bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotransformation of (–)-verbenone by Aspergillus tamarii and Aspergillus terreus
Authors: Yildirim Kudret , Yilmazer-Keskin Semra
Published: June 2010

The biotransformations of (–)-verbenone by Aspergillus tamarii and Aspergillus terreus were described. The biotransformation of (–)-verbenone with A. tamarii and A. terreus for 7 days gave (–)-10-hydroxyverbenone. The biotransformation of (–)-verbenone by A. tamarii resulted in a higher yield. A. tamarii and A. terreus were first two microorganisms to hydroxylate (–)-verbenone.
Explorations in statistics: power
Authors: Curran-Everett Douglas
Published: June 2010

Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This fifth installment of Explorations in Statistics revisits power, a concept fundamental to the test of a null hypothesis. Power is the probability that we reject the null hypothesis when it is false. Four things affect power: the probability with which we are willing to reject–by mistake–a true null hypothesis, the magnitude of the difference we want to be able to detect, the variability of the underlying population, and the number of observations in our sample. In an application to an Institutional Animal Care and Use Committee or to the National Institutes of Health, we define power to justify the sample size we propose.
What is transmitted in “synaptic transmission”?
Authors: Montagna Erik , de Azevedo Adriana M. S. , Romano Camilla , Ranvaud Ronald
Published: June 2010

Even students that obtain a high grade in neurophysiology often carry away a serious misconception concerning the final result of the complex set of events that follows the arrival of an action potential at the presynaptic terminal. The misconception consists in considering that “at a synapse, information is passed on from one neuron to the next” is equivalent to (and often expressed explicitly as) “the action potential passes from one neuron to the next.” More than half of four groups of students who were asked to comment on an excerpt from a recent physiology textbook that openly stated the misconception had no clear objection to the text presented. We propose that the first culprit in generating this misconception is the term “synaptic transmission,” which promotes the notion of transferring something or passing something along (implicitly unchanged). To avoid establishing this misconception, the first simple suggestion is to use words like “synaptic integration” rather than “synaptic transmission” right from the start. More generally, it would be important to focus on the function of synaptic events rather than on rote listing of all the numerous steps that are known to occur, which are so complex as to saturate the mind of the student.
Introduction of student-led physiology tutorial classes to a traditional curriculum
Authors: Kommalage Mahinda , Imbulgoda Naduni
Published: June 2010

The curriculum in the University of Ruhuna Medical School is of the traditional type. Most teaching activities are faculty member-led activities. Since student-centered learning processes are considered to improve certain skills and attitudes, we introduced student-led group classes (SGCs) in physiology. Depending on the outcome of the SGCs, we planned to develop it further. We designed this study to compare student perceptions on newly introduced SGCs with traditional tutorials (TTs). Student perceptions were assessed using a mixed qualitative and quantitative method. Students recognized and appreciated some favorable features of the SGC, such as the opportunity for discussion, quality of the knowledge, active participation, improvement of presentation ability, and increased breadth of knowledge. However, the majority of students preferred the TT over the SGC despite the highlighted benefits of the SGC. Students appreciated the focused learning for examinations, written preparation, and more tutor involvement in the TT. Students requested a hybrid of the TT and SGC by incorporating mandatory written answers to the SGC with greater contributions from faculty members. Assessment methods that were not aligned with the SGC and ingrained passive didactic teaching-learning methods by students and faculty members had a negative effect on the implementation of SGCs. Cultural and economical factors also contributed adversely. In the second step of this Plan-Do-Check-Act process, we are planning to introduce new formative assessment to assess higher-order cognitive skills and a compulsory tutor training program. Some favorable components from the TT will be incorporated to the SGC.
The impact of a faculty development program: evaluation based on the self-assessment of medical educators from preclinical and clinical disciplines
Authors: Sarikaya Ozlem , Kalaca Sibel , Yeğen Berrak Ç. , Cali Sanda
Published: June 2010

Self-assessment tools have previously been used to assess the impact of a faculty development program on the teaching skills of medical educators. In this study, we aimed to assess the impact of a faculty development program on the teaching performances of faculty members in relation to their medical disciplines and academic positions. A faculty-training program consisted of “training skills” and “student assessment instruments” courses. The impact of the program was evaluated by self-reporting of faculty members (a total of 225 reports) 1–2 yr after the program. Both courses were found to be beneficial by nearly all of the attendants. Clinicians benefited more from some topics in the student assessment course and could apply the structured learning and assessment guides, structured oral examination, and objective structured clinical examination more efficiently than their peers from preclinical departments. In conclusion, the results demonstrated that the participants of the faculty development program modified their teaching activities according to the demands of their clinical practice. The correlations between the benefits and behavioral changes were statistically significant.
Explicit constructivism: a missing link in ineffective lectures?
Authors: Prakash E. S.
Published: June 2010

This study tested the possibility that interactive lectures explicitly based on activating learners’ prior knowledge and driven by a series of logical questions might enhance the effectiveness of lectures. A class of 54 students doing the respiratory system course in the second year of the Bachelor of Medicine and Bachelor of Surgery program in my university was randomized to two groups to receive one of two types of lectures, “typical” lectures ( n = 28, 18 women and 10 men) or “constructivist” lectures ( n = 26, 19 women and 7 men), on the same topic: the regulation of respiration. Student pretest scores in the two groups were comparable ( P > 0.1). Students that received the constructivist lectures did much better in the posttest conducted immediately after the lectures (6.8 ± 3.4 for constructivist lectures vs. 4.2 ± 2.3 for typical lectures, means ± SD, P = 0.004). Although both types of lectures were well received, students that received the constructivist lectures appeared to have been more satisfied with their learning experience. However, on a posttest conducted 4 mo later, scores obtained by students in the two groups were not any different (6.9 ± 3 for constructivist lectures vs. 6.9 ± 3.7 for typical lectures, P = 0.94). This study adds to the increasing body of evidence that there is a case for the use of interactive lectures that make the construction of knowledge and understanding explicit, easy, and enjoyable to learners.
A housefly sensory-motor integration laboratory
Authors: Griff Edwin R. , Kane Thomas C.
Published: June 2010

Insects have many interesting behaviors that can be observed in an introductory biology laboratory setting. In the present article, we describe several reflexes using the housefly Musca domestica that can be used to introduce students to sensory and motor responses and encourage them to think about the underlying neural circuits and integration of sensory information that mediate the behaviors.
Development, implementation, and assessment of a distance module in endocrine physiology
Authors: Rangel Elaine Maria Leite , Costa Mendes Isabel Amélia , Cárnio Evelin Capellari , Marchi Alves Leila Maria , de Godoy Simone , de Almeida Crispim Juliane
Published: June 2010

This study aimed to develop, implement, and assess a distance module in endocrine physiology in TelEduc for undergraduate nursing students from a public university in Brazil, with a sample size of 44 students. Stage 1 consisted of the development of the module, through the process of creating a distance course by means of the Web. Stage 2 was the planning of the module's practical functioning, and stage 3 was the planning of student evaluations. In the experts' assessment, the module complied with pedagogical and technical requirements most of the time. In the practical functioning stage, 10 h were dedicated for on-site activities and 10 h for distance activities. Most students (93.2%) were women between 19 and 23 yr of age (75%). The internet was the most used means to remain updated for 23 students (59.0%), and 30 students (68.2%) accessed it from the teaching institution. A personal computer was used by 23 students (56.1%), and most of them (58.1%) learned to use it alone. Access to a forum was more dispersed (variation coefficient: 86.80%) than access to chat (variation coefficient: 65.14%). Average participation was 30 students in forums and 22 students in the chat. Students' final grades in the module averaged 8.5 (SD: 1.2). TelEduc was shown to be efficient in supporting the teaching-learning process of endocrine physiology.
A calcium-induced calcium release mechanism supports luteinizing hormone-induced testosterone secretion in mouse Leydig cells
Authors: Costa Roberta Ribeiro , Varanda Wamberto Antonio , Franci Celso Rodrigues
Published: June 2010

Leydig cells are responsible for the synthesis and secretion of testosterone, processes controlled by luteinizing hormone (LH). Binding of LH to a G protein-coupled receptor in the plasma membrane results in an increase in cAMP and in intracellular Ca2+ concentration ([Ca2+]i). Here we show, using immunofluorescence, that Leydig cells express ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). Measurements of intracellular calcium changes using the fluorescent calcium-sensitive dye fluo-3 and confocal microscopy show that both types of receptors are involved in a calcium-induced calcium release (CICR) mechanism, which amplifies the initial Ca2+ influx through plasma membrane T-type calcium channels (CaV3). The RyRs and IP3Rs are functional, as judged from both their activation by caffeine and IP3 and block by ryanodine and 2-aminoethoxydiphenyl borate (2-APB), respectively. RyRs are the principal players involved in the release of Ca2+ from the endoplasmic reticulum, as evidenced by the fact that global Ca2+ changes evoked by LH are readily blocked by 100 μM ryanodine but not by 2-APB or xestospongin C. Finally, steroid production by Leydig cells is inhibited by ryanodine but not by 2-APB. These results not only broaden our understanding of the role played by calcium in Leydig cells but also show, for the first time, that RyRs have an important role in determining testosterone secretion by the testis.
Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-β1-mediated tissue fibrosis
Authors: Avraham Tomer , Yan Alan , Zampell Jamie C. , Daluvoy Sanjay V. , Haimovitz-Friedman Adriana , Cordeiro Andrew P. , Mehrara Babak J.
Published: June 2010

Although radiation therapy is a major risk factor for the development of lymphedema following lymphadenectomy, the mechanisms responsible for this effect remain unknown. The purpose of this study was therefore to determine the effects of radiation on lymphatic endothelial cells (LECs) and lymphatic function. The tails of wild-type or acid sphingomyelinase (ASM)-deficient mice were treated with 0, 15, or 30 Gy of radiation and then analyzed for LEC apoptosis and lymphatic function at various time points. To analyze the effects of radiation fibrosis on lymphatic function, we determined the effects of transforming growth factor (TGF)-β1 blockade after radiation in vivo. Finally, we determined the effects of radiation and exogenous TGF-β1 on LECs in vitro. Radiation caused mild edema that resolved after 12–24 wk. Interestingly, despite resolution of tail edema, irradiated animals displayed persistent lymphatic dysfunction. Radiation caused loss of capillary lymphatics and was associated with a dose-dependent increase in LEC apoptosis. ASM−/− mice had significantly less LEC apoptosis; however, this finding did not translate to improved lymphatic function at later time points. Short-term blockade of TGF-β1 function after radiation markedly decreased tissue fibrosis and significantly improved lymphatic function but did not alter LEC apoptosis. Radiation therapy decreases lymphatic reserve by causing depletion of lymphatic vessels and LECs as well as promoting soft tissue fibrosis. Short-term inhibition of TGF-β1 activity following radiation improves lymphatic function and is associated with decreased soft tissue fibrosis. ASM deficiency confers LEC protection from radiation-induced apoptosis but does not prevent lymphatic dysfunction.
Increased group I metabotropic glutamate receptor activity in paraventricular nucleus supports elevated sympathetic vasomotor tone in hypertension
Authors: Li De-Pei , Pan Hui-Lin
Published: June 2010

The sympathetic nerve activity is elevated in cardiovascular diseases such as hypertension. Enhanced glutamatergic inputs in the paraventricular nucleus (PVN) of the hypothalamus contribute to heightened sympathetic outflow in spontaneously hypertensive rats (SHR). We determined the role of group I metabotropic glutamate receptors (mGluR) in the PVN in the control of sympathetic vasomotor tone in hypertension. Lumbar sympathetic nerve activity (LSNA), arterial blood pressure (ABP), and heart rate (HR) were recorded in anesthetized SHR and Wistar-Kyoto (WKY) rats. Bilateral microinjection of 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), a selective mGluR5 receptor antagonist, or (S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), a selective mGluR1 receptor antagonist, into the PVN had no significant effect on LSNA and ABP in WKY rats. Strikingly, MPEP and LY367385 dose dependently decreased LSNA, ABP, and HR in SHR. The MPEP-induced decreases in LSNA and ABP were significantly greater than those inhibited by LY367385 in SHR. Furthermore, bilateral microinjection of (S)-3,5-dihydroxyphenylglycine (S-DHPG), a selective group I mGluR agonist, into the PVN caused a similar dose-dependent increase in LSNA, ABP, and HR in both groups. S-DHPG-induced responses were attenuated by MPEP or LY367385 alone and were abolished by a combination of MPEP and LY367385 in WKY rats and SHR. In addition, microinjection of the NMDA receptor antagonist attenuated the sympathoexcitatory responses induced by S-DHPG in both WKY rats and SHR. Collectively, this study provides important new evidence that the resting sympathetic vasomotor tone is maintained by tonic activation of group I mGluRs in the PVN in hypertension. Activation of NMDA receptors are involved in the sympathoexcitatory effect of group I mGluRs in the PVN.
Excess diuresis and natriuresis during acute sleep deprivation in healthy adults
Authors: Kamperis Konstantinos , Hagstroem Soren , Radvanska Eva , Rittig Soren , Djurhuus Jens Christian
Published: June 2010

The transition from wakefulness to sleep is associated with a pronounced decline in diuresis, a necessary physiological process that allows uninterrupted sleep. The aim of this study was to assess the effect of acute sleep deprivation (SD) on urine output and renal water, sodium, and solute handling in healthy young volunteers. Twenty young adults (10 male) were recruited for two 24-h studies under standardized dietary conditions. During one of the two admissions, subjects were deprived of sleep. Urine output, electrolyte excretions, and osmolar excretions were calculated. Activated renin, angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide were measured in plasma, whereas prostaglandin E2 and melatonin were measured in urine. SD markedly increased the diuresis and led to excess renal sodium excretion. The effect was more pronounced in men who shared significantly higher diuresis levels during SD compared with women. Renal water handling and arginine vasopressin levels remained unaltered during SD, but the circadian rhythm of the hormones of the renin-angiotensin-aldosterone system was significantly affected. Urinary melatonin and prostaglandin E2 excretion levels were comparable between SD and baseline night. Hemodynamic changes were characterized by the attenuation of nocturnal blood pressure dipping and an increase in creatinine clearance. Acute deprivation of sleep induces natriuresis and osmotic diuresis, leading to excess nocturnal urine production, especially in men. Hemodynamic changes during SD may, through renal and hormonal processes, be responsible for these observations. Sleep architecture disturbances should be considered in clinical settings with nocturnal polyuria such as enuresis in children and nocturia in adults.
Adenosine A2 receptors modulate tubuloglomerular feedback
Authors: Carlström Mattias , Wilcox Christopher S. , Welch William J.
Published: June 2010

Adenosine can mediate the tubuloglomerular (TGF) response via activation of A1 receptors on the afferent arteriole, but both adenosine A1 and A2 receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A2 receptors offset the effect of A1 receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (ΔPSF) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min of intratubular perfusion (10 nl/min) with ATF alone, or with ATF plus the A2A receptor antagonist (ZM-241385; 10−7 or 10−5 mol/l), A1 receptor antagonist (PSB-36; 10−8 mol/l), or with a combination of A1 (PSB-36; 10−8 mol/l) and A2A (ZM-241385; 10−7 mol/l) antagonists. The maximal TGF response (ΔPSF) with ATF alone was 11.7 ± 1.0 mmHg. Specific A2 inhibition (low dose) enhanced the maximal TGF response (15.7 ± 0.8 mmHg; P < 0.01), whereas a high dose (unspecific inhibition) attenuated the response (5.0 ± 0.4 mmHg; P < 0.001). A1 inhibition alone led to a paradoxical TGF response, with an increase in PSF of 3.1 ± 0.5 mmHg ( P < 0.05). Simultaneous application of A1 and A2 antagonists abolished the TGF response (ΔPSF: 0.4 ± 0.3 mmHg). In conclusion, adenosine A2 receptors modulate the TGF response by counteracting the effects of adenosine A1 receptors.
Cell Specific Dopamine Modulation of the Transient Potassium Current in the Pyloric Network by the Canonical D1 Receptor Signal Transduction Cascade
Authors: Zhang Hongmei , Rodgers Edmund W. , Krenz Wulf-Dieter C. , Clark Merry C. , Baro Deborah J.
Published: June 2010

Dopamine (DA) modifies the motor pattern generated by the pyloric network in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus , by directly acting on each of the circuit neurons. The 14 pyloric neurons fall into six cell types, and DA actions are cell type specific. The transient potassium current mediated by shal channels ( IA) is a common target of DA modulation in most cell types. DA shifts the voltage dependence of IAin opposing directions in pyloric dilator (PD) versus lateral pyloric (LP) neurons. The mechanism(s) underpinning cell-type specific DA modulation of IAis unknown. DA receptors (DARs) can be classified as type 1 (D1R) or type 2 (D2R). D1Rs and D2Rs are known to increase and decrease intracellular cAMP concentrations, respectively. We hypothesized that the opposing DA effects on PD and LP IAwere due to differences in DAR expression patterns. In the present study, we found that LP expressed somatodendritic D1Rs that were concentrated near synapses but did not express D2Rs. Consistently, DA modulation of LP IAwas mediated by a Gs-adenylyl cyclase-cAMP-protein kinase A pathway. Additionally, we defined antagonists for lobster D1Rs (flupenthixol) and D2Rs (metoclopramide) in a heterologous expression system and showed that DA modulation of LP IAwas blocked by flupenthixol but not by metoclopramide. We previously showed that PD neurons express D2Rs, but not D1Rs, thus supporting the idea that cell specific effects of DA on IAare due to differences in receptor expression.
Amygdalofugal Influence on Processing of Taste Information in the Nucleus of the Solitary Tract of the Rat
Authors: Kang Yi , Lundy Robert F.
Published: June 2010

Previous studies have shown that corticofugal input to the first central synapse of the ascending gustatory system, the nucleus of the solitary tract (NST), can alter the way taste information is processed. Activity in other forebrain structures, such as the central nucleus of the amygdala (CeA), similarly influence activation of NST taste cells, although the effects of amygdalofugal input on neural coding of taste information is not well understood. The present study examined responses of 110 NST neurons to 15 taste stimuli before, during, and after electrical stimulation of the CeA in rats. The taste stimuli consisted of different concentrations of NaCl (0.03, 0.1, 0.3 M), sucrose (0.1, 0.3, 1.0 M), citric acid (0.005, 0.01 M), quinine HCl (0.003, 0.03 M), and 0.03 M MSG, 0.1 M KCl, as well as 0.1 M NaCl, 0.01 M citric acid, and 0.03 M MSG mixed with 10 μM amiloride. In 66% of NST cells sampled (73/110) response rates to the majority of effective taste stimuli were either inhibited or augmented. Nevertheless, the magnitude of effect across stimuli was often differential, which provides a neurophysiological mechanism to alter neural coding. Subsequent analysis of across-unit patterns showed that amygdalofugal input plays a role in shaping spatial patterns of activation and could potentially influence the perceptual similarity and/or discrimination of gustatory stimuli by altering this feature of neural coding.
Design and Realization of a Wide-Band EBG Antenna Based on FSS and Operating in the Ku-Band
Authors: Moustafa Lina , Jecko Bernard
Published: June 2010

EBG antennas are used for directive, omnidirectional, and sectoral applications. Nevertheless, the domain of use of these antennas can be extended to other applications where we can take advantage of their interesting performances notably in terms of directivity and compactness. One of these applications can be the broadband application where the needed bandwidths are much larger than the bandwidths offered by actual EBG antenna designs. Many solutions have been proposed in the literature to widen this bandwidth. This paper deals with the EBG band-widening method based on the use of FSS and focuses on the ability of the EBG resonator to have a broadband behavior if its upper interface is built of FSS chosen and arranged adequately. First, the behavior of the new EBG material formed by combining different FSSs, and the one of the new EBG resonator is briefly described. Then, a prototype operating in the Ku-band is proposed to validate the theoretical concept. Finally, an experimental validation is realized.
Risk Navigator SRM: An Applied Risk Management Tool
Authors: Hoag Dana L. K. , Parsons Jay
Published: June 2010

Risk Navigator SRM is a ten‐step risk management program for agricultural producers, which is based on the strategic planning process. The ten steps are designed to integrate disparate and difficult risk management concepts into a single system that is easy to use, yet still effective. With the aid of computers and the internet, producers can work through each step toward a final comprehensive plan. The website includes 25 decision tools that help producers accomplish each step and provides links to complementary educational programs, like a national agricultural risk education library, the award‐winning risk management simulation program called Ag Survivor, and a recently published book that describes the program and provides additional depth and explanations. The ten‐step program has been presented in over 200 workshops with over 90 percent approval by participants. The website has averaged over 1,000 unique visitors per month from 120 countries.
Decreased Risk of Squamous Cell Carcinoma of the Head and Neck in Users of Nonsteroidal Anti-Inflammatory Drugs
Authors: Ahmadi Neda , Goldman Radoslav , Seillier-Moiseiwitsch Françoise , Noone Anne-Michelle , Kosti Ourania , Davidson Bruce J.
Published: June 2010

We evaluated the chemopreventive effect of nonsteroidal anti-inflammatory drug (NSAID) use in head and neck squamous cell carcinomas (HNSCC) by conducting a case-control study based on the administration of a standardized questionnaire to 71 incident HNSCC cases and same number of healthy controls. NSAID use was associated with a 75% reduction in risk of developing HNSCC. A significant risk reduction was noted in association with frequency of NSAID use. Restricting the analysis to aspirin users revealed a significant 90% reduction in risk of developing HNSCC. This study provides evidence for a significant reduction in the risk of developing HNSCC in users of NSAIDs, and specifically aspirin users.
Immunomodulatory Agents with Antivascular Activity in the Treatment of Non-Small Cell Lung Cancer: Focus on TLR9 Agonists, IMiDs and NGR-TNF
Authors: Corti Angelo , Giovannini Monica , Belli Carmen , Villa Eugenio
Published: June 2010

Standard treatments for nonsmall cell lung cancer (NSCLC), such as surgery, chemotherapy, and radiotherapy, often lead to disappointing results. Unfortunately, also the various immunotherapeutic approaches so far tested have not produced satisfactory results to be widely applied in the clinical practice. However, the recent development of new immunomodulatory agents may open promising therapeutic options. This paper focuses on PF3512676, lenalidomide, and NGR-TNF, that is, drugs belonging to three different classes of immunomodulatory agents, that are also capable to affect tumor blood vessels with different mechanisms, and discusses the potential role of such agents in NSCLC treatment strategy.
Circulating Levels of Inflammatory Markers in Intrauterine Growth Restriction
Authors: Boutsikou Theodora , Mastorakos George , Kyriakakou Marialena , Margeli Alexandra , Hassiakos Demetrios , Papassotiriou Ioannis , Kanaka-Gantenbein Christina , Malamitsi-Puchner Ariadne
Published: June 2010

We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B—probably reflecting brain and adipose tissue inflammation—in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates—despite the lower birth weight, reflecting reduced fat mass in the former—might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded.
Hyaluronan Immobilized Polyurethane as a Blood Contacting Material
Authors: Gong Feirong , Lu Yue , Guo Hui , Cheng Shujun , Gao Yun
Published: June 2010

Hyaluronan (hyaluronic acid, HA) was immobilized onto the surface of amino-functionalized polyurethane films with the goal of obtaining a novel kind of biomaterial which had the potential in blood-contacting applications. The amino-functionalized polyurethane was prepared by synthesized acidic polyurethane whose pendant carboxyl groups were treated with an excess amount of 1,3-diaminopropane in the presence of N,N-carbonyldiimidazole (CDI). Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy (RS), scanning electron microscopy (SEM), and water contact angle measurement were used to confirm the surface changes at each step of treatment, both in morphologies and chemical compositions. APTT and PT results showed that HA immobilization could prolong the blood coagulation time, thus HA-immobilized polyurethane (PU-HA) exhibited improved blood compatibility. Cytotoxicity analysis showed that the PU-HA films synthesized in this study were cytocompatible and could support human vein endothelial cells (HUVECs) adhesion and proliferation.
Existence of Solutions of a Discrete Fourth‐Order Boundary Value Problem
Authors: Ma Ruyun , Gao Chenghua , Chang Yongkui
Published: June 2010

Let a, b be two integers with b − a ≥ 5 and let 𝕋2 = {a + 2, a + 3, …, b − 2}. We show the existence of solutions for nonlinear fourth‐order discrete boundary value problem Δ4u(t − 2) = f(t, u(t), Δ2u(t − 1)), t ∈ 𝕋2, u(a + 1) = u(b − 1) = Δ2u(a) = Δ2u(b − 2) = 0 under a nonresonance condition involving two‐parameter linear eigenvalue problem. We also study the existence and multiplicity of solutions of nonlinear perturbation of a resonant linear problem.
From Material Level to Structural Use of Mineral-Based Composites—An Overview
Authors: Orosz Katalin , Blanksvärd Thomas , Täljsten Björn , Fischer Gregor
Published: June 2010

This paper surveys different material combinations and applications in the field of mineral-based strengthening of concrete structures. Focus is placed on mechanical behaviour on material and component levels in different cementitious composites; with the intention of systematically maping the applicable materials and material combinations for mineral-based strengthening. A comprehensive description of a particular strengthening system developed in Sweden and Denmark, denominated as Mineral-based Composites (MBCs), together with tests from composite material properties to structural elements is given. From tests and survey it can be concluded that the use of mineral-based strengthening system can be effectively used to increase the load bearing capacity of the strengthened structure. The paper concludes with suggestions on further development in the field of mineral-based strengthening.
Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas
Authors: Walter Anne , Barysch Marjam J. , Behnke Silvia , Dziunycz Piotr , Schmid Bruno , Ritter Erika , Gnjatic Sacha , Kristiansen Glen , Moch Holger , Knuth Alexander , Dummer Reinhard , van den Broek Maries
Published: June 2010

Purpose: Nonmelanoma skin cancer is the most common cancer and comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of SCC increases drastically in immunosuppressed individuals, suggesting a critical role of the immune system in controlling SCC. To find an explanation for the selective immunosurveillance of SCC, we investigated the expression of cancer-testis (CT) antigens and MHC class I (MHC-I) and the infiltration by immune cells in BCC and SCC.

Experimental Design: We determined the expression of 23 different CT-antigens in 63 BCC and 40 SCC biopsies of immunocompetent and in 20 biopsies of immunosuppressed SCC patients by reverse transcription-PCR and immunohistochemistry. IgG responses to 36 tumor antigens were measured by Western blotting and ELISA. MHC-I expression and CD8+ T-cell infiltration were analyzed by immunohistochemistry in BCC and SCC of immunocompetent and immunosuppressed patients and in imiquimod-treated BCC patients.

Results: We found expression of at least one CT-antigen in 81% of BCC and in 40% of SCC. We did not detect CT-antigen–specific serum IgG. Most SCC, but not BCC, expressed MHC-I and were infiltrated with CD8+ cells. Imiquimod-treated BCC expressed MHC-I and were infiltrated by CD8+ T cells.

Conclusions: We propose that immunosurveillance controls SCC, but not BCC, because the latter lacks MHC-I. This fits with the increased incidence of SCC in immunosuppressed individuals and may explain the relatively low prevalence of CT-antigen expression in SCC as a result of CD8+ T-cell–driven immunoediting. Clin Cancer Res; 16(14); 3562–70. ©2010 AACR.
The Lack, Need, and Opportunities for Decision-Making and Informational Tools to Educate Primary-Care Physicians and Women about Breast Cancer Chemoprevention
Authors: Ravdin Peter M.
Published: June 2010

This perspective on Vogel et al. (beginning on page 696 in this issue of the journal) examines tamoxifen and raloxifene prescription patterns and why these agents are little used for breast cancer prevention despite their effectiveness in definitive trials, Food and Drug Administration approval, and American Society of Clinical Oncology Guidelines Committee endorsement for this purpose. The complexity of weighing the positive and negative aspects of the drugs and estimating net benefit is discussed, as is the need for informational resources such as interactive Internet-based tools to allow better individualized decisions about the options for chemoprevention. Cancer Prev Res; 3(6); 686–8. ©2010 AACR.
Spatiotemporal Distribution of PAX6 and MEIS2 Expression and Total Cell Numbers in the Ganglionic Eminence in the Early Developing Human Forebrain
Authors: Larsen Karen B. , Lutterodt Melissa C. , Laursen Henning , Græm Niels , Pakkenberg Bente , Møllgård Kjeld , Møller Morten
Published: June 2010

The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in nuclei of radial glia cells in the neocortical proliferative zones and controls the differentiation and neurogenetic fate of these cells in the dorsal telencephalon in rodents. Animal studies on the Meis2 gene have revealed expression in the developing telencephalon and Meis2 is known to regulate the expression of Pax6 in the eye and pancreas. Because of this functional relation between Pax6 and Meis2, we studied the spatial and temporal expression of PAX6, and MEIS2 using a developmental series of human fetal brains at 7–19 postconceptional weeks with emphasis on the forebrain to investigate whether the two genes are expressed in the same regions and zones in the same time window. We demonstrate by in situ hybridization and immunohistochemistry that the two homeobox genes are expressed during early fetal brain development in humans. PAX6 mRNA and protein were located in the proliferative zones of the neocortex and in single cells in the cortical preplate at 7 fetal weeks and in the developing cortical plate from 8 or 9 to 19 fetal weeks. The expression of PAX6 expanded into the ganglionic eminence just prior to the stage at which a stereological estimation showed an exponential rise in total cell number in this area. The MEIS2 gene was also present in the proliferative zones of the human fetal neocortex and a higher expression of MEIS2 than PAX6 was observed in these areas at 9 fetal weeks. Further, MEIS2 was expressed at a very high level in the developing ganglionic eminence and at a more moderate level in the cortical plate.
S-Adenosylmethionine Is Decreased in the Cerebrospinal Fluid of Patients with Alzheimer’s Disease
Authors: Linnebank Michael , Popp Julius , Smulders Yvo , Smith Desiree , Semmler Alexander , Farkas Melinda , Kulic Luka , Cvetanovska Gabriela , Blom Henk , Stoffel-Wagner Birgit , Kölsch Heike , Weller Michael , Jessen Frank
Published: June 2010

Background: Increased plasma homocysteine levels have been described as an independent risk factor for Alzheimer’s disease (AD), but the underlying pathophysiology is unclear. Objective: This single-center, cross-sectional, correlational study analyzed homocysteine metabolism in 60 AD patients and 60 control subjects. Methods: Fasting plasma levels of vitamin B12, folate and homocysteine as well as cerebrospinal fluid (CSF) levels of folate derivates, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine were measured. In addition, the apolipoprotein E (APOE) genotype was determined. Results: As expected, the APOE4 allele was significantly overrepresented in AD patients compared with controls (p < 0.001). Homocysteine plasma levels in the highest quartile were more frequent in the AD patients than in the controls (p = 0.008). In addition, AD patients had significantly lower CSF levels of the methyl group donor SAM (193 ± 31 vs. 207 ± 37 nmol/l; p = 0.032). Accordingly, the SAM/SAH ratio, which represents the methylation capacity, was significantly lower in the CSF of the AD patients (7.6 ± 2.4 vs. 9.1 ± 2.8; p = 0.003). Further, explorative analysis of all subjects showed that CSF SAM levels were lower in carriers of the APOE4 allele compared with noncarriers (189 ± 30 vs. 207 ± 36 nmol/l; p = 0.010). Of the individuals with CSF SAM levels in the lowest quartile, 63% carried the APOE4 allele compared with 17% of the individuals with CSF SAM levels in the highest quartile (Pearson: χ2 = 9.9; p = 0.002; odds ratio 0.126, 95% confidence interval 0.32–0.49). Conclusion: These data suggest that AD is associated with lower CSF SAM levels and that this is at least partly due to an association of the APOE4 allele with reduced SAM levels in the CSF.
ICF-Based Disability Survey in a Rural Population of Adults and Older Adults Living in Cinco Villas, Northeastern Spain: Design, Methods and Population Characteristics
Authors: de Pedro-Cuesta Jesús , Comín Comín Magdalena , Virués-Ortega Javier , Almazán Isla Javier , Avellanal Fuencisla , Alcalde Cabero Enrique , Burzaco Olga , Castellote Juan Manuel , Cieza Alarcos , Damián Javier , Forjaz Maria João , Frades Belén , Franco Esther , Larrosa Luis Alberto , Magallón Rosa , Martín García Gloria , Martínez Cristina , Martínez Martín Pablo , Pastor-Barriuso Roberto , Peña Jiménez Ana , Población Martínez Adolfo , Reed Geoffrey , Ruíz Cristina
Published: June 2010

Background: This article describes the methods of a door-to-door screening survey exploring the distribution of disability and its major determinants in northeastern Spain. This study will set the basis for the development of disability-related services for the rural elderly in northeastern Spain. Methods: The probabilistic sample was composed of 1,354 de facto residents from a population of 12,784 Social Security card holders (age: ≧50 years). Cognitive and disability screenings were conducted (period: June 2008–June 2009). Screening instruments were the MMSE and the World Health Organization Disability Assessment Schedule. Participants screened positive for disability underwent an assessment protocol focusing on primary care diagnoses, disability, lifestyle, and social and health service usage. Participants screened positive for cognitive functioning went through in-depth neurological evaluation. Results: The study sample is described. Usable data were available for 1,216 participants. A total of 625 individuals (51.4%) scored within the positive range in the disability screening, while 135 (11.1%) scored within the positive range of the cognitive screening. The proportion of positively screened individuals was higher for women and increased with age. Conclusions: Screening surveys represent a feasible design for examining the distribution of disability and its determinants among the elderly. Data quality may benefit from methodological developments tailored to rural populations with a low education level.
Recanalization within One Hour after Intravenous Tissue Plasminogen Activator Is Associated with Favorable Outcome in Acute Stroke Patients
Authors: Kimura Kazumi , Iguchi Yasuyuki , Shibazaki Kensaku , Aoki Junya , Watanabe Masao , Kobayashi Kazuto , Sakamoto Yuki
Published: June 2010

Background/Aim: Early recanalization after tissue plasminogen activator (t-PA) infusion greatly improves outcome in stroke patients. However, the time threshold of early recanalization for a favorable outcome remains unclear. The aim of this study was to assess patient outcome 3 months after t-PA therapy among patients with early, delayed and without recanalization. Methods: Consecutive patients with major brain artery occlusion on magnetic resonance angiography (MRA) before t-PA infusion were enrolled. We divided the patients into 3 groups according to the findings of follow-up MRA 1 and 24 h after t-PA: the early group who had recanalization within 1 h after t-PA; the delayed group who had recanalization between 1 and 24 h, and the no recanalization group. We then assessed the outcomes (modified Rankin score 0–1) 3 months after t-PA therapy among the 3 groups. Results: A total of 92 patients (53 men, mean age 75.8 ± 10.3 years) were enrolled. A favorable outcome was most frequently observed in the early group (n = 39, 40.6%), followed by the delayed group (n = 25, 18.2%), and the no recanalization group (n = 28, 10.5%; p = 0.037). After adjusting for age, atrial fibrillation and NIHSS score, the adjusted OR for early recanalization when compared with no recanalization was 7.11 (95% CI 1.177–43.063; p = 0.032) for a favorable outcome, while the adjusted OR for delayed recanalization was 1.75 (95% CI 0.104–29.356; p = 0.698). Conclusion: Early recanalization within 1 h after intravenous t-PA is associated with a favorable outcome in stroke patients.
Effect of Topical Application of Virgin Coconut Oil on Skin Components and Antioxidant Status during Dermal Wound Healing in Young Rats
Authors: Nevin K.G. , Rajamohan T.
Published: June 2010

Objectives: The present study was undertaken to evaluate the effect of a topical application of virgin coconut oil (VCO) on excision wounds in young rats. Methods: Three sets of experiments with 3 groups of female Sprague-Dawley rats each consisting of 6 animals were used for studying wound closure time, antioxidant status and biochemical parameters. Group 1 was the control; groups 2 and 3 were treated with 0.5 and 1.0 ml VCO, respectively, 24 h after wound creation for 10 days. After the experimental period, the healing property of VCO was evaluated by monitoring the time taken for complete epithelization as well as levels of various parameters of the wound’s granulation tissue. The collagen solubility pattern, glycohydrolase activity, and histopathology of the granulation tissue were also analyzed. The antioxidant status during wound healing was monitored continuously for 14 days. Results: VCO-treated wounds healed much faster, as indicated by a decreased time of complete epithelization and higher levels of various skin components. Pepsin-soluble collagen showed a significant increase in VCO- treated wounds, indicating a higher collagen cross-linking. Glycohydrolase activities were also found to be increased due to a higher turnover of collagen. Antioxidant enzyme activities, and reduced glutathione and malondialdehyde levels were found to be increased on the 10th day after wounding, which were found to have returned to normal levels on day 14 in the treated wounds. The lipid peroxide levels were found to be lower in the treated wounds. A histopathological study showed an increase in fibroblast proliferation and neovascularization in VCO-treated wounds compared to controls. Conclusion: The beneficial effect of VCO can be attributed to the cumulative effect of various biologically active minor components present in it.
The London APP Mutation (Val717Ile) Associated with Early Shifting Abilities and Behavioral Changes in Two Italian Families with Early-Onset Alzheimer’s Disease
Authors: Talarico G. , Piscopo P. , Gasparini M. , Salati E. , Pignatelli M. , Pietracupa S. , Malvezzi-Campeggi L. , Crestini A. , Boschi S. , Lenzi G.L. , Confaloni A. , Bruno G.
Published: June 2010

Background/Aims: Mutations in the amyloid precursor protein gene were the first to be recognized as a cause of Alzheimer’s disease (AD). Methods: We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation. Results: In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far. Two subjects of the other family with AD diagnosis were carriers of the same mutation. Conclusion: All AD subjects showed a cognitive profile characterized by early impairment in long-term memory, shifting abilities and affective symptoms beginning in the fifth decade of life.
Reductions in Platelet 18-kDa Translocator Protein Density Are Associated with Adult Separation Anxiety in Patients with Bipolar Disorder
Authors: Abelli Marianna , Chelli Beatrice , Costa Barbara , Lari Lisa , Cardini Alessandra , Gesi Camilla , Muti Matteo , Lucacchini Antonio , Martini Claudia , Cassano Giovanni B. , Pini Stefano
Published: June 2010

Background: Recent studies indicate that adult separation anxiety disorder is a discrete diagnostic entity and worthy of attention. Previously, we found a significant association between platelet expression of the 18-kDa translocator protein (TSPO) and adult separation anxiety in patients with panic disorder or major depression. The aim of this study was to explore whether adult separation anxiety might be a factor differentiating TSPO expression in a sample of patients with bipolar disorder. Methods: The equilibrium binding parameters of the specific TSPO ligand [3H]PK 11195 were estimated on the platelet membranes of 24 adult outpatients with a DSM-IV diagnosis of bipolar disorder (with or without separation anxiety disorder) and 14 healthy controls. Patients were assessed by SCID-I, HAM-D, YMRS, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation Anxiety Self-Report Checklist (ASA-27). Results: A significant reduction in mean platelet TSPO density was found in bipolar patients with respect to controls. However, the lower density was only evident in the subgroup of bipolar patients who also fulfilled DSM-IV criteria for adult separation anxiety disorder. Individual TSPO density values correlated significantly and negatively with both SCI-SAS-A and ASA-27 total scores. Conclusions: TSPO expression may be a useful biological marker of adult separation anxiety co-occurring with other anxiety and mood disorders, including bipolar disorder.