bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyamine transport is mediated by both endocytic and solute carrier transport mechanisms in the gastrointestinal tract
Authors: Uemura Takeshi , Stringer David E. , Blohm-Mangone Karen A. , Gerner Eugene W.
Published: June 2010

The polyamines spermidine and spermine, and their precursor putrescine, are required for cell growth and cellular functions. The high levels of tissue polyamines are implicated in carcinogenesis. The major sources of exogenous polyamines are diet and intestinal luminal bacteria in gastrointestinal (GI) tissues. Both endocytic and solute carrier-dependent mechanisms have been described for polyamine uptake. Knocking down of caveolin-1 protein increased polyamine uptake in colon cancer-derived HCT116 cells. Dietary supplied putrescine was accumulated in GI tissues and liver in caveolin-1 knockout mice more than wild-type mice. Knocking out of nitric oxide synthase (NOS2), which has been implicated in the release of exogenous polyamines from internalized vesicles, abolished the accumulation of dietary putrescine in GI tissues. Under conditions of reduced endogenous tissue putrescine contents, caused by treatment with the polyamine synthesis inhibitor difluoromethylornithine (DFMO), small intestinal and colonic mucosal polyamine contents increased with dietary putrescine levels, even in mice lacking NOS2. Knocking down the solute carrier transporter SLC3A2 in HCT116-derived Hkh2 cells reduced the accumulation of exogenous putrescine and total polyamine contents in DFMO treated cells, relative to non-DFMO-treated cells. These data demonstrate that exogenous putrescine is transported into GI tissues by caveolin-1- and NOS2-dependent mechanisms, but that the solute carrier transporter SLC3A2 can function bidirectionally to import putrescine under conditions of low tissue polyamines.
Muscle protein breakdown has a minor role in the protein anabolic response to essential amino acid and carbohydrate intake following resistance exercise
Authors: Glynn Erin L. , Fry Christopher S. , Drummond Micah J. , Dreyer Hans C. , Dhanani Shaheen , Volpi Elena , Rasmussen Blake B.
Published: June 2010

Muscle protein breakdown (MPB) is increased following resistance exercise, but ingestion of carbohydrate during postexercise recovery can decrease MPB with no effect on muscle protein synthesis (MPS). We sought to determine whether a combination of essential amino acids (EAA) with low carbohydrate or high carbohydrate could effectively reduce MPB following resistance exercise and improve muscle protein net balance (NB). We hypothesized that higher levels of carbohydrate and resulting increases in circulating insulin would inhibit MPB and associated signaling, resulting in augmented NB. Thirteen male subjects were assigned to one of two groups receiving equivalent amounts of EAA (∼20 g) but differing carbohydrate levels (low = 30, high = 90 g). Groups ingested nutrients 1 h after an acute bout of leg resistance exercise. Leg phenylalanine kinetics (e.g., MPB, MPS, NB), signaling proteins, and mRNA expression were assessed on successive muscle biopsies using stable isotopic techniques, immunoblotting, and real-time quantitative PCR, respectively. MPB tended to decrease ( P < 0.1) and MPS increased ( P < 0.05) similarly in both groups following nutrient ingestion. No group differences were observed, but muscle ring finger 1 (MuRF1) protein content and MuRF1 mRNA expression increased following resistance exercise and remained elevated following nutrient ingestion, while autophagy marker (light-chain 3B-II) decreased after nutrient ingestion ( P < 0.05). Forkhead box-O3a phosphorylation, total muscle atrophy F-box (MAFbx) protein, and MAFbx and caspase-3 mRNA expression were unchanged. We conclude that the enhanced muscle protein anabolic response detected when EAA+carbohydrate are ingested postresistance exercise is primarily due to an increase in MPS with minor changes in MPB, regardless of carbohydrate dose or circulating insulin level.
Genome duplication events have led to a diversification in the CPT I gene family in fish
Authors: Morash Andrea J. , Le Moine Christophe M. R. , McClelland Grant B.
Published: June 2010

The enzyme carnitine palmitoyltransferase (CPT) I is a major regulator of mitochondrial fatty acid oxidation in vertebrates. Numerous genome duplication events throughout evolution have given rise to three (in mammals) or multiple (in fish) genetically and functionally different isoforms of this enzyme. In particular, these isoforms represent a diversification of kinetic and regulatory properties stemming from mutations at the genomic and proteomic levels. Phylogenetic reconstructions reveal a comprehensive view of the CPT I family in vertebrates and genomic modifications leading to structural changes in proteins and functional differences between tissues and taxa. In a model fish species (rainbow trout), the presence of five CPT I isoforms suggests repeated duplication events in bony fishes and salmonids. Subsequently, an array of nucleotide and amino acid substitutions in the isoforms may contribute to a tissue-specific and a previously observed species-specific difference in the IC50for malonyl-CoA. Moreover, all five isoforms are expressed in trout at the mRNA level in skeletal muscle, heart, liver, kidney, and intestine. In general, transcript levels of the β-isoforms were higher in muscle tissues, while levels of the α-isoforms were higher in other tissues. Rainbow trout also exhibit developmental plasticity in relative mRNA expression of CPT I isoforms from fry to juvenile to adult stage. Thus the evolution of CPT I has resulted in a very diverse family of isoforms. These differences represent a degree of specificity in the ability of species to regulate function at the protein and tissue levels, which, in turn, may allow for precise control of lipid oxidation in individual tissues during physiological perturbations.
Uremia induces abnormal oxygen consumption in tubules and aggravates chronic hypoxia of the kidney via oxidative stress
Authors: Palm Fredrik , Nangaku Masaomi , Fasching Angelica , Tanaka Tetsuhiro , Nordquist Lina , Hansell Peter , Kawakami Takahisa , Nishijima Fuyuhiko , Fujita Toshiro
Published: June 2010

In addition to causing uremic symptoms, uremic toxins accelerate the progression of renal failure. To elucidate the pathophysiology of uremic states, we investigated the effect of indoxyl sulfate (IS), a representative uremic toxin, on oxygen metabolism in tubular cells. We demonstrated an increase in oxygen consumption by IS in freshly isolated rat and human proximal tubules. Studies utilizing ouabain, the Na-K-ATPase inhibitor, and apocynin, the NADPH oxidase inhibitor, as well as the in vivo gene-silencing approach to knock down p22phox showed that the increase in tubular oxygen consumption by IS is dependent on Na-K-ATPase and oxidative stress. We investigated whether the enhanced oxygen consumption led to subsequent hypoxia of the kidney. An increase in serum IS concentrations in rats administered indole was associated with a decrease in renal oxygenation (8 h). The remnant kidney in rats developed hypoxia at 16 wk. Treatment of the rats with AST-120, an oral adsorbent that removes uremic toxins, reduced serum IS levels and improved oxygenation of the kidney. Amelioration of hypoxia in the remnant kidney was associated with better renal functions and less histological injury. Reduction of serum IS levels also led to a decrease in oxidative stress in the kidney. Our ex vivo and in vivo studies implicated that uremic states may deteriorate renal dysfunction via dysregulating oxygen metabolism in tubular cells. The abnormal oxygen metabolism in tubular cells by uremic toxins was, at least in part, mediated by oxidative stress.
Partial weight suspension: a novel murine model for investigating adaptation to reduced musculoskeletal loading
Authors: Wagner Erika B. , Granzella Nicholas P. , Saito Hiroaki , Newman Dava J. , Young Laurence R. , Bouxsein Mary L.
Published: June 2010

We developed a new model of hypodynamic loading to support mice in chronic conditions of partial weight bearing, enabling simulations of reduced gravity environments and related clinical conditions. The novel hardware allows for reduced loading between 10 and 80% of normal body weight on all four limbs and enables characteristic quadrupedal locomotion. Ten-week-old female BALB/cByJ mice were supported for 21 days under Mars-analog suspension (38% weight bearing) and compared with age-matched and jacketed (100% weight bearing) controls. After an initial adaptation, weight gain did not differ between groups, suggesting low levels of animal stress. Relative to age-matched controls, mice exposed to Mars-analog loading had significantly lower muscle mass (−23% gastrocnemius wet mass, P < 0.0001); trabecular and cortical bone morphology (i.e., trabecular bone volume: −24% at the distal femur, and cortical thickness: −11% at the femoral midshaft, both P < 0.001); and biomechanical properties of the femoral midshaft (i.e., −27% ultimate moment, P < 0.001). Bone formation indexes were decreased compared with age-matched full-weight-bearing mice, whereas resorption parameters were largely unchanged. Singly housed, full-weight-bearing controls with forelimb jackets were largely similar to age-matched, group-housed controls, although a few variables differed and warrant further investigation. Altogether, these data provide strong rationale for use of our new model of partial weight bearing to further explore the musculoskeletal response to reduced loading environments.
Local thermal control of the human cutaneous circulation
Authors: Johnson John M. , Kellogg Dean L.
Published: June 2010

The level of skin blood flow is subject to both reflex thermoregulatory control and influences from the direct effects of warming and cooling the skin. The effects of local changes in temperature are capable of maximally vasoconstricting or vasodilating the skin. They are brought about by a combination of mechanisms involving endothelial, adrenergic, and sensory systems. Local warming initiates a transient vasodilation through an axon reflex, succeeded by a plateau phase due largely to nitric oxide. Both phases are supported by sympathetic transmitters. The plateau phase is followed by the die-away phenomenon, a slow reversal of the vasodilation that is dependent on intact sympathetic vasoconstrictor nerves. The vasoconstriction with local skin cooling is brought about, in part, by a postsynaptic upregulation of α2c-adrenoceptors and, in part, by inhibition of the nitric oxide system at at least two points. There is also an early vasodilator response to local cooling, dependent on the rate of cooling. The mechanism for that transient vasodilation is not known, but it is inhibited by intact sympathetic vasoconstrictor nerve function and by intact sensory nerve function.
Comparison of Measurements of Autoantibodies to Glutamic Acid Decarboxylase and Islet Antigen-2 in Whole Blood Eluates from Dried Blood Spots Using the RSR-Enzyme Linked Immunosorbent Assay Kits and In-House Radioimmunoassays
Authors: Persson Anders , Becker Charlotte , Hansson Ida , Nilsson Anita , Törn Carina
Published: June 2010

To evaluate the performance of dried blood spots (DBSs) with subsequent analyses of glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A) with the RSR-ELISAs, we selected 80 children newly diagnosed with type 1 diabetes and 120 healthy women. DBSs from patients and controls were used for RSR-ELISAs while patients samples were analysed also with in-house RIAs. The RSR-ELISA-GADA performed well with a specificity of 100%, albeit sensitivity (46%) was lower compared to in RIA (56%;P=.008). No prozone effect was observed after dilution of discrepant samples. RSR-ELISA-IA-2A achieved specificity of 69% and sensitivity was lower (59%) compared with RIA (66%;P<.001). Negative or low positive patients and control samples in the RSR-ELISA-IA-2A increased after dilution. Eluates from DBS can readily be used to analyse GADA with the RSR-ELISA, even if low levels of autoantibodies were not detected. Some factor could disturb RSR-ELISA-IA-2A analyses.
Literature-Based Discovery of IFN-γand Vaccine-Mediated Gene Interaction Networks
Authors: Özgür Arzucan , Xiang Zuoshuang , Radev Dragomir R. , He Yongqun
Published: June 2010

Interferon-gamma (IFN-γ) regulates various immune responses that are often critical for vaccine-induced protection. In order to annotate the IFN-γ-related gene interaction network from a large amount of IFN-γresearch reported in the literature, a literature-based discovery approach was applied with a combination of natural language processing (NLP) and network centrality analysis. The interaction network of human IFN-γ(Gene symbol: IFNG) and its vaccine-specific subnetwork were automatically extracted using abstracts from all articles in PubMed. Four network centrality metrics were further calculated to rank the genes in the constructed networks. The resulting generic IFNG network contains 1060 genes and 26313 interactions among these genes. The vaccine-specific subnetwork contains 102 genes and 154 interactions. Fifty six genes such as TNF, NFKB1, IL2, IL6, and MAPK8 were ranked among the top 25 by at least one of the centrality methods in one or both networks. Gene enrichment analysis indicated that these genes were classified in various immune mechanisms such as response to extracellular stimulus, lymphocyte activation, and regulation of apoptosis. Literature evidence was manually curated for the IFN-γrelatedness of 56 genes and vaccine development relatedness for 52 genes. This study also generated many new hypotheses worth further experimental studies.
Existence of Concave Positive Solutions for Boundary Value Problem of Nonlinear Fractional Differential Equation with p‐Laplacian Operator
Authors: Wang Jinhua , Xiang Hongjun , Liu ZhiGang
Published: June 2010

We consider the existence and multiplicity of concave positive solutions for boundary value problem of nonlinear fractional differential equation with p‐Laplacian operator , 0 < t < 1, u(0) = u′(1) = 0, u′′(0) = 0, , where 0 < γ < 1, 2 < α < 3, 0 < ρ ⩽ 1, denotes the Caputo derivative, and f : [0,1]×[0, +∞) × R → [0, +∞) is continuous function, ϕp(s) = |s|p−2s, p > 1,  (ϕp) −1 = ϕq, 1/p + 1/q = 1. By using fixed point theorem, the results for existence and multiplicity of concave positive solutions to the above boundary value problem are obtained. Finally, an example is given to show the effectiveness of our works.
An In Vitro Comparison of Different Diagnostic Methods in Detection of Residual Dentinal Caries
Authors: Unlu Nimet , Ermis Rabia Banu , Sener Sevgi , Kucukyilmaz Ebru , Cetin Ali Riza
Published: June 2010

The aim of this study was to investigate the efficiency of different diagnostic methods in detection of residual dentinal caries in excavated cavities. Fifty extracted molar with deep dentinal carious lesions were excavated using a slow-speed handpiece. All cavities were assessed by laser fluorescence(LF) device, electronic caries monitor(ECM), and caries detector dye(CDD) by three independent observers blindly. The measurements were repeated after two weeks. Specimens containing dentin slices 150 μm in thickness were prepared for histological analyses. The existence and absence of carious dentin was determined using a lightmicroscope. The average intraobserver accuracy was 1.00 (perfect agreement) for CDD, 0.86 (excellent agreement) for ECM, and 0.50 (good agreement) for LF. The average interobserver accuracy values were 0.92 (excellent agreement), (0.36 marginal agreement) and 0.48 (good agreement), for CDD, ECM, and LF, respectively. The average specificity was 0.60 for CDD, 73% for ECM, and 0.50 for LF. The average sensitivity was 0.55 for CDD, 0.85 for LF, and 0.47 for ECM. The average accuracy values were 0.53, 0.51, and 0.81 for CDD, ECM, and LF, respectively. LF had the greatest sensitivity and accuracy values of any of the methods tested. As a conclusion, LF device is appeared to most reliable method in detection of remain caries in cavity. However, because of its technical sensitivity it may susceptible to variations in measurements. To pay attention to the rule of usage and repeated measurements can minimize such variations in clinical practice. It was concluded that LF is an improvement on the currently available aids for residual caries detection.
How Can Brain Learn to Control a Nonholonomic System?
Authors: Homma Noriyasu , Kato Shinpei , Goto Takakuni , Bukovsky Ivo , Kawashima Ryuta , Yoshizawa Makoto
Published: June 2010

Humans can often conduct both linear and nonlinear control tasks after a sufficient number of trials, even if they initially do not have sufficient knowledge about the system's dynamics and the way to control it. Theoretically, it is well known that some nonlinear systems cannot be stabilized asymptotically by any linear controllers and we have reported by an f-MRI experiment that different types of information may be involved in linear and nonlinear control tasks, respectively, from a brain function mapping point of view. In this paper, from a controllability analysis, we still show a possibility that human may use a linear control scheme for such nonlinear control tasks by switching the linear controllers with a virtual constraint. It is suggested that the proposed virtual constraint can play an important role to overcome a limitation of the linear controllers and to mimic human control behavior.
Sperm DNA Integrity in Men Treated for Childhood Cancer
Authors: Romerius Patrik , Ståhl Olof , Moëll Christian , Relander Thomas , Cavallin-Ståhl Eva , Gustafsson Helen , Löfvander Thapper Kerstin , Jepson Katarina , Spanò Marcello , Wiebe Thomas , Lundberg Giwercman Yvonne , Giwercman Aleksander
Published: June 2010

Purpose: It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account.

Experimental Design: In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay.

Results: In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), −0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6–10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083–5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1–4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3–18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given.

Conclusions: DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring. Clin Cancer Res; 16(15); 3843–50. ©2010 AACR.
Long-term Follow-up in Cancer Prevention Trials (It Ain't Over 'Til It's Over)
Authors: Cuzick Jack
Published: June 2010

The update of the Study of Tamoxifen and Raloxifene by Vogel et al. (beginning on p. 696 in this issue of the journal) highlights the overall importance of long-term follow-up of cancer prevention trials, which need long follow-up to fully determine agent risks and benefits. Biomarkers (e.g., reduced cervical intraepithelial neoplasia 3 after human papillomavirus vaccination) can provide an early indication of efficacy but almost never replace the cancer end point in determining the ultimate utility of an agent. Long follow-up is also important to fully determine preventive benefit, as illustrated by the tamoxifen trials, where only 60% as many treated women were needed to prevent one cancer at 10 years as at approximately 5 years, the time of the early reports. Cancer Prev Res; 3(6); 689–91. ©2010 AACR.
Prevalence of Migraine, Probable Migraine and Tension-Type Headache in the Croatian Population
Authors: Vuković Vlasta , Plavec Davor , Pavelin Sanda , Jančuljak Davor , Ivanković Mira , Demarin Vida
Published: June 2010

Background/Aim: Population-based epidemiological studies about headaches, especially migraine, have been carried out in many countries. The aim of this study was to assess the 1-year prevalence of migraine, probable migraine and tension-type headache (TTH) in the Croatian population. Methods: The design of the study was a cross-sectional survey of an adult population sample using a self-completed questionnaire. Results: The 1-year crude prevalence of migraine without and with aura in this study was 7.5%, of probable migraine 11.3%, and of TTH 21.2%. The 1-year age- and sex-adjusted prevalence of migraine was 6.2%, of probable migraine 8.8%, and of TTH 20.7%; the prevalence of migraine combined with probable migraine was 15.0%. Total crude prevalence of headache (combination of migraine, probable migraine and TTH) was 39.9%. Prevalence of migraine was higher in continental than in Mediterranean areas of Croatia. Multivariate regression analysis showed that the highest risk of suffering from any kind of headache is observed for the following people: living in Dubrovnik, being female, having elementary or high school education, being married, employed and living in an urban or suburban area. Conclusion: The prevalence of migraine and probable migraine is similar as in other Western countries. Certain demographic characteristics differ among patients with and without headache.
Interaction of Epicutaneously Applied Lipids with Stratum Corneum Depends on the Presence of either Emulsifiers or Hydrogenated Phosphatidylcholine
Authors: Wohlrab J. , Klapperstück T. , Reinhardt H.-W. , Albrecht M.
Published: June 2010

The barrier function of the stratum corneum (SC) significantly determines the interaction of epicutaneously applied substances with the skin organ. Although the exact molecular processes are still unclear, it is undoubted that the intercellular lipid composition and order of the SC is significantly involved in this interaction. Topically substituted phases, especially those of lipophilic composition, seem to interact very intensely with lipid membranes; they can be integrated, form separate phases, or even permeate through the SC into the viable skin. The latter is not desired, especially in barrier-protective preparations with a lipophilic phase. The present paper investigates the penetration behavior of topically applied, DiI-labeled lipids into human ex vivo skin depending on the phase organization of different o/w emulsifiers compared to emulsifier-free preparations containing hydrogenated phosphatidylcholine by means of fluorescence indication. Results are presented for intact and defined damaged epidermal barrier. In addition, the washout effect based on skin samples treated by artificial watering after lipid incubation, and the influence of the phase transition temperature of the SC membrane were studied. The results show that in intact and damaged skin, the penetration depth of the lipids increases directly proportionally with the hydrophilic-lipophilic balance (HLB value), while the washout effect and the HLB value proved to be inversely related. An increase in penetration depth with higher HLB values was also apparent when the phase transition temperature of the physiological membranes was exceeded. Altogether, the results clearly demonstrate that the characteristics of the emulsifying phase of a preparation significantly determine the interaction of a substituted lipophilic phase with the SC. Especially bipolar lipids, like phosphatidylcholines, showed intradermal dispersion patterns which hint at an especially intense interaction with physiological membranes.
Diagnostic Impact of CSF Biomarkers in a Local Hospital Memory Clinic
Authors: Kester Maartje I. , Boelaarts Leo , Bouwman Femke H. , Vogels Raymond L. , Groot Erwin R. , van Elk Evert J. , Blankenstein Marinus A. , van der Flier Wiesje M. , Scheltens Philip
Published: June 2010

Background: CSF biomarkers amyloid-β 1–42 (Aβ42), total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) are useful diagnostic markers for Alzheimer’s disease (AD). We examined the impact of these biomarkers in the diagnostic process in a non-academic memory clinic. Methods: One hundred and nine patients with available CSF were included from the local hospital memory clinic. Initially, patients were clinically diagnosed, and the clinician indicated their confidence in the diagnosis. Next the CSF results were presented, and the clinician re-evaluated his initial diagnosis. The main outcomes were changes in initial diagnosis and diagnostic confidence. Results: Forty-seven patients were initially diagnosed with AD, 26 were diagnosed with another type of dementia, 18 were diagnosed with mild cognitive impairment, and 18 received a non-dementia diagnosis. All biomarkers distinguished between AD and non-dementia (p < 0.01); tau and ptau-181 also distinguished AD from other types of dementia (p < 0.001). After CSF biomarker levels were revealed, 11 diagnoses changed. In 31% of the diagnoses, the clinician gained confidence, while in 10% confidence decreased. Conclusion: We found that knowledge of CSF biomarker profiles changed the diagnosis in 10% of the cases, and confidence in the diagnosis increased for one third of the patients.
Urinary Pigment Epithelium-Derived Factor as a Marker of Diabetic Nephropathy
Authors: Chen Haibing , Zheng Zhi , Li Rongxia , Lu Junxi , Bao Yuqian , Ying Xiafang , Zeng Rong , Jia Weiping
Published: June 2010

Background: Pigment epithelium-derived factor (PEDF), a serine protease inhibitor, regulates extracellular matrix production in the kidney. We sought the association between urinary PEDF (uPEDF) and development of nephropathy among patients with type 2 diabetes (T2DM). Methods: Two human studies were performed in which uPEDF was determined by ELISA. These studies included (1) a cross-sectional study of T2DM (n = 228) and healthy controls (n = 49) and (2) a longitudinal study of hypertensive T2DM with microalbuminuria (MA; n = 42) treated with irbesartan for 6 months. An animal study was performed in which PEDF was measured in the kidney and urine samples of control rats, rats rendered diabetic with streptozotocin that were also fed a high-fat diet, and diabetic rats treated with irbesartan for 3 months. Results: Cross-sectional study: compared to controls, uPEDF was significantly higher in patients with diabetic nephropathy. uPEDF independently correlated with MA. In the MA group, uPEDF in patients with diabetic retinopathy was significantly higher than that in patients without diabetic retinopathy. Longitudinal study: irbesartan significantly decreased uPEDF in T2DM with MA. Animal study: in diabetic rats, increased PEDF was observed in both the urine and kidney samples. uPEDF showed a significant correlation with the expression of PEDF in the kidney. Irbesartan could significantly decrease the PEDF expression in the kidneys of diabetic rats as well as uPEDF. Conclusion: uPEDF may serve as a novel marker for screening for nephropathy among patients with T2DM and monitoring the response to therapy.
Comparison of Risperidone Orodispersible Tablet and Intramuscular Haloperidol in the Treatment of Acute Psychotic Agitation: A Randomized Open, Prospective Study
Authors: Lim Hyun Kook , Kim Jung Jin , Pae Chi Un , Lee Chang Uk , Lee Chul , Paik In Ho
Published: June 2010

Objectives: Psychotic agitation of psychiatric patients is a common manifestation that needs emergent management. Traditionally, parenteral or intramuscular injection of antipsychotics was conducted for treatment of psychotic agitation. Considering that the rapidly absorbed form of risperidone (risperidone orodispersible tablet) could be used for the agitated patient, comparison of oral risperidone and intramuscular haloperidol was performed in emergency treatment of psychotic agitation in this study. Methods: 124 patients with psychotic agitation were recruited at the emergency room or inpatient ward. They were randomly assigned to either the group of oral risperidone or intramuscular haloperidol. Efficacy of both treatments was measured and compared using the 5-item acute agitation cluster from the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and the Clinical Global Impression-Severity of Illness Scale (CGI-S). Tolerability and safety were also compared between the two groups. Results: The PANSS-EC and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by group interaction effect (F = 459.7, p < 0.0001). There were no serious adverse events in both groups. Conclusion: For the emergency treatment of psychotic agitation, risperidone orodispersible tablet was as effective and tolerable as intramuscular administration of haloperidol. Therefore, we might choose oral medication instead of intramuscular injection for treatment of patients with acute psychotic agitation.
A Symptom-Specific Analysis of the Effect of High-Frequency Left or Low-Frequency Right Transcranial Magnetic Stimulation over the Dorsolateral Prefrontal Cortex in Major Depression
Authors: Rossini D. , Lucca A. , Magri L. , Malaguti A. , Smeraldi E. , Colombo C. , Zanardi R.
Published: June 2010

Background: We have investigated the efficacy of high-frequency left (HFL) versus low-frequency right (LFR) repetitive transcranial magnetic stimulation (rTMS) in depression, focusing on specific symptoms as possible predictors of outcome for these two different types of stimulation. Method: Seventy-four outpatients with a major depressive episode treated with an adequate antidepressant dosage for at least 4 weeks were included in our study and randomly assigned to two different groups: HFL or LFR rTMS. The Hamilton Rating Scale for Depression (HAM-D) items were pooled into 6 factors to evaluate specific symptoms as possible predictors of response. Results: Twenty-one out of 32 patients (65.6%) and 24 out of 42 patients (57.1%) were responders in the HFL and LFR groups, respectively. No significant difference in response rate was observed. Considering the whole sample, we found an inverse correlation between activity and HAM-D score reduction and a significant positive relation between somatic anxiety and outcome. An inverse correlation between psychic anxiety and HAM-D score reduction emerged considering the HFL group. In the LFR group, there was a significant negative relationship between baseline activity and the outcome. Conclusion: These findings support the hypothesis that LFR rTMS could be as effective as HFL rTMS and more suitable for patients with a higher anxiety degree, particularly in bipolar patients.
Membrane Cholesterol Depletion by Methyl-β-Cyclodextrin Enhances the Expression of Cardiac Differentiation Markers
Authors: Pontes Soares Carolina , Portilho Débora Morueco , da Silva Sampaio Luzia , Einicker-Lamas Marcelo , Morales Marcelo Marcos , Costa Manoel Luis , dos Santos Mermelstein Cláudia
Published: June 2010

Cholesterol is a sterol lipid that plays pleiotropic roles in the plasma membrane; it is involved in maintaining membrane fluidity and permeability and the structure of lipid microdomains. Despite its importance, the consequences of membrane cholesterol depletion during cardiac differentiation have not been described. Therefore, we investigated the cellular and molecular mechanisms associated with cholesterol depletion in cultures of chick cardiac cells. We used methyl-β-cyclodextrin (MCD) to deplete membrane cholesterol and investigate its role in cardiac differentiation by following the expression of several markers including the transcriptional factor Nkx2.5, the myofibrillar protein tropomyosin, the cytoskeletal intermediate filament protein desmin, the caveolar protein caveolin-3, the cadherin/β-catenin adhesion complex, and the junctional protein connexin 43. Confocal microscopy showed that desmin-positive cells were located more externally in the aggregates in relation to the more internally located caveolin-3-positive cells. Desmin and caveolin-3 were co-localized in filamentous structures in the subsarcolemmal region of well-spread cells outside the aggregates. β-Catenin was concentrated in regions of cell-cell contact, and tropomyosin in sarcomeric structures. Western blot tests showed that immediately following cholesterol depletion, there was a slight decrease in the expression of caveolin-3 and desmin, and at the same time there was a sharp increase in the expression of cadherin, tropomyosin, Nkx2.5 and connexin 43. Further, we found an increase in the expression of cardiac β-myosin heavy chain 7, a marker of the cardiac hypertrophic phenotype. These observations suggest that membrane cholesterol plays a significant role in regulating cardiomyocyte differentiation.
Changes in Events Alter How People Remember Recent Information
Authors: Swallow Khena M. , Barch Deanna M. , Head Denise , Maley Corey J. , Holder Derek , Zacks Jeffrey M.
Published: June 2010

Observers spontaneously segment larger activities into smaller events. For example, “washing a car” might be segmented into “scrubbing,” “rinsing,” and “drying” the car. This process, called event segmentation, separates “what is happening now” from “what just happened.” In this study, we show that event segmentation predicts activity in the hippocampus when people access recent information. Participants watched narrative film and occasionally attempted to retrieve from memory objects that recently appeared in the film. The delay between object presentation and test was always 5 sec. Critically, for some of the objects, the event changed during the delay whereas for others the event continued. Using fMRI, we examined whether retrieval-related brain activity differed when the event changed during the delay. Brain regions involved in remembering past experiences over long periods, including the hippocampus, were more active during retrieval when the event changed during the delay. Thus, the way an object encountered just 5 sec ago is retrieved from memory appears to depend in part on what happened in those 5 sec. These data strongly suggest that the segmentation of ongoing activity into events is a control process that regulates when memory for events is updated.
Cardiorespiratory Fitness and the Flexible Modulation of Cognitive Control in Preadolescent Children
Authors: Pontifex Matthew B. , Raine Lauren B. , Johnson Christopher R. , Chaddock Laura , Voss Michelle W. , Cohen Neal J. , Kramer Arthur F. , Hillman Charles H.
Published: June 2010

The influence of cardiorespiratory fitness on the modulation of cognitive control was assessed in preadolescent children separated into higher- and lower-fit groups. Participants completed compatible and incompatible stimulus–response conditions of a modified flanker task, consisting of congruent and incongruent arrays, while ERPs and task performance were concurrently measured. Findings revealed decreased response accuracy for lower- relative to higher-fit participants with a selectively larger deficit in response to the incompatible stimulus–response condition, requiring the greatest amount of cognitive control. In contrast, higher-fit participants maintained response accuracy across stimulus–response compatibility conditions. Neuroelectric measures indicated that higher-fit, relative to lower-fit, participants exhibited global increases in P3 amplitude and shorter P3 latency, as well as greater modulation of P3 amplitude between the compatible and incompatible stimulus–response conditions. Similarly, higher-fit participants exhibited smaller error-related negativity (ERN) amplitudes in the compatible condition, and greater modulation of the ERN between the compatible and incompatible conditions, relative to lower-fit participants who exhibited large ERN amplitudes across both conditions. These findings suggest that lower-fit children may have more difficulty than higher-fit children in the flexible modulation of cognitive control processes to meet task demands.
Apples and Oranges: The Logic of the Early and Later Arabic Logicians
Authors: Spevack Aaron
Published: June 2010

In a recent article in Islamic Law and Society, Khaled El-Rouayheb proposed that opposition to logic was probably never the predominant view of Sunni Muslim scholars. El-Rouayheb also expressed doubt in the position of later scholars who argued that there existed two approaches to the study of logic, one whose permissibility was debated, and another whose permissibility was agreed upon. In response to El-Rouayheb, Mufti Ali argued in his own article that opposition to logic was the predominant view of Sunni Muslim scholars between the thirteenth and fifteenth centuries. In this article, I argue, pace Ali, that there is merit to the claim that neither opposition to, nor support for, logic achieved predominance, especially between the thirteenth and fifteenth centuries, even if favorable opinions came to be viewed as the soundest position in later centuries. I also argue, pace El-Rouayheb, that there is merit to the proposition that there are two distinct approaches to logic, one that mixes objectionable elements from Greek philosophy, and one that, in varying degrees, may have rid itself of these elements. Additionally, I argue that the thirteenth through fifteenth centuries may have marked a transitional period during which the two approaches became more distinct, although some jurists who ruled on logic did not always notice, or acknowledge, the distinction.
The Anthropology of the Malay Peasantry: Critical Reflections on Colonial and Indigenous Scholarship
Authors: Ibrahim Zawawi
Published: June 2010

There has been a continuous anthropological interest in the Malay peasantry for the past 70 years. This has resulted in a rich theoretical and empirical literature. This article offers a critical genealogical account of knowledge production spanning some four generations of anthropologists. The first two generations were dominated by Western anthropologists — notably Raymond Firth and Michael Swift — working in the context of late colonialism. The latter two generations were represented by indigenous scholars who consciously dealt with the intellectual legacies of the past while, at the same time, opening up new research vistas. Using a close reading of some of the key anthropological texts produced on the Malay peasantry, as well as an analysis of the institutionalisation of professional anthropology in Malaysia, the article discusses the tensions of inter-generational continuities and ruptures. While acknowledging the enormous debt that many indigenous scholars clearly owed to their Western mentors it is argued that there emerged a qualitative break with the past during the late 1970s and 1980s. This saw indigenous anthropologists grappling with post-peasantry studies and opening up new fields of inquiry to do with larger issues of agrarian change, capitalist modernity, ideational formation and contemporary politics.
A Question of Honour: Why the Taliban Fight and What to Do About It
Authors: Atran Scott
Published: June 2010

Afghanistan is not like Iraq. What may work well in Iraq, or elsewhere, may not be a wise policy in Afghanistan. The original alliance between the Taliban and Al-Qaeda was largely one of convenience between a poverty-stricken national movement and a transnational cause that brought material help. Unlike Al-Qaeda, the Taliban are interested in their homeland, not ours. The Taliban know how costly keeping Qaeda can be. Even if the Taliban took control of Afghanistan it is not clear that Al-Qaeda would be welcome again. Afghanistan and the tribal areas of Pakistan must be dealt with on their own terms. There’s a good chance that enough of the factions in the Taliban coalition would decide for themselves to disinvite their troublesome guest if we contained them by maintaining pressure without trying to subdue them or hold their territory, intervening only when we see movement to help Al-Qaeda or act beyond the region. We’re winning against Al-Qaeda and its kin in places where anti-terrorism efforts are local and built on an understanding that the ties binding terrorist networks today are more cultural and familial than political or ideological.
A twelfth century Scottish treatise : the ordo 'Ulpianus de edendo'
Authors: Gouron André
Published: June 2010

The treatise on procedure Ulpianus de edendo was written between 1168 and 1185. Its author was a Scottish churchman who also made the formulary, given by the ms. London, Brit. Libr., Harley 2355, for a lawyer in a case of a pars ecclesiae. The work borrows from Placentinus' Summa Codicis, but not by purely mechanical ways. Its style is clear, always logical, and often axiomatic, far from Bolognese traditions. The glosses, as furnished by several manuscripts, support the hypothesis of influences of the Ulpianus among English writings, maybe from the Lincoln school.
Stephanus on the condictio de bene depensis (ο απο καλου δαπανηματος κονδικτικιος)
Authors: de Jong Hylkje
Published: June 2010

In the middle of the 6th century A.D. the antecessor Stephanus taught the codification of Emperor Justinian, explaining the Latin text of the Digest in Greek. In particular, he discussed the condictiones from D. 12,1 in detail. From fragment 11,2 it would appear that Stephanus introduced a specific name for the condictio, namely ο απο καλου δαπανηματος κονδικτικιος. This name refers to the facts of the casus. Only when ο δανειακος κονδικτικιος cannot be granted to the bona fide borrower, ο απο καλου δαπανηματος κονδικτικιος can be granted by virtue of justice and equity. For this to apply it is necessary, however, that the money lent has been spent.
'Flemish law' in Central Germany
Authors: Lück Heiner
Published: June 2010

In the general context of 12th- and 13th-century migrations in Europe, several communities from the Low Countries settled in central Germany, in territories now divided between the Länder Saxony, Saxony-Anhalt and Thuringia. Many of these settlements were concentrated in the region between Berlin and Wittenberg, still known today as the Fläming (from Flamen, German for Flemings, but also a generic name for populations from the Low Countries); the settlements also include areas around Burg and Magdeburg, a few localities around Leipzig and Naumburg, and the Goldene Aue, near the Kyffhäuser Hills. The law in those Flemish-Dutch settlements can to some extent be traced back through local customs and place-names, as well as through references in charters granting a distinctive legal status to the colonists. Characteristic features of the legal migration are the equal division of property after death and the terms Schulze and Schultheiß, which may in some cases go back to Netherlandish origins and influences.
The concept of dispensation : theological approaches to the excercise of papal power (13th – 14th centuries)
Authors: Marmursztejn Elsa
Published: June 2010

In the wake of studies showing that medieval intellectual production, far from confining itself to distinct faculties or disciplines, resulted from a constant circulation of knowledge, this paper analyzes the relations between theology and law through the controversial case of the dispensation from the vow of chastity, between ca. 1215 and ca. 1315. Focusing on the different aspects of the compelling power of the vow, the possibility to make up for it or to change it and the papal power of dispensation in spite of the particular dignity of the vow and the decretal forbiding any dispensation from it, the reflexion of canonists and theologians shows the interweaving of their disciplines, the changes of some individual positions and the absence of expected solidarities.
The state of emergency in the Weimar Republic Legal disputes over Article 48 of the Weimar Constitution
Authors: de Wilde Marc
Published: June 2010

The article analyzes the debate on 'constitutional dictatorship' that took place at the first annual conference of the Association of German Constitutional Lawyers in Jena in 1924. In their keynote lectures, Carl Schmitt and Erwin Jacobi argued that Article 48 of the Weimar Constitution authorized the President of the Reich to derogate from the rule-of-law provisions of the constitution if this was necessary to save its 'political substance'. Advocating a 'doctrine of derogation', they implicitly criticized one of the main methodological assumptions of legal positivism, i.e., that legal norms and politics, law and power, had to remain strictly separated. They thereby set the stage for the emerging 'conflict of methods and directions' that was to haunt German jurisprudence in subsequent years.
Better than a sack full of Latin: Anticlericalism in the Middle Dutch Dit es de Frenesie
Authors: Jongenelen Bas , Parsons Ben
Published: June 2010

This article offers the first substantial survey of the Middle Dutch satire Dit es de Frenesie since the work of C.P. Serrure in the mid nineteenth century. It contests much of the conventional wisdom surrounding De Frenesie, challenging the poem's usual classification as an early boerde or fabliau. Instead it is argued that the text is an experimental work, which blends together elements of several satiric traditions without committing itself to any one. The implications of this maneuver and others within the text are considered, revealing the poem's clear sympathy with the newly educated and articulate laity. De Frenesie itself is appended in both the original Middle Dutch and an English verse translation.
Remonstrant-Counter-Remonstrant Debates: Crafting a Principled Defense of Toleration after the Synod of Dordrecht (1619–1650)
Authors: Voogt Gerrit
Published: June 2010

The debate about toleration occasioned by the condemnation, exile and later return of the Remonstrant leaders during and after the Truce in the Dutch Revolt has often been noted but not examined in detail. Based on the plethora of pamphlets and tracts for and against toleration that these years produced, this article analyzes the arguments and motivations for religious coexistence and freedom of conscience formulated by Simon Episcopius, Johannes Uytenbogaert, and other Remonstrants, in constant polemic interaction with their Contra-Remonstrant opponents. In the course of the debate the Erastian role of the magistrate was hollowed out and the importance of religious inclusion emphasized, but with the understanding that absent a reconciliation with their Gomarist counterparts, the pluriform reality existing within the Dutch Republic should be maintained and safeguarded. Accused of a sectarianism incongruent with their former position, the Remonstrant protagonists were compelled to develop a principled defense of their request for the free practice of their faith as well as of their refusal to tolerate the intolerant. Accused of licentiousness, they reluctantly formulated their own restrictive creedal formula. They presented the unmolested presence in the Republic of various sects as an enriching rather than a nefarious situation, rejected dogmatism and the monopolizing of truth, and argued plausibly that the freedom of conscience guaranteed by the 1579 Union of Utrecht is meaningless unless it include the freedom to practice one's faith.