bluuebunny/crossref_metadata_2025 huggingface dataset:
SEM and EDS Characterisation of Layering TiOxGrowth onto the Cutting Tool Surface in Hard Drilling Processes of Ti-Al-V Alloys
Authors: Álvarez M. , Salguero J. , Sánchez J. A. , Huerta M. , Marcos M.
Published: September 2011

Scanning electron microscopy (SEM) has been used to identify and analyse the secondary adhesion effect precursors formed during the dry drilling processes of Ti-6Al-4V alloy over the rake face and flute of the drilling tools. Subsequent analysis with energy dispersive spectroscopy (EDS) was enabled to distinguish its compositional characteristics. Thus, according to the EDS obtained data, a stratified multi built-up layer (MBUL) composed by TiOxis formed over the rake face of the tool. Furthermore, this multi-layer adhered allows initially the built-up edge (BUE) development close to the edge of the tool by a mechanical adhesion mechanism. In a second step, it is responsible for the formation of a thicker secondary BUL which avoids the chip flow, and it provokes the tool collapse. These mechanisms are different from those observed in the dry machining of other alloys such as steels, nickel-based alloys, or aluminium alloys.
Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
Authors: Haegert David G.
Published: September 2011

Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in naïve CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of naïve T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of naïve CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of naïve CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes.
Use of Silica Tubes as Nanocontainers for Corrosion Inhibitor Storage
Authors: Ávila-Gonzalez Cesia , Cruz-Silva Rodolfo , Menchaca Carmina , Sepulveda-Guzman Selene , Uruchurtu Jorge
Published: September 2011

A new alkyd paint anticorrosion smart coating was developed by using silica nanoparticles as corrosion inhibitor nanocontainers. Silica particles were mixed with the paint at different concentrations to study their performance and ensure their free transportation to the damaged metal. The filling up of silica particles was done preparing three solutions: distilled water, acetone, and a mixture of both, with Fe(NO3)3and silica particles immersed in each of the solutions to adsorb the inhibitor. Acetone solution was the best alternative determined by weight gain analysis made with the inhibitor adsorbed in silica nanocontainers. Steel samples were painted with inhibitor silica nanocontainer coatings and immersed in an aqueous solution of 3% sodium chloride. Polarization curves and electrochemical noise techniques were used to evaluate the corrosion inhibitor system behavior. Good performance was obtained in comparison with samples without inhibitor nanocontainer coating.
Preoperative Parathyroid Needle Localization: A Minimally Invasive Novel Technique in Reoperative Settings
Authors: Winters Ryan , Friedlander Paul , Noureldine Salem , Ekaidi Ibrahim , Moroz Krzysztof , Kandil Emad
Published: September 2011

Background. Reoperative parathyroid surgery for primary hyperparathyroidism can be challenging. Numerous preoperative localization techniques have been employed to facilitate a more focused surgical exploration. This paper describes a novel, minimally invasive, and highly successful method of parathyroid localization.Methods. Patients with recurrent or persistent primary hyperparathyroidism underwent parathyroidectomy following CT scan or ultrasound-guided wire localization of the parathyroid. Accurate placement was confirmed by fine-needle aspiration with immunocytochemistry or PTH washout. The guide wire was leftin situto guide surgical excision of the gland. Curative resection was established by monitoring intact serum PTH levels after excision of the adenoma.Results. All ten patients underwent successful redo-targeted parathyroidectomy. Nine of the ten patients were discharged on the day of surgery. One patient was observed overnight due to transient postoperative hypocalcemia, which resolved with calcium supplementation.Conclusion. Placement of a localization wire via preoperative high-resolution ultrasound or CT can expedite reoperative parathyroid surgery. It allows identification of parathyroid adenoma via a minimally invasive approach, especially in cases where a sestamibi scan is inconclusive.
Variation of the Side Chain Branch Position Leads to Vastly Improved Molecular Weight and OPV Performance in 4,8-dialkoxybenzo[1,2-b:4,5-b′]dithiophene/2,1,3-benzothiadiazole Copolymers
Authors: Coffin Robert C. , MacNeill Christopher M. , Peterson Eric D. , Ward Jeremy W. , Owen Jack W. , McLellan Claire A. , Smith Gregory M. , Noftle Ronald E. , Jurchescu Oana D. , Carroll David L.
Published: September 2011

Through manipulation of the solubilizing side chains, we were able to dramatically improve the molecular weight(Mw)of 4,8-dialkoxybenzo[1,2-b:4,5-b′]dithiophene (BDT)/2,1,3-benzothiadiazole (BT) copolymers. When dodecyl side chains (P1) are employed at the 4- and 8-positions of the BDT unit, we obtain a chloroform-soluble copolymer fraction withMwof 6.3 kg/mol. Surprisingly, by moving to the commonly employed 2-ethylhexyl branch (P2),Mwdecreases to 3.4 kg/mol. This is despite numerous reports that this side chain increases solubility andMw. By moving the ethyl branch in one position relative to the polymer backbone (1-ethylhexyl,P3),Mwis dramatically increased to 68.8 kg/mol. As a result of thisMwincrease, the shape of the absorption profile is dramatically altered, withλmax= 637 nm compared with 598 nm forP1and 579 nm forP2. The hole mobility as determined by thin film transistor (TFT) measurements is improved from~1×10−6 cm2/Vs forP1andP2to7×10−4 cm2/Vs forP3, while solar cell power conversion efficiency in increased to2.91%forP3relative to0.31%and0.19%forP1andP2, respectively.
The Asymptotic Behavior for Second‐Order Neutral Stochastic Partial Differential Equations with Infinite Delay
Authors: Chen Huabin
Published: September 2011

By establishing two Lemmas, the exponential stability and the asymptotical stability for mild solution to the second‐order neutral stochastic partial differential equations with infinite delay are obtained, respectively. Our results can generalize and improve some existing ones. Finally, an illustrative example is given to show the effectiveness of the obtained results.
Bayesian Network-Based High-Level Context Recognition for Mobile Context Sharing in Cyber-Physical System
Authors: Park Han-Saem , Oh Keunhyun , Cho Sung-Bae
Published: September 2011

With the recent proliferation of smart phones, they become useful tools to implement high-confidence cyber-physical systems. Among many applications, context sharing systems in mobile environment attract attention with the popularization of social media. Mobile context sharing systems can share more information than web-based social network services because they can use a variety of information from mobile sensors. To share high-level contexts such as activity, emotion, and user relationship, a user had to annotate them manually in previous works. This paper proposes a mobile context sharing system that can recognize high-level contexts automatically by using Bayesian networks based on mobile logs. We have developed a ContextViewer application which consists of a phonebook and a map browser to show the feasibility of the system. Experiments of evaluating Bayesian networks and performing the SUS test confirm that the proposed system is useful.
Mapping the Fundamental Niches of Two Freshwater Microalgae,Chlorella vulgaris(Trebouxiophyceae) andPeridinium cinctum(Dinophyceae), in 5-Dimensional Ion Space
Authors: Evens Terence J. , Niedz Randall P.
Published: September 2011

The fundamental niche defined by five ions,NO3 −,PO4 3−, K+, Na+, andCl−, was mapped forChlorella vulgaris(Trebouxiophyceae) andPeridinium cinctum(Dinophyceae) growth rates and maximum cell densities in batch cultures. A five dimensional ion-mixture experimental design was projected across a total ion concentration gradient of 1 to 30 mM to delineate the ion-based, “potential” niche space, defined as the entiren-dimensional hypervolume demarcated by the feasible ranges of the independent factors under consideration. The growth rate-based, fundamental niche volumes overlapped for ca. 94% of the ion mixtures, although the regions of maximal growth rates and cell densities were different for each alga. BothC. vulgarisandP. cinctumexhibited similar positive responses to cations and negative responses to anions. It was determined that total ion concentration for these five ions, from 1 to 30 mM, did not directly affect either growth rate or maximal cell density for either alga, although it did play an interactive role with several ions. This study is the first that we are aware of to attempt the mapping of a multivariate, ion-based, fundamental niche volume. The implications of the experimental design utilized and the potential utility of this type of approach are discussed.
Biostimulation for the Enhanced Degradation of Herbicides in Soil
Authors: Kanissery Ramdas Gopinath , Sims Gerald K.
Published: September 2011

Cleanup of herbicide-contaminated soils has been a dire environmental concern since the advent of industrial era. Although microorganisms are excellent degraders of herbicide compounds in the soil, some reparation may need to be brought about, in order to stimulate them to degrade the herbicide at a faster rate in a confined time frame. “Biostimulation” through the appropriate utilization of organic amendments and nutrients can accelerate the degradation of herbicides in the soil. However, effective use of biostimulants requires thorough comprehension of the global redox cycle during the microbial degradation of the herbicide molecules in the soil. In this paper, we present the prospects of using biostimulation as a powerful remediation strategy for the rapid cleanup of herbicide-polluted soils.
Glass Fibre-Reinforced Composite Post and Core Used in Decayed Primary Anterior Teeth: A Case Report
Authors: Verma Leena , Passi Sidhi
Published: September 2011

Aesthetic requirement of severely mutilated primary anterior teeth in the case of early childhood caries has been a challenge to pediatric dentist. Among restorative treatment options, prefabricated crown and biological and resin composite restoration either by means of direct or indirect technique are mentioned in the literature. This paper presents the clinical sequence of rehabilitation of maxillary anterior primary teeth. Endodontic treatment was followed by the placement of a glass fibre-reinforced composite resin post. The crown reconstruction was done with composite restoration. Resin glass fibre post has best properties in elasticity, translucency, adaptability, tenaciousness, and resistance to traction and to impact. Along with ease of application, fiber can be used as an alternative to traditionally used materials in the management of early childhood caries.
Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
Authors: Kazzaz Jeffrey A. , Strayer Marlene S. , Wu Jichuan , Malone Daniel J. , Koo Hshi-chi , Shaffer Thomas H. , Davis Jonathan M. , Strayer David S. , Wolfson Marla R.
Published: September 2011

We compared lung delivery methods of recombinant adenovirus (rAd): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2–4 h. rAd transgene expression was improved in alveolar epithelial cells, and the level and distribution of luciferase expression when delivered in PFC-rAd suspensions consistently peaked at 24 h. These results demonstrate that PFC-rAd suspensions improve distribution and enhance rAd-mediated gene expression which has important implications in improving lung function by gene therapy.
Prostate Cancer Incidence Rates in Africa
Authors: Chu Lisa W. , Ritchey Jamie , Devesa Susan S. , Quraishi Sabah M. , Zhang Hongmei , Hsing Ann W.
Published: September 2011

African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973–2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7–38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7–19.8). These rates were considerably lower than those of 80.0–195.3 observed among African Americans. Rates in Africa increased over time (1987–2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa.
Lipid-Lowering and Antioxidative Activities of Aqueous Extracts ofOcimum sanctumL. Leaves in Rats Fed with a High-Cholesterol Diet
Authors: Suanarunsawat Thamolwan , Devakul Na Ayutthaya Watcharaporn , Songsak Thanapat , Thirawarapan Suwan , Poungshompoo Somlak
Published: September 2011

The present study was conducted to investigate the lipid-lowering and antioxidative activities ofOcimum sanctumL. (OS) leaf extracts in liver and heart of rats fed with high-cholesterol (HC) diet for seven weeks. The results shows that OS suppressed the high levels of serum lipid profile and hepatic lipid content without significant effects on fecal lipid excretion. Fecal bile acids excretion was increased in HC rats treated with OS. The high serum levels of TBARS as well as AST, ALT, AP, LDH, CK-MB significantly decreased in HC rats treated with OS. OS suppressed the high level of TABARS and raised the low activities of GPx and CAT without any impact on SOD in the liver. As for the cardiac tissues, OS lowered the high level of TABARS, and raised the activities of GPx, CAT, and SOD. Histopathological results show that OS preserved the liver and myocardial tissues. It can be concluded that OS leaf extracts decreased hepatic and serum lipid profile, and provided the liver and cardiac tissues with protection from hypercholesterolemia. The lipid-lowering effect is probably due to the rise of bile acids synthesis using cholesterol as precursor, and antioxidative activity to protect liver from hypercholesterolemia.
Effects of Calcination Temperatures on Photocatalytic Activity of Ordered Titanate Nanoribbon/SnO2Films Fabricated during an EPD Process
Authors: Zhao Li , Ran Jingrun , Shu Zhan , Dai Guotian , Zhai Pengcheng , Wang Shimin
Published: September 2011

Ordered titanate nanoribbon (TNR)/SnO2films were fabricated by electrophoretic deposition (EPD) process using hydrothermally prepared titanate nanoribbon as a precursor. The formation mechanism of ordered TNR film on the fluorine-doped SnO2coated (FTO) glass was investigated by scanning electron microscopy (SEM). The effects of calcination temperatures on the phase structure and photocatalytic activity of ordered TNR/SnO2films were investigated and discussed. The X-ray diffraction (XRD) results indicate that the phase transformation of titanate to anatase occurs at 400°C and with increasing calcination temperature, the crystallization of anatase increases. At 600°C, the nanoribbon morphology still hold and the TiO2/SnO2film exhibits the highest photocatalytic activity due to the good crystallization, unique morphology, and efficient photogenerated charge carriers separation and transfer at the interface of TiO2and SnO2.
Pelvic Organ Distribution of Mesenchymal Stem Cells Injected Intravenously after Simulated Childbirth Injury in Female Rats
Authors: Cruz Michelle , Dissaranan Charuspong , Cotleur Anne , Kiedrowski Matthew , Penn Marc , Damaser Margot
Published: September 2011

The local route of stem cell administration utilized presently in clinical trials for stress incontinence may not take full advantage of the capabilities of these cells. The goal of this study was to evaluate if intravenously injected mesenchymal stem cells (MSCs) home to pelvic organs after simulated childbirth injury in a rat model. Female rats underwent either vaginal distension (VD) or sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after injury. Four or 10 days later pelvic organs and muscles were imaged for visualization of GFP-positive cells. Significantly more MSCs home to the urethra, vagina, rectum, and levator ani muscle 4 days after VD than after sham VD. MSCs were present 10 days after injection but GFP intensity had decreased. This study provides basic science evidence that intravenous administration of MSCs could provide an effective route for cell-based therapy to facilitate repair after injury and treat stress incontinence.
Mixed Signature: An Invariant Descriptor for 3D Motion Trajectory Perception and Recognition
Authors: Yang Jianyu , Li Y. F. , Wang Keyi , Wu Yuan , Altieri Giuseppe , Scalia Massimo
Published: September 2011

Motion trajectory contains plentiful motion information of moving objects, for example, human gestures and robot actions. Motion perception and recognition via trajectory are
useful for characterizing them and a flexible descriptor of motion trajectory plays important
role in motion analysis. However, in the existing tasks, trajectories were mostly used in raw
data and effective descriptor is lacking. In this paper, we present a mixed invariant signature
descriptor with global invariants for motion perception and recognition. The mixed signature
is viewpoint invariant for local and global features. A reliable approximation of the mixed
signature is proposed to reduce the noise in high‐order derivatives. We use this descriptor for
motion trajectory description and explore the motion perception with DTW algorithm for
salient motion features. To achieve better accuracy, we modified the CDTW algorithm for
trajectory matching in motion recognition. Furthermore, a controllable weight parameter is
introduced to adjust the global features for tasks in different circumstances. The conducted
experiments validated the proposed method.
Androgen-Independent Molecular Imaging Vectors to Detect Castration-Resistant and Metastatic Prostate Cancer
Authors: Jiang Ziyue Karen , Sato Makoto , Wei Liu H. , Kao Chinghai , Wu Lily
Published: September 2011

Prostate-specific promoters are frequently employed in gene-mediated molecular imaging and therapeutic vectors to diagnose and treat castration-resistant prostate cancer (CRPC) that emerges from hormone ablation therapy. Many of the conventional prostate-specific promoters rely on the androgen axis to drive gene expression. However, considering the cancer heterogeneity and varying androgen receptor status, we herein evaluated the utility of prostate-specific enhancing sequence (PSES), an androgen-independent promoter in CRPC. The PSES is a fused enhancer derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen gene regulatory region. We augmented the activity of PSES by the two-step transcriptional amplification (TSTA) system to drive the expression of imaging reporter genes for either bioluminescent or positron emission tomography (PET) imaging. The engineered PSES–TSTA system exhibits greatly elevated transcriptional activity, androgen independency, and strong prostate specificity, verified in cell culture and preclinical animal experimentations. These advantageous features of PSES–TSTA elicit superior gene expression capability for CRPC in comparison with the androgen-dependent PSA promoter–driven system. In preclinical settings, we showed robust PET imaging capacity of PSES–TSTA in a castrated prostate xenograft model. Moreover, intravenous administrated PSES–TSTA bioluminescent vector correctly identified tibial bone marrow metastases in 9 of 9 animals, whereas NaF- and FDG-PET was unable to detect the lesions. Taken together, this study showed the promising utility of a potent, androgen-independent, and prostate cancer–specific expression system in directing gene-based molecular imaging in CRPC, even in the context of androgen deprivation therapy. Cancer Res; 71(19); 6250–60. ©2011 AACR.
Relationship between Quantitative GRB7 RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple-Negative Breast Cancer
Authors: Sparano Joseph A. , Goldstein Lori J. , Childs Barrett H. , Shak Steven , Brassard Diana , Badve Sunil , Baehner Frederick L. , Bugarini Roberto , Rowley Steve , Perez Edith A. , Shulman Lawrence N. , Martino Silvana , Davidson Nancy E. , Kenny Paraic A. , Sledge George W. , Gray Robert
Published: September 2011

Purpose: To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy.

Experimental Design: RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests.

Results: Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8–14.1] in the low and 20.4% (95% CI, 16.5–25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy.

Conclusions: GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered. Clin Cancer Res; 17(22); 7194–203. ©2011 AACR.
Progesterone and 1,25-Dihydroxyvitamin D3 Inhibit Endometrial Cancer Cell Growth by Upregulating Semaphorin 3B and Semaphorin 3F
Authors: Nguyen Huyen , Ivanova Vessela S. , Kavandi Leyla , Rodriguez Gustavo C. , Maxwell George L. , Syed Viqar
Published: September 2011

Class 3 semaphorins (SEMA), SEMA3B and SEMA3F, are secreted proteins that regulate angiogenesis, tumor growth, and metastasis by binding to their transmembrane receptor complex consisting of plexins and neuropilins (NP). Expression of SEMAs and their receptors was assessed in tissue microarrays by immunohistochemistry. SEMA3B, SEMA3F, and plexin A3 were expressed strongly in normal endometrial tissues, whereas grade-dependent decreases were found in endometrial carcinomas. No change was observed in the expression of plexin A1, NP1, and NP2 in normal versus endometrial cancer tissues. Endometrial cancer cells showed decreased expression of SEMA3B, SEMA3F, and plexin A3 compared with their normal counterparts. Treatment of cancer cells with progesterone (P4) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for a period of 72 hours induced a significant upregulation of SEMA3B and SEMA3F as well as inhibited growth of cancer cells by increasing caspase-3 activity. Cotreatment of cell lines with P4 or 1,25(OH)2D3 and their respective antagonists confirmed the specificity of their actions. Transfection of siRNA-targeting SEMA3B and SEMA3F in endometrial cancer cells attenuated P4 or 1,25(OH)2D3-induced growth inhibition. Restoration of SEMA3B or SEMA3F expression in cancer cells caused growth inhibition, reduced soft agar colony formation, and cell invasiveness by inhibiting expression of matrix metalloproteinase-2 (MMP-2), MMP-9, integrin αvβ3, and proangiogenic genes and by upregulating antiangiogenic genes. Thus, we have identified two new P4 and 1,25(OH)2D3-regulated antitumor genes for endometrial cancer. These results suggest that the loss of SEMAs contribute to the malignant phenotype of endometrial cancer cells and that reexpression of SEMAs by ectopic expression or with anticancer agents P4 or 1,25(OH)2D3 can be a promising therapeutic treatment against endometrial cancer. Mol Cancer Res; 9(11); 1479–92. ©2011 AACR.
Intercommunication between the Neuroendocrine and Immune Systems: Focus on Myasthenia Gravis
Authors: Mays Jacqueline , Butts Cherié L.
Published: September 2011

Crosstalk exists between the nervous, endocrine, and immune systems, and perturbations in these interactions have been associated with disease. This includes production of neuroendocrine factors that alter immune system activity and increase susceptibility to or severity of immune-related conditions, such as myasthenia gravis (MG) – a T-cell-dependent, B-cell-mediated autoimmune disorder. MG results from impairment of transmission to the neuromuscular junction and involves the thymus – especially in early-onset disease, but the exact mechanism by which the thymus impacts disease is unclear. MG afflicts millions of individuals worldwide each year, and both men and women can develop symptoms. However, prevalence and age of onset differs between men and women. Women exhibit higher incidence and earlier age of onset compared to men, and disease fluctuates during pregnancy. This suggests that sex hormones play a role in influencing disease outcome. In this review, we will consider what is known about the manifestation of MG, theories on how different forms of MG are influenced or alleviated by steroid hormones, current treatment options, and what measures could be important to consider in the future.
Evidence of Conserved Neuroendocrine Interactions in the Thymus: Intrathymic Expression of Neuropeptides in Mammalian and Non-Mammalian Vertebrates
Authors: Silva Alberto B. , Palmer Donald B.
Published: September 2011

The function of lymphoid organs and immune cells is often modulated by hormones, steroids and neuropeptides produced by the neuroendocrine and immune systems. The thymus intrinsically produces these factors and a comparative analysis of the expression of neuropeptides in the thymus of different species would highlight the evolutionary importance of neuroendocrine interaction in T cell development. In this review, we highlight the evidence which describes the intrathymic expression and function of various neuropeptides and their receptors, in particular somatostatin, substance P, vasointestinal polypeptide, calcitonin gene-related peptide and neuropeptide Y, in mammals (human, rodent) and non-mammals (avian, amphibian and teleost), and conclude that neuropeptides play a conserved role in vertebrate thymocyte development.
Thymulin-Based Gene Therapy and Pituitary Function in Animal Models of Aging
Authors: Reggiani Paula C. , Poch Brenda , Cónsole Gloria M. , Rimoldi Omar J. , Schwerdt Jose I. , Tüngler Victoria , Garcia-Bravo Margarita M. , Dardenne Mireille , Goya Rodolfo G.
Published: September 2011

Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. After its discovery and initial characterization in the 1970s, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysiotropic peptide. Additionally, thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. In recent years, a synthetic DNA sequence coding for a biologically active analog of thymulin, metFTS, was constructed and cloned in different adenoviral vectors. These include bidirectional regulatable Tet-Off vector systems that simultaneously express metFTS and green fluorescent protein and that can be downregulated reversibly by the addition of the antibiotic doxycycline. A number of recent studies suggest that thymulin gene therapy may be a suitable therapeutic strategy to prevent some of the endocrine and reproductive alterations that typically appear in congenitally athymic (nude) mice, taken as a suitable model of neuroendocrine and reproductive aging. The present article briefly reviews the literature on the physiology of the thymulin-pituitary axis as well as on the new molecular tools available to exploit the therapeutic potential of thymulin.
Growth Hormone Is a Modulator of Lymphocyte Migration
Authors: Smaniotto Salete , Alves Martins-Neto Adalberto , Dardenne Mireille , Savino Wilson
Published: September 2011

Cell migration is crucial for intrathymic T cell differentiation and export of mature T lymphocytes to the peripheral lymphoid organs. The intrinsic regulation of T cell migration, mediated by adhesion molecules and chemokines, can be influenced by a number of endogenous factors, such as hormones, as for instance growth hormone (GH). Laminin deposition was enhanced in GH-treated mice and in GH-transgenic animals, compared with corresponding controls, and thymocyte adhesion to laminin was increased by in vivoGH treatment. An enhancing effect was also observed ex vivo in relation to the number of migrating cells in laminin-coated transwell chambers. Additionally, we found that the chemokine CXCL12, in conjunction with laminin, further enhanced the migration of thymocytes previously exposed to high concentrations of GH in vivo. Moreover, an increase in CXCL12 production has been detected in the thymus of GH-transgenic mice as well as in primary thymic epithelial cell cultures derived from these animals, as compared to age-matched wild-type counterparts. In keeping with these data, in vivo experiments showed that GH favors the trafficking of naive CD4+CD8– recent thymic emigrants to the peripheral lymph nodes. In addition, we found that migration of lymphocytes from mesenteric lymph nodes of GH-transgenic mice, triggered by the chemokine CXCL12, in conjunction with laminin or fibronectin, was enhanced, when compared to lymphocytes from control mice. Since GH-based therapy has been used in human and experimental infectious diseases, this hormone can be envisioned as an additional therapeutic tool in situations in which increasing lymphocyte numbers and migration are required for correcting a given pathological state.
Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity
Authors: Leposavić Gordana , Pilipović Ivan , Perišić Milica
Published: September 2011

Ageing is associated with a progressive decline in thymic cytoarchitecture followed by a less efficient T cell development and decreased emigration of naïve T cells to the periphery. These thymic changes are linked to increased morbidity and mortality from infectious, malignant and autoimmune diseases in old age. Therefore, it is of paramount importance to understand the thymic homeostatic processes across the life span, as well as to identify factors and elucidate mechanisms driving or contributing to the thymic involution. Catecholamines (CAs) derived from sympathetic nerves and produced locally by thymic cells represent an important component of the thymic microenvironment. In young rats, they provide a subtle tonic suppressive influence on T cell development acting via β2- and α1-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and thymocytes. In the face of thymic involution, a progressive increase in the thymic noradrenaline level, reflecting a rise in the density of noradrenergic nerve fibers and CA-synthesizing cells, occurs. In addition, the density of β2- and α1-AR-expressing thymic nonlymphoid cells and the α1-AR thymocyte surface density also exhibit a pronounced increase with age. The data obtained from studies investigating effects of AR blockade on T cell development indicated that age-related changes in CA-mediated thymic communications, certainly those involving α1-ARs, may contribute to diminished thymopoietic efficiency in the elderly. Having in mind thymic plasticity in the course of ageing, and broadening possibilities for pharmacological modulation of CA signaling, we here present and discuss the progress in research related to a role of CAs in thymic homeostasis and age-related decay in the thymic naïve T cell output.
Saitohin and APOE Polymorphisms Influence Cognition and Function in Persons with Advanced Alzheimer Disease
Authors: Schutte Debra L. , Reed David , DeCrane Susan , Ersig Anne L.
Published: September 2011

Background/Aims: Alzheimer disease (AD) is characterized by variability in the onset and progression of cognitive, functional and behavioral symptoms. The purpose of this study was to identify genetic correlates of symptom variability in persons with moderate-to-advanced AD. Methods: Repeated measures of cognition, function and behavior were collected from institutionalized persons with AD over 12 months. Candidate genes were assayed. Results: Single polymorphisms within the saitohin and APOE genes were associated with increased cognitive impairment and functional dependence. The APOE-ε4 allele was associated with increased baseline physical agitation. Conclusion: The development of predictive profiles for the clinical symptoms of AD may increase our ability to identify clinical subgroups for more targeted intervention.
Cytokine-Induced Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells via Nitric Oxide-Mediated Process in vitro
Authors: Kheansaard Wasinee , Panichob Prapaporn , Fucharoen Suthat , Tanyong Dalina I.
Published: September 2011

Background/Aim: β-Thalassemia/hemoglobin E (β-thal/HbE) is a common hereditary anemia in Thailand. Ineffective erythropoiesis due to apoptosis and decreased lifespan of circulating thalassemic red blood cells are the major causes of anemia. Changes to bone marrow microenvironment could contribute to apoptotic events. This study examined the effects of cytokines interleukin-1β, tumor necrosis factor-α and interferon-γ on apoptosis of β-thal/HbE erythroid progenitor cells in vitro, including nitric oxide-mediated apoptotic processes. Methods: Percent apoptosis of erythroid progenitor cells from 5 β-thal/HbE patients and 5 normal control subjects was examined using flow cytometry. In addition, the inducible nitric oxide synthase (iNOS) mRNA level and nitrite production were measured using quantitative PCR and the Griess method, respectively. Results: Upon cytokine treatment, a higher percent apoptosis was obtained with β-thal/HbE erythroid progenitor cells compared with control, and the maximum effect was observed using 20 ng/ml interferon-γ on day 14 of culture. There was an increase in iNOS mRNA level and a concomitant elevation of nitrite concentration in culture medium. Apoptosis and nitrite level were abrogated when β-thal/HbE and control cells were treated with S-methylisothiourea sulfate, an iNOS inhibitor. Conclusion: The marked sensitivity of erythroid progenitor cells from β-thal/HbE patients to cytokine-induced apoptosis via an NO-mediated process reflects a proapoptotic status of such thalassemic red blood cells.
The European Adolescent Assessment Dialogue (EuroADAD): A Psychometric Evaluation
Authors: Czobor Pál , Bácskai Erika , Oberg David , Haack Marie-Jeanne , Gerevich József
Published: September 2011

Background: The Adolescent Drug Abuse Diagnosis (ADAD) has been a gold standard for assessing drug use and associated problems in adolescents. Criticism of the instrument has been increasing. A new instrument, the European Adolescent Assessment Dialogue (EuroADAD) that builds on ADAD’s strengths but seeks to address its limitations is now available, but has not been subjected to comprehensive psychometric evaluation. Objective: To examine the psychometric properties of the EuroADAD across various settings in adolescent populations who developed or were at a high risk of developing substance use and psychosocial adaptation problems. Participants and Settings: Three of the samples were collected in Hungary, including: institutionalized youths from juvenile residential facility (n = 295); adolescents from outpatient psychiatry facility (n = 278), and controls (n = 59). An additional sample was collected in the Netherlands, and consisted of adolescent boys from an independent residential institution for youth with severe behavioral problems (n = 51). Procedure: The EuroADAD was administered by trained interviewers. Data were collected through face-to-face interviews and self-report questionnaires. Results:Reliability: the intraclass correlation was high for all domains of the EuroADAD; reliability analyses indicated good test-retest reliability, and internal consistency. Validity: difference among study samples was significant (p < 0.05) for the majority of the domains, with juvenile institution and psychiatric outpatient subjects exhibiting higher severity in most areas compared to controls. The Hungarian and Dutch samples were comparable, expect for the legal domain, due to the higher severity of behavioral problems in the Dutch sample. Several domains of the instrument, including ‘alcohol’, ‘drugs’ and ‘legal’ showed an association with trait aggression as measured by the Buss-Perry Aggression Questionnaire and with Novelty Seeking on the Cloninger Temperament and Character Inventory. Conclusion: Based on the pattern and significance of group differences, and correlations with other measures, the scale has good criterion, and convergent and discriminant construct validity. The EuroADAD is a reliable and valid tool for the assessment of alcohol and drug use, and related psychosocial problems in adolescents.
Cardioprotective Effects of Low-Dose Cyclosporin A Added to Histidine-Tryptophan-Ketoglutarate Cardioplegia Solution prior to Total Myocardial Ischemia: An in vitro Rabbit Heart Study
Authors: Pritzwald-Stegmann P. , Hoyer A. , Kempfert J. , Dhein S. , Mohr F.W.
Published: September 2011

Background/Aims: Mitochondrial permeability transition pore (MPTP) opening appears to play a key role in myocardial cell survival after ischemia-reperfusion injury and can be inhibited by cyclosporin A (CsA). We investigated whether low-dose CsA added to histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution could improve myocardial protection during longer periods of global myocardial ischemia as encountered during cardiac surgery. Methods: Rabbit hearts perfused on a Langendorff apparatus were arrested with cold HTK solution containing 1 µmol/l CsA. After 90 min of ischemia, the hearts were reperfused and pmax, max dp/dt, min dp/dt, myocardial stiffness, pO2, coronary flow and heart rate recorded. Tissue ATP and malondialdehyde (MDA) were measured to assess cell energy content and oxidative stress, respectively. Results: CsA-treated hearts recovered pmax (p = 0.026), max dp/dt (p = 0.028) and min dp/dt (p = 0.025) more quickly and to a greater extent than non-treated hearts. They required markedly less oxygen (p = 0.041) in the first 10 min of reperfusion. Hearts treated with CsA produced 44% less MDA (1.09 vs. 1.93, p = 0.008), while ATP levels were unchanged. Conclusions: HTK cardioplegia solution containing CsA at a dose well below that expected to cause systemic immunosuppressive effects leads to a significant and timelier recovery of myocardial contractility, while consuming less oxygen.
Pharyngocutaneous Fistula Complicating Laryngectomy: Can Metronidazole Help?
Authors: Stathas Theodoros , Mallis Antonios , Mastronikolis Nicholas S. , Naxakis Stefanos S. , Dimaka Konstantina , Panogeorgou Theodora , Stavrou Stavros , Margaritis Vasilios , Kourousis Christos , Papadas Theodoros A.
Published: September 2011

Aim: To evaluate the use of metronidazole as a prophylactic agent against pharyngocutaneous fistula (PCF) formation. Patients and Methods: Seventy patients who underwent total laryngectomy between 2000 and 2008 in our department were divided into two groups. The first group (M+ group) was placed on a 10-day metronidazole regimen (2 days prior to surgery and 7 days following). The second group (M– group) received only regular preoperative chemoprophylaxis. Results: In total, 17 (24.3%) incidents of PCF were reported, 3 of which were in the M+ group, with the remainder in the M– group. A statistically significant reduction in the PCF rate was noted in favor of metronidazole in the overall population (p = 0.005), as well as in the patient group that had received radiotherapy prior to surgery (p = 0.03). Conclusion: Metronidazole administered for a total of 10 days pre- and postoperatively seems to lower the incidence rate of PCF formation.
Positive FP-CIT SPECT (DaTSCAN) in Clinical Alzheimer’s Disease – An Unexpected Finding?
Authors: Bittner Verena , Ullrich Gerhard , Thormann Markus , Müller Notger G. , Friederichs Christin , Amthauer Holger , Heinze Hans-Jochen , Bittner Daniel M.
Published: September 2011

Clinically, Alzheimer’s disease (AD) is by far the most common cause of dementia. Criteria for the diagnosis of dementia with Lewy bodies (DLB) are highly specific but not at all sensitive, which is reflected by the higher number of DLB cases detected histopathologically at autopsy. Imaging of dopamine transporter with FP-CIT SPECT is one possibility to increase sensitivity. Pathological confirmation was also included in the revised consensus criteria for the diagnosis of DLB. However, in the absence of parkinsonism, one of the core features, a clinical diagnosis of AD is more likely. The role of FP-CIT SPECT in DLB diagnosis remains to be clarified. Based on our 3 case reports and a review of the literature, the utility of this imaging method in the differential diagnosis of AD and DLB is highlighted.
Diagnostic Yield of Extensive Infectious Panel Testing in Acute Pericarditis
Authors: Abu Fanne Rami , Banai Shmuel , Chorin Udi , Rogowski Ori , Keren Gad , Roth Arie
Published: September 2011

Objective: In an attempt to reconsider our local strategy, we evaluated patients with viral/idiopathic pericarditis in order to assess the diagnostic yield of our standard infectious panel, the characteristics of myocardial involvement, the utility of investigating myocardial involvement and the incidence of coronary evaluation tests. Methods: Seventy-six consecutive cases of idiopathic/viral acute pericarditis treated between March 2005 and March 2008 were retrospectively enrolled. Telephonic questionnaires were answered by all. Results: Myopericarditis was recorded in 45/71 (63.4%) consecutive patients. Sore throat on presentation (38 vs. 12%; p = 0.027) was the only symptom independently associated with myopericarditis. The following clinical features were significantly correlated with pericarditis rather than myopericarditis: age (42 ± 16 vs. 32 ± 12; p = 0.008), C-reactive protein (131 ± 75 vs. 78 ± 58; p = 0.009) and lower CPK and troponin levels (mean 96 vs. mean 489; p < 0.001 and mean 0 vs. mean 10; p < 0.001, respectively). The infectious panel revealed 6 positive results. After an average 3 years’ fol- low-up, recurrence was documented in 5 patients (7%). No patient initially regarded idiopathic developed systemic disease during follow-up. Conclusions: Among patients presenting with presumed idiopathic/viral pericarditis, myopericarditis is relatively common and has a benign evolution. Extensive serological investigation with a broad infectious panel proved to be diagnostically and therapeutically futile in our area.
Anti-Infective Locks for Treatment of Central Line-Associated Bloodstream Infection: A Systematic Review and Meta-Analysis
Authors: O’Horo John C. , Silva Germana L.M. , Safdar Nasia
Published: September 2011

Central line-associated bloodstream infections (CLABSI) are associated with considerable morbidity, mortality and economic costs. In most cases, catheter removal is considered an essential component of managing CLABSI. However, in patients with poor access, catheter salvage may have to be attempted rather than removal and replacement of catheters. Anti-infective lock therapy (ALT) – instilling an antibiotic or antiseptic into the catheter lumen – is a novel way of treating CLABSI while attempting to salvage the catheter. However, data on the efficacy of ALT for catheter salvage is limited. In this systematic review, we critically review the evidence regarding the use of ALT for catheter salvage. We identified 8 studies including a total of 396 patients that compared ALT with systemic antibiotic therapy alone or an alternate method of catheter salvage (guidewire replacement). We found that the combination of systemic antibiotics and culture-guided lock therapy was superior to systemic antibiotics alone (OR: 0.20, 95% CI: 0.10–0.39), with 10% of locked patients requiring replacement compared to 33% of subjects without locks. There was a 20% relapse rate in the ALT group and a 30% relapse rate in the control group (OR: 0.43, 95% CI: 0.18–1.03). There was insufficient data on catheter exchange over a wire compared with ALT to permit conclusions. Our data support the use of ALT in conjunction with systemic antibiotics for catheter salvage. Large randomized controlled trials of ALT examining dose, dwell times and relapse rates stratified by infecting pathogen are needed.