolony formation and provides clues for controlling biofilm formation.

  4. Cost analysis of adjuvant management strategies in early stage (stage I) testicular seminoma

    PubMed Central

    Cox, John A; Gajjar, Shefali R; Lanni, Thomas B; Swanson, Todd A

    2015-01-01

    Background Acceptable post-orchiectomy adjuvant therapy strategies for stage I seminoma patients include surveillance, para-aortic radiation therapy (RT), dog-leg RT, and a single cycle of carboplatin. The required follow-up recommendations were amended by the National Comprehensive Cancer Network (NCCN) in 2012. Given a cause-specific survival of nearly 100%, a closer analysis of the reimbursement for each treatment strategy is warranted. Methods NCCN guidelines were used to design treatment plans for each acceptable adjuvant treatment strategy. Follow-up charges were generated for 10 years based on 2012 (version 1.2012; unchanged in current version 1.2013) and 2011 NCCN (version 2.2011) surveillance recommendations. The 2012 Medicare reimbursement rates were used to calculate each treatment strategy and incremental cost-effectiveness ratios to compare the treatment options. Results Under the current NCCN follow-up recommendations, the total reimbursements generated over 10 years of surveillance, para-aortic RT, dog-leg RT, and carboplatin were $10,643, $11,678, $9,662, and $10,405, respectively. This is compared with the reimbursements as per the 2011 NCCN recommendations: $20,986, $11,517, $9,394, and $20,365 respectively. Factoring the rates of relapse into a salvage model, observation was found to be more costly and less effective ($–1,831, $−7,318, $–7,010) in the adjuvant management of stage I seminoma patients Conclusion Based on incremental cost-effectiveness ratios, para-aortic RT, dog-leg RT, and carboplatin are cost-effective options for the treatment of stage I seminoma when compared with observation; however, surveillance could potentially spare as many as 80%–85% of men diagnosed with stage I seminoma from additional therapy after radical inguinal orchiectomy. Such cost and reimbursement analyses are becoming increasingly relevant, but are not meant to usurp sound clinical judgment. Further studies are required to validate these findings

  5. Infection of some cayenne pepper varieties (Capsicum frustescens L.) by Tobacco mosaic virus at different growth stages

    NASA Astrophysics Data System (ADS)

    Damiri, N.; Sofita, I. S.; Effend, T. A.; Rahim, S. E.

    2017-09-01

    This research aimed to study the infection of three varieties of cayenne pepper (Capsicum frustescens L.) by Tobacco Mosaic Virus when they were inoculated at 2, 4, 6, 8 and 10 weeks old after planting. This experiment was conducted in a green house, at the Plant pests and diseases department, Agriculture Faculty, Sriwijaya University, Indralaya, South Sumatra Indonesia from March to October 2014. The study was arranged in factorial completely randomized design with three replicates. First factor was varieties of cayenne pepper namely green, white and small. Second factor was growth stage. Results of the study showed that TMV inoculated at different growth stages of three cayenne pepper varieties affected the incubation period of TMV symptom, time for flowering and productions. The infection of TMV on various ages affected the disease severity on cayenne pepper variety. The highest disease severity was taking place on small cayenne pepper variety that was inoculated at the early stages of age namely 2 weeks after planting. Inoculation of TMV at younger stages of all Cayenne peppers varieties caused a significant reduction in the number of fruits and its weights. TMV has caused a reduction of more than 50% in weight of cayenne pepper fruits regardless of the variety.

  6. Thyroid gland development in Rachycentron canadum during early life stages.

    PubMed

    Otero, Adriana P S; Rodrigues, Ricardo V; Sampaio, Luís A; Romano, Luis A; Tesser, Marcelo B

    2014-09-01

    The aim of this study was to describe the ontogeny of thyroid follicles in cobia Rachycentron canadum. Larvae were sampled daily (n=15 - 20) from hatching until 15 dah (days after hatching). Following, larvae were sampled every two days by 28 dah; a new sample was taken at 53 dah. The samples were dehydrated, embedded in Paraplast, and sections of 3 µm were dewaxed, rehydrated and stained with HE and PAS. A single follicle was already present 1 dah and three follicles were found 8 dah. The number of follicles increased up to 19 on 53 dah. The diameter of follicles and follicular cell height were lower 1 dah (6.83 ± 1.00 and 4.6 ± 0.01 µm), but increased from 8 dah (24.03 ± 0.46 µm e 6.43 ± 0.46 µm). From 8 dah, the presence of reabsorption vesicles was observed in the colloid and from the 19 dah some follicles did not present colloid. The early thyroid follicle appearance in cobia larvae as well as the high quantity of follicles without colloid and/or with vesicles even after the metamorphosis, might be the explanation of the fast growth of the cobia.

  7. Nature versus nurture? Consequences of short captivity in early stages.

    PubMed

    Horreo, Jose L; Valiente, America G; Ardura, Alba; Blanco, Aida; Garcia-Gonzalez, Claudia; Garcia-Vazquez, Eva

    2018-01-01

    Biological changes occurring as a consequence of domestication and/or captivity are not still deeply known. In Atlantic salmon (S almo salar ), endangered (Southern Europe) populations are enhanced by supportive breeding, which involves only 6 months of captive rearing following artificial spawning of wild-collected adults. In this work, we assess whether several fitness-correlated life-history traits (migratory behavior, straying rate, age at maturity, and growth) are affected by early exposure to the captive environment within a generation, before reproduction thus before genetic selection. Results showed significant differences in growth and migratory behavior (including straying), associated with this very short period of captivity in natural fish populations, changing even genetic variability (decreased in hatchery-reared adults) and the native population structure within and between rivers of the species. These changes appeared within a single generation, suggesting very short time of captivity is enough for initiating changes normally attributed to domestication. These results may have potential implications for the long-term population stability/viability of species subjected to restoration and enhancement processes and could be also considered for the management of zoo populations.

  8. Dyadic Intervention for Family Caregivers and Care Receivers in Early-Stage Dementia

    ERIC Educational Resources Information Center

    Whitlatch, Carol J.; Judge, Katherine; Zarit, Steven H.; Femia, Elia

    2006-01-01

    Purpose: The Early Diagnosis Dyadic Intervention (EDDI) program provides a structured, time-limited protocol of one-on-one and dyadic counseling for family caregivers and care receivers who are in the early stages of dementia. The goals and procedures of EDDI are based on previous research suggesting that dyads would benefit from an intervention…

  9. 13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

  10. 13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

  11. Advancing Early Detection of Autism Spectrum Disorder by Applying an Integrated Two-Stage Screening Approach

    ERIC Educational Resources Information Center

    Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.

    2010-01-01

    Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of Filipek et al. (1999), and to expand the evidence…

  12. Density-dependent blood stage Plasmodium falciparum suppresses malaria super-infection in a malaria holoendemic population.

    PubMed

    Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W; Moormann, Ann M; Davenport, Miles P

    2013-11-01

    Recent studies of Plasmodium berghei malaria in mice show that high blood-stage parasitemia levels inhibit the development of subsequent liver-stage infections. Whether a similar inhibitory effect on liver-stage Plasmodium falciparum by blood-stage infection occurs in humans is unknown. We have analyzed data from a treatment-time-to-infection cohort of children < 10 years of age residing in a malaria holoendemic area of Kenya where people experience a new blood-stage infection approximately every 2 weeks. We hypothesized that if high parasitemia blocked the liver stage, then high levels of parasitemia should be followed by a "skipped" peak of parasitemia. Statistical analysis of "natural infection" field data and stochastic simulation of infection dynamics show that the data are consistent with high P. falciparum parasitemia inhibiting liver-stage parasite development in humans.

  13. Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

    PubMed

    Anand, Sarah; Thomas, Samantha; Hyslop, Terry; Adcock, Janet; Corbet, Kelly; Gasparetto, Cristina; Lopez, Richard; Long, Gwynn D; Morris, Ashley K; Rizzieri, David A; Sullivan, Keith M; Sung, Anthony D; Sarantopoulos, Stefanie; Chao, Nelson J; Horwitz, Mitchell E

    2017-07-01

    Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Time-resolved metabolomics analysis of individual differences during the early stage of lipopolysaccharide-treated rats.

    PubMed

    Dai, Die; Gao, Yiqiao; Chen, Jiaqing; Huang, Yin; Zhang, Zunjian; Xu, Fengguo

    2016-10-03

    Lipopolysaccharide (LPS) can lead to uncontrollable cytokine production and eventually cause fatal sepsis syndrome. Individual toxicity difference of LPS has been widely reported. In our study we observed that two thirds of the rats (24/36) died at a given dose of LPS, while the rest (12/36) survived. Tracking the dynamic metabolic change in survival and non-survival rats in the early stage may reveal new system information to understand the inter-individual variation in response to LPS. As the time-resolved datasets are very complex and no single method can elucidate the problem clearly and comprehensively, the static and dynamic metabolomics methods were employed in combination as cross-validation. Intriguingly, some common results have been observed. Lipids were the main different metabolites between survival and non-survival rats in pre-dose serum and in the early stage of infection with LPS. The LPS treatment led to S-adenosly-methionine and total cysteine individual difference in early stage, and subsequent significant perturbations in energy metabolism and oxidative stress. Furthermore, cytokine profiles were analyzed to identify potential biological associations between cytokines and specific metabolites. Our collective findings may provide some heuristic guidance for elucidating the underlying mechanism of individual difference in LPS-mediated disease.

  15. Innate Immunity to Respiratory Infection in Early Life

    PubMed Central

    Lambert, Laura; Culley, Fiona J.

    2017-01-01

    Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung. PMID:29184555

  16. Influence of hope, social support, and self-esteem in early stage dementia.

    PubMed

    Cotter, Valerie T; Gonzalez, Elizabeth W; Fisher, Kathleen; Richards, Kathy C

    2018-02-01

    Background People in the early stages of dementia adjust to the illness through stages of awareness, coping, and evaluation. Studies have found that hope, social support, and self-esteem facilitate coping, adjustment, and adaptation in chronic illness. Objective The purpose of this descriptive study was to examine the relationships between hope, social support, and self-esteem in individuals with early stage dementia. Methods Data were obtained from 53 individuals with early stage dementia. The scores on the Herth Hope Index, Social Support Questionnaire Short-Form, and the State Self-Esteem Scale were analyzed using linear regression. Results Hope was moderately associated with self-esteem ( r = .49, p < .001). Hope accounted for 25% of the variance in self-esteem and was a key component in predicting self-esteem. No significant relationship was found between social support and self-esteem. Conclusion Findings suggest that hope may be an important factor to help individuals manage potential threats to self-esteem in the experience of early stage dementia. Strategies to inspire hope and then enhance self-esteem are promising for individuals living with early stage dementia.

  17. [Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

    PubMed

    Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

    2012-10-01

    The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

  18. Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

    PubMed

    Ingley, Spencer J; Johnson, Jerald B

    2016-03-01

    How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

  19. Good daily habits during the early stages of life determine success throughout life.

    PubMed

    Kohyama, Jun

    2016-01-01

    This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.

  20. Efficient harvesting methods for early-stage snake and turtle embryos.

    PubMed

    Matsubara, Yoshiyuki; Kuroiwa, Atsushi; Suzuki, Takayuki

    2016-04-01

    Reptile development is an intriguing research target for understating the unique morphogenesis of reptiles as well as the evolution of vertebrates. However, there are numerous difficulties associated with studying development in reptiles. The number of available reptile eggs is usually quite limited. In addition, the reptile embryo is tightly adhered to the eggshell, making it a challenge to isolate reptile embryos intact. Furthermore, there have been few reports describing efficient procedures for isolating intact embryos especially prior to pharyngula stage. Thus, the aim of this review is to present efficient procedures for obtaining early-stage reptilian embryos intact. We first describe the method for isolating early-stage embryos of the Japanese striped snake. This is the first detailed method for obtaining embryos prior to oviposition in oviparous snake species. Second, we describe an efficient strategy for isolating early-stage embryos of the soft-shelled turtle. © 2016 Japanese Society of Developmental Biologists.

  1. Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

    PubMed Central

    Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

    2013-01-01

    Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

  2. Nigericin is a potent inhibitor of the early stage of vaccinia virus replication.

    PubMed

    Myskiw, Chad; Piper, Jessica; Huzarewich, Rhiannon; Booth, Tim F; Cao, Jingxin; He, Runtao

    2010-12-01

    Poxviruses remain a significant public health concern due to their potential use as bioterrorist agents and the spread of animal borne poxviruses, such as monkeypox virus, to humans. Thus, the identification of small molecule inhibitors of poxvirus replication is warranted. Vaccinia virus is the prototypic member of the Orthopoxvirus genus, which also includes variola and monkeypox virus. In this study, we demonstrate that the carboxylic ionophore nigericin is a potent inhibitor of vaccinia virus replication in several human cell lines. In HeLa cells, we found that the 50% inhibitory concentration of nigericin against vaccinia virus was 7.9 nM, with a selectivity index of 1038. We present data demonstrating that nigericin targets vaccinia virus replication at a post-entry stage. While nigericin moderately inhibits both early vaccinia gene transcription and translation, viral DNA replication and intermediate and late gene expression are severely compromised in the presence of nigericin. Our results demonstrate that nigericin has the potential to be further developed into an effective antiviral to treat poxvirus infections. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  3. Congenital syphilis: early- and late-stage findings of rhagades and dental anomalies.

    PubMed

    Khetarpal, Shilpi; Kempf, Ellen; Mostow, Eliot

    2011-01-01

    Congenital syphilis occurs via vertical transmission when Treponema pallidum crosses the placenta after the 16th week of gestation. Manifestations of congenital syphilis vary from asymptomatic infection to stillbirth. We present a case of congenital syphilis in a Vietnamese orphan who presented with rhagades, hearing deficit, and abnormal dentition after adoption in the United States. He demonstrated both early- and late-stage findings of congenital syphilis. He is presumed to be 5 years old, and it is uncertain if he received treatment. Upon arrival to the United States, his rapid plasma reagin test was negative, but his fluorescent treponemal antibody-absorption test was positive, so no further treatment was recommended. It is possible that other late congenital syphilis stigmata may develop in his later years. The Centers for Disease Control recommends screening all pregnant women for syphilis at the beginning of prenatal care. Clinicians should be made aware of the manifestations of congenital syphilis, especially when caring for international orphans and children born to mothers who lacked prenatal care. © 2010 Wiley Periodicals, Inc.

  4. Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons

    PubMed Central

    Moore, David J.; Letendre, Scott; Poehlman Roediger, Mollie; Eberly, Lynn; Weintrob, Amy; Ganesan, Anuradha; Johnson, Erica; Del Rosario, Raechel; Agan, Brian K.; Hale, Braden R.

    2013-01-01

    Objective: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls. Methods: We performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV−) military beneficiaries. HIV+ patients were categorized as earlier (<6 years of HIV, no AIDS-defining conditions, and CD4 nadir >200 cells/mm3) or later stage patients (n = 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests. Results: HIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm3, and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm3). NCI was diagnosed among 38 (19%, 95% confidence interval 14%–25%) HIV+ patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p = 0.72). The prevalence of NCI among HIV+ patients was similar to HIV− patients. Conclusions: HIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment. PMID:23303852

  5. [An unexpected stage of alkalosis in the dynamics of the early posthemorrhagic period].

    PubMed

    Beliaev, A V

    2000-01-01

    A study was made on acid-base metabolism in early posthemorrhagic period as exemplified by examination of patients presenting with gastrointestinal hemorrhage. It has been ascertained that hemorrhage is accompanied by a mixed variant of the acid-base state (ABS) deviation, namely metabolic lactate-acidosis and respiratory alkalosis. In the time-related course of posthemorrhagic period such deviations persist in patients with lethal outcome; with the disease running a favourable course the above deviations are found to return to normal quite soon. The development of complications leads to staging in ABC, its stages being as follows: stage I--the initial stage, stage II--persisting metabolic acidosis and respiratory alkalosis, stage III--alkalosis, stage IV--normalization, with stage III of ABS being encouraged by hypocapnia caused by function disorders of the lungs in early posthemorrhagic period, normalization of cell metabolism, increase in the rate of urination as a reflection of the third earlier identified stage of water metabolism, with the H+ excretion in the urine at the previous level. The identified ABS stage III threatens coming trouble, being accompanied by metabolic deviations together with a risk of function disorder of the myocardium.

  6. A novel acute HIV infection staging system based on 4th generation immunoassay.

    PubMed

    Ananworanich, Jintanat; Fletcher, James L K; Pinyakorn, Suteeraporn; van Griensven, Frits; Vandergeeten, Claire; Schuetz, Alexandra; Pankam, Tippawan; Trichavaroj, Rapee; Akapirat, Siriwat; Chomchey, Nitiya; Phanuphak, Praphan; Chomont, Nicolas; Michael, Nelson L; Kim, Jerome H; de Souza, Mark

    2013-05-29

    Fourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging). Screening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2. Using 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

  7. [Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

    PubMed

    Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

    2013-01-01

    A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

  8. Urine biomarkers in the early stages of diseases: current status and perspective.

    PubMed

    Jing, Jian; Gao, Youhe

    2018-02-01

    As a noninvasive and easily available biological fluid, the urine is becoming an important source for disease biomarker study. Change is essential for the usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate more changes, especially in the early stages of diseases. In this review, we summarize current status and discuss perspectives on the discovery of urine biomarkers in the early stages of diseases. We emphasize the advantages of urine biomarkers compared to plasma biomarkers for the diagnosis of diseases at early stages, propose a urine biomarker research roadmap, and highlight a novel membrane storage technique that enables large-scale urine sample collection and storage efficiently and economically. It is anticipated that urine biomarker studies will greatly promote early diagnosis, prevention, treatment, and prognosis of a variety of diseases, and provide strong support for translational and precision medicine.

  9. Living with early-stage dementia: a review of qualitative studies.

    PubMed

    Steeman, Els; de Casterlé, Bernadette Dierckx; Godderis, Jan; Grypdonck, Mieke

    2006-06-01

    This paper presents a literature review whose aim was to provide better understanding of living with early-stage dementia. Even in the early stages, dementia may challenge quality of life. Research on early-stage dementia is mainly in the domain of biomedical aetiology and pathology, providing little understanding of what it means to live with dementia. Knowledge of the lived experience of having dementia is important in order to focus pro-active care towards enhancing quality of life. Qualitative research is fundamentally well suited to obtaining an insider's view of living with early-stage dementia. We performed a meta-synthesis of qualitative research findings. We searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the references of pertinent articles, the references cited in a recently published book on the subjective experience of dementia, one thesis, and the journal Dementia. Thirty-three pertinent articles were identified, representing 28 separate studies and 21 different research samples. Findings were coded, grouped, compared and integrated. Living with dementia is described from the stage a person discovers the memory impairment, through the stage of being diagnosed with dementia, to that of the person's attempts to integrate the impairment into everyday life. Memory loss often threatens perceptions of security, autonomy and being a meaningful member of society. At early stages of memory loss, individuals use self-protecting and self-adjusting strategies to deal with perceived changes and threats. However, the memory impairment itself may make it difficult for an individual to deal with these changes, thereby causing frustration, uncertainty and fear. Our analysis supports the integration of proactive care into the diagnostic process, because even early-stage dementia may challenge quality of life. Moreover, this care should actively involve both the individual with dementia and their family so that both parties can adjust positively

  10. Driving behaviors in early stage dementia: a study using in-vehicle technology.

    PubMed

    Eby, David W; Silverstein, Nina M; Molnar, Lisa J; LeBlanc, David; Adler, Geri

    2012-11-01

    According to the Alzheimer's Association (2011), (1) in 8 people age 65 and older, and about one-half of people age 85 and older, have Alzheimer's disease in the United States (US). There is evidence that drivers with Alzheimer's disease and related dementias are at an increased risk for unsafe driving. Recent advances in sensor, computer, and telecommunication technologies provide a method for automatically collecting detailed, objective information about the driving performance of drivers, including those with early stage dementia. The objective of this project was to use in-vehicle technology to describe a set of driving behaviors that may be common in individuals with early stage dementia (i.e., a diagnosis of memory loss) and compare these behaviors to a group of drivers without cognitive impairment. Seventeen drivers with a diagnosis of early stage dementia, who had completed a comprehensive driving assessment and were cleared to drive, participated in the study. Participants had their vehicles instrumented with a suite of sensors and a data acquisition system, and drove 1-2 months as they would under normal circumstances. Data from the in-vehicle instrumentation were reduced and analyzed, using a set of algorithms/heuristics developed by the research team. Data from the early stage dementia group were compared to similar data from an existing dataset of 26 older drivers without dementia. The early stage dementia group was found to have significantly restricted driving space relative to the comparison group. At the same time, the early stage dementia group (which had been previously cleared by an occupational therapist as safe to drive) drove as safely as the comparison group. Few safety-related behavioral errors were found for either group. Wayfinding problems were rare among both groups, but the early stage dementia group was significantly more likely to get lost. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

    PubMed

    Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

    2016-01-01

    Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

  12. Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

    PubMed Central

    Saludes, Verónica; González, Victoria; Planas, Ramon; Matas, Lurdes; Ausina, Vicente; Martró, Elisa

    2014-01-01

    Hepatitis C virus (HCV) infection represents a major public health issue. Hepatitis C can be cured by therapy, but many infected individuals are unaware of their status. Effective HCV screening, fast diagnosis and characterization, and hepatic fibrosis staging are highly relevant for controlling transmission, treating infected patients and, consequently, avoiding end-stage liver disease. Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays. Additionally, the use of point-of-care tests can increase HCV screening opportunities. However, active HCV infection must be confirmed by direct diagnosis methods. Additionally, HCV genotyping is required prior to starting any treatment. Increasingly, high-volume clinical laboratories use different types of automated platforms, which have simplified sample processing, reduced hands-on-time, minimized contamination risks and human error and ensured full traceability of results. Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods, such as imaging techniques and serum-based tests. However, no single test is currently available that is able to completely replace liver biopsy. This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests. PMID:24707126

  13. Two-stage revision for the culture-negative infected total hip arthroplasty : A comparative study.

    PubMed

    Ibrahim, M S; Twaij, H; Haddad, F S

    2018-01-01

    Periprosthetic joint infection (PJI) remains a challenging complication following total hip arthroplasty (THA). It is associated with high levels of morbidity, mortality and expense. Guidelines and protocols exist for the management of culture-positive patients. Managing culture-negative patients with a PJI poses a greater challenge to surgeons and the wider multidisciplinary team as clear guidance is lacking. We aimed to compare the outcomes of treatment for 50 consecutive culture-negative and 50 consecutive culture-positive patients who underwent two-stage revision THA for chronic infection with a minimum follow-up of five years. There was no significant difference in the outcomes between the two groups of patients, with a similar rate of re-infection of 6%, five years post-operatively. Culture-negative PJIs were associated with older age, smoking, referral from elsewhere and pre-operative antibiotic treatment. The samples in the culture-negative patients were negative before the first stage (aspiration), during the first-stage (implant removal) and second-stage procedures (re-implantation). Adherence to strict protocols for selecting and treating culture-negative patients with a PJI using the same two-stage revision approach that we employ for complex culture-positive PJIs is important in order to achieve control of the infection in this difficult group of patients. Cite this article: Bone Joint J 2018;(1 Supple A)100-B:3-8. ©2018 The British Editorial Society of Bone and Joint Surgery.

  14. Susceptibility to Plasmodium liver stage infection is altered by hepatocyte polyploidy.

    PubMed

    Austin, Laura S; Kaushansky, Alexis; Kappe, Stefan H I

    2014-05-01

    Plasmodium parasites infect hepatocytes of their mammalian hosts and undergo obligate liver stage development. The specific host cell attributes that are important for liver infection remain largely unknown. Several host signalling pathways are perturbed in infected hepatocytes, some of which are important in the generation of hepatocyte polyploidy. To test the functional consequence of polyploidy on liver infection, we infected hepatocytes with the rodent malaria parasite Plasmodium yoelii both in vitro and in vivo and examined the ploidy of infected and uninfected hepatocytes by flow cytometry. In both hepatoma cell lines and in the mouse liver, the fraction of polyploid cells was higher in the infected cell population than in the uninfected cell population. When the data were reanalysed by comparing the extent of Plasmodium infection within each ploidy subset, we found that infection rates were elevated in more highly polyploid cells and lower in diploid cells. Furthermore, we found that the parasite's preference for host cells with high ploidy is conserved among rodent malaria species and the human malaria parasite Plasmodium falciparum. This parasite preference for host cells of high ploidy cannot be explained by differences in hepatocyte size or DNA replication. We conclude that Plasmodium preferentially infects and develops in polyploid hepatocytes. © 2014 John Wiley & Sons Ltd.

  15. Susceptibility to Plasmodium liver stage infection is altered by hepatocyte polyploidy

    PubMed Central

    Austin, Laura S.; Kaushansky, Alexis; Kappe, Stefan H.I.

    2014-01-01

    Summary Plasmodium parasites infect hepatocytes of their mammalian hosts and within undergo obligate liver stage development. The specific host cell attributes that are important for liver infection remain largely unknown. Several host signaling pathways are perturbed in infected hepatocytes, some of which are important in the generation of hepatocyte polyploidy. To test the functional consequence of polyploidy in liver infection, we infected hepatocytes with the rodent malaria parasite Plasmodium yoelii both in vitro and in vivo and examined the ploidy of infected and uninfected hepatocytes by flow cytometry. In both hepatoma cell lines and in the mouse liver, the fraction of polyploid cells was higher in the infected cell population than in the uninfected cell population. When the data were reanalyzed by comparing the extent of Plasmodium infection within each ploidy subset, we found that infection rates were elevated in more highly polyploid cells and lower in diploid cells. Furthermore, we found that the parasite’s preference for host cells with high ploidy is conserved among rodent malaria species and the human malaria parasite Plasmodium falciparum. This parasite preference for host cells of high ploidy cannot be explained by differences in hepatocyte size or DNA replication. We conclude that Plasmodium preferentially infects and develops in polyploid hepatocytes. PMID:24612025

  16. Eosinophils contribute to early clearance of Pneumocystis murina infection

    PubMed Central

    Eddens, Taylor; Elsegeiny, Waleed; Nelson, Michael P.; Horne, William; Campfield, Brian T.; Steele, Chad; Kolls, Jay K.

    2015-01-01

    Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4+ T-cell counts in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV infected individuals taking immunosuppressive drug regimens targeting T-cell activation are also susceptible. Given the crucial role of CD4+ T-cells in host defense against Pneumocystis, we used RNA-sequencing of whole lung early in infection in wild type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild type mice, a strong eosinophil signature was observed at day 14 post-Pneumocystis challenge and eosinophils were increased in the bronchoalveolar lavage fluid of wild type mice. Furthermore, eosinophilopoiesis-deficient Gata1tm6Sho/J mice were more susceptible to Pneumocystis infection when compared to BALB/c controls and bone marrow derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1−/− mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. pIL5 treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden compared to mice treated with control plasmid. Additionally, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57Bl/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1tm6Sho/J mice. Taken together, these results demonstrate that an early role of CD4+ T-cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development for Pneumocystis pneumonia in the immunosuppressed population. PMID:25994969

  17. Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

    EPA Science Inventory

    Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

  18. Immunodiagnostic identification of dairy cows infected with Prototheca zopfii at various clinical stages and discrimination between infected and uninfected cows.

    PubMed

    Roesler, U; Scholz, H; Hensel, A

    2001-02-01

    Protothecosis is a severe form of mastitis in cattle that is caused by colorless algae of the genus Prototheca. So far, no suitable serological test for the identification of infected animals is available for routine diagnosis. In this study an indirect enzyme-linked immunosorbent assay (ELISA) for the identification of infected cows and for discriminating among infected cows at various clinical stages was developed. Immunoglobulin G (IgG) in serum and IgA and IgG1 in whey were used as antibody isotypes. The ELISA was evaluated using serum and whey from animals at different clinical stages of infection. A total of 12 cows with acute clinical manifestation of protothecal mastitis, 22 cows with clinical signs of chronic mastitis, 40 Prototheca zopfii-negative cows, and 18 cows with chronic clinical signs and earlier cultures positive for P. zopfii but with presently negative culturing results were investigated. A sensitivity of 96% and a specificity of 94% were calculated for the ELISA based on IgA levels. Intra-assay and interassay variations were calculated to be 6.08 and 6.32%, respectively. Based on these data, this ELISA was found to be suitable for discrimination between infected and uninfected animals and might therefore be useful for screening affected herds.

  19. Immunodiagnostic Identification of Dairy Cows Infected with Prototheca zopfii at Various Clinical Stages and Discrimination between Infected and Uninfected Cows

    PubMed Central

    Roesler, Uwe; Scholz, Holger; Hensel, Andreas

    2001-01-01

    Protothecosis is a severe form of mastitis in cattle that is caused by colorless algae of the genus Prototheca. So far, no suitable serological test for the identification of infected animals is available for routine diagnosis. In this study an indirect enzyme-linked immunosorbent assay (ELISA) for the identification of infected cows and for discriminating among infected cows at various clinical stages was developed. Immunoglobulin G (IgG) in serum and IgA and IgG1 in whey were used as antibody isotypes. The ELISA was evaluated using serum and whey from animals at different clinical stages of infection. A total of 12 cows with acute clinical manifestation of protothecal mastitis, 22 cows with clinical signs of chronic mastitis, 40 Prototheca zopfii-negative cows, and 18 cows with chronic clinical signs and earlier cultures positive for P. zopfii but with presently negative culturing results were investigated. A sensitivity of 96% and a specificity of 94% were calculated for the ELISA based on IgA levels. Intra-assay and interassay variations were calculated to be 6.08 and 6.32%, respectively. Based on these data, this ELISA was found to be suitable for discrimination between infected and uninfected animals and might therefore be useful for screening affected herds. PMID:11158103

  20. Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters

    PubMed Central

    Baseler, Laura; Scott, Dana P.; Saturday, Greg; Horne, Eva; Rosenke, Rebecca; Thomas, Tina; Meade-White, Kimberly; Haddock, Elaine; Feldmann, Heinz

    2016-01-01

    Background Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). Methodology/Principal Findings Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. Conclusions/Significance Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central

  1. Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters.

    PubMed

    Baseler, Laura; Scott, Dana P; Saturday, Greg; Horne, Eva; Rosenke, Rebecca; Thomas, Tina; Meade-White, Kimberly; Haddock, Elaine; Feldmann, Heinz; de Wit, Emmie

    2016-11-01

    Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.

  2. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

    PubMed

    Kong, Fan-Yun; Wei, Xiao; Zhou, Kai; Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.

  3. Effects of chronic crude oil exposure on early developmental stages of the Northern krill (Meganyctiphanes norvegica).

    PubMed

    Arnberg, Maj; Moodley, Leon; Dunaevskaya, Evgenia; Ramanand, Sreerekha; Ingvarsdóttir, Anna; Nilsen, Marianne; Ravagnan, Elisa; Westerlund, Stig; Sanni, Steinar; Tarling, Geraint A; Bechmann, Renée K

    2017-01-01

    Rising oil and gas activities in northern high latitudes have led to an increased risk of petroleum pollution in these ecosystems. Further, seasonal high UV radiation at high latitudes may elevate photo-enhanced toxicity of petroleum pollution to marine organisms. Zooplanktons are a key ecological component of northern ecosystems; therefore, it is important to assess their sensitivity to potential pollutants of oil and gas activity. As ontogenetic development may be particularly sensitive, the aim of this study was to examine the impact of chronic exposure to oil water dispersion (OWD) on development and feeding of early life stages of the Northern krill, Meganyctiphanes norvegica. In a range of experiments, embryonic, nonfeeding, and feeding larval stages were exposed to concentrations of between 0.01 and 0.1 mg/L of oil or photo-modified oil for 19 and 21 d. No significant effects on egg respiration, hatching success, development, length and larval survival were observed from these treatments. Similarly, evolution of fatty acid composition patterns during ontogenetic development was unaffected. The results indicates a high degree of resilience of these early developmental stages to such types and concentrations of pollutants. However, feeding and motility in later calyptopis-stage larvae were significantly impaired at exposure of 0.1 mg/L oil. Data indicate that feeding larval stage of krill was more sensitive to OWD than early nonfeeding life stages. This might be attributed to the narcotic effects of oil pollutants, their direct ingestion, or accumulated adverse effects over early development.

  4. All-optical photoacoustic imaging and detection of early-stage dental caries

    NASA Astrophysics Data System (ADS)

    Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

    2015-02-01

    Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

  5. Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model.

    PubMed

    Bartholomeusz, Cali F; Cropley, Vanessa L; Wannan, Cassandra; Di Biase, Maria; McGorry, Patrick D; Pantelis, Christos

    2017-05-01

    This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.

  6. EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

    PubMed

    Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

    2018-05-02

    EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  7. Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits.

    PubMed

    MacDonald, Alan B

    2007-01-01

    Brain structure in health is a dynamic energized equation incorporating chemistry, neuronal structure, and circuitry components. The chemistry "piece" is represented by multiple neurotransmitters such as Acetylcholine, Serotonin, and Dopamine. The neuronal structure "piece" incorporates synapses and their connections. And finally circuits of neurons establish "architectural blueprints" of anatomic wiring diagrams of the higher order of brain neuron organizations. In Alzheimer's disease, there are progressive losses in all of these components. Brain structure crumbles. The deterioration in Alzheimer's is ordered, reproducible, and stepwise. Drs. Braak and Braak have described stages in the Alzheimer disease continuum. "Progressions" through Braak Stages benchmark "Regressions" in Cognitive function. Under the microscope, the Stages of Braak commence in brain regions near to the hippocampus, and over time, like a tsunami wave of destruction, overturn healthy brain regions, with neurofibrillary tangle damaged neurons "marching" through the temporal lobe, neocortex and occipital cortex. In effect the destruction ascends from the limbic regions to progressively destroy the higher brain centers. Rabies infection also "begins low and finishes high" in its wave of destruction of brain tissue. Herpes Zoster infections offer the paradigm of clinical latency of infection inside of nerves before the "marching commences". Varicella Zoster virus enters neurons in the pediatric years. Dormant virus remains inside the neurons for 50-80 years, tissue damage late in life (shingles) demonstrates the "march of the infection" down neural pathways (dermatomes) as linear areas of painful blisters loaded with virus from a childhood infection. Amalgamation of Zoster with Rabies models produces a hybrid model to explain all of the Braak Stages of Alzheimer's disease under a new paradigm, namely "Alzheimer's neuroborreliosis" in which latent Borrelia infections ascend neural circuits through

  8. Early-stage valuation of medical devices: the role of developmental uncertainty.

    PubMed

    Girling, Alan; Young, Terry; Brown, Celia; Lilford, Richard

    2010-08-01

    At the concept stage, many uncertainties surround the commercial viability of a new medical device. These include the ultimate functionality of the device, the cost of producing it and whether, and at what price, it can be sold to a health-care provider (HCP). Simple assessments of value can be made by estimating such unknowns, but the levels of uncertainty may mean that their operational value for investment decisions is unclear. However, many decisions taken at the concept stage are reversible and will be reconsidered later before the product is brought to market. This flexibility can be exploited to enhance early-stage valuations. To develop a framework for valuing a new medical device at the concept stage that balances benefit to the HCP against commercial costs. This is done within a simplified stage-gated model of the development cycle for new products. The approach is intended to complement existing proposals for the evaluation of the commercial headroom available to new medical products. A model based on two decision gates can lead to lower bounds (underestimates) for product value that can serve to support a decision to develop the product. Quantifiable uncertainty that can be resolved before the device is brought to market will generally enhance early-stage valuations of the device, and this remains true even when some components of uncertainty cannot be fully described. Clinical trials and other evidence-gathering activities undertaken as part of the development process can contribute to early-stage estimates of value.

  9. Operative treatment of early infection after internal fixation of limb fractures (exclusive of severe open fractures).

    PubMed

    Bonnevialle, P

    2017-02-01

    Early infection after open reduction and internal fixation (ORIF) of a limb bone is defined as bacteriologically documented, deep and/or superficial surgical-site infection (SSI) diagnosed within 6months after the surgical procedure. This interval is arbitrarily considered sufficient to obtain fracture healing. The treatment of early infection after ORIF should be decided by a multidisciplinary team. The principles are the same as for revision arthroplasty. Superficial SSIs should be differentiated from deep SSIs, based on the results of bacteriological specimens collected using flawless technique. A turning point in the local microbial ecology occurs around the third or fourth week, when a biofilm develops around metallic implants. This biofilm protects the bacteria. The treatment relies on both non-operative and operative measures, which are selected based on the time to occurrence of the infection, condition of the soft tissues, and stage of bone healing. Both the surgical strategy and the antibiotic regimen should be determined during a multidisciplinary discussion. When treating superficial SSIs after ORIF, soft-tissue management is the main challenge. The treatment differs according to whether the hardware is covered or exposed. Defects in the skin and/or fascia can be managed using reliable reconstructive surgery techniques, either immediately or after a brief period of vacuum-assisted closure. In deep SSIs, deciding whether to leave or to remove the hardware is difficult. If the hardware is removed, the fracture site can be stabilised provisionally using either external fixation or a cement rod. Once infection control is achieved, several measures can be taken to stimulate bone healing before the end of the classical 6-month interval. If the hardware was removed, then internal fixation must be performed once the infection is eradicated. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

    PubMed

    Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

    2017-09-18

    Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

  11. Effects of education on the progression of early- versus late-stage mild cognitive impairment.

    PubMed

    Ye, Byoung Seok; Seo, Sang Won; Cho, Hanna; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Back, Joung Hwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, Sangyun; Han, Seol-Heui; Lee, Jae-Hong; Cheong, Hae-Kwan; Na, Duk L

    2013-04-01

    Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

  12. Emergency 1-stage anterior approach for cervical spine infection complicated by epidural abscess

    PubMed Central

    Li, Haoxi; Chen, Zhaoxiong; Yong, Zhiyao; Li, Xinhua; Huang, Yufeng; Wu, Desheng

    2017-01-01

    Abstract It was a retrospective analysis. The aim of the study was to explore the safety and reliability of emergency 1-stage radical debridement and reconstruction using titanium mesh filled with autologous bone for patients with cervical spine infection complicated by epidural abscess. At present, cervical spine infection complicated by epidural abscess is known as a severe spine disease. Recently, case report of this disease is showing quite an increasing tendency, particularly in economically undeveloped areas and countries. Regarding the treatment of this disease, 1-stage radical debridement and reconstruction has been widely adopted; however, emergency 1-stage anterior approach surgery without medication is considered as a relatively taboo, since it is generally acknowledged that such operation would possibly cause unexpected infection. Nevertheless, regular elective surgery may require longer time for preparation. In addition, long hour compression and stimulation of the abscess may leave the patients with irreversible spinal neural impairment. However, our department has finished 14 cases of cervical spine infection complicated with epidural abscess without 1 single case of postoperative infection. A retrospective study was conducted on 14 patients (9 males and 5 females; average age 57.4 years) who were diagnosed with cervical spine infection complicated by epidural abscess from January 2005 to December 2014. All the patients were admitted to hospital with varying degrees of neurological function losses, and then underwent 1-stage anterior focal debridement and reconstruction using titanium mesh within 24 hours after admission. They received postoperative standard antibiotic chemotherapy for 10 to 12 weeks. They were followed up for 18 to 36 months, an average of 27.4 months. X-ray, computed tomography (CT), and MRI (magnetic resonance imaging (MRI) were used to determine the fusion state and vertebral stability. American Spinal Injury Association (ASIA

  13. Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

    PubMed

    Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

    2015-07-31

    HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Viral RNA at Two Stages of Reovirus Infection Is Required for the Induction of Necroptosis.

    PubMed

    Berger, Angela K; Hiller, Bradley E; Thete, Deepti; Snyder, Anthony J; Perez, Encarnacion; Upton, Jason W; Danthi, Pranav

    2017-03-15

    Necroptosis, a regulated form of necrotic cell death, requires the activation of the RIP3 kinase. Here, we identify that infection of host cells with reovirus can result in necroptosis. We find that necroptosis requires sensing of the genomic RNA within incoming virus particles via cytoplasmic RNA sensors to produce type I interferon (IFN). While these events that occur prior to the de novo synthesis of viral RNA are required for the induction of necroptosis, they are not sufficient. The induction of necroptosis also requires late stages of reovirus infection. Specifically, efficient synthesis of double-stranded RNA (dsRNA) within infected cells is required for necroptosis. These data indicate that viral RNA interfaces with host components at two different stages of infection to induce necroptosis. This work provides new molecular details about events in the viral replication cycle that contribute to the induction of necroptosis following infection with an RNA virus. IMPORTANCE An appreciation of how cell death pathways are regulated following viral infection may reveal strategies to limit tissue destruction and prevent the onset of disease. Cell death following virus infection can occur by apoptosis or a regulated form of necrosis known as necroptosis. Apoptotic cells are typically disposed of without activating the immune system. In contrast, necroptotic cells alert the immune system, resulting in inflammation and tissue damage. While apoptosis following virus infection has been extensively investigated, how necroptosis is unleashed following virus infection is understood for only a small group of viruses. Here, using mammalian reovirus, we highlight the molecular mechanism by which infection with a dsRNA virus results in necroptosis. Copyright © 2017 American Society for Microbiology.

  15. Viral RNA at Two Stages of Reovirus Infection Is Required for the Induction of Necroptosis

    PubMed Central

    Berger, Angela K.; Hiller, Bradley E.; Thete, Deepti; Snyder, Anthony J.; Perez, Encarnacion; Upton, Jason W.

    2017-01-01

    ABSTRACT Necroptosis, a regulated form of necrotic cell death, requires the activation of the RIP3 kinase. Here, we identify that infection of host cells with reovirus can result in necroptosis. We find that necroptosis requires sensing of the genomic RNA within incoming virus particles via cytoplasmic RNA sensors to produce type I interferon (IFN). While these events that occur prior to the de novo synthesis of viral RNA are required for the induction of necroptosis, they are not sufficient. The induction of necroptosis also requires late stages of reovirus infection. Specifically, efficient synthesis of double-stranded RNA (dsRNA) within infected cells is required for necroptosis. These data indicate that viral RNA interfaces with host components at two different stages of infection to induce necroptosis. This work provides new molecular details about events in the viral replication cycle that contribute to the induction of necroptosis following infection with an RNA virus. IMPORTANCE An appreciation of how cell death pathways are regulated following viral infection may reveal strategies to limit tissue destruction and prevent the onset of disease. Cell death following virus infection can occur by apoptosis or a regulated form of necrosis known as necroptosis. Apoptotic cells are typically disposed of without activating the immune system. In contrast, necroptotic cells alert the immune system, resulting in inflammation and tissue damage. While apoptosis following virus infection has been extensively investigated, how necroptosis is unleashed following virus infection is understood for only a small group of viruses. Here, using mammalian reovirus, we highlight the molecular mechanism by which infection with a dsRNA virus results in necroptosis. PMID:28077640

  16. Association Between Early Idiopathic Neonatal Jaundice and Urinary Tract Infections

    PubMed Central

    Özcan, Murat; Sarici, S Ümit; Yurdugül, Yüksel; Akpinar, Melis; Altun, Demet; Özcan, Begüm; Serdar, Muhittin A; Sarici, Dilek

    2017-01-01

    Background and purpose: Etiologic role, incidence, demographic, and response-to-treatment characteristics of urinary tract infection (UTI) among neonates, its relationship with significant neonatal hyperbilirubinemia, and abnormalities of the urinary system were studied in a prospective investigation in early (≤10 days) idiopathic neonatal jaundice in which all other etiologic factors of neonatal hyperbilirubinemia were ruled out. Patients and methods: Urine samples for microscopic and bacteriologic examination were obtained with bladder catheterization from 155 newborns with early neonatal jaundice. Newborns with a negative urine culture and with a positive urine culture were defined as group I and group II, respectively, and the 2 groups were compared with each other. Results: The incidence of UTI in whole of the study group was 16.7%. Serum total and direct bilirubin levels were statistically significantly higher in group II when compared with group I (P = .005 and P = .001, respectively). Decrease in serum total bilirubin level at the 24th hour of phototherapy was statistically significantly higher in group I compared with group II (P = .022). Conclusions: Urinary tract infection should be investigated in the etiologic evaluation of newborns with significant hyperbilirubinemia. The possibility of UTI should be considered in jaundiced newborns who do not respond to phototherapy well or have a prolonged duration of phototherapy treatment. PMID:28469520

  17. Angiostrongylus cantonensis (Nematode: Metastrongiloidea): in vitro cultivation of infective third-stage larvae to fourth-stage larvae.

    PubMed

    Lin, Rong-Jyh; He, Jie-Wen; Chung, Li-Yu; Lee, June-Der; Wang, Jiun-Jye; Yen, Chuan-Min

    2013-01-01

    The present study to attempt to cultivate Angiostrongylus cantonensis from third-stage larvae (AcL3) to fourth-stage larvae (AcL4) in vitro in defined complete culture medium that contained with Minimum Essential Medium Eagle (MEM), supplemented amino acid (AA), amine (AM), fatty acid (FA), carbohydrate (CA) and 20% fetal calf serum (FCS) was successful. When AcL3 were cultured in the defined complete culture medium at 37°C in a 5% CO2 atmosphere, the larvae began to develop to AcL4 after 30 days of cultivation, and were enclosed within the sheaths of the third molts of the life cycle. Under these conditions, the larvae developed uniformly and reached to the fourth-stage 36 days. The morphology of AcL3 develop to AcL4 were recording and analyzing. Then comparison of A. cantonensis larval morphology and development between in vitro cultivation in defined complete culture medium and in vivo cultivation in infective BALB/c mice. The larvae that had been cultivated in vitro were smaller than AcL4 of infective BALB/c mice. However the AcL3 that were cultured using defined incomplete culture medium (MEM plus 20% FCS with AA+AM, FA, CA, AA+AM+FA, FA+CA, CA+AA+AM or not) did not adequately survive and develop. Accordingly, the inference is made that only the defined complete medium enable AcL3 develop to AcL4 in vitro. Some nematodes have been successfully cultured into mature worms but only a few researches have been made to cultivate A. cantonensis in vitro. The present study is the first to have succeeded in developing AcL3 to AcL4 by in vitro cultivation. Finally, the results of in vitro cultivation studies herein contribute to improving media for the effective development and growth of A. cantonensis. The gap in the A. cantonensis life cycle when the larvae are cultivated in vitro from third-stage larvae to fourth-stage larvae can thus be solved.

  18. Falls and Fall Prevention in Older Adults With Early-Stage Dementia: An Integrative Review.

    PubMed

    Lach, Helen W; Harrison, Barbara E; Phongphanngam, Sutthida

    2017-05-01

    Older adults with mild cognitive impairment (MCI) and early-stage dementia have an increased risk of falling, with risks to their health and quality of life. The purpose of the current integrative review was to evaluate evidence on fall risk and fall prevention in this population. Studies were included if they examined falls or fall risk factors in older adults with MCI or early-stage dementia, or reported interventions in this population; 40 studies met criteria. Evidence supports the increased risk of falls in individuals even in the early stages of dementia or MCI, and changes in gait, balance, and fear of falling that may be related to this increased fall risk. Interventions included exercise and multifactorial interventions that demonstrated some potential to reduce falls in this population. Few studies had strong designs to provide evidence for recommendations. Further study in this area is warranted. [Res Gerontol Nurs. 2017; 10(03):139-148.]. Copyright 2016, SLACK Incorporated.

  19. A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

    PubMed

    Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

    2017-06-01

    A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

  20. The parasitic castration and gigantism of Lymnaea truncatula infected with the larval stages of Fasciola hepatica.

    PubMed

    Wilson, R A; Denison, J

    1980-01-01

    The shells of Lymnaea truncatula infected with the larval stages of Fasciola hepatica were significantly longer than those of comparable uninfected controls. The dry mass (tissue, shell + parasite) of the same infected snails, 56 days after infection, was approximately twice that of the controls (tissue + shell). The increased mass of infected snails was not due to a disproportionate increase in shell weight relative to tissues. Infected snails maintained at 20 degrees C had virtually ceased egg production by 21 days post-infection whereas control snails continued to lay eggs steadily for the duration of the experiment. The dry mass of snail tissue plus the cumulative dry weight of eggs produced was taken as an indication of the ability of control snails to generate biomass. Similarly the tissue mass plus cumulative egg weight and parasite weight was taken as an indication of the ability of the infected snails to generate biomass. The control and infected snails were not significantly different in this respect indicating that the gigantism of infected snails could be the result of a switch in nutrient supply from reproduction to somatic tissue growth and parasite growth. Castration was brought about 17-21 days after infection as a result of the direct consumption of the ovotestis by a proportion of the redial population. In a separate experiment it was demonstrated that a population of infected snails maintained at 20 degrees C survived as long as a similar group of control snails. The findings with this host-parasite system are discussed in relation to possible mechanisms causing castration and gigantism in other digene-snail interactions, and in relation to parasitic castration in other groups. It is concluded that the observed gigantism of infected snails is more likely to have a nutritional rather than endocrine origin.

  1. Nurses' experiences using a nursing information system: early stage of technology implementation.

    PubMed

    Lee, Ting-Ting

    2007-01-01

    Adoption of information technology in nursing practice has become a trend in healthcare. The impact of this technology on users has been widely studied, but little attention has been given to its influence at the beginning stage of implementation. Knowing the barriers to adopting technology could shorten this transition stage and minimize its negative influences. The purpose of this study was to explore nurses' experiences in the early stage of implementing a nursing information system. Focus groups were used to collect data at a medical center in Taiwan. The results showed that nurses had problems with the system's content design, had insufficient training, were concerned about data security, were stressed by added work, and experienced poor interdisciplinary cooperation. To smooth this beginning stage, the author recommends involving nurses early in the system design, providing sufficient training in keyboard entry skills, redesigning workflow, and improving interdisciplinary communication.

  2. Dynamics of a Class of HIV Infection Models with Cure of Infected Cells in Eclipse Stage.

    PubMed

    Maziane, Mehdi; Lotfi, El Mehdi; Hattaf, Khalid; Yousfi, Noura

    2015-12-01

    In this paper, we propose two HIV infection models with specific nonlinear incidence rate by including a class of infected cells in the eclipse phase. The first model is described by ordinary differential equations (ODEs) and generalizes a set of previously existing models and their results. The second model extends our ODE model by taking into account the diffusion of virus. Furthermore, the global stability of both models is investigated by constructing suitable Lyapunov functionals. Finally, we check our theoretical results with numerical simulations.

  3. Two-Stage Cementless Revision Total Hip Arthroplasty for Infected Primary Hip Arthroplasties.

    PubMed

    Camurcu, Yalkin; Sofu, Hakan; Buyuk, Abdul Fettah; Gursu, Sarper; Kaygusuz, Mehmet Akif; Sahin, Vedat

    2015-09-01

    The main purpose of the present study was to analyze the clinical features, the most common infective agents, and the results of two-stage total hip revision using a teicoplanin-impregnated spacer. Between January 2005 and July 2011, 41 patients were included. At the clinical status analysis, physical examination was performed, Harris hip score was noted, isolated microorganisms were recorded, and the radiographic evaluation was performed. The mean Harris hip score was improved from 38.9 ± 9.6 points to 81.8 ± 5.8 points (P<0.05). Infection was eradicated in 39 hips. Radiographic evidence of stability was noted in 37 acetabular revision components, and all femoral stems. Two-stage revision of the infected primary hip arthroplasty is a time-consuming but a reliable procedure with high rates of success. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Photons from the early stages of relativistic heavy-ion collisions

    NASA Astrophysics Data System (ADS)

    Oliva, L.; Ruggieri, M.; Plumari, S.; Scardina, F.; Peng, G. X.; Greco, V.

    2017-07-01

    We present results about photon-production in relativistic heavy-ion collisions. The main novelty of our study is the calculation of the contribution of the early-stage photons to the photon spectrum. The initial stage is modeled by an ensemble of classical gluon fields which decay to a quark-gluon plasma via the Schwinger mechanism, and the evolution of the system is studied by coupling classical field equations to relativistic kinetic theory; photon production is then computed by including the pertinent collision processes into the collision integral. We find that the contribution of the early-stage photons to the direct photon spectrum is substantial for pT≈2 GeV and higher, the exact value depending on the collision energy; therefore, we identify this part of the photon spectrum as the sign of the early stage. Moreover, the amount of photons produced during the early stage is not negligible with respect to those produced by a thermalized quark-gluon plasma: We support the idea that there is no dark age in relativistic heavy-ion collisions.

  5. Hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro.

    PubMed

    Ng, Shengyong; March, Sandra; Galstian, Ani; Hanson, Kirsten; Carvalho, Tânia; Mota, Maria M; Bhatia, Sangeeta N

    2014-02-01

    Homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. In vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. Existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possibly due to missing microenvironmental support signals. One cue that could influence the infection capacity of cultured human hepatocytes is the dissolved oxygen concentration. We developed a microscale human liver platform comprised of precisely patterned primary human hepatocytes and nonparenchymal cells to model liver-stage malaria, but the oxygen concentrations are typically higher in the in vitro liver platform than anywhere along the hepatic sinusoid. Indeed, we observed that liver-stage Plasmodium parasite development in vivo correlates with hepatic sinusoidal oxygen gradients. Therefore, we hypothesized that in vitro liver-stage malaria infection efficiencies might improve under hypoxia. Using the infection of micropatterned co-cultures with Plasmodium berghei, Plasmodium yoelii or Plasmodium falciparum as a model, we observed that ambient hypoxia resulted in increased survival of exo-erythrocytic forms (EEFs) in hepatocytes and improved parasite development in a subset of surviving EEFs, based on EEF size. Further, the effective cell surface oxygen tensions (pO2) experienced by the hepatocytes, as predicted by a mathematical model, were systematically perturbed by varying culture parameters such as hepatocyte density and height of the medium, uncovering an optimal cell surface pO2 to maximize the number of mature EEFs. Initial mechanistic experiments revealed that treatment of primary human hepatocytes with the hypoxia mimetic, cobalt(II) chloride, as well as a HIF-1

  6. Confidence interval estimation of the difference between two sensitivities to the early disease stage.

    PubMed

    Dong, Tuochuan; Kang, Le; Hutson, Alan; Xiong, Chengjie; Tian, Lili

    2014-03-01

    Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

    PubMed

    Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

    2012-12-01

    Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. PTT functional recovery in early stage II PTTD after tendon balancing and calcaneal lengthening osteotomy.

    PubMed

    Brilhault, Jean; Noël, Vincent

    2012-10-01

    The decision to offer surgery for Stage II posterior tibial tendon deficiency (PTTD) is a difficult one since orthotic treatment has been documented to be a viable alternative to surgery at this stage. Taking this into consideration we limited our treatment to bony realignment by a lengthening calcaneus Evans osteotomy and tendon balancing. The goal of the study was to clinically evaluate PTT functional recovery with this procedure. The patient population included 17 feet in 13 patients. Inclusion was limited to early Stage II PTTD flatfeet with grossly intact but deficient PTT. Deficiency was assessed by the lack of hindfoot inversion during single heel rise test. The surgical procedure included an Evans calcaneal opening wedge osteotomy with triceps surae and peroneus brevis tendon lengthening. PTT function at follow up was evaluated by an independent examiner. Evaluation was performed at an average of 4 (range, 2 to 6.3) years. One case presented postoperative subtalar pain that required subtalar fusion. Every foot could perform a single heel rise with 13 feet having active inversion of the hindfoot during elevation. The results of this study provide evidence of PTT functional recovery without augmentation in early Stage II. It challenges our understanding of early Stage II PTTD as well as the surgical guidelines recommending PTT augmentation at this specific stage.

  9. Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

    PubMed Central

    Panas, Michael W.; Mao, Rong; Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.; Rebman, Alison W.; Montoya, Jose G.; Soloski, Mark J.; Steere, Allen C.; Dattwyler, Raymond J.; Arnaboldi, Paul M.; Aucott, John N.

    2015-01-01

    The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. PMID:26447113

  10. Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

    DTIC Science & Technology

    2015-12-01

    early stage ovarian cancer to help researchers worldwide identify biomarkers that can aid early detection and inform novel targets for therapy. This...to detect differentially expressed genes after transformation using Voom. When using the top 5 genes to build the classifier, it predicted...to analyze expression of micro-RNA in these samples. Thus, at the end of the third year of funding we started a parallel analysis of RNAseq, DNA- CNV

  11. Funding opportunities for clinical investigators in the early stages of career development in cardiovascular research.

    PubMed

    Mentz, Robert J; Becker, Richard C

    2013-11-01

    Contemporary cardiovascular research offers junior investigators the opportunity to explore the gamut of biomedical questions. Despite the recent reduction in the availability of funding mechanisms that have historically served as the primary pathways for investigators in the early stages of career development, there remain numerous traditional and non-traditional funding opportunities. This article highlights these opportunities in order to assist early career investigators in the development of a personalized research trajectory, which optimizes the potential for career success.

  12. Evaluation of Elecsys Syphilis Assay for Routine and Blood Screening and Detection of Early Infection

    PubMed Central

    Kremastinou, J.; Polymerou, V.; Lavranos, D.; Aranda Arrufat, A.; Harwood, J.; Martínez Lorenzo, M. J.; Ng, K. P.; Queiros, L.; Vereb, I.

    2016-01-01

    Treponema pallidum infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against T. pallidum. The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected T. pallidum antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results. PMID:27358468

  13. Hydrodynamic instability of elastic-plastic solid plates at the early stage of acceleration.

    PubMed

    Piriz, A R; Sun, Y B; Tahir, N A

    2015-03-01

    A model is presented for the linear Rayleigh-Taylor instability taking place at the early stage of acceleration of an elastic-plastic solid, when the shock wave is still running into the solid and is driven by a time varying pressure on the interface. When the the shock is formed sufficiently close to the interface, this stage is considered to follow a previous initial phase controlled by the Ritchmyer-Meshkov instability that settles new initial conditions. The model reproduces the behavior of the instability observed in former numerical simulation results and provides a relatively simpler physical picture than the currently existing one for this stage of the instability evolution.

  14. [Treatment of non-small cell lung carcinoma in early stages].

    PubMed

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  15. Effects of temperature on survival and development of early life stage Pacific and western brook lampreys

    Meeuwig, M.H.; Bayer, J.M.; Seelye, J.G.

    2005-01-01

    We examined the effects of temperature (10, 14, 18, and 22??C) on survival and development of Pacific lampreys Lampetra tridentata and western brook lampreys L. richardsoni during embryological and early larval stages. The temperature for zero development was estimated for each species, and the response to temperature was measured as the proportion of individuals surviving to hatch, surviving to the larval stage, and exhibiting abnormalities at the larval stage (i.e., malformations of the body). The estimated temperature for zero development was 4.850C for Pacific lampreys and 4.97??C for western brook lampreys. Survival was greatest at 18??C, followed by 14, 10, and 22??C, significant differences being observed between 22??C and the other temperatures. Overall survival was significantly greater for western brook lampreys than for Pacific lampreys; however, the overall difference in proportion of individuals surviving was only 0.02. Overall survival significantly decreased from the time of hatch (proportion surviving = 0.85) to the larval stage (0.82; i.e., during the free-embryo stage). The proportion of individuals exhibiting abnormalities at the larval stage was greatest at 22??C, followed by 18, 10, and 14??C, significant differences being observed between 22??C and the other temperatures. These data provide baseline information on the thermal requirements of early life stage Pacific and western brook lampreys and will aid in assessment and prediction of suitable spawning and rearing habitats for these species.

  16. Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages

    DeBoer, Jason A.; Pope, Kevin L.

    2015-01-01

    Determining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age-0 larval’; age 0 during autumn: ‘age-0 juvenile’; and age 1 during autumn: ‘age-1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age-0 larval, age-0 juvenile and age-1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage-specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year-class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.

  17. Sydenham chorea: clinical, EEG, MRI and SPECT findings in the early stage of the disease.

    PubMed

    Heye, N; Jergas, M; Hötzinger, H; Farahati, J; Pöhlau, D; Przuntek, H

    1993-02-01

    An 18-year-old man suffered from acute Sydenham chorea appearing coincidently with beta-haemolytic streptococcal throat infection. Imaging techniques documented lesions of basal ganglia and substantia nigra. In the early course of the disease vascular lesions may be important pathogenetic mechanisms of this acquired movement disorder.

  18. IgG avidity test for the diagnosis of acute Toxoplasma gondii infection in early pregnancy.

    PubMed

    Pour Abolghasem, Shabnam; Bonyadi, Mohammad Reza; Babaloo, Zohre; Porhasan, Abolfazl; Nagili, Behroz; Gardashkhani, Omid Ali; Salehi, Parviz; Hashemi, Mohammad; Varshoghi, Mojtaba; Gaffari, Gafar Olade

    2011-12-01

    Toxoplasmosis is well known as an important infection in pregnant women. Although many serologic methods are available, diagnosis of early Toxoplasmosis may be extremely difficult. To detect the Toxoplasma IgG antibodies developed at the early stage of infection in pregnant women. 225 pregnant women, who were in the 2nd to 4th month of their pregnancy, enrolled in this study. Anti-toxoplasma IgG, IgM and IgG avidity were evaluated by ELISA method. The patients were categorized into three groups as follows: Group A, 124 cases; IgG+, IgM+, 55.1%; group B, 99 cases; IgG+, IgM-, 44%; and group C, 2 cases; IgG -, IgM +, 0.9%. Fifty five percent of the pregnant women had positive IgG and IgM among which 7.1% had low avidity which revealed an active infection in the pregnant women. In the current study, 44% of pregnant women had positive IgG and negative IgM, all of which had high avidity, which is an indication that in our population the level of toxoplasmosis infection is high and most women have had contacts with this parasite before pregnancy. In this study, the low avidity test was 7.1% showing that the occurrence of toxoplasmosis infection is still a serious issue. Observation of 45.8% high avidity among group A suggests that either IgM has a high half-life or there is a false positive IgM as a result of rheumatologic disorders. Therefore, avidity test is important in predicting maternal toxoplasmosis which is of value in disease treatment.

  19. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

    PubMed

    Park, Jin-Young; Heo, Eun Jin; Lee, Jeong-Won; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-03-01

    Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

  20. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

    PubMed Central

    Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-01-01

    Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

  1. Divergent evolution of arrested development in the dauer stage of Caenorhabditis elegans and the infective stage of Heterodera glycines

    PubMed Central

    Elling, Axel A; Mitreva, Makedonka; Recknor, Justin; Gai, Xiaowu; Martin, John; Maier, Thomas R; McDermott, Jeffrey P; Hewezi, Tarek; McK Bird, David; Davis, Eric L; Hussey, Richard S; Nettleton, Dan; McCarter, James P; Baum, Thomas J

    2007-01-01

    Background The soybean cyst nematode Heterodera glycines is the most important parasite in soybean production worldwide. A comprehensive analysis of large-scale gene expression changes throughout the development of plant-parasitic nematodes has been lacking to date. Results We report an extensive genomic analysis of H. glycines, beginning with the generation of 20,100 expressed sequence tags (ESTs). In-depth analysis of these ESTs plus approximately 1,900 previously published sequences predicted 6,860 unique H. glycines genes and allowed a classification by function using InterProScan. Expression profiling of all 6,860 genes throughout the H. glycines life cycle was undertaken using the Affymetrix Soybean Genome Array GeneChip. Our data sets and results represent a comprehensive resource for molecular studies of H. glycines. Demonstrating the power of this resource, we were able to address whether arrested development in the Caenorhabditis elegans dauer larva and the H. glycines infective second-stage juvenile (J2) exhibits shared gene expression profiles. We determined that the gene expression profiles associated with the C. elegans dauer pathway are not uniformly conserved in H. glycines and that the expression profiles of genes for metabolic enzymes of C. elegans dauer larvae and H. glycines infective J2 are dissimilar. Conclusion Our results indicate that hallmark gene expression patterns and metabolism features are not shared in the developmentally arrested life stages of C. elegans and H. glycines, suggesting that developmental arrest in these two nematode species has undergone more divergent evolution than previously thought and pointing to the need for detailed genomic analyses of individual parasite species. PMID:17919324

  2. SPIRIT advance care planning intervention in early stage dementias: An NIH stage I behavioral intervention development trial.

    PubMed

    Song, Mi-Kyung; Ward, Sandra E; Hepburn, Kenneth; Paul, Sudeshna; Shah, Raj C; Morhardt, Darby J

    2018-06-02

    People in the early stages of Alzheimer's disease and related dementias (ADRD) are encouraged to engage in advance care planning (ACP) while they are still competent to appoint a surrogate decision maker and meaningfully participate in ACP discussions with the surrogate. In this NIH Stage I behavioral intervention development trial, we will adapt and test an efficacious ACP intervention, SPIRIT (Sharing Patient's Illness Representation to Increase Trust), with people with mild dementia and their surrogates to promote open, honest discussions while such discussions about end-of-life care are possible. We will first adapt SPIRIT (in person) to target people with mild dementia and their surrogates through a process of modification-pretesting-refinement using stakeholders (persons with mild dementia, family caregivers, and clinicians) and experts, including adapting the delivery mode to interactive web-based videoconference format (SPIRIT-remote). Then in a 3-group RCT with 120 patient-surrogate dyads, we will evaluate the feasibility and acceptability of SPIRIT in-person and SPIRIT remote, and preliminary efficacy of SPIRIT compared to usual care on preparedness outcomes for end-of-life decision making (dyad congruence on goals of care, patient decisional conflict, and surrogate decision-making confidence) shortly after the intervention. This Stage I research of SPIRIT will generate valuable insights regarding how to improve ACP for people with mild dementia who will progress to an advanced stage of the disease in the foreseeable future. ClinicalTrials.gov NCT03311711, Registered 10/12/2017. Copyright © 2018. Published by Elsevier Inc.

  3. Minimally Invasive Surgical Staging in Early-stage Ovarian Carcinoma: A Systematic Review and Meta-analysis.

    PubMed

    Bogani, Giorgio; Borghi, Chiara; Leone Roberti Maggiore, Umberto; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Lopez, Carlos; Sabatucci, Ilaria; Scaffa, Cono; Indini, Alice; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

    Few studies investigated the efficacy and safety of minimally invasive surgery for the treatment of early-stage epithelial ovarian cancer (eEOC). In this context, we aimed to review the current evidence comparing laparoscopy and the laparotomic approach for staging procedures in eEOC. This systematic review was registered in the International Prospective Register of Systematic Reviews. Overall, 3065 patients were included: 1450 undergoing laparoscopy and 1615 undergoing laparotomic staging. Patients undergoing laparoscopy experienced a longer (but not statistically significant) operative time (weighted mean difference [WMD] = 28.3 minutes; 95% confidence interval [CI], -2.59 to 59.2), a lower estimated blood loss (WMD = -156.5 mL; 95% CI, -216.4 to -96.5), a shorter length of hospital stay (WMD = -3.7 days; 95% CI, -5.2 to -2.1), and a lower postoperative complication rate (odds ratio [OR] = 0.48; 95% CI, 0.29-0.81) than patients undergoing laparotomy. The upstaging (OR = 0.81; 95% CI, 0.55-1.20) and cyst rupture (OR = 1.32; 95% CI, 0.52-3.38) rates were similar between groups. Laparoscopic staging is associated with a shorter time to chemotherapy than laparotomic procedures (WMD = -5.16 days; 95% CI, -8.68 to -1.64). Survival outcomes were not influenced by the route of surgery. Pooled data suggested that the minimally invasive surgical approach is equivalent to laparotomy for the treatment of eEOC and may be superior in terms of perioperative outcomes. However, because of the low level of evidence of the included studies, further randomized trials are warranted. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

  4. HIV Trafficking Between Blood and Semen During Early Untreated HIV Infection.

    PubMed

    Chaillon, Antoine; Smith, Davey M; Vanpouille, Christophe; Lisco, Andrea; Jordan, Parris; Caballero, Gemma; Vargas, Milenka; Gianella, Sara; Mehta, Sanjay R

    2017-01-01

    Understanding the dynamics of HIV across anatomic compartments is important to design effective eradication strategies. In this study, we evaluated viral trafficking between blood and semen during primary HIV infection in 6 antiretroviral-naive men who have sex with men. Deep sequencing data of HIV env were generated from longitudinal blood plasma, peripheral blood mononuclear cells, and seminal plasma samples. The presence or absence of viral compartmentalization was assessed using tree-based Slatkin-Maddison and distance-based Fst methods. Phylogeographic analyses were performed using a discrete Bayesian asymmetric approach of diffusion with Markov jump count estimation to evaluate the gene flow between blood and semen during primary HIV infection. Levels of DNA from human herpesviruses and selected inflammatory cytokines were also measured on genital secretions collected at baseline to evaluate potential correlates of increased viral migration between anatomic compartments. We detected varying degrees of compartmentalization in all 6 individuals evaluated. None of them maintained viral compartmentalization between blood and seminal plasma throughout the analyzed time points. Phylogeographic analyses revealed that the HIV population circulating in blood plasma populated the seminal compartment during the earliest stages of infection. In our limited data set, we found no association between local inflammation or herpesvirus shedding at baseline and viral trafficking between semen and blood. The early spread of virus from blood plasma to genital tract and the complex viral interplay between these compartments suggest that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.

  5. Impact of Early Initiation of Antiretroviral Therapy in Patients with Acute HIV Infection in Vienna, Austria

    PubMed Central

    Herout, Sandra; Mandorfer, Mattias; Breitenecker, Florian; Reiberger, Thomas; Grabmeier-Pfistershammer, Katharina; Rieger, Armin; Aichelburg, Maximilian C.

    2016-01-01

    Background It is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART. Methods We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis. Results Among the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004). Conclusions Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits. PMID:27065239

  6. New concept in histopathological grading and staging of chronic hepatitis C infection at Sharkia Governorate, Egypt.

    PubMed

    Mangoud, Amal M; Eissa, Mostafa H; Sabee, Essam I; Ibrahem, Ibrahem A; Ismail, Alaa; Morsy, Tosson A; Nor Edin, Essam; Mostafa, Yousry; Abuel-Magd, Yousry; Afefy, Afefy F; el-Shorbagy, Eman; el-Sadawy, Mahmoud; Ragab, Hosnia; Mahrous, Seham; Abdel Menem, Amal; Etewa, Samia; Hassan, Mostafa I; Lakouz, Khalid; Abdel-Aziz, Khalid; Saber, Mahmoud; el-Hady, Gaber

    2004-04-01

    Hepatitis C virus (HCV) has been estimated by the WHO to infect 170 million patients worldwide, with a high prevalence rate (about 24.5%) among Egyptians. The disease could be presented with variable hepatic lesions ranging from mild inflammation, fibrosis, cirrhosis to even end stage liver disease and hepatocellular carcinoma. The Knodell histology activity index, published in 1981, was the first system of its type and is widely regarded as the benchmark for objective, semi-quantitative reproducible description of the various morphological lesions of chronic hepatitis. Other proposals for semi-quantitative evaluation have followed. In this study, when applying these systems on the present cases (109 liver biopsies taken from Egyptian patients infected with HCV), the authors found that the presented histopathological features may be unusual for any of the known scoring systems. Therefore, they suggested a new system for grading and staging of liver diseases in Egyptian patients infected with HCV. Accordingly, the degrees of necroinflammations are classified into 3 grades (1-3) and the progression of fibrosis is classified into 3 stages (1-3). The reduced numbers of grades and stages proposed in this study may be attributed to the rapid course among Egyptians who differ in environmental circumstances from abroad.

  7. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  8. Funding opportunities for investigators in the early stages of career development.

    PubMed

    Sumandea, C Amelia; Balke, C William

    2009-03-10

    Many sources of advice and guidance are available to the early career investigator. Generally, mentors serve as the primary source of information, although program and review officers are the most underutilized resources. This article organizes these opportunities to enable early career investigators to plot a rational trajectory for career success. A list of the major agencies that provide grant support for early career investigators is included. In addition, funding opportunities are organized on the basis of the stage in career development pathway and the type of terminal degree.

  9. Portfolio management in early stage drug discovery - a traveler's guide through uncharted territory.

    PubMed

    Betz, Ulrich A K

    2011-07-01

    Portfolio management in drug development has become a best practice in the pharmaceutical industry. By contrast, early on in the value chain - the discovery phase - portfolio management is still in its infancy. Nevertheless, owing to the attrition of R&D projects from phase to phase and the cost of capital involved, these early phases of drug discovery play a significant part for the overall cost of bringing new, innovative drugs to the market. This paper describes various approaches to manage a portfolio of projects in early-stage drug discovery and provides crucial factors that determine the success of such an approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis

    PubMed Central

    Kunutsor, Setor K.; Whitehouse, Michael R.; Blom, Ashley W.; Beswick, Andrew D.

    2015-01-01

    Background The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain. Objective To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome. Design Systematic review and meta-analysis. Data Sources MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators. Study Selection Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified. Review Methods Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics. Results In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies. Conclusion Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual

  11. Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection.

    PubMed

    Jitmuang, Anupop; Yuenyongviwat, Varah; Charoencholvanich, Keerati; Chayakulkeeree, Methee

    2017-12-28

    Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012. Patient characteristics, clinical data, treatments and outcomes were evaluated. A total of 178 patients were included, among whom 162 had non-mycobacterial PJI and 16 had mycobacterial PJI. Rapidly growing mycobacteria (RGM) (11) and M. tuberculosis (MTB) (5) were the causative pathogens of mycobacterial PJI. PJI duration and time until onset were significantly different between mycobacterial and non-mycobacterial PJI. Infection within 90 days of arthroplasty was significantly associated with RGM infection (OR 21.86; 95% CI 4.25-112.30; p < .001). Implant removal was associated with improved favorable outcomes at 6 months (OR 5.96; 95% CI 1.88-18.88; p < .01) and 12 months (OR 3.96; 95% CI 1.15-13.71; p = .03) after the infection. RGM were the major pathogens of early onset PJI after THA and TKA. Both a high clinical index of suspicion and mycobacterial cultures are recommended when medically managing PJI with negative cultures or non-response to antibiotics. Removal of infected implants was associated with favorable outcomes.

  12. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

    ERIC Educational Resources Information Center

    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  13. Test Design Optimization in CAT Early Stage with the Nominal Response Model

    ERIC Educational Resources Information Center

    Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E.

    2007-01-01

    The early stage of computerized adaptive testing (CAT) refers to the phase of the trait estimation during the administration of only a few items. This phase can be characterized by bias and instability of estimation. In this study, an item selection criterion is introduced in an attempt to lessen this instability: the D-optimality criterion. A…

  14. Early-Stage Chunking of Finger Tapping Sequences by Persons Who Stutter and Fluent Speakers

    ERIC Educational Resources Information Center

    Smits-Bandstra, Sarah; De Nil, Luc F.

    2013-01-01

    This research note explored the hypothesis that chunking differences underlie the slow finger-tap sequencing performance reported in the literature for persons who stutter (PWS) relative to fluent speakers (PNS). Early-stage chunking was defined as an immediate and spontaneous tendency to organize a long sequence into pauses, for motor planning,…

  15. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

  16. Concurrent Data Elicitation Procedures, Processes, and the Early Stages of L2 Learning: A Critical Overview

    ERIC Educational Resources Information Center

    Leow, Ronald P.; Grey, Sarah; Marijuan, Silvia; Moorman, Colleen

    2014-01-01

    Given the current methodological interest in eliciting direct data on the cognitive processes L2 learners employ as they interact with L2 data during the early stages of the learning process, this article takes a critical and comparative look at three concurrent data elicitation procedures currently employed in the SLA literature: Think aloud (TA)…

  17. Laminarin improves developmental competence of porcine early stage embryos by inhibiting oxidative stress.

    PubMed

    Jiang, Hao; Liang, Shuang; Yao, Xue-Rui; Jin, Yong-Xun; Shen, Xing-Hui; Yuan, Bao; Zhang, Jia-Bao; Kim, Nam-Hyung

    2018-04-23

    Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group. Notably, LMA attenuated the intracellular reactive oxygen species generation induced by H 2 O 2 . Furthermore, LMA not only increased intracellular glutathione levels, but also ameliorated mitochondrial membrane potential. In addition, the expression of a zygotic genome activation related gene (YAP1), pluripotency-related genes (OCT4, NANOG, and SOX2), and hatching-related genes (COX2, GATA4, and ITGA5) were up-regulated following LMA supplementation during porcine early stage embryo development. These results demonstrate that LMA has beneficial effects on the development of porcine early stage embryos via regulation of oxidative stress. This evidence provides a novel method for embryo development improvement associated with exposure to LMA. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Photodynamic therapy of early stage cancer of lung, esophagus, and stomach with two different photosensitizers

    NASA Astrophysics Data System (ADS)

    Chissov, Valery I.; Sokolov, Victor V.; Trakhtenberg, A. K.; Mamontov, A. S.; Vaschakmadze, L. A.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Belous, T. A.; Gladunov, V. K.; Aristarkhova, E. I.; Zharkova, Natalia N.; Menenkov, V. D.

    1996-01-01

    The paper presents the results of photodynamic therapy (PDT) of early-stage cancer of lung (17 patients), esophagus (8 patients) and stomach (10 patients). Fifteen patients had second primary tumors. New drugs photoheme and photosens were used as photosensitizers. Complete remission was obtained in 87%. The patients are followed up without relapses to 2.5 years.

  19. Fish early life stage: Developing AOPs to support targeted reduction and replacement

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...

  20. Couple-Focused Group Intervention for Women With Early Stage Breast Cancer

    ERIC Educational Resources Information Center

    Manne, Sharon L.; Ostroff, Jamie S.; Winkel, Gary; Fox, Kevin; Grana, Generosa; Miller, Eric; Ross, Stephanie; Frazier, Thomas

    2005-01-01

    This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions…

  1. Communication in the Early Stage of Language Development in Children with CHARGE Syndrome

    ERIC Educational Resources Information Center

    Peltokorpi, Sini; Huttunen, Kerttu

    2008-01-01

    CHARGE syndrome is characterized by multiple physical abnormalities, and impaired vision and hearing. In this pilot study, communication in the early stage of language development in three one- to eight-year-old children with CHARGE syndrome was explored using video recorded free-play interaction sessions and a parental questionnaire. The children…

  2. Association Between Increased Vascular Density and Loss of Protective RAS in Early-stage NPDR

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

    2016-01-01

    Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The renin-angiotensin system (RAS) is implicated in the pathogenesis of DR and in the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population that is instrumental in vascular repair.

  3. 40 CFR 797.1600 - Fish early life stage toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

  4. 40 CFR 797.1600 - Fish early life stage toxicity test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

  5. 40 CFR 797.1600 - Fish early life stage toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

  6. Sydney, Australia Community Meets Classroom: Celebrating Families and Difference in the Early Stages of Primary Education

    ERIC Educational Resources Information Center

    Burns, Kellie

    2006-01-01

    Teachers and teacher educators are often hard pressed to find resources that creatively integrate lesbian, gay, bisexual, transgender (LGBT), and intersex issues into the early stages of primary education. While there is a growing number of academics who stress the importance of addressing topics of sexual and gender diversity during the early…

  7. Memory Club: A Group Intervention for People with Early-Stage Dementia and Their Care Partners

    ERIC Educational Resources Information Center

    Zarit, Steven H.; Femia, Elia E.; Watson, Jennifer; Rice-Oeschger, Laura; Kakos, Bernadette

    2004-01-01

    Purpose: Diagnosis of dementia in its early stages presents a window of opportunity for examining the immediate and long-term consequences of the illness at a point when the individual with memory loss can still participate in decision making. Design and Methods: Memory Club is a l0-session group program designed to provide information about…

  8. Stimuli-disassembling gold nanoclusters for diagnosis of early stage oral cancer by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Kim, Chang Soo; Ingato, Dominique; Wilder-Smith, Petra; Chen, Zhongping; Kwon, Young Jik

    2018-01-01

    A key design consideration in developing contrast agents is obtaining distinct, multiple signal changes in diseased tissue. Plasmonic gold nanoparticles (Au NPs) have been developed as contrast agents due to their strong surface plasmon resonance (SPR). This study aims to demonstrate that stimuli-responsive plasmonic Au nanoclusters (Au NCs) can be used as a contrast agent for optical coherence tomography (OCT) in detecting early-stage cancer. Au NPs were clustered via acid-cleavable linkers to synthesize Au NCs that disassemble under mildly acidic conditions into individual Au NPs, simultaneously diminishing SPR effect (quantified by scattering intensity) and increasing Brownian motion (quantified by Doppler variance). The acid-triggered morphological and accompanying optico-physical property changes of the acid-disassembling Au NCs were confirmed by TEM, DLS, UV/Vis, and OCT. Stimuli-responsive Au NCs were applied in a hamster check pouch model carrying early-stage squamous carcinoma tissue. The tissue was visualized by OCT imaging, which showed reduced scattering intensity and increased Doppler variance in the dysplastic tissue. This study demonstrates the promise of diagnosing early-stage cancer using molecularly programmable, inorganic nanomaterial-based contrast agents that are capable of generating multiple, stimuli-triggered diagnostic signals in early-stage cancer.[Figure not available: see fulltext.

  9. "It's the Bread and Butter of Our Practice": Experiencing the Early Years Foundation Stage

    ERIC Educational Resources Information Center

    Roberts-Holmes, Guy

    2012-01-01

    This article presents the experiences of nursery and primary head teachers (n = 12) on the English Early Years Foundation Stage (EYFS) after its first year of implementation in 2010. Findings are drawn from a subset of data (head teachers of primary and nursery schools) which forms part of a larger Department for Children, Schools and Families…

  10. Towards a Conceptualization of the Early Career Stage of Principalship: Current Research, Idiosyncrasies and Future Directions

    ERIC Educational Resources Information Center

    Oplatka, Izhar

    2012-01-01

    This review aims at providing a synthesis of the scholarship that has sought to expand the understanding of the early career stage of principalship by documenting the experiences and tasks of new principals (NPs) in the first three years in the post, and their personal and organizational determinants. The synthesis is based on empirical research…

  11. Responding to the Challenges of Active Citizenship through the Revised UK Early Years Foundation Stage Curriculum

    ERIC Educational Resources Information Center

    Baker, Fiona S.

    2013-01-01

    The revised UK Early Years Foundation Stage (EYFS) now places a stronger emphasis on personal, social and emotional development (PSED) as one of its three prime areas. PSED has three characteristics of learning: active learning, creating and thinking critically, and playing and exploring. These aspects of the revised EYFS closely align with the…

  12. Predictive Coding Accelerates Word Recognition and Learning in the Early Stages of Language Development

    ERIC Educational Resources Information Center

    Ylinen, Sari; Bosseler, Alexis; Junttila, Katja; Huotilainen, Minna

    2017-01-01

    The ability to predict future events in the environment and learn from them is a fundamental component of adaptive behavior across species. Here we propose that inferring predictions facilitates speech processing and word learning in the early stages of language development. Twelve- and 24-month olds' electrophysiological brain responses to heard…

  13. Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing.

    PubMed

    Parisi, Maria Candida Ribeiro; Godoy-Santos, Alexandre Leme; Ortiz, Rafael Trevisan; Sposeto, Rafael Barban; Sakaki, Marcos Hideyo; Nery, Marcia; Fernandes, Tulio Diniz

    2013-01-01

    One of the most common gold standards for the treatment of Charcot neuroarthropathy (CN) in the early Eichenholtz stages I and II is immobilization with the total contact casting and lower limb offloading. However, the total amount of offloading is still debatable. This study evaluates the clinical and radiographic findings in the treatment of early stages of CN (Eichenholtz stages I and II) with a walker boot and immediate total weight-bearing status. Twenty-two patients with type 2 diabetes mellitus (DM) and CN of Eichenholtz stages I and II were selected for non-operative treatment. All patients were educated about their condition, and full weight bearing was allowed as tolerated. Patients were monitored on a fortnightly basis in the earlier stages, with clinical examination, temperature measurement, and standardized weight-bearing radiographs. Their American Orthopedic Foot and Ankle Society (AOFAS) scores were determined before and after the treatment protocol. No cutaneous ulcerations or infections were observed in the evaluated cases. The mean measured angles at the beginning and end of the study, although showing relative increase, did not present a statistically significant difference (p > 0.05). Mean AOFAS scores showed a statistically significant improvement by the end of the study (p < 0.005). The treatment of early stages of CN (Eichenholtz stages I and II) with emphasis on walker boot and immediate weight bearing has shown a good functional outcome, non-progressive deformity on radiographic assessment, and promising results as a safe treatment option.

  14. Dual odontogenic origins develop at the early stage of rat maxillary incisor development.

    PubMed

    Kriangkrai, Rungarun; Iseki, Sachiko; Eto, Kazuhiro; Chareonvit, Suconta

    2006-03-01

    Developmental process of rat maxillary incisor has been studied through histological analysis and investigation of tooth-related gene expression patterns at initial tooth development. The tooth-related genes studied here are fibroblast growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium and/or ectomesenchyme at the stage of epithelial thickening to the early bud stage of tooth development. Both the histological observation and tooth-related gene expression patterns during early stage of maxillary incisor development demonstrate that dual odontogenic origins aligned medio-laterally in the medial nasal process develop, subsequently only single functional maxillary incisor dental placode forms. The cascade of tooth-related gene expression patterns in rat maxillary incisor studied here is quite similar to those of the previous studies in mouse mandibular molar, even though the origins of oral epithelium and ectomesenchyme involved in development of maxillary incisor and mandibular molar are different. Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development.

  15. Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

    PubMed

    Nagasaka, Misako; Gadgeel, Shirish M

    2018-01-01

    Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

  16. Single-stage revision for fungal peri-prosthetic joint infection: a single-centre experience.

    PubMed

    Klatte, T O; Kendoff, D; Kamath, A F; Jonen, V; Rueger, J M; Frommelt, L; Gebauer, M; Gehrke, T

    2014-04-01

    Fungal peri-prosthetic infections of the knee and hip are rare but likely to result in devastating complications. In this study we evaluated the results of their management using a single-stage exchange technique. Between 2001 and 2011, 14 patients (ten hips, four knees) were treated for a peri-prosthetic fungal infection. One patient was excluded because revision surgery was not possible owing to a large acetabular defect. One patient developed a further infection two months post-operatively and was excluded from the analysis. Two patients died of unrelated causes. After a mean of seven years (3 to 11) a total of ten patients were available for follow-up. One patient, undergoing revision replacement of the hip, had a post-operative dislocation. Another patient, undergoing revision replacement of the knee, developed a wound infection and required revision 29 months post-operatively following a peri-prosthetic femoral fracture. The mean Harris hip score increased to 74 points (63 to 84; p < 0.02) in those undergoing revision replacement of the hip, and the mean Hospital for Special Surgery knee score increased to 75 points (70 to 80; p < 0.01) in those undergoing revision replacement of the knee. A single-stage revision following fungal peri-prosthetic infection is feasible, with an acceptable rate of a satisfactory outcome.

  17. Following iron speciation in the early stages of magnetite magnetosome biomineralization

    DOE PAGES

    Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; ...

    2016-02-26

    Understanding magnetosome magnetite biomineralization is of fundamental interest to devising the strategies for bioinspired synthesis of magnetic materials at the nanoscale. Thus, we investigated the early stages of magnetosome formation in this work and correlated the size and emergent crystallinity of magnetosome nanoparticles with the changes in chemical environment of iron and oxygen by utilizing advanced analytical electron microscopy techniques. We observed that magnetosomes in the early stages of biomineralization with the sizes of 5–10 nm were amorphous, with a majority of iron present as Fe 3+, indicative of ferric hydroxide. The magnetosomes with intermediate sizes showed partially crystalline structuremore » with a majority of iron present as Fe 3+ and trace amounts of Fe 2+. The fully maturated magnetosomes were indexed to magnetite. Furthermore, our approach provides spatially resolved structural and chemical information of individual magnetosomes with different particle sizes, attributed to magnetosomes at different stages of biomineralization.« less

  18. Association Between Increased Vascular Density and Loss of Protective RAS in Early-Stage NPDR

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K . V.; Parsons-Wingerter, Patricia

    2016-01-01

    Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The prevailing paradigm of NPDR progression is that vessels drop out prior to abnormal, vision-impairing regrowth at late-stage proliferative diabetic retinopathy (DR). However, surprising results for our previous preliminary study 1 with NASA's VESsel GENeration Analysis (VESGEN) software showed that vessels proliferated considerably during moderate NPDR compared to drop out at both mild and severe NPDR. Validation of our hypothesis will support development of successful early-stage regenerative therapies such as vascular repair by circulating angiogenic cells (CACs). The renin-angiotensin system (RAS)is implicated in the pathogenesis of DR and in the function of CACs, a critical bone marrow-derived population that is instrumental in vascular repair.

  19. The power of personality in discriminating between healthy aging and early-stage Alzheimer's disease.

    PubMed

    Duchek, Janet M; Balota, David A; Storandt, Martha; Larsen, Randy

    2007-11-01

    This study examined differences in personality in the earliest stages of dementia of the Alzheimer type (DAT) relative to healthy aging, and the power of personality in discriminating healthy aging from early-stage DAT. Four groups of participants (middle-aged controls, older controls, persons with very mild DAT, and persons with mild DAT) and their families were administered Costa and McCrae's NEO Five-Factor Inventory. On the basis of both self-report and informant report, there was an increase in neuroticism and a decrease in conscientiousness in persons with very mild DAT relative to healthy individuals without it, and in persons with mild DAT relative to those with very mild DAT. Moreover, informant reports of neuroticism and conscientiousness capture substantial unique variance in discriminating healthy aging and very mild DAT, above and beyond standard neuropsychological tests. Discussion focuses on the importance of personality traits as a noncognitive indicator of early-stage DAT.

  20. The treatment of recurrent chronic infected knee arthroplasty with a 2-stage procedure.

    PubMed

    Antoci, Valentin; Phillips, Matthew J; Antoci, Valentin; Krackow, Kenneth A

    2009-01-01

    We report the case of a patient with recurrent periprosthetic infections after total knee arthroplasty associated with bone destruction and massive bone loss that was successfully treated with a 2-stage procedure-resection arthroplasty with insertion of an antibiotic-impregnated cement rod-spacer and systemic antibiotics and then a resection arthrodesis of the knee with the use of an intercalary allograft fixed with a long intramedullary nail. This technique is a viable option for the treatment of recurrent periprosthetic infections after total knee arthroplasty associated with bone destruction, massive bone loss, and severe instability.

  1. Ion currents involved in oocyte maturation, fertilization and early developmental stages of the ascidian Ciona intestinalis.

    PubMed

    Tosti, Elisabetta; Gallo, Alessandra; Silvestre, Francesco

    2011-01-01

    Electrophysiological techniques were used to study the role of ion currents in the ascidian Ciona intestinalis oocyte plasma membrane during different stages of growth, meiosis, fertilization and early development. Three stages of immature oocytes were discriminated in the ovary, with the germinal vesicle showing specific different features of growth and maturation. Stage-A (pre-vitellogenic) oocytes exhibited the highest L-type calcium current activity and were incompetent for meiosis resumption. Stage-B (vitellogenic) oocytes showed a progressive disappearance of calcium currents and the first appearance of sodium currents that remained high during the maturation process, up to the post-vitellogenic stage-C oocytes. The latter had acquired meiotic competence, undergoing spontaneous in vitro maturation and interacting with the spermatozoon. However, fertilized oocytes did not produce normal larvae, suggesting that cytoplasmic maturation may affect embryo development. In mature oocytes at the metaphase I stage, sodium currents were present and remained high up to the zygote stage. Oocytes fertilized in the absence of sodium showed significant reduction of the fertilization current amplitude and high development of anomalous "rosette" embryos. Current amplitudes became negligible in embryos at the 2- and 4-cell stage, whereas resumption of all the current activities occurred at the 8-cell embryo. Taken together, these results suggest: (i) an involvement of L-type calcium currents in initial oocyte meiotic progression and growth; (ii) a role of sodium currents at fertilization; (iii) a role of the fertilization current in ensuring normal embryo development. Copyright © 2011 Wiley Periodicals, Inc.

  2. Balancing risk and benefit in early-stage classical Hodgkin lymphoma.

    PubMed

    Bröckelmann, Paul J; Sasse, Stephanie; Engert, Andreas

    2018-04-12

    With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP escalated ) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [ 18 F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP escalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients. © 2018 by The American Society of Hematology.

  3. Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

    PubMed

    Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

    2018-04-01

    Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

  4. Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients.

    PubMed

    Park, Ji Young; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Kim, Dae-Yeon; Sohn, Insuk; Lee, Shin-Wha; Sung, Chang Ohk; Kim, Kyu-Rae

    2013-03-01

    Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62-2.27) was demonstrated in USC than in G3EC (P < 0.001). In conclusion, our study reveals that USC is associated with a poorer prognosis compared with G3EC, only in patients with early stage carcinoma, suggesting that different treatment strategies should be considered according to the histologic type in order to improve treatment outcome.

  5. Prognostic model for survival in patients with early stage cervical cancer.

    PubMed

    Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

    2011-02-15

    In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

  6. Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

    NASA Astrophysics Data System (ADS)

    Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

    2016-03-01

    Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

  7. Cysts mark the early stage of metastatic tumor development in non-small cell lung cancer

    PubMed Central

    Thakur, Chitra; Rapp, Ulf R.; Rudel, Thomas

    2018-01-01

    Identifying metastatic tumor growth at an early stage has been one of the biggest challenges in the treatment of lung cancer. By genetic lineage tracing approach in a conditional model of Non-Small Cell Lung Cancer (NSCLC) in mice, we demonstrate that cystic lesions represent an early stage of metastatic invasion. We generated a mouse model for NSCLC which incorporated a heritable DsRed fluorescent tag driven by the ubiquitous CAG promoter in the alveolar type II cells of the lung. We found early cystic lesions in a secondary organ (liver) that lacked the expression of bona fide lung makers namely Scgb1a1 and surfactant protein C Sftpc and were DsRed positive hence identifying lung as their source of origin. This demonstrates the significant potential of alveolar type II cells in orchestrating the process of metastasis, rendering it as one of the target cell types of the lung of therapeutic importance in human NSCLC. PMID:29464089

  8. Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

    2014-01-01

    Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

  9. Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.

    PubMed

    Alaoui, Lamine; Palomino, Gustavo; Zurawski, Sandy; Zurawski, Gerard; Coindre, Sixtine; Dereuddre-Bosquet, Nathalie; Lecuroux, Camille; Goujard, Cecile; Vaslin, Bruno; Bourgeois, Christine; Roques, Pierre; Le Grand, Roger; Lambotte, Olivier; Favier, Benoit

    2018-05-01

    Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.

  10. Two-stage revision of septic knee prosthesis with articulating knee spacers yields better infection eradication rate than one-stage or two-stage revision with static spacers.

    PubMed

    Romanò, C L; Gala, L; Logoluso, N; Romanò, D; Drago, L

    2012-12-01

    The best method for treating chronic periprosthetic knee infection remains controversial. Randomized, comparative studies on treatment modalities are lacking. This systematic review of the literature compares the infection eradication rate after two-stage versus one-stage revision and static versus articulating spacers in two-stage procedures. We reviewed full-text papers and those with an abstract in English published from 1966 through 2011 that reported the success rate of infection eradication after one-stage or two-stage revision with two different types of spacers. In all, 6 original articles reporting the results after one-stage knee exchange arthoplasty (n = 204) and 38 papers reporting on two-stage revision (n = 1,421) were reviewed. The average success rate in the eradication of infection was 89.8% after a two-stage revision and 81.9% after a one-stage procedure at a mean follow-up of 44.7 and 40.7 months, respectively. The average infection eradication rate after a two-stage procedure was slightly, although significantly, higher when an articulating spacer rather than a static spacer was used (91.2 versus 87%). The methodological limitations of this study and the heterogeneous material in the studies reviewed notwithstanding, this systematic review shows that, on average, a two-stage procedure is associated with a higher rate of eradication of infection than one-stage revision for septic knee prosthesis and that articulating spacers are associated with a lower recurrence of infection than static spacers at a comparable mean duration of follow-up. IV.

  11. Astronomical Constraints on the Duration of Early Jurassic Stages and Global Carbon Cycle and Climatic Perturbations

    NASA Astrophysics Data System (ADS)

    Ruhl, M.; Hesselbo, S. P.; Hinnov, L.; Jenkyns, H. C.; Storm, M.; Xu, W.; Riding, J. B.; Ullmann, C. V.

    2015-12-01

    The Early Jurassic (201.3 to 174.1 Ma) is bracketed by the end-Triassic mass extinction and global warming event, and the Toarcian-Aalenian shift to (global) icehouse conditions (McElwain et al., 1999; Hesselbo et al., 2002; Ruhl et al., 2011; Korte et al., in review). It is further marked by the early Toarcian Oceanic Anoxic Event (T-OAE), with possibly the largest exogenic carbon cycle perturbation of the Mesozoic and related perturbations in global geochemical cycles, climate and the environment, which are linked to large igneous province emplacement in the Karoo-Ferrar region (Jenkyns, 2010; Burgess et al., 2015). Furthermore, Early Jurassic continental rifting and the break-up of Pangaea and subsequent Early Jurassic opening of the Hispanic Corridor and Viking Strait respectively linked the equatorial Tethys Ocean to Eastern Panthalassa and the high-latitude Arctic Boreal realm. This initiated changes in (global) ocean currents and Earth's heat distribution and ultimately was followed by the opening of the proto-North Atlantic (Porter et al., 2013; Korte et al., in review). Here, we present high-resolution (sub-precession scale) elemental concentration data from the Mochras borehole (UK), which represents ~1300m of possibly the most complete and expanded lower Jurassic hemi-pelagic marine sedimentary archive known. We construct a floating ~9 Myr astronomical time-scale for the complete Early Jurassic Pliensbachian stage and biozones. Combined with radiometric and astrochronological constraints on early Jurassic stage boundaries, we construct a new Early Jurassic Time-Scale. With this we assess the duration and rate of change of early Jurassic global carbon cycle and climatic perturbations and we asses fundamental changes in the nature and expression of Early Jurassic long (100 - 1000 kyr) eccentricity cycles.

  12. Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.

    PubMed

    Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

    2016-04-01

    To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. © 2016 Associated Professional Sleep Societies, LLC.

  13. Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

    PubMed

    Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

    2016-04-01

    Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Financial Implication of Radioactive Iodine Therapy for Early-Stage Papillary Thyroid Cancer.

    PubMed

    Al-Qurayshi, Zaid; Bu Ali, Daniah; Srivastav, Sudesh; Kandil, Emad

    2017-01-01

    The aim of this study was to evaluate disease-specific survival and cost related to radioactive iodine therapy (RAI) utilization in patients with early-stage papillary thyroid carcinoma (PTC). This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2012. A total of 38,374 patients with PTC were identified. Of those, 56.3% had adjuvant RAI. RAI administration was not associated with a survival advantage in patients with PTC stage I (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.11, 14.54; p = 0.85) or stage II (HR 0.50, 95% CI 0.05, 4.88; p = 0.55). Patients with PTC stage III who underwent adjuvant RAI had an improved survival (HR 0.30, 95% CI 0.10, 0.91; p = 0.033). In 2012, RAI was used in 45.5% of patients with stage I and in 71.4% of patients with stage II. The total expenditure on adjuvant RAI for PTC stage I throughout the study period was estimated to be USD 82.3 million with an annual average of USD 9.1 (±2.0) million/year. If the decline rate in the utilization of RAI continued, the model projected that the annual expenditure would decrease by USD 0.14 million/year. There is a high prevalence of adjuvant RAI utilization for early-stage PTC that is causing financial burden on the health system with no evidence of survival benefit. © 2017 S. Karger AG, Basel.

  15. Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

    PubMed Central

    Alam, Syed Benazir

    2015-01-01

    ABSTRACT RNA viruses often depend on host factors for multiplication inside cells due to the constraints of their small genome size and limited coding capacity. One such factor that has been exploited by several plant and animal viruses is heat shock protein 70 (HSP70) family homologs which have been shown to play roles for different viruses in viral RNA replication, viral assembly, disassembly, and cell-to-cell movement. Using next generation sequence analysis, we reveal that several isoforms of Hsp70 and Hsc70 transcripts are induced to very high levels during cucumber necrosis virus (CNV) infection of Nicotiana benthamiana and that HSP70 proteins are also induced by at least 10-fold. We show that HSP70 family protein homologs are co-opted by CNV at several stages of infection. We have found that overexpression of Hsp70 or Hsc70 leads to enhanced CNV genomic RNA, coat protein (CP), and virion accumulation, whereas downregulation leads to a corresponding decrease. Hsc70-2 was found to increase solubility of CNV CP in vitro and to increase accumulation of CNV CP independently of viral RNA replication during coagroinfiltration in N. benthamiana. In addition, virus particle assembly into virus-like particles in CP agroinfiltrated plants was increased in the presence of Hsc70-2. HSP70 was found to increase the targeting of CNV CP to chloroplasts during infection, reinforcing the role of HSP70 in chloroplast targeting of host proteins. Hence, our findings have led to the discovery of a highly induced host factor that has been co-opted to play multiple roles during several stages of the CNV infection cycle. IMPORTANCE Because of the small size of its RNA genome, CNV is dependent on interaction with host cellular components to successfully complete its multiplication cycle. We have found that CNV induces HSP70 family homologs to a high level during infection, possibly as a result of the host response to the high levels of CNV proteins that accumulate during infection

  16. Stage-structured infection transmission and a spatial epidemic: a model for Lyme disease.

    PubMed

    Caraco, Thomas; Glavanakov, Stephan; Chen, Gang; Flaherty, Joseph E; Ohsumi, Toshiro K; Szymanski, Boleslaw K

    2002-09-01

    A greater understanding of the rate at which emerging disease advances spatially has both ecological and applied significance. Analyzing the spread of vector-borne disease can be relatively complex when the vector's acquisition of a pathogen and subsequent transmission to a host occur in different life stages. A contemporary example is Lyme disease. A long-lived tick vector acquires infection during the larval blood meal and transmits it as a nymph. We present a reaction-diffusion model for the ecological dynamics governing the velocity of the current epidemic's spread. We find that the equilibrium density of infectious tick nymphs (hence the risk of human disease) can depend on density-independent survival interacting with biotic effects on the tick's stage structure. The local risk of infection reaches a maximum at an intermediate level of adult tick mortality and at an intermediate rate of juvenile tick attacks on mammalian hosts. If the juvenile tick attack rate is low, an increase generates both a greater density of infectious nymphs and an increased spatial velocity. However, if the juvenile attack rate is relatively high, nymph density may decline while the epidemic's velocity still increases. Velocities of simulated two-dimensional epidemics correlate with the model pathogen's basic reproductive number (R0), but calculating R0 involves parameters of both host infection dynamics and the vector's stage-structured dynamics.

  17. One-stage revision of infected hip arthroplasty: outcome of 39 consecutive hips.

    PubMed

    Ilchmann, Thomas; Zimmerli, Werner; Ochsner, Peter Emil; Kessler, Bernhard; Zwicky, Lukas; Graber, Peter; Clauss, Martin

    2016-05-01

    There are various options for treating periprosthetic joint infection (PJI). Two-stage exchange has traditionally been the gold standard. However, if the appropriate surgical intervention is chosen according to a rational algorithm, the outcome is similar when using all types of interventions. In an observational cohort study, the outcome of patients with PJI after hip replacement treated with one-stage revision was analysed. All patients fulfilling all criteria for one-stage exchange according to the Infectious Diseases Society of America (IDSA) guidelines and six without preoperative identification of a microorganism were included. Implant removal, debridement and cemented or uncemented reimplantations were performed in a single intervention. If a cemented device was implanted, commercially available gentamicin cement was used in all cases. Antibiotic treatment was administered intravenously for at least 2 weeks, followed by oral therapy for a total duration of 3 months. Patients had standardised clinical and radiological follow-up visits. Between 1996 and 2011, 38 patients (39 hips) were treated with a one-stage procedure and followed for at least 2 years. Coagulase-negative staphylococci were the most frequent pathogens, and polymicrobial infection was observed in five cases. In 25 hips, an uncemented revision stem was implanted, and 37 hips received an acetabular reinforcement ring. The mean follow-up was 6.6 (2.0-15.1) years. No patient had persistent, recurrent or new infection. There were four stem revisions for aseptic loosening. The mean Harris Hip Score was 81 points (26-99) at the final follow-up. Excellent cure rate and function seen in our study suggest that one-stage exchange is a safe procedure, even without local antibiotic treatment, provided that the patient has no sinus tract or severe soft tissue damage, no major bone grafting is required and the microorganism is susceptible to orally administered agents with high bioavailability.

  18. Identification of early B cell precursors (stage 1 and 2 hematogones) in the peripheral blood.

    PubMed

    Kurzer, Jason H; Weinberg, Olga K

    2018-05-25

    Differentiating malignant B-lymphoblasts from early benign B cell precursors (hematogones) is a vital component of the diagnosis of B-lymphoblastic leukaemia. It has been previously reported that only late-stage B cell precursors circulate in the peripheral blood. Consequently, flow cytometric detection of cells with immunophenotypic findings similar to earlier stage precursors in the peripheral blood justifiably raises concern for involvement by B-lymphoblastic leukaemia. We report here, however, that benign early B cell precursors can indeed be detected in the peripheral blood, thus complicating the interpretation of flow cytometric findings derived from these sample types. A retrospective search of our collective databases identified 13 cases containing circulating early stage B cell precursors. The patients ranged in age from 15 days to 85 years old. All positive cases demonstrated that the earlier B cell precursors were associated with later stage precursors, a finding that could help differentiate these cells from B-lymphoblastic leukaemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study.

    PubMed

    Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

    2012-04-01

    Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. To explore processes underpinning the implementation of CKD management in primary care. Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity.

  20. [Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

    PubMed

    Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

    2017-02-20

    Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

  1. Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

    PubMed

    Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

    2011-01-01

    Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.

  2. Adjuvant therapy in early-stage non-small cell lung cancer.

    PubMed

    Serke, Monika

    2010-01-01

    Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

  3. Optimization of a novel enzyme treatment process for early-stage processing of sheepskins.

    PubMed

    Lim, Y F; Bronlund, J E; Allsop, T F; Shilton, A N; Edmonds, R L

    2010-01-01

    An enzyme treatment process for early-stage processing of sheepskins has been previously reported by the Leather and Shoe Research Association of New Zealand (LASRA) as an alternative to current industry operations. The newly developed process had marked benefits over conventional processing in terms of a lowered energy usage (73%), processing time (47%) as well as water use (49%), but had been developed as a "proof of principle''. The objective of this work was to develop the process further to a stage ready for adoption by industry. Mass balancing was used to investigate potential modifications for the process based on the understanding developed from a detailed analysis of preliminary design trials. Results showed that a configuration utilising a 2 stage counter-current system for the washing stages and segregation and recycling of enzyme float prior to dilution in the neutralization stage was a significant improvement. Benefits over conventional processing include a reduction of residual TDS by 50% at the washing stages and 70% savings on water use overall. Benefits over the un-optimized LASRA process are reduction of solids in product after enzyme treatment and neutralization stages by 30%, additional water savings of 21%, as well as 10% savings of enzyme usage.

  4. Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling.

    PubMed

    Sachdeva, Meenakshi; Sharma, Aman; Arora, Sunil K

    2015-01-01

    Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs). The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART). Phenotypic and functional characteristics of circulating myeloid DCs (mDCs) in 56 ART-naive patients (23 in early and 33 in advanced stage of disease), 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs) were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS)-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR. The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase (SHP)-1 and a reduced expression of positive regulators like Janus kinase (JAK)2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells. Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral replication at this stage of disease, needs

  5. Driving in Early-Stage Alzheimer's Disease: An Integrative Review of the Literature.

    PubMed

    Davis, Rebecca L; Ohman, Jennifer M

    2017-03-01

    One of the most difficult decisions for individuals with Alzheimer's disease (AD) is when to stop driving. Because driving is a fundamental activity linked to socialization, independent functioning, and well-being, making the decision to stop driving is not easy. Cognitive decline in older adults can lead to getting lost while driving, difficulty detecting and avoiding hazards, as well as increased errors while driving due to compromised judgment and difficulty in making decisions. The purpose of the current literature review was to synthesize evidence regarding how individuals with early-stage AD, their families, and providers make determinations about driving safety, interventions to increase driving safety, and methods to assist cessation and coping for individuals with early-stage AD. The evidence shows that changes in driving ability start early and progress throughout the trajectory of AD. Some individuals with mild cognitive impairment or early-stage AD may be safe to drive for a period of time. Support groups aimed at helping with the transition have been shown to be helpful for individuals who stop driving. Research and practice must support interventions to help individuals maintain safety while driving, as well as cope with driving cessation. [Res Gerontol Nurs. 2017; 10(2):86-100.]. Copyright 2016, SLACK Incorporated.

  6. Distribution of early life history stages of fishes in selected pools of the upper Mississippi River

    Holland, L.E.

    1986-01-01

    Effective management of the fishery resources of the Upper Mississippi River and successful mitigation of the loss of critical habitat depend in part on an understanding of the reproductive and early life history requirements of the affected fishes. However, little is known about the use of nursery areas by fishes in the river. Of the nearly 130 species identified in the adult ichthyofauna, only a few are represented proportionally in the available data on early life stages because study designs have not included consideration of the early stages, collection gears have not adequately sampled the young, and eggs and larvae of some species are difficult to sample by conventional approaches. For the species collected, information is available on seasonal variations in total densities, composition, and catch among different habitat types. However, the data are most accurate for species with buoyant early life stages, such as freshwater drum (Aplodinotus grunniens) and gizzard shad (Dorosoma cepedianum). Eggs and larvae of freshwater drum dominate collections made in the main channel, whereas other larval fishes are usually most abundant in backwater habitats. The species found there usually deposit eggs on the substrate or on vegetation. Habitat preferences (as indicated by relative abundance) often shift as development proceeds and physical and behavioral changes occur in the larvae. Only limited information is available on the distribution of larvae within habitats, but it is clear that variations within habitats are significant.

  7. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

    PubMed

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

  8. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

    PubMed Central

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

  9. Involvement of Clostridium botulinum ATCC 3502 Sigma Factor K in Early-Stage Sporulation

    PubMed Central

    Kirk, David G.; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu

    2012-01-01

    A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σK is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods. PMID:22544236

  10. Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.

    PubMed

    Popken, Jens; Schmid, Volker J; Strauss, Axel; Guengoer, Tuna; Wolf, Eckhard; Zakhartchenko, Valeri

    2016-04-22

    Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling

  11. Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

    PubMed

    Gadgeel, Shirish M

    2017-01-01

    On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

  12. Involvement of Clostridium botulinum ATCC 3502 sigma factor K in early-stage sporulation.

    PubMed

    Kirk, David G; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu; Lindström, Miia

    2012-07-01

    A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σ(K) is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods.

  13. Occurrence of lymph node metastasis in early-stage parotid gland cancer.

    PubMed

    Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

    2012-02-01

    Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

  14. Usability of tablet computers by people with early-stage dementia.

    PubMed

    Lim, Fabian S; Wallace, Tim; Luszcz, Mary A; Reynolds, Karen J

    2013-01-01

    Tablet computers are generally associated with an intuitive interface. The adoption and use of tablet computers within the early-stage dementia context could potentially assist in daily living and provide users with a source for leisure activities and social networking. As dementia mainly affects the older adult population, it is expected that many people with dementia and even their carers do not use tablet computers as part of their everyday living. This paper explores the usability of tablet computers within the early-stage dementia context as a source of leisure for people with dementia. The main advantage of the use of tablet computers in this manner is to provide carers some reprieve from the constant care and attention often required in caring for people with dementia. Seven-day in-home trials were conducted to determine whether people with early-stage dementia were -capable of using a tablet computer independently. Twenty-one people with early-stage dementia and carer dyads participated in the trial. Feedback was gathered through questionnaires from both the person with dementia and their carer regarding the use of a tablet computer as part of their everyday living. Approximately half the participants with dementia were able to engage with and use the tablet computer independently, which proved to be helpful to their carers. No significant traits were observed to help identify those who were less likely to use a tablet computer. Carer relief was quantified by the amount of time participants with dementia spent using the device without supervision. The results and feedback from the trial provide significant insights to introducing new technology within the early-stage dementia context. Users' needs must be considered on a case-by-case basis to successfully facilitate the uptake of tablet computers in the dementia context. The trial has provided sufficient justification to further explore more uses of tablet computers in the dementia context, and not just for

  15. Infections of Larval Stages of Dicrocoelium dendriticum and Brachylaima sp. in Brown Garden Snail, Helix aspersa, in Turkey.

    PubMed

    Köse, Mustafa; Eser, Mustafa; Kartal, Kürşat; Bozkurt, Mehmet Fatih

    2015-10-01

    The aim of this study was to determine the presence and prevalence of larval stages of Dicrocoelium dendriticum and Brachylaima sp. in the first intermediate host, a species of land snail, Helix aspersa, in Turkey. A total of 211 snails were collected in April-May 2014 from pastures in Mersin District. Larval stages of D. dendriticum were identified under a light microscope. Hepatopancreas from naturally infected H. aspersa snails were examined histologically. The prevalence of larval stages of D. dendriticum and Brachylaima sp. in H. aspersa snails was found to be 2.4% and 1.9%, respectively, in Mersin, Turkey. Cercariae were not matured in sporocysts at the beginning of April; however, it was observed that cercariae matured and started to leave sporocysts by early-May. Thus, it was concluded that H. aspersa acts as an intermediate host to D. dendriticumin and Brachylaima sp. in Mersin, Turkey. A digenean trematode Brachylaima sp. was seen for the first time in Turkey.

  16. Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection.

    PubMed

    Wang, Yiming; Kwon, Soon Jae; Wu, Jingni; Choi, Jaeyoung; Lee, Yong-Hwan; Agrawal, Ganesh Kumar; Tamogami, Shigeru; Rakwal, Randeep; Park, Sang-Ryeol; Kim, Beom-Gi; Jung, Ki-Hong; Kang, Kyu Young; Kim, Sang Gon; Kim, Sun Tae

    2014-12-01

    Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L.) in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10) by RT-PCR, and phytoalexins (sakuranetin and momilactone A) with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05) in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

  17. Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells

    SciT

    Hong, Dun; Orthopedic Department, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000; Chen, Hai-Xiao, E-mail: Hxchen-1@163.net

    Bone remodeling relies on a dynamic balance between bone formation and resorption, mediated by osteoblasts and osteoclasts, respectively. Under certain stimuli, osteoprogenitor cells may differentiate into premature osteoblasts and further into mature osteoblasts. This process is marked by increased alkaline phosphatase (ALP) activity and mineralized nodule formation. In this study, we induced osteoblast differentiation in mouse osteoprogenitor MC3T3-E1 cells and divided the process into three stages. In the first stage (day 3), the MC3T3-E1 cell under osteoblast differentiation did not express ALP or deposit a mineralized nodule. In the second stage, the MC3T3-E1 cell expressed ALP but did not formmore » a mineralized nodule. In the third stage, the MC3T3-E1 cell had ALP activity and formed mineralized nodules. In the present study, we focused on morphological and proteomic changes of MC3T3-E1 cells in the early stage of osteoblast differentiation - a period when premature osteoblasts transform into mature osteoblasts. We found that mean cell area and mean stress fiber density were increased in this stage due to enhanced cell spreading and decreased cell proliferation. We further analyzed the proteins in the signaling pathway of regulation of the cytoskeleton using a proteomic approach and found upregulation of IQGAP1, gelsolin, moesin, radixin, and Cfl1. After analyzing the focal adhesion signaling pathway, we found the upregulation of FLNA, LAMA1, LAMA5, COL1A1, COL3A1, COL4A6, and COL5A2 as well as the downregulation of COL4A1, COL4A2, and COL4A4. In conclusion, the signaling pathway of regulation of the cytoskeleton and focal adhesion play critical roles in regulating cell spreading and actin skeleton formation in the early stage of osteoblast differentiation.« less

  18. Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

    PubMed Central

    Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

    2016-01-01

    Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

  19. Notch and Delta mRNAs in early-stage and mid-stage Drosophila embryos exhibit complementary patterns of protein producing potentials

    PubMed Central

    Shepherd, Andrew; Wesley, Uma; Wesley, Cedric

    2010-01-01

    Notch and Delta proteins generate Notch signaling that specifies cell fates during animal development. There is an intriguing phenomenon in Drosophila embryogenesis that has not received much attention and whose significance to embryogenesis is unknown. Notch and Delta mRNAs expressed in early-stage embryos are shorter than their counterparts in mid-stage embryos. We show here that the difference in sizes is due to mRNA 3′ processing at alternate polyadenylation sites. While the early-stage Notch mRNA has a lower protein-producing potential than the mid-stage Notch mRNA, the early-stage Delta mRNA has a higher protein-producing potential than the mid-stage Delta mRNA. Our data can explain the complementary patterns of Notch and Delta protein levels in early-stage and mid-stage embryos. Our data also raise the possibility that the manner and regulation of Notch signaling change in the course of embryogenesis and that this change is effected by 3′ UTR and mRNA 3′ processing factors. PMID:20201103

  20. [Inflammasome and its role in immunological and inflammatory response at early stage of burns].

    PubMed

    Zhang, Fang; Li, Jiahui; Xia, Zhaofan

    2014-06-01

    Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

  1. Early, asymptomatic stage of degenerative joint disease in canine hip joints.

    PubMed

    Lust, G; Summers, B A

    1981-11-01

    The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

  2. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

    PubMed Central

    Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

    2016-01-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

  3. Does a regular Wessex Head Injury Matrix assessment identify early signs of infections in people with Prolonged Disorders of Consciousness?

    PubMed

    Dhamapurkar, Samira Kashinath; Wilson, Barbara A; Rose, Anita; Florschutz, Gerhard; Watson, Peter; Shiel, Agnes

    2018-06-12

    Patients with brain injury are at high risk for infections. Although infection and cognitive deterioration are established for people with dementia, this has not been shown for patients with a prolonged disorder of consciousness (PDOC). This study determines whether regular Wessex Head Injury Matrix (WHIM) assessments can identify early signs of infections in patients with PDOC. Retrospective and prospective approaches were used to assess the WHIM scores of patients with a PDOC (N = 21 in the retrospective study and 22 in the prospective study). The WHIM total scores decreased due to infections in 17 of the 21 cases of infection (p < 0.001) in the retrospective study and 15 (p = 0.001) of the 22 prospective cases of infection. Patients in a minimally conscious state (MCS) showed a bigger proportion of change between their baseline score and the scores taken in the pre-infection stage in both the retrospective and prospective studies when compared to patients in a vegetative state (VS). The findings suggest the importance of serial WHIM assessments throughout the period of recovery, not only to measure cognitive changes but also to highlight underlying physical changes such as infections that will impact the response to rehabilitation and recovery.

  4. Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

    PubMed Central

    Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

    2014-01-01

    Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

  5. Anorectal Manometric Dysfunctions in Newly Diagnosed, Early-Stage Parkinson's Disease

    PubMed Central

    Sung, Hye Young; Kim, Yeong-In; Lee, Kwang-Soo

    2012-01-01

    Background and Purpose Anorectal dysmotility is common in advanced Parkinson's disease (PD), but there have been few evaluations in newly diagnosed PD patients. Methods We conducted anorectal manometric evaluations in 19 newly diagnosed, drug-naïve, early-stage PD patients. All of the PD patients were questioned regarding the presence of anorectal symptoms. Results Anorectal manometry was abnormal in 12 of the 19 patients. These abnormalities were more common in patients with more severe anorectal symptoms, as measured using a self-reported scale. However, more than 40% of patients with no or minimal symptoms also exhibited manometric abnormalities. Conclusions These results suggest that anorectal dysmotility manifests in many early-stage PD patients, which this represent evidence for the involvement of neuronal structures in such nonmotor manifestations in PD. PMID:23091527

  6. Early-season avian deaths from West Nile virus as warnings of human infection

    Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

    2003-01-01

    An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

  7. Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis

    PubMed Central

    Lopera, Damaris; Urán-Jiménez, Martha Eugenia

    2016-01-01

    Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 106 or 2 × 106 P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 106 yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 106 yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis. PMID:27642235

  8. Diagnostic and prognostic value of procalcitonin for early intracranial infection after craniotomy

    PubMed Central

    Yu, Y.; Li, H.J.

    2017-01-01

    Intracranial infection is a common clinical complication after craniotomy. We aimed to explore the diagnostic and prognostic value of dynamic changing procalcitonin (PCT) in early intracranial infection after craniotomy. A prospective study was performed on 93 patients suspected of intracranial infection after craniotomy. Routine peripheral venous blood was collected on the day of admission, and C reactive protein (CRP) and PCT levels were measured. Cerebrospinal fluid (CSF) was collected for routine biochemical, PCT and culture assessment. Serum and CSF analysis continued on days 1, 2, 3, 5, 7, 9, and 11. The patients were divided into intracranial infection group and non-intracranial infection group; intracranial infection group was further divided into infection controlled group and infection uncontrolled group. Thirty-five patients were confirmed with intracranial infection after craniotomy according to the diagnostic criteria. The serum and cerebrospinal fluid PCT levels in the infected group were significantly higher than the non-infected group on day 1 (P<0.05, P<0.01). The area under curve of receiver operating characteristics was 0.803 for CSF PCT in diagnosing intracranial infection. The diagnostic sensitivity and specificity of CSF PCT was superior to other indicators. The serum and CSF PCT levels have potential value in the early diagnosis of intracranial infection after craniotomy. Since CSF PCT levels have higher sensitivity and specificity, dynamic changes in this parameter could be used for early detection of intracranial infection after craniotomy, combined with other biochemical indicators. PMID:28443989

  9. Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy.

    PubMed

    Li, Changyou; Xu, Jing; Wang, Qi; Geng, Shaoqing; Yan, Zheng; You, Jin; Li, Zhenfeng; Zou, Xiao

    2018-05-01

    The present study was performed to explore the prognostic significance of periostin expression in a cohort of patients with early-stage breast cancer treated with breast conserving surgery following radiotherapy. A tissue microarray of tumor samples from 259 patients with early-stage breast cancer was assayed for periostin, estrogen receptor (ER), progesterone receptor (PR), ErbB2 receptor tyrosine kinase 2 and Ki-67 expression by immunohistochemistry. The association of periostin with other clinicopathological parameters and clinical outcomes, including local recurrence free survival (RFS), distant metastasis free survival (DFS) and overall survival (OS), were assessed through log-rank tests and univariate and multivariate analysis. Periostin expression was identified in 91 of the 259 tissue samples (35%). The periostin status was significantly associated with histological grade (P=0.001), nodal status (P=0.023), molecular subtype (P<0.01), ER status (P<0.01), PR status (P<0.01) and Ki-67 expression (P=0.011). Furthermore, periostin expression was associated with an increased risk of five-year local recurrence (95.8% vs. 89.0%; P=0.017) and distant metastasis (92.3% vs. 79.1%; P=0.001) in patients with early stage breast cancer. Multivariate analysis using Cox's proportional hazards model demonstrated that periostin expression was an independent predictor of all clinical outcomes in breast cancer (RFS, P=0.018; DFS, P=0.025; OS, P=0.047). Therefore, it was concluded that periostin is associated with an increased risk of local relapse and distant metastasis in early-stage breast cancer treated with conserving surgery and radiotherapy. This association should be further investigated in larger cohorts to validate the clinical significance of periostin expression.

  10. SU-F-R-24: Identifying Prognostic Imaging Biomarkers in Early Stage Lung Cancer Using Radiomics

    SciT

    Zeng, X; Wu, J; Cui, Y

    2016-06-15

    Purpose: Patients diagnosed with early stage lung cancer have favorable outcomes when treated with surgery or stereotactic radiotherapy. However, a significant proportion (∼20%) of patients will develop metastatic disease and eventually die of the disease. The purpose of this work is to identify quantitative imaging biomarkers from CT for predicting overall survival in early stage lung cancer. Methods: In this institutional review board-approved HIPPA-compliant retrospective study, we retrospectively analyzed the diagnostic CT scans of 110 patients with early stage lung cancer. Data from 70 patients were used for training/discovery purposes, while those of remaining 40 patients were used for independentmore » validation. We extracted 191 radiomic features, including statistical, histogram, morphological, and texture features. Cox proportional hazard regression model, coupled with the least absolute shrinkage and selection operator (LASSO), was used to predict overall survival based on the radiomic features. Results: The optimal prognostic model included three image features from the Law’s feature and wavelet texture. In the discovery cohort, this model achieved a concordance index or CI=0.67, and it separated the low-risk from high-risk groups in predicting overall survival (hazard ratio=2.72, log-rank p=0.007). In the independent validation cohort, this radiomic signature achieved a CI=0.62, and significantly stratified the low-risk and high-risk groups in terms of overall survival (hazard ratio=2.20, log-rank p=0.042). Conclusion: We identified CT imaging characteristics associated with overall survival in early stage lung cancer. If prospectively validated, this could potentially help identify high-risk patients who might benefit from adjuvant systemic therapy.« less

  11. In vivo laser confocal microscopy findings of radial keratoneuritis in patients with early stage Acanthamoeba keratitis.

    PubMed

    Kobayashi, Akira; Yokogawa, Hideaki; Yamazaki, Natsuko; Ishibashi, Yasuhisa; Oikawa, Yosaburo; Tokoro, Masaharu; Sugiyama, Kazuhisa

    2013-07-01

    To investigate in vivo corneal changes of keratoneuritis in early stage Acanthamoeba keratitis (AK) using in vivo laser confocal microscopy. Single-center, prospective, clinical study. Thirteen eyes (12 patients; 5 men and 7 women; mean age ± standard deviation, 22.3 ± 4.2 years) with keratoneuritis resulting from early stage AK were included in this study. In vivo laser confocal microscopy was performed, paying special attention to keratoneuritis. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of abnormal cells and deposits. In all patients, Acanthamoeba cysts were observed clearly in the basal epithelial cell layer as highly reflective round particles with a diameter of 10 to 20 μm. Bowman's layer infiltration of Acanthamoeba cysts was observed in only 1 case, and no cases showed stromal or nerve infiltration of Acanthamoeba cysts. In the stroma, all cases showed highly reflective activated keratocytes forming a honeycomb pattern; these changes were significant around the keratoneuritis. Infiltration of inflammatory cells, possibly polymorphonuclear cells, was observed along with keratocyte bodies in all cases. Numerous highly reflective spindle-shaped materials were observed around the keratoneuritis. Most notably, highly reflective patchy lesions were observed around the keratoneuritis in 11 cases (84.6%). Inflammatory cells also were observed in the endothelial cell layer in 4 cases (30.8%). In vivo laser confocal microscopy identified consistent corneal abnormalities around keratoneuritis in early stage AK patients, of which highly reflective patchy lesions may be characteristic of keratoneuritis. Further morphologic studies of corneas with early stage AK in a larger number of patients may elucidate the clinical significance of radial keratoneuritis and may help us to understand the interaction between Acanthamoeba organisms and host corneal cells or nerves. Copyright © 2013 American

  12. Early stages of figure-ground segregation during perception of the face-vase.

    PubMed

    Pitts, Michael A; Martínez, Antígona; Brewer, James B; Hillyard, Steven A

    2011-04-01

    The temporal sequence of neural processes supporting figure-ground perception was investigated by recording ERPs associated with subjects' perceptions of the face-vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects' figure-ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ∼ 150-200 msec) when that region was perceived as figure versus background. These components likely reflect an early "border ownership" stage, and a subsequent "figure-ground segregation" stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure-ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure-ground perception, each which are subject to modifications by selective attention.

  13. Early Stages of Figure–Ground Segregation during Perception of the Face–Vase

    PubMed Central

    Pitts, Michael A.; Martínez, Antígona; Brewer, James B.; Hillyard, Steven A.

    2011-01-01

    The temporal sequence of neural processes supporting figure–ground perception was investigated by recording ERPs associated with subjects’ perceptions of the face–vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects’ figure–ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ~150–200 msec) when that region was perceived as figure versus background. These components likely reflect an early “border ownership” stage, and a subsequent “figure–ground segregation” stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure–ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure–ground perception, each which are subject to modifications by selective attention. PMID:20146604

  14. Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens

    PubMed Central

    2018-01-01

    Objective Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. Methods Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. Results A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). Conclusion Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age. PMID:29185274

  15. Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis.

    PubMed

    Bogani, Giorgio; Fucà, Giovanni; Maltese, Giuseppa; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Sabatucci, Ilaria; Lecce, Francesca; Raspagliesi, Francesco; Lorusso, Domenica

    2016-11-01

    We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Early Stage Breast Cancer in Older Women: Predictions and Outcomes of Therapy

    DTIC Science & Technology

    2000-10-01

    found that the proportion of U.S. women with early stage breast cancer who are receiving appropriate care (defined by NIH Consensus statement) declined...surgery increased, and because women undergoing breast-conserving surgery are more likely to receive inappropriate care . We have now shown that patients... Care 2000;38:719-727. 6. Ann B. Nattinger’s Curriculum Vitae. 3 / Annual Report: Grant #DAMD17-96-1-6262 4.) INTRODUCTION Almost half of the incident

  17. [Fat emulsion tolerance in preterm infants of different gestational ages in the early stage after birth].

    PubMed

    Tang, Hui; Yang, Chuan-Zhong; Li, Huan; Wen, Wei; Huang, Fang-Fang; Huang, Zhi-Feng; Shi, Yu-Ping; Yu, Yan-Liang; Chen, Li-Lian; Yuan, Rui-Qin; Zhu, Xiao-Yu

    2017-06-01

    To investigate the fat emulsion tolerance in preterm infants of different gestational ages in the early stage after birth. A total of 98 preterm infants were enrolled and divided into extremely preterm infant group (n=17), early preterm infant group (n=48), and moderate-to-late preterm infant group (n=33). According to the dose of fat emulsion, they were further divided into low- and high-dose subgroups. The umbilical cord blood and dried blood filter papers within 3 days after birth were collected. Tandem mass spectrometry was used to measure the content of short-, medium-, and long-chain acylcarnitines. The extremely preterm infant and early preterm infant groups had a significantly lower content of long-chain acylcarnitines in the umbilical cord blood and dried blood filter papers within 3 days after birth than the moderate-to-late preterm infant group (P<0.05), and the content was positively correlated with gestational age (P<0.01). On the second day after birth, the low-dose fat emulsion subgroup had a significantly higher content of short-, medium-, and long-chain acylcarnitines than the high-dose fat emulsion subgroup among the extremely preterm infants (P<0.05). In the early preterm infant and moderate-to-late preterm infant groups, there were no significant differences in the content of short-, medium-, and long-chain acylcarnitines between the low- and high-dose fat emulsion subgroups within 3 days after birth. Compared with moderate-to-late preterm infants, extremely preterm infants and early preterm infants have a lower capacity to metabolize long-chain fatty acids within 3 days after birth. Early preterm infants and moderate-to-late preterm infants may tolerate high-dose fat emulsion in the early stage after birth, but extremely preterm infants may have an insufficient capacity to metabolize high-dose fat emulsion.

  18. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

    PubMed

    Duffy, T A; Iwanowicz, L R; McCormick, S D

    2014-07-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

  19. Improved early outcome for end-stage dilated cardiomyopathy in children.

    PubMed

    McMahon, Anne-Marie; van Doorn, Carin; Burch, Michael; Whitmore, Pauline; Neligan, Sophie; Rees, Philip; Radley-Smith, Rosemary; Goldman, Allan; Brown, Katherine; Cohen, Gordon; Tsang, Victor; Elliott, Martin; de Leval, Marc R

    2003-12-01

    To review the impact of management changes on the early outcomes of end-stage dilated cardiomyopathy in children. We conducted a retrospective study of all consecutive children with end-stage dilated cardiomyopathy who received hospital treatment since 1992. Over the past 3 years the following management changes were made: (1) more aggressive use of mechanical cardiac assistance; (2) high priority listing for transplantation; and (3) ABO incompatible transplants for infants. Outcomes for 46 patients admitted between 1992 and 1999 (group I) were compared with 53 patients between 2000 and March 2003 (group II). In group I, 12 (26%) patients received mechanical support with recovery in 3 and transplantation in 5 (1 died). In group II, 19 (36%) patients received extracorporeal membrane oxygenation, with recovery in 5 and transplantation in 12 (all survived). The use of mechanical assistance was associated with high morbidity related to bleeding, end-organ failure, and long-term mechanical ventilation. Five patients in group II received ABO incompatible transplants and all survived. There have been no episodes of rejection or need for increased immunosuppressive therapy. Hospital mortality has been significantly reduced (group I, 37% vs group II, 11%; P <.05). Recent refinements in the management of end-stage dilated cardiomyopathy in children have significantly reduced early mortality. Identification of markers of early myocardial recovery and development of mechanical devices for longer term and more physiologic support are essential to achieve further improvements in outcome.

  20. Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

    PubMed Central

    Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

    2013-01-01

    Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

  1. Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women

    PubMed Central

    Obeidat, Rana F.

    2015-01-01

    To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers’ support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system. PMID:27981122

  2. Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

    SciT

    None, None

    Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

  3. Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

    PubMed Central

    Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

    2016-01-01

    Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

  4. Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

    DOE PAGES

    None, None

    2016-03-22

    Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

  5. Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

    SciT

    Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

    2016-04-01

    Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literaturemore » are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.« less

  6. On the role of extracellular polymeric substances during early stages of Xylella fastidiosa biofilm formation.

    PubMed

    Lorite, Gabriela S; de Souza, Alessandra A; Neubauer, Daniel; Mizaikoff, Boris; Kranz, Christine; Cotta, Mônica A

    2013-02-01

    The structural integrity and protection of bacterial biofilms are intrinsically associated with a matrix of extracellular polymeric substances (EPS) produced by the bacteria cells. However, the role of these substances during biofilm adhesion to a surface remains largely unclear. In this study, the influence of EPS on Xylella fastidiosa biofilm formation was investigated. This bacterium is associated with economically important plant diseases; it presents a slow growth rate and thus allows us to pinpoint more precisely the early stages of cell-surface adhesion. Scanning electron microscopy and atomic force microscopy show evidence of EPS production in such early stages and around individual bacteria cells attached to the substrate surface even a few hours after inoculation. In addition, EPS formation was investigated via attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FTIR). To this end, X. fastidiosa cells were inoculated within an ATR liquid cell assembly. IR-ATR spectra clearly reveal EPS formation already during the early stages of X. fastidiosa biofilm formation, thereby providing supporting evidence for the hypothesis of the relevance of the EPS contribution to the adhesion process. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Ontogenetic development in the morphology and behavior of loach ( Misgurnus anguillicaudatus) during early life stages

    NASA Astrophysics Data System (ADS)

    Gao, Lei; Duan, Ming; Cheng, Fei; Xie, Songguang

    2014-09-01

    Loach ( Misgurnus anguillicaudatus) are a commercially important fish in China and an ideal aquaculture species. However, culturists experience high larval and juvenile mortality during mass production. To provide insight into ways to improve larviculture techniques, we describe the morphological characteristics and behavior of loach during the larval and early juvenile stages. Yolksac larvae ranged from 2.8 to 4.0 mm body length (BL) between days 0 to 4; preflexion larvae ranged from 3.6 to 5.5 mm BL between days 4 to 6; flexion larvae ranged from 4.8 to 8.1 mm BL between days 5 and 14; and postflexion larvae ranged from 7.1 to 15.7 mm BL between days 11 to 27; the minimum length and age of juveniles was 14.1 mm BL and 23 d, respectively. Loach are demersal from hatch through to the early juvenile stages. A suite of morphological characteristics (e.g., external gill filament and ventral mouth opening) and behavioral traits have developed to adapt to demersal living. We observed positive allometric growth in eye diameter, head length, head height, and pectoral fin length during the early larval stages, reflecting the priorities in the development of the organs essential for survival. Our results provide a basis for developing techniques to improve the survival of larval and juvenile loach during mass production.

  8. Recurrence of Early Stage Colon Cancer Predicted by Expression Pattern of Circulating microRNAs

    PubMed Central

    Shivapurkar, Narayan; Weiner, Louis M.; Marshall, John L.; Madhavan, Subha; Deslattes Mays, Anne; Juhl, Hartmut; Wellstein, Anton

    2014-01-01

    Systemic treatment of patients with early-stage cancers attempts to eradicate occult metastatic disease to prevent recurrence and increased morbidity. However, prediction of recurrence from an analysis of the primary tumor is limited because disseminated cancer cells only represent a small subset of the primary lesion. Here we analyze the expression of circulating microRNAs (miRs) in serum obtained pre-surgically from patients with early stage colorectal cancers. Groups of five patients with and without disease recurrence were used to identify an informative panel of circulating miRs using quantitative PCR of genome-wide miR expression as well as a set of published candidate miRs. A panel of six informative miRs (miR-15a, mir-103, miR-148a, miR-320a, miR-451, miR-596) was derived from this analysis and evaluated in a separate validation set of thirty patients. Hierarchical clustering of the expression levels of these six circulating miRs and Kaplan-Meier analysis showed that the risk of disease recurrence of early stage colon cancer can be predicted by this panel of miRs that are measurable in the circulation at the time of diagnosis (P = 0.0026; Hazard Ratio 5.4; 95% CI of 1.9 to 15). PMID:24400111

  9. The Treatment Effect of Porous Titanium Alloy Rod on the Early Stage Talar Osteonecrosis of Sheep

    PubMed Central

    Zhang, Yong-Quan; Zhang, Zhi-Yong; Guo, Zheng

    2013-01-01

    Osteonecrosis of the talus (ONT) may severely affect the function of the ankle joint. Most orthopedists believe that ONT should be treated at an early stage, but a concise and effective surgical treatment is lacking. In this study, porous titanium alloy rods were prepared and implanted into the tali of sheep with early-stage ONT (IM group). The curative effect of the rods was compared to treatment by core decompression (DC group). No significant differences in bone reconstruction were observed between the two groups at 1 month after intervention. After 3 months, the macroscopic view of gross specimens of the IM group showed ordinary contours, but the specimens of the DC group showed obvious partial bone defects and cartilage degeneration. Quantitative analysis of the reconstructed trabeculae by micro-CT and histological study suggested that the curative effect of the IM group was superior to that of the DC group at 3 months after intervention. These favorable short-term results of the implantation of porous titanium alloy rods into the tali of sheep with early-stage ONT may provide insight into an innovative surgical treatment for ONT. PMID:23516485

  10. Finite element simulation of ultrasonic waves in corroded reinforced concrete for early-stage corrosion detection

    NASA Astrophysics Data System (ADS)

    Tang, Qixiang; Yu, Tzuyang

    2017-04-01

    In reinforced concrete (RC) structures, corrosion of steel rebar introduces internal stress at the interface between rebar and concrete, ultimately leading to debonding and separation between rebar and concrete. Effective early-stage detection of steel rebar corrosion can significantly reduce maintenance costs and enable early-stage repair. In this paper, ultrasonic detection of early-stage steel rebar corrosion inside concrete is numerically investigated using the finite element method (FEM). Commercial FEM software (ABAQUS) was used in all simulation cases. Steel rebar was simplified and modeled by a cylindrical structure. 1MHz ultrasonic elastic waves were generated at the interface between rebar and concrete. Two-dimensional plain strain element was adopted in all FE models. Formation of surface rust in rebar was modeled by changing material properties and expanding element size in order to simulate the rust interface between rebar and concrete and the presence of interfacial stress. Two types of surface rust (corroded regions) were considered. Time domain and frequency domain responses of displacement were studied. From our simulation result, two corrosion indicators, baseline (b) and center frequency (fc) were proposed for detecting and quantifying corrosion.

  11. New features of triacylglycerol biosynthetic pathways of peanut seeds in early developmental stages.

    PubMed

    Yu, Mingli; Liu, Fengzhen; Zhu, Weiwei; Sun, Meihong; Liu, Jiang; Li, Xinzheng

    2015-11-01

    The peanut (Arachis hypogaea L.) is one of the three most important oil crops in the world due to its high average oil content (50 %). To reveal the biosynthetic pathways of seed oil in the early developmental stages of peanut pods with the goal of improving the oil quality, we presented a method combining deep sequencing analysis of the peanut pod transcriptome and quantitative real-time PCR (RT-PCR) verification of seed oil-related genes. From the sequencing data, approximately 1500 lipid metabolism-associated Unigenes were identified. The RT-PCR results quantified the different expression patterns of these triacylglycerol (TAG) synthesis-related genes in the early developmental stages of peanut pods. Based on these results and analysis, we proposed a novel construct of the metabolic pathways involved in the biosynthesis of TAG, including the Kennedy pathway, acyl-CoA-independent pathway and proposed monoacylglycerol pathway. It showed that the biosynthetic pathways of TAG in the early developmental stages of peanut pods were much more complicated than a simple, unidirectional, linear pathway.

  12. Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women.

    PubMed

    Obeidat, Rana F

    2015-01-01

    To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers' support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system.

  13. In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

    PubMed

    El-Beshbishi, Samar N; Taman, Amira; El-Malky, Mohamed; Azab, Manar S; El-Hawary, Amira K; El-Tantawy, Dina A

    2013-10-01

    The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Development sites, feeding modes and early stages of seven European Palloptera species (Diptera, Pallopteridae).

    PubMed

    Rotheray, Graham E

    2014-12-19

    Two hundred and ninety-eight rearing records and 87 larvae and puparia were obtained of seven species of Palloptera Fallén (Diptera, Pallopteridae), mainly in Scotland during 2012-2013. The third stage larva and puparium of each species were assessed morphologically and development sites and feeding modes investigated by rearing, observation and feeding tests. Early stages appear to be distinguished by the swollen, apico-lateral margins of the prothorax which are coated in vestiture and a poorly developed anal lobe with few spicules. Individual pallopteran species are separated by features of the head skeleton, locomotory spicules and the posterior respiratory organs. Five species can be distinguished by unique character states. Observations and feeding tests suggest that the frequently cited attribute of zoophagy is accidental and that saprophagy is the primary larval feeding mode with autumn/winter as the main period of development. Food plants were confirmed for flowerhead and stem developing species and rain is important for maintaining biofilms on which larvae feed. Due to difficulties in capturing adults, especially males, the distribution and abundance of many pallopteran species is probably underestimated. Better informed estimates are possible if early stages are included in biodiversity assessments. To facilitate this for the species investigated, a key to the third stage larva and puparium along with details on finding them, is provided. 

  15. Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

    PubMed

    Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

    1986-03-01

    Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

  16. The relationship of subepidermal moisture and early stage pressure injury by visual skin assessment.

    PubMed

    Kim, Chul-Gyu; Park, Seungmi; Ko, Ji Woon; Jo, Sungho

    2018-05-08

    The purpose of this study was to examine the relationship of subepidermal moisture and early stage pressure injury by visual skin assessment in elderly Korean. Twenty-nine elderly participated at a particular nursing home. Data were collected for 12 weeks by one wound care nurse. Visual skin assessment and subepidermal moisture value were measured at both buttocks, both ischia, both trochanters, sacrum, and coccyx of each subject once a week. Subepidermal moisture value of stage 1 pressure injury was significantly higher than that of no injury and blanching erythema. After adjustment with covariates, odds ratios of blanching erythema to normal skin and stage 1 pressure injury to blanching erythema/normal skin were statistically significant (p < 0.05). Odds ratio of blanching erythema to normal skin was 1.003 (p = .047) by 1-week prior subepidermal moisture value, and that of concurrent subepidermal moisture value was 1.004 (p = .011). Odds ratio of stage 1 pressure injury to normal skin/blanching erythema was 1.003 (p = .005) by 1-week prior subepidermal moisture value, and that for concurrent subepidermal moisture value was 1.007 (p = .030). Subepidermal moisture was associated with concurrent and future (1 week later) skin damage at both trochanters. Subepidermal moisture would be used to predict early skin damage in clinical nursing field for the effective pressure injury prevention. Copyright © 2018. Published by Elsevier Ltd.

  17. Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish.

    PubMed

    Félix, Luís M; Serafim, Cindy; Valentim, Ana M; Antunes, Luís M; Matos, Manuela; Coimbra, Ana M

    2017-09-05

    Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages). Exposure at the 256-cell stage to ketamine induced an up-regulation of casp8 and pcna at 8 hpf while changes in pcna at the mRNA level were observed at 24 hpf. After the 50% epiboly stage exposure, the mRNA levels of casp9 were increased at 8 and 24 hpf while aifm1 was affected at 24 hpf. Both tp53 and pcna expressions were increased at 8 hpf. After exposure during the 1-4 somites stage, no meaningful changes on transcript levels were observed. The distribution of apoptotic cells and the caspase-like enzymatic activities of caspase-3 and -9 were not affected by ketamine exposure. It is proposed that ketamine exposure at the 256-cell stage induced a cooperative mechanism between proliferation and cellular death while following exposure at the 50% epiboly, a p53-dependent and -independent caspase activation may occur. Finally, at the 1-4 somites stage, the defence mechanisms are already fully in place to protect against ketamine-insult. Thus, ketamine teratogenicity seems to be dependent on the functional mechanisms present in each developmental stage. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Can early hepatic fibrosis stages be discriminated by combining ultrasonic parameters?

    PubMed

    Bouzitoune, Razika; Meziri, Mahmoud; Machado, Christiano Bittencourt; Padilla, Frédéric; Pereira, Wagner Coelho de Albuquerque

    2016-05-01

    In this study, we put forward a new approach to classify early stages of fibrosis based on a multiparametric characterization using backscatter ultrasonic signals. Ultrasonic parameters, such as backscatter coefficient (Bc), speed of sound (SoS), attenuation coefficient (Ac), mean scatterer spacing (MSS), and spectral slope (SS), have shown their potential to differentiate between healthy and pathologic samples in different organs (eye, breast, prostate, liver). Recently, our group looked into the characterization of stages of hepatic fibrosis using the parameters cited above. The results showed that none of them could individually distinguish between the different stages. Therefore, we explored a multiparametric approach by combining these parameters in two and three, to test their potential to discriminate between the stages of liver fibrosis: F0 (normal), F1, F3, and/without F4 (cirrhosis), according to METAVIR Score. Discriminant analysis showed that the most relevant individual parameter was Bc, followed by SoS, SS, MSS, and Ac. The combination of (Bc, SoS) along with the four stages was the best in differentiating between the stages of fibrosis and correctly classified 85% of the liver samples with a high level of significance (p<0.0001). Nevertheless, when taking into account only stages F0, F1, and F3, the discriminant analysis showed that the parameters (Bc, SoS) and (Bc, Ac) had a better classification (93%) with a high level of significance (p<0.0001). The combination of the three parameters (Bc, SoS, and Ac) led to a 100% correct classification. In conclusion, the current findings show that the multiparametric approach has great potential in differentiating between the stages of fibrosis, and thus could play an important role in the diagnosis and follow-up of hepatic fibrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

    PubMed

    Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

    2018-05-01

    Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  20. Impact of end stage kidney disease on costs and outcomes of Clostridium difficile infection.

    PubMed

    Goyal, Abhinav; Chatterjee, Kshitij; Yadlapati, Sujani; Rangaswami, Janani

    2017-09-01

    To assess the impact of end stage kidney disease (ESKD) on the outcomes of Clostridium difficile infection (CDI), including complications of infection, length of hospital stay, overall mortality, and healthcare burden. The National Inpatient Sample (NIS) database created by the Agency of Healthcare Research and Quality (AHRQ) was used, covering the years 2009 through 2013. Manufacturer-provided sampling weights were used to produce national estimates. All-cause unadjusted in-hospital mortality was significantly higher for patients with CDI and ESKD than for patients without ESKD (11.6% vs. 7.7%, p<0.001). The in-hospital mortality remained higher even after adjusting for age, sex, race, and Charlson index group using multivariate logistic regression (odds ratio 1.47, confidence interval 1.41-1.53). The median length of stay was found to be longer by 2days in the ESKD group (9 vs. 7 days, p<0.001). The average cost of hospitalization for patients with CDI and ESKD was also significantly higher compared to the non-ESKD group (USD $35 588 vs. $23 505, in terms of the 2013 value of the USD, p<0.001). The presence of end stage kidney disease in hospitalized patients with Clostridium difficile infection is associated with higher mortality, a longer length of stay, and a higher cost of hospitalization. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Neratinib for the treatment of HER2-positive early stage breast cancer.

    PubMed

    Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

    2017-08-01

    Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

  2. Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma.

    PubMed

    Naboulsi, Wael; Megger, Dominik A; Bracht, Thilo; Kohl, Michael; Turewicz, Michael; Eisenacher, Martin; Voss, Don Marvin; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

    2016-01-04

    Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing an accurate and early tumor diagnosis. To identify potential markers for such applications, we analyzed a patient cohort consisting of 50 patients (50 HCC and 50 adjacent nontumorous tissue samples as controls) using two independent proteomics approaches. We performed label-free discovery analysis on 19 HCC and corresponding tissue samples. The data were analyzed considering events known to take place in early events of HCC development, such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). 31 proteins were selected for verification experiments. For this analysis, the second set of the patient cohort (31 HCC and corresponding tissue samples) was analyzed using selected (multiple) reaction monitoring (SRM/MRM). We present the overexpression of ATP-dependent RNA helicase (DDX39), Fibulin-5 (FBLN5), myristoylated alanine-rich C-kinase substrate (MARCKS), and Serpin H1 (SERPINH1) in HCC for the first time. We demonstrate Versican core protein (VCAN) to be significantly associated with well differentiated and low-stage HCC. We revealed for the first time the evidence of VCAN as a potential biomarker for early-HCC diagnosis.

  3. Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species

    DTIC Science & Technology

    2007-08-01

    ERDC/TN ANSRP-07-2 August 2007 Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species by J...4. TITLE AND SUBTITLE Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species 5a. CONTRACT NUMBER 5b...heralding apoptosis . Data analysis. An apoptotic index (API) was established by calculating the percentage of embryos in each life stage with

  4. Outcome of Early Initiation of Peritoneal Dialysis in Patients with End-Stage Renal Failure

    PubMed Central

    Oh, Kook-Hwan; Hwang, Young-Hwan; Cho, Jung-Hwa; Kim, Mira; Ju, Kyung Don; Joo, Kwon Wook; Kim, Dong Ki; Kim, Yon Su; Ahn, Curie

    2012-01-01

    Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone. PMID:22323864

  5. Maternal Filarial Infection Influences the Development of Regulatory T Cells in Children from Infancy to Early Childhood.

    PubMed

    Bal, Madhusmita; Ranjit, Manoranjan; Achary, K Gopinath; Satapathy, Ashok K

    2016-11-01

    Children born from filarial infected mothers are comparatively more susceptible to filarial infection than the children born to uninfected mothers. But the mechanism of such increased susceptibility to infection in early childhood is not exactly known. Several studies have shown the association of active filarial infection with T cell hypo-responsiveness which is mediated by regulatory T cells (Tregs). Since the Tregs develop in the thymus from CD4+ CD25hi thymocytes at an early stage of the human fetus, it can be hypothesized that the maternal infection during pregnancy affects the development of Tregs in children at birth as well as early childhood. Hence the present study was designed to test the hypothesis by selecting a cohort of pregnant mothers and children born to them subsequently in a filarial endemic area of Odisha, India. A total number of 49 pregnant mothers and children born to them subsequently have been followed up (mean duration 4.4 years) in an area where the microfilariae (Mf) rate has come down to <1% after institution of 10 rounds of annual mass drug administration (MDA). The infection status of mother, cord and children were assessed through detection of microfilariae (Mf) and circulating filarial antigen (CFA). Expression of Tregs cells were measured by flow cytometry. The levels of IL-10 were evaluated by using commercially available ELISA kit. A significantly high level of IL-10 and Tregs have been observed in children born to infected mother compared to children of uninfected mother at the time of birth as well as during early childhood. Moreover a positive correlation between Tregs and IL-10 has been observed among the children born to infected mother. From these observations we predict that early priming of the fetal immune system by filarial antigens modulate the development of Tregs, which ultimately scale up the production of IL-10 in neonates and creates a milieu for high rate of acquisition of infection in children born to infected

  6. Maternal Filarial Infection Influences the Development of Regulatory T Cells in Children from Infancy to Early Childhood

    PubMed Central

    Bal, Madhusmita; Ranjit, Manoranjan; Achary, K. Gopinath; Satapathy, Ashok K.

    2016-01-01

    Background Children born from filarial infected mothers are comparatively more susceptible to filarial infection than the children born to uninfected mothers. But the mechanism of such increased susceptibility to infection in early childhood is not exactly known. Several studies have shown the association of active filarial infection with T cell hypo-responsiveness which is mediated by regulatory T cells (Tregs). Since the Tregs develop in the thymus from CD4+ CD25hi thymocytes at an early stage of the human fetus, it can be hypothesized that the maternal infection during pregnancy affects the development of Tregs in children at birth as well as early childhood. Hence the present study was designed to test the hypothesis by selecting a cohort of pregnant mothers and children born to them subsequently in a filarial endemic area of Odisha, India. Methodology and Principal finding A total number of 49 pregnant mothers and children born to them subsequently have been followed up (mean duration 4.4 years) in an area where the microfilariae (Mf) rate has come down to <1% after institution of 10 rounds of annual mass drug administration (MDA). The infection status of mother, cord and children were assessed through detection of microfilariae (Mf) and circulating filarial antigen (CFA). Expression of Tregs cells were measured by flow cytometry. The levels of IL-10 were evaluated by using commercially available ELISA kit. A significantly high level of IL-10 and Tregs have been observed in children born to infected mother compared to children of uninfected mother at the time of birth as well as during early childhood. Moreover a positive correlation between Tregs and IL-10 has been observed among the children born to infected mother. Significance From these observations we predict that early priming of the fetal immune system by filarial antigens modulate the development of Tregs, which ultimately scale up the production of IL-10 in neonates and creates a milieu for high rate

  7. Socioeconomic Factors Are Associated With Readmission After Lobectomy for Early Stage Lung Cancer.

    PubMed

    Medbery, Rachel L; Gillespie, Theresa W; Liu, Yuan; Nickleach, Dana C; Lipscomb, Joseph; Sancheti, Manu S; Pickens, Allan; Force, Seth D; Fernandez, Felix G

    2016-11-01

    Data regarding risk factors for readmissions after surgical resection for lung cancer are limited and largely focus on postoperative outcomes, including complications and hospital length of stay. The current study aims to identify preoperative risk factors for postoperative readmission in early stage lung cancer patients. The National Cancer Data Base was queried for all early stage lung cancer patients with clinical stage T2N0M0 or less who underwent lobectomy in 2010 and 2011. Patients with unplanned readmission within 30 days of hospital discharge were identified. Univariate analysis was utilized to identify preoperative differences between readmitted and not readmitted cohorts; multivariable logistic regression was used to identify risk factors resulting in readmission. In all, 840 of 19,711 patients (4.3%) were readmitted postoperatively. Male patients were more likely to be readmitted than female patients (4.9% versus 3.8%, p < 0.001), as were patients who received surgery at a nonacademic rather than an academic facility (4.6% versus 3.6%; p = 0.001) and had underlying medical comorbidities (Charlson/Deyo score 1+ versus 0; 4.8% versus 3.7%; p < 0.001). Readmitted patients had a longer median hospital length of stay (6 days versus 5; p < 0.001) and were more likely to have undergone a minimally invasive approach (5.1% video-assisted thoracic surgery versus 3.9% open; p < 0.001). In addition to those variables, multivariable logistic regression analysis identified that median household income level, insurance status (government versus private), and geographic residence (metropolitan versus urban versus rural) had significant influence on readmission. The socioeconomic factors identified significantly influence hospital readmission and should be considered during preoperative and postoperative discharge planning for patients with early stage lung cancer. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Hallux abductus interphalangeus in normal feet, early-stage hallux limitus, and hallux valgus.

    PubMed

    Castillo-Lopez, Jose M; Ramos-Ortega, Javier; Reina-Bueno, Maria; Domínguez-Maldonado, Gabriel; Palomo-Toucedo, Inmaculada C; Munuera, Pedro V

    2014-03-01

    Excessive deviation of the distal phalanx in abduction frequently occurs in advanced stages of hallux rigidus but not in hallux valgus. Therefore, theoretically there should be no significant differences in the hallux interphalangeal angle (HIPA) between individuals with normal feet, those with hallux valgus, and those with mild hallux limitus. The objective of the present study was thus to determine if significant differences in HIPA exist in the early stages of hallux valgus or hallux limitus deformities. The hallux interphalangeal angle was measured in three groups of participants: a control group with normal feet (45 participants), a hallux valgus group (49 participants), and a hallux limitus group (48 participants). Both of the pathologies were at an early stage. A dorsoplantar radiograph under weightbearing conditions was taken for each individual, and measurements (HIPA and hallux abductus angle [HAA]) were taken using AutoCAD (Autodesk Inc, San Rafael, California) software. Intergroup comparisons of HIPA, and correlations between HIPA, HAA, and hallux dorsiflexion were calculated. The comparisons revealed no significant differences in the values of HIPA between any of the groups (15.2 ± 5.9 degrees in the control group, 15.5 ± 3.9 degrees in the hallux valgus group, and 16.15 ± 4.3 in the hallux limitus group; P  =  0.634). The Pearson correlation coefficients in particular showed no correlation between hallux dorsiflexion, HAA, and HIPA. For the study participants, there were similar deviations of the distal phalanx of the hallux with respect to the proximal phalanx in normal feet and in feet with the early stages of the hallux limitus and hallux valgus deformities.

  9. Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

    PubMed Central

    Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

    2015-01-01

    Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

  10. Sentinel lymph node detection rates using indocyanine green in women with early-stage cervical cancer.

    PubMed

    Beavis, Anna L; Salazar-Marioni, Sergio; Sinno, Abdulrahman K; Stone, Rebecca L; Fader, Amanda N; Santillan-Gomez, Antonio; Tanner, Edward J

    2016-11-01

    Our study objective was to determine feasibility and mapping rates using indocyanine green (ICG) for sentinel lymph node (SLN) mapping in early-stage cervical cancer. We performed a retrospective review of all women who underwent SLN mapping with ICG during primary surgical management of early-stage cervical cancer by robotic-assisted radical hysterectomy (RA-RH) or fertility-sparing surgery. Patients were treated at two high-volume centers from 10/2012 to 02/2016. Completion pelvic lymphadenectomy was performed after SLN biopsy; additionally, removal of clinically enlarged/suspicious nodes was part of the SLN treatment algorithm. Thirty women with a median age of 42.5 and BMI of 26.5 were included. Most (90%) had stage IB disease, and 67% had squamous histology. RA-RH was performed in 86.7% of cases. One patient underwent fertility-sparing surgery. Median cervical tumor size was 2.0cm. At least one SLN was detected in all cases (100%), with bilateral mapping achieved in 87%. SLN detection was not impacted by tumor size and was most commonly identified in the hypogastric (40.3%), obturator (26.0%), and external iliac (20.8%) regions. Five cases of lymphatic metastasis were identified (16.7%): three in clinically enlarged SLNs, one in a clinically enlarged non-SLN, and one case with cytokeratin positive cells in an SLN. All metastatic disease would have been detected even if full lymphadenectomy had been omitted from our treatment algorithm, CONCLUSIONS: SLN mapping with ICG is feasible and results in high detection rates in women with early-stage cervical cancer. Prospective studies are needed to determine if SLN mapping can replace lymphadenectomy in this setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

    PubMed Central

    Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

    2016-01-01

    Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced

  12. Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

    2012-01-01

    Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

  13. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

    PubMed Central

    Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

    2014-01-01

    Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

  14. Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

    PubMed

    Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

    2014-06-01

    Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.

    PubMed

    Lampaki, Sofia; Lazaridis, George; Zarogoulidis, Konstantinos; Kioumis, Ioannis; Papaiwannou, Antonis; Tsirgogianni, Katerina; Karavergou, Anastasia; Tsiouda, Theodora; Karavasilis, Vasilis; Yarmus, Lonny; Darwiche, Kaid; Freitag, Lutz; Sakkas, Antonios; Kantzeli, Angeliki; Baka, Sofia; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul

    2015-01-01

    Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the

  16. Managing uncertainty - a qualitative study of surgeons' decision-making for one-stage and two-stage revision surgery for prosthetic hip joint infection.

    PubMed

    Moore, Andrew J; Blom, Ashley W; Whitehouse, Michael R; Gooberman-Hill, Rachael

    2017-04-12

    Approximately 88,000 primary hip replacements are performed in England and Wales each year. Around 1% go on to develop deep prosthetic joint infection. Between one-stage and two-stage revision arthroplasty best treatment options remain unclear. Our aims were to characterise consultant orthopaedic surgeons' decisions about performing either one-stage or two-stage revision surgery for patients with deep prosthetic infection (PJI) after hip arthroplasty, and to identify whether a randomised trial comparing one-stage with two-stage revision would be feasible. Semi-structured interviews were conducted with 12 consultant surgeons who perform revision surgery for PJI after hip arthroplasty at 5 high-volume National Health Service (NHS) orthopaedic departments in England and Wales. Surgeons were interviewed before the development of a multicentre randomised controlled trial. Data were analysed using a thematic approach. There is no single standardised surgical intervention for the treatment of PJI. Surgeons balance multiple factors when choosing a surgical strategy which include multiple patient-related factors, their own knowledge and expertise, available infrastructure and the infecting organism. Surgeons questioned whether it was appropriate that the two-stage revision remained the best treatment, and some surgeons' willingness to consider more one-stage revisions had increased over recent years and were influenced by growing evidence showing equivalence between surgical techniques, and local observations of successful one-stage revisions. Custom-made articulating spacers was a practice that enabled uncertainty to be managed in the absence of definitive evidence about the superiority of one surgical technique over the other. Surgeons highlighted the need for research evidence to inform practice and thought that a randomised trial to compare treatments was needed. Most surgeons thought that patients who they treated would be eligible for trial participation in instances

  17. Spatial variations in mortality in pelagic early life stages of a marine fish (Gadus morhua)

    NASA Astrophysics Data System (ADS)

    Langangen, Øystein; Stige, Leif C.; Yaragina, Natalia A.; Ottersen, Geir; Vikebø, Frode B.; Stenseth, Nils Chr.

    2014-09-01

    Mortality of pelagic eggs and larvae of marine fish is often assumed to be constant both in space and time due to lacking information. This may, however, be a gross oversimplification, as early life stages are likely to experience large variations in mortality both in time and space. In this paper we develop a method for estimating the spatial variability in mortality of eggs and larvae. The method relies on survey data and physical-biological particle-drift models to predict the drift of ichthyoplankton. Furthermore, the method was used to estimate the spatially resolved mortality field in the egg and larval stages of Barents Sea cod (Gadus morhua). We analyzed data from the Barents Sea for the period between 1959 and 1993 when there are two surveys available: a spring and a summer survey. An individual-based physical-biological particle-drift model, tailored to the egg and larval stages of Barents Sea cod, was used to predict the drift trajectories from the observed stage-specific distributions in spring to the time of observation in the summer, a drift time of approximately 45 days. We interpreted the spatial patterns in the differences between the predicted and observed abundance distributions in summer as reflecting the spatial patterns in mortality over the drift period. Using the estimated mortality fields, we show that the spatial variations in mortality might have a significant impact on survival to later life stages and we suggest that there may be trade-offs between increased early survival in off shore regions and reduced probability of ending up in the favorable nursing grounds in the Barents Sea. In addition, we show that accounting for the estimated mortality field, improves the correlation between a simulated recruitment index and observation-based indices of juvenile abundance.

  18. Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation?

    PubMed

    Luu, Carrie; Amaral, Marisa; Klapman, Jason; Harris, Cynthia; Almhanna, Khaldoun; Hoffe, Sarah; Frakes, Jessica; Pimiento, Jose M; Fontaine, Jacques P

    2017-12-14

    To evaluate the accuracy of endoscopic ultrasound (EUS) in early esophageal cancer (EC) performed in a high-volume tertiary cancer center. A retrospective review of patients undergoing esophagectomy was performed and patients with cT1N0 and cT2N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student's t test and Fisher's exact test or χ 2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS accuracy. Between 2000 and 2015, 139 patients with clinical stageIorIIA esophageal cancer undergoing esophagectomy were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location included the middle third of the esophagus in 11 (8%) and lower third and gastroesophageal junction in 128 (92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients (21%) were under-staged by EUS; of those, 19 (14%) had unrecognized nodal disease. Positron emission tomography (PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients (6%) in whom both EUS and PET were negative for nodal involvement. EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.

  19. Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

    PubMed Central

    Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

    2013-01-01

    Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

  20. Practice patterns and long-term survival for early-stage rectal cancer.

    PubMed

    Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

    2013-12-01

    Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

  1. Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori.

    PubMed

    Sakai, Hiroki; Kirino, Yohei; Katsuma, Susumu; Aoki, Fugaku; Suzuki, Masataka G

    2016-01-01

    The gonad develops as a testis in male or an ovary in female. In the silkworm, B. mori , little is known about testis and ovary in the embryonic stages and early larval stages. In this study, we performed morphological and histomorphological observations of ovaries and testes from the late embryonic stage to the 1st instar larval stage. Results obtained with lack of accurate information on sex of examined individuals may be misleading, thus we performed phenotypic observations of gonads by utilizing sex-limited strain that enables us to easily discriminate female embryos from male ones based on those egg colors. In testis, four testicular follicles were clearly observed in the testis at the first instar larval stage, and boundary layers were formed between the testicular follicles. At the late embryonic stage, the testis consisted of four testicular follicles, while the boundary layers were still obscure. In ovary, four ovarioles were easily recognizable in the ovary at the first instar larval stage, and boundary layers were formed between the ovarioles. However, in the late embryonic stage, it was quite difficult to identify four ovarioles. Morphological characteristics were almost similar between testis and ovary in early developmental stages. Our present study demonstrates that the most reliable difference between testis and ovary in early developmental stages is the attaching point of the duct. Formation and development of the duct may be sensitive to the sex-determining signal and display sexual dimorphism in early embryonic stages.

  2. Lexical Access in Early Stages of Visual Word Processing: A Single-Trial Correlational MEG Study of Heteronym Recognition

    ERIC Educational Resources Information Center

    Solomyak, Olla; Marantz, Alec

    2009-01-01

    We present an MEG study of heteronym recognition, aiming to distinguish between two theories of lexical access: the "early access" theory, which entails that lexical access occurs at early (pre 200 ms) stages of processing, and the "late access" theory, which interprets this early activity as orthographic word-form identification rather than…

  3. A transcriptomic insight into the infective juvenile stage of the insect parasitic nematode, Heterorhabditis indica.

    PubMed

    Somvanshi, Vishal S; Gahoi, Shachi; Banakar, Prakash; Thakur, Prasoon Kumar; Kumar, Mukesh; Sajnani, Manisha; Pandey, Priyatama; Rao, Uma

    2016-03-01

    Nematodes are the most numerous animals in the soil. Insect parasitic nematodes of the genus Heterorhabditis are capable of selectively seeking, infecting and killing their insect-hosts in the soil. The infective juvenile (IJ) stage of the Heterorhabditis nematodes is analogous to Caenorhabditis elegans dauer juvenile stage, which remains in 'arrested development' till it finds and infects a new insect-host in the soil. H. indica is the most prevalent species of Heterorhabditis in India. To understand the genes and molecular processes that govern the biology of the IJ stage, and to create a resource to facilitate functional genomics and genetic exploration, we sequenced the transcriptome of H. indica IJs. The de-novo sequence assembly using Velvet-Oases pipeline resulted in 13,593 unique transcripts at N50 of 1,371 bp, of which 53 % were annotated by blastx. H. indica transcripts showed higher orthology with parasitic nematodes as compared to free living nematodes. In-silico expression analysis showed 30 % of transcripts expressing with ≥100 FPKM value. All the four canonical dauer formation pathways like cGMP-PKG, insulin, dafachronic acid and TGF-β were active in the IJ stage. Several other signaling pathways were highly represented in the transcriptome. Twenty-four orthologs of C. elegans RNAi pathway effector genes were discovered in H. indica, including nrde-3 that is reported for the first time in any of the parasitic nematodes. An ortholog of C. elegans tol-1 was also identified. Further, 272 kinases belonging to 137 groups, and several previously unidentified members of important gene classes were identified. We generated high-quality transcriptome sequence data from H. indica IJs for the first time. The transcripts showed high similarity with the parasitic nematodes, M. hapla, and A. suum as opposed to C. elegans, a species to which H. indica is more closely related. The high representation of transcripts from several signaling pathways in the IJs

  4. Conditional mutagenesis in vivo reveals cell type- and infection stage-specific requirements for LANA in chronic MHV68 infection

    PubMed Central

    Salinas, Eduardo; Sifford, Jeffrey M.; Oldenburg, Darby G.

    2018-01-01

    Gammaherpesvirus (GHV) pathogenesis is a complex process that involves productive viral replication, dissemination to tissues that harbor lifelong latent infection, and reactivation from latency back into a productive replication cycle. Traditional loss-of-function mutagenesis approaches in mice using murine gammaherpesvirus 68 (MHV68), a model that allows for examination of GHV pathogenesis in vivo, have been invaluable for defining requirements for specific viral gene products in GHV infection. But these approaches are insufficient to fully reveal how viral gene products contribute when the encoded protein facilitates multiple processes in the infectious cycle and when these functions vary over time and from one host tissue to another. To address this complexity, we developed an MHV68 genetic platform that enables cell-type-specific and inducible viral gene deletion in vivo. We employed this system to re-evaluate functions of the MHV68 latency-associated nuclear antigen (mLANA), a protein with roles in both viral replication and latency. Cre-mediated deletion in mice of loxP-flanked ORF73 demonstrated the necessity of mLANA in B cells for MHV68 latency establishment. Impaired latency during the transition from draining lymph nodes to blood following mLANA deletion also was observed, supporting the hypothesis that B cells are a major conduit for viral dissemination. Ablation of mLANA in infected germinal center (GC) B cells severely impaired viral latency, indicating the importance of viral passage through the GC for latency establishment. Finally, induced ablation of mLANA during latency resulted in complete loss of affected viral genomes, indicating that mLANA is critically important for maintenance of viral genomes during stable latency. Collectively, these experiments provide new insights into LANA homolog functions in GHV colonization of the host and highlight the potential of a new MHV68 genetic platform to foster a more complete understanding of viral gene

  5. In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary Emphysema.

    PubMed

    Hellbach, Katharina; Yaroshenko, Andre; Meinel, Felix G; Yildirim, Ali Ö; Conlon, Thomas M; Bech, Martin; Mueller, Mark; Velroyen, Astrid; Notohamiprodjo, Mike; Bamberg, Fabian; Auweter, Sigrid; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz

    2015-07-01

    The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema. Female 8- to 10-week-old C57Bl/6N mice were used throughout all experiments. Pulmonary emphysema was induced by orotracheal injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control mice (n = 11) received orotracheal injection of phosphate-buffered saline. To monitor the temporal patterns of emphysema development over time, the mice were imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered saline. X-ray transmission and dark-field images were acquired with a prototype grating-based small-animal scanner. In vivo pulmonary function tests were performed before killing the animals. In addition, lungs were obtained for detailed histopathological analysis, including mean cord length (MCL) quantification as a parameter for the assessment of emphysema. Three blinded readers, all of them experienced radiologists and familiar with dark-field imaging, were asked to grade the severity of emphysema for both dark-field and transmission images. Histopathology and MCL quantification confirmed the introduction of different stages of emphysema, which could be clearly visualized and differentiated on the dark-field radiograms, whereas early stages were not detected on transmission images. The correlation between MCL and dark-field signal intensities (r = 0.85) was significantly higher than the correlation between MCL and transmission signal intensities (r = 0.37). The readers' visual ratings for dark-field images correlated significantly better with MCL (r = 0.85) than visual ratings for transmission images (r = 0.36). Interreader agreement and the diagnostic accuracy of both quantitative and visual assessment were significantly higher

  6. Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

    PubMed

    Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

    2017-10-01

    Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  7. Changes of statistical structural fluctuations unveils an early compacted degraded stage of PNS myelin

    NASA Astrophysics Data System (ADS)

    Poccia, Nicola; Campi, Gaetano; Ricci, Alessandro; Caporale, Alessandra S.; di Cola, Emanuela; Hawkins, Thomas A.; Bianconi, Antonio

    2014-06-01

    Degradation of the myelin sheath is a common pathology underlying demyelinating neurological diseases from Multiple Sclerosis to Leukodistrophies. Although large malformations of myelin ultrastructure in the advanced stages of Wallerian degradation is known, its subtle structural variations at early stages of demyelination remains poorly characterized. This is partly due to the lack of suitable and non-invasive experimental probes possessing sufficient resolution to detect the degradation. Here we report the feasibility of the application of an innovative non-invasive local structure experimental approach for imaging the changes of statistical structural fluctuations in the first stage of myelin degeneration. Scanning micro X-ray diffraction, using advances in synchrotron x-ray beam focusing, fast data collection, paired with spatial statistical analysis, has been used to unveil temporal changes in the myelin structure of dissected nerves following extraction of the Xenopus laevis sciatic nerve. The early myelin degeneration is a specific ordered compacted phase preceding the swollen myelin phase of Wallerian degradation. Our demonstration of the feasibility of the statistical analysis of SµXRD measurements using biological tissue paves the way for further structural investigations of degradation and death of neurons and other cells and tissues in diverse pathological states where nanoscale structural changes may be uncovered.

  8. Relationship between early and late stages of information processing: an event-related potential study

    PubMed Central

    Portella, Claudio; Machado, Sergio; Arias-Carrión, Oscar; Sack, Alexander T.; Silva, Julio Guilherme; Orsini, Marco; Leite, Marco Antonio Araujo; Silva, Adriana Cardoso; Nardi, Antonio E.; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

    2012-01-01

    The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP) components, including P200, N200, premotor potential (PMP) and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2), N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) and the reaction time (RT). In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) was found. Therefore, we propose that if the secondary processing of visual input (P200 latency) occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency), motor response processing (PMP latency), reorganization of attention and working memory update (P300 latency), and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude). PMID:23355929

  9. Efficient and Rapid Isolation of Early-stage Embryos from Arabidopsis thaliana Seeds

    PubMed Central

    Raissig, Michael T.; Gagliardini, Valeria; Jaenisch, Johan; Grossniklaus, Ueli; Baroux, Célia

    2013-01-01

    In flowering plants, the embryo develops within a nourishing tissue - the endosperm - surrounded by the maternal seed integuments (or seed coat). As a consequence, the isolation of plant embryos at early stages (1 cell to globular stage) is technically challenging due to their relative inaccessibility. Efficient manual dissection at early stages is strongly impaired by the small size of young Arabidopsis seeds and the adhesiveness of the embryo to the surrounding tissues. Here, we describe a method that allows the efficient isolation of young Arabidopsis embryos, yielding up to 40 embryos in 1 hr to 4 hr, depending on the downstream application. Embryos are released into isolation buffer by slightly crushing 250-750 seeds with a plastic pestle in an Eppendorf tube. A glass microcapillary attached to either a standard laboratory pipette (via a rubber tube) or a hydraulically controlled microinjector is used to collect embryos from droplets placed on a multi-well slide on an inverted light microscope. The technical skills required are simple and easily transferable, and the basic setup does not require costly equipment. Collected embryos are suitable for a variety of downstream applications such as RT-PCR, RNA sequencing, DNA methylation analyses, fluorescence in situ hybridization (FISH), immunostaining, and reporter gene assays. PMID:23770918

  10. Early life stages contribute strongly to local adaptation in Arabidopsis thaliana.

    PubMed

    Postma, Froukje M; Ågren, Jon

    2016-07-05

    The magnitude and genetic basis of local adaptation is of fundamental interest in evolutionary biology. However, field experiments usually do not consider early life stages, and therefore may underestimate local adaptation and miss genetically based tradeoffs. We examined the contribution of differences in seedling establishment to adaptive differentiation and the genetic architecture of local adaptation using recombinant inbred lines (RIL) derived from a cross between two locally adapted populations (Italy and Sweden) of the annual plant Arabidopsis thaliana We planted freshly matured, dormant seeds (>180 000) representing >200 RILs at the native field sites of the parental genotypes, estimated the strength of selection during different life s