bluuebunny/crossref_metadata_2025 huggingface dataset:
Antidepressant Agents for the Treatment of Chronic Pain and Depression
Authors: Jann Michael W. , Slade Julian H.
Published: October 2007

Depression and painful somatic symptoms commonly occur together. Depression and chronic pain can have devastating effects on a patient's health, productivity, and overall quality of life. When moderate‐to‐severe pain exists, it can impair patient function while making treatment more difficult or resistant, with increased severity in depressive symptoms and worse outcomes. A variety of chronic pain syndromes exist, including diabetic neuropathy. A high prevalence of patients with chronic pain display depressive symptoms. Treatment for these conditions relies on pharmacologic therapy coupled with diligent, periodic assessments of changes in symptom severity. The link between pain and depression lies in the central and peripheral nervous systems. The brain stem serves as an important connection between the higher brain centers and the spinal cord. In the brain stem, the neurotransmitters serotonin and norepinephrine modulate pain transmission through ascending and descending neural pathways. Both serotonin and norepinephrine are also key neurotransmitters involved with the pathophysiology of depression. Tricyclic antidepressants are effective treatments for pain and depression; selective serotonin reuptake inhibitors provide less benefit. Duloxetine and venlafaxine, which are serotonin and norepinephrine reuptake inhibitors, were shown in clinical trials to alleviate pain and depressive symptoms. Diabetic neuropathy and other chronic pain syndromes were also shown to benefit from duloxetine and venlafaxine. Antidepressants remain fundamental therapeutic agents for depression and anxiety disorders. Their extended use into chronic pain, depression with physical pain, physical pain with or without depression, and other potential medical conditions should be recognized.
Combination Ketamine and Propofol for Procedural Sedation and Analgesia
Authors: Slavik Victoria C. , Zed Peter J.
Published: October 2007

The combination of ketamine and propofol for procedural sedation and analgesia theoretically may be beneficial, with the rationale being that using lower doses of each agent may result in a reduction of the undesirable adverse effects of both agents while maintaining optimal conditions for performing procedures. To examine the current evidence for the efficacy and safety of ketamine and propofol in combination for procedural sedation and analgesia, we searched the MEDLINE (1966‐March 2007), EMBASE (1980‐March 2007), and Cochrane Database of Systematic Reviews (through the first quarter of 2007) databases for reports describing the use of ketamine and propofol in combination for procedural sedation and analgesia. Additional published reports were identified through a manual search of references from retrieved articles. Prospective, comparative, full‐text reports of studies performed in humans that were published in English were reviewed for inclusion. Both authors independently evaluated all studies. Studies in adult and pediatric patients were included if they evaluated efficacy or safety end points. Eight clinical trials were included, seven of which compared a combination of propofol and ketamine with propofol monotherapy. In these trials, variable milligram:milligram ratios of propofol and ketamine were used, ranging from 10:1–2:1, and the optimum dose of these agents in combination is unclear. Combination propofol and ketamine has not demonstrated superior clinical efficacy compared with propofol alone for procedural sedation and analgesia. Conflicting data exist regarding reduced hemodynamic and respiratory complications in patients receiving the combination compared with propofol monotherapy. At higher doses, the addition of ketamine to propofol may incur more adverse effects. Compatibility data for the two agents combined in a syringe are limited. The available evidence does not support the use of a fixed‐dose ketamine‐propofol combination for procedural sedation and analgesia. Further research is needed to elucidate the role, if any, of this combination for procedural sedation and analgesia.
Immunosuppression by Embryonic Stem Cells
Authors: Koch Cody A. , Geraldes Pedro , Platt Jeffrey L.
Published: October 2007

Embryonic stem cells or their progeny inevitably differ genetically from those who might receive the cells as transplants. We tested the barriers to engraftment of embryonic stem cells and the mechanisms that determine those barriers. Using formation of teratomas as a measure of engraftment, we found that semiallogeneic and fully allogeneic embryonic stem cells engraft successfully in mice, provided a sufficient number of cells are delivered. Successfully engrafted cells did not generate immunological memory; unsuccessfully engrafted cells did. Embryonic stem cells reversibly, and in a dose-dependent manner, inhibited T-cell proliferation to various stimuli and the maturation of antigen-presenting cells induced by lipopolysaccharide. Inhibition of both was owed at least in part to production of transforming growth factor-β by the embryonic stem cells. Thus, murine embryonic stem cells exert “immunosuppression” locally, enabling engraftment across allogeneic barriers.

Disclosure of potential conflicts of interest is found at the end of this article.
Gdnf Upregulates c-Fos Transcription via the Ras/Erk1/2 Pathway to Promote Mouse Spermatogonial Stem Cell Proliferation
Authors: He Zuping , Jiang Jiji , Kokkinaki Maria , Golestaneh Nady , Hofmann Marie-Claude , Dym Martin
Published: October 2007

Glial cell line-derived neurotrophic factor (GDNF) plays a crucial role in regulating the proliferation of spermatogonial stem cells (SSC). The signaling pathways mediating the function of GDNF in SSC remain unclear. This study was designed to determine whether GDNF signals via the Ras/ERK1/2 pathway in the C18-4 cells, a mouse SSC line. The identity of this cell line was confirmed by the expression of various markers for germ cells, proliferating spermatogonia, and SSC, including GCNA1, Vasa, Dazl, PCNA, Oct-4, GFRα1, Ret, and Plzf. Western blot analysis revealed that GDNF activated Ret tyrosine phosphorylation. All 3 isoforms of Shc were phosphorylated upon GDNF stimulation, and GDNF induced the binding of the phosphorylated Ret to Shc and Grb2 as indicated by immunoprecipitation and Western blotting. The active Ras was induced by GDNF, which further activated ERK1/2 phosphorylation. GDNF stimulated the phosphorylation of CREB-1, ATF-1, and CREM-1, and c-fos transcription. Notably, the increase in ERK1/2 phosphorylation, c-fos transcription, bromodeoxyuridine incorporation, and metaphase counts induced by GDNF, was completely blocked by pretreatment with PD98059, a specific inhibitor for MEK1, the upstream regulator of ERK1/2. GDNF stimulation eventually upregulated cyclin A and CDK2 expression. Together, these data suggest that GDNF induces CREB/ATF-1 family member phosphorylation and c-fos transcription via the Ras/ERK1/2 pathway to promote the proliferation of SSC. Unveiling GDNF signaling cascades in SSC has important implications in providing attractive targets for male contraception as well as for the regulation of stem cell renewal vs. differentiation.

Disclosure of potential conflicts of interest is found at the end of this article.
Toll-Like Receptors 3 and 4 Are Expressed by Human Bone Marrow-Derived Mesenchymal Stem Cells and Can Inhibit Their T-Cell Modulatory Activity by Impairing Notch Signaling
Authors: Liotta Francesco , Angeli Roberta , Cosmi Lorenzo , Filì Lucia , Manuelli Cinzia , Frosali Francesca , Mazzinghi Benedetta , Maggi Laura , Pasini Annalisa , Lisi Veronica , Santarlasci Veronica , Consoloni Lara , Angelotti Maria Lucia , Romagnani Paola , Parronchi Paola , Krampera Mauro , Maggi Enrico , Romagnani Sergio , Annunziato Francesco
Published: October 2007

Bone marrow (BM)-derived mesenchymal stem cells (MSCs) are multipotent, nonhemopoietic progenitors that also possess regulatory activity on immune effector cells through different mechanisms. We demonstrate that human BM-derived MSCs expressed high levels of Toll-like receptors (TLRs) 3 and 4, which are both functional, as shown by the ability of their ligands to induce nuclear factor κB (NF-κB) activity, as well as the production of interleukin (IL)-6, IL-8, and CXCL10. Of note, ligation of TLR3 and TLR4 on MSCs also inhibited the ability of these cells to suppress the proliferation of T cells, without influencing their immunophenotype or differentiation potential. The TLR triggering effects appeared to be related to the impairment of MSC signaling to Notch receptors in T cells. Indeed, MSCs expressed the Notch ligand Jagged-1, and TLR3 or TLR4 ligation resulted in its strong downregulation. Moreover, anti-Jagged-1 neutralizing antibody and N[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling, hampered the suppressive activity of MSCs on T-cell proliferation. These data suggest that TLR3 and TLR4 expression on MSCs may provide an effective mechanism to block the immunosuppressive activity of MSCs and therefore to restore an efficient T-cell response in the course of dangerous infections, such as those sustained by double-stranded RNA viruses or Gram-negative bacteria, respectively.

Disclosure of potential conflicts of interest is found at the end of this article.
Ribosomal Protein S19 Deficiency Leads to Reduced Proliferation and Increased Apoptosis but Does Not Affect Terminal Erythroid Differentiation in a Cell Line Model of Diamond-Blackfan Anemia
Authors: Miyake Koich , Utsugisawa Taiju , Flygare Johan , Kiefer Thomas , Hamaguchi Isao , Richter Johan , Karlsson Stefan
Published: October 2007

Diamond-Blackfan anemia (DBA) is a congenital red-cell aplasia in which 25% of the patients have a mutation in the ribosomal protein (RP) S19 gene. It is not known how the RPS19 deficiency impairs erythropoiesis and proliferation of hematopoietic progenitors. To elucidate molecular mechanisms in RPS19-deficient DBA, we analyzed the effects of RPS19 deficiency on erythropoietin (EPO)-induced signal transduction, cell cycle, and apoptosis in RPS19-deficient TF-1 cells. We did not find any abnormality in EPO-induced signal transduction. However, RPS19-deficient TF-1 cells showed G0/G1 arrest (82% vs. 58%; p < .05) together with accumulation of p21 and p27. The fraction of apoptotic cells detected by Annexin V analysis also increased compared with control cells (13% vs. 3.1%; p < .05). Western blot analysis of apoptosis-related proteins showed that the level of bcl-2 and Bad was decreased and Bax was increased in RPS19-deficient TF-1 cells. Moreover, primary CD34-positive cells from DBA patients detected by Annexin V analysis also generated a higher number of apoptotic cells compared with normal CD34-positive cells during in vitro culture (38% vs. 8.9%; n = 5; p < .001). Finally, we show that although RPS19 silencing reduces EPO-induced development of erythroid progenitors expressing glycophorin A (GPA), RPS19 silencing in cells already expressing GPA does not affect GPA expression. These findings indicate that RPS19 deficiency causes apoptosis and accelerated loss of erythroid progenitors in RPS19-deficient DBA.

Disclosure of potential conflicts of interest is found at the end of this article.
The 5th International Society for Stem Cell Research (ISSCR) Annual Meeting, June 2007
Authors: Rajasekhar Vinagolu K. , Dalerba Piero , Passegué Emmanuelle , Lagasse Eric , Najbauer Joseph
Published: October 2007

This report presents highlights of discussions that focused on the biology of cancer stem cells as conducted at the fifth Annual Meeting of the International Society for Stem Cell Research, held in Cairns, Australia, June 17–20, 2007. The function of adult stem cells is believed to depend on their niches, that is, the microenvironment in which these stem cells reside. A similar concept applies to understanding the development of cancer, as it is becoming increasingly clear that only a small subset of cancer cell populations is capable of initiating/sustaining tumor formation. These tumorigenic cells, commonly referred to as cancer stem cells, also appear to reside in particular niches, and they bear the known, albeit dysfunctional, stem cell characteristics of self-renewal and differentiation. Dysregulation of stem cell niches is thought to contribute to tumorigenesis by affecting the complex network of signaling interactions that occur between stem cells and their neighboring cells, thus imbalancing the physiological controls on self-renewal and differentiation processes. This hypothesis was widely explored at the conference to shed new light on the mechanisms of tumor origin and progression and to unveil novel antitumor therapeutic approaches.

Disclosure of potential conflicts of interest is found at the end of this article.
The HOXB4 Homeoprotein Differentially Promotes Ex Vivo Expansion of Early Human Lymphoid Progenitors
Authors: Haddad Rima , Pflumio Françoise , Vigon Isabelle , Visentin Géraldine , Auvray Céline , Fichelson Serge , Amsellem Sophie
Published: October 2007

The HOXB4 homeoprotein is known to promote the expansion of mouse and human hematopoietic stem cells (HSCs) and progenitors of the myeloid lineages. However, the putative involvement of HOXB4 in lymphopoiesis and particularly in the expansion of early lymphoid progenitor cells has remained elusive. Based on the ability of the HOXB4 protein to passively enter hematopoietic cells, our group previously designed a long-term culture procedure of human HSCs that allows ex vivo expansion of these cells. Here, this method has been further used to investigate whether HOXB4 could cause similar expansion on cells originating from CD34+ hematopoietic progenitor cells (HPCs) committed at various levels toward the lymphoid lineages. We provide evidence that HOXB4 protein delivery promotes the expansion of primitive HPCs that generate lymphoid progenitors. Moreover, HOXB4 acts on lymphomyeloid HPCs and committed T/natural killer HPCs but not on primary B-cell progenitors. Our results clarify the effect of HOXB4 in the early stages of human lymphopoiesis, emphasizing the contribution of this homeoprotein in the maintenance of the intrinsic lymphomyeloid differentiation potential of defined HPC subsets. Finally, this study supports the potential use of HOXB4 protein for HSC and HPC expansion in a therapeutic setting and furthers our understanding of the mechanisms of the molecular regulation of hematopoiesis.

Disclosure of potential conflicts of interest is found at the end of this article.
Adenoviral Vector-Mediated Transfer of the Indian Hedgehog Gene Modulates Lymphomyelopoiesis In Vivo
Authors: Kobune Masayoshi , Kato Junji , Kawano Yutaka , Sasaki Katsunori , Uchida Hiroaki , Takada Kohichi , Takahashi Sho , Takimoto Rishu , Niitsu Yoshiro
Published: October 2007

Indian hedgehog (Ihh) plays an essential role in angiogenesis, hematogenesis, and epiphysis formation during embryogenesis. In the present study, we injected an adenoviral vector (Adv) carrying the mock-control (Adv-control) or Ihh (Adv-Ihh) gene into severe combined immunodeficiency (SCID) or BALB/c mice to evaluate the effects of lhh on the regulation of postnatal hematopoiesis in vivo. After the i.v. injection of Adv-Ihh, the expression of vector-derived Ihh mRNA was detected in the liver. Four weeks after administration of Adv-Ihh to SCID mice, we observed an increase in the number of c-Kit+ cells and clonogenic cells per 105 mononuclear cells in the bone marrow compared with Adv-control-administered mice. Moreover, after administration of Adv-Ihh to BALB/c mice, the number of splenic B220+IgMlowCD23intCD21int B lymphocytes and CD4+ T lymphocytes was strongly increased. Furthermore, the number of thymic double-negative (DN)2, DN3, CD8+ immature single-positive, and CD4+/CD8− cells was significantly elevated relative to the number in mice that received the control Adv vector. Our results suggest that enhanced signaling by Ihh can modulate the proliferation and differentiation of splenic B lymphocytes and thymic T lymphocytes during bone marrow hematopoiesis in vivo. Thus, modulation of the hedgehog signaling pathway may provide a therapeutic strategy to stimulate lymphomyelopoiesis in vivo.

Disclosure of potential conflicts of interest is found at the end of this article.
Efficiency analysis for multi‐view spatially multiplexed autostereoscopic 2‐D/3‐D displays
Authors: Woodgate Graham J. , Harrold Jonathan
Published: October 2007

Abstract— The wide‐viewing freedom often requested by users of autostereoscopic displays can be delivered by spatial multiplexing of multiple views in which a sequence of images is directed into respective directions by a suitable autostereoscopic optical system. This gives rise to two important design considerations — the optical efficiency and the resolution efficiency of the device. Optical efficiency is particularly important in portable devices such as cell phones. A comparison is given between lens and barrier systems for various spatial multiplexing arrangements. Parallax‐barrier displays suffer from reduced optical efficiency as the number of views presented increases whereas throughput efficiency is independent of the number of views for lens displays. An autostereoscopic optical system is presented for the emerging class of highly efficient polarizer‐free displays. Resolution efficiency can be evaluated by investigating quantitative and subjective comparisons of resolution losses and pixel appearance in each 3‐D image. Specifically, 2.2‐in.‐diagonal 2‐D/3‐D panel performance has been assessed using Nyquist boundaries, human‐visual contrast‐sensitivity models, and autostereoscopic‐display optical output simulations. Four‐view vertical Polarization‐Activated Microlens technology with either QVGA mosaic or VGA striped pixel arrangements is a strong candidate for an optimum compromise between display brightness, viewing angle, and 3‐D pixel appearance.
Development of a 42‐in. 2‐D/3‐D switchable display using multi‐view technology for public‐information‐display applications
Authors: Kim K. J. , Kang H. , Jang M. K. , Ahn B. C. , Chung I. J. , Park T. S. , Chang J. W. , Lee K. I. , Kim S. T.
Published: October 2007

Abstract— A 42‐in. 2‐D/3‐D switchable display operating in a parallax‐barrier‐type system consisting of liquid‐crystal displays (LCDs) has been developed. The system displays 2‐D images in full resolution, without any degradation to the original 2‐D images, and 3‐D autostereoscopic images with resolutions higher than SVGA with wide viewing zones electrically controlled by the parallax‐barrier system. The system is intended for use in public‐information displays (PIDs), a booming field, and as displays for gaming, medical, and simulation applications.
Circuits using uniform TFTs based on amorphous In‐Ga‐Zn‐O
Authors: Hayashi Ryo , Ofuji Masato , Kaji Nobuyuki , Takahashi Kenji , Abe Katsumi , Yabuta Hisato , Sano Masafumi , Kumomi Hideya , Nomura Kenji , Kamiya Toshio , Hirano Masahiro , Hosono Hideo
Published: October 2007

Abstract— High‐performance and excellent‐uniformity thin‐film transistors (TFTs) having bottom‐gate structures are fabricated using an amorphous indium‐gallium‐zinc‐oxide (IGZO) film and an amorphous‐silicon dioxide film as the channel layer and the gate insulator layer, respectively. All of the 94 TFTs fabricated with an area 1 cm2 show almost identical transfer characteristics: the average saturation mobility is 14.6 cm2/(V‐sec) with a small standard deviation of 0.11 cm2/(V‐sec). A five‐stage ring‐oscillator composed of these TFTs operates at 410 kHz at an input voltage of 18 V. Pixel‐driving circuits based on these TFTs are also fabricated with organic light‐emitting diodes (OLED) which are monolithically integrated on the same substrate. It is demonstrated that light emission from the OLED cells can be switched and modulated by a 120‐Hz ac signal input. Amorphous‐IGZO‐based TFTs are prominent candidates for building blocks of large‐area OLED‐display electronics.
Comparison of some characteristics of thin‐film‐electroluminescent ZnS: Er, F planar and edge emitters
Authors: Vlasenko Nataliya A. , Oleksenko Pavel F. , Veligura Ludmila I. , Mukhlyo Miroslav O. , Denisova Zinaida L. , Zinchenko Viktor F.
Published: October 2007

Abstract— The following main differences have been revealed in the characteristics of an edge thin‐film‐electroluminescent ZnS: Er,F emitter compared to those of a similar planar emitter: (1) the 1.535‐μm band more highly dominates over other bands in the EL spectrum; (2) the voltage (V) dependence of the intensity of this band is the strongest; (3) the 1.535‐μm band narrows with increasing voltage and its frequency. The above differences are explained, firstly, by smaller optical losses in the ZnS: Er,F film for the near‐infrared emission than for the visible one and, secondly, by an optical amplification over the 1.535‐μm band in the edge emitter.
Ferroelectric properties of LC systems including chiral dopants with different molecular structure
Authors: Shkolnikova Nataliya I. , Kutulya Lidiya A. , Drushlyak Tatyana G. , Pivnenko Nikolay S. , Popova Ekaterina V. , Kopeychenko Evgene Yu.
Published: October 2007

Abstract— New ferroelectric liquid crystals (FLCs) on the basis of the eutectic mixture of phenylbenzoate derivatives including chiral components (CCs) with a different number and position of carbonyl groups in their molecular core have been investigated. The ferroelectric characteristics such as the spontaneous polarization, smectic tilt angle, rotational viscosity, and repolarization time as well as their concentration dependences are analyzed. On the basis of the previous and obtained results, the influence of peculiarities of the molecular structure of CCs on mentioned properties of FLCs are generalized.
Selection of nanostructures for porous field‐emission display
Authors: Mammana Victor P. , Hering Vitor R. , Paulo Alexandre C. , Santos Thebano E. A. , Thielo Marcelo R. , Mammana Suelene S. , den Engelsen Daniel , Mammana Alaide P.
Published: October 2007

Abstract— This paper describes the evaluation of nanostructures to be integrated into porous field‐emission displays (pFEDs), based on a multilayer of copper and polyimide, pierced by holes. The evaluation work is based on diode‐mode measurements performed with carbon nanotubes and nanostructured copper oxide samples obtained through wet chemical processes. A special characterization tool, based on the curve method, was used to obtain current vs. field characteristics in a repetitive and reproducible method. Histograms of threshold fields for 46 samples are presented, allowing for a comparison between different methods of nanostructure formation, which shows that carbon nanotubes yield a threshold field which is at least five times smaller than that for copper oxides.
Letter:Mechanisms for on/off currents in dual‐gate a‐Si:H thin‐film transistors using indium‐tin‐oxide top‐gate electrodes
Authors: Liang Chung‐Yu , Gan Feng‐Yuan , Yeh Fon‐Shan , Chang Ting‐Chang
Published: October 2007

Abstract—Two types of dual‐gate a‐Si:H TFTs were made with transparent indium‐tin‐oxide (ITO) top‐gate electrodes of different lengths to investigate the static characteristics of these devices. By changing the length of the ITO top gate, we found that the variations in the on‐currents of these dual‐gate TFTs with dual‐gate driving are due to the high resistance of the parasitic intrinsic a‐Si:H regions between the back electron channel and the source/drain contact. In the off‐state of the dual‐gate‐driven TFTs, the Poole‐Frenkel effect is also enhanced due to back‐channel hole accumulation in the vicinity of the source/drain contact. Furthermore, we observed for the first time that under illumination the dual‐gate‐driven a‐Si:H TFTs exhibit extremely low photo‐leakage currents, much lower than that of single‐gate‐driven TFTs in a certain range (reverse subthreshold region) of negative gate voltages. The high on/off current ratio under backside illumination makes dual‐gate TFTs suitable devices for use as switching elements in liquid‐crystal displays (LCDs) or for other applications.
Tolerance (PICT) of the Bacterial Communities to Copper in Vineyards Soils from Spain
Authors: Díaz‐Raviña M. , de Anta R. Calvo , Bååth E.
Published: October 2007

To detect effects of Cu pollution, the Cu tolerance of soil bacterial communities extracted from several vineyards located in NW Spain was measured. Bacterial community tolerance was estimated by means of the thymidine (TdR) and leucine (Leu) incorporation techniques using either IC50 values (the log of the metal concentration that reduced incorporation to 50%) or the percentage of activity at one specific Cu concentration (10−6 mol L−1). The tolerance measurements by the TdR incorporation technique were similar to those obtained by the Leu incorporation method, indicating that the two methods were equivalent in terms of suitability for detecting the toxicity of Cu to soil bacterial communities. The two tolerance indices considered (IC50 values and percentage of activity) were closely correlated (r = 0.975, P < 0.001), showing that both were equally good in measuring Cu tolerance of the bacterial community. An increased bacterial community tolerance to Cu, indicating a pollution effect, was observed in vineyard soils with more than 100 mg Cu kg−1 soil. Thus, the long‐term use of Cu in vineyards has a toxic effect on the soil bacterial community, resulting in an increased tolerance. An effect of increased levels of Cu could not be detected when measuring bacterial community activity, pointing to the increased sensitivity to detect toxicity in field studies using tolerance measurements.
Responses of a Non–N‐Limited Forest Plantation to the Application of Alkaline‐Stabilized Dewatered Dairy Factory Sludge
Authors: Omil Beatriz , Mosquera‐Losada Rosa , Merino Agustín
Published: October 2007

Amendment of forest soils with dewatered dairy factory sludge (DDFS), characterized by low heavy metal contents and high amounts of degradable C, can prevent the depletion of soil nutrients that results from intensive harvesting in forest plantations. However, this practice involves environmental risks when N supplies exceed the demand of plants or when the strong acidity of the soil favors the mobility of trace metals. These aspects were assessed in a young radiata pine plantation growing in a sandy, acidic, and organic N‐rich soil for the 7 yr after application of a DDFS. The supply of limiting nutrients (mainly P, Mg, and Ca) provided by application of the DDFS, along with control of the ground vegetation, improved the nutritional status of the stand and led to increases in timber volume of more than 60 to 100%. Increases in soil inorganic N were observed during the first months after amendment. Data from soil incubation experiments revealed that some of the additional N was immobilized and, to a lesser extent, denitrified due to the readily available organic C content of the DDFS. Leaching and increased plant uptake of N were prevented by a combination of the latter processes and the low rate of nitrification. The strong acidity of the soil enhanced the availability of Mn and Zn to plants, although the maximum concentrations did not reach levels harmful to organisms. We conclude that although application of DDFS has positive effects on tree nutrition and growth and the environmental risks are low, repeated application may favor mobility of N and availability of heavy metals.
The Treatment Performance of Different Subsoils in Ireland Receiving On‐Site Wastewater Effluent
Authors: Gill L. W. , O'Súlleabháin C. , Misstear B. D. R. , Johnston P. J.
Published: October 2007

Current Irish guidelines require a comprehensive site assessment of a percolation area for wastewater disposal before planning permission is granted for dwellings in rural areas. For a site to be deemed suitable, the subsoil must have a percolation value equivalent to a field saturated hydraulic conductivity in the range 0.08 to 4.2 m d−1 using a falling head percolation test. A minimum of 1.2 m of unsaturated subsoil must also exist below the invert of the percolation area receiving effluent from a septic tank (or 0.6 m for secondary treated effluent). During a 2‐yr period, the three‐dimensional performance of four percolation areas treating domestic wastewater was monitored. At each site samples were taken at 0, 10, and 20 m along each of the four percolation trenches at depths of 0.3, 0.6, and 1.0 m below each trench to ascertain the attenuation effects of the unsaturated subsoil. The two sites with septic tanks installed performed at least as well as the other two sites with secondary treatment systems installed and appeared to discharge a better quality effluent in terms of nutrient load. An average of 2.1 and 6.8 g total N d−1 remained after passing through 1‐m depth of subsoil beneath the trenches receiving septic tank effluent compared with 12.7 and 16.7 g total N d−1 on the sites receiving secondary effluent. The research also indicates that the septic tank effluent was of an equivalent quality to the secondary treated effluent in terms of indicator bacteria (E. coli) after percolating through 0.6‐m depth of unsaturated subsoil.
The Leaching Characteristics of Selenium from Coal Fly Ashes
Authors: Wang Tian , Wang Jianmin , Burken Joel G. , Ban Heng , Ladwig Ken
Published: October 2007

The leaching characteristics of selenium from several bituminous and subbituminous coal fly ashes under different pH conditions were investigated using batch methods. Results indicated that pH had a significant effect on selenium leaching from bituminous coal ash. The minimum selenium leaching occurred in the pH range between 3 and 4, while the maximum selenium leaching occurred at pH 12. The release of selenium from subbituminous coal ashes was very low for the entire experimental pH range, possibly due to the high content of calcium which can form hydration or precipitation products as a sink for selenium. The adsorption results for different selenium species indicated that Se(VI) was hardly adsorbable on either bituminous coal ashes or subbituminous coal ashes at any pH. However, Se(IV) was highly adsorbed by bituminous coal ashes under acidic pH conditions and was mostly removed by subbituminous coal ashes across the entire pH range. This result suggests that the majority of selenium released from the tested fly ashes was Se(IV). A speciation‐based model was developed to simulate the adsorption of Se(IV) on bituminous coal fly ash, and the pH‐independent adsorption constants of HSeO3− and SeO32− were determined. The modeling approach is useful for understanding and predicting the release process of selenium from fly ash.
Soil Water Nitrate and Ammonium Dynamics under a Sewage Effluent–Irrigated Eucalypt Plantation
Authors: Livesley S. J. , Adams M. A. , Grierson P. F.
Published: October 2007

Managed forests and plantations are appropriate ecosystems for land‐based treatment of effluent, but concerns remain regarding nutrient contamination of ground‐ and surface waters. Monthly NO3–N and NH4–N concentrations in soil water, accumulated soil N, and gross ammonification and nitrification rates were measured in the second year of a second rotation of an effluent irrigated Eucalyptus globulus plantation in southern Western Australia to investigate the separate and interactive effects of drip and sprinkler irrigation, effluent and water irrigation, irrigation rate, and harvest residues retention. Nitrate concentrations of soil water were greater under effluent irrigation than water irrigation but remained <15 mg L−1 when irrigated at the normal rate (1.5–2.0 mm d−1), and there was little evidence of downward movement. In contrast, NH4–N concentrations of soil water at 30 and 100 cm were generally greater under effluent irrigation than water irrigation when irrigated at the normal rate because of direct effluent NH4–N input and indirect ammonification of soil organic N. Drip irrigation of effluent approximately doubled peak NO3–N and NH4–N concentrations in soil water. Harvest residue retention reduced concentrations of soil water NO3–N at 30 cm during active sprinkler irrigation, but after 1 yr of irrigation there was no significant difference in the amount of N stored in the soil system, although harvest residue retention did enhance the “nitrate flush” in the following spring. Gross mineralization rates without irrigation increased with harvest residue retention and further increased with water irrigation. Irrigation with effluent further increased gross nitrification to 3.1 mg N kg−1 d−1 when harvest residues were retained but had no effect on gross ammonification, which suggested the importance of heterotrophic nitrification. The downward movement of N under effluent irrigation was dominated by NH4–N rather than NO3–N. Improving the capacity of forest soils to store and transform N inputs through organic matter management must consider the dynamic equilibrium between N input, uptake, and immobilization according to soil C status, and the effect changing microbial processes and environmental conditions can have on this equilibrium.
Glucose Control, Self-Care Behaviors, and the Presence of the Chronic Care Model in Primary Care Clinics
Authors: Parchman Michael L. , Pugh Jacqueline A. , Wang Chen-Pin , Romero Raquel L.
Published: October 2007

OBJECTIVE—The purpose of this study was to examine the relationship between A1C and the extent to which care delivered to patients with type 2 diabetes in primary care clinics is consistent with the chronic care model (CCM), after controlling for self-care behaviors.

RESEARCH DESIGN AND METHODS—This was a cross-sectional, observational study of care provided to 618 patients with type 2 diabetes across 20 small, autonomous primary care clinics in South Texas. Subjects completed an exit survey. The medical record was abstracted for A1C values. Clinicians completed the Assessment of Chronic Illness Care (ACIC) survey, a validated measure of the extent to which care delivered is consistent with the CCM.

RESULTS—There was a significant relationship between ACIC score and A1C, but this relationship varied according to self-care behavior for exercise and was strongest for those who did not adhere to exercise recommendations: for every 1-point increase in ACIC score, A1C was 0.144% lower (P < 0.001). The relationship between ACIC score and A1C for those who adhered to their diet was similar to that for those who did not, after adjusting for exercise, but the overall level of control was better for those who adhered to their diet.

CONCLUSIONS—Characteristics of the primary care clinic where one receives care are an important predictor of glucose control. If resources for implementing the CCM are limited, one might want to focus on clinics with low ACIC scores that serve a population of patients who are sedentary because this population may be likely to realize the most benefit from improved glucose control.
Exploring the Substitution of Exenatide for Insulin in Patients With Type 2 Diabetes Treated With Insulin in Combination With Oral Antidiabetes Agents
Authors: Davis Stephen N. , Johns Don , Maggs David , Xu Hangtao , Northrup Justin H. , Brodows Robert G.
Published: October 2007

OBJECTIVE— This 16-week study explored the safety of substituting exenatide for insulin in patients with type 2 diabetes using insulin in combination with oral antidiabetes agents.

RESEARCH DESIGN AND METHODS— Successful maintenance of glycemic control was predefined as an A1C increase of <0.5%. A total of 49 patients (aged 53 ± 8 years, with BMI 34 ± 4 kg/m2, A1C 8.1 ± 1.1%, and duration of diabetes 11 ± 7 years) were randomized to either substitute exenatide for insulin or remain on their current insulin regimen. Patients who either completed ≥8 weeks of study or discontinued because of loss of glycemic control were included in primary efficacy analysis.

RESULTS— A total of 62% (18 of 29) of the exenatide-treated patients maintained glycemic control compared with 81% (13 of 16) of the insulin-treated patients. Of the 11 exenatide-treated patients who did not maintain control, 5 discontinued before week 16 because of loss of glucose control. The overall safety profile was generally consistent with previous exenatide trials. The mean overall hypoglycemia rates were 1.72 and 0.97 events/patient-year for the exenatide and insulin reference groups, respectively.

CONCLUSIONS— This pilot study suggests that it is feasible to sustain glycemic control when substituting exenatide for insulin. Although it is not possible to characterize clear predictors of outcome given the size and exploratory nature of the study, the data suggest that patients with longer disease duration, who are taking higher doses of insulin and have less endogenous β-cell function, may experience deterioration in glucose control if exenatide is substituted for insulin therapy.
Dietary Cod Protein Improves Insulin Sensitivity in Insulin-Resistant Men and Women
Authors: Ouellet Véronique , Marois Julie , Weisnagel S. John , Jacques Hélène
Published: October 2007

OBJECTIVE—The purpose of this article was to compare the effects of cod protein to those of other animal proteins on insulin sensitivity in insulin-resistant human subjects.

RESEARCH DESIGN AND METHODS—Insulin sensitivity (M/I) was assessed using a hyperinsulinemic-euglycemic clamp in 19 insulin-resistant subjects fed a cod protein diet and a similar diet containing lean beef, pork, veal, eggs, milk, and milk products (BPVEM) for 4 weeks in a crossover design study. Both diets were formulated to differ only in protein source, thus providing equivalent amounts of dietary fibers and monounsaturated, polyunsaturated (including n-3), and saturated fatty acids (1.1:1.8:1.0). β-Cell function, estimated by oral glucose tolerance test–derived parameters, was also assessed.

RESULTS—There was a significant improvement in insulin sensitivity (P = 0.027) and a strong tendency for a better disposition index (β-cell function × M/I) (P = 0.055) in subjects consuming the cod protein diet compared with those consuming the BPVEM diet. When median baseline M/I (4.8 × 10−3 mg · kg−1 · min−1 · pmol−1) was taken into account, an interaction on the 30-min C-peptide–to–30-min glucose ratio, used as an index of β-cell function, was observed between diet and M/I status (P = 0.022). Indeed, this ratio strongly tended to increase in subjects with low M/I consuming the cod protein diet compared with those consuming the BPVEM diet (P = 0.065).

CONCLUSIONS—Dietary cod protein improves insulin sensitivity in insulin-resistant individuals and thus could contribute to prevention of type 2 diabetes by reducing the metabolic complications related to insulin resistance.
Pancreatic Fat Content and β-Cell Function in Men With and Without Type 2 Diabetes
Authors: Tushuizen Maarten E. , Bunck Mathijs C. , Pouwels Petra J. , Bontemps Saskia , van Waesberghe Jan Hein T. , Schindhelm Roger K. , Mari Andrea , Heine Robert J. , Diamant Michaela
Published: October 2007

OBJECTIVE—Insulin resistance, associated with increased lipolysis, results in a high exposure of nonadipose tissue to lipids. Experimental data indicate that fatty infiltration of pancreatic islets may also contribute to β-cell dysfunction, but whether this occurs in humans in vivo is unknown.

RESEARCH DESIGN AND METHODS—Using proton magnetic resonance spectroscopy and oral glucose tolerance tests, we studied the association of pancreatic lipid accumulation in vivo and various aspects of β-cell function in 12 insulin-naive type 2 diabetic and 24 age- and BMI-matched nondiabetic men.

RESULTS—Patients versus control subjects had higher A1C, fasting plasma glucose, and insulin and triglyceride levels and lower HDL cholesterol, but similar waist circumference. Median (interquartile range) pancreatic fat content in patients and control subjects was 20.4% (13.4–43.6) and 9.7% (7.0–20.2), respectively (P = 0.032). Pancreatic fat correlated negatively with β-cell function parameters, including the insulinogenic index adjusted for insulin resistance, early glucose-stimulated insulin secretion, β-cell glucose sensitivity, and rate sensitivity (all P < 0.05), but not potentiation. However, these associations were significantly affected by the diabetic state, such that a significant association of pancreatic fat with β-cell dysfunction was only present in the nondiabetic group (all P < 0.01), suggesting that once diabetes occurs, factors additional to pancreatic fat account for further β-cell function decline. In control subjects, the association of pancreatic fat and β-cell function remained significant after correction for BMI, fasting plasma glucose, and triglycerides (P = 0.006).

CONCLUSIONS—These findings indicate that pancreatic lipid content may contribute to β-cell dysfunction and possibly to the subsequent development of type 2 diabetes in susceptible humans.
Long-Term Predictors of Insulin Resistance
Authors: Risérus Ulf , Ärnlöv Johan , Berglund Lars
Published: October 2007

OBJECTIVE—Predictors of insulin resistance have hitherto only been examined in cross-sectional studies without information on lifestyle factors. Few researchers have measured insulin sensitivity directly and compared different metabolic and lifestyle predictors in a large population.

RESEARCH DESIGN AND METHODS—Our aim was to investigate independent long-term predictors of insulin sensitivity in a large population-based sample (the Uppsala Longitudinal Study of Adult Men cohort) of 50-year-old men who underwent a euglycemic clamp 20 years later (n = 770). Subjects with diabetes and treatment of cardiovascular disease at baseline were excluded. In linear regression models, metabolic (BMI, triglycerides, HDL cholesterol, glucose, and blood pressure) and lifestyle factors (physical activity, smoking, saturated fat biomarkers, and socioeconomic status) were independent variables at baseline (age 50 years) and insulin sensitivity–dependent variables at follow-up (age 70 years). A subsample of only normal-weight men from the initial population was also examined (n = 440).

RESULTS—BMI was the strongest predictor of insulin sensitivity even after addition of metabolic factors. One SD (±2.8) increase in BMI corresponded to a mean 19% decrease in insulin sensitivity. After addition of lifestyle factors, all factors except triglycerides and smoking were significant predictors. BMI remained the strongest predictor (β = −0.67 [95% CI −0.83 to −0.51], P < 0.0001) followed by physical activity, HDL cholesterol, saturated fat, and socioeconomic status (all P < 0.05). BMI remained the strongest predictor in normal-weight subjects also (P < 0.001). In addition, after adjustment for baseline insulin concentrations, BMI remained the strongest predictor (P < 0.001).

CONCLUSIONS—Multiple factors, including novel factors such as saturated fat and socioeconomic status, independently predict insulin sensitivity after 20 years. BMI is, however, the single strongest predictor, even in normal-weight subjects.
The Effect of Glucosamine on Serum HDL Cholesterol and Apolipoprotein AI Levels in People With Diabetes
Authors: Albert Stewart G. , Fishman Oiknine Rachel , Parseghian Shant , Mooradian Arshag D. , Haas Michael J. , McPherson Timothy
Published: October 2007

OBJECTIVE—Dietary and nutritional supplements are modulators of HDL cholesterol levels and production of apolipoprotein (apo) AI. Previously, in vitro treatment of hepatocyte cell lines with glucosamine increased apoAI production by stabilization of apoAI mRNA. The hypothesis is that the neutraceutical glucosamine, when given in conventional doses (1,500 mg/day) may increase apoAI and HDL cholesterol levels in subjects with diabetes and low HDL cholesterol.

RESEARCH DESIGN AND METHODS—Twelve subjects (three men and nine women) with type 1 (n = 2) and type 2 (n = 10) diabetes, aged 55 ± 12 years (mean ± SD), who had low HDL cholesterol (1.03 ± 0.20 mmol/l), were randomly assigned to a double-blind, placebo-controlled, cross-over trial of 500 mg glucosamine or placebo orally three times daily for 2 weeks, followed by a 4-week washout phase and a 2-week cross-over to the alternate therapy.

RESULTS—Fasting serum glucose, fructosamine, and total cholesterol remained stable during the drug and placebo phases. Glucosamine had no significant effect after therapy on serum levels of HDL cholesterol (from baseline of 1.02 ± 0.15 to 1.05 ± 0.16 mmol/l compared with placebo from 1.04 ± 0.21 to 1.06 ± 0.16 mmol/l) nor in changes in apoAI levels (from baseline of 147 ± 15 to 140 ± 126 mg/dl with glucosamine and from 146 ± 25 to 142 ± 17 mg/dl with placebo).

CONCLUSIONS—These observations suggest that glucosamine at commonly consumed doses does not have significant effects on glycemic control, lipid profile, or levels of apoAI in diabetic subjects after 2 weeks of supplementation.
Comparison of Accuracy Measures of Two Screening Tests for Gestational Diabetes Mellitus
Authors: van Leeuwen Marsha , Zweers Egbert J.K. , Opmeer Brent C. , van Ballegooie Evert , ter Brugge Henk G. , de Valk Harold W. , Mol Ben W.J. , Visser Gerard H.A.
Published: October 2007

OBJECTIVE— To compare the accuracy measures of the random glucose test and the 50-g glucose challenge test as screening tests for gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS— In this prospective cohort study, pregnant women without preexisting diabetes in two perinatal centers in the Netherlands underwent a random glucose test and a 50-g glucose challenge test between 24 and 28 weeks of gestation. If one of the screening tests exceeded predefined threshold values, the 75-g oral glucose tolerance test (OGTT) was performed within 1 week. Furthermore, the OGTT was performed in a random sample of women in whom both screening tests were normal. GDM was considered present when the OGTT (reference test) exceeded predefined threshold values. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the two screening tests. The results were corrected for verification bias.

RESULTS— We included 1,301 women. The OGTT was performed in 322 women. After correction for verification bias, the random glucose test showed an area under the ROC curve of 0.69 (95% CI 0.61–0.78), whereas the glucose challenge test had an area under the curve of 0.88 (0.83–0.93). There was a significant difference in area under the curve of the two tests of 0.19 (0.11–0.27) in favor of the 50-g glucose challenge test.

CONCLUSIONS— In screening for GDM, the 50-g glucose challenge test is more useful than the random glucose test.
White Blood Cells Telomere Length Is Shorter in Males With Type 2 Diabetes and Microalbuminuria
Authors: Tentolouris Nicholas , Nzietchueng Rosine , Cattan Valerie , Poitevin Gaël , Lacolley Patrick , Papazafiropoulou Athanasia , Perrea Despoina , Katsilambros Nicholas , Benetos Athanase
Published: October 2007

OBJECTIVE—To examine differences in telomere (terminal restriction fragment [TRF]) length and pulse wave velocity (PWV)—an index of arterial stiffness—in patients with type 2 diabetes with and without microalbuminuria (MA).

RESEARCH DESIGN AND METHODS—A total of 84 men with type 2 diabetes, 40 with MA and 44 without MA (aged 63.5 ± 9.0 vs. 61.2 ± 9.8 years), were studied. TRF length was determined in white blood cells. MA was defined as albumin excretion rate (AER) in the range of 30–300 mg/24 h in at least two of three 24-h urine collections. PWV was assessed using applanation tonometry. Markers of oxidative stress were also measured.

RESULTS—TRF length was shorter in patients with MA than in those without MA (6.64 ± 0.74 vs. 7.23 ± 1.01 kb, respectively, P = 0.004). PWV was significantly higher in the patients with MA. Multivariate linear regression analysis in the total sample demonstrated an independent association between TRF length and age (P = 0.02), MA status (P = 0.04) or AER (P = 0.002), and plasma nitrotyrosine levels (P = 0.02). AER was associated significantly with PWV (P < 0.01).

CONCLUSIONS—Subjects with type 2 diabetes and MA have shorter TRF length and increased arterial stiffness than those without MA. Additionally, TRF length is associated with age, AER, and nitrosative stress. As shorter TRF length indicates older biological age, the increased arterial stiffness in patients with type 2 diabetes who have MA may be due to the more pronounced “aging ” of these subjects.