bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic analysis ofTrichoderma atroviridemycelia stressed by organophosphate pesticide dichlorvos
Authors: Tang Jun , Liu Lixing , Huang Xiuli , Li Yingying , Chen Yunpeng , Chen Jie
Published: March 2010

The proteomic approach is a powerful tool to study microbial response to environmental stress. To evaluate the responses of Trichoderma spp. to the organophosphate pesticide dichlorvos, mycelia of Trichoderma atroviride T23 were exposed to dichlorvos at concentrations of 0, 100, 300, 500, and 1000 µg/mL, respectively. Changes in protein expression were investigated using two-dimensional sodium dodecyl sulfate – polyacrylamide gel electrophoresis. Sixteen protein spots were differentially expressed. They were identified by MALDI–TOF/TOF MS and were found to be linked to energy metabolism, transport, signal transduction, and stress tolerance. Among stress-related proteins, glutathione peroxidase-like protein (GPX), 1,4-benzoquinone reductase, and HEX1 were upregulated by and cyclophilin A induced by 1000 µg/mL dichlorvos when compared with the control. These proteins were considered to be associated with fungal adaptation to adverse conditions. The results will help us to understand molecular mechanisms through which Trichoderma responds to organophosphate pesticides.
The effects of glyphosate on the in vitro linear growth of selected microfungi from a boreal forest soil
Authors: Tanney Joey B. , Hutchison Leonard J.
Published: March 2010

Glyphosate-based herbicides are used extensively in forestry and agriculture to control broadleaf plant competition. A review of the literature offers conflicting results regarding the impact of glyphosate on fungal growth. This study investigated the effects of 7 glyphosate concentrations (1, 2, 5, 10, 50, 100, and 1000 µg·mL–1) of Roundup (35.6% glyphosate) on the number of colony-forming units (CFUs) of soilborne microfungi from a boreal forest soil sample and on the in vitro linear growth of 20 selected species of microfungi representative of this boreal forest soil. Concentrations of glyphosate at 50 µg·mL–1and higher significantly decreased the number of CFUs observed. At glyphosate concentrations equal to 5 µg·mL–1, 13 fungal species exhibited colony diameters less than 50% than that of their respective controls. Several species showed an inhibition of pigmentation and sporulation when subjected to glyphosate concentrations of 1 µg·mL–1. Differential sensitivity was observed among species at the various concentrations, suggesting the possibility of a shift towards tolerant species of fungi when they are exposed to glyphosate.
Mode of action of thuricin S, a new class IId bacteriocin fromBacillus thuringiensis
Authors: Chehimi Sonia , Pons Anne-Marie , Sablé Sophie , Hajlaoui Mohamed-Rabeh , Limam Férid
Published: March 2010

Different methods were used to elucidate the mode of action of thuricin S, a new class IId bacteriocin produced by Bacillus thuringiensis subsp. entomocidus HD198. According to cell viability tests, thuricin S was shown to exert a bactericidal effect on the sensitive cells of Bacillus thuringiensis subsp. darmastadiensis 10T. The use of the fluorescent probe 3,3′-dipropylthiadicarbocyanine iodide as an indicator proved that thuricin S interacts with the cytoplasmic membrane to dissipate the transmembrane potential. It was also demonstrated that thuricin S acts as a pore-forming bacteriocin, since it allows the nonpermeable stain propidium iodide to enter the cells. The loss of membrane integrity and the morphological changes in sensitive cells were visualized by scanning electron microscopy.
Central NO–cGMP pathway in thermoregulation and survival rate during polymicrobial sepsis
Authors: Oliveira-Pelegrin G.R. , Branco L.G.S. , Rocha M.J.A.
Published: March 2010

Sepsis induces production of inflammatory mediators such as nitric oxide (NO) and causes physiological alterations, including changes in body temperature (Tb). We evaluated the involvement of the central NO–cGMP pathway in thermoregulation during sepsis induced by cecal ligation and puncture (CLP), and analyzed its effect on survival rate. Male Wistar rats with a Tb probe inserted in their abdomen were intracerebroventricularly injected with 1 µL NG-nitro-l-arginine methyl ester (l-NAME, 250 µg), a nonselective NO synthase (NOS) inhibitor; or aminoguanidine (250 µg), an inducible NOS inhibitor; or 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 0.25 µg), a guanylate cyclase inhibitor. Thirty minutes after injection, sepsis was induced by cecal ligation and puncture (CLP), or the rats were sham operated. The animals were divided into 2 groups for determination of Tb for 24 h and assessment of survival during 3 days. The drop in Tb seen in the CLP group was attenuated by pretreatment with the NOS inhibitors (p < 0.05) and blocked with ODQ. CLP rats pretreated with either of the inhibitors showed higher survival rates than vehicle injected groups (p < 0.05), and were even higher in the ODQ pretreated group. Our results showed that the effect of NOS inhibition on the hypothermic response to CLP is consistent with the role of nitrergic pathways in thermoregulation.
Seasonal patterns and influence of temperature on the daily activity of the diurnal neotropical rodent Necromys lasiurus
Authors: Vieira E. M. , Baumgarten L. C. , Paise G. , Becker R. G.
Published: March 2010

We investigated the relation between temperature and diel activity patterns of Necromys lasiurus (Lund, 1841) in 10 sites of open vegetation (grassland fields) in the Cerrado (savanna-like vegetation) of central Brazil. We used live traps equipped with timing devices during two trapping sessions: in the end of the dry season (session 1, October 2001) and in the wet season (session 2, January–February 2002). Necromys lasiurus is basically a diurnal rodent with more pronounced crepuscular and nocturnal activity in the dry season than in the wet season. Only in the wet season did we detect significant between-gender differences, with males being less active than females in the first hours after sunrise but more active between 0900 and 1200. There was no significant activity–temperature relation in the dry season, but in the wet season, both genders showed a positive relation between ambient temperature and activity. Individuals might be avoiding hot midday hours in the end of the dry season to minimize time exposure to a physiologically stressful condition caused by the joint action of high temperatures and extremely low relative humidity (<15%). In the rainy season, the high relative humidity (80%–90%) might allow the animals to show a positive relation between activity and ambient temperature.
What Have We Learned About Interventions to Reduce Medical Errors?
Authors: Woodward Helen I. , Mytton Oliver T. , Lemer Claire , Yardley Iain E. , Ellis Benjamin M. , Rutter Paul D. , Greaves Felix E.C. , Noble Douglas J. , Kelley Edward , Wu Albert W.
Published: March 2010

Medical errors and adverse events are now recognized as major threats to both individual and public health worldwide. This review provides a broad perspective on major effective, established, or promising strategies to reduce medical errors and harm. Initiatives to improve safety can be conceptualized as a “safety onion” with layers of protection, depending on their degree of remove from the patient. Interventions discussed include those applied at the levels of the patient (patient engagement and disclosure), the caregiver (education, teamwork, and checklists), the local workplace (culture and workplace changes), and the system (information technology and incident reporting systems). Promising interventions include forcing functions, computerized prescriber order entry with decision support, checklists, standardized handoffs and simulation training. Many of the interventions described still lack strong evidence of benefit, but this should not hold back implementation. Rather, it should spur innovation accompanied by evaluation and publication to share the results.
The Role of Behavioral Science Theory in Development and Implementation of Public Health Interventions
Authors: Glanz Karen , Bishop Donald B.
Published: March 2010

Increasing evidence suggests that public health and health-promotion interventions that are based on social and behavioral science theories are more effective than those lacking a theoretical base. This article provides an overview of the state of the science of theory use for designing and conducting health-promotion interventions. Influential contemporary perspectives stress the multiple determinants and multiple levels of determinants of health and health behavior. We describe key types of theory and selected often-used theories and their key concepts, including the health belief model, the transtheoretical model, social cognitive theory, and the ecological model. This summary is followed by a review of the evidence about patterns and effects of theory use in health behavior intervention research. Examples of applied theories in three large public health programs illustrate the feasibility, utility, and challenges of using theory-based interventions. This review concludes by identifying cross-cutting themes and important future directions for bridging the divides between theory, practice, and research.
Mold Exposure and Health Effects Following Hurricanes Katrina and Rita
Authors: Barbeau Deborah N. , Grimsley L. Faye , White LuAnn E. , El-Dahr Jane M. , Lichtveld Maureen
Published: March 2010

The extensive flooding in the aftermath of Hurricanes Katrina and Rita created conditions ideal for indoor mold growth, raising concerns about the possible adverse health effects associated with indoor mold exposure. Studies evaluating the levels of indoor and outdoor molds in the months following the hurricanes found high levels of mold growth. Homes with greater flood damage, especially those with >3 feet of indoor flooding, demonstrated higher levels of mold growth compared with homes with little or no flooding. Water intrusion due to roof damage was also associated with mold growth. However, no increase in the occurrence of adverse health outcomes has been observed in published reports to date. This article considers reasons why studies of mold exposure after the hurricane do not show a greater health impact.
Health in All Policies—The Finnish Initiative: Background, Principles, and Current Issues
Authors: Puska Pekka , Ståhl Timo
Published: March 2010

Many historical developments, such as the Alma Ata Declaration or the Ottawa Charter, have drawn attention to the need for intersectoral work and for considering the health aspects of different policy proposals. In the 1970s, Finland started broad actions to change national diets to reduce the high mortality associated with cardiovascular diseases (CVDs). This and other work in Finland have involved many sectors and policies, resulted in significant public health improvements, and paved the way for the Health in All Policies (HiAP) initiative started during the Finnish European Union (EU) presidency in 2006. The initiative and the principles have encouraged further developments in Finland and have been linked with related developments within the EU and the World Health Organization (WHO).
Plastics and Health Risks
Authors: Halden Rolf U.
Published: March 2010

By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from plastics are a boon to public health (e.g., disposable syringes, intravenous bags). However, plastics also pose health risks. Of principal concern are endocrine-disrupting properties, as triggered for example by bisphenol A and di-(2-ethylhexyl) phthalate (DEHP). Opinions on the safety of plastics vary widely, and despite more than five decades of research, scientific consensus on product safety is still elusive. This literature review summarizes information from more than 120 peer-reviewed publications on health effects of plastics and plasticizers in lab animals and humans. It examines problematic exposures of susceptible populations and also briefly summarizes adverse environmental impacts from plastic pollution. Ongoing efforts to steer human society toward resource conservation and sustainable consumption are discussed, including the concept of the 5 Rs—i.e., reduce, reuse, recycle, rethink, restrain—for minimizing pre- and postnatal exposures to potentially harmful components of plastics.
Prevention Trials: Their Place in How We Understand the Value of Prevention Strategies
Authors: Colditz Graham A. , Taylor Philip R.
Published: March 2010

Several key factors bear on the interpretation of prevention trials and observational studies that inform prevention strategies. These factors include the underlying disease process and aspects of the intervention: sustainability of behavior change, the time course of the intervention within the disease process, dose and duration of exposure needed to effect risk reduction, durability of the impact of intervention, and methodological problems in implementing and interpreting randomized trials and observational studies to evaluate prevention strategies. The question asked through an intent-to-treat analysis of a randomized controlled trial (RCT) differs from that in the observational setting. Furthermore, the long duration necessary to conduct prevention trials and the resulting lack of adherence to therapy can bias results toward the null. A broader range of approaches to evaluate prevention interventions and programs with improved knowledge synthesis and translation to public health practice will speed our progress toward achieving public health and prevention of chronic diseases.
Teen Fertility in Transition: Recent and Historic Trends in the United States
Authors: Santelli John S. , Melnikas Andrea J.
Published: March 2010

After considerable declines in teen birth and pregnancy rates between 1991 and 2005, teen birth rates rose unexpectedly in 2006 and 2007. To understand these recent trends, we examined historical changes in fertility, trends in sexual behaviors, social forces, and public policies that may influence teen fertility. Although social forces such as poverty are critical in shaping adolescent reproductive choices, these do not explain rapid change in teen pregnancy risk since 1991. These recent changes, including increases in teen births since 2005, follow closely changes in teen contraceptive use. Likewise, contraceptive use is critical in explaining differences between U.S. and European fertility patterns. Public policies related to HIV prevention and sexuality education may have played a critical role in influencing teen pregnancy risk.
Modalities for Imaging of Prostate Cancer
Authors: Hou A. H. , Swanson D. , Barqawi A. B.
Published: March 2010

Prostate cancer is the second most common cause of cancer deaths among males in the United States. Prostate screening by digital rectal examination and prostate-specific antigen has shifted the diagnosis of prostate cancer to lower grade, organ confined disease, adding to overdetection and overtreatment of prostate cancer. The new challenge is in differentiating clinically relevant tumors from ones that may otherwise never have become evident if not for screening. The rapid evolution of imaging modalities and the synthesis of anatomic, functional, and molecular data allow for improved detection and characterization of prostate cancer. However, the appropriate use of imaging is difficult to define, as many controversial studies regarding each of the modalities and their utilities can be found in the literature. Clinical practice patterns have been slow to adopt many of these advances as a result. This review discusses the more established imaging techniques, including Ultrasonography, Magnetic Resonance Imaging, MR Spectroscopy, Computed Tomography, and Positron Emission Tomography. We also review several promising techniques on the horizon, including Dynamic Contrast-Enhanced MRI, Diffuse-Weighted Imaging, Superparamagnetic Nanoparticles, and Radionuclide Scintigraphy.
Mesoscopic Modeling of Multiphysicochemical Transport Phenomena in Porous Media
Authors: Kang Qinjun , Wang Moran , Mukherjee Partha P. , Lichtner Peter C.
Published: March 2010

We present our recent progress on mesoscopic modeling of multiphysicochemical transport phenomena in porous media based on the lattice Boltzmann method. Simulation examples include injection of CO2-saturated brine into a limestone rock, two-phase behavior and flooding phenomena in polymer electrolyte fuel cells, and electroosmosis in homogeneously charged porous media. It is shown that the lattice Boltzmann method can account for multiple, coupled physicochemical processes in these systems and can shed some light on the underlying physics occurring at the fundamental scale. Therefore, it can be a potential powerful numerical tool to analyze multiphysicochemical processes in various energy, earth, and environmental systems.
The Role of Cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies
Authors: Sobolewski Cyril , Cerella Claudia , Dicato Mario , Ghibelli Lina , Diederich Marc
Published: March 2010

It is well admitted that the link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways, which act during the different steps of tumorigenesis. The cyclooxygenases (COXs) are a family of enzymes, which catalyze the rate-limiting step of prostaglandin biosynthesis. This family contains three members: ubiquitously expressed COX-1, which is involved in homeostasis; the inducible COX-2 isoform, which is upregulated during both inflammation and cancer; and COX-3, expressed in brain and spinal cord, whose functions remain to be elucidated. COX-2 was described to modulate cell proliferation and apoptosis mainly in solid tumors, that is, colorectal, breast, and prostate cancers, and, more recently, in hematological malignancies. These findings prompt us to analyze here the effects of a combination of COX-2 inhibitors together with different clinically used therapeutic strategies in order to further improve the efficiency of future anticancer treatments. COX-2 modulation is a promising field investigated by many research groups.
Differential Roles for Octanoylated and Decanoylated Ghrelins in Regulating Appetite and Metabolism
Authors: Schwandt Sara E. , Peddu Sarath C. , Riley Larry G.
Published: March 2010

Since its identification in 1999, ghrelin has been identified in all vertebrate groups. The “active core” of ghrelin is highly conserved among vertebrates, suggesting its biological activity to be also conserved. In fish, both acylated forms of ghrelin have been identified; however, the ratio of the ghrelin-C8 to ghrelin-C10 is not as great as observed in mammals. In the tilapia (Oreochromis mossambicus), ghrelin-C10 is the major form of ghrelin. Since fish are known to inhabit every ecological niche on earth, studies on fish have provided valuable insight into vertebrate physiology in general; it is likely that understanding the role of both acylated forms of ghrelin, in more detail, in fish will result into novel insights in the biology of ghrelin within vertebrates. In this paper we discuss ghrelin's role in regulating appetite and metabolism in fish, in general, and provide evidence that the two tilapia ghrelins exhibit different biological roles.
ZnO-Nanorod Dye-Sensitized Solar Cells: New Structure without a Transparent Conducting Oxide Layer
Authors: Lai Ming-Hong , Tubtimtae Auttasit , Lee Ming-Way , Wang Gou-Jen
Published: March 2010

Conventional nanorod-based dye-sensitized solar cells (DSSCs) are fabricated by growing nanorods on top of a transparent conducting oxide (TCO, typically fluorine-doped tin oxide—FTO). The heterogeneous interface between the nanorod and TCO forms a source for carrier scattering. This work reports on a new DSSC architecture without a TCO layer. The TCO-less structure consists of ZnO nanorods grown on top of a ZnO film. The ZnO film replaced FTO as the TCO layer and the ZnO nanorods served as the photoanode. The ZnO nanorod/film structure was grown by two methods: (1) one-step chemical vapor deposition (CVD) (2) two-step chemical bath deposition (CBD). The thicknesses of the nanorods/film grown by CVD is more uniform than that by CBD. We demonstrate that the TCO-less DSSC structure can operate properly as solar cells. The new DSSCs yield the best short-current density of 3.96 mA/ and a power conversion efficiency of 0.73% under 85 mW/ of simulated solar illumination. The open-circuit voltage of 0.80 V is markedly higher than that from conventional ZnO DSSCs.
Nanoprodrugs of NSAIDs Inhibit the Growth of U87‐MG Glioma Cells
Authors: Lee Bong-Seop , Yuan Xiangpeng , Xu Qijin , Ko Minhee K. , Nalla Aruna K. , Frankiel Ilana , Shear Talia , Black Keith L. , Yu John S.
Published: March 2010

Several recent reports have demonstrated that nonsteroidal anti‐inflammatory drugs (NSAIDs) inhibit the growth of various malignant cells suggesting their application as anticancer agents. In this study, we prepared six nanometer‐sized prodrugs (nanoprodrugs) of NSAIDs, ibuprofen, indomethacin, and naproxen through the spontaneous emulsification mechanism using monomeric and dimeric derivatives of the NSAIDs. We evaluated their effect on the proliferation of U87‐MG glioma cells by cell counting, WST‐1 cell proliferation reagent, and propidium iodide incorporation. The two ibuprofen nanoprodrugs inhibited the cell growth more potently than the indomethacin nanoprodrugs, whereas the naproxen nanoprodrugs did not show any significant effect. Remarkably, ibuprofen did not show any effect at an equimolar concentration. Approximately, 4.4% of the ibuprofen nanoprodrugs was found in the cell, whereas no ibuprofen could be detected suggesting that the superior effect of the nanoprodrugs can be attributed to the efficient cellular uptake of the nanoprodrugs.
On Differential Subordinations of Multivalent Functions Involving a Certain Fractional Derivative Operator
Authors: Choi Jae Ho
Published: March 2010

We investigate several results concerning the differential subordination of analytic and multivalent functions which is defined by using a certain fractional derivative operator. Some special cases are also considered.
Peptide Vaccination Breaks Tolerance to HER-2/neuby Generating Vaccine-Specific FasL+ CD4+ T Cells: First Evidence for Intratumor Apoptotic Regulatory T Cells
Authors: Gritzapis Angelos D. , Voutsas Ioannis F. , Lekka Eftychia , Papamichail Michael , Baxevanis Constantin N.
Published: March 2010

BALB/c mice transgenic (Tg) for the transforming rat neu oncogene (BALB-neuT) are genetically predestined to develop mammary carcinogenesis in a process similar to that in humans. We crossed HLA-A2.1/HLA-DR1 (A2.1/DR1) Tg mice with BALB-neuT mice to generate A2.1/DR1 × BALB-neuT triple Tg (A2.1/DR1 × neuT+) mice, which represent an improvement over BALB-neuT mice for evaluating vaccination regimens to overcome tolerance against HER-2/neu. A vaccine formulation strategy, consisting of synthetic peptides from the rat HER-2/neu oncogene combined with granulocyte macrophage colony-stimulating factor, was highly effective in preventing the growth of established transplantable tumors in male A2.1/DR1 × neuT+ mice. Vaccination with HER-2(435–443) (p435) CTL peptide alone induced weak antitumor responses, which were characterized by increased numbers of regulatory T cells (Treg) and low numbers of vaccine-specific CD8+ CTL and helper T cells (Th). The administration of p435 plus HER-2(776–790) (p776; helper peptide) reversed this situation, inducing functionally active, peptide-specific CTL and Th. There was a striking change in the intratumoral balance of Tregs (decrease) and vaccine-specific Th (increase) that directly correlated with tumor rejection. Intratumoral administration of anti-FasL antibody promoted tumor growth. The decrease in Tregs (Fas+) was due to apoptosis induced by cell contact with Fas ligand+ (L)+ Th. Mice vaccinated with p435 plus p776 exhibited long-lasting antitumor immunity. Our vaccine regimen also significantly delayed the outgrowth of mammary carcinomas in female A2.1/DR1 × neuT+ animals. We provide a mechanism to overcome tolerance against HER-2/neu, which proposes a combined vaccination with two (Th and CTL) HER-2 peptides against HER-2/neu–expressing tumors. Cancer Res; 70(7); 2686–96
Tumor Stroma–Derived Wnt5a Induces Differentiation of Basal Cell Carcinoma of Ptch-Mutant Mice via CaMKII
Authors: Nitzki Frauke , Zibat Arne , König Simone , Wijgerde Mark , Rosenberger Albert , Brembeck Felix H. , Carstens Per-Ole , Frommhold Anke , Uhmann Anja , Klingler Stefan , Reifenberger Julia , Pukrop Tobias , Aberger Fritz , Schulz-Schaeffer Walter , Hahn Heidi
Published: March 2010

Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other tumors, if translated into tumor therapies. We show that BCCs induced in conditional Ptchflox/floxERT2+/− knockout mice regress with time and show a more differentiated phenotype. Differentiation is accompanied by Wnt5a expression in the tumor stroma, which is first detectable at the fully developed tumor stage. Coculture experiments revealed that Wnt5a is upregulated in tumor-adjacent macrophages by soluble signals derived from BCC cells. In turn, Wnt5a induces the expression of the differentiation marker K10 in tumor cells, which is mediated by Wnt/Ca2+ signaling in a CaMKII-dependent manner. These data support a role of stromal Wnt5a in BCC differentiation and regression, which may have important implications for development of new treatment strategies for this tumor. Taken together, our results establish BCC as an easily accessible model of tumor regression. The regression of BCC despite sustained Hedgehog signaling activity seems to be mediated by tumor-stromal interactions via Wnt5a signaling. Cancer Res; 70(7); 2739–48
Tumor-Suppressive Functions of Leucine Zipper Transcription Factor–Like 1
Authors: Wei Qun , Zhou Wen , Wang Weining , Gao Boning , Wang Linbo , Cao Jiang , Liu Zhi-Ping
Published: March 2010

Human leucine zipper transcription factor–like 1 (LZTFL1) is a novel gene with unknown biological functions. It is located in the chromosome region 3p21.3, a hotspot for tumor suppressor genes. To understand the biological functions of LZTFL1, we surveyed the expression level of LZTFL1 in tumor and normal samples in tissue microarrays and a clinical archive of 84 gastric cancer specimens using immunohistochemistry. We found that LZTFL1 is expressed highly in the epithelial cells of normal tissues and is significantly downregulated in the corresponding tumor samples. The expression level of LZTFL1 correlated significantly with the survival outcomes of the patients and had significant inverse correlation with tumor metastasis. Overexpression of LZTFL1 in tumor cells inhibited anchorage-independent cell growth and cell migration in vitro and repressed tumor growth in vivo. Furthermore, we show that LZTFL1 expression is upregulated on epithelial cell differentiation and is graded along the crypt-villus axis of the intestine, with weakest expression level in the proliferative zone of the crypt and highest expression level at the apex of the differentiation zone in the villus. Expression of LZTFL1 overlaps with that of E-cadherin at the plasma membrane. Our results indicate that LZTFL1 is a tumor suppressor and that loss of LZTFL1 expression has significant clinical outcomes. LZTFL1 expression may serve as an independent prognostic marker for survival outcome of gastric cancer patients. We propose that LZTFL1 may inhibit tumorigenesis by stabilizing E-cadherin–mediated adherens junction formation and promoting epithelial cell differentiation. Cancer Res; 70(7); 2942–50
Imaging of Human Lymph Nodes Using Optical Coherence Tomography: Potential for Staging Cancer
Authors: McLaughlin Robert A. , Scolaro Loretta , Robbins Peter , Hamza Saud , Saunders Christobel , Sampson David D.
Published: March 2010

Histologic assessment is the gold standard technique for the identification of metastatic involvement of lymph nodes in malignant disease, but can only be performed ex vivo and often results in the unnecessary excision of healthy lymph nodes, leading to complications such as lymphedema. Optical coherence tomography (OCT) is a high-resolution, near-IR imaging modality capable of visualizing microscopic features within tissue. OCT has the potential to provide in vivo assessment of tissue involvement by cancer. In this morphologic study, we show the capability of OCT to image nodal microarchitecture through an assessment of fresh, unstained ex vivo lymph node samples. Examples include both benign human axillary lymph nodes and nodes containing metastatic breast carcinoma. Through accurate correlation with the histologic gold standard, OCT is shown to enable differentiation of lymph node tissue from surrounding adipose tissue, reveal nodal structures such as germinal centers and intranodal vessels, and show both diffuse and well circumscribed patterns of metastatic node involvement. Cancer Res; 70(7); 2579–84
Voreloxin, a First-in-Class Anticancer Quinolone Derivative, in Relapsed/Refractory Solid Tumors: A Report on Two Dosing Schedules
Authors: Advani Ranjana H. , Hurwitz Herbert I. , Gordon Michael S. , Ebbinghaus Scot W. , Mendelson David S. , Wakelee Heather A. , Hoch Ute , Silverman Jeffrey A. , Havrilla Nancy A. , Berman Craig J. , Fox Judith A. , Allen Roberta S. , Adelman Daniel C.
Published: March 2010

Purpose: Voreloxin, a novel replication-dependent DNA-damaging agent, intercalates DNA and inhibits topoisomerase II. Voreloxin induces site-selective DNA double-strand breaks and apoptosis. We report the phase 1 experience of voreloxin in patients with relapsed/refractory solid tumors, including dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), pharmacokinetics, and clinical activity.

Experimental Design: Two dose-escalation studies evaluated voreloxin administered i.v. every 3 weeks (SPO-0001) or weekly for 3 weeks every 28 days (SPO-0002). In SPO-0001, patients were classified as heavily pretreated (HP) or minimally pretreated (MP) based on therapeutic history.

Results: In the SPO-0001 study, 41 patients (24 HP/17 MP) were treated in eight dose cohorts (3-75 mg/m2). At 60 mg/m2, four HP patients experienced DLTs: grade 4 neutropenia (n = 3, one with fever) and grade 3 febrile neutropenia/pneumonia (n = 1). At 75 mg/m2, two MP patients experienced DLTs: grade 4 neutropenia/thrombocytopenia (n = 1) or grade 2 oral thrush for >29 days (n = 1). Therefore, the MTD was 48 mg/m2 (HP patients) and 60 mg/m2 (MP patients). In the SPO-0002 study, 21 patients were treated in six dose cohorts (3-24 mg/m2). At 18 mg/m2, two patients experienced DLTs: grade 3 neutropenia, one with pleural effusion (>14 days each). The MTD was 15 mg/m2. Voreloxin exhibited low clearance (2 L/h/m2), a long terminal half-life (22 hours), and dose-proportional exposure. Overall, 31 of 62 patients had stable disease and 1 patient (ovarian cancer) had a partial response per Rustin criteria.

Conclusions: Voreloxin showed an acceptable safety profile with clinical activity in patients with relapsed/refractory solid tumors. The MTD was schedule-dependent. Voreloxin is currently in clinical studies of ovarian cancer and acute myeloid leukemia. Clin Cancer Res; 16(7); 2167–75. ©2010 AACR.
In vitro and In vivo Radiation Sensitization of Human Tumor Cells by a Novel Checkpoint Kinase Inhibitor, AZD7762
Authors: Mitchell James B. , Choudhuri Rajani , Fabre Kristin , Sowers Anastasia L. , Citrin Deborah , Zabludoff Sonya D. , Cook John A.
Published: March 2010

Purpose: Inhibition of checkpoint kinase 1 has been shown to enhance the cytotoxicity of DNA-damaging targeted chemotherapy through cell cycle checkpoint abrogation and impaired DNA damage repair. A novel checkpoint kinase 1/2 inhibitor, AZD7762, was evaluated for potential enhancement of radiosensitivity for human tumor cells in vitro and in vivo xenografts.

Experimental Design: Survival of both p53 wild-type and mutant human cell lines was evaluated by clonogenic assay. Dose modification factors (DMF) were determined from survival curves (ratio of radiation doses for control versus drug treated at 10% survival). Flow cytometry, Western blot, and radiation-induced tumor regrowth delay assays were conducted.

Results: AZD7762 treatment enhanced the radiosensitivity of p53-mutated tumor cell lines (DMFs ranging from 1.6-1.7) to a greater extent than for p53 wild-type tumor lines (DMFs ranging from 1.1-1.2). AZD7762 treatment alone exhibited little cytotoxicity to any of the cell lines and did not enhance the radiosensitivity of normal human fibroblasts (1522). AZD7762 treatment abrogated radiation-induced G2 delay, inhibited radiation damage repair (assessed by γ-H2AX), and suppressed radiation-induced cyclin B expression. HT29 xenografts exposed to five daily radiation fractions and to two daily AZD7762 doses exhibited significant radiation enhancement compared with radiation alone.

Conclusions: AZD7762 effectively enhanced the radiosensitivity of mutated p53 tumor cell lines and HT29 xenografts and was without untoward toxicity when administered alone or in combination with radiation. The results of this study support combining AZD7762 with radiation in clinical trials. Clin Cancer Res; 16(7); 2076–84. ©2010 AACR.
Comparable Sensitivities of Urine Cotinine and Breath Carbon Monoxide at Follow-Up Time Points of Three Months or More in a Smoking Cessation Trial
Authors: Fritz Michael , Wallner Reinhild , Grohs Ursula , Kemmler Georg , Saria Alois , Zernig Gerald
Published: March 2010

To control for likely overreporting of abstinence in clinical trials of smoking cessation aids, field convention demands the corroboration of subjects’ self-reports by a biochemical/pharmacological marker. It is, however, currently debated if urinary cotinine (UC), a metabolite of nicotine, should be preferred because of its higher sensitivity, although sample collection for and analysis of cotinine are much more expensive and work intensive than carbon monoxide (CO) measurements in exhaled air. In the present study, it turned out that UC was of only moderately higher sensitivity than CO (99.4% vs. 96.3%; p = 0.02), the difference being significant only at group sizes of >164. UC identified participants as smokers who escaped CO detection in 4.9% of the cases, whereas CO identified smokers who escaped UC detection in 2.7% of the cases (p = 0.014). Our findings suggest that the costs/disadvantages of using UC instead of CO may outweigh its benefit as a pharmacological marker of (non)smoking status.
Differential DMRT1 Expression in the Gonads of Podarcis sicula (Reptilia: Lacertidae)
Authors: Capriglione T. , Vaccaro M.C. , Morescalchi M.A. , Tammaro S. , De Iorio S.
Published: March 2010

DMRT genes encode a large family of transcription factors which share an unusual cysteine-rich DNA-binding motif, the DM domain. DM family members have been studied in the context of sexual development; in particular, the DMRT1 gene appeared to be the one most directly involved in sex determination, but its activity is largely unexplored and possible downstream targets of this factor have yet to be identified. DMRT1 of the lacertid lizard Podarcis sicula (PsDMRT1) was isolated as a model to study differential gene expression during the seasonal reproductive cycle of an ectothermal species. The adult testis of P. sicula exhibits full activity in spring, complete regression in summer and a slow autumnal recrudescence without spermiation. We cloned a 591-bp partial ORF of the PsDMRT1 fragment, whose putative amino acid sequence contains the conserved DM domain. Northern blot analysis of mRNA from different tissues of P. sicula individuals captured in spring demonstrated DMRT1 transcripts only in testis. Semi-quantitative RT-PCR and in situ hybridization experiments showed peak PsDMRT1 expression in spring, lower expression in autumn and no expression during the period of gonad regression. A possible correlation between androgen level variations and PsDMRT1 transcripts is hypothesized and discussed. Finally, data showed that PsDMRT1 is expressed only in spermatogenic cells, before the second meiotic division, suggesting that its role is confined to the proliferation and maintenance of spermatogonia and spermatocytes.
GJB2 Mutations and Genotype-Phenotype Correlation in 335 Patients from Germany with Nonsyndromic Sensorineural Hearing Loss: Evidence for Additional Recessive Mutations Not Detected by Current Methods
Authors: Bartsch O. , Vatter A. , Zechner U. , Kohlschmidt N. , Wetzig C. , Baumgart A. , Nospes S. , Haaf T. , Keilmann A.
Published: March 2010

We report on 335 patients (319 families) with mild-to-profound nonsyndromic sensorineural hearing loss. We identified 178 mutated GJB2 alleles representing 29 different sequence changes (including 3 novel mutations: Q7P, N14D, H100Q), and 2 alleles with the deletion del(GJB6-D13S1830) of the GJB6 gene. Eleven GJB2 mutations (119 mutated alleles) were truncating (T), and 18 mutations (59 alleles) were nontruncating (NT). Biallelic GJB2 mutations were found in 71 patients (21.2%; 67 families; 25 different genotypes). Audiograms of 62 patients (56 families) with biallelic GJB2 mutations typically indicated a profound hearing loss with T/T mutations, moderate hearing loss with T/NT mutations, and mild hearing impairment with NT/NT mutations (p < 0.01, Student’s t test). From 37 patients (34 families) with biallelic GJB2 mutations, audiograms at different ages were available and indicated progressive hearing loss (>15 dB) in 10 patients (27.0%, 10 families). Interestingly, we identified an unexpectedly large subset of patients (n = 29; 8.7%) presenting with only one GJB2 mutation (n = 14 T/wild-type; n = 15 NT/wild-type). This strongly suggests the presence of additional recessive mutations that are not detected by current GJB2 mutation and GJB6 deletion analyses.
Cognitive Function and Anticoagulation Control in Patients With Atrial Fibrillation
Authors: Flaker Greg C. , Pogue Janice , Yusuf Salim , Pfeffer Marc A. , Goldhaber Samuel Z. , Granger Christopher B. , Anand Inderjit S. , Hart Robert , Connolly Stuart J.
Published: March 2010

Background—

Patients with atrial fibrillation usually are elderly and may have cognitive dysfunction. These patients may receive less effective oral anticoagulation, resulting in more vascular events and bleeding.

Methods and Results—

In an analysis of cognitive function associated with the time in therapeutic range (TTR) in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events, 2510 patients (mean age, 71±9.5 years) from 27 countries completed the Mini-Mental State Examination (MMSE). Of these patients, 171 (6.8%) had an MMSE score <24, suggesting dementia, and 194 (7.7%) had intermediate scores of 24 to 25. Low MMSE scores were correlated with a low TTR. Even mild cognitive impairment was associated with a TTR below the median (<65%). Patients with an MMSE score <26 had more vascular events (6.7% versus 3.6% per 100 patient-years;
P
=0.002) and more bleeding (9.6% versus 7% per 100 patient-years;
P
=0.04). After controlling for TTR, the MMSE no longer conferred increased risk, suggesting that if improved anticoagulation was provided, vascular events and bleeding would be reduced. Other independent factors associated with a TTR <65% were region of the world, recent initiation of vitamin K antagonist, type of anticoagulant, and concurrent use of amiodarone or insulin. After adjustment for these factors, lower MMSE scores still predicted a reduced TTR.

Conclusions—

Cognitive dysfunction is common in elderly patients with atrial fibrillation and is related to less effective anticoagulation and more vascular events. The MMSE identifies patients with atrial fibrillation in whom extra efforts are needed to maintain effective anticoagulation and improve outcomes.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00243178.
Biosecurity Reconsidered: Calibrating Biological Threats and Responses
Authors: Koblentz Gregory D.
Published: March 2010

Advances in science and technology, the rise of globalization, the emergence of new diseases, and the changing nature of conflict have increased the risks posed by naturally occurring and man-made biological threats. A growing acceptance of a broader definition of security since the end of the Cold War has facilitated the rise of biosecurity issues on the international security agenda. Developing strategies to counter biological threats is complicated by the lack of agreement on the definition of biosecurity, the diverse range of biological threats, and competing perspectives on the most pressing biological threats. A comprehensive definition of biosecurity that encompasses naturally occurring, accidental, and deliberate disease outbreaks can help to further research, analysis, and policymaking. Operationalizing this broad conception of biosecurity requires a taxonomy of biological threats based on a levels-of-analysis approach that identifies which types of actors are potential sources of biological threats and the groups most at risk from these threats. A biosecurity taxonomy can provide a common framework for the multidisciplinary research and analysis necessary to assess and manage these risks. It also has implications for how to prevent and respond to biological threats, as well as for the future of biosecurity research.
When the Levee Breaks: The Impact of the Sino-Soviet Split and the Invasion of Czechoslovakia on Romanian-Soviet Relations, 1967–1970
Authors: Munteanu Mircea
Published: March 2010

Romania's position regarding the Soviet invasion of Czechoslovakia in 1968 was the culmination of almost a decade of increasingly autonomous moves vis-à-vis Moscow. Based on new evidence from the Romanian archives, this article paints a more complete picture of Nicolae Ceauşescu's reaction to the invasion of Czechoslovakia, placing it in the context of the international system and especially the Sino-Soviet split. Following the invasion, Romania remained just as committed as before to the goal of ensuring its maneuverability on the world scene, especially with regard to sovereignty and independence. Although Romanian leaders tried not to provoke the Soviet Union outright, they did not back down on important issues concerning Sino-Romanian relations and did not embrace Moscow's call for a common Warsaw Pact foreign policy. Romania did agree to certain compromises, but only because Ceauşescu believed that Romania would remain largely unaffected by them.
Mobile Communities: Are We Talking About a Village, a Clan, or a Small Group?
Authors: Ling Rich , Stald Gitte
Published: March 2010

A central issue in the adoption and use of information and communication technology is the degree to which it either contributes to or detracts from the development of social cohesion in the small group. When considering this question, one need recognize that the social dynamics of the mobile telephone are different from those of the Internet. The device affords point-to-point interaction that makes us individually addressable regardless of where we or our interlocutors may be. This analysis draws on survey material from Scandinavia. It is based on a random sample of approximately 1,800 persons in Norway surveyed in December 2007 and January 2008. The data were collected with a Web-based survey of a known population, as supplemented with telephone interviews to cover those who traditionally do not use the Web (generally, persons older than 50 years of age). Data from two surveys of 15- to 24-year-old Danes were included: one from 2004 (343 respondents) and one from 2006 (629 respondents). Research reported here, and by others, has found that the mobile telephone contributes to the development and maintenance of social cohesion within the closest sphere of friends and family. If community is construed to be more restricted and a result of this type of cohesion, then it is different in character than that used when discussing net-based networking.
Social Connectivity in America: Changes in Adult Friendship Network Size From 2002 to 2007
Authors: Hua Wang  , Wellman Barry
Published: March 2010

There is some panic in the United States about a possible decline in social connectivity. The authors used two American national surveys to analyze how changes in the number of friends are related to changes in Internet use. The authors found that friendships continue to be abundant among adult Americans between the ages of 25 to 74 and that they grew from 2002 to 2007. This trend is similar among Internet nonusers, light users, moderate users, and heavy users and across communication contexts: offline, virtual only, and migratory from online to offline. Heavy users are particularly active, having the most friends both online and offline. Intracohort change consistently outweighs cohort replacement in explaining overall growth in friendship.
Legacies and Traditions of Counseling Psychology: When the Past Is Our Future
Authors: Cook Stephen W. , Vacha-Haase Tammi
Published: March 2010

The Legacies & Traditions Forum has a rich past of documenting individual contributions to the profession of counseling psychology. The history of this forum, as well as early contributors and journal articles, are identified.Themes that emerged from a review of past oral biographies include changes in the work setting for counseling psychologists, value of supportive environments, and barriers that early leaders experienced. In general, contributors to the forum have been pioneers in the profession, with many holding leadership roles in governing at the national level, and early involvement in social justice. The two-tier survey process implemented to identify those who most warrant being interviewed at this time for the forum is described. The newest co-editors will continue to invite biographical manuscripts based on the highlighted process, while also expanding the forum to include articles focusing on critical events or historically important topics within the field of counseling psychology.
Development of the Faith Activities in the Home Scale (FAITHS)
Authors: Lambert Nathaniel M. , Dollahite David C.
Published: March 2010

This article reports the development of the Faith Activities In The Home Scale (FAITHS). The initial FAITHS measure was improved on and expanded by using qualitative data of two separate samples and then empirically tested on three separate samples. Study 1 comprised two samples totaling 57 highly religious families from New England and California that represented the three major Abrahamic faiths (Christianity, Judaism, and Islam) and focused on item development. Qualitative data were used to expand the breadth of survey items and to verify that religious families participate in the activities presented in the scale. The objective of Study 2 was to examine the FAITHS’s reliability and validity using three samples of college students from a Southeastern university. The FAITHS demonstrated adequate validity and reliability. In addition to introducing a needed scale, the current study illustrates the importance of using qualitative data in scale development and improvement.