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Sample records for przelozenie wielkich pni

  1. PNI Biomarkers and Health Outcomes in College Women

    PubMed Central

    Lee, Shih-Yu; Vasireddi, Mugdha; Chen, Yu Ping; Wang, Yong Tai; Hilliard, Julia

    2014-01-01

    Sleep disturbance has been found to trigger a stress response with a subsequent activation of the psychoneuroimmunological (PNI) pathway associated with adverse health outcomes. This study aimed to assess the association among selected PNI biomarkers, sleep disturbances, and adverse health outcomes (depressive symptoms, physical symptoms). A stratified, quota sample (14 poor sleepers and 15 good sleepers) was drawn from a pool of healthy college women from a larger scale of study. The participants reported their sleep, stress, depressive, and physical symptoms. Wrist actigraphy was used to collect objective sleep data, and the Enzyme-Linked ImmunoSorbent Assay was used to assess PNI biomarkers. Poor sleep quality, higher stress perception, elevated serum serotonin, and lower serum interleukin-10 explained 75.3% of the variances for the depressive symptoms. Poor sleep quality along with delayed peak activity rhythms accounted 31.4% of the physical symptoms. High serotonin and tumor necrosis factor-α were the significant predictors for poor sleep efficiency, and serotonin was the single significant predictor for poor daytime functioning. Stress and sleep disturbances negatively impact the health of college women and should be as part of regular check-ups on campus. PNI effects on health outcomes should be further explored. Educational materials in the areas of sleep hygiene, health impacts from sleep disturbances, and strategies to maintain synchronized circadian rhythms should be mandatorily included in the college curriculum.

  2. 76 FR 3881 - Notice of Intent To Grant Exclusive Patent License; PNI Corporation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ... Department of the Navy Notice of Intent To Grant Exclusive Patent License; PNI Corporation AGENCY: Department... Government-owned inventions described in U.S. Patent No. 6,820,025: Method and Apparatus for Motion Tracking of an Articulated Rigid Body, Navy Case No. 82,816.//U.S. Patent No. 7,089,148: Method and...

  3. Low Prognostic Nutritional Index (PNI) Predicts Unfavorable Distant Metastasis-Free Survival in Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis

    PubMed Central

    Hong, Shaodong; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Chen, Yong

    2016-01-01

    Background Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC). Methods A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool “Cutoff Finder”. DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores. Results The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P<0.001) as well as multivariate analysis (P<0.001) before propensity score matching. In subgroup analyses, PNI could also stratify different risks of distant metastases. Propensity score-matched analyses confirmed the prognostic value of PNI, excluding other interpretations and selection bias. In the external validation cohort, patients with high PNI also had significantly lower risk of distant metastases than those with low PNI (Hazards Ratios, 0.487; P<0.001). The PNI consistently showed a higher AUC value at 1-year (0.780), 3-year (0.793) and 5-year (0.812) in comparison with other prognostic scores. Conclusion PNI, an inexpensive and easily assessable inflammatory index, could aid clinicians in developing individualized treatment and follow-up strategies for patients

  4. New aspects in the phase behaviour of poly-N-isopropyl acrylamide: systematic temperature dependent shrinking of PNiPAM assemblies well beyond the LCST

    NASA Astrophysics Data System (ADS)

    Bischofberger, Irmgard; Trappe, Veronique

    2015-10-01

    We investigate the phase behaviour of aqueous dispersions of poly-N-isopropyl acrylamide (PNiPAM) microgels above their lower critical solution temperature (LCST) and find that beyond a well-defined concentration the systems exhibit a peculiar behaviour: the microgels assemble into space-spanning gels that shrink in time while maintaining the shape of the container in which they have been formed. Over a wide range of concentrations this shrinking behaviour is independent of PNiPAM concentration, but systematically depends on temperature in a temperature range significantly exceeding the LCST. The overall shrinking characteristics are consistent with those expected for scaffolds made of materials that exhibit thermal contraction. However, for the PNiPAM assemblies contraction is irreversible and can be as large as 90%. Such characteristics disclose complex interactions between fully collapsed PNiPAM and water well beyond the LCST, the origin of which has yet to be elucidated.

  5. New aspects in the phase behaviour of poly-N-isopropyl acrylamide: systematic temperature dependent shrinking of PNiPAM assemblies well beyond the LCST.

    PubMed

    Bischofberger, Irmgard; Trappe, Veronique

    2015-01-01

    We investigate the phase behaviour of aqueous dispersions of poly-N-isopropyl acrylamide (PNiPAM) microgels above their lower critical solution temperature (LCST) and find that beyond a well-defined concentration the systems exhibit a peculiar behaviour: the microgels assemble into space-spanning gels that shrink in time while maintaining the shape of the container in which they have been formed. Over a wide range of concentrations this shrinking behaviour is independent of PNiPAM concentration, but systematically depends on temperature in a temperature range significantly exceeding the LCST. The overall shrinking characteristics are consistent with those expected for scaffolds made of materials that exhibit thermal contraction. However, for the PNiPAM assemblies contraction is irreversible and can be as large as 90%. Such characteristics disclose complex interactions between fully collapsed PNiPAM and water well beyond the LCST, the origin of which has yet to be elucidated. PMID:26493499

  6. New aspects in the phase behaviour of poly-N-isopropyl acrylamide: systematic temperature dependent shrinking of PNiPAM assemblies well beyond the LCST

    PubMed Central

    Bischofberger, Irmgard; Trappe, Veronique

    2015-01-01

    We investigate the phase behaviour of aqueous dispersions of poly-N-isopropyl acrylamide (PNiPAM) microgels above their lower critical solution temperature (LCST) and find that beyond a well-defined concentration the systems exhibit a peculiar behaviour: the microgels assemble into space-spanning gels that shrink in time while maintaining the shape of the container in which they have been formed. Over a wide range of concentrations this shrinking behaviour is independent of PNiPAM concentration, but systematically depends on temperature in a temperature range significantly exceeding the LCST. The overall shrinking characteristics are consistent with those expected for scaffolds made of materials that exhibit thermal contraction. However, for the PNiPAM assemblies contraction is irreversible and can be as large as 90%. Such characteristics disclose complex interactions between fully collapsed PNiPAM and water well beyond the LCST, the origin of which has yet to be elucidated. PMID:26493499

  7. A new p-Ni1-xO : Li/n-Si heterojunction solar cell fabricated by RF magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Hao Hsu, Feng; Wang, Na Fu; Zen Tsai, Yu; Cheng, Yu Song; Phon Houng, Mau

    2013-07-01

    This study reports the fabrication of p-type Ni1-xO : Li/n-Si heterojunction solar cells (HJSCs) by depositing Li-doped Ni1-xO (p-Ni1-xO : Li) on a n-Si substrate (P+/n) using RF magnetron sputtering. Films deposited on glass substrates at various working pressures were first analysed to estimate the optoelectrical properties of p-Ni1-xO : Li thin films. These experimental results show that the best working pressure was 6 mTorr, which produced a surface roughness of 2.85 nm, a grain size of 19.8 nm, a resistivity of 2.7 Ω cm, a visible transmittance of 49.16%, a work function of 5.32 eV, and a refractive index of 2.54. Although the p-Ni1-xO : Li thin film has a relatively high work function, its conversion efficiency is 2.338% (Voc: 345 mV, Jsc: 22.048 mA cm-2, and FF: 0.307). This study proposes that reduce interface states and improve the optoelectrical properties of p-NiO are two important issues because they can directly and significantly affect the conversion efficiency of p-Ni1-xO : Li/n-Si HJSC. In summary, this high Voc value indicates that p-Ni1-xO : Li thin film is more suitable than ZnO/n-Si structures as an emitter layer for transparent conducting oxide/n-Si HJSC applications.

  8. Specific Types of Coal Macerals from Orzesze and Ruda Beds from "Pniówek" Coal Mine (Upper Silesian Coal Basin - Poland) as a Manifestation of Thermal Metamorphism

    NASA Astrophysics Data System (ADS)

    Adamczyk, Zdzisław; Komorek, Joanna; Lewandowska, Małgorzata

    2014-03-01

    Subject of the research were coal samples from the seams of Orzesze and Ruda beds from "Pniówek" coal mine. All samples represent methabituminous coal B, which present high vitrinite content (V mmf > 60%). Optical character of vitrinite from all analyzed coal samples is biaxial negative and it is characterized by low differentiation of bireflectance. The experiments have shown that the coal rank of investigated samples is generally decreasing with increasing both depth of coal seams and the distance between sampling point and the Carboniferous roof. It may suggests inversion of coalification. Specific types of macerals, typical for thermally metamorphosed coals have been found for all analysed coal samples. It was found, presence of such components like: fluorescing bituminous substance (FBS) filling of cellular spaces in semifusinite, fusinite, and funginite; pseudomorphs after megaspores exhibiting strong bireflectance, and anisotropic semifusinite. Petrographic components with a structure similar to structure of coke and pyrolytic carbon were observed rarely. Presence of colotelinite grains which are visible darker, impregnated with bituminous substance and exhibiting weak fluorescence may be related with influence of temperature on coal. Carbonates occur as filling of cellular spaces in semifusinite, in examined coal samples and there are the effect of thermal alteration of coal. Przedmiotem badań były próbki węgla z pokładów warstw orzeskich i rudzkich KWK Pniówek. Badane próbki reprezentują węgiel średniouwęglony typu B (metabitumiczny), wysokowitrynitowy. Stwierdzono, że witrynit z badanych próbek ma dwuosiowy ujemny charakter optyczny i wykazuje małe zróżnicowanie w wartościach dwójodbicia. Przeprowadzone badania wykazały, że stopień uwęglenia badanych próbek generalnie maleje wraz ze wzrostem głębokości występowania pokładów węgla oraz ze wzrostem odległości miejsca opróbowania od stropu karbonu co może wskazywać na

  9. Mechanisms of Perineural Invasion.

    PubMed

    Bakst, Richard L; Wong, Richard J

    2016-04-01

    Perineural invasion (PNI) is the neoplastic invasion of nerves. PNI is widely recognized as an important adverse pathological feature of many malignancies, including pancreatic, prostate, and head and neck cancers and is associated with a poor prognosis. Despite widespread acknowledgment of the clinical significance of PNI, the mechanisms underlying its pathogenesis remain largely unknown. Recent theories of PNI pathogenesis have placed a significant emphasis on the active role of the nerve microenvironment, with PNI resulting from well-orchestrated reciprocal interactions between cancer and host. Elucidating the mechanisms involved in PNI may translate into targeted therapies for this ominous process. PMID:27123385

  10. An Exploration of Preference for Numerical Information in Relation to Math Self-Concept and Statistics Anxiety in a Graduate Statistics Course

    ERIC Educational Resources Information Center

    Williams, Amanda

    2014-01-01

    The purpose of the current research was to investigate the relationship between preference for numerical information (PNI), math self-concept, and six types of statistics anxiety in an attempt to establish support for the nomological validity of the PNI. Correlations indicate that four types of statistics anxiety were strongly related to PNI, and…

  11. Evaluation of the association between perineural invasion and clinical and histopathological features of cervical cancer

    PubMed Central

    Wei, You-Sheng; Yao, De-Sheng; Long, Ying

    2016-01-01

    Perineural invasion (PNI) has been investigated as a new prognostic factor in a number of carcinomas. However, studies on PNI in cervical cancer are limited, and inconsistent conclusions have been reported by different groups. The aim of the present study was to analyze the relationship between perineural invasion (PNI) and clinical and histopathological features of cervical cancer, and to evaluate the clinical significance of PNI of cervical cancer. Retrospective review identified 206 patients with cervical cancer who underwent radical hysterectomy plus pelvic lymphadenectomy between December 2012 and August 2014. The association between PNI and clinical and histopathological features of cervical cancer and post-operative radiotherapy was evaluated based on univariate and multivariate analyses. PNI of cervical cancer was identified in 33 of 206 (16%) cervical cancer patients. Univariate analysis demonstrated that PNI was associated with clinical stage, tumor grade, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis (P<0.05), but not associated with age and histopathological types (P>0.05). Multivariate analysis suggests that LVSI and lymph node metastasis were associated with PNI of cervical cancer (P<0.05). In addition, post-operative radiotherapy was significantly more recommended for patients with PNI than those without PNI (P<0.001). In conclusion, PNI of cervical cancer is associated with LVSI and lymph node metastasis and can be used as an index for the determination of post-operative radiotherapy for cervical cancer patients. PMID:27588197

  12. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    SciTech Connect

    Lin, Charles; Tripcony, Lee; Keller, Jacqui; Poulsen, Michael; Martin, Jarad; Jackson, James; Dickie, Graeme

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  13. Adjuvant radiotherapy for early head and neck squamous cell carcinoma with perineural invasion: A systematic review.

    PubMed

    Bur, Andrés M; Lin, Alexander; Weinstein, Gregory S

    2016-04-01

    Perineural invasion (PNI) is widely regarded as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Treatment guidelines recommend adjuvant radiotherapy (RT) for patients with adverse pathologic features, including PNI. The purpose of this study was to systematically review the literature to determine if patients with PNI as their only indication for adjuvant therapy benefit from adjuvant RT. In total, 339 abstracts were reviewed for relevance leaving 85 articles, which were evaluated in detail. Thirteen retrospective studies addressed the role of adjuvant RT for patients with PNI. Evidence is lacking to recommend adjuvant RT for all patients with HNSCC with PNI. However, the literature suggests that large nerve or multifocal PNI may predict worse outcome and may be a more appropriate indication for adjuvant therapy. We advocate that patients decide whether to undergo adjuvant therapy after a discussion of the limitations of current evidence. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2350-E2357, 2016. PMID:26613965

  14. Galanin modulates the neural niche to favour perineural invasion in head and neck cancer

    PubMed Central

    Scanlon, Christina Springstead; Banerjee, Rajat; Inglehart, Ronald C; Liu, Min; Russo, Nickole; Hariharan, Amirtha; van Tubergen, Elizabeth A; Corson, Sara L; Asangani, Irfan A; Mistretta, Charlotte M; Chinnaiyan, Arul M; D’Silva, Nisha J

    2015-01-01

    Perineural invasion (PNI) is an indicator of poor survival in multiple cancers. Unfortunately, there is no targeted treatment for PNI since the molecular mechanisms are largely unknown. PNI is an active process, suggesting that cancer cells communicate with nerves. However, nerve-tumour crosstalk is understudied due to the lack of in vivo models to investigate the mechanisms. Here, we developed an in vivo model of PNI to characterise this interaction. We show that the neuropeptide galanin (GAL) initiates nerve-tumour crosstalk via activation of its G-protein-coupled receptor, GALR2. Our data reveal a novel mechanism by which GAL from nerves stimulates GALR2 on cancer cells to induce NFATC2-mediated transcription of cyclooxygenase-2 and GAL. Prostaglandin E2 promotes cancer invasion, and in a feedback mechanism, GAL released by cancer induces neuritogenesis, facilitating PNI. This study describes a novel in vivo model for PNI and reveals the dynamic interaction between nerve and cancer. PMID:25917569

  15. Temperature-dependent intermolecular force measurement of poly(N-isopropylacrylamide) grafted surface with protein.

    PubMed

    Cho, Eun Chul; Kim, Yong Deuk; Cho, Kilwon

    2005-06-15

    We have investigated the temperature dependence of the intermolecular force between poly(N-isopropylacrylamide) (PNiPAM) grafted surface and bovine serum albumin (BSA) in phosphate buffer (pH 7.4) using atomic force microscopy at the nanonewton scale. These observations show that the interaction force is nearly zero below the phase transition temperature of PNiPAM and that it increases steeply during the phase transition. Since the PNiPAM chains are grafted onto the aminosilane (gamma-aminopropyltriethoxysilane)-treated silicon wafer, we measured the force-distance curve of BSA-immobilized tips for the bare and the aminosilane-treated silicon wafer. These surfaces show no temperature dependence and their values are different from those of the PNiPAM-grafted surfaces at 30 degrees C. The results indicate that the measured adhesion force is between the PNiPAM-grafted surface and the BSA-immobilized tip. Our studies on the intermolecular force between other surfaces (CH(3)- and COOH-terminated self-assembled monolayers) and the BSA-immobilized tip indicate that the variation in the intermolecular force between the PNiPAM surface and BSA with temperature can be attributed to the changes in the properties of the PNiPAM chains. From consideration of the PNiPAM phase transition mechanism, it is speculated that the intermolecular force between the PNiPAM-grafted surface and BSA would be affected by changes in the arrangement of the bound water molecules around the PNiPAM chain and by changes in the conformation (i.e., in the chain mobility) of the PNiPAM chain during the phase transition. PMID:15897061

  16. Management of squamous cell and basal cell carcinomas of the head and neck with perineural invasion.

    PubMed

    Gupta, Aakriti; Veness, Michael; De'Ambrosis, Brian; Selva, Dinesh; Huilgol, Shyamala C

    2016-02-01

    Perineural invasion (PNI) occurring in non-melanoma skin cancers (NMSC) is associated with an increased risk of locoregional recurrence and reduced disease-free survival. This necessitates early and accurate diagnosis, appropriate risk-stratification and a clear management strategy. The diagnosis of PNI is based on careful clinical assessment, imaging and histopathology. Surgery, preferably with margin control, and definitive or adjuvant radiotherapy (ART) are established treatment strategies for PNI. Clinical uncertainty remains over the role of ART in incidental PNI. This review synthesises current literature to ascertain which clinicopathological features impart a higher risk to individuals with PNI in NMSC, in order to provide treatment algorithms, including the identification of patient subsets that are most likely to benefit from ART. This includes those with extratumoural PNI, involvement of larger-calibre nerves, tumour invasion beyond dermis, recurrent tumour or diffuse intratumoural spread. Patients with clinical PNI may be optimally managed by a multidisciplinary head and neck cancer service that is best placed to offer skull base surgery and intensity-modulated radiation therapy (IMRT). The management options presented are stratified by histological subtype and a new classification of PNI into low-risk, medium-risk and high-risk groups. PMID:25759949

  17. Desmoplastic melanoma, neurotropism, and neurotrophin receptors--what we know and what we do not.

    PubMed

    Frydenlund, Noah; Mahalingam, Meera

    2015-07-01

    Desmoplastic melanoma (DM) is a relatively rare cytomorphologic variant of melanoma with a marked propensity for perineural invasion (PNI). Historically, DMs that display PNI have been grouped under the umbrella term of neurotropic melanoma (NM). However, definitions for NM and desmoplastic NM are not consistent in the literature, presenting a barrier to a comprehensive understanding of these lesions. In this review, we parse the literature on DM, NM, and desmoplastic NM, to clarify definitions and ascertain the incidence of PNI, with a view toward understanding its prognostic relevance. Neurotrophins, which represent a family of signaling peptides important to the development and maintenance of the peripheral nervous system, have been implicated in the pathogenesis of PNI in select lineage-unrelated malignancies. Given this, we also detail evidence linking neurotrophins and their receptors (TrkA, RET, p75NGFR, and NCAM) to the pathogenesis of PNI in melanoma. PMID:26050260

  18. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury.

    PubMed

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  19. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

    PubMed Central

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  20. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    SciTech Connect

    Feng, Felix Y.; Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  1. Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy

    PubMed Central

    Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

    2016-01-01

    Abstract To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy. Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer. We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups. Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212–1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760–10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221–1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985–1.325, P = 0.078). PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence. PMID:27149460

  2. Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy: A Retrospective Analysis of 7781 Gastric Cancer Patients.

    PubMed

    Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

    2016-05-01

    To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212-1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760-10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221-1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985-1.325, P = 0.078).PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence. PMID:27149460

  3. Initial construction and validation of the Pathological Narcissism Inventory.

    PubMed

    Pincus, Aaron L; Ansell, Emily B; Pimentel, Claudia A; Cain, Nicole M; Wright, Aidan G C; Levy, Kenneth N

    2009-09-01

    The construct of narcissism is inconsistently defined across clinical theory, social-personality psychology, and psychiatric diagnosis. Two problems were identified that impede integration of research and clinical findings regarding narcissistic personality pathology: (a) ambiguity regarding the assessment of pathological narcissism vs. normal narcissism and (b) insufficient scope of existing narcissism measures. Four studies are presented documenting the initial derivation and validation of the Pathological Narcissism Inventory (PNI). The PNI is a 52-item self-report measure assessing 7 dimensions of pathological narcissism spanning problems with narcissistic grandiosity (Entitlement Rage, Exploitativeness, Grandiose Fantasy, Self-sacrificing Self-enhancement) and narcissistic vulnerability (Contingent Self-esteem, Hiding the Self, Devaluing). The PNI structure was validated via confirmatory factor analysis. The PNI correlated negatively with self-esteem and empathy, and positively with shame, interpersonal distress, aggression, and borderline personality organization. Grandiose PNI scales were associated with vindictive, domineering, intrusive, and overly-nurturant interpersonal problems, and vulnerable PNI scales were associated with cold, socially avoidant, and exploitable interpersonal problems. In a small clinical sample, PNI scales exhibited significant associations with parasuicidal behavior, suicide attempts, homicidal ideation, and several aspects of psychotherapy utilization. PMID:19719348

  4. A novel role of BELL1-like homeobox genes, PENNYWISE and POUND-FOOLISH, in floral patterning.

    PubMed

    Yu, Lifeng; Patibanda, Varun; Smith, Harley M S

    2009-02-01

    Flowers are determinate shoots comprised of perianth and reproductive organs displayed in a whorled phyllotactic pattern. Floral organ identity genes display region-specific expression patterns in the developing flower. In Arabidopsis, floral organ identity genes are activated by LEAFY (LFY), which functions with region-specific co-regulators, UNUSUAL FLORAL ORGANS (UFO) and WUSCHEL (WUS), to up-regulate homeotic genes in specific whorls of the flower. PENNYWISE (PNY) and POUND-FOOLISH (PNF) are redundant functioning BELL1-like homeodomain proteins that are expressed in shoot and floral meristems. During flower development, PNY functions with a co-repressor complex to down-regulate the homeotic gene, AGAMOUS (AG), in the outer whorls of the flower. However, the function of PNY as well as PNF in regulating floral organ identity in the central whorls of the flower is not known. In this report, we show that combining mutations in PNY and PNF enhance the floral patterning phenotypes of weak and strong alleles of lfy, indicating that these BELL1-like homeodomain proteins play a role in the specification of petals, stamens and carpels during flower development. Expression studies show that PNY and PNF positively regulate the homeotic genes, APETALA3 and AG, in the inner whorls of the flower. Moreover, PNY and PNF function in parallel with LFY, UFO and WUS to regulate homeotic gene expression. Since PNY and PNF interact with the KNOTTED1-like homeodomain proteins, SHOOTMERISTEMLESS (STM) and KNOTTED-LIKE from ARABIDOPSIS THALIANA2 (KNAT2) that regulate floral development, we propose that PNY/PNF-STM and PNY/PNF-KNAT2 complexes function in the inner whorls to regulate flower patterning events. PMID:19082619

  5. Hyperactive self-inactivating piggyBac for transposase-enhanced pronuclear microinjection transgenesis.

    PubMed

    Marh, Joel; Stoytcheva, Zoia; Urschitz, Johann; Sugawara, Atsushi; Yamashiro, Hideaki; Owens, Jesse B; Stoytchev, Ilko; Pelczar, Pawel; Yanagimachi, Ryuzo; Moisyadi, Stefan

    2012-11-20

    We have developed a unique method for mouse transgenesis. The transposase-enhanced pronuclear microinjection (PNI) technique described herein uses the hyperactive piggyBac transposase to insert a large transgene into the mouse genome. This procedure increased transgene integration efficiency by fivefold compared with conventional PNI or intracytoplasmic sperm injection-mediated transgenesis. Our data indicate that the transposase-enhanced PNI technique additionally requires fewer embryos to be microinjected than traditional methods to obtain transgenic animals. This transposase-mediated approach is also very efficient for single-cell embryo cytoplasmic injections, offering an easy-to-implement transgenesis method to the scientific community. PMID:23093669

  6. [Preoperative evaluation of surgery for intractable aspiration based on the prognostic nutritional index].

    PubMed

    Uchida, Masaya; Hashimoto, Keiko; Mukudai, Shigeyuki; Ushijima, Chihisa; Dejima, Kenji

    2014-12-01

    Because there is no absolute indicator of the nutritional status and prognosis in patients with severe aspiration problems, it is quite difficult to arrive at a true long-time prognosis. By performing surgery for intractable aspiration on such patients, both the prognosis and QOL of the patients could be expected to improve. In our department, we have experienced patients dying within 6 months after surgery. In these cases, the patient's preoperative nutritional status was not good. Therefore, we consider that, when we adopt this procedure, there should be some indicators we should use which could have an effect on the prognosis of such nutritionally-challenged patients. In patients who underwent surgery for intractable aspiration; we examined the relationship between their survival and the prognostic nutritional index (PNI) which is an indicator of the risk of complications such as post-operative events in the surgical field. We investigated the relationship between the prognosis and the postoperative indicators of each of the following: WBC, CRP, serum albumin level, and PNI. Out of a total of 31 cases, the average O-PNI of eight cases in which death occurred was 29.45, and the average of six cases in which death occurred within 6 months after surgery was 28.26. The average O-PNI of the survivors was 36.01. A significant association was noted between the early postoperative deaths and some of the four indicators namely that serum albumin level and O-PNI. Based on the ROC curve, the O-PNI offered higher precision than the albumin level. The cut-off value of the O-PNI value for early postoperative mortality rate was 32. The early postoperative mortality rate was 44.4% in patients with less than 32 O-PNI in the preoperative examination, but if it were O-PNI 32 or more, the early postoperative mortality rate was 9.1%, significantly lower. Therefore, O-PNI could be useful as one of the prognostic evaluation factors in the case of preoperative surgery for intractable

  7. The gene for the serpin thrombin inhibitor (P17), protease nexin I, is located on human chromosome 2q33-q35 and on syntenic regions in the mouse and sheep genomes

    SciTech Connect

    Carter, R.E.; Burkin, D.J.; Fournier, R.E.K.

    1995-05-01

    Protease nexin I (PNI) is the most important physiologic regulator of {alpha}-thrombin in tissues. PNI is highly expressed and developmentally regulated in the nervous system where it is concentrated at neuromuscular junctions and also central synapses in the hippocampus and striatum. Approximately 10% of identified proteins at mammalian neuromuscular junctions are serine protease inhibitors, consistent with their central role in balancing serine protease activity to develop, maintain, and remodel synapses. Southern blot hybridization of PNI cDNA to somatic cell hybrids placed the structural gene for PNI (locus PI7) on human chromosome 2q33-q35 and to syntenic chromosomes in the mouse (chromosome 1) and sheep (chromosome 2). 30 refs., 2 figs.

  8. Perineural invasion associated with increased cancer-specific mortality after external beam radiation therapy for men with low- and intermediate-risk prostate cancer

    SciTech Connect

    Beard, Clair . E-mail: cbeard@lroc.harvard.edu; Schultz, Delray; Loffredo, Marian; Cote, Kerri; Renshaw, Andrew A.; Hurwitz, Mark D.; D'Amico, Anthony V.

    2006-10-01

    Purpose: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients with prostate cancer after standard-dose external beam radiation therapy (RT). Methods and Materials: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test. Results: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p = 0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI+ patients vs. 5% for PNI- patients (p = 0.0008). Conclusions: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients.

  9. Perineural Invasion is a Marker for Pathologically Advanced Disease in Localized Prostate Cancer

    SciTech Connect

    Lee, Irwin H. . E-mail: irwinlee@med.umich.edu; Roberts, Rebecca; Shah, Rajal B.; Wojno, Kirk J.; Wei, John T.; Sandler, Howard M.

    2007-07-15

    Purpose: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer. Methods and Materials: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage). Results: For the overall population, PNI was associated with a significantly increased frequency of upgrading and of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation. Conclusions: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy.

  10. Relationship Between Perineural Invasion in Prostate Needle Biopsy Specimens and Pathologic Staging After Radical Prostatectomy

    PubMed Central

    Niroomand, Hassan; Nowroozi, Mohammadreza; Ayati, Mohsen; Jamshidian, Hassan; Arbab, Amir; Momeni, Seyed Ali; Ghadian, Alireza; Ghorbani, Hamidreza

    2016-01-01

    Background Prostate cancer is the second most common malignancy among men worldwide and the sixth cause of cancer-related death. Some authors have reported a relationship between perineural invasion (PNI), Gleason score, and the invasion of peripheral organs during prostatectomy. However, it is not yet clear whether pathological evidence of PNI is necessary for risk stratification in selecting treatment type. Objectives The clinical and pathological stages of prostate cancer are compared in patients under radical prostatectomy and in patients without perineural invasion. Patients and Methods This cross-sectional study was conducted using a sample of 109 patients who attended a tertiary health care center from 2008 to 2013. The selection criteria were PNI in prostate biopsy with Gleason scores less than six, seven, and eight to ten. The participants were enrolled in a census manner, and they underwent clinical staging. After radical prostatectomy, the rates of pathological staging were compared. The under-staging and over-staging rates among those with and without perineural invasion in biopsy samples were compared. Results The concordance between Gleason scores according to biopsy and pathology was 36.7% (40 subjects). The concordance rate was 46.4% and 33.3% among those with and without PNI, respectively. The concordance rates were significantly varied in different subclasses of Gleason scores in patients without PNI (P = 0.003); the highest concordance rate was a Gleason score of 7 (63.6%) and the lowest was a Gleason score of eight to ten (25%). However, there were no significant differences in patients with PNI (P > 0.05). Conclusions Although the presence of PNI in prostate biopsy is accompanied by higher surgical stages, PNI is not an appropriate independent factor in risk stratification.

  11. Preoperative body mass index-to-prognostic nutritional index ratio predicts pancreatic fistula after pancreaticoduodenectomy

    PubMed Central

    Tamura, Toshihisa; Minagawa, Noritaka; Hirata, Keiji

    2016-01-01

    Background Estimating or scoring the risk of post-operative pancreatic fistula (POPF) may help with selection of high-risk patients and individualized patient consent. However, there are no simple and reliable preoperative predictors of POPF used in daily clinical practice. Methods We investigated the utility of body mass index-to-prognostic nutritional index (BMI/PNI) ratio as a preoperative marker to predict the development of POPF in 87 patients undergoing pancreaticoduodenectomy. Results The overall incidence of clinical (grade B/C) POPF was 17% (15 of 87 patients). Among various pre-, intra-, and post-operative variables analyzed, higher BMI and lower PNI were identified as independent predictors for POPF by multivariate analysis. We therefore investigated BMI/PNI ratio as a preoperative predictor for POPF. BMI/PNI ratio was significantly higher in patients with POPF than in those without POPF (0.54 vs. 0.45, P=0.0007). A receiver operating characteristic (ROC) curve analysis demonstrated a fair capability of BMI/PNI ratio to predict the occurrence of POPF (area under the ROC curve 0.781). With a cut-off value of 0.5, the sensitivity, specificity, and diagnostic accuracy of BMI/PNI ratio to predict POPF was 73%, 74%, and 74%, respectively. In particular, when restricted to a subgroup of elderly (≥75 years old) male patients, the sensitivity, specificity, and diagnostic accuracy of BMI/PNI ratio was 100%, 100%, and 100%, respectively. Conclusions The BMI/PNI ratio is a simple preoperative marker to predict the occurrence of POPF after pancreaticoduodenectomy. PMID:27275468

  12. Precisely Determining Ultralow level UO22+ in Natural Water with Plasmonic Nanowire Interstice Sensor

    NASA Astrophysics Data System (ADS)

    Gwak, Raekeun; Kim, Hongki; Yoo, Seung Min; Lee, Sang Yup; Lee, Gyoung-Ja; Lee, Min-Ku; Rhee, Chang-Kyu; Kang, Taejoon; Kim, Bongsoo

    2016-01-01

    Uranium is an essential raw material in nuclear energy generation; however, its use raises concerns about the possibility of severe damage to human health and the natural environment. In this work, we report an ultrasensitive uranyl ion (UO22+) detection method in natural water that uses a plasmonic nanowire interstice (PNI) sensor combined with a DNAzyme-cleaved reaction. UO22+ induces the cleavage of DNAzymes into enzyme strands and released strands, which include Raman-active molecules. A PNI sensor can capture the released strands, providing strong surface-enhanced Raman scattering signal. The combination of a PNI sensor and a DNAzyme-cleaved reaction significantly improves the UO22+ detection performance, resulting in a detection limit of 1 pM and high selectivity. More importantly, the PNI sensor operates perfectly, even in UO22+-contaminated natural water samples. This suggests the potential usefulness of a PNI sensor in practical UO22+-sensing applications. We anticipate that diverse toxic metal ions can be detected by applying various ion-specific DNA-based ligands to PNI sensors.

  13. Precisely Determining Ultralow level UO2(2+) in Natural Water with Plasmonic Nanowire Interstice Sensor.

    PubMed

    Gwak, Raekeun; Kim, Hongki; Yoo, Seung Min; Lee, Sang Yup; Lee, Gyoung-Ja; Lee, Min-Ku; Rhee, Chang-Kyu; Kang, Taejoon; Kim, Bongsoo

    2016-01-01

    Uranium is an essential raw material in nuclear energy generation; however, its use raises concerns about the possibility of severe damage to human health and the natural environment. In this work, we report an ultrasensitive uranyl ion (UO2(2+)) detection method in natural water that uses a plasmonic nanowire interstice (PNI) sensor combined with a DNAzyme-cleaved reaction. UO2(2+) induces the cleavage of DNAzymes into enzyme strands and released strands, which include Raman-active molecules. A PNI sensor can capture the released strands, providing strong surface-enhanced Raman scattering signal. The combination of a PNI sensor and a DNAzyme-cleaved reaction significantly improves the UO2(2+) detection performance, resulting in a detection limit of 1 pM and high selectivity. More importantly, the PNI sensor operates perfectly, even in UO2(2+)-contaminated natural water samples. This suggests the potential usefulness of a PNI sensor in practical UO2(2+)-sensing applications. We anticipate that diverse toxic metal ions can be detected by applying various ion-specific DNA-based ligands to PNI sensors. PMID:26791784

  14. Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain

    PubMed Central

    Masuda, Takahiro; Ozono, Yui; Mikuriya, Satsuki; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Iwatsuki, Ken; Uneyama, Hisayuki; Ichikawa, Reiko; Salter, Michael W.; Tsuda, Makoto; Inoue, Kazuhide

    2016-01-01

    Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing ATP within the spinal cord after PNI is unknown. Here we show that PNI increases expression of vesicular nucleotide transporter (VNUT) in the spinal cord. Extracellular ATP content ([ATP]e) within the spinal cord was increased after PNI, and this increase was suppressed by exocytotic inhibitors. Mice lacking VNUT did not show PNI-induced increase in [ATP]e and had attenuated hypersensitivity. These phenotypes were recapitulated in mice with specific deletion of VNUT in spinal dorsal horn (SDH) neurons, but not in mice lacking VNUT in primary sensory neurons, microglia or astrocytes. Conversely, ectopic VNUT expression in SDH neurons of VNUT-deficient mice restored PNI-induced increase in [ATP]e and pain. Thus, VNUT is necessary for exocytotic ATP release from SDH neurons which contributes to neuropathic pain. PMID:27515581

  15. Precisely Determining Ultralow level UO22+ in Natural Water with Plasmonic Nanowire Interstice Sensor

    PubMed Central

    Gwak, Raekeun; Kim, Hongki; Yoo, Seung Min; Lee, Sang Yup; Lee, Gyoung-Ja; Lee, Min-Ku; Rhee, Chang-Kyu; Kang, Taejoon; Kim, Bongsoo

    2016-01-01

    Uranium is an essential raw material in nuclear energy generation; however, its use raises concerns about the possibility of severe damage to human health and the natural environment. In this work, we report an ultrasensitive uranyl ion (UO22+) detection method in natural water that uses a plasmonic nanowire interstice (PNI) sensor combined with a DNAzyme-cleaved reaction. UO22+ induces the cleavage of DNAzymes into enzyme strands and released strands, which include Raman-active molecules. A PNI sensor can capture the released strands, providing strong surface-enhanced Raman scattering signal. The combination of a PNI sensor and a DNAzyme-cleaved reaction significantly improves the UO22+ detection performance, resulting in a detection limit of 1 pM and high selectivity. More importantly, the PNI sensor operates perfectly, even in UO22+-contaminated natural water samples. This suggests the potential usefulness of a PNI sensor in practical UO22+-sensing applications. We anticipate that diverse toxic metal ions can be detected by applying various ion-specific DNA-based ligands to PNI sensors. PMID:26791784

  16. Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain.

    PubMed

    Masuda, Takahiro; Ozono, Yui; Mikuriya, Satsuki; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Iwatsuki, Ken; Uneyama, Hisayuki; Ichikawa, Reiko; Salter, Michael W; Tsuda, Makoto; Inoue, Kazuhide

    2016-01-01

    Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing ATP within the spinal cord after PNI is unknown. Here we show that PNI increases expression of vesicular nucleotide transporter (VNUT) in the spinal cord. Extracellular ATP content ([ATP]e) within the spinal cord was increased after PNI, and this increase was suppressed by exocytotic inhibitors. Mice lacking VNUT did not show PNI-induced increase in [ATP]e and had attenuated hypersensitivity. These phenotypes were recapitulated in mice with specific deletion of VNUT in spinal dorsal horn (SDH) neurons, but not in mice lacking VNUT in primary sensory neurons, microglia or astrocytes. Conversely, ectopic VNUT expression in SDH neurons of VNUT-deficient mice restored PNI-induced increase in [ATP]e and pain. Thus, VNUT is necessary for exocytotic ATP release from SDH neurons which contributes to neuropathic pain. PMID:27515581

  17. Stromal-derived factor-1α/CXCL12-CXCR4 chemotactic pathway promotes perineural invasion in pancreatic cancer

    PubMed Central

    Xu, Qinhong; Wang, Zheng; Chen, Xin; Duan, Wanxing; Lei, Jianjun; Zong, Liang; Li, Xuqi; Sheng, Liang; Ma, Jiguang; Han, Liang; Li, Wei; Zhang, Lun; Guo, Kun; Ma, Zhenhua; Wu, Zheng; Wu, Erxi; Ma, Qingyong

    2015-01-01

    Perineural invasion (PNI) is considered as an alternative route for the metastatic spread of pancreatic cancer cells; however, the molecular changes leading to PNI are still poorly understood. In this study, we show that the CXCL12/CXCR4 axis plays a pivotal role in the neurotropism of pancreatic cancer cells to local peripheral nerves. Immunohistochemical staining results revealed that CXCR4 elevation correlated with PNI in 78 pancreatic cancer samples. Both in vitro and in vivo PNI models were applied to investigate the function of the CXCL12/CXCR4 signaling in PNI progression and pathogenesis. The results showed that the activation of the CXCL12/CXCR4 axis significantly increased pancreatic cancer cells invasion and promoted the outgrowth of the dorsal root ganglia. CXCL12 derived from the peripheral nerves stimulated the invasion and chemotactic migration of CXCR4-positive cancer cells in a paracrine manner, eventually leading to PNI. In vivo analyses revealed that the abrogation of the activated signaling inhibited tumor growth and invasion of the sciatic nerve toward the spinal cord. These data indicate that the CXCL12/CXCR4 axis may be a novel therapeutic target to prevent the perineural dissemination of pancreatic cancer. PMID:25605248

  18. Phrenic Nerve Injury After Catheter Ablation of Atrial Fibrillation

    PubMed Central

    Sacher, Frederic; Jais, Pierre; Stephenson, Kent; O'Neill, Mark D; Hocini, Meleze; Clementy, Jacques; Stevenson, William G; Haissaguerre, Michel

    2007-01-01

    Phrenic Nerve Injury (PNI) has been well studied by cardiac surgeons. More recently it has been recognized as a potential complication of catheter ablation with a prevalence of 0.11 to 0.48 % after atrial fibrillation (AF) ablation. This review will focus on PNI after AF ablation Anatomical studies have shown a close relationship between the right phrenic nerve and it's proximity to the superior vena cava (SVC), and the antero-inferior part of the right superior pulmonary vein (RSPV). In addition, the proximity of the left phrenic nerve to the left atrial appendage has been well established. Independent of the type of ablation catheter (4mm, 8 mm, irrigated tip, balloon) or energy source used (radiofrequency (RF), ultrasound, cryothermia, and laser); the risk of PNI exists during ablation at the critical areas listed above. Although up to thirty-one percent of patients with PNI after AF ablation remain asymptomatic, dyspnea remain the cardinal symptom and is present in all symptomatic patients. Despite the theoretical risk for significant adverse effect on functional status and quality of life, short-term outcomes from published studies appear favorable with 81% of patients with PNI having a complete recovery after 7 ± 7 months. Conclusion Existing studies have described PNI as an uncommon but avoidable complication in patients undergoing pulmonary vein isolation for AF. Prior to ablation at the SVC, antero-inferior RSPV ostium or the left atrial appendage, pacing should be performed before energy delivery. If phrenic nerve capture is documented, energy delivery should be avoided at this site. Electrophysiologist's vigilance as well as pacing prior to ablation at high risk sites in close proximity to the phrenic nerve are the currently available tools to avoid the complication of PNI. PMID:17235367

  19. A Preoperative Nutritional Index for Predicting Cancer-Specific and Overall Survival in Chinese Patients With Laryngeal Cancer

    PubMed Central

    Fu, Yan; Chen, Shu-Wei; Chen, Shi-Qi; Ou-Yang, Dian; Liu, Wei-Wei; Song, Ming; Yang, An-Kui; Zhang, Quan

    2016-01-01

    Abstract Pinato prognostic nutritional index (PNI) adequately predicts long-term outcomes of various malignancies. However, its value in predicting outcomes in laryngeal squamous cell carcinoma (LSCC) is unknown. All patients newly diagnosed with LSCC presenting to the Department of Head and Neck Oncology at Sun Yat-sen University Cancer Center between January 1, 1990 and July 31, 2010 were eligible. The PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count/L. The Cutoff Finder software program was used to classify the patients into 3 groups for which the PNI score was at least 70% sensitive, at least 70% specific, or equivocal. Cancer-specific survival was estimated using the Kaplan–Meier method, and predictors were assessed with Cox regression analysis. Median time between surgery and PNI administration for the 975 eligible patients was 83 months. Index score groups were significantly associated with age, T stage, TNM stage, and type of surgery. Five-year CSS and OS were 57.3% and 56.6% in patients with PNI scores below 48.65 (low-probability of survival), 72.8% and 71.3% with scores between 48.65 and 56.93 (moderate-probability of survival), and 77.6% and 75.3% with scores above 56.93 (high-probability of survival); 10-year CSS and OS were 44.2% and 42.7%, 61.6% and 55.6%, 68.3% and 63.5%, respectively. The PNI score groups significantly predicted CSS and OS (P < 0.001). The PNI is an inexpensive and readily available score that predicted survival in patients with LSCC after curative laryngectomy. PMID:26986105

  20. Slug silencing inhibited perineural invasion through regulation of EMMPRIN expression in human salivary adenoid cystic carcinoma.

    PubMed

    Wu, Baolei; Wei, Jianhua; Hu, Zhiqiang; Shan, Chun; Wang, Lei; Zhang, Chenping; Yang, Xi; Yang, Xinjie; Lei, Delin

    2016-02-01

    Salivary adenoid cystic carcinoma (SACC) is the most frequent salivary gland malignancy with a unique characteristic that has been named perineural invasion (PNI). EMMPRIN is a transmembrane glycoprotein that has been demonstrated to promote PNI in SACC. Slug, one of the most effective promoters of the epithelial-to-mesenchymal transition (EMT), has been found to be associated with PNI in SACC. The aim of the present study was to investigate the roles and relationships of Slug, EMMPRIN, and E-cadherin in the PNI process of SACC. The expression levels of Slug, EMMPRIN, and E-cadherin in 115 primary SACC cases were statistically analyzed by immunohistochemistry. Simultaneously, the SACC cell line SACC-83 was transfected with recombinant plasmids of silencing Slug (si-Slug) and/or silencing EMMPRIN (si-EMMPRIN). The functions of Slug and EMMPRIN in the EMT and PNI process were assessed by reverse transcription PCR (RT-PCR), western blotting, morphological observation, scratch test, migration assay, and in vitro perineural invasion assay. The immunohistochemical statistics revealed that the high expression of Slug and EMMPRIN and the low expression of E-cadherin were significantly associated with the PNI of SACC (P < 0.05). Slug expression was significantly associated with EMMPRIN expression (P < 0.05), and Slug expression and EMMPRIN expression were both significantly negatively associated with E-cadherin expression (P < 0.05). Slug and EMMPRIN silencing both significantly inhibited EMMPRIN expression but promoted E-cadherin expression in SACC-83 cells (P < 0.01). The series of in vitro assays revealed that silencing of Slug, EMMPRIN, or both induced cell morphology changes and inhibited tumor cell motility and PNI ability in SACC-83 cells (P < 0.01). These results suggested that Slug silencing could inhibit the EMT process by downregulating EMMPRIN and then upregulating E-cadherin in the PNI process of SACC. The present study indicated that Slug

  1. Ecoimmunology for psychoneuroimmunologists: Considering context in neuroendocrine-immune-behavior interactions.

    PubMed

    Demas, Gregory E; Carlton, Elizabeth D

    2015-02-01

    The study of immunity has become an important area of investigation for researchers in a wide range of areas outside the traditional discipline of immunology. For the last several decades, psychoneuroimmunology (PNI) has strived to identify key interactions among the nervous, endocrine and immune systems and behavior. More recently, the field of ecological immunology (ecoimmunology) has been established within the perspectives of ecology and evolutionary biology, sharing with PNI an appreciation of the environmental influences on immune function. The primary goal of ecoimmunology is to understand immune function within a broadly integrative, organismal context, typically from an ultimate, evolutionary perspective. To accomplish this ecoimmunology, like PNI, has become a broadly integrative field of investigation, combining diverse approaches from evolution and ecology to endocrinology and neurobiology. The disciplines of PNI and ecoimmunology, with their unique yet complementary perspectives and methodologies, have much to offer one another. Researchers in both fields, however, remain largely unaware of each other's findings despite attempts at integration. The goal of this review is to share with psychoneuroimmunologists and other mechanistically-oriented researchers some of the core concepts and principles, as well as relevant recent findings, within ecoimmunology with the hope that this information will prove relevant to their own research programs. More broadly, our goal is to attempt to integrate both the proximate and ultimate perspectives offered by PNI and ecoimmunology respectively into a common theoretical framework for understanding neuro-endocrine-immune interactions and behavior in a larger ecological, evolutionary context. PMID:25218837

  2. Repression of Lateral Organ Boundary Genes by PENNYWISE and POUND-FOOLISH Is Essential for Meristem Maintenance and Flowering in Arabidopsis1[OPEN

    PubMed Central

    Khan, Madiha; Ragni, Laura; Tabb, Paul; Salasini, Brenda C.; Chatfield, Steven; Datla, Raju; Lock, John; Kuai, Xiahezi; Després, Charles; Proveniers, Marcel; Yongguo, Cao; Xiang, Daoquan; Morin, Halima; Rullière, Jean-Pierre; Citerne, Sylvie; Hepworth, Shelley R.; Pautot, Véronique

    2015-01-01

    In the model plant Arabidopsis (Arabidopsis thaliana), endogenous and environmental signals acting on the shoot apical meristem cause acquisition of inflorescence meristem fate. This results in changed patterns of aerial development seen as the transition from making leaves to the production of flowers separated by elongated internodes. Two related BEL1-like homeobox genes, PENNYWISE (PNY) and POUND-FOOLISH (PNF), fulfill this transition. Loss of function of these genes impairs stem cell maintenance and blocks internode elongation and flowering. We show here that pny pnf apices misexpress lateral organ boundary genes BLADE-ON-PETIOLE1/2 (BOP1/2) and KNOTTED-LIKE FROM ARABIDOPSIS THALIANA6 (KNAT6) together with ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1). Inactivation of genes in this module fully rescues pny pnf defects. We further show that BOP1 directly activates ATH1, whereas activation of KNAT6 is indirect. The pny pnf restoration correlates with renewed accumulation of transcripts conferring floral meristem identity, including FD, SQUAMOSA PROMOTER-BINDING PROTEIN LIKE genes, LEAFY, and APETALA1. To gain insight into how this module blocks flowering, we analyzed the transcriptome of BOP1-overexpressing plants. Our data suggest a central role for the microRNA156-SQUAMOSA PROMOTER BINDING PROTEIN-LIKE-microRNA172 module in integrating stress signals conferred in part by promotion of jasmonic acid biosynthesis. These data reveal a potential mechanism by which repression of lateral organ boundary genes by PNY-PNF is essential for flowering. PMID:26417006

  3. Floral Induction in Arabidopsis by FLOWERING LOCUS T Requires Direct Repression of BLADE-ON-PETIOLE Genes by the Homeodomain Protein PENNYWISE1[OPEN

    PubMed Central

    Andrés, Fernando; Romera-Branchat, Maida; Martínez-Gallegos, Rafael; Patel, Vipul; Schneeberger, Korbinian; Jang, Seonghoe; Altmüller, Janine; Nürnberg, Peter; Coupland, George

    2015-01-01

    Flowers form on the flanks of the shoot apical meristem (SAM) in response to environmental and endogenous cues. In Arabidopsis (Arabidopsis thaliana), the photoperiodic pathway acts through FLOWERING LOCUS T (FT) to promote floral induction in response to day length. A complex between FT and the basic leucine-zipper transcription factor FD is proposed to form in the SAM, leading to activation of APETALA1 and LEAFY and thereby promoting floral meristem identity. We identified mutations that suppress FT function and recovered a new allele of the homeodomain transcription factor PENNYWISE (PNY). Genetic and molecular analyses showed that ectopic expression of BLADE-ON-PETIOLE1 (BOP1) and BOP2, which encode transcriptional coactivators, in the SAM during vegetative development, confers the late flowering of pny mutants. In wild-type plants, BOP1 and BOP2 are expressed in lateral organs close to boundaries of the SAM, whereas in pny mutants, their expression occurs in the SAM. This ectopic expression lowers FD mRNA levels, reducing responsiveness to FT and impairing activation of APETALA1 and LEAFY. We show that PNY binds to the promoters of BOP1 and BOP2, repressing their transcription. These results demonstrate a direct role for PNY in defining the spatial expression patterns of boundary genes and the significance of this process for floral induction by FT. PMID:26417007

  4. Floral Induction in Arabidopsis by FLOWERING LOCUS T Requires Direct Repression of BLADE-ON-PETIOLE Genes by the Homeodomain Protein PENNYWISE.

    PubMed

    Andrés, Fernando; Romera-Branchat, Maida; Martínez-Gallegos, Rafael; Patel, Vipul; Schneeberger, Korbinian; Jang, Seonghoe; Altmüller, Janine; Nürnberg, Peter; Coupland, George

    2015-11-01

    Flowers form on the flanks of the shoot apical meristem (SAM) in response to environmental and endogenous cues. In Arabidopsis (Arabidopsis thaliana), the photoperiodic pathway acts through FLOWERING LOCUS T (FT) to promote floral induction in response to day length. A complex between FT and the basic leucine-zipper transcription factor FD is proposed to form in the SAM, leading to activation of APETALA1 and LEAFY and thereby promoting floral meristem identity. We identified mutations that suppress FT function and recovered a new allele of the homeodomain transcription factor PENNYWISE (PNY). Genetic and molecular analyses showed that ectopic expression of BLADE-ON-PETIOLE1 (BOP1) and BOP2, which encode transcriptional coactivators, in the SAM during vegetative development, confers the late flowering of pny mutants. In wild-type plants, BOP1 and BOP2 are expressed in lateral organs close to boundaries of the SAM, whereas in pny mutants, their expression occurs in the SAM. This ectopic expression lowers FD mRNA levels, reducing responsiveness to FT and impairing activation of APETALA1 and LEAFY. We show that PNY binds to the promoters of BOP1 and BOP2, repressing their transcription. These results demonstrate a direct role for PNY in defining the spatial expression patterns of boundary genes and the significance of this process for floral induction by FT. PMID:26417007

  5. Ecoimmunology for Psychoneuroimmunologists: Considering Context in Neuroendocrine-Immune-Behavior Interactions

    PubMed Central

    Demas, Gregory E.; Carlton, Elizabeth D.

    2014-01-01

    The study of immunity has become an important area of investigation for researchers in a wide range of areas outside the traditional discipline of immunology. For the last several decades, psychoneuroimmunology (PNI) has strived to identify key interactions among the nervous, endocrine and immune systems and behavior. More recently, the field of ecological immunology (ecoimmunology) has been established within the perspectives of ecology and evolutionary biology, sharing with PNI an appreciation of the environmental influences on immune function. The primary goal of ecoimmunology is to understand immune function within a broadly integrative, organismal context, typically from an ultimate, evolutionary perspective. To accomplish this ecoimmunology, like PNI, has become a broadly integrative field of investigation, combining diverse approaches from evolution and ecology to endocrinology and neurobiology. The disciplines of PNI and ecoimmunology, with their unique yet complementary perspectives and methodologies, have much to offer one another. Researchers in both fields, however, remain largely unaware of each other's findings despite attempts at integration. The goal of this review is to share with psychoneuroimmunologists and other mechanistically-oriented researchers some of the core concepts and principles, as well as relevant recent findings, within ecoimmunology with the hope that this information will prove relevant to their own research programs. More broadly, our goal is to attempt to integrate both the proximate and ultimate perspectives offered by PNI and ecoimmunology respectively into a common theoretical framework for understanding neuro-endocrine-immune interactions and behavior in a larger ecological, evolutionary context. PMID:25218837

  6. En Bloc Resection of Desmoplastic Neurotropic Melanoma with Perineural Invasion of the Intracranial Trigeminal and Intraparotid Facial Nerve: Case Report and Review of the Literature

    PubMed Central

    Erkan, Serkan; Acharya, Aanand N.; Savundra, James; Lewis, Stephen B.; Rajan, Gunesh P.

    2015-01-01

    Background Desmoplastic neurotropic melanoma (DNM) is a rare, highly malignant, and locally invasive form of cutaneous melanoma with a tendency for perineural invasion (PNI). Methods We report a case of a 61-year-old man presenting with right-sided trigeminal neuralgia and progressive facial paresis due to the PNI of the intracranial trigeminal nerve and the intraparotid facial nerve from DNM. We also present a review of the literature with six cases of DNM with PNI of the intracranial trigeminal nerve identified. Results The combined transtemporal-infratemporal fossa approach was performed to achieve total en bloc resection of the tumor mass followed by postoperative radiotherapy (PORT). After 24 months of follow-up, the patient remains disease free with no signs of recurrence on magnetic resonance imaging. Conclusion We recommend the en bloc resection of the tumor mass followed by PORT for the management of DNM with PNI. A high index of suspicion for PNI as a cause of cranial neuropathies is essential for the early detection and treatment of patients with known melanoma. PMID:26929895

  7. Repression of Lateral Organ Boundary Genes by PENNYWISE and POUND-FOOLISH Is Essential for Meristem Maintenance and Flowering in Arabidopsis.

    PubMed

    Khan, Madiha; Ragni, Laura; Tabb, Paul; Salasini, Brenda C; Chatfield, Steven; Datla, Raju; Lock, John; Kuai, Xiahezi; Després, Charles; Proveniers, Marcel; Yongguo, Cao; Xiang, Daoquan; Morin, Halima; Rullière, Jean-Pierre; Citerne, Sylvie; Hepworth, Shelley R; Pautot, Véronique

    2015-11-01

    In the model plant Arabidopsis (Arabidopsis thaliana), endogenous and environmental signals acting on the shoot apical meristem cause acquisition of inflorescence meristem fate. This results in changed patterns of aerial development seen as the transition from making leaves to the production of flowers separated by elongated internodes. Two related BEL1-like homeobox genes, PENNYWISE (PNY) and POUND-FOOLISH (PNF), fulfill this transition. Loss of function of these genes impairs stem cell maintenance and blocks internode elongation and flowering. We show here that pny pnf apices misexpress lateral organ boundary genes BLADE-ON-PETIOLE1/2 (BOP1/2) and KNOTTED-LIKE FROM ARABIDOPSIS THALIANA6 (KNAT6) together with ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1). Inactivation of genes in this module fully rescues pny pnf defects. We further show that BOP1 directly activates ATH1, whereas activation of KNAT6 is indirect. The pny pnf restoration correlates with renewed accumulation of transcripts conferring floral meristem identity, including FD, SQUAMOSA PROMOTER-BINDING PROTEIN LIKE genes, LEAFY, and APETALA1. To gain insight into how this module blocks flowering, we analyzed the transcriptome of BOP1-overexpressing plants. Our data suggest a central role for the microRNA156-SQUAMOSA PROMOTER BINDING PROTEIN-LIKE-microRNA172 module in integrating stress signals conferred in part by promotion of jasmonic acid biosynthesis. These data reveal a potential mechanism by which repression of lateral organ boundary genes by PNY-PNF is essential for flowering. PMID:26417006

  8. En Bloc Resection of Desmoplastic Neurotropic Melanoma with Perineural Invasion of the Intracranial Trigeminal and Intraparotid Facial Nerve: Case Report and Review of the Literature.

    PubMed

    Erkan, Serkan; Acharya, Aanand N; Savundra, James; Lewis, Stephen B; Rajan, Gunesh P

    2016-03-01

    Background Desmoplastic neurotropic melanoma (DNM) is a rare, highly malignant, and locally invasive form of cutaneous melanoma with a tendency for perineural invasion (PNI). Methods We report a case of a 61-year-old man presenting with right-sided trigeminal neuralgia and progressive facial paresis due to the PNI of the intracranial trigeminal nerve and the intraparotid facial nerve from DNM. We also present a review of the literature with six cases of DNM with PNI of the intracranial trigeminal nerve identified. Results The combined transtemporal-infratemporal fossa approach was performed to achieve total en bloc resection of the tumor mass followed by postoperative radiotherapy (PORT). After 24 months of follow-up, the patient remains disease free with no signs of recurrence on magnetic resonance imaging. Conclusion We recommend the en bloc resection of the tumor mass followed by PORT for the management of DNM with PNI. A high index of suspicion for PNI as a cause of cranial neuropathies is essential for the early detection and treatment of patients with known melanoma. PMID:26929895

  9. Piezoelectric Nanoindentation

    SciTech Connect

    Rar, Andrei; Pharr, George Mathews; Oliver, Warren C.; Karapetian, Edgar; Kalinin, Sergei V

    2006-01-01

    Piezoelectric nanoindentation (PNI) has been developed to quantitatively address electromechanical coupling and pressure-induced dynamic phenomena in ferroelectric materials on the nanoscale. In PNI, an oscillating voltage is applied between the back side of the sample and the indenter tip, and the first harmonic of bias-induced surface displacement at the area of indenter contact is detected. PNI is implemented using a standard nanoindentation system equipped with a continuous stiffness measurement system. The piezoresponse of polycrystalline lead zirconate titanate (PZT) and BaTiO{sub 3} piezoceramics was studied during a standard nanoindentation experiment. For PZT, the response was found to be load independent, in agreement with theoretical predictions. In polycrystalline barium titanate, a load dependence of the piezoresponse was observed. The potential of piezoelectric nanoindentation for studies of phase transitions and local structure-property relations in piezoelectric materials is discussed.

  10. Novel immunological and nutritional-based prognostic index for gastric cancer

    PubMed Central

    Sun, Kai-Yu; Xu, Jian-Bo; Chen, Shu-Ling; Yuan, Yu-Jie; Wu, Hui; Peng, Jian-Jun; Chen, Chuang-Qi; Guo, Pi; Hao, Yuan-Tao; He, Yu-Long

    2015-01-01

    AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer. PMID:26019461

  11. Antagonistic Interaction of BLADE-ON-PETIOLE1 and 2 with BREVIPEDICELLUS and PENNYWISE Regulates Arabidopsis Inflorescence Architecture1[C][W][OA

    PubMed Central

    Khan, Madiha; Xu, Mingli; Murmu, Jhadeswar; Tabb, Paul; Liu, Yuanyuan; Storey, Kathryn; McKim, Sarah M.; Douglas, Carl J.; Hepworth, Shelley R.

    2012-01-01

    The transition to flowering in many plant species, including Arabidopsis (Arabidopsis thaliana), is marked by the elongation of internodes to make an inflorescence upon which lateral branches and flowers are arranged in a characteristic pattern. Inflorescence patterning relies in part on the activities of two three-amino-acid loop-extension homeodomain transcription factors: BREVIPEDICELLUS (BP) and PENNYWISE (PNY) whose interacting products also promote meristem function. We examine here the genetic interactions between BP-PNY whose expression is up-regulated in stems at the floral transition, and the lateral organ boundary genes BLADE-ON-PETIOLE1 (BOP1) and BOP2, whose expression is restricted to pedicel axils. Our data show that bp and pny inflorescence defects are caused by BOP1/2 gain of function in stems and pedicels. Compatible with this, inactivation of BOP1/2 rescues these defects. BOP expression domains are differentially enlarged in bp and pny mutants, corresponding to the distinctive patterns of growth restriction in these mutants leading to compacted internodes and clustered or downward-oriented fruits. Our data indicate that BOP1/2 are positive regulators of KNOTTED1-LIKE FROM ARABIDOPSIS THALIANA6 expression and that growth restriction in BOP1/2 gain-of-function plants requires KNOTTED1-LIKE FROM ARABIDOPSIS THALIANA6. Antagonism between BOP1/2 and BP is explained in part by their reciprocal regulation of gene expression, as evidenced by the identification of lignin biosynthetic genes that are repressed by BP and activated by BOP1/2 in stems. These data reveal BOP1/2 gain of function as the basis of bp and pny inflorescence defects and reveal how antagonism between BOP1/2 and BP-PNY contributes to inflorescence patterning in a model plant species. PMID:22114095

  12. Comprehensive Evaluation of Peripheral Nerve Regeneration in the Acute Healing Phase Using Tissue Clearing and Optical Microscopy in a Rodent Model

    PubMed Central

    Keating, Cameron P.; Senthil-Kumar, Prabhu; Zhao, Jie; Randolph, Mark A.; Winograd, Jonathan M.; Evans, Conor L.

    2014-01-01

    Peripheral nerve injury (PNI), a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout nerves in a PNI model

  13. Downregulation of p53 promotes in vitro perineural invasive activity of human salivary adenoid cystic carcinoma cells through epithelial-mesenchymal transition-like changes.

    PubMed

    Yang, Xiangming; Jing, Da; Liu, Lijun; Shen, Zhiyuan; Ju, Jun; Ma, Chao; Sun, Moyi

    2015-04-01

    Salivary adenoid cystic carcinoma (SACC) is a malignant tumor that is characterized by perineural invasion (PNI). p53 is an essential tumor-suppressor gene and p53 mutations play a critical role in tumor occurrence and progression (e.g., pancreatic, prostate and head and neck cancer). However, the regulatory role of the p53 gene in SACC and the PNI process remains unknown. In the present study, we employed RNA interference technique to downregulate p53 gene expression in SACC-83 cells to explore the role of p53 in the PNI process. Our results showed that the downregulation of the p53 gene induced significant 'epithelial-mesenchymal transition (EMT)-like changes' in SACC-83 cells, including decreased expression levels of epithelial markers (E-cadherin, EMA and CK5) and increased expression levels of mesenchymal markers (vimentin, N-cadherin and C-cadherin). The downregulation of p53 also caused a lower apoptotic index of Annexin V-FITC/PI and a lower number of SACC-83 cells in the second G0/G1 phase of the cell cycle. Furthermore, the downregulation of the p53 gene resulted in a significant increase in PNI activity in the SACC-83 cells. Thus, our findings revealed that downregulation of p53 promoted in vitro PNI activity through 'EMT-like changes' in SACC-83 cells. The present study suggests the essential regulatory role of p53 in the PNI activity of SACC cells, and implies that p53 may be a new target gene for the clinical treatment of SACC. PMID:25625376

  14. Prognostic Value of Perineural Invasion in Esophageal and Esophagogastric Junction Carcinoma: A Meta-Analysis

    PubMed Central

    Gao, Aiqin; Wang, Linlin; Li, Juan; Li, Hongyu; Han, Yali; Sun, Yuping

    2016-01-01

    Objective. Here we aimed to clarify the prognostic significance of perineural invasion (PNI) in esophageal and esophagogastric junction (EGJ) carcinoma. Methods. A comprehensive literature search for relevant reports published up to July 2015 was performed using Pubmed and Embase databases. The pooled HR and 95% CI for overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic value. The association of PNI with pathological characteristics was evaluated by OR and 95% CI. Results. A total of 13 cohorts were retrieved, covering 2770 patients treated by surgery. The cumulative analysis revealed a statistical correlation between PNI and poor OS (HR = 1.76, 95% CI: 1.54–2.20, and P < 0.00001), as well as poor DFS (HR = 1.96, 95% CI: 1.42–2.71, and P < 0.001). Moreover, analysis of 1475 patients showed improved PNI in T3 + T4 (OR = 0.39, 95% CI: 0.21–0.70, and P = 0.002), N+ (OR = 0.52, 95% CI: 0.40–0.69, and P < 0.00001), and G3 + G4 (OR = 0.66, 95% CI: 0.48–0.90, and P = 0.008) patients compared with T1 + T2, N−, and G1 + G2 ones, respectively. No significant heterogeneity was found between the studies. Conclusions. PNI is an adverse prognostic biomarker in esophageal and EGJ carcinoma. Moreover, PNI implies advanced T, N stage and poor cell differentiation. PMID:27051075

  15. Perioperative anaesthetic management of penetrating neck injury associated with Rh blood type in a young adult

    PubMed Central

    Wang, Tao; Zhou, Yeting; Shi, Jiaohui; Wang, Zhichun

    2013-01-01

    We describe here a young adult patient with penetrating neck injuries (PNI) with an Rh negative blood type and discuss the perioperative anaesthetic management of single-stage surgical exploration under general anaesthesia and extracorporeal circulation in this patient. The patient had zone II PNI and he was in a haemodynamically progressive unstable state, and the knife penetrated the left internal jugular vein, superior thyroid artery and recurrent laryngeal nerve; the trachea and the oesophagus were swelling at a rapid rate. Eight weeks after operation, the patient was discharged from the hospital without any complications. PMID:23429024

  16. Psychoneuroimmunology and the pediatric surgeon.

    PubMed

    Tagge, Edward P; Natali, Elizabeth Lee; Lima, Evan; Leek, Dustin; Neece, Cameron L; Randall, Kiti Freier

    2013-08-01

    The mind-body connection is receiving increasing scrutiny in a large number of clinical settings, although research has lagged in the pediatric specialties. Psychoneuroimmunology (PNI) is a novel interdisciplinary scientific field that examines the relationship of the mind to the patient's neurologic, endocrine, and immune systems by examining critical parameters such as the effects of mental stress on wound healing and infection rates. Techniques that modify a patient's emotional and mental responses to illness and surgery have positive effects on their physiology resulting in improved recoveries and higher patient satisfaction rates. In the appropriate clinical settings, an awareness of PNI can enhance outcomes for pediatric surgical patients. PMID:23870208

  17. Perineural invasion on prostate needle biopsy does not predict biochemical failure following brachytherapy for prostate cancer

    SciTech Connect

    Weight, Christopher J.; Ciezki, Jay P.; Reddy, Chandana A.; Zhou Ming; Klein, Eric A.

    2006-06-01

    Purpose: To determine if the presence of perineural invasion (PNI) predicts biochemical recurrence in patients who underwent low-dose-rate brachytherapy for the treatment of localized prostate cancer. Methods and Materials: A retrospective case control matching study was performed. The records of 651 patients treated with brachytherapy between 1996 and 2003 were reviewed. Sixty-three of these patients developed biochemical failure. These sixty-three patients were then matched in a one-to-one ratio to patients without biochemical failure, controlling for biopsy Gleason score, clinical stage, initial prostate-specific antigen, age, and the use of androgen deprivation. The pathology of the entire cohort was then reviewed for evidence of perineural invasion on initial prostate biopsy specimens. The biochemical relapse free survival rates for these two groups were compared. Results: Cases and controls were well matched, and there were no significant differences between the two groups in age, Gleason grade, clinical stage, initial prostate-specific antigen, and the use of androgen deprivation. PNI was found in 19 (17%) patients. There was no significant difference in the rates of PNI between cases and controls, 19.6% and 14.3% respectively (p 0.45). PNI did not correlate with biochemical relapse free survival (p 0.40). Conclusion: Perineural invasion is not a significant predictor of biochemical recurrence in patients undergoing brachytherapy for prostate cancer.

  18. Evidence for the Criterion Validity and Clinical Utility of the Pathological Narcissism Inventory

    ERIC Educational Resources Information Center

    Thomas, Katherine M.; Wright, Aidan G. C.; Lukowitsky, Mark R.; Donnellan, M. Brent; Hopwood, Christopher J.

    2012-01-01

    In this study, the authors evaluated aspects of criterion validity and clinical utility of the grandiosity and vulnerability components of the Pathological Narcissism Inventory (PNI) using two undergraduate samples (N = 299 and 500). Criterion validity was assessed by evaluating the correlations of narcissistic grandiosity and narcissistic…

  19. Evidence for the criterion validity and clinical utility of the Pathological Narcissism Inventory

    PubMed Central

    Thomas, Katherine M.; Wright, Aidan G.C.; Lukowitsky, Mark R.; Donnellan, M. Brent; Hopwood, Christopher J.

    2012-01-01

    In this study we evaluated aspects of criterion validity and clinical utility of the grandiosity and vulnerability components of the Pathological Narcissism Inventory (PNI) using two undergraduate samples (Ns = 299, 500). Criterion validity was assessed by evaluating the correlations of narcissistic grandiosity and narcissistic vulnerability with established indices of normal personality traits, psychopathology and clinical concerns, and pathological personality traits. Overall, the pattern of correlations supported the convergent and discriminate validity of grandiose and vulnerable conceptualizations of pathological narcissism as measured by the PNI. Clinical utility was assessed by evaluating the extent to which clinicians without specific training in pathological narcissism as well as clinicians with expertise in pathological narcissism could accurately predict the correlates of PNI grandiosity and vulnerability with normal and pathological personality traits and psychopathology. The rcontrast-cv coefficient (Westen & Rosenthal, 2003) provided a global index of accuracy in clinicians’ predictions that was more fully elaborated by examining systematic discrepancies across groups. Overall, novice and expert clinicians were generally able to predict criterion correlations, with some exceptions (e.g., counter to predictions, pathological narcissism was negatively associated with treatment resistance). These results provide further evidence regarding the validity and utility of the narcissistic grandiosity and narcissistic vulnerability constructs as measured by the PNI. PMID:22315481

  20. Increased arachidonic acid-containing phosphatidylcholine is associated with reactive microglia and astrocytes in the spinal cord after peripheral nerve injury.

    PubMed

    Xu, Dongmin; Omura, Takao; Masaki, Noritaka; Arima, Hideyuki; Banno, Tomohiro; Okamoto, Ayako; Hanada, Mitsuru; Takei, Shiro; Matsushita, Shoko; Sugiyama, Eiji; Setou, Mitsutoshi; Matsuyama, Yukihiro

    2016-01-01

    Peripheral nerve injury (PNI) triggers cellular and molecular changes in the spinal cord. However, little is known about how the polyunsaturated fatty acid-containing phosphatidylcholines (PUFA-PCs) are regulated in the spinal cord after PNI and the association of PUFA-PCs with the non-neuronal cells within in the central nervous system (CNS). In this study, we found that arachidonic acid-containing phosphatidylcholine (AA-PC), [PC(16:0/20:4)+K](+), was significantly increased in the ipsilateral ventral and dorsal horns of the spinal cord after sciatic nerve transection, and the increased expression of [PC(16:0/20:4)+K](+) spatiotemporally resembled the increase of reactive microglia and the astrocytes. From the lipidomics point of view, we conclude that [PC(16:0/20:4)+K](+) could be the main phospholipid in the spinal cord influenced by PNI, and the regulation of specific phospholipid molecule in the CNS after PNI is associated with the reactive microglia and astrocytes. PMID:27210057

  1. Increased arachidonic acid-containing phosphatidylcholine is associated with reactive microglia and astrocytes in the spinal cord after peripheral nerve injury

    PubMed Central

    Xu, Dongmin; Omura, Takao; Masaki, Noritaka; Arima, Hideyuki; Banno, Tomohiro; Okamoto, Ayako; Hanada, Mitsuru; Takei, Shiro; Matsushita, Shoko; Sugiyama, Eiji; Setou, Mitsutoshi; Matsuyama, Yukihiro

    2016-01-01

    Peripheral nerve injury (PNI) triggers cellular and molecular changes in the spinal cord. However, little is known about how the polyunsaturated fatty acid-containing phosphatidylcholines (PUFA-PCs) are regulated in the spinal cord after PNI and the association of PUFA-PCs with the non-neuronal cells within in the central nervous system (CNS). In this study, we found that arachidonic acid-containing phosphatidylcholine (AA-PC), [PC(16:0/20:4)+K]+, was significantly increased in the ipsilateral ventral and dorsal horns of the spinal cord after sciatic nerve transection, and the increased expression of [PC(16:0/20:4)+K]+ spatiotemporally resembled the increase of reactive microglia and the astrocytes. From the lipidomics point of view, we conclude that [PC(16:0/20:4)+K]+ could be the main phospholipid in the spinal cord influenced by PNI, and the regulation of specific phospholipid molecule in the CNS after PNI is associated with the reactive microglia and astrocytes. PMID:27210057

  2. Prognostic factors affecting early colectomy in patients with moderate to severe ulcerative colitis treated with calcineurin inhibitors

    PubMed Central

    Ban, Hiromitsu; Bamba, Shigeki; Nishida, Atsushi; Inatomi, Osamu; Shioya, Makoto; Takahashi, Ken-Ichiro; Imaeda, Hirotsugu; Murata, Masaki; Sasaki, Masaya; Tsujikawa, Tomoyuki; Andoh, Akira

    2016-01-01

    Calcineurin inhibitors (CNIs) such as cyclosporine A (CSA) and tacrolimus (FK506) are often used as a second-line drug for steroid-refractory or steroid-dependent patients with ulcerative colitis (UC). The aim of the present study was to determine the prognostic factors for early colectomy. A total of 85 hospitalized patients with UC (CSA, 50 patients; FK506, 35 patients) were enrolled. Colectomy carried out within 60 days of starting CNI therapy was defined as ‘early colectomy’. To assess the prognostic factors affecting early colectomy, clinical practical variables, including the Onodera-prognostic nutritional index (O-PNI): 10xAlb+0.005× (total lymphocyte count), were analyzed. The results demonstrated that the significant factors predicting early colectomy were i) disease severity, ii) immunomodulator-naïve history, iii) lower serum hematocrit, iv) lower serum albumin and v) lower O-PNI. In addition, the significant factors predicting overall colectomy were as follows: i) C7-HRP positivity and ii) >10,000 mg of prednisolone used prior to the initiation of CNI treatment. The combination of hematocrit and O-PNI enhanced the prediction of early colectomy. Clinical variables such as hematocrit and O-PNI were the significant factors predicting colectomy. These results may be used as a guide to predict the outcome of patients with UC in clinical settings.

  3. Impact of the Preoperative Controlling Nutritional Status (CONUT) Score on the Survival after Curative Surgery for Colorectal Cancer

    PubMed Central

    Iseki, Yasuhito; Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Ohtani, Hiroshi; Sugano, Kenji; Ikeya, Tetsuro; Muguruma, Kazuya; Tanaka, Hiroaki; Toyokawa, Takahiro; Sakurai, Katsunobu; Hirakawa, Kosei

    2015-01-01

    Background Recently, the preoperative immune-nutritional status has been reported to correlate with the survival rate in patients with colorectal cancer (CRC). However, there have been no reports on the relationship between the controlling nutritional status (CONUT) score and the clinical outcome after curative surgery for CRC. We herein evaluated the prognostic significance of the CONUT score in patients with CRC, and then compared the accuracy of the CONUT score and the prognostic nutritional index (PNI) as a predictor of survival. Methods We retrospectively reviewed a database of 204 patients who underwent curative surgery for Stage II/III CRC. Patients were divided into two groups according to the CONUT score and the PNI. Results The five-year cancer-specific survival (CSS) rate was significantly higher at 92.7% in the low CONUT group, compared to a rate of 81.0% in the high CONUT group (p=0.0016). The five-year CSS was 71.2% in the low PNI group and 92.3% in the high PNI group, which showed a significant difference (p=0.0155). A multivariate analysis showed that lymph node metastasis and the CONUT score were independent risk factors for CSS. Conclusion This study suggested that the CONUT score is a strong independent predictor of the survival among CRC patients. PMID:26147805

  4. Gamma radiation induced synthesis of poly(N-isopropylacrylamide) mediated by Reversible Addition-Fragmentation Chain Transfer (RAFT) process

    NASA Astrophysics Data System (ADS)

    Kiraç, Feyza; Güven, Olgun

    2015-07-01

    Poly(N-isopropylacrylamide) (PNiPAAm) is synthesized by gamma radiation induced Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization. The monomer is polymerized in the presence of two different trithiocarbonate-based RAFT agents i.e., Cyanomethyldodecyltrithiocarbonate (CDTC) and 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid (DMPA) in dimethylformamide (DMF) at room temperature under nitrogen atmosphere. Number-average molecular weights (Mn) and dispersities of the polymers were determined by Size Exclusion Chromatography (SEC). Dispersities (Ɖ) of the resulting polymers are narrow, i.e., Ɖ≤1.18, indicating the occurrence of well-controlled polymerization via radiation induced RAFT process. %Conversion is determined by gravimetric method and also confirmed by Proton Nuclear Magnetic Resonance (1H-NMR) Spectroscopy. By selecting proper [Monomer]/[RAFT] ratio and controlling conversion it is possible to synthesize PNiPAAm in the molecular weight range of 2400-72400 with extremely low molecular weight distributions with the anticipation of preparing corresponding size-controlled nanogels. The phase transition of PNiPAAm with low dispersity synthesized by RAFT is sharper than PNiPAAm synthesized by free radical polymerization.

  5. Stellar population and chemical evolution in spirals (as constrained by PNe)

    NASA Astrophysics Data System (ADS)

    Carigi, Leticia

    2015-08-01

    I present a review of the connection between chemical evolution models (CEM) and planetary nebulae (PN).I give special attention to the use of PN as observational constraints in CEM to infer the chemical history of spiral and irregular galaxies.I suggest some chemical abundance ratios of PN as more reliable tools to build CEMs.

  6. Special needs require special attention: a pilot project implementing the paediatric pain profile for children with profound neurological impairment in an in-patient setting following surgery.

    PubMed

    Hunt, Katie A; Franck, Linda S

    2011-09-01

    There is a lack of knowledge regarding the implementation of pain assessment tools for children with profound neurological impairment (PNI) in in-patient settings. This article describes a pilot project to evaluate the Paediatric Pain Profile (PPP) for children with PNI undergoing surgery. Five families of children 5 to 16 years of age with a primary diagnosis of cerebral palsy and admitted for surgical procedures were interviewed. Nineteen nurses completed questionnaires and children's pain management documentation was audited. The project identified issues in three areas of pain management: implementation process, individualised pain management and partnership. The PPP required pre-admission assessment and parental involvement, and was considered time-consuming by nurses. Individualised pain assessment and intervention was difficult to achieve, as was shared assessment and documentation among parents and nurses. Despite initial resistance to change, with greater use there was growing appreciation of the value of components of the PPP. Further exploration of the PPP tool in practice is required before its use can be widely recommended for children with PNI in in-patient settings. Future studies are required to determine which of the available pain assessment tools has the greatest accuracy and utility for assessment of post-operative pain in children with PNI. PMID:21828163

  7. Adjuvant poly(N-isopropylacrylamide) generates more efficient monoclonal antibodies against truncated recombinant histidine-rich protein2 of Plasmodium falciparum for malaria diagnosis.

    PubMed

    Verma, Reena; Ravichandran, Ramakrishnan; Jayaprakash, Naatamai S; Kumar, Ashok; Vijayalakshmi, Mookambeswaran A; Venkataraman, Krishnan

    2015-05-01

    Adjuvants play an important role in eliciting immune responses and subsequent generation of antibodies with high specificity. Recently, poly(N-isopropylacrylamide) (PNiPAAm), also known as a "smart" polymer, has been proposed as a potential adjuvant for making antibodies and vaccines. This material exhibits efficient delivery, protection against degradation, and preservation of antigen epitopes. In this work, we used both CFA and smart polymer to develop a highly specific murine monoclonal antibody (mAb) against recombinant truncated histidine rich protein2 (HRP2) of Plasmodium falciparum. Our results indicate that the mAbs developed using these adjuvants were able to recognize recombinant HRP2 and native PfHRP2 protein from spent medium. The mAbs generated against recombinant truncated HRP2 showed better sensitivity to the antigen and importantly mAbs generated using PNiPAAm adjuvant were in the range of 10(8)-10(9) M(-1). The mAbs generated using PNiPAAm are very efficient and sensitive in detecting HRP2. To the best of our knowledge, this is the first report of such comparison having been made between these two adjuvants and we propose that the smart polymer has huge potential as an alternative to CFA. Additionally, we discuss the utility of the mAbs generated through PNiPAAm for specific diagnosis of malaria caused by P. falciparum. PMID:25641957

  8. Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain

    PubMed Central

    Masuda, Takahiro; Iwamoto, Shosuke; Yoshinaga, Ryohei; Tozaki-Saitoh, Hidetoshi; Nishiyama, Akira; Mak, Tak W.; Tamura, Tomohiko; Tsuda, Makoto; Inoue, Kazuhide

    2014-01-01

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the purinergic P2X4 receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain. PMID:24818655

  9. Translational bioinformatics in psychoneuroimmunology: methods and applications.

    PubMed

    Yan, Qing

    2012-01-01

    Translational bioinformatics plays an indispensable role in transforming psychoneuroimmunology (PNI) into personalized medicine. It provides a powerful method to bridge the gaps between various knowledge domains in PNI and systems biology. Translational bioinformatics methods at various systems levels can facilitate pattern recognition, and expedite and validate the discovery of systemic biomarkers to allow their incorporation into clinical trials and outcome assessments. Analysis of the correlations between genotypes and phenotypes including the behavioral-based profiles will contribute to the transition from the disease-based medicine to human-centered medicine. Translational bioinformatics would also enable the establishment of predictive models for patient responses to diseases, vaccines, and drugs. In PNI research, the development of systems biology models such as those of the neurons would play a critical role. Methods based on data integration, data mining, and knowledge representation are essential elements in building health information systems such as electronic health records and computerized decision support systems. Data integration of genes, pathophysiology, and behaviors are needed for a broad range of PNI studies. Knowledge discovery approaches such as network-based systems biology methods are valuable in studying the cross-talks among pathways in various brain regions involved in disorders such as Alzheimer's disease. PMID:22933157

  10. Role of perineural invasion as a prognostic factor in laryngeal cancer

    PubMed Central

    MESOLELLA, MASSIMO; IORIO, BRIGIDA; MISSO, GABRIELLA; LUCE, AMALIA; CIMMINO, MARIANO; IENGO, MAURIZIO; LANDI, MARIO; SPERLONGANO, PASQUALE; CARAGLIA, MICHELE; RICCIARDIELLO, FILIPPO

    2016-01-01

    The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT. PMID:27073523

  11. Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis.

    PubMed

    Shan, Chun; Wei, Jianhua; Hou, Rui; Wu, Baolei; Yang, Zihui; Wang, Lei; Lei, Delin; Yang, Xinjie

    2016-01-01

    Perineural invasion (PNI) is a striking biological behavior observed in salivary adenoid cystic carcinoma (SACC). The present study was designed to establish a co-culture model of SACC cells with Schwann cells (SCs), and then study epithelial-mesenchymal transition (EMT) and the Schwann-like differentiation of SACC cells to investigate the likely molecular mechanism of PNI. The co-culture models of SCs with tumor cells (SACC-83, SACC-LM and MEC-1) were established using a Transwell system. An elevated concentration of brain-derived neurotrophic factor (BDNF) was detected by ELISA assay in the co-cultured medium of the SACC-83 group and SACC-LM group rather than the MEC-1 group. The EMT process and Schwann-like differentiation in SACC-83 cells were analyzed by RT-PCR, western blotting, immunofluorescence, photography, and migration and perineural invasion assays. The SACC-83 cells under the co-culture condition with SCs changed to a mesenchymal morphology and had higher migration and invasion capabilities compared with the solely cultured SACC-83 cells, accompanied by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The co-cultured SACC-83 cells also developed Schwann-like differentiation with increased expression of SC markers, S100A4 and GFAP. However, inhibition of tropomyosin-related kinase B (TrkB) by K252a markedly blocked these effects. Additionally, the expression and correlation of TrkB, E-cadherin and S100A4 were analyzed by immunohistochemistry in 187 primary SACC cases. The levels of TrkB and S100A4 expression were both positively associated with PNI in the SACC cases, while E-cadherin expression was negatively associated with PNI. Elevated expression of TrkB was significantly correlated with the downregulated expression of E-cadherin and the upregulated expression of S100A4 in the SACC cases. Our results suggest that SCs play a pivotal role in the PNI process by inducing the EMT process and the Schwann-like differentiation

  12. Neurofibromin protein loss in desmoplastic melanoma subtypes: implicating NF1 allelic loss as a distinct genetic driver?

    PubMed

    Kadokura, Alexander; Frydenlund, Noah; Leone, Dominick A; Yang, Shi; Hoang, Mai P; Deng, April; Hernandez-Perez, Marier; Biswas, Asok; Singh, Rajendra; Yaar, Ron; Mahalingam, Meera

    2016-07-01

    Loss of the NF1 allele, coding for the protein neurofibromin, and polymorphism in the proto-oncogene RET (RETp) are purportedly common in desmoplastic melanoma (DM). DM is categorized into pure (PDM) and mixed (MDM) subtypes, which differ in prognosis. Most NF1 mutations result in a truncated/absent protein, making immunohistochemical screening for neurofibromin an ideal surrogate for NF1 allelic loss. Using antineurofibromin, our aims were to ascertain the incidence of neurofibromin loss in DM subtypes and to evaluate the relationship with RET, perineural invasion (PNI) and established histopathologic prognosticators. A total of 78 archival samples of DM met criteria for inclusion (54 cases of non-DM serving as controls). Immunohistochemistry was performed for neurofibromin, whereas direct DNA sequencing was used for RETp and BRAF mutation status. Statistical analyses included χ(2) test as well as Fisher exact test. Neurofibromin loss was more common in DM than non-DM (69% versus 54%; P=.02). In DM, significant differences in neurofibromin loss were noted in the following: non-head and neck versus head and neck biopsy site (88% versus 55%) and PDM versus MDM variants (80% versus 56%). No significant associations were noted with sex, presence of a junctional component, Breslow depth, ulceration, mitoses, host response, RETp, BRAF status, or PNI. RETp was marginally associated with PNI-positive DM versus PNI-negative DM (36 versus 18%; P=.08). Our findings, the largest to date investigating neurofibromin in DM, validate the incidence of NF1 mutations/allelic loss in DM and suggest that the DM subtypes have distinct genetic drivers. PMID:26980030

  13. [The effect of forest exploitation on structure, diversity, and floristic composition of palmito-dominated Atlantic forests at Misiones, Argentina].

    PubMed

    Chediack, Sandra E

    2008-06-01

    The effect of forest exploitation--timber and palmito (Euterpe edulis, Palmae) extraction--on structure, diversity, and floristic composition of forests known as palmitals of the Atlantic Forest of Argentina was analyzed. These palmitals are located in Misiones (54 degrees 13' W and 25 degrees 41' S). Three 1 ha permanent plots were established: two in the "intangible" zone of the Iguazu National Park (PNI), and another in an exploited forest site bordering the PNI. Three 0.2 ha non-permanent plots were also measured. One was located in the PNI reserve zone where illegal palmito extraction occurs. The other two were in logged forest. All trees and palmitos with DBH >10 cm were identified and DBH and height were measured. For each of the six sites, richness and diversity of tree species, floristic composition, number of endemic species, and density of harvestable tree species were estimated. The harvest of E. edulis increases density of other tree species, diminishing palmito density. Forest explotation (logging and palmito harvest) is accompanied by an increase in diversity and density of heliophilic species, which have greater timber value in the region. However, this explotation also diminishes the density of palmito, of endemic species which normally grow in low densities, and of species found on the IUCN Red List. Results suggest that forest structure may be managed for timber and palmito production. The "intangible" zone of the PNI has the greatest conservation value in the Atlantic Forest, since a greater number of endemisms and endangered species are found here. PMID:19256439

  14. Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury.

    PubMed

    Chang, Hung-Ming; Huang, Yi-Lun; Lan, Chyn-Tair; Wu, Un-In; Hu, Ming-E; Youn, Su-Chung

    2008-03-01

    Peripheral nerve injury (PNI) produces functional changes in lesioned neurons in which oxidative stress is considered to be the main cause of neuronal damage. As superoxide dismutase (SOD) is an important antioxidative enzyme involved in redox regulation of oxidative stress, the present study determined whether melatonin would exert its beneficial effects by preserving the SOD reactivity following PNI. Adult rats subjected to hypoglossal nerve transection were intraperitoneally injected with melatonin at ones for 3, 7, 14, 30 and 60 days successively. The potential neuroprotective effects of melatonin were quantitatively demonstrated by neuronal nitric oxide synthase (nNOS), mitochondrial manganese SOD (Mn-SOD), and cytosolic copper-zinc SOD (Cu/Zn-SOD) immunohistochemistry. The functional recovery of the lesioned neurons was evaluated by choline acetyltransferase (ChAT) immunohistochemistry along with the electromyographic (EMG) recordings of denervation-induced fibrillation activity. The results indicate that following PNI, the nNOS immunoreactivity was significantly increased in lesioned neurons peaking at 14 days. The up-regulation of nNOS temporally coincided with the reduction of ChAT and SOD in which the Cu/Zn-SOD showed a greater diminution than Mn-SOD. However, following melatonin administration, the nNOS augmentation was successfully suppressed and the activities of Mn-SOD, Cu/Zn-SOD, and ChAT were effectively preserved at all postaxotomy periods. EMG data also showed a decreased fibrillation in melatonin-treated groups, suggesting a potential effect of melatonin in promoting functional recovery. In association with its significant capacity in preserving SOD reactivity, melatonin is suggested to serve as a powerful therapeutic agent for treating PNI-relevant oxidative damage. PMID:18289169

  15. Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway

    PubMed Central

    Chang, Hung-Ming; Shyu, Ming-Kwang; Tseng, Guo-Fang; Liu, Chiung-Hui; Chang, Hung-Shuo; Lan, Chyn-Tair; Hsu, Wen-Ming; Liao, Wen-Chieh

    2013-01-01

    Background Adequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches. Methodology and Principal Findings Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2±5.0%, 336.8±3.0%, and 80.0±5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles. Conclusions As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI. PMID:23301073

  16. The interaction of thrombin with platelet protease nexin

    SciTech Connect

    Knupp, C.L. )

    1989-10-01

    Thrombin interacts with a platelet protein which is immunologically related to fibroblast protease nexin and has been termed platelet protease nexin I (PNI). Conflicting hypotheses about the relationship of the thrombin-PNI complex formation to platelet activation have been proposed. The studies presented here demonstrate that the platelet-associated and supernatant complexes with added 125I-thrombin are formed only under conditions which produce platelet activation in normal and chymotrypsin-modified platelets. The platelet-associated complex is formed prior to the appearance of complexes in supernatants. Appearance of the supernatant complex coincides with the appearance of thrombospondin in the reaction supernatants. Excess native thrombin, dansylarginine N-(3-ethyl-1,5-pentanediyl) amide or hirudin can prevent radiolabeled platelet-associated complex formation if added before 125I-thrombin. DAPA or hirudin can prevent or dissociate complex formation if added up to one minute after thrombin but not at later time points. The surface associated complex is accessible to trypsin although a portion remains with the cytoskeletal proteins when thrombin-activated platelets are solubilized with Triton X 100. The surface-associated complex formation parallels many aspects of the specific measurable thrombin binding, yet it does not appear to involve other identified surface glycoprotein thrombin receptors or substrates. Although the time course of appearance of the complexes in supernatants is consistent with other data which suggest that PNI may be released from platelet granules during platelet activation, other explanations for the appearance of PNI on the platelet surface and in supernatants during platelet activation are possible.

  17. Current progress in use of adipose derived stem cells in peripheral nerve regeneration

    PubMed Central

    Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

    2015-01-01

    Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

  18. The role of psychoneuroimmunology in personalized and systems medicine.

    PubMed

    Yan, Qing

    2012-01-01

    Psychoneuroimmunology (PNI) may provide the scientific basis for personalized and systems medicine. The exploration of the extensive interactions among psychological and behavioral factors, the nervous system, the immune system, and the endocrine system may help understand the mechanisms underlying health, wellness, and diseases. PNI theories based on systems biology methodologies may contribute to the identification of patient patterns for establishing psychological and physiological profiles for personalized medicine. A biopsychosocial model will help elucidate the systemic interrelationships between psychosocial and bio-physiological factors for the development of systems medicine. Many evidences have supported the close relationships between stress, depression, inflammation, and disorders including obesity, cardiovascular disease, diabetes, arthritis, skin diseases, infectious diseases, and sleep disorders. As inflammation is a critical connection among different diseases, the elucidation of the associations may contribute to the findings of systemic therapeutic targets. With the understanding of the translational implications of PNI, integrative interventions in multiple dimensions can be applied to modulate stress responses and promote healthier behaviors. These interventions include combination drug therapies, diets, nutritional supplements, meditation, and other behavioral and mind-body strategies. PMID:22933138

  19. Polar Network Index as a Magnetic Proxy for the Solar Cycle Studies

    NASA Astrophysics Data System (ADS)

    Priyal, Muthu; Banerjee, Dipankar; Karak, Bidya Binay; Muñoz-Jaramillo, Andrés; Ravindra, B.; Choudhuri, Arnab Rai; Singh, Jagdev

    2014-09-01

    The Sun has a polar magnetic field which oscillates with the 11 yr sunspot cycle. This polar magnetic field is an important component of the dynamo process which operates in the solar convection zone and produces the sunspot cycle. We have direct systematic measurements of the Sun's polar magnetic field only from about the mid-1970s. There are, however, indirect proxies which give us information about this field at earlier times. The Ca-K spectroheliograms taken at the Kodaikanal Solar Observatory during 1904-2007 have now been digitized with 4k × 4k CCD and have higher resolution (~0.86 arcsec) than the other available historical data sets. From these Ca-K spectroheliograms, we have developed a completely new proxy (polar network index, hereafter PNI) for the Sun's polar magnetic field. We calculate PNI from the digitized images using an automated algorithm and calibrate our measured PNI against the polar field as measured by the Wilcox Solar Observatory for the period 1976-1990. This calibration allows us to estimate the polar fields for the earlier period up to 1904. The dynamo calculations performed with this proxy as input data reproduce reasonably well the Sun's magnetic behavior for the past century.

  20. Reduced frontal cortex thickness and cortical volume associated with pathological narcissism.

    PubMed

    Mao, Yu; Sang, Na; Wang, Yongchao; Hou, Xin; Huang, Hui; Wei, Dongtao; Zhang, Jinfu; Qiu, Jiang

    2016-07-22

    Pathological narcissism is often characterized by arrogant behavior, a lack of empathy, and willingness to exploit other individuals. Generally, individuals with high levels of narcissism are more likely to suffer mental disorders. However, the brain structural basis of individual pathological narcissism trait among healthy people has not yet been investigated with surface-based morphometry. Thus, in this study, we investigated the relationship between cortical thickness (CT), cortical volume (CV), and individual pathological narcissism in a large healthy sample of 176 college students. Multiple regression was used to analyze the correlation between regional CT, CV, and the total Pathological Narcissism Inventory (PNI) score, adjusting for age, sex, and total intracranial volume. The results showed that the PNI score was significantly negatively associated with CT and CV in the right dorsolateral prefrontal cortex (DLPFC, key region of the central executive network, CEN), which might be associated with impaired emotion regulation processes. Furthermore, the PNI score showed significant negative associations with CV in the right postcentral gyrus, left medial prefrontal cortex (MPFC), and the CT in the right inferior frontal cortex (IFG, overlap with social brain network), which may be related to impairments in social cognition. Together, these findings suggest a unique structural basis for individual differences in pathological narcissism, distributed across different gray matter regions of the social brain network and CEN. PMID:27129440

  1. BLADE-ON-PETIOLE1 and 2 regulate Arabidopsis inflorescence architecture in conjunction with homeobox genes KNAT6 and ATH1

    PubMed Central

    Khan, Madiha; Tabb, Paul; Hepworth, Shelley R.

    2012-01-01

    Inflorescence architecture varies widely among flowering plants, serving to optimize the display of flowers for reproductive success. In Arabidopsis thaliana, internode elongation begins at the floral transition, generating a regular spiral arrangement of upwardly-oriented flowers on the primary stem. Post-elongation, differentiation of lignified interfascicular fibers in the stem provides mechanical support. Correct inflorescence patterning requires two interacting homeodomain transcription factors: the KNOTTED1-like protein BREVIPEDICELLUS (BP) and its BEL1-like interaction partner PENNYWISE (PNY). Mutations in BP and PNY cause short internodes, irregular spacing and/or orientation of lateral organs, and altered lignin deposition in stems. Recently, we showed that these defects are caused by the misexpression of lateral organ boundary genes, BLADE-ON-PETIOLE1 (BOP1) and BOP2, which function downstream of BP-PNY in an antagonistic fashion. BOP1/2 gain-of-function in stems promotes expression of the boundary gene KNOTTED1-LIKE FROM ARABIDOPSIS THALIANA6 (KNAT6) and shown here, ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1), providing KNAT6 with a BEL1-like co-factor. Our further analyses show that defects caused by BOP1/2 gain-of-function require both KNAT6 and ATH1. These data reveal how BOP1/2-dependent activation of a boundary module in stems exerts changes in inflorescence architecture. PMID:22751300

  2. POLAR NETWORK INDEX AS A MAGNETIC PROXY FOR THE SOLAR CYCLE STUDIES

    SciTech Connect

    Priyal, Muthu; Banerjee, Dipankar; Ravindra, B.; Singh, Jagdev; Karak, Bidya Binay; Muñoz-Jaramillo, Andrés; Choudhuri, Arnab Rai E-mail: dipu@iiap.res.in

    2014-09-20

    The Sun has a polar magnetic field which oscillates with the 11 yr sunspot cycle. This polar magnetic field is an important component of the dynamo process which operates in the solar convection zone and produces the sunspot cycle. We have direct systematic measurements of the Sun's polar magnetic field only from about the mid-1970s. There are, however, indirect proxies which give us information about this field at earlier times. The Ca-K spectroheliograms taken at the Kodaikanal Solar Observatory during 1904-2007 have now been digitized with 4k × 4k CCD and have higher resolution (∼0.86 arcsec) than the other available historical data sets. From these Ca-K spectroheliograms, we have developed a completely new proxy (polar network index, hereafter PNI) for the Sun's polar magnetic field. We calculate PNI from the digitized images using an automated algorithm and calibrate our measured PNI against the polar field as measured by the Wilcox Solar Observatory for the period 1976-1990. This calibration allows us to estimate the polar fields for the earlier period up to 1904. The dynamo calculations performed with this proxy as input data reproduce reasonably well the Sun's magnetic behavior for the past century.

  3. Poly(N-isopropylacrylamide)-tethered silicate platelets for colloidal dispersion of conjugated polymers with thermoresponsive and photoluminescence properties.

    PubMed

    Lan, Yi-Fen; Hsieh, Bi-Zen; Lin, Hsiao-Chu; Su, Yu-An; Chan, Ying-Nan; Lin, Jiang-Jen

    2010-07-01

    Poly(N-isopropylacrylamide)-tethered nanosilicate platelets (NSP-PNiPAAm) have been synthesized by covalently bonding the polymer onto the surfaces of silicate platelets of nanometer dimension, and this class of nanohybrids has proved to be effective for dispersing water-insoluble conjugated polymers (CPs). Simple pulverization of poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) with NSP-PNiPAAm rendered the powder material dispersible in water, whereupon it displayed thermoresponsive properties at 37.5 degrees C and CP particle size variation between ca. 50 and 100 nm by SEM observation. The same dispersion had a maximum UV-vis absorption at 524 nm and PL emission at 605 nm. The PL emission was significantly higher at 4 degrees C than at 45 degrees C. Being coated as a film, it showed an orange emission under an ultraviolet lamp, consistent with the PL measurement. The water-borne process of dispersing the CP in aqueous media by the presence of NSP-PNiPAAm and followed by film formation to demonstrate a unique method of manipulating hydrophobic conjugated polymers in a facile manner. PMID:20302288

  4. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury

    PubMed Central

    2011-01-01

    In this review, we first provide a brief historical perspective, discussing how peripheral nerve injury (PNI) may have caused World War I. We then consider the initiation, progression, and resolution of the cellular inflammatory response after PNI, before comparing the PNI inflammatory response with that induced by spinal cord injury (SCI). In contrast with central nervous system (CNS) axons, those in the periphery have the remarkable ability to regenerate after injury. Nevertheless, peripheral nervous system (PNS) axon regrowth is hampered by nerve gaps created by injury. In addition, the growth-supportive milieu of PNS axons is not sustained over time, precluding long-distance regeneration. Therefore, studying PNI could be instructive for both improving PNS regeneration and recovery after CNS injury. In addition to requiring a robust regenerative response from the injured neuron itself, successful axon regeneration is dependent on the coordinated efforts of non-neuronal cells which release extracellular matrix molecules, cytokines, and growth factors that support axon regrowth. The inflammatory response is initiated by axonal disintegration in the distal nerve stump: this causes blood-nerve barrier permeabilization and activates nearby Schwann cells and resident macrophages via receptors sensitive to tissue damage. Denervated Schwann cells respond to injury by shedding myelin, proliferating, phagocytosing debris, and releasing cytokines that recruit blood-borne monocytes/macrophages. Macrophages take over the bulk of phagocytosis within days of PNI, before exiting the nerve by the circulation once remyelination has occurred. The efficacy of the PNS inflammatory response (although transient) stands in stark contrast with that of the CNS, where the response of nearby cells is associated with inhibitory scar formation, quiescence, and degeneration/apoptosis. Rather than efficiently removing debris before resolving the inflammatory response as in other tissues

  5. Past and Future Drought Regimes in Turkey

    NASA Astrophysics Data System (ADS)

    Sen, Burak; Topcu, Sevilay; Turkes, Murat; Sen, Baha

    2010-05-01

    Climate variability in the 20th century was characterized by apparent precipitation variability at both temporal and spatial scales. In addition to the well-known characteristic seasonal and year-to-year variability, some marked and long-term changes in precipitation occurred in Turkey, particularly after the early 1970s. Drought, originating from a deficiency of precipitation over an extended time period (which is usually a season or more) has become a recurring phenomenon in Turkey in the past few decades. Spatially coherent with the significant drought events since early 1970s, water stress and shortages for all water user sectors have also reached their critical points in Turkey. Analyzing the historical occurrence of drought provides an understanding of the range of climate possibilities for a country, resulting in more informed management decision-making. However, future projections about spatial and temporal changes in drought characteristics such as frequency, intensity and duration can be challenging for developing appropriate mitigation and adaptation strategies. Hence, the objectives of this study are (i) to analyze the spatial and temporal dimensions of historical droughts in Turkey, (2) to predict potential intensity, frequency and duration of droughts in Turkey for the future (2070-2100). The Standardized Precipitation Index (SPI) and the Percent to Normal Index (PNI) have been used to assess the drought characteristics. Rainfall datasets for the reference period, 1960-1990, were acquired from 52 stations (representative of all kinds of regions with different rainfall regimes in the country) of the Turkish State Meteorological Service (TSMS). The future rainfall series for the 2070-2100 period were simulated using a regional climate model (RegCM3) for IPCC's SRESS-A2 scenario conditions. For verification of RegCM3 simulations, the model was performed for the reference period and simulated rainfall data were used for computing two drought indices (SPI

  6. Purinergic Modulation of Spinal Neuroglial Maladaptive Plasticity Following Peripheral Nerve Injury.

    PubMed

    Cirillo, Giovanni; Colangelo, Anna Maria; Berbenni, Miluscia; Ippolito, Vita Maria; De Luca, Ciro; Verdesca, Francesco; Savarese, Leonilde; Alberghina, Lilia; Maggio, Nicola; Papa, Michele

    2015-12-01

    Modulation of spinal reactive gliosis following peripheral nerve injury (PNI) is a promising strategy to restore synaptic homeostasis. Oxidized ATP (OxATP), a nonselective antagonist of purinergic P2X receptors, was found to recover a neuropathic behavior following PNI. We investigated the role of intraperitoneal (i.p.) OxATP treatment in restoring the expression of neuronal and glial markers in the mouse spinal cord after sciatic spared nerve injury (SNI). Using in vivo two-photon microscopy, we imaged Ca(2+) transients in neurons and astrocytes of the dorsal horn of spinal cord at rest and upon right hind paw electrical stimulation in sham, SNI, and OxATP-treated mice. Neuropathic behavior was investigated by von Frey and thermal plantar test. Glial [glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1)] and GABAergic [vesicular GABA transporter (vGAT) and glutamic acid decarboxylase 65/76 (GAD65/67)] markers and glial [glutamate transporter (GLT1) and GLAST] and neuronal amino acid [EAAC1, vesicular glutamate transporter 1 (vGLUT1)] transporters have been evaluated. In SNI mice, we found (i) increased glial response, (ii) decreased glial amino acid transporters, and (iii) increased levels of neuronal amino acid transporters, and (iv) in vivo analysis of spinal neurons and astrocytes showed a persistent increase of Ca(2+) levels. OxATP administration reduced glial activation, modulated the expression of glial and neuronal glutamate/GABA transporters, restored neuronal and astrocytic Ca(2+) levels, and prevented neuropathic behavior. In vitro studies validated that OxATP (i) reduced levels of reactive oxygen species (ROS), (ii) reduced astrocytic proliferation, (iii) increase vGLUT expression. All together, these data support the correlation between reactive gliosis and perturbation of the spinal synaptic homeostasis and the role played by the purinergic system in modulating spinal plasticity following PNI. PMID:25352445

  7. Modulation of Matrix Metalloproteinases Activity in the Ventral Horn of the Spinal Cord Re-stores Neuroglial Synaptic Homeostasis and Neurotrophic Support following Peripheral Nerve Injury

    PubMed Central

    Cirillo, Giovanni; Colangelo, Anna Maria; De Luca, Ciro; Savarese, Leonilde; Barillari, Maria Rosaria; Alberghina, Lilia; Papa, Michele

    2016-01-01

    Modulation of extracellular matrix (ECM) remodeling after peripheral nerve injury (PNI) could represent a valid therapeutic strategy to prevent maladaptive synaptic plasticity in central nervous system (CNS). Inhibition of matrix metalloproteinases (MMPs) and maintaining a neurotrophic support could represent two approaches to prevent or reduce the maladaptive plastic changes in the ventral horn of spinal cord following PNI. The purpose of our study was to analyze changes in the ventral horn produced by gliopathy determined by the suffering of motor neurons following spared nerve injury (SNI) of the sciatic nerve and how the intrathecal (i.t.) administration of GM6001 (a MMPs inhibitor) or the NGF mimetic peptide BB14 modulate these events. Immunohistochemical analysis of spinal cord sections revealed that motor neuron disease following SNI was associated with increased microglial (Iba1) and astrocytic (GFAP) response in the ventral horn of the spinal cord, indicative of reactive gliosis. These changes were paralleled by decreased glial aminoacid transporters (glutamate GLT1 and glycine GlyT1), increased levels of the neuronal glutamate transporter EAAC1, and a net increase of the Glutamate/GABA ratio, as measured by HPLC analysis. These molecular changes correlated to a significant reduction of mature NGF levels in the ventral horn. Continuous i.t. infusion of both GM6001 and BB14 reduced reactive astrogliosis, recovered the expression of neuronal and glial transporters, lowering the Glutamate/GABA ratio. Inhibition of MMPs by GM6001 significantly increased mature NGF levels, but it was absolutely ineffective in modifying the reactivity of microglia cells. Therefore, MMPs inhibition, although supplies neurotrophic support to ECM components and restores neuro-glial transporters expression, differently modulates astrocytic and microglial response after PNI. PMID:27028103

  8. Modulation of Matrix Metalloproteinases Activity in the Ventral Horn of the Spinal Cord Re-stores Neuroglial Synaptic Homeostasis and Neurotrophic Support following Peripheral Nerve Injury.

    PubMed

    Cirillo, Giovanni; Colangelo, Anna Maria; De Luca, Ciro; Savarese, Leonilde; Barillari, Maria Rosaria; Alberghina, Lilia; Papa, Michele

    2016-01-01

    Modulation of extracellular matrix (ECM) remodeling after peripheral nerve injury (PNI) could represent a valid therapeutic strategy to prevent maladaptive synaptic plasticity in central nervous system (CNS). Inhibition of matrix metalloproteinases (MMPs) and maintaining a neurotrophic support could represent two approaches to prevent or reduce the maladaptive plastic changes in the ventral horn of spinal cord following PNI. The purpose of our study was to analyze changes in the ventral horn produced by gliopathy determined by the suffering of motor neurons following spared nerve injury (SNI) of the sciatic nerve and how the intrathecal (i.t.) administration of GM6001 (a MMPs inhibitor) or the NGF mimetic peptide BB14 modulate these events. Immunohistochemical analysis of spinal cord sections revealed that motor neuron disease following SNI was associated with increased microglial (Iba1) and astrocytic (GFAP) response in the ventral horn of the spinal cord, indicative of reactive gliosis. These changes were paralleled by decreased glial aminoacid transporters (glutamate GLT1 and glycine GlyT1), increased levels of the neuronal glutamate transporter EAAC1, and a net increase of the Glutamate/GABA ratio, as measured by HPLC analysis. These molecular changes correlated to a significant reduction of mature NGF levels in the ventral horn. Continuous i.t. infusion of both GM6001 and BB14 reduced reactive astrogliosis, recovered the expression of neuronal and glial transporters, lowering the Glutamate/GABA ratio. Inhibition of MMPs by GM6001 significantly increased mature NGF levels, but it was absolutely ineffective in modifying the reactivity of microglia cells. Therefore, MMPs inhibition, although supplies neurotrophic support to ECM components and restores neuro-glial transporters expression, differently modulates astrocytic and microglial response after PNI. PMID:27028103

  9. Clinical, demographic and histopathological prognostic factors for urothelial carcinoma of the bladder

    PubMed Central

    Pala, Emel Ebru; Cakır, Ebru; Sezer, Ozlem; Bayol, Umit; Divrik, Rauf Taner; Cakmak, Ozgur

    2015-01-01

    Introduction Our aim is to evaluate the influence of clinical and histopathological parameters, including age, gender, tumor stage, grade, tumor differentiation, necrosis, lymphovascular/perineural invasion (LVI/PNI) and concomitant carcinoma in situ (CIS), on outcomes of patients with urothelial carcinoma of the bladder (UCB). Material and methods A total of 84 patients who underwent radical cystectomy (RC) (n = 11) and radical cystoprostatectomy (n = 73) for muscle-invasive bladder cancer at our hospital between 2007-2013, were included in the study. Results The mean age of patients at diagnosis was 66.1, of whom 75 were males and 9 were females. Of the 84 patients, 38 were ≤65 years and 46 were >65 years. Mean tumor diameter was 3.66 cm. There were 38 cases which showed divergent differentiations. Concomitant CIS was observed in 30 tumors, 41 cases showed tumor necrosis, 44 PNI and 61 LVI. The rate of overall survival (OS) in patients aged ≤65 years was statistically significantly higher than in those aged >65 years. A negative statistical relationship was found between OS with lymph node metastasis (LNM) and tumor differentiation. On the other hand, necrosis did not remain significant on multivariate analysis. No statistically significant relationship was found between smoking, tumor stage, PNI, LVI and concomitant CIS and OS. Conclusions In this study, advanced age, LNM, tumor differentiation were found to be independent prognostic risk factors associated with OS after RC. These additional factors, which may explain the different clinical course in patients with similar tumor stage and lymph node status, should be taken into consideration in treatment planning. PMID:25914835

  10. Direct osmolyte-macromolecule interactions confer entropic stability to folded states.

    PubMed

    Rodríguez-Ropero, Francisco; van der Vegt, Nico F A

    2014-07-01

    Protective osmolytes are chemical compounds that shift the protein folding/unfolding equilibrium toward the folded state under osmotic stresses. The most widely considered protection mechanism assumes that osmolytes are depleted from the protein's first solvation shell, leading to entropic stabilization of the folded state. However, recent theoretical and experimental studies suggest that protective osmolytes may directly interact with the macromolecule. As an exemplary and experimentally well-characterized system, we herein discuss poly(N-isopropylacrylamide) (PNiPAM) in water whose folding/unfolding equilibrium shifts toward the folded state in the presence of urea. On the basis of molecular dynamics simulations of this specific system, we propose a new microscopic mechanism that explains how direct osmolyte-macromolecule interactions confer stability to folded states. We show that urea molecules preferentially accumulate in the first solvation shell of PNiPAM driven by attractive van der Waals dispersion forces with the hydrophobic isopropyl groups, leading to the formation of low entropy urea clouds. These clouds provide an entropic driving force for folding, resulting in preferential urea binding to the folded state and a decrease of the lower folding temperature in agreement with experiment. The simulations further indicate that thermodynamic nonideality of the bulk solvent opposes this driving force and may lead to denaturation, as illustrated by simulations of PNiPAM in aqueous solutions with dimethylurea. The proposed mechanism provides a new angle on relations between the properties of protecting and denaturing osmolytes, salting-in or salting-out effects, and solvent nonidealities. PMID:24927256

  11. A Systematic Review of the Prognostic Role of Hematologic Scoring Systems in Patients With Renal Cell Carcinoma Undergoing Nephrectomy With Curative Intent.

    PubMed

    Grimes, Nathan; Tyson, Matthew; Hannan, Cathal; Mulholland, Colin

    2016-08-01

    The objective is to evaluate the prognostic benefit of the Glasgow Prognostic Score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and Prognostic Nutrition Index (PNI) in patients with localized renal cell carcinoma undergoing nephrectomy with curative intent. Embase and MEDLINE databases were searched for all publications before April 2015. Duplicates were excluded, and inclusion/exclusion criteria were applied to all abstracts; of those remaining, full articles were obtained and inclusion/exclusion criteria were again applied, and the remaining articles were included and critically appraised. Eight articles were included in this review. Three articles were included for GPS. Outcomes included recurrence-free survival, cancer-specific survival (CSS), and overall survival (OS). All articles demonstrated better prognosis associated with a lower GPS on multivariate analysis: 1-year recurrence-free survival hazard ratio (HR), 7.0 (P = .001); CSS HR, 6.7 to 8.6 (P < .001); and OS HR 4.2 (P < .001). Four articles were included for NLR. All articles demonstrated elevated NLR to be associated with a poorer prognosis. Two articles demonstrated elevated NLR to be associated with a lower progression-free survival. One article demonstrated elevated NLR to be associated with a lower CSS (HR, 1.02, P = .009), and 2 articles demonstrated elevated NLR to be associated with a lower OS (HR, 1.02-1.6). No articles were included for PLR, and only 1 article was identified for PNI. There may be a role for modified GPS and NLR in patients with renal cell carcinoma undergoing nephrectomy with curative intent. Evidence for PLR and PNI is minimal. PMID:26949171

  12. Twelve-Month Prostate-Specific Antigen Values and Perineural Invasion as Strong Independent Prognostic Variables of Long-Term Biochemical Outcome After Prostate Seed Brachytherapy

    SciTech Connect

    Ding, William; Lee, John; Chamberlain, David; Cunningham, James; Yang Lixi; Tay, Jonathan

    2012-11-15

    Purpose: To determine whether post-treatment prostate-specific antigen (ptPSA) values at 12 months and other clinical parameters predict long-term PSA relapse-free survival (PRFS) following prostate seed brachytherapy. Methods and Materials: Records of 204 hormone-naieve patients with localized adenocarcinoma of the prostate treated at St. Mary's Regional Medical Center in Reno, NV, and at Carson Tahoe Regional Medical Center in Carson City, NV, between 1998 and 2003, using I-125 or Pd-103 seed brachytherapy, were retrospectively analyzed. Treatment planning was done using a preplanned, modified peripheral loading technique. A total of 185 of 204 patients had PSA records at 12 months after implant. Variables included were age, initial pretreatment PSA, Gleason score, T stage, National Comprehensive Cancer Network (NCCN) risk group (RG), perineural invasion (PNI), external beam boost, dose, and ptPSA levels at 12 months with cutpoints at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml. Results: Median follow-up was 80 months, and median age was 69 years. The numbers of patients stratified by NCCN low, intermediate, and high RG were 110:65:10, respectively. Monotherapy and boost prescription doses were 145 Gy and 110 Gy for I-125, and 125 Gy and 100 Gy for Pd-103 seeds, respectively. The median dose (D90) was 95.4% of the prescribed dose. The 5-year PRFS at the 12-months ptPSA levels of {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml were 98.5%, 85.7%, 61.5%, and 22.2%, respectively. The 10-year PRFS at the 12-months ptPSA levels of {<=}1 and 1.01 to 2.00 ng/ml were 90.5% and 85.7%, respectively. In multivariate analysis, both ptPSA and PNI were significant independent predictors of PRFS. Hazard ratios (HR) for ptPSA levels at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml at 12 months were 1, 4.96, 27.57, and 65.10, respectively. PNI had an HR of 6.1 (p = 0.009). Conclusions: Presence of PNI and ptPSA values at 12 months are strong prognostic variables for

  13. Psyche and soma: New insights into the connection.

    PubMed

    Kumar, Rahul; Yeragani, Vikram K

    2010-01-01

    The interaction of Psyche and Soma are well known and this interaction happens through a complex network of feedback, medication, and modulation among the central and autonomic nervous systems, the endocrine system, the immune system, and the stress system. These systems, which were previously considered pristinely independent, in fact, interact at myriad levels. Psychoneuroimmunology (PNI) is an emerging discipline that focuses on various interactions among these body systems and provides the underpinnings of a scientific explanation for what is commonly referred to as the mind-body connection. This article reviews the relevant literature with an emphasis on Indian research. PMID:21836684

  14. A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis

    PubMed Central

    Kato, Akihiko; Tsuji, Takayuki; Sakao, Yukitoshi; Ohashi, Naro; Yasuda, Hideo; Fujimoto, Taiki; Takita, Takako; Furuhashi, Mitsuyoshi; Kumagai, Hiromichi

    2013-01-01

    Background/Aims Systemic inflammation-based prognostic scores have prognostic power in patients with cancer, independently of tumor stage and site. Although inflammatory status is associated with mortality in hemodialysis (HD) patients, it remains to be determined as to whether these composite scores are useful in predicting clinical outcomes. Methods We calculated the 6 prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic nutritional index (PNI), which have been established as a useful scoring system in cancer patients. We enrolled 339 patients on regular HD (age: 64 ± 13 years; time on HD: 129 ± 114 months; males/females = 253/85) and followed them for 42 months. The area under the receiver-operating characteristics curve was used to determine which scoring system was more predictive of mortality. Results Elevated GPS, mGPS, NLR, PLR, PI and PNI were all associated with total mortality, independent of covariates. If GPS was raised, mGPS, NLR, PLR and PI were also predictive of all-cause mortality and/or hospitalization. GPS and PNI were associated with poor nutritional status. Using overall mortality as an endpoint, the area under the curve (AUC) was significant for a GPS of 0.701 (95% CI: 0.637-0.765; p < 0.01) and for a PNI of 0.616 (95% CI: 0.553-0.768; p = 0.01). However, AUC for hypoalbuminemia (<3.5 g/dl) was comparable to that of GPS (0.695, 95% CI: 0.632-0.759; p < 0.01). Conclusion GPS, based on serum albumin and highly sensitive C-reactive protein, has the most prognostic power for mortality prediction among the prognostic scores in HD patients. However, as the determination of serum albumin reflects mortality similarly to GPS, other composite combinations are needed to provide additional clinical utility beyond that of albumin alone in HD patients. PMID:24403910

  15. Neural Ablation and Regeneration in Pain Practice

    PubMed Central

    Choi, Eun Ji; Choi, Yun Mi; Jang, Eun Jung; Kim, Ju Yeon; Kim, Tae Kyun

    2016-01-01

    A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration. PMID:26839664

  16. [Nutritional screening before surgery for esophageal cancer - current status and evaluation results].

    PubMed

    Shimakawa, Takeshi; Asaka, Shinich; Sagawa, Masano; Shimazaki, Asako; Yamaguchi, Kentaro; Usui, Takebumi; Yokomizo, Hajime; Shiozawa, Shunichi; Yoshimatsu, Kazuhiko; Katsube, Takao; Naritaka, Yoshihiko

    2014-10-01

    The incidence of postoperative complications and mortality are usually higher in patients with preoperative malnutrition. Malnutrition often preexists, particularly in patients undergoing surgery for esophageal cancer, which is substantially invasive. It is therefore important to understand the nutritional condition of patients and actively control perioperative nutrition.Our hospital has been providing nutritional status screening for patients before resection of esophageal cancer, and we report the current status and evaluation results in this article.This screening included 158 patients requiring radical resection of esophageal cancer.Age, comorbidity with diabetes, body mass index(BMI), serum albumin(Alb), Onodera's prognostic nutritional index(PNI), and Glasgow prognostic score(GPS)were used as nutritional indicators to stratify patients for analysis.Evaluation parameters included the incidence of postoperative complications(any complication, pulmonary complications, psychiatric disorder, and anastomotic leakage)and rates of long-term postoperative hospitalization.The analysis indicated that age, BMI, serum Alb, PNI, and GPS are useful for predicting the onset of postoperative complications and prolonged postoperative hospitalization.For such patients, more active nutritional control should be provided. PMID:25335724

  17. Psychosomatic plasticity: An "emergent property" of personality research?

    PubMed

    Jawer, Michael

    2006-03-01

    Psychosomatic plasticity, defined as an extreme capacity to turn suggestions into bodily realities, is as phenomenon well worth investigating because it challenges mainstream conceptions about the relationship between mind and body in health as well as illness. The field of psychoneuroimmunology (PNI) offers a framework within which to understand this phenomenon because PNI makes a compelling case for the biological unity of self. Hartmann's Boundaries concept is particularly applicable because it suggests that the minds of "thin-boundary" persons are relatively fluid and able to make numerous connections. Wilson and Barber's identification of the fantasy prone person and Thalbourne's transliminality concept are similarly relevant. Taking these explorations a step further, this author proposes that the flow of feeling within individuals represents the key to psychosomatic plasticity. Blushing, psoriasis, and immune reactions are offered as examples, as are more anomalous reports such as those provided by heart transplantation recipients and cases said to be indicative of reincarnation. In each instance, persons who are highly sensitive (ie, have a speedier and more direct flow of feeling) are more likely to evidence physical reactions. Psychosomatic plasticity represents an emerging area of interest in personality research, one that clearly merits further investigation. PMID:16781625

  18. Psychosocial influences on immunity, including effects on immune maturation and senescence

    PubMed Central

    Coe, Christopher L.; Laudenslager, Mark L.

    2009-01-01

    Studies investigating the influence of psychosocial factors on immunity played a critical and formative role in the field of psychoneuroimmunology (PNI), and have been a major component of articles published in Brain, Behavior and Immunity (BBI). An analysis of papers during the first two decades of BBI from 1987–2006 revealed three behavior-related topics were most prominent: 1) stress-induced changes in immune responses, 2) immune correlates of psychopathology and personality, and 3) behavioral conditioning of immunity. Important subthemes included the effect of early rearing conditions on immune maturation in the developing infant and, subsequently, psychosocial influences affecting the decline of immunity in the senescent host. The responsiveness of cell functioning in the young and elderly helped to validate the view that our immune competence is malleable. Many technical advances in immune methods were also evident. Initially, there was a greater reliance on in vitro proliferative and cytolytic assays, while later studies were more likely to use cell subset enumerations, cytokine quantification, and indices of latent virus reactivation. The reach of PNI extended from the traditional clinical entities of infection, autoimmunity, and cancer to attain a broader relevance to inflammatory physiology, and thus to asthma, cardiovascular and gastrointestinal disease. There continue to be many theoretical and applied ramifications of these seminal findings. Fortunately, the initial controversies about whether psychological processes could really impinge upon and modify immune responses have now receded into the pages of history under the weight of the empirical evidence. PMID:17706917

  19. Neural Ablation and Regeneration in Pain Practice.

    PubMed

    Choi, Eun Ji; Choi, Yun Mi; Jang, Eun Jung; Kim, Ju Yeon; Kim, Tae Kyun; Kim, Kyung Hoon

    2016-01-01

    A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration. PMID:26839664

  20. Macrophage-derived reactive oxygen species protects against autoimmune priming with a defined polymeric adjuvant.

    PubMed

    Shakya, Akhilesh Kumar; Kumar, Ashok; Holmdahl, Rikard; Nandakumar, Kutty Selva

    2016-01-01

    Understanding the nature of adjuvants and the immune priming events in autoimmune diseases, such as rheumatoid arthritis, is a key challenge to identify their aetiology. Adjuvants are, however, complex structures with inflammatory and immune priming properties. Synthetic polymers provide a possibility to separate these functions and allow studies of the priming mechanisms in vivo. A well-balanced polymer, poly-N-isopropyl acrylamide (PNiPAAm) mixed with collagen type II (CII) induced relatively stronger autoimmunity and arthritis compared with more hydrophilic (polyacrylamide) or hydrophobic (poly-N-isopropylacrylamide-co-poly-N-tertbutylacrylamide and poly-N-tertbutylacrylamide) polymers. Clearly, all the synthesized polymers except the more hydrophobic poly-N-tertbutylacrylamide induced arthritis, especially in Ncf1-deficient mice, which are deficient in reactive oxygen species (ROS) production. We identified macrophages as the major infiltrating cells present at PNiPAAm-CII injection sites and demonstrate that ROS produced by the macrophages attenuated the immune response and the development of arthritis. Our results reveal that thermo-responsive polymers with high immune priming capacity could trigger an autoimmune response to CII and the subsequent arthritis development, in particular in the absence of NOX2 derived ROS. Importantly, ROS from macrophages protected against the autoimmune priming, demonstrating a critical regulatory role of macrophages in immune priming events. PMID:26455429

  1. Psychoneuroimmunology and cancer: A decade of discovery, paradigm shifts, and methodological innovations

    PubMed Central

    McDonald, Paige Green; O’Connell, Mary; Lutgendorf, Susan K.

    2013-01-01

    This article introduces the supplemental issue of “Cancer, Brain, Behavior, and Immunity” and outlines important discoveries, paradigm shifts, and methodological innovations that have emerged in the past decade to advance mechanistic and translational understanding of biobehavioral influences on tumor biology, cancer treatment-related sequelae, and cancer outcomes. We offer a heuristic framework for research on biobehavioral pathways in cancer. The shifting survivorship landscape is highlighted and we propose that the changing demographics suggest prudent adoption of a life course perspective of cancer and cancer survivorship. We note opportunities for psychoneuroimmunology (PNI) research to ameliorate the long-term, unintended consequences of aggressive curative intent and call attention to the critical role of reciprocal translational pathways between animal and human studies. Lastly, we briefly summarize the articles included in this compilation and offer our perspectives on future research directions. HighlightsThis article introduces the National Cancer Institute sponsored special issue Cancer, Brain, Behavior, and Immunity and highlights the last decade of PNI-cancer research. PMID:23333846

  2. What drives hydrophobic polymer collapse and re-entry transitions in miscible good solvents?

    NASA Astrophysics Data System (ADS)

    Rodriguez Ropero, Francisco; Hajari, Timir; van der Vegt, Nico F. A.

    Herein, we study co-nonsolvency of poly(N-isopropylacrylamide) (PNiPAM) in methanol aqueous solutions. Our results show that both the coil-to-globule transition at low methanol concentrations and the globule-to-coil re-entrance at high methanol concentrations are entropy driven. At low alcohol content, methanol preferentially binds to the PNiPAM globule and drives polymer collapse. Rather than being driven by electrostatic, hydrogen bonding or bridging-type interactions with the globule, preferential methanol binding is found to result from a significant increase of the chain configurational entropy, stabilizing methanol-enriched globular structures over wet globular structures in neat water. The globule-to-coil re-entrance at high methanol concentrations is instead driven by changes in solvent-excluded volume of the coil and globular states imparted by a decrease in solvent density with increasing methanol content of the solution. The co-nonsolvency mechanism proposed in this contribution provides a new angle on how to develop Coarse Grained simulation models for responsive soft matter systems. Moreover, several of the solvation effects described in this contribution can be incorporated in theories for cosolvent-induced conformational transitions in dilute polymer solutions. This research was supported by the German Research Foundation (DFG) within the Collaborative Research Center ``Multiscale Simulation Methods for Soft Matter Systems'' (SFB-TRR146).

  3. Ni-Supported Pd Nanoparticles with Ca Promoter: A New Catalyst for Low-Temperature Ammonia Cracking

    PubMed Central

    Polanski, Jaroslaw; Bartczak, Piotr; Ambrozkiewicz, Weronika; Sitko, Rafal; Siudyga, Tomasz; Mianowski, Andrzej; Szade, Jacek; Balin, Katarzyna; Lelątko, Józef

    2015-01-01

    In this paper we report a new nanometallic, self-activating catalyst, namely, Ni-supported Pd nanoparticles (PdNPs/Ni) for low temperature ammonia cracking, which was prepared using a novel approach involving the transfer of nanoparticles from the intermediate carrier, i.e. nano-spherical SiO2, to the target carrier technical grade Ni (t-Ni) or high purity Ni (p-Ni) grains. The method that was developed allows a uniform nanoparticle size distribution (4,4±0.8 nm) to be obtained. Unexpectedly, the t-Ni-supported Pd NPs, which seemed to have a surface Ca impurity, appeared to be more active than the Ca-free (p-Ni) system. A comparison of the novel PdNPs/Ni catalyst with these reported in the literature clearly indicates the much better hydrogen productivity of the new system, which seems to be a highly efficient, flexible and durable catalyst for gas-phase heterogeneous ammonia cracking in which the TOF reaches a value of 2615 mmolH2/gPd min (10,570 molNH3/molPd(NP) h) at 600°C under a flow of 12 dm3/h (t-Ni). PMID:26308929

  4. A mechanical auxiliary ventricle. Histologic responses to long-term, intermittent pumping in calves.

    PubMed

    Kantrowitz, A; Freed, P S; Zhou, Y; Mandell, G; DeDecker, P; Riddle, J; Wilson, D; Mullaney, T P

    1995-01-01

    The mechanical auxiliary ventricle (MAV) is an avalvular, inseries left ventricular assist device (LVAD) comprised of a 60 cc Biomer blood pump implanted in the descending thoracic aorta, a percutaneous access device (PAD), and an external pneumatic drive. In four calves the MAV was implanted and activated intermittently for 192, 249, 423, and 785 days, respectively; no anticoagulants were administered. When the animals were killed, the implants were retrieved, and autopsies, including gross, light microscopic, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) examinations, were performed. The MAV was securely attached to the aorta in every animal. A thin, even smooth, pseudoneointimal layer (PNI) contiguous with the aorta at the level of the suture line covered the MAV's blood-contacting surface. Areas of calcification beneath the PNI, expected in growing animals with implanted pumping devices, were noted. At autopsy there was no evidence of thrombosis or infection in the regions of the blood pump or the PAD. These findings confirm the calves' benign histologic response to the MAV, and together with the results of hematologic and biochemiccal studies, and bench tests of system components being reported elsewhere, indicate the system's readiness for limited clinical investigation in selected patients with chronic congestive failure. PMID:8573821

  5. [Psychoneuroimmunology].

    PubMed

    Kemeny, M

    1995-01-01

    Psychoneuroimmunology (PNI) focuses on the connection between the mind and the body. This area of investigation concentrates on ways in which the mind and brain communicate with the immune system. U.S. psychologists, George Solomon and Robert Ader, demonstrated in animals that tension can damage immune functions. Today, immunologists, micro-biologists and endocrinologists are studying this relationship. The brain and immune system communicate in two principle ways: by means of hormones which the brain regulates, and nerve fibers which communicate with immune cells. Extreme tension can alter the function of immune cells. Immunological alterations can be associated with areas of stress. Some experimental interventions which increase the ability to deal with tension stimulate certain immunological processes. For example, helping individuals develop problem-solving techniques has increased certain immunological functions in persons with AIDS and cancer. How a person understands his own emotions can affect the immune system, as well as the extent of social support he receives. The study of PNI is part of a multidisciplinary effort to determine if psychological factors have an impact on health due to their effect on the immune system. PMID:11362480

  6. EphA2 silencing promotes growth, migration, and metastasis in salivary adenoid cystic carcinoma: in vitro and in vivo study

    PubMed Central

    Wang, Meng; Zhao, Xiao-Ping; Xu, Zhi; Yan, Ting-Lin; Song, Yong; Song, Kai; Huang, Chun-Ming; Wang, Lin; Zhou, Xiao-Cheng; Jiang, Er-Hui; Shao, Zhe; Shang, Zheng-Jun

    2016-01-01

    EphA2 is associated with tumor growth and distant metastasis in numerous human tumors. Considering the controversial effects of EphA2 in different tumors and the lack of reports in salivary adenoid cystic carcinoma (SACC), we evaluated the effects of EphA2 inhibition by short hairpin RNA on SACC through in vivo and in vitro researches for the first time. Real-time reverse transcriptase-PCR and western blot analysis were conducted to verify the interference effect on SACC cells. Using Cell Counting Kit-8, wound healing, Transwell and Matrigel adhesion assays, we confirm that inhibition of EphA2 promotes the migration, invasion and adhesion ability of SACC cells. In vivo research, we prove that silencing of EphA2 significantly accelerates tumor growth and lung metastasis ability by establishing xenograft models in mice, including subcutaneous inoculation and tail vein injection. In addition, immunostaining of EphA2, E-cadherin and Slug from 40 specimens and in vitro simulation of perineural invasion (PNI) assay imply that suppression of EphA2 partially contribute to epithelial-mesenchymal transition and enhancement of PNI in SACC. In conclusion, all the data suggest that EphA2 may act as a tumor suppressor in SACC progression. PMID:27186278

  7. EphA2 silencing promotes growth, migration, and metastasis in salivary adenoid cystic carcinoma: in vitro and in vivo study.

    PubMed

    Wang, Meng; Zhao, Xiao-Ping; Xu, Zhi; Yan, Ting-Lin; Song, Yong; Song, Kai; Huang, Chun-Ming; Wang, Lin; Zhou, Xiao-Cheng; Jiang, Er-Hui; Shao, Zhe; Shang, Zheng-Jun

    2016-01-01

    EphA2 is associated with tumor growth and distant metastasis in numerous human tumors. Considering the controversial effects of EphA2 in different tumors and the lack of reports in salivary adenoid cystic carcinoma (SACC), we evaluated the effects of EphA2 inhibition by short hairpin RNA on SACC through in vivo and in vitro researches for the first time. Real-time reverse transcriptase-PCR and western blot analysis were conducted to verify the interference effect on SACC cells. Using Cell Counting Kit-8, wound healing, Transwell and Matrigel adhesion assays, we confirm that inhibition of EphA2 promotes the migration, invasion and adhesion ability of SACC cells. In vivo research, we prove that silencing of EphA2 significantly accelerates tumor growth and lung metastasis ability by establishing xenograft models in mice, including subcutaneous inoculation and tail vein injection. In addition, immunostaining of EphA2, E-cadherin and Slug from 40 specimens and in vitro simulation of perineural invasion (PNI) assay imply that suppression of EphA2 partially contribute to epithelial-mesenchymal transition and enhancement of PNI in SACC. In conclusion, all the data suggest that EphA2 may act as a tumor suppressor in SACC progression. PMID:27186278

  8. ‘Strategic Sequences’ in Adipose Derived Stem Cell Nerve Regeneration

    PubMed Central

    Widgerow, Alan D.; Salibian, Ara A.; Kohan, Emil; SartiniFerreira, Tadeu; Afzel, Hassaan; Tham, Thanh; Evans, Gregory RD

    2014-01-01

    Background Peripheral nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques utilizing human adipose derived stem cells (hADSCs) for nerve regeneration, and derive a comprehensive approach to hADSC therapy for PNI. Methods A literature review was conducted using the electronic database PubMed to search for current experimental approaches to repairing peripheral nerve injuries using hADSCs. Key search elements focused on specific components of nerve regeneration paradigms, including, 1) support cells, 2) scaffolds and 3) nerve conduits. Results Strategic sequences were developed by optimizing the components of different experimental regenerative therapies. These sequences focus on priming hADSCs within a specialized growth medium, a hydrogel matrix base, and a collagen nerve conduit to achieve neuromodulatory nerve regeneration. Human ADSCs may exert their neuroregenerative influence through paracrine effects on surrounding Schwann cells in addition to physical interactions with injured tissue. Conclusions hADSCs may play a key role in nerve regeneration by acting primarily as support for local neurotrophic mediation and modulation of nerve growth rather than that of a primary neuronal differentiation agent. PMID:24375471

  9. Parameningeal Rhabdomyosarcoma: Outcomes and Opportunities

    SciTech Connect

    Yang, Joanna C.; Wexler, Leonard H.; Meyers, Paul A.; Wolden, Suzanne L.

    2013-01-01

    Purpose: To examine patterns of failure in patients with parameningeal rhabdomyosarcoma (PM-RMS) treated with intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-seven patients with PM-RMS received chemotherapy and IMRT for definitive treatment. The median age was 9 years (range, 0.5-35 years). The high-risk features were as follows: 40% alveolar histology, 72% group III and 26% group IV disease, 57% either intracranial extension (ICE) (n=25) or cranial neuropathy (n=21). The median time to RT from the start of chemotherapy was 15 weeks (range, 2-54 weeks). Patients received 50.4 Gy in 1.8-Gy fractions to the primary tumor by use of IMRT. Thirteen patients aged {>=}14 years with alveolar histology received 36 Gy prophylactic nodal irradiation (PNI) to bilateral cervical nodes. Events were defined as local, regional (nodal), central nervous system (CNS), or distant failures. Results: With a median follow-up time of 3.3 years (range, 0.5-12.8 years), 18 patients experienced failure: 5 local, 2 regional, 6 distant, and 7 CNS. The 5-year local failure-free survival was 86%. Age, histology, and time to RT did not influence the risk of local failure. The 5-year regional failure-free survival was 92%: 100% for embryonal and 74% for alveolar (P=.03). However, there were no lymph node failures in patients with alveolar histology who were given PNI. The 5-year CNS failure-free survival was 83%: 100% without and 70% with ICE (P=.01); 95% without and 69% with cranial neuropathy (P=.02). The estimated 5-year event-free survival and overall survival were 61% for group III and 58% for group IV patients. Conclusions: Distant failure was the most common type of failure among group IV patients. Patients with alveolar histology seem to benefit from PNI. The presence of ICE or cranial neuropathy portends a high risk of CNS failure, the most common pattern of failure among non-group IV patients. These patients may benefit from the addition of novel CNS

  10. Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis

    PubMed Central

    Fisher, Sarah B; Patel, Sameer H; Kooby, David A; Weber, Sharon; Bloomston, Mark; Cho, Clifford; Hatzaras, Ioannis; Schmidt, Carl; Winslow, Emily; Staley III, Charles A; Maithel, Shishir K

    2012-01-01

    Objectives Criteria for the selection of patients for adjuvant chemotherapy in intrahepatic cholangiocarcinoma (IHCC) are lacking. Some authors advocate treating patients with lymph node (LN) involvement; however, nodal assessment is often inadequate or not performed. This study aimed to identify surrogate criteria based on characteristics of the primary tumour. Methods A total of 58 patients who underwent resection for IHCC between January 2000 and January 2010 at any of three institutions were identified. Primary outcome was overall survival (OS). Results Median OS was 23.0 months. Median tumour size was 6.5 cm and the median number of lesions was one. Overall, 16% of patients had positive margins, 38% had perineural invasion (PNI), 40% had lymphovascular invasion (LVI) and 22% had LN involvement. A median of two LNs were removed and a median of zero were positive. Lymph nodes were not sampled in 34% of patients. Lymphovascular and perineural invasion were associated with reduced OS [9.6 months vs. 32.7 months (P= 0.020) and 10.7 months vs. 32.7 months (P= 0.008), respectively]. Lymph node involvement indicated a trend towards reduced OS (10.7 months vs. 30.0 months; P= 0.063). The presence of either LVI or PNI in node-negative patients was associated with a reduction in OS similar to that in node-positive patients (12.1 months vs. 10.7 months; P= 0.541). After accounting for adverse tumour factors, only LVI and PNI remained associated with decreased OS on multivariate analysis (hazard ratio 4.07, 95% confidence interval 1.60–10.40; P= 0.003). Conclusions Lymphovascular and perineural invasion are separately associated with a reduction in OS similar to that in patients with LN-positive disease. As nodal dissection is often not performed and the number of nodes retrieved is frequently inadequate, these tumour-specific factors should be considered as criteria for selection for adjuvant chemotherapy. PMID:22762399

  11. Use of Ornamental Trees in Dating of Abandoned Cemeteries on the Example of Thuja Occidentalis and Thuja Orientalis

    NASA Astrophysics Data System (ADS)

    Opała, Magdalena; Majgier, Leszek

    2012-01-01

    i Thuja occidentalis. Te obce dla flory polskiej gatunki, doskonale zaadaptowały się do zastanych warunków siedliskowych i klimatycznych. W pracy przedstawiono próbę zastosowania metody datowania dendrochronologicznego do określenia wieku porzuconych cmentarzy z Krainy Wielkich Jezior Mazurskich. Badaniem objęto 5 porzuconych cmentarzy. Ogółem pobrano 15 wywiertów z drzew. Po zastosowaniu standardowej metody dendrochronologicznej, utworzono lokalne chronologie przyrostowe dla badanych gatunków. Badania wykazały, iż najstarsze okazały się być okazy Thuja occidentalis występujące na cmentarzu Słabowo, których wiek wynosi ponad 70 lat. Na pozostałych obiektach rosnące okazy obydwu gatunków żywotników datowane są na lata 60. i początek lat 70.XX wiek. W porównaniu z informacjami historycznymi o wieku i pochodzeniu badanych obiektów rosnące na nich okazy żywotników są znacznie młodsze niż wiek założenia cmentarzy. Przedstawiona metoda okazała się być niezwykle pomocna w poznaniu czasu wprowadzenia żywotników Thuja occidentalis i Thuja orientalis na badanych cmentarzach.

  12. Finite-size correction to the pionium lifetime due to ω and η' contributions

    NASA Astrophysics Data System (ADS)

    Chliapnikov, P. V.; Ronjin, V. M.

    2009-10-01

    It is shown that for pNi interactions at 24 GeV/c, the fractions of the π±ωπmnplus and \\pi^{\\pm }_{\\eta ^{\\prime } }\\pi^{\\mp } pairs with one pion from the ω and η' decays, respectively, at small values of the relative momentum Q <= 4 MeV/c of pions in the c.m. system of the π+π- pair are fω = 0.150 ± 0.019 and f_{\\eta ^{\\prime } } =0.0102\\pm 0.0034 . With these values of fω and f_{\\eta ^{\\prime } } , the uncertainty in the pionium breakup probability and the corresponding overestimation of the pionium lifetime in the DIRAC experiment at CERN are ΔPbr/Pbr = (3.0 ± 1.0)% and Δτ/τ = (7.8 ± 2.6)%.

  13. Faunistic Catalog of the Caddisflies (Insecta: Trichoptera) of Parque Nacional do Itatiaia and its Surroundings in Southeastern Brazil

    PubMed Central

    Dumas, Leandro Lourenço; Nessimian, Jorge Luiz

    2012-01-01

    The Atlantic Forest is considered one of the world's biological diversity hotspots, and is increasingly threatened by the rapid destruction and fragmentation of its natural areas. The caddisflies (Trichoptera) of Itatiaia massif, an Atlantic Forest highland area, are inventoried and cataloged here. The catalog is based on examination of bibliographies, field work on many localities of Itatiaia massif (including Parque Nacional do Itatiaia — PNI), and the entomological collection Professor José Alfredo Pinheiro Dutra (DZRJ), Universidade Federal do Rio de Janeiro. A total of 92 species are recorded, representing about 17% of the known Brazilian Trichoptera fauna. Leptoceridae, Hydropsychidae, and Philopotamidae are the families most represented. The high species richness, as well as the remarkable patterns of species distribution, may be related to the characteristics of Mantiqueira mountain range. PMID:22958122

  14. Faunistic catalog of the caddisflies (Insecta: Trichoptera) of Parque Nacional do Itatiaia and its surroundings in southeastern Brazil.

    PubMed

    Dumas, Leandro Lourenço; Nessimian, Jorge Luiz

    2012-01-01

    The Atlantic Forest is considered one of the world's biological diversity hotspots, and is increasingly threatened by the rapid destruction and fragmentation of its natural areas. The caddisflies (Trichoptera) of Itatiaia massif, an Atlantic Forest highland area, are inventoried and cataloged here. The catalog is based on examination of bibliographies, field work on many localities of Itatiaia massif (including Parque Nacional do Itatiaia - PNI), and the entomological collection Professor José Alfredo Pinheiro Dutra (DZRJ), Universidade Federal do Rio de Janeiro. A total of 92 species are recorded, representing about 17% of the known Brazilian Trichoptera fauna. Leptoceridae, Hydropsychidae, and Philopotamidae are the families most represented. The high species richness, as well as the remarkable patterns of species distribution, may be related to the characteristics of Mantiqueira mountain range. PMID:22958122

  15. An integrated device for magnetically-driven drug release and in situ quantitative measurements: Design, fabrication and testing

    NASA Astrophysics Data System (ADS)

    Bruvera, I. J.; Hernández, R.; Mijangos, C.; Goya, G. F.

    2015-03-01

    We have developed a device capable of remote triggering and in situ quantification of therapeutic drugs, based on magnetically-responsive hydrogels of poly (N-isopropylacrylamide) and alginate (PNiPAAm). The heating efficiency of these hydrogels measured by their specific power absorption (SPA) values showed that the values between 100 and 300 W/g of the material were high enough to reach the lower critical solution temperature (LCST) of the polymeric matrix within few minutes. The drug release through application of AC magnetic fields could be controlled by time-modulated field pulses in order to deliver the desired amount of drug. Using B12 vitamin as a concept drug, the device was calibrated to measure amounts of drug released as small as 25(2)×10-9 g, demonstrating the potential of this device for very precise quantitative control of drug release.

  16. Psychoneuroimmune implications of type 2 diabetes: redux.

    PubMed

    O'Connor, Jason C; Johnson, Daniel R; Freund, Gregory G

    2009-05-01

    A sizable body of knowledge has arisen demonstrating that type 2 diabetes (T2D) is associated with alterations in the innate immune system. The resulting proinflammatory-leaning imbalance is implicated in the development of secondary disease complications and comorbidities, such as delayed wound healing, accelerated progress of atherosclerosis, and retinopathy, in people who have T2D. New experimental data and the results of recently published health-related quality-of-life surveys indicate that individuals who have T2D experience diminished feelings of happiness, well being, and satisfaction with life. These emotional and psychological consequences of T2D point to altered neuroimmunity as a previously unappreciated complication of T2D. This article discusses recent data detailing the impact of T2D on a person's PNI response. PMID:19389586

  17. Risk Factors Associated with Loco-Regional Failure after Surgical Resection in Patients with Resectable Pancreatic Cancer

    PubMed Central

    Kim, Hyun Ju; Lee, Woo Jung; Kang, Chang Moo; Hwang, Ho Kyoung; Bang, Seung Min; Song, Si Young; Seong, Jinsil

    2016-01-01

    Purpose To evaluate the risk factors associated with loco-regional failure after surgical resection and to identify the subgroup that can obtain benefits from adjuvant radiotherapy (RT). Materials and Methods We identified patients treated with surgical resection for resectable pancreatic cancer at Severance hospital between January 1993 and December 2014. Patients who received any neoadjuvant or adjuvant RT were excluded. A total of 175 patients were included. Adjuvant chemotherapy was performed in 107 patients with either a gemcitabine-based regimen (65.4%) or 5-FU based one (34.9%). Results The median loco-regional failure-free survival (LRFFS) and overall survival (OS) were 23.9 and 33.6 months, respectively. A recurrence developed in 108 of 175 patients (61.7%). The predominant pattern of the first failure was distant (42.4%) and 47 patients (26.9%) developed local failure as the first site of recurrence. Multivariate analysis identified initial CA 19–9 ≥ 200 U/mL, N1 stage, perineural invasion (PNI), and resection margin as significant independent risk factors for LRFFS. Patients were divided into four groups according to the number of risk factors, including initial CA 19–9, N stage, and PNI. Patients exhibiting two risk factors had 3.2-fold higher loco-regional failure (P < 0.001) and patients with all risk factors showed a 6.5-fold increase (P < 0.001) compared with those with no risk factors. In the analysis for OS, patients with more than two risk factors also had 3.3- to 6-fold higher risk of death with statistical significance. Conclusion The results suggest that patients who exhibit more than two risk factors have a higher risk of locoregional failure and death. This subgroup could be benefited by the effective local adjuvant treatment. PMID:27332708

  18. Clinical Implication of Inflammation-Based Prognostic Score in Pancreatic Cancer

    PubMed Central

    Yamada, Suguru; Fujii, Tsutomu; Yabusaki, Norimitsu; Murotani, Kenta; Iwata, Naoki; Kanda, Mitsuro; Tanaka, Chie; Nakayama, Goro; Sugimoto, Hiroyuki; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

    2016-01-01

    Abstract A variety of systemic inflammation-based prognostic scores have been explored; however, there has been no study to clarify which score could best reflect survival in resected pancreatic cancer patients. Between 2002 and 2014, 379 consecutive patients who underwent curative resection of pancreatic cancer were enrolled. The Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), and prognostic nutritional index (PNI) scores for each patient were calculated. Survival of each score was evaluated, and correlations between the score selected on the basis of the prognostic significance and various clinicopathological factors were analyzed. In the analysis of the GPS, the median survival time (MST) was 28.1 months for score 0, 25.6 for score 1, and 17.0 for score 2. As for mGPS, the MST was 25.8 months for score 0, 27.7 for score 1, and 17.0 for score 2. Both scores were found to be significant. On the contrary, there were no statistical differences in MST between various scores obtained using the NLR, PLR, PI, or PNI. Multivariate analysis revealed that lymph node metastasis, positive peritoneal washing cytology, and a GPS score of 2 were significant prognostic factors. There was also statistically significant correlation between the GPS score and tumor location (head), tumor size (≥2.0 cm), bile duct invasion, and duodenal invasion. Our study demonstrated that the GPS could be an independent predictive marker and was superior to other inflammation-based prognostic scores in patients with resected pancreatic cancer. PMID:27149487

  19. Mechanism of Polymer Collapse in Miscible Good Solvents.

    PubMed

    Rodríguez-Ropero, Francisco; Hajari, Timir; van der Vegt, Nico F A

    2015-12-24

    We propose a physical mechanism for co-nonsolvency of a stimulus-responsive polymer in water/methanol mixed solution based on results obtained with molecular simulations. Even though the phenomenon is well known, the mechanism behind co-nonsolvency is still under debate. Herein, we study co-nonsolvency of poly(N-isopropylacrylamide) (PNiPAM) in methanol aqueous solutions, the most widely studied and experimentally well-characterized system. Our results show that at low alcohol content of the solution methanol preferentially binds to the PNiPAM globule and drives polymer collapse. The energetics of electrostatic, hydrogen bonding, or bridging-type interactions with the globule is found to play no role. Instead, preferential methanol binding results in a significant increase in the globule's configurational entropy, stabilizing methanol-enriched globular structures over wet globular structures in neat water. This mechanism drives the reduction of the lower critical solution temperature with increasing methanol content in the co-nonsolvency regime and eventually leads to polymer collapse. The globule-to-coil re-entrance at high methanol concentrations is instead driven by changes in solvent-excluded volume of the coil and globular states imparted by a decrease in solvent density with increasing methanol content of the solution: with increasing proportion of larger solvent particles (methanol), the entropic (cavity formation) cost of redistributing solvent molecules upon polymer re-entrance becomes smaller. This effect provides a natural explanation for the experimentally observed dependence of the re-entrance transition on chain molecular weight. PMID:26619003

  20. Irradiation for locoregionally recurrent, never-irradiated oral cavity cancers

    PubMed Central

    Lok, Benjamin H.; Chin, Christine; Riaz, Nadeem; Ho, Felix; Hu, Man; Hong, Julian C.; Shi, Weiji; Zhang, Zhigang; Sherman, Eric; Wong, Richard J.; Morris, Luc G.; Ganly, Ian; Wolden, Suzanne L.; Rao, Shyam S.; Lee, Nancy Y.

    2016-01-01

    Background The purpose of this study was to report the clinical outcomes and related prognostic factors of patients who underwent radiotherapy (RT) for the treatment of recurrent, never-irradiated oral cavity cancer (recurrent OCC). Methods The records of consecutive patients with nonmetastatic recurrent OCC who presented to and were treated with RT at our institution between 1989 and 2011 were reviewed. The Kaplan–Meier method was used to calculate overall survival (OS). The cumulative incidences of disease-specific death, local failure, regional failure, and distant metastasis were calculated with death as a competing risk. Results One hundred twenty-three patients were identified. Median follow-up for living patients was 54 months and 16 months for all patients. Ninety-one patients had salvage surgery followed by adjuvant RT. Definitive RT was utilized in the remaining 32 patients. The 5-year OS was 40%. The 5-year cumulative incidence of disease-specific death, local failure, regional failure, and distant metastasis was 55%, 34%, 22%, and 20%, respectively. Recurrent T classification and lack of salvage surgery were independently associated with worse disease-specific death and decreased OS, respectively. Subset analysis of patients who underwent salvage surgery demonstrated that age, recurrent T classification, and perineural invasion (PNI) were independently associated with decreased OS; recurrent T classification and thicker tumors were independently associated with worse disease-specific death; and positive/close margins and primary T classification were independently associated with increased local failure. Conclusion In this group of patients with recurrent OCC, clinical outcomes were similar or improved when compared with other recurrent OCC-specific reports. In the salvage surgery subset, tumor thickness and PNI are recurrent pathologic features associated with outcomes that were only previously demonstrated in studies of primary disease. Because of

  1. A longitudinal study of pain, personality, and brain plasticity following peripheral nerve injury.

    PubMed

    Goswami, Ruma; Anastakis, Dimitri J; Katz, Joel; Davis, Karen D

    2016-03-01

    We do not know precisely why pain develops and becomes chronic after peripheral nerve injury (PNI), but it is likely due to biological and psychological factors. Here, we tested the hypotheses that (1) high Pain Catastrophizing Scale (PCS) scores at the time of injury and repair are associated with pain and cold sensitivity after 1-year recovery and (2) insula gray matter changes reflect the course of injury and improvements over time. Ten patients with complete median and/or ulnar nerve transections and surgical repair were tested ∼3 weeks after surgical nerve repair (time 1) and ∼1 year later for 6 of the 10 patients (time 2). Patients and 10 age-/sex-matched healthy controls completed questionnaires that assessed pain (patients) and personality and underwent quantitative sensory testing and 3T MRI to assess cortical thickness. In patients, pain intensity and neuropathic pain correlated with pain catastrophizing. Time 1 pain catastrophizing trended toward predicting cold pain thresholds at time 2, and at time 1 cortical thickness of the right insula was reduced. At time 2, chronic pain was related to the time 1 pain-PCS relationship and cold sensitivity, pain catastrophizing correlated with cold pain threshold, and insula thickness reversed to control levels. This study highlights the interplay between personality, sensory function, and pain in patients following PNI and repair. The PCS-pain association suggests that a focus on affective or negative components of pain could render patients vulnerable to chronic pain. Cold sensitivity and structural insula changes may reflect altered thermosensory or sensorimotor awareness representations. PMID:26588697

  2. Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

    NASA Astrophysics Data System (ADS)

    Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V.; Noll, Thomas; Funk, Richard H. W.; Engelmann, Katrin; Werner, Carsten

    2015-08-01

    Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na+/K+-ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro. The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty.

  3. Conserved dopamine neurotrophic factor-transduced mesenchymal stem cells promote axon regeneration and functional recovery of injured sciatic nerve.

    PubMed

    Liu, Yi; Nie, Lin; Zhao, Hua; Zhang, Wen; Zhang, Yuan-Qiang; Wang, Shuai-Shuai; Cheng, Lei

    2014-01-01

    Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. Scanning electron microscopy of the collagen tubes demonstrated their ability to be resorbed in vivo. We observed notable overexpression of the CDNF protein in the distal sciatic nerve after application of CDNF-MSCs. Quantitative analysis of neurofilament 200 (NF200) and S100 immunohistochemistry showed significant enhancement of axonal and Schwann cell regeneration in the group receiving CDNF-MSCs (CDNF-MSCs group) compared with the control groups. Myelination thickness, axon diameter and the axon-to fiber diameter ratio (G-ratio) were significantly higher in the CDNF-MSCs group at 8 and 12 weeks after nerve transection surgery. After surgery, the sciatic functional index, target muscle weight, wet weight ratio of gastrocnemius muscle and horseradish peroxidase (HRP) tracing demonstrated functional recovery. Light and electron microscopy confirmed successful regeneration of the sciatic nerve. The greater numbers of HRP-labeled neuron cell bodies and increased sciatic nerve index values (SFI) in the CDNF-MSCs group suggest that CDNF exerts neuroprotective effects in vivo. We also observed higher target muscle weights and a significant improvement in muscle atrophism in the CDNF-MSCs group. Collectively, these findings indicate that CDNF gene therapy delivered by MSCs is capable of promoting nerve regeneration and functional recovery, likely because of the significant neuroprotective and neurotrophic effects of CDNF and the superior environment offered by MSCs and collagen tubes. PMID

  4. Conserved Dopamine Neurotrophic Factor-Transduced Mesenchymal Stem Cells Promote Axon Regeneration and Functional Recovery of Injured Sciatic Nerve

    PubMed Central

    Liu, Yi; Nie, Lin; Zhao, Hua; Zhang, Wen; Zhang, Yuan-Qiang; Wang, Shuai-Shuai; Cheng, Lei

    2014-01-01

    Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. Scanning electron microscopy of the collagen tubes demonstrated their ability to be resorbed in vivo. We observed notable overexpression of the CDNF protein in the distal sciatic nerve after application of CDNF-MSCs. Quantitative analysis of neurofilament 200 (NF200) and S100 immunohistochemistry showed significant enhancement of axonal and Schwann cell regeneration in the group receiving CDNF-MSCs (CDNF-MSCs group) compared with the control groups. Myelination thickness, axon diameter and the axon-to fiber diameter ratio (G-ratio) were significantly higher in the CDNF-MSCs group at 8 and 12 weeks after nerve transection surgery. After surgery, the sciatic functional index, target muscle weight, wet weight ratio of gastrocnemius muscle and horseradish peroxidase (HRP) tracing demonstrated functional recovery. Light and electron microscopy confirmed successful regeneration of the sciatic nerve. The greater numbers of HRP-labeled neuron cell bodies and increased sciatic nerve index values (SFI) in the CDNF-MSCs group suggest that CDNF exerts neuroprotective effects in vivo. We also observed higher target muscle weights and a significant improvement in muscle atrophism in the CDNF-MSCs group. Collectively, these findings indicate that CDNF gene therapy delivered by MSCs is capable of promoting nerve regeneration and functional recovery, likely because of the significant neuroprotective and neurotrophic effects of CDNF and the superior environment offered by MSCs and collagen tubes. PMID

  5. New Criteria to Assess Seismic and Rock Burst Hazard in Coal Mines / Nowe Kryteria Dla Oceny Zagrożenia Sejsmicznego I Tąpaniami W Kopalniach Węgla Kamiennego

    NASA Astrophysics Data System (ADS)

    Mutke, Grzegorz; Dubiński, Józef; Lurka, Adam

    2015-09-01

    The paper presents new criteria of seismic and rock burst hazard assessment in Polish hard coal mines where longwall mining system is common practice. The presented criteria are based on the results of continuous recording of seismic events and analysis of selected seismological parameters: spatial location of seismic event in relation to mining workings, seismic energy, seismic energy release per unit coal face advance, b-value of Gutenberg-Richter law, seismic energy index EI, seismic moment M0, weighted value of peak particle velocity PPVW. These parameters are determined in a moving daily time windows or time windows with fixed number of seismic tremors. Time changes of these parameters are then compared with mean value estimated in the analyzed area. This is the basis to indicate the zones of high seismic and rock burst hazard in specific moment in time during mining process. Additionally, the zones of high seismic and rock burst hazard are determined by utilization of passive seismic tomography method. All the calculated seismic parameters in moving time windows are used to quantify seismic and rock burst hazard by four level scales. In practice, assessment of seismic and rock burst hazard is used to make daily decision about using rock burst prevention activities and correction of further exploitation of monitored coal panel. Zagrożenie sejsmiczne i związane z nim genetycznie zagrożenie tąpnięciem w dalszym ciągu należą do najgroźniejszych zagrożeń naturalnych występujących w polskich kopalniach węgla kamiennego. W ostatnich latach w kopalniach Górnośląskiego Zagłębia Węglowego (GZW) rocznie rejestrowano 1000÷1500 wstrząsów o energii sejsmicznej Es ≥ 1·105J (magnituda lokalna ML ≥ 1.7), a najsilniejsze z nich osiągały energię Es = 4 ·109J (ML = 4.1). W latach 1991-2010 odnotowano w GZW 101 tąpnięć, z których około 66% miało miejsce w wyrobiskach chodnikowych, powodując ich uszkodzenia lub całkowite zniszczenie, a w

  6. Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients

    PubMed Central

    Song, Anna; Eo, Wankyu; Lee, Sookyung

    2015-01-01

    AIM: To investigate the impact of systemic inflammation-based prognostic markers on overall survival in relapsed/refractory metastatic colorectal cancer (mCRC) patients. METHODS: To investigate prognostic markers in mCRC patients, this study was performed with patients who have experienced relapsed/refractory mCRC with standard chemotherapy or were inapplicable to conventional treatment modality because of poor performance status, age, or comorbidity. We reviewed the medical records of 177 mCRC patients managed with Korean Medicine (KM) treatment modality using an anticancer agent of Rhus verniciflua Stokes extract from June 2006 to April 2013. The clinicopathologic characteristics, laboratory test, the systemic inflammation markers including the modified Glasgow prognostic score (mGPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR), and prognostic nutritional index (PNI) were analyzed. The overall survival of patients was calculated with the Kaplan-Meier method and the statistical significance was compared using with the log-rank test. To compare the impact of systemic inflammation based markers, the hazard ratio (HR) of mGPS, NLR, PLR, LMR, and PNI for overall survival were evaluated with the Cox proportional hazards regression. RESULTS: The majority of mCRC patients had relapsed/refractory to standard chemotherapy; 128 patients (72.3%) had undergone more than second line chemotherapy, and the median time from diagnosis of mCRC to initiation of KM was 9.4 mo. The median overall survival of enrolled patients was 8.3 mo. On univariate analyses, the inflammation markers of higher mGPS (P < 0.001), NLR ≥ 5 (P < 0.001), PLR > 300 (P = 0.004), LMR ≤ 3.4 (P < 0.001), and PNI ≤ 45.3 (P = 0.001) were significantly associated with decreased survival time. On stepwise multivariate proportional hazards model, mGPS at 2 vs 0 (HR = 3.212, 95%CI: 1.437-7.716, P = 0.004), and LMR ≤ 3.4 (HR = 1.658, 95%CI: 1

  7. Algorithms for resource allocation of substance abuse prevention funds based on social indicators: a case study on state of Florida--Part 3.

    PubMed

    Kim, S; Wurster, L; Williams, C; Hepler, N

    1998-01-01

    The purpose of Part 3 is to develop an algorithm for an equitable distribution of state prevention funds to its substate jurisdictions based on the need for prevention services. In this series, the need for prevention services is measured in terms of the existing social indicators observed at the county level. In order to establish a conceptual link as well as the empirical relevance of the selected social indicators as proxy measurements of the estimated need for prevention at the county level, we have employed both concurrent and construct validity tests using the following three constructs as the criterion variables in a multiple regressing setting: 1) county-based composite drug use index score (COMDRUG) measured via the statewide drug survey; 2) county-based proportions of prevention target populations using the conceptual definition advanced by the Institute of Medicine (IOM); and 3) the composite risk factor score (COMRISK) assembled from a list of twenty-two risk and protective factors observed for each county. These constructs were identified previously in Parts 1 and 2. While employing eight social indicators to estimate the overall prevention needs observed at the county level, the social indicators thus selected were able to explain 69 percent of the variations in COMDRUG, 68 percent of the variation in the proportions of students in need of prevention services using IOM definition, and 60 percent of the variation in COMRISK. Following successful validations of the social indicators as viable media with which to estimate county-based prevention needs, the ensuing multiple regression equation is, then, used to build a resource allocation model by determining the proportion of each county's share of the total statewide COMDRUG-predicted from the social indicators and, then, by weighting the latter proportion by the population size of each county under age eighteen. In this way, we have devised county-based Prevention Needs Index (PNI) scores based solely

  8. Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

    SciTech Connect

    Huang Jiayi; Vicini, Frank A.; Williams, Scott G.; Ye Hong; McGrath, Samuel; Ghilezan, Mihai; Krauss, Daniel; Martinez, Alvaro A.; Kestin, Larry L.

    2012-07-15

    Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleason score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National

  9. Ni2P nanosheets/Ni foam composite electrode for long-lived and pH-tolerable electrochemical hydrogen generation.

    PubMed

    Shi, Yanmei; Xu, You; Zhuo, Sifei; Zhang, Jingfang; Zhang, Bin

    2015-02-01

    The continuous consumption of fossil fuels and accompanying environmental problems are driving the exploration of low-cost and effective electrocatalysts to produce clean hydrogen. A Ni2P nanosheets/Ni foam composite, as a non-noble metal electrocatalyst, has been prepared through a facile chemical conversion pathway using surface oxidized Ni foam as precursor and low concentration of trioctylphosphine (TOP) as a phosphorus source. Further investigation shows the oxidized layer of Ni foam can orient the formation of Ni2P nanosheets and facilitate the reaction with TOP. The Ni2P/Ni, acting as a robust 3D self-supported superaerophobic hydrogen-evolving cathode, shows superior catalytic performance, stability, and durability in aqueous media over a wide pH value of 0-14, making it a versatile catalyst system for hydrogen generation. Such highly active, stable, abundant, and low-cost materials hold enormously promising potential applications in the fields of catalysis, energy conversion, and storage. PMID:25564726

  10. Electrodeposition of amorphous Ni P coatings onto Nd Fe B permanent magnet substrates

    NASA Astrophysics Data System (ADS)

    Ma, C. B.; Cao, F. H.; Zhang, Z.; Zhang, J. Q.

    2006-12-01

    Decorative and protective Ni-P amorphous coatings were electroplated onto NdFeB permanent magnet from an ortho-phosphorous acid contained bath. The influences of the main electroplating technological parameters including current density, bath pH, bath temperature and H 3PO 3 on the structure and chemical composition of Ni-P coatings were investigated by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques in conjunction with X-ray diffraction (XRD), scanning transmission electron microscopy (SEM) and X-ray energy-dispersive spectrometry (EDX). The optimized amorphous Ni-P coated NdFeB can stand for ca. 180 h against neutral 3.0 wt.% NaCl salt spray without any pitting corrosion. Meanwhile, the results also showed that large phosphorous content is the precondition for Ni-P coatings to possess the amorphous structure, but too much high phosphorous content can damage the amorphous structure due to the separation of superfluous P from Ni 2P/Ni 3P and the resultant formation of multi-phase coatings (such as Ni 2P-P).

  11. Mechanism of intramolecular transformations of nickel phosphanido hydride complexes.

    PubMed

    Latypov, Shamil K; Polyancev, Fedor M; Ganushevich, Yulia S; Miluykov, Vasily A; Sinyashin, Oleg G

    2016-02-01

    In solution, nickel phosphanido hydride complexes ([NiH{P(Ar)(H)}(dtbpe)], Ar = Dmp, Mes*) undergo a degenerate intramolecular exchange, with the Ni-H and P-H hydrogens and both halves of the dtbpe moiety interchanging. This intramolecular rearrangement was shown to occur in three steps: first, the hydride proton migrates to phosphorus, then the P-Aryl moiety rotates around the P-Ni bond, and finally the back migration of one proton to Ni completes the process. Both migration and rotation were determined to be characterized by high barriers (on the NMR time scale) and to depend on the type of aryl group at the terminal phosphorus. Compared to that observed for the Ni complexes, the same isomeric preference, but with a slower rate of intramolecular rearrangement, is predicted for the corresponding Pt complexes. An opposite isomeric preference, however, is expected for the corresponding Pd complexes. Thus, it is likely that some of the catalytic reactions of Pd and Pt complexes are driven by the relative thermodynamic stabilities of their main forms. PMID:26407302

  12. Valence Band Dependent Charge Transport in Bulk Molecular Electronic Devices Incorporating Highly Conjugated Multi-[(Porphinato)Metal] Oligomers.

    PubMed

    Bruce, Robert C; Wang, Ruobing; Rawson, Jeff; Therien, Michael J; You, Wei

    2016-02-24

    Molecular electronics offers the potential to control device functions through the fundamental electronic properties of individual molecules, but realization of such possibilities is typically frustrated when such specialized molecules are integrated into a larger area device. Here we utilize highly conjugated (porphinato)metal-based oligomers (PM(n) structures) as molecular wire components of nanotransfer printed (nTP) molecular junctions; electrical characterization of these "bulk" nTP devices highlights device resistances that depend on PM(n) wire length. Device resistance measurements, determined as a function of PM(n) molecular length, were utilized to evaluate the magnitude of a phenomenological β corresponding to the resistance decay parameter across the barrier; these data show that the magnitude of this β value is modulated via porphyrin macrocycle central metal atom substitution [β(PZn(n); 0.065 Å(-1)) < β(PCu(n); 0.132 Å(-1)) < β(PNi(n); 0.176 Å(-1))]. Cyclic voltammetric data, and ultraviolet photoelectron spectroscopic studies carried out at gold surfaces, demonstrate that these nTP device resistances track with the valence band energy levels of the PM(n) wire, which were modulated via porphyrin macrocycle central metal atom substitution. This study demonstrates the ability to fabricate "bulk" and scalable electronic devices in which function derives from the electronic properties of discrete single molecules, and underscores how a critical device function--wire resistance--may be straightforwardly engineered by PM(n) molecular composition. PMID:26829704

  13. The development of military medical care for peripheral nerve injuries during World War I.

    PubMed

    Hanigan, William

    2010-05-01

    Although the clinical and electrical diagnoses and treatments of peripheral nerve injuries (PNIs) had been described prior to World War I, many reports were fragmented and incomplete. Individual physicians' experiences were not extensive, and in 1914 the patient with a PNI remained a subject of medical curiosity, and was hardly a focus of comprehensive care. World War I altered these conditions; casualties with septic wounds and PNIs swamped the general hospitals. By 1915, specialized hospitals or wards were developed to care for neurological injuries. In the United Kingdom, Sir Robert Jones developed the concept of Military Orthopedic Centres, with coordinated specialized care and rehabilitation. Military appointments of neurologists and electrotherapists sharpened clinical diagnoses and examinations. Surgical techniques were introduced, then discarded or accepted as surgeons developed skills to meet the new conditions. The US Surgeon General, William Gorgas, and his consultant in neurosurgery, Charles Frazier, went a step further, with the organization of a research laboratory as well as the establishment of a Peripheral Nerve Commission and Registry. Despite these developments and good intentions, postwar follow-up for PNIs remained incomplete at best. Records were lost, personnel transferred, and patients discharged from the system. The lack of a standardized grading system seriously impaired the ability to record clinical changes and compare outcomes. Nevertheless, specialized treatment of a large number of PNIs during World War I established a foundation for comprehensive care that influenced military medical services in the next world war. PMID:20568941

  14. Development of automated high throughput single molecular microfluidic detection platform for signal transduction analysis

    NASA Astrophysics Data System (ADS)

    Huang, Po-Jung; Baghbani Kordmahale, Sina; Chou, Chao-Kai; Yamaguchi, Hirohito; Hung, Mien-Chie; Kameoka, Jun

    2016-03-01

    Signal transductions including multiple protein post-translational modifications (PTM), protein-protein interactions (PPI), and protein-nucleic acid interaction (PNI) play critical roles for cell proliferation and differentiation that are directly related to the cancer biology. Traditional methods, like mass spectrometry, immunoprecipitation, fluorescence resonance energy transfer, and fluorescence correlation spectroscopy require a large amount of sample and long processing time. "microchannel for multiple-parameter analysis of proteins in single-complex (mMAPS)"we proposed can reduce the process time and sample volume because this system is composed by microfluidic channels, fluorescence microscopy, and computerized data analysis. In this paper, we will present an automated mMAPS including integrated microfluidic device, automated stage and electrical relay for high-throughput clinical screening. Based on this result, we estimated that this automated detection system will be able to screen approximately 150 patient samples in a 24-hour period, providing a practical application to analyze tissue samples in a clinical setting.

  15. New Criteria to Assess Seismic and Rock Burst Hazard in Coal Mines / Nowe Kryteria Dla Oceny Zagrożenia Sejsmicznego I Tąpaniami W Kopalniach Węgla Kamiennego

    NASA Astrophysics Data System (ADS)

    Mutke, Grzegorz; Dubiński, Józef; Lurka, Adam

    2015-09-01

    The paper presents new criteria of seismic and rock burst hazard assessment in Polish hard coal mines where longwall mining system is common practice. The presented criteria are based on the results of continuous recording of seismic events and analysis of selected seismological parameters: spatial location of seismic event in relation to mining workings, seismic energy, seismic energy release per unit coal face advance, b-value of Gutenberg-Richter law, seismic energy index EI, seismic moment M0, weighted value of peak particle velocity PPVW. These parameters are determined in a moving daily time windows or time windows with fixed number of seismic tremors. Time changes of these parameters are then compared with mean value estimated in the analyzed area. This is the basis to indicate the zones of high seismic and rock burst hazard in specific moment in time during mining process. Additionally, the zones of high seismic and rock burst hazard are determined by utilization of passive seismic tomography method. All the calculated seismic parameters in moving time windows are used to quantify seismic and rock burst hazard by four level scales. In practice, assessment of seismic and rock burst hazard is used to make daily decision about using rock burst prevention activities and correction of further exploitation of monitored coal panel. Zagrożenie sejsmiczne i związane z nim genetycznie zagrożenie tąpnięciem w dalszym ciągu należą do najgroźniejszych zagrożeń naturalnych występujących w polskich kopalniach węgla kamiennego. W ostatnich latach w kopalniach Górnośląskiego Zagłębia Węglowego (GZW) rocznie rejestrowano 1000÷1500 wstrząsów o energii sejsmicznej Es ≥ 1·105J (magnituda lokalna ML ≥ 1.7), a najsilniejsze z nich osiągały energię Es = 4 ·109J (ML = 4.1). W latach 1991-2010 odnotowano w GZW 101 tąpnięć, z których około 66% miało miejsce w wyrobiskach chodnikowych, powodując ich uszkodzenia lub całkowite zniszczenie, a w

  16. Effect of bovine viral diarrhea virus infection on fertility of dairy heifers.

    PubMed

    Muñoz-Zanzi, Claudia A; Thurmond, Mark C; Hietala, Sharon K

    2004-04-15

    A prospective field study in heifers from birth to first breeding was undertaken on two commercial dairies to assess the effect of bovine viral diarrhea virus (BVDV) congenital and post-natal infection (PNI) on fertility. A high BVDV Type 2 antibody titer (1:4096) at 10 months of age was associated with 32 more days to conceive, compared with a low titer (1:128). Conversely, infection with BVDV by 5-6 months of age and high BVDV Type 2 titers 1 month before conception or breeding was associated with improved fertility. Heifers with evidence of congenital BVDV infection had lower fertility than non-infected heifers (15-42 days longer time-to-first AI), which depended on BVDV Type 2 titers at 10 months of age. Neospora caninum infection was associated with additional services per conception (SPC) and Leptospira interrogans infection was associated with a delay in the time-to-first breeding. It appears that under field conditions, the effect of subclinical BVDV infection on subsequent heifer fertility may be due to a complex of interrelationships among multiple BVDV infections that depend on the type and timing of infection relative to reproductive development and events. PMID:15036997

  17. Rare Earth Elements of Orzeskie Beds of South-West Part Upper Silesian Coal Basin (Poland) / Pierwiastki Ziem Rzadkich Z Pokładów Węgla Warstw Orzeskich Południowo-Zachodniej Części Gzw (Polska)

    NASA Astrophysics Data System (ADS)

    Adamczyk, Zdzisław; Białecka, Barbara; Moszko, Joanna Całusz; Komorek, Joanna; Lewandowska, Małgorzata

    2015-03-01

    The subject of the research concerned the coal samples from 360/1, 361 and 362/1 seams of the Orzesze beds in the "Pniówek" coal mine. The obtained samples were characterized by low ash content - 2.22- 6.27% of the mass. The chemical composition of the ash indicates the presence of aluminosilicate minerals in the analyzed coal samples - most likely clay minerals, the presence of which has been confirmed in microscopic tests of the petrographic composition of channel samples of coal. The content of rare earth elements (REE sum) in the ash of the tested coal seams ranged from 364 to 1429 ppm. Variation of the REE content has been observed within a single seam. The fraction of REE indicates a relation with a mineral substance. No relation of the REE fraction and the presence of red beds has been found based on the tested samples. The content of REE found in ash, normalized to chondrites, is characterized by LREE enrichment in relation to HREE. The Eu anomaly is most likely related to tuff and tonstein levels occurring in Orzesze beds, which accompany the coal seams in the Upper Silesian Coal Basin (i.a., south of the studied area). The research has indicated that LREE in the tested samples are more related to the mineral substance, while HREE have a stronger affinity with organic substances. Przedmiotem badań były próbki węgla z pokładów 360/1, 361 i 362/1 warstw orzeskich KWK Pniówek. Próbki te charakteryzują się niewielką zawartością popiołu 2,22-6,27% mas. Skład chemiczny popiołów wskazuje na obecność w analizowanych próbkach węgla minerałów z grupy glinokrzemianów najprawdopodobniej minerałów ilastych, których obecność była stwierdzona w badaniach mikroskopowych składu petrograficznego próbek bruzdowych węgla. Zawartości pierwiastków ziem rzadkich (suma REE) w popiołach badanych pokładów węgla wahają się od 364 do 1429 ppm. Obserwuje się zróżnicowanie zawartości REE w obrębie jednego pok

  18. Indian Council of Medical Research consensus document for the management of tongue cancer

    PubMed Central

    D’Cruz, Anil K.; Sharma, Shilpi; Agarwal, Jaiprakash P.; Thakar, Alok; Teli, Ashraf; Arya, Supreeta; Desai, Chirag; Chaturvedi, Pankaj; Sebastian, Paul; Verghese, Bipin T.; Kane, Shubhada; Sucharita, V; Kaur, Tanvir; Shukla, D. K.; Rath, Goura Kishor

    2015-01-01

    EXECUTIVE SUMMARY The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.Early diagnosis is imperative in improving outcomes and preserving quality of life. High index of suspicion is to be maintained for leukoplakia (high risk site).Evaluation of a patient with newly diagnosed tongue cancer should include essential tests: Magnetic resonance imaging (MRI) is investigative modality of choice when indicated. Computed tomography (CT) scan is an option when MRI is unavailable. In early lesions when imaging is not warranted ultrasound may help guide management of the neck.Early stage cancers (stage I & II) require single modality treatment – either surgery or radiotherapy. Surgery is preferred. Adjuvant radiotherapy is indicated for T3/T4 cancers, presence of high risk features [lymphovascular emboli (LVE), perineural invasion (PNI), poorly differentiated, node +, close margins). Adjuvant chemoradiation (CTRT) is indicated for positive margins and extranodal disease.Locally advanced operable cancers (stage III & IVA) require combined multimodality treatment - surgery + adjuvant treatment. Adjuvant treatment is indicated in all and in the presence of high risk features as described above.Locally advanced inoperable cancers (stage IVB) are treated with palliative chemo-radiotherapy, chemotherapy, radiotherapy, or symptomatic treatment depending upon the performance status. Select cases may be considered for neoadjuvant chemotherapy followed by surgical salvage.Metastatic disease (stage IVC) should be treated with a goal for palliation. Chemotherapy may be offered to patients with good performance status. Local treatment in the form of radiotherapy may be added for palliation of symptoms.Intense follow-up every 3 months is required for initial 2 years as most recurrences occur in the first 24 months. After 2nd year follow up is done at 4-6 months interval. At each follow up

  19. Indian Council of Medical Research consensus document for the management of tongue cancer.

    PubMed

    D'Cruz, Anil K; Sharma, Shilpi; Agarwal, Jaiprakash P; Thakar, Alok; Teli, Ashraf; Arya, Supreeta; Desai, Chirag; Chaturvedi, Pankaj; Sebastian, Paul; Verghese, Bipin T; Kane, Shubhada; Sucharita, V; Kaur, Tanvir; Shukla, D K; Rath, Goura Kishor

    2015-01-01

    The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.Early diagnosis is imperative in improving outcomes and preserving quality of life. High index of suspicion is to be maintained for leukoplakia (high risk site).Evaluation of a patient with newly diagnosed tongue cancer should include essential tests: Magnetic resonance imaging (MRI) is investigative modality of choice when indicated. Computed tomography (CT) scan is an option when MRI is unavailable. In early lesions when imaging is not warranted ultrasound may help guide management of the neck.Early stage cancers (stage I & II) require single modality treatment - either surgery or radiotherapy. Surgery is preferred. Adjuvant radiotherapy is indicated for T3/T4 cancers, presence of high risk features [lymphovascular emboli (LVE), perineural invasion (PNI), poorly differentiated, node +, close margins). Adjuvant chemoradiation (CTRT) is indicated for positive margins and extranodal disease.Locally advanced operable cancers (stage III & IVA) require combined multimodality treatment - surgery + adjuvant treatment. Adjuvant treatment is indicated in all and in the presence of high risk features as described above.Locally advanced inoperable cancers (stage IVB) are treated with palliative chemo-radiotherapy, chemotherapy, radiotherapy, or symptomatic treatment depending upon the performance status. Select cases may be considered for neoadjuvant chemotherapy followed by surgical salvage.Metastatic disease (stage IVC) should be treated with a goal for palliation. Chemotherapy may be offered to patients with good performance status. Local treatment in the form of radiotherapy may be added for palliation of symptoms.Intense follow-up every 3 months is required for initial 2 years as most recurrences occur in the first 24 months. After 2(nd) year follow up is done at 4-6 months interval. At each follow up screening for local

  20. Dynamics of suspensions of hydrodynamically structured particles: analytic theory and applications to experiments.

    PubMed

    Riest, Jonas; Eckert, Thomas; Richtering, Walter; Nägele, Gerhard

    2015-04-14

    We present an easy-to-use analytic toolbox for the calculation of short-time transport properties of concentrated suspensions of spherical colloidal particles with internal hydrodynamic structure, and direct interactions described by a hard-core or soft Hertz pair potential. The considered dynamic properties include self-diffusion and sedimentation coefficients, the wavenumber-dependent diffusion function determined in dynamic scattering experiments, and the high-frequency shear viscosity. The toolbox is based on the hydrodynamic radius model (HRM) wherein the internal particle structure is mapped on a hydrodynamic radius parameter for unchanged direct interactions, and on an existing simulation data base for solvent-permeable and spherical annulus particles. Useful scaling relations for the diffusion function and self-diffusion coefficient, known to be valid for hard-core interaction, are shown to apply also for soft pair potentials. We further discuss extensions of the toolbox to long-time transport properties including the low-shear zero-frequency viscosity and the long-time self-diffusion coefficient. The versatility of the toolbox is demonstrated by the analysis of a previous light scattering study of suspensions of non-ionic PNiPAM microgels [Eckert et al., J. Chem. Phys., 2008, 129, 124902] in which a detailed theoretical analysis of the dynamic data was left as an open task. By the comparison with Hertz potential based calculations, we show that the experimental data are consistently and accurately described using the Verlet-Weis corrected Percus-Yevick structure factor as input, and for a solvent penetration length equal to three percent of the excluded volume radius. This small amount of solvent permeability of the microgel particles has a significant dynamic effect at larger concentrations. PMID:25707362

  1. Strategies for regeneration of components of nervous system: scaffolds, cells and biomolecules

    PubMed Central

    Tian, Lingling; Prabhakaran, Molamma P.; Ramakrishna, Seeram

    2015-01-01

    Nerve diseases including acute injury such as peripheral nerve injury (PNI), spinal cord injury (SCI) and traumatic brain injury (TBI), and chronic disease like neurodegeneration disease can cause various function disorders of nervous system, such as those relating to memory and voluntary movement. These nerve diseases produce great burden for individual families and the society, for which a lot of efforts have been made. Axonal pathways represent a unidirectional and aligned architecture allowing systematic axonal development within the tissue. Following a traumatic injury, the intricate architecture suffers disruption leading to inhibition of growth and loss of guidance. Due to limited capacity of the body to regenerate axonal pathways, it is desirable to have biomimetic approach that has the capacity to graft a bridge across the lesion while providing optimal mechanical and biochemical cues for tissue regeneration. And for central nervous system injury, one more extra precondition is compulsory: creating a less inhibitory surrounding for axonal growth. Electrospinning is a cost-effective and straightforward technique to fabricate extracellular matrix (ECM)-like nanofibrous structures, with various fibrous forms such as random fibers, aligned fibers, 3D fibrous scaffold and core-shell fibers from a variety of polymers. The diversity and versatility of electrospinning technique, together with functionalizing cues such as neurotrophins, ECM-based proteins and conductive polymers, have gained considerable success for the nerve tissue applications. We are convinced that in the future the stem cell therapy with the support of functionalized electrospun nerve scaffolds could be a promising therapy to cure nerve diseases. PMID:26813399

  2. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

    PubMed Central

    Saloman, Jami L.; Albers, Kathryn M.; Li, Dongjun; Hartman, Douglas J.; Crawford, Howard C.; Muha, Emily A.; Rhim, Andrew D.; Davis, Brian M.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations. PMID:26929329

  3. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

    PubMed

    Saloman, Jami L; Albers, Kathryn M; Li, Dongjun; Hartman, Douglas J; Crawford, Howard C; Muha, Emily A; Rhim, Andrew D; Davis, Brian M

    2016-03-15

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations. PMID:26929329

  4. Essential elucidation for preparation of supported nickel phosphide upon nickel phosphate precursor

    SciTech Connect

    Liu, Xuguang; Xu, Lei; Zhang, Baoquan

    2014-04-01

    Preparation of supported nickel phosphide (Ni{sub 2}P) depends on nickel phosphate precursor, generally related to its chemical composition and supports. Study of this dependence is essential and meaningful for the preparation of supported Ni{sub 2}P with excellent catalytic activity. The chemical nature of nickel phosphate precursor is revealed by Raman and UV–vis spectra. It is found that initial P/Ni mole ratio ≥0.8 prohibits the Ni-O-Ni bridge bonding (i.e., nickel oxide). This chemical bonding will not result in Ni{sub 2}P structure, verified by XRD characterization results. The alumina (namely, γ-Al{sub 2}O{sub 3}, θ-Al{sub 2}O{sub 3}, or α-Al{sub 2}O{sub 3}) with distinct physiochemical properties also results in diverse chemical nature of nickel phosphate, and then different nickel phosphides. The influence of alumina support on producing Ni{sub 2}P was explained by the theory of surface energy heterogeneity, calculated by the NLDFT method based on N{sub 2}-sorption isotherm. The uniform surface energy of α-Al{sub 2}O{sub 3} results only in the nickel phosphosate precursor and thus the Ni{sub 2}P phase. - Graphical abstract: Surface energy heterogeneity in alumina (namely α-Al{sub 2}O{sub 3}, θ-Al{sub 2}O{sub 3}, and γ-Al{sub 2}O{sub 3}) supported multi-oxidic precursors with different reducibilities and thus diverse nickel phosphides (i.e., Ni{sub 3}P, Ni{sub 12}P{sub 5}, Ni{sub 2}P). - Highlights: • Preparing pure Ni{sub 2}P. • Elucidating nickel phosphate precursor. • Associating with surface energy.

  5. Novel room-temperature spin-valve-like magnetoresistance in magnetically coupled nano-column Fe3O4/Ni heterostructure.

    PubMed

    Xiao, Wen; Song, Wendong; Herng, Tun Seng; Qin, Qing; Yang, Yong; Zheng, Ming; Hong, Xiaoliang; Feng, Yuan Ping; Ding, Jun

    2016-08-25

    Herein, we design a room-temperature spin-valve-like magnetoresistance in a nano-column Fe3O4/Ni heterostructure without using a non-magnetic spacer or pinning layer. An Fe3O4 nano-column film is self-assembled on a Ni underlayer by the thermal decomposition method. The wet-chemical self-assembly is facile, economical and scalable. The magnetoresistance (MR) response of the Ni underlayer in the heterostructure under positive and negative out-of-plane magnetic fields differ by ∼0.25 at room temperature and ∼0.43 at 100 K. We attribute the spin-valve-like magnetoresistance to the unidirectional magnetic anisotropy of the Ni underlayer when being magnetically coupled by the Fe3O4 nano-column film. The out-of-plane negative-field magnetization is higher than the positive-field magnetization, affirming the unidirectional magnetic anisotropy of the Fe3O4/Ni heterostructure. Temperature-dependent magnetic and resistivity studies illustrate a close correlation between the magnetization transition of Fe3O4 and resistivity transition of Ni and prove a magnetic coupling between the Fe3O4 and Ni. First-principles calculations reveal that the Fe3O4/Ni model under a negative magnetic field is energetically more stable than that under a positive magnetic field. Furthermore, partial density of states (PDOS) analysis demonstrates the unidirectional magnetic anisotropy of the Ni 3d orbital. This is induced by the strong ferromagnetic coupling between Fe3O4 and Ni via oxygen-mediated Fe 3d-O 2p-Ni 3d hybridizations. PMID:27526860

  6. Induction of neurite outgrowth in 3D hydrogel-based environments.

    PubMed

    Assunção-Silva, Rita C; Oliveira, Cátia Costa; Ziv-Polat, Ofra; Gomes, Eduardo D; Sahar, Abraham; Sousa, Nuno; Silva, Nuno A; Salgado, António J

    2015-09-01

    The ability of peripheral nervous system (PNS) axons to regenerate and re-innervate their targets after an injury has been widely recognized. However, despite the considerable advances made in microsurgical techniques, complete functional recovery is rarely achieved, especially for severe peripheral nerve injuries (PNIs). Therefore, alternative therapies that can successfully repair peripheral nerves are still essential. In recent years the use of biodegradable hydrogels enriched with growth-supporting and guidance cues, cell transplantation, and biomolecular therapies have been explored for the treatment of PNIs. Bearing this in mind, the aim of this study was to assess whether Gly-Arg-Gly-Asp-Ser synthetic peptide (GRGDS)-modified gellan gum (GG) based hydrogels could foster an amenable environment for neurite/axonal growth. Additionally, strategies to further improve the rate of neurite outgrowth were also tested, namely the use of adipose tissue derived stem cells (ASCs), as well as the glial derived neurotrophic factor (GDNF). In order to increase its stability and enhance its bioactivity, the GDNF was conjugated covalently to iron oxide nanoparticles (IONPs). The impact of hydrogel modification as well as the effect of the GDNF-IONPs on ASC behavior was also screened. The results revealed that the GRGDS-GG hydrogel was able to support dorsal root ganglia (DRG)-based neurite outgrowth, which was not observed for non-modified hydrogels. Moreover, the modified hydrogels were also able to support ASCs attachment. In contrast, the presence of the GDNF-IONPs had no positive or negative impact on ASC behavior. Further experiments revealed that the presence of ASCs in the hydrogel improved axonal growth. On the other hand, GDNF-IONPs alone or combined with ASCs significantly increased neurite outgrowth from DRGs, suggesting a beneficial role of the proposed strategy for future applications in PNI regenerative medicine. PMID:26480959

  7. Mucoadhesive thermo-responsive chitosan-g-poly(N-isopropylacrylamide) polymeric micelles via a one-pot gamma-radiation-assisted pathway.

    PubMed

    Sosnik, Alejandro; Imperiale, Julieta C; Vázquez-González, Brenda; Raskin, Maya Menaker; Muñoz-Muñoz, Franklin; Burillo, Guillermina; Cedillo, Gerardo; Bucio, Emilio

    2015-12-01

    Thermo-sensitive graft copolymer amphiphiles of chitosan (CS) and poly(N-isopropylacrylamide) (PNiPAAm), CS-g-PNIPAAm, were successfully synthesized by a catalyst-less one-pot gamma (γ)-radiation-assisted free radical polymerization at three different radiation doses: 5, 10 and 20 kGy. The chemical structure of the copolymers was confirmed by FTIR and solid-state (13)C NMR and the grafting extent by (1)H NMR and gravimetric analysis. In general, the higher the dose, the smaller the grafting due to the more significant NiPAAm homopolymerization. Due to the grafting of poly(NiPAAm) blocks, aqueous solutions of the different copolymers underwent a sharp transition upon heating above 32 °C, the characteristic lower critical solution temperature (LCST) of poly(NiPAAm). Then, the critical micellar concentration (CMC), the size and size distribution and the zeta-potential were characterized by dynamic light scattering (DLS) and the polymeric micelles visualized in suspension and quantified by Nanoparticle Tracking Analysis (NTA), at 37 °C. CMC values were in the 0.0012-0.0025%w/v range and micelles displayed sizes between 99 and 203 nm with low polydispersity (<0.160) and highly positive zeta-potential (>+15 mV) that suggested the partial conservation of the amine groups upon NiPAAm grafting. Consequently, polymeric micelles displayed the intrinsic mucoadhesiveness of CS, as established in vitro by the mucin solution assay. Finally, the encapsulation capacity of the micelles was assessed with the highly hydrophobic protease inhibitor antiretroviral indinavir free base (IDV). Polymeric micelles led to a significant 24-fold increase of the aqueous solubility from 63 μg/mL to 1.45 mg/mL, a performance remarkably better than different poly(ethylene oxide)-b-poly(propylene oxide) block copolymers assessed before. Overall results highlight the potential of this nanotechnology platform to expand the application of polymeric micelles to mucosal administration routes. PMID

  8. Multi-electron systems in strong magnetic fields II: A fixed-phase diffusion quantum Monte Carlo application based on trial functions from a Hartree-Fock-Roothaan method

    NASA Astrophysics Data System (ADS)

    Boblest, S.; Meyer, D.; Wunner, G.

    2014-11-01

    -Fock calculations. The guiding functions are created from single-electron orbitals ψi which are either products of a wave function in the z-direction (the direction of the magnetic field) and an expansion of the wave function perpendicular to the direction of the magnetic field in terms of Landau states, ψi(ρ,φ,z)=Pi(z)∑n=0NLtinϕni(ρ,φ), or a full two-dimensional expansion using separate z-wave functions for each Landau level, i.e. ψi(ρ,φ,z)=∑n=0NLPni(z)ϕni(ρ,φ). In the first form, the tin are expansion coefficients, and the expansion is cut off at some maximum Landau level quantum number NL. In the second form, the expansion coefficients are contained in the respective Pni. Restrictions: The method itself is very flexible and not restricted to a certain interval of magnetic field strengths. However, it is only variational for the lowest-lying state in each symmetry subspace and the accompanying Hartree-Fock method can only obtain guiding functions in the regime of strong magnetic fields. Unusual features: The program needs approximate wave functions computed with another method as input. Running time: 1 min-several days. The example provided takes approximately 50 min to run on 1 processor.

  9. The Sentry Autonomous Underwater Vehicle: Field Trial Results and Future Capabilities

    NASA Astrophysics Data System (ADS)

    Yoerger, D. R.; Bradley, A. M.; Martin, S. C.; Whitcomb, L. L.

    2006-12-01

    The Sentry autonomous underwater vehicle combines an efficient long range survey capability with the ability to maneuver at low speeds. These attributes will permit Sentry to perform a variety of conventional and unconventional surveys including long range sonar surveys, hydrothermal plume surveys and near-bottom photo surveys. Sentry's streamlined body and fore and aft tilting planes, each possessing an independently controlled thruster, enable efficient operation in both near-bottom and cruising operations. Sentry is capable of being configured in two modes: hover mode, which commands Sentry's control surfaces to be aligned vertically, and forward flight mode, which allows Sentry's control surfaces to actuate between plus or minus 45 degrees. Sentry is equipped for full 6-Degrees of freedom position measurement. Vehicle heading, roll, and pitch are instrumented with a TCM2 PNI heading and attitude sensor. A Systron Donner yaw rate sensor instrumented heading rate. Depth is instrumented by a Paroscientific depth sensor. A 300kHz RD Instruments Doppler Sonar provides altitude and XYZ velocity measurements. In April 2006, we conducted our first deep water field trials of Sentry in Bermuda. These trials enabled us to examine a variety of issues, including the control software, vehicle safety systems, launch and recovery procedures, operation at depth, heading and depth controllers over a range of speeds, and power consumption. Sentry employ's a control system based upon the Jason 2 control system for low-level control, which has proven effective and reliable over several hundred deep-water dives. The Jason 2 control system, developed jointly at Johns Hopkins University and Woods Hole Oceanographic Institution, was augmented to manage Sentry-specific devices (sensors, actuators, and power storage) and to employ a high-level mission controller that supported autonomous mission scripting and error detection and response. This control suite will also support the Nereus

  10. Metal Complexes of Dithiolate Ligands: 5,6-Dihydro-1,4-dithiin-2,3-dithiolato (dddt(2-)), 5,7-Dihydro-1,4,6-trithiin-2,3-dithiolato (dtdt(2-)), and 2-Thioxo-1,3-dithiole-4,5-dithiolato (dmit(2-)). Synthesis, Electrochemical Studies, Crystal and Electronic Structures, and Conducting Properties.

    PubMed

    Faulmann, Christophe; Errami, Ahmed; Donnadieu, Bruno; Malfant, Isabelle; Legros, Jean-Pierre; Cassoux, Patrick; Rovira, Carme; Canadell, Enric

    1996-06-19

    the [M(dtdt)(2)](-) complexes always yields the neutral [M(dtdt)(2)](0) species. The crystal structure of [Pt(dddt)(2)][Ni(dmit)(2)](2) (4) has been determined and is consistent with the low compaction powder conductivity (5 x 10(-)(5) S cm(-)(1) at room temperature) {4 = C(20)H(8)Ni(2)PtS(28), a = 20.336(4) Å, b = 7.189(2) Å, c = 14.181(2) Å, beta = 97.16(2) degrees, V = 2057(1) Å(3), monoclinic, C2/m, Z = 2}. The crystal structures of the semiconducting NIOS compounds (BTP)[Ni(dmit)(2)](3) (5) and (SMe(3))[Ni(dmit)(2)](2) (6) have been determined {5 = C(43)H(22)PNi(3)S(30), a = 11.927(2) Å, b = 24.919(2) Å, c = 11.829(3) Å, alpha = 93.11(1) degrees, beta = 110.22(1) degrees, gamma = 83.94(1) degrees, V = 3284(1) Å(3), triclinic, P&onemacr;, Z = 2; 6 = C(15)H(9)Ni(2)S(21), a = 7.882(1) Å, b = 11.603(2) Å, c = 17.731(2) Å, alpha = 77.44(1) degrees, beta = 94.39(1) degrees, gamma = 81.27(1) degrees, V = 1563(1) Å(3), triclinic, P&onemacr;, Z = 2}. The parent compound (SEt(3))[Ni(dmit)(2)](z) (unknown stoichiometry) is also a semiconductor with a single-crystal conductivity at room temperature of 10 S cm(-)(1). By contrast, the single-crystal conductivity at room temperature of (SMeEt(2))[Pd(dmit)(2)](2) (7) is rather high (100 S cm(-)(1)). 7 behaves as a pseudometal down to 150 K and undergoes an irreversible metal-insulator transition below this temperature. The crystal structure of 7 has been determined {7 = C(17)H(13)NPd(2)S(21), a = 7.804(4) Å, b = 36.171(18) Å, c = 6.284(2) Å, alpha = 91.68(4) degrees, beta = 112.08(4) degrees, gamma = 88.79(5) degrees, V = 1643(1) Å(3), triclinic, P&onemacr;, Z = 2}. The electronic structure of (SMeEt(2))[Pd(dmit)(2)](2) (7) and the possible origin of the metal-insulator transition at 150 K are discussed on the basis of tight-binding band structure calculations. PMID:11666575

  11. Acid Mine Drainage Treatment by Perlite Nanomineral, Batch and Continuous Systems

    NASA Astrophysics Data System (ADS)

    Shabani, Kumars Seifpanahi; Ardejani, Faramarz Doulati; Badii, Khshayar; Olya, Mohammad Ebrahim

    2014-03-01

    ąsteczek do rozmiarów rzędu nano- cząsteczek. Perlit poddany został następnie badaniom z wykorzystaniem dyfrakcji promieniowania rentgenowskiego, rentgenowskiej analizy fluorescencyjnej, skaningowej mikroskopii elektronowej, transmisyjnej mikroskopii elektronowej, spektroskopii w podczerwieni z transformatą Fouriera. Przeprowadzono także badania powierzchni właściwej w oparciu o równanie BET. Wyniki badań kwaśnych wód kopalnianych wykazują ich kwasowość na poziomie 5.1, a zawartość jonów Cu2+, Fe2+ i Mn2 wynosi odpowiednio 10.5, 4.1, 8.3 ppm. W pierwszym etapie analizowano system działania okresowego, zbadano wpływ następujących parametrów: ilości czynnika absorbującego i temperatury. Następnie przebadano modele izotermiczne i kinetyczne. Na podstawie uzyskanych wyników wykazano, że izoterma Langmuira oraz model pseudo-kinetycznego drugiego rzędu wykazują lepszą zgodność z danymi eksperymentalnymi niż pozostałe modele izotermiczne i kinetyczne. Uzyskane parametry termodynamiczne: ΔG°, ΔH° i ΔS° wskazują, że adsorpcja jonów Cu2+, Fe2+ i Mn2 z kwaśnych wód kopalnianych przebiega spontanicznie i jest procesem endotermicznym. W końcowym etapie badania nanocząsteczki perlitu- adsorbentu zostały umieszczone wewnątrz szklanej kolumny i wykorzystane do usuwania jonów metali ciężkich z kwaśnych wód kopalnianych podawanych z prędkością przepływu 1, 3, 5 ml/min. Krzywe przebicia wskazują, że kolumna została nasycona odpowiednio po 180, 240 i 315 dla odpowiednich prędkości przepływu. Uzyskane wyniki wskazują, że ten występujący lokalnie w dużych ilościach, tani i łatwo dostępny minerał krzemianowy wykazuje wysoką skuteczność w usuwaniu z kwaśnych wód kopalniach zanieczyszczeń w postaci metali ciężkich, dlatego też może być z powodzeniem wykorzystany do oczyszczania znacznych ilości wód a także na skalę przemysłową

  12. [Tuberculosis in compromised hosts].

    PubMed

    2003-11-01

    among patients with pulmonary tuberculosis was 8.4 percent. The mean age of gastric resection was 50.2 +/- 16.6 years, and the mean interval from gastrectomy to pulmonary tuberculosis was 13.6 +/- 11.0 years. On admission to our hospital, 34 out of 55 cases were smear positive by sputum examination for acid-fast bacilli and 39 cases had cavitary lesions on chest X-ray. Gastrectomy was done due to carcinoma of the stomach in 31 cases, gastric and/or duodenal ulcer in 21 cases, adenomatous polyp in two cases, and accidental injury in one case. 52 patients improved, but three cases died due to pulmonary tuberculosis. No one had recurrence of carcinoma of the stomach. Body weight, Body Mass Index, Prognostic Nutritional Index (PNI; 10x serum albumin concentration +0.005 x peripheral lymphocyte count) which was proposed by Onodera, serum albumin level and serum total cholesterol level were lower in the gastrectomy group than in the non-gastrectomy group. I calculated the odds of tuberculosis among gastrectomy patients to be 3.8 times that of appropriate controls. This study confirms that gastrectomy is one of the risk factor(s) of tuberculosis. However, whether gastrectomy in itself is a risk factor or whether it is secondarily associated with another risk factor such as underweight status and/or inadequate nutrition following surgery remains unclear. 3. Immunodefficiency and tuberculosis in dialysis patients: Hajime INAMOTO (Division of Dialysis, Keio University School of Medicine). The patients who have renal insufficiency is fatal, but they can live much longer by dialysis. The number of lymphocytes of the patients whose serum creatinine was 10 mg/dl or more has decreased to about 50% of the people who have normal kidney. When the lymphocyte was cultured after it was stimulated with PHA, the DNA synthesis of the patients' lymphocyte was much lower than that of the modest people's. In the dialysis food, the nutrient such as vitamins, minerals, etc. were lacked. The density