Interventions Targeting Racial/Ethnic Disparities in Stroke Prevention and Treatment.
Systemic racism is a public health crisis. Systemic racism and racial/ethnic injustice produce racial/ethnic disparities in health care and health. Substantial racial/ethnic disparities in stroke care and health exist and result predominantly from unequal treatment. This special report aims to summarize selected interventions to reduce racial/ethnic disparities in stroke prevention and treatment. It reviews the social determinants of health and the determinants of racial/ethnic disparities in care. It provides a focused summary of selected interventions aimed at reducing stroke risk factors, increasing awareness of stroke symptoms, and improving access to care for stroke because these interventions hold the promise of reducing racial/ethnic disparities in stroke death rates. It also discusses knowledge gaps and future directions.


Increased cholesteryl ester transfer activity in plasma from analbuminemic patients.
Hypercholesterolemia associated with analbuminemia, an inherited disease manifesting low plasma albumin concentration, is characterized by enhanced LDL cholesterol levels and reduced HDL cholesterol levels. In addition, compared with normal counterparts, the esterified cholesterol:triglyceride ratio tends to be higher in analbuminemic apoB-containing lipoproteins and lower in analbuminemic HDL. The aim of the present study was to investigate the mechanism that may account for the association of a hypoalbuminemic state with alterations in the concentration and composition of plasma lipoprotein fractions. To this end, endogenous cholesterol esterification activity, phospholipid transfer activity, and cholesteryl ester transfer activity were measured in total plasma from three analbuminemic patients and five control subjects. Whereas endogenous cholesterol esterification and phospholipid transfer rates were not significantly affected in analbuminemia, the transfer of radiolabeled cholesteryl esters from HDL toward apoB-containing lipoproteins was constantly higher in analbuminemic plasmas than in normal control plasma (473.6+/-107.3% x h(-1) x mL(-1) versus 227.5+/-84.0% x h(-1) x mL(-1), respectively; P=.036). The rise in cholesteryl ester transfer protein (CETP) activity in analbuminemic plasma was due to a significant increase in the transfer of radiolabeled cholesteryl esters toward LDL but not toward the triglyceride-rich lipoproteins. The CETP mass was higher in analbuminemic patients than in control subjects, but the difference did not reach the significance level (5.18+/-0.82 mg/L versus 3.13+/-1.19 mg/L respectively; P=.07). Since abnormally elevated nonesterified fatty acid (NEFA) levels were shown to be associated with analbuminemic lipoproteins, mostly LDL, the direct role of lipoprotein-bound NEFA in enhancing CETP activity was suspected. In support of this view, supplementation of total plasmas with fatty acid-poor albumin was shown to reduce CETP activity to a significantly greater extent in analbuminemic plasmas than in normal control plasma. It is concluded that hyperlipidemia associated with the hypoalbuminemic state can relate, at least in part, to the combined effect of CETP and NEFA in promoting the transfer of cholesteryl esters from the antiatherogenic HDL toward the proatherogenic apoB-containing lipoproteins.


Development of a high-temperature oven for the 28 GHz electron cyclotron resonance ion source.
We have been developing the 28 GHz ECR ion source in order to accelerate high-intensity uranium beams at the RIKEN RI-beam Factory. Although we have generated U(35+) beams by the sputtering method thus far, we began developing a high-temperature oven with the aim of increasing and stabilizing the beams. Because the oven method uses UO2, a crucible must be heated to a temperature higher than 2000 °C to supply an appropriate amount of UO2 vapor to the ECR plasma. Our high-temperature oven uses a tungsten crucible joule-heated with DC current of approximately 450 A. Its inside dimensions are ϕ11 mm × 13.5 mm. Since the crucible is placed in a magnetic field of approximately 3 T, it is subject to a magnetic force of approximately 40 N. Therefore, we used ANSYS to carefully design the crucible, which was manufactured by machining a tungsten rod. We could raise the oven up to 1900 °C in the first off-line test. Subsequently, UO2 was loaded into the crucible, and the oven was installed in the 28 GHz ECR ion source and was tested. As a result, a U(35+) beam current of 150 μA was extracted successfully at a RF power of approximately 3 kW.


Predictive testing for autoimmunity.
Many chemicals, in particular drugs, cause systemic allergy or autoimmune-like disorders. Due to complex pathogenesis and strong dependence on genetic make-up, these immunotoxicological effects are usually missed in standard toxicity testing. Besides, animal studies that demonstrate chemically induced systemic allergy or autoimmune-like disorders are scarce. Here, animal models are presented that would fit into a predictive two-tiered strategy, designed to allow screening for immunostimulatory potential in the first tier, and more elaborate testing for allergenic or autoimmunogenic potential of selected chemicals in the second tier. The popliteal lymph node assay (PLNA), with or without reporter antigens, would fit in the first tier, and relevant route of exposure protocols with selected strains of mice or rats may be further developed to compose the second tier. To date, the relevant route of exposure models mentioned here (with 'normal' inbred mice and/or Brown Norway rats) has been tested with only a few chemicals, and the PLNA, although tested with over 100 chemicals, is not validated as yet. Conceivably, a major challenge in immunotoxicology is to incorporate the present knowledge on chemical-induced systemic allergy and autoimmunity in further development and validation of predictive models and strategies.


Prediction of Talc Content in Wheat Flour Based on a Near-Infrared Spectroscopy Technique.
A procedure for the prediction of talc content in wheat flour based on radial basis function (RBF) neural network and near-infrared spectroscopy (NIRS) data is described. In this study, 41 wheat flour samples adulterated with different concentrations of talc were used. The diffuse reflectance spectra of all samples were collected by NIRS analyzer in the spectral range of 400 to 2,500 nm. A sample of outliers was eliminated by Mahalanobis distance based on near-infrared spectral scanning, and the remaining 40 wheat flour samples were used for spectral characteristic analysis. A calibration set of 26 samples and a prediction set of 14 samples of wheat flour were built as a result of sample set partitioning based on joint x-y distances division. A comparison of Savitzky-Golay smoothing, multiplicative scatter correction (MSC), first derivation, second derivation, and standard normal variation in the modeling showed that MSC has the best preprocessing effect. To develop a simpler, more efficient prediction model, the correlation coefficient method (CCM) was used to reduce spectral redundancy and determine the maximum correlation informative wavelength (MIW). From the full 1,050 wavelengths, 59 individual MIWs were finally selected. The optimal combined detection model was CCM-MSC-RBF based on the selected MIWs, with a determination of prediction coefficients of prediction (Rp) of 0.9999, root-mean-square error of prediction of 0.0765, and residual predictive deviation of 65.0909. The study serves as a proof of concept that NIRS technology combined with multivariate analysis has the potential to provide a fast, nondestructive and reliable assay for the prediction of talc content in wheat flour.


Health promotion and prevention in higher music education: results of a longitudinal study.
Music-related symptoms can already be found among student musicians during their years of university training. The goals of the present study were to ascertain the state and developmental course of the student musicians' health and to test the effectiveness of a preventive curriculum given to student musicians during their first two semesters at university. Within a longitudinal, observational study, we assessed students' psychological and physical health during the first 2 years of university training. We compared data from the group of students who had followed the prevention program (intervention group, IG, n = 144) with data of a comparison group (CG, n = 103) of students who had not followed the program. Using standardized questionnaires, we measured physical and psychological symptoms as well as health behavior in a sequential plan (duration, 3.5 yrs). Student musicians (n = 247) showed elevated ratings in psychological and physical health in comparison with nonmusicians of the same age. These ratings decreased at the end of the students' second year. The prevention program had a preventive effect on the students' psychological health: while IG students remained stable in their performance and powers of concentration, CG students got worse in those same areas. However, the prevention program did not reduce physical symptoms. In comparison with their younger colleagues, upper-level students took more courses in body-oriented methods, relaxation, and mental techniques, which focus on preventive measures for musicians. At present, the study offers evidence supporting the use of the prevention curriculum for young musicians. In higher music education, preventive education has a positive impact on students' performance and their attitude toward health. The preventive curriculum does not have an effect on preexisting physical symptoms, and those symptoms related to the students musicians' activity should rather be treated in an additional therapeutic setting.


Sex and age moderate the trajectory of guilt among children and adolescents with and without recent suicidal ideation.
We aimed to examine whether the trajectories of ecologically derived guilt differ among a transdiagnostic sample of youth with and without recent suicidal ideation and whether sex and age moderated this association. We assessed guilt 3 times a day over a 2-week period via ecological momentary assessment (EMA) technology in 102 children recruited from the community, outpatient, and inpatient settings. The average age of children was 10.95 y.o. (SD = 2.26, range 8-16) and the majority were male (54.9%) and White (76.5%). We found that the real-world guilt during a two-week EMA period was higher among youth with greater suicidal ideation severity in the past six months. Moreover, there was a significant moderating effect of sex and age on this association, such that the association between suicidal ideation severity and guilt was particularly strong among females compared to males and youth who were 10 years old or older. The findings were maintained when we adjusted for the relevant demographic and clinical characteristics, including age, minority status, parental income, EMA response rate, and current internalising symptoms. These preliminary findings highlight the clinical relevance of assessing and targeting feelings of guilt in the day-to-day lives of youth, particularly for females and older youth.


Proteolytic Activity at Alkaline pH in Oat Leaves, Isolation of an Aminopeptidase.
Proteolytic activity in oat leaf extracts was measured with both azocasein and ribulose bisphosphate carboxylase (Rubisco) as substrates over a wide range of pH (3.0-9.2). With either azocasein or Rubisco activity peaks appeared at pH 4.8, 6.6, and 8.4. An aminopeptidase (AP) which hydrolyzes leucine-nitroanilide was partially purified. Purification consisted of a series of six steps which included ammonium sulfate precipitation, gel filtration, and two ionic exchange chromatographies. The enzyme was purified more than 100-fold. The apparent K(m) for leucine-nitroanilide is 0.08 millimolar at its pH optimum of 8.4. AP may be a cystein protease since it is inhibited by heavy metals and activated by 2-mercaptoethanol. Isolated chloroplasts were also able to hydrolyze leucine-nitroanilide at a pH optimum of 8.4, indicating that AP could be localized inside the photosynthetic organelles.


The presence of medical students in practice consultations. Rates of patient consent.
To measure the frequency of nonconsent encountered by medical students and describe the influence of gender. An observational study of general practice teaching consultations. 63 students (40% female), 67 general practitioners (30% female), and 2572 patients (56% female). 3.4% of all patients (79% female) did not give consent (4.6% for male students; 1.6% for female; OR = 3.0, 95% CI 1.7-5.3). The rates of nonconsent did not vary between age groups for men but occurred mainly in the 15-44 years age group for women. Male students encountered more nonconsenting female patients than female students, particularly in consultations with female GPs. Consent to allow medical students to be present in general practice consultations is usually provided. It is typically declined for male students by young women attending women doctors.


Do older veterans experience change in posttraumatic cognitions following treatment for posttraumatic stress disorder?
It is unclear whether PTSD treatments improve negative posttraumatic cognitions (NPCs) and if changes in NPCs mediate treatment outcomes in older veterans. The current study examined if prolonged exposure therapy (PE) and relaxation therapy (RT) reduce NPCs over time in older adult veterans with PTSD. This study analyzed data from a randomized controlled trial of 86 older male veterans with PTSD randomized to PE or RT. The Posttraumatic Cognitions Inventory (PTCI; Foa et al., 1999), which includes a total score and three subscales, Negative Cognitions of the Self (Self), Negative Cognitions of the World (World), and Self-Blame (Blame), was used to assess NPCs at pretreatment, posttreatment, and 6-month follow-up. Changes in NPCs differed by treatment condition. Veterans who received PE had significantly reduced overall NPCs and NPCs about the self at posttreatment, but these NPCs were no longer significantly different from baseline at the follow-up assessment. In contrast, NPCs about the world and self-blame did not significantly change following PE. NPCs did not change following RT. Effects of PE on decreased 6-month follow-up clinician-rated PTSD symptoms were conveyed through intervening effects of decreased posttreatment PTCI total scores, suggesting the utility of targeting posttraumatic cognitions as a mechanism of long-term PTSD symptom reduction. Given that reductions in overall negative cognitions are associated with lower clinician-administered PTSD scores 6 months after PE, clinicians could consider monitoring changes in these cognitions over the course of treatment. RT is not a recommended treatment approach to target NPCs in older adults with PTSD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Analysis of factors affecting the therapeutic gain in high dose rate gynecological implants relative to low dose rate implants.
The radiobiological efficacy of high dose rate (HDR) intracavitary implant relative to that of low dose rate (LDR) implants has been represented quantitatively by the therapeutic factor lamba defined as [EDRtum/ERDorgan]HDR/[ERDtum/ERDorgan]LDR where ERD is the extrapolated response dose. The ERDs for the tumor and a critical organ are calculated using the linear-quadratic model and depend on the values of alpha/beta ratio, the tumor and normal tissue repair time constants (mu 1 and mu 1), number (N) of HDR fractions, the dose per fraction (d), and the fractional tumor and organ dose (ft and fl) relative to the dose at the reference point. We have studied the variation of gamma with d, mu t, mu l, ft, and ft and have derived specific conditions for which lamba can have a value equal to or greater than unity leading to a therapeutic gain in HDR. It is found that lamba is less than unity for commonly used parameter values, specifically when mu t is assumed to be equal to mu l. However, if mu t is greater than mu l, lamba can have a value greater than unity for many possible values of ft and fl.


Mononuclear Nickel(II) Complexes with Schiff Base Ligands: Synthesis, Characterization, and Catalytic Activity in Norbornene Polymerization.
The nickel(II) catalyst has manifested higher catalytic activity compared to that of other late transition metal catalysts for norbornene polymerization. Therefore, several structurally similar trans-nickel(II) compounds of N,O-chelate bidentate ligands were synthesized and characterized. Both the electronic effect and the steric hindrance influence polymerization. The molecular structures of 2, 4 and 5 were further confirmed by single-crystal X-ray diffraction.


Nanofibers made of globular proteins.
Strong nanofibers composed entirely of a model globular protein, namely, bovine serum albumin (BSA), were produced by electrospinning directly from a BSA solution without the use of chemical cross-linkers. Control of the spinnability and the mechanical properties of the produced nanofibers was achieved by manipulating the protein conformation, protein aggregation, and intra/intermolecular disulfide bonds exchange. In this manner, a low-viscosity globular protein solution could be modified into a polymer-like spinnable solution and easily spun into fibers whose mechanical properties were as good as those of natural fibers made of fibrous protein. We demonstrate here that newly formed disulfide bonds (intra/intermolecular) have a dominant role in both the formation of the nanofibers and in providing them with superior mechanical properties. Our approach to engineer proteins into biocompatible fibrous structures may be used in a wide range of biomedical applications such as suturing, wound dressing, and wound closure.


Purification and characterization of bitiscetin, a novel von Willebrand factor modulator protein from Bitis arietans snake venom.
We have screened 20 snake venoms and purified a novel snake venom protein, named bitiscetin, from Bitis arietans venom that specifically binds to human von Willebrand factor (vWF) and induces platelet agglutination. Bitiscetin showed a heterodimeric structure composed of disulfide-linked alpha (16kDa) and beta (13kDa) subunits on SDS-PAGE and showed a basic nature with pI value of 9.1, in contrast to botrocetin (pI 4.6), a vWF modulator isolated from another snake (Bothrops jararaca) venom. Bitiscetin-induced platelet agglutination was dependent on vWF and platelet membrane glycoprotein (GP) Ib, but not on Ca2+ and GPIIb/IIIa. vWF bound to bitiscetin but not to botrocetin electroblotted to a PVDF membrane after SDS-PAGE and this binding was diminished after reduction of disulfide bonds of bitiscetin. Bitiscetin did not cross-react to anti-botrocetin monoclonal antibodies. These results suggest that bitiscetin directly interacts with vWF and requires the protein conformation for its interaction as well as botrocetin, but its interaction manner with vWF appears to be different from that of botrocetin.


The Pegasus Overture alternating-pressure mattress overlay.
Pressure sores affect approximately 10% of the adult population and occur in various hospitals and community settings (Department of Health, 1992). It is therefore essential to adopt a logical approach when selecting the optimum piece of equipment for patients at risk of pressure sore development. Alternating-pressure mattresses have been used for many years in both hospitals and community environments to prevent and treat pressure sores. In September 1995, Pegasus Airwave Limited launched a new alternating-pressure mattress overlay, the Overture. It is designed for use with patients who have mobility problems and are at low to medium risk of developing pressure sores or have superficial tissue damage. This article describes the features of the Overture and its suitability for use in different care settings.


EC3, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha4 integrin and attenuates lymphocyte infiltration of Langerhans islets in pancreas and salivary glands in nonobese diabetic mice.
The venom of Echis carinatus suchoreki contains a monomeric disintegrin echistatin (Mr 5,500 Da) that strongly inhibits alphaIIbbeta3, alphavbeta3, and alpha5beta1 integrins and a heterodimeric disintegrin called EC3 (M(r) 14,762 Da). At nanomolar concentration, EC3 inhibits adhesion of human cell lines expressing alpha4beta1 and alpha4beta7 to immobilized VCAM-1; it has a lower inhibitory effect on alpha5beta1-mediated cell adhesion. In this study, we demonstrated that EC3, in contrast to echistatin, inhibited binding of monoclonal anti-alpha4 and anti-alpha5 antibodies to cells expressing alpha4beta7. In a dose-dependent manner and to the same extent, EC3 inhibited adhesion of Jurkat cells and murine splenic lymphocytes to immobilized VCAM-1, whereas echistatin was not active. EC3 injected intraperitoneally into nonobese diabetic (NOD mice) suppressed development of insulitis and sialoadenitis, whereas echistatin had no significant effect. We propose that the effect of EC3 is mediated, at least, in part, by blocking alpha4beta1 and alpha4beta7 on murine lymphocytes.


Multistep mechanism of probiotic bacterium, the effect on innate immune system.
The etiology and pathogenesis of inflammatory bowel disease are still not fully understood. However, evidence from both animal models and clinical observations suggests luminal bacteria as the most probable inducer of this disease. The intestinal bacterial microbiota may be modified by dietary addition of viable probiotic bacteria, thereby constituting an alternative approach to disease prevention and treatment. The aim of this study was to evaluate and compare the effects of two probiotic regiments; Lactobacillus GG and a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium lactis (YO-MIX Y 109 FRO 1000) in both normal and trinitrobenzenesulfonic acid colitis-induced rats. Colon morphology and damage were evaluated histologically; colonic tissues were used for mRNA analysis, using real-time PCR. Administration of both probiotics reduced the expression of proinflammatory cytokines tumor necrosis factor-alpha and IL-6 and increased the expression of mucin 2 in compared with colitis group and reduced the inflammatory response. These results provide additional support for the positive effect of probiotics in the gut and may shed light on the mechanism by which probiotic bacteria exert their action in an animal model.


Pediatric vocal fold paralysis: a long-term retrospective study.
To review our experience of pediatric vocal fold paralysis (VFP), with particular emphasis on etiological factors, associated airway pathologic conditions, and treatment and prognostic outcomes. Retrospective case review of a cohort of patients presenting with VFP. Tertiary referral center. A consecutive sample of 102 patients presenting with VFP to Great Ormond Street Hospital for Children, London, England, over a 14-year period from 1980 to 1994. There was an almost equal distribution of unilateral (52% [n = 53]) and bilateral (48% [n = 49]) VFP. Iatrogenic causes (43% [n = 44]) formed the largest group, followed by idiopathic VFP (35% [n = 36]), neurological causes (16% [n = 16]), and finally birth trauma (5% [n = 5]). Associated upper airway pathologic conditions were noted in 66% (n = 23) of patients who underwent tracheotomy. Tracheotomy was necessary in only 57% (n = 28) of children with bilateral VFP. Prognosis was variable depending upon the cause, with neurological VFP having the highest rate of recovery (71% [5/7]) and iatrogenic VFP the lowest rate (46% [12/26]). Recovery after an interval of up to 11 years was seen in idiopathic bilateral VFP; this has significant implications when considering lateralization procedures in these patients.


XRCC1 genetic polymorphism Arg339Gln, Arg194Trp, Arg280His and gastric cancer risk: an evidence based decision.
The purpose of this study is to investigate the associations of the x-ray repair cross-complementing 1 gene (XRCC1) single nucleotide polymorphisms (SNPs) Arg194Trp, Arg280His, and Arg399Gln with gastric cancer risk. The PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, CINAHL, International Bibliography of the Social Sciences, and Social Sciences Citation Index were searched. Two authors independently searched for relevant studies in any language from 1966 to Jan 2013. Seventeen studies with a total population of 10427 participants were identified. The results showed there were no associations of Arg399Gln polymorphism with gastric cancer, no matter in the co-dominant model, dominant model or recessive model. For Arg194Trp and Arg280His polymorphism, still no significant differences were found between control groups and GC groups in samples regardless of race. However, significant associations between Arg194Trp polymorphism and gastric cancer were found in Asian. The Asia with mutant genotype (Trp/Trp+Arg/Trp) had a higher risk of GC compared with the Asian with wild genotype (Arg/Arg). Our meta-analysis indicates that genetic polymorphism of the XRCC1 Arg399Gln and Arg280His do not have an association with gastric cancer risk. However, for Arg194Trp polymorphism, mutant gene carriers had a higher GC risk in Asian.


Detection of CCR5Δ32 Mutant Alleles in Heterogeneous Cell Mixtures Using Droplet Digital PCR.
The C-C chemokine receptor type 5 (CCR5 or CD195) is one of the co-receptor binding sites of the human immunodeficiency virus (HIV). Transplantations of hematopoietic stem cells with the CCR5Δ32 knockout mutation could represent an effective tool for the complete cure of HIV; these methods having passed the stage of proof-of-principle. At the same time, using the modern CRISPR/Cas9 genome editing method, we can effectively reproduce the CCR5Δ32 mutation in any wild-type cells. Thus, the task of searching for and accurately quantifying the content of mutant CCR5Δ32 alleles in heterogeneous cell mixtures becomes relevant. In this study, we describe the generation of an artificial CCR5Δ32 mutation using CRISPR/Cas9 followed by multiplex droplet digital polymerase chain reaction (ddPCR) to quantify its content in cell mixtures. The system we have developed allows us to quickly and accurately measure the content of cells with the CCR5Δ32 mutation, down to 0.8%.


Pre-clinical results with Clariscan (NC100150 Injection); experience from different disease models.
A superparamagnetic nanoparticle (NC100150 Injection) was investigated in two different animal models; renal perfusion in pigs and tumour imaging in mice. In the pig model, qualitative first-pass perfusion maps following a bolus injection of NC100150 Injection enabled good visualisation of hypoperfused regions of the renal cortex following partial ligation of the renal artery. High temporal resolution was found to be essential to accurately capture the first passage of the contrast agent through the kidney due to the very rapid blood flow in normal renal cortex. In the tumour model (LS174T cells implanted in nude mice), NC100150 Injection was found to cause a gradual (over 60 min) signal increase on T1-w images in part of the tumours which was attributed to contrast agent leakage from the vascular space to the extravascular space in areas of increased capillary permeability. This observation is consistent with previous reports on the molecular cut-off size for vascular extraction for this tumour cell line. The specific enhancement of tumour tissue suggest potential utility of NC100150 Injection as an angiogenesis marker.


Sucrose and Malic Acid as the Compounds Exported to the Apical Bud of Pea following CO(2) Labeling of the Fruit : No Evidence for a Senescence Factor.
The G2 line of peas (Pisum sativum L.) displays senescence and death of the apical bud only in long days and in the presence of fruit. As the removal of fruit prevents senescence, one possible mechanism by which fruits induce senescence is that the fruits produce some ;senescence factor' under long day conditions, which is then transported to the apical bud. Allowing developing fruits to photosynthesize in the presence of (14)CO(2) results in the recovery of label in the apical bud. In order to determine the chemical nature of this radiolabeled material, fruits of G2 peas, growing under long days, were exposed to (14)CO(2) at the time when the first senescence symptoms start to appear. The radiolabeled material from apical buds was then extracted, purified, and identified. Using HPLC and GC-MS the major labeled compound found in the apical bud following exposure of pea fruits to (14)CO(2) was identified as sucrose, while malic acid was identified as the major ethyl acetate-soluble compound. These compounds accounted for about 73 and 16%, respectively, of the radioactivity in the apical bud. No other compounds were present in significant amounts. As neither of these chemicals is likely to have any kind of senescence effect, we report no evidence for a senescence factor.


[Expression and mutation of c-kit gene in gastrointestinal stromal tumor].
To investigate the effect of the expression and mutation of c-kit gene and its relationship with clinical pathology and prognosis of gastrointestinal stromal tumor (GIST). Immunohistochemical and PCR-SSCP techniques were used to detect c-kit protein expression and c-kit gene exon 11 mutation in 82 patients with GIST. The positive c-kit protein expression and c-kit gene mutation rates were 97.6% (80/82) and 41.5% (34/82). Correlating the results of these two methods and clinicopathological factors, the c-kit expression and c-kit gene mutation rates were 95.0% (19/20) and 0 in benign GIST, and were 98.4% (61/62), 54.8% (34/62) in malignant GIST. Mutation positive GIST showed higher frequency of adjacent tissue invasion, metastasis and recurrence as compared with mutation negative ones. c-kit protein is an important diagnostic marker of gastrointestinal stromal tumor. c-kit gene mutation may play a significant role in the pathogenesis of GIST and also may be a prognostic marker.


Being a qualitative researcher.
This article, from a keynote address, is the result of some of the things which I learned about qualitative research during my many years of doing and teaching it. The main point I make is that qualitative researchers should present a good story which is based on evidence but focused on meaning rather than measurement. In qualitative inquiry, the researchers' selves are involved, their experiences become a resource. Researchers cannot distance themselves from the other participants, although they cannot fully present their meaning and experience. I also discuss voice, paradigm, and innovation as potentially problematic issues in qualitative research. These are terms often used but not always examined for their meaning in qualitative inquiry. If researchers are aware and sensitive, rather than overemotional or self-absorbed, qualitative research can be enlightening, person-centered, and humanistic.


Crystallization and preliminary X-ray analysis of ginkbilobin-2 from Ginkgo biloba seeds: a novel antifungal protein with homology to the extracellular domain of plant cysteine-rich receptor-like kinases.
The antifungal protein ginkbilobin-2 (Gnk2) from Ginkgo biloba seeds does not show homology to other pathogenesis-related proteins, but does show homology to the extracellular domain of plant cysteine-rich receptor-like kinases. Native Gnk2 purified from ginkgo nuts and the selenomethionine derivative of recombinant Gnk2 (SeMet-rGnk2) were crystallized by the sitting-drop vapour-diffusion method using different precipitants. X-ray diffraction data were collected from Gnk2 at 2.38 A resolution and from SeMet-rGnk2 at 2.79 A resolution using a synchrotron-radiation source. The crystals of both proteins belonged to the primitive cubic space group P2(1)3, with unit-cell parameters a = b = c = 143.2 A.


Amnesia after Midazolam and Ketamine Sedation in Children: A Secondary Analysis of a Randomized Controlled Trial.
The incidence of peri-procedural amnesia following procedural sedation in children is unclear and difficult to determine. This study aimed to apply quantitative and qualitative approaches to better understand amnesia following dental sedation of children. After Institutional Review Board Approval, children scheduled for sedation for dental procedures with oral midazolam (OM), oral midazolam and ketamine (OMK), or intranasal midazolam and ketamine (IMK) were recruited for examination of peri-procedural amnesia. Amnesia during the dental session was assessed using a three-stage method, using identification of pictures and an animal toy. On the day following the sedation, primary caregivers answered two questions about their children's memory. One week later, the children received a semi-structured interview. Behavior and level of sedation during the dental session were recorded. Quantitative data were analyzed using descriptive statistics and comparison tests. Qualitative data were analyzed using content analysis. Triangulation was used. Thirty-five children (age: 36 to 76 months) participated in the quantitative analysis. Most children showed amnesia for the dental procedure (82.9%, n = 29/35) and remembered receiving the sedation (82.1%, n = 23/28 for oral administration; 59.3%, n = 16/27 for intranasal administration). The occurrence of amnesia for the dental procedure was slightly higher in the oral midazolam group compared with the other groups (44.8%, n = 13/29 for OM, 13.8%, n = 4/29 for OMK, and 41.4%, n = 12/29 for IMK). Twenty-eight children participated in the qualitative approach. The major theme identified was that some children could remember their procedures in detail. We conclude that peri-procedural amnesia of the dental procedure was common following sedation.


In Vivo Gibberellin Biosynthesis in Endosperm of Sechium edule Sw. Seeds.
Biosynthesis of gibberellins (GAs) was studied in vivo in endosperms of Sechium edule Sw. Exogenous ent-[(14)C]kaurene was metabolized into four major products: GA(12), GA(4), GA(7) and 16, 17-dihydro-16-hydroxy-GA(15) alcohol glucoside. Other minor metabolites were also observed including ent-kaurenol and ent-kaurenal. Conversion of ent-[(14)C]kaurene to ent-kaurenol glucoside by endosperm cell-free preparations in the presence of UDPG was observed. However, the finding was not confirmed in in vivo studies and is probably artifactual. Overall evidence coming from the analysis of endogenous GAs and in vitro and in vivo biosynthetic studies are discussed in relation to the possible existence in the Sechium seeds of a different route, along with the known pathway, branching from ent-kaurene or ent-7-alpha-hydroxykaurenoic acid and this also leading to biologically active GAs.


A cyclodextrin dimer with a photocleavable linker as a possible carrier for the photosensitizer in photodynamic tumor therapy.
A cyclodextrin dimer has been synthesized with two beta-cyclodextrins linked by a flexible chain containing a carbon-carbon double bond. This dimer binds and solubilizes a phthalocyanine-based photosensitizer that generates singlet oxygen on irradiation. When the complex is irradiated, the singlet oxygen cleaves the carbon-carbon link, and the cyclodextrins are released, liberating the photosensitizer into the light path. Ideas about how this phenomenon could be used to make photodynamic tumor therapy into a more selective process are described.


On the joint effects of stimulus quality and word frequency in lexical decision: Conditions that promote staged versus cascaded processing.
Additive effects of Stimulus Quality and Word Frequency on RT in the context of lexical decision when the foils are orthographically legal were first reported more than 4 decades ago, and subsequently replicated numerous times. Two accounts are considered that make different a priori predictions when the foils are orthographically illegal. Yap and Balota's (2007) Familiarity Discrimination account predicts additive effects of these two factors on mean RT and across the RT distribution because it assumes a staged normalization process that deals with the effect of low Stimulus Quality; a subsequent process produces the effect of Word Frequency. In contrast, O'Malley and Besner's (2008) context-dependent thresholding/cascading account predicts an interaction because the use of illegal foils eliminates the need for thresholding at the letter level normally used to protect against lexical capture (identifying a nonword as a word) in experiments where Stimulus Quality is a factor, and hence the system reverts to processes in cascade. Critically, the present experiment yielded an interaction in which low-frequency words were more impaired by low Stimulus Quality than were high-frequency words. These data are inconsistent with the Familiarity Discrimination account as currently constituted, but consistent with a context-specific cascaded account. Further discussion considers how the Familiarity account may be modified so as to accommodate these data. Most generally, these data add to the view that processing is highly malleable (context dependent) rather than the received view, especially in regard to computational accounts, in which interactive-activation dynamics dominate. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


A simple questionnaire survey method for studying migration and residential displacement in informal settlements in South Africa.
"My aim in this article is to describe a cheap and reliable questionnaire survey method which can be used to identify patterns in migration and residential displacement." The method is described in the context of measuring migration in informal settlements in South Africa. "The merit of the method which I have described...lies in the fact that it allows questions of residential movement to be addressed in a routine manner, in much the same way that questions are used concerning, for example, household income."


A photon counting technique for quantitatively evaluating progression of peritoneal tumor dissemination.
We recently established a mouse model of peritoneal dissemination of human gastric carcinoma, including the formation of ascites, by orthotopic transplantation of cultured gastric carcinoma cells. To clarify the processes of expansion of the tumors in this model, nude mice were sacrificed and autopsied at different points of time after the orthotopic transplantation of the cancer cells for macroscopic and histopathologic examination of the tumors. The cancer cells grew actively in the gastric submucosa and invaded the deeper layers to reach the serosal plane. The tumor cells then underwent exfoliation and became free followed by the formation of metastatic lesions initially in the greater omentum and subsequent colonization and proliferation of the tumors on the peritoneum. Although this model allowed the detection of even minute metastases, it was not satisfactory from the viewpoint of quantitative and objective evaluation. To resolve these problems, we introduced a luciferase gene into this tumor cell line with a high metastasizing potential and carried out in vivo photon counting analysis. This photon counting technique was found to allow objective and quantitative evaluation of the progression of peritoneal dissemination on a real-time basis. This animal metastatic model is useful for monitoring the responses of tumors to anticancer agents.


Why anisogamy drives ancestral sex roles.
There is a clear tendency in nature for males to compete more strongly for fertilizations than females, yet the ultimate reasons for this are still unclear. Many researchers-dating back to Darwin and Bateman-have argued that the difference is ultimately driven by the fact that males (by definition) produce smaller and more numerous gametes than females. However, this view has recently been challenged, and a formal validation of the link between anisogamy and sex roles has been lacking. Here, we develop mathematical models that validate the intuition of Darwin and Bateman, showing that there is a very simple and general reason why unequal gamete numbers result in unequal investment in sexually competitive traits. This asymmetry does not require multiple mating by either sex, and covers traits such as mate searching, where the male bias has been difficult to explain. Furthermore, our models show males and females are predicted to diverge more strongly when the fertilization probability of each female gamete is high. Sex roles thus ultimately trace back to anisogamy and the resulting consequences for the fertilization process.


Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: a microdialysis study.
There is little evidence to date to indicate if mesoaccumbens dopamine function at the neurochemical level is altered during early abstinence from chronic i.v. nicotine self-administration. Thus, a quantitative microdialysis (no-net-flux) approach was used to measure basal extracellular concentrations and extraction fractions of dopamine in the nucleus accumbens (ACB) of rats that self-administered nicotine i.v. for 25 days, as well as in rats serving as yoked comparison groups (yoked nicotine and yoked saline). After 24-48 h of the final self-administration session, there was a significant reduction in basal extracellular dopamine levels in the ACB of the self-administration group compared with the yoked saline group (1.35+/-0.15 nM versus 3.70+/-0.28 nM). The basal extracellular dopamine levels in the yoked nicotine group (1.46+/-0.20 nM) were not significantly different compared with the nicotine self-administration group. The in vivo extraction fraction of dopamine, an indirect measure of dopamine uptake, was significantly increased in the nicotine self-administration (86%) and yoked nicotine (91%) groups compared with the yoked saline group (77%). In addition, a marked reduction in the elevation of extracellular dopamine levels in the ACB occurred after a nicotine challenge as measured by conventional microdialysis in the self-administration (112% of basal) and yoked nicotine (121% of basal) groups as compared with a yoked saline (154% of basal) group. The reduced basal ACB dopamine levels in the nicotine groups during early abstinence appears to be due to increased clearance, suggesting increased dopamine uptake is occurring as a result of the chronic nicotine treatment. The reduced elevation of extracellular dopamine levels in the ACB upon nicotine challenge suggests a functional desensitization or downregulation phenomenon involving acetylcholine receptors (nicotinic nAChRs). Overall, these results provide clear evidence for a neuroadaptive change that alters dopamine transmission in the ACB during abstinence from chronic i.v. nicotine exposure.


Radiological findings in a case of multiple focal nodular hyperplasia associated with portal vein atresia and portopulmonary hypertension.
We present here the radiological findings of a rare case of multiple focal nodular hyperplasia that was associated with portal vein atresia and portopulmonary hypertension in a young woman. This case illustrates and supports the pathophysiological hypotheses that were previously proposed for the coexistence of these three abnormalities.


Guanine of the third strand of C.G*G triplex serves as an effective hole trap.
We have examined the structural and electronic effects of the one-electron oxidation of the C.GG triplex, where G is located in a quite different environment from the G of duplex DNA. Upon photoirradiation of an external photosensitizer (riboflavin) with the C.GG triplex, oxidative DNA cleavage occurred exclusively at guanine repeat sequences in the third strand of triple helix DNA. Hole transport through the C.GG triplex also occurred, resulting in selective cleavage at G in the third strand. Thus, the hole generated in the duplex can migrate to GGG in the third strand and is trapped exclusively at Gs in the third strand. These experimental results, together with molecular orbital calculations, suggest that the origin of the selective strand cleavage can be explained as follows: (i) guanine repeat sequences in the third strand are more easily oxidized than in duplex DNA and (ii) in their radical cation states, G of the third strand rapidly deprotonates and reacts with oxygen and/or water, leading to strand cleavage. These results indicate that the oxidative damage preferentially occurred at Gs of the third strand owing to thermodynamic and kinetic features of the one-electron oxidation of the C.GG triplex.


Design and biomechanical study of a modified pedicle screw.
In pedicle screw fixation, the heads of monoaxial screws need to be directed in the same straight line to accommodate the rod placement by backing out during operation, which decreases the insertional torque and internal fixation strength. While polyaxial screws facilitate the assembly of the connecting rod, but its ball-in-cup locking mechanism reduces the static compressive bending yield strength as compared with monoaxial screws. Our study aimed to assess the mechanical performance of a modified pedicle screw. In this study, the tail of the screw body of the modified pedicle screw was designed to be a cylinder-shaped structure that well matched the inner wall of the screw head and the screw head only rotated around the cyclinder. Monoaxial screws, modified screws and polyaxial screws were respectively assembled into 3 groups of vertebrectomy models simulated by ultra high molecular weight polyethylene (UHMWPE) blocks. This model was developed according to a standard for destructive mechanical testing published by the American Society for Testing Materials (ASTM F1717-04). Each screw design had 6 subgroups, including 3 for static tension, load compression and torsion tests, and the rest for dynamic compression tests. In dynamic tests, the cyclic loads were 25%, 50%, and 75% of the compressive bending ultimate loads respectively. Yield load, yield ultimate load, yield stiffness, torsional stiffness, cycles to failure and modes of failure for the 3 types of screws were recorded. The results of modified screws were compared with those of monoaxial and polyaxial screws. In static tests, results of bending stiffness, yield load, yield torque and torsional stiffness indicated no significant differences between the modified and monoaxial screws (P > 0.05), but both differed significantly from those of polyaxial screws (P < 0.05). In dynamic compression tests, both modified and monoaxial screws showed failures that occurred at the insertion point of screw body into the UHMWPE block, while the polyaxial screw group showed screw body swung up and down the screw head because of loosening of the ball-in-cup mechanism. The modified screw is well-designed and biomechanically improved. And it can provide sufficient stability for segment fixation as monoaxial screws.


You in Mind: a preventive mental health television series.
This study of BBC Television's 'You in Mind' series provides preliminary evidence for the benefits of a mass media approach to preventive mental health. The series was seen by a large national audience who appraised it positively. It had a greater impact in the area of understanding problems as opposed to seeing what to do about them, and a greater impact on the viewer's perceptions of the problems of people the viewers knew, as opposed to the problems of the viewers themselves. Measures of intentions to change behaviour, even when corrected for over-reporting, suggest that a significant minority of the audience had changed or intended to change their behaviour as a result of the series. However, no specific pre-post changes in coping or help-seeking were found. These findings are discussed in terms of the potential and limitations of the mass media for mental health promotion.


External electric field will control the selectivity of enzymatic-like bond activations.
Controlling the selectivity of a chemical reaction is a Holy Grail in chemistry. This paper reports theoretical results of unprecedented effects induced by moderately strong electric fields on the selectivity of two competing nonpolar bond activation processes, C-H hydroxylation vs C=C epoxidation, promoted by an active species that is common to heme-enzymes and to metallo-organic catalysts. The molecular system by itself shows no selectivity whatsoever. However, the presence of an electric field induces absolute selectivity that can be controlled at will. Thus, the choice of the orientation and direction of the field vis-à-vis the molecular axes drives the reaction in the direction of complete C-H hydroxylation or complete C=C epoxidation.


Pediatric traumatic cataract and surgery outcomes in eastern China: a hospital-based study.
To evaluate the etiologies, management, and outcomes of pediatric traumatic cataract in eastern China. Pediatric traumatic cataract were reviewed for demographic information, type of injury, mode of injury, time of injury, interval between injury and first visiting doctors, hospital of first visiting, surgeries, complications and prognosis. A total of 117 eyes of 117 patients (96 boys and 21 girls) with unilateral injuries (66 right and 51 left eyes) were included in the study. The mean (SEM) age at diagnosis was (6.6±3.2) years (range, 1.3-13.8 years). Each cataract was categorized according to the type of trauma: closed-globe (n=26) or open-globe (n=91) injuries. The most common injuring objects were sharp metal objects (37.61%). The most common complication in open-globe injuries was corneal laceration, whereas traumatic mydriasis was most common in closed-globe injuries. Of 68 eyes in patients with open-globe injuries who received cataract extraction, intraocular lens (IOLs) were primarily implanted in 47 eyes (68.12%), whereas 18 eyes with closed-globe injuries received cataract extraction, and IOLs were primarily implanted in 17 eyes (94.4%). The surgical procedures included reconstruction of the anterior segment, synechiolysis, excision of the membrane, lensectomy, vitrectomy and related techniques. Postoperative vision was significantly improved compared with preoperative vision. Pediatric traumatic cataract should be treated in time to attenuate the complications, and education on pediatric traumatic cataract and improvements in pediatric health care are needed for the early detection of cataract in children.


Infections in traumatised patients: a growing medico-surgical concern.
Accidents and trauma are a leading global cause of mortality in young adults. Infections are one of the most important causes of death in traumatized patients. This is because of factors related to host and those due to trauma itself. Trauma jeopardizes the host's tissue integrity and immune effector mechanisms. Severely traumatized patients admitted to the ICUs are prone to get nosocomial infections due to open wounds and indwelling life saving devices. Massive blood loss also impairs the distribution of polymorphs, complement and antibiotics to the damaged tissues. Finally, diagnosis of infections in traumatized patients poses a challenge to clinicians due to various factors.


Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome.
To investigate the role of epidermal growth factor (EGF) in visceral hypersensitivity and its effect on the serotonin transporter (SERT). A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's correlation analysis. SERT function was examined by tritiated serotonin (5-HT) uptake experiments. Rat intestinal epithelial cells (IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor (EGFR). EGF levels were significantly lower in the rats with visceral hypersensitivity as measured in plasma (2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, P < 0.01) and in colonic tissue (3.244 ± 0.135 ng/100 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P < 0.01) compared with controls. Moreover, the EGF levels were positively correlated with SERT levels (r = 0.820, P < 0.01). EGF displayed dose- and time-dependent increased SERT gene expressions in IEC-6 cells. An EGFR kinase inhibitor inhibited the effect of EGF on SERT gene upregulation. SERT activity was enhanced following treatment with EGF (592.908 ± 31.515 fmol/min per milligram vs 316.789 ± 85.652 fmol/min per milligram protein, P < 0.05) and blocked by the EGFR kinase inhibitor in IEC-6 cells (590.274 ± 25.954 fmol/min per milligram vs 367.834 ± 120.307 fmol/min per milligram protein, P < 0.05). A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.


Allergic contact dermatitis in response to budesonide reactivated by inhalation of the allergen.
Up to 5% of patients with dermatitis who are consecutively patch tested are allergic to one or more corticosteroids. However, few reports of allergic mucosal and skin symptoms in patients with asthma and rhinitis caused by inhaled corticosteroids exist. Our purpose was to determine whether inhalation of budesonide would result in reactivation of patch test reactions caused by budesonide. The study, which was randomized, double-blind, and placebo-controlled, was ethically reviewed by the Medical Faculty, University of Lund, Sweden. Fifteen nonasthmatic patients who were initially given a diagnosis of budesonide hypersensitivity on patch testing from less than 1 up to 8 years before the study were provoked with budesonide or placebo by inhalation 6 weeks after they had been patch tested with budesonide, its R and S diastereomers, and potentially cross-reacting substances. Lung function was studied by using spirometry and repeated peak expiratory flow measurements. In 4 of 7 patients who inhaled budesonide, reactivation of previously positive patch test reactions was noted within 24 hours, in contrast to 0 of 8 patients who inhaled placebo (P =.026). No adverse pulmonary responses could be detected. This study shows that allergic skin reactions may occur in patients with contact allergy to budesonide when inhaled forms of the drug are used.


Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T-cell lymphoma.
The clonotypic T-cell antigen receptor (TCR) provides unique Valpha and Vbeta sequences with potential as idiotypic targets for immunoregulation. For T-cell malignancies, vaccination with the TCR could induce therapeutic anti-idiotypic responses. To facilitate this approach, we have developed DNA vaccines that include the genes encoding TCR sequences from a T-cell lymphoma (TCL). To combine requirements for stable folding with a simple minimized single-chain construction, we used a three-domain ValphaVbetaCbeta sequence. To promote anti-TCR immunity, we fused a pathogen-derived sequence from tetanus toxin to the 3'-end of the single-chain TCR. The fusion gene vaccine induced anti-idiotypic antibodies and generated protection against the TCL. The critical requirement for the conformational integrity of the delivered TCR antigen was highlighted by the observation that DNA fusion vaccines containing either ValphaVbeta or VbetaCbeta sequences failed to generate antibodies reactive with the native TCR or provide protection. This is the first report of a DNA vaccine able to induce anti-idiotypic immunity against TCL, and it presents a simple strategy for selectively eliminating T-cell clones in vivo.


Functional difference between the ventral visual cortex and the intraparietal sulcus in visual working memory of material properties.
A recent study showed that objects' roughness (smooth or rough) was held in visual working memory (VWM) in the ventral visual cortex and the intraparietal sulcus (IPS). Here, we investigated the functional differences between these areas in the context of VWM of material properties. We focused on the process in which participants accurately extracted and maintained in their memories the glossiness and roughness of a sphere. Human participants performed two types of delayed material (glossiness or roughness) discrimination tasks in which they judged which task was to be performed based on the differences in the material properties of two sequentially presented sample spheres. This task allowed us to investigate how the visual system in the human brain could properly extract a material property and hold the information in VWM. By decoding the task information (glossiness or roughness) from the brain activity patterns in the delay period, we found that both the ventral visual cortex and the IPS contributed to maintenance in memory of material properties. We also showed different decoding patterns in the areas over the course of each trial; the ventral visual cortex performed at levels above chance performance in extracting a material property, and the IPS performed at levels above chance performance in maintaining the property in memory. These results suggest that, in VWM, material properties are visually processed in the ventral visual cortex, and the visual information is sent to the IPS to be robustly maintained.


Serum leptin, adiponectin and endometrial cancer risk in Chinese women.
To investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. We conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls. Patients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8±2.2 ug/L vs. 19.8±1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7±180.5 ug/L vs. 2,583.9±147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001). Increased leptin or decreased adiponectin levels are associated with endometrial carcinoma.


Direct Observation of Cell Surface Sialylation by Atomic Force Microscopy Employing Boronic Acid-Sialic Acid Reversible Interaction.
Tracing cell surface sialylation dynamics at a scale of the glycolipoprotein microdomain (lipid rafts) formations remains an intriguing challenge of cellular biology. Here, we demonstrate that this goal is accessible, taking advantage of a boronic acid (BA)-based reversible molecular recognition chemistry. A BA-end-functionalized poly(ethylene glycol) was decorated onto an atomic force microscopy (AFM) cantilever, which provided a dynamic and sialic acid (SA)-specific imaging mode. Using this technique, we were able to heat map the SA expression levels not only on protein-decorated substrates but also directly on the cell surfaces, with a submicrometer scale resolution that may be relevant to that of the lipid rafts formation. The SA specificity and the binding reversibility of the probe were confirmed from its pH-dependent characteristics and an inhibition assay using free state SA. This finding may provide a noninvasive means for assessing a variety of SA-involved glycosylation dynamics spanning from physiology to pathology.


Prescribing patterns of duloxetine in France: a prescription assessment study in real-world conditions.
Duloxetine is a serotonin and norepinephrine reuptake inhibitor approved in the European Union for the treatment of major depressive disorder, generalized anxiety disorder, and diabetic peripheral neuropathic pain in adults. This study aimed to assess the real-world conditions of duloxetine use in France. Between April 2009 and January 2010, 290 dispensing pharmacies, randomly selected from a nationally representative list, included 1,104 patients who presented a duloxetine prescription and consented to the study. Demographic, clinical, and prescription data were extracted from pharmacy records and requested from prescribing physicians. Of the 294 patients with full data available, the mean age (standard deviation) was 54.5 (13.5) years; 74.1% were female; and 86.7% presented with a renewal prescription. 73.5% of patients had major depressive disorder; 3.4% generalized anxiety disorder; and 3.4% diabetic peripheral neuropathic pain. Overall, 78.2% (95% CI: 73.1; 82.8) of patients received duloxetine for an EU-approved indication; 95.2% (95% CI: 92.1; 97.4) of patients had no contra-indication to duloxetine; and 99.0% (95% CI: 97.0; 99.8) received an approved dose. Combining these three criteria, the overall approved use of duloxetine was 73.7% (95% CI: 68.3; 78.7). The strengths and limitations of the study design are discussed.


Calcitonin gene-related peptide increases microcirculation after mechanically induced ischemia in an experimental island flap.
Vasoconstriction, as a result of mechanical manipulation of blood vessels during microsurgery, may produce a decrease in blood supply and endanger flap viability. A study was undertaken to determine the effects of the topical vasodilator calcitonin gene-related peptide on the microcirculation of flaps after mechanically induced ischemia. A neurovascular island flap based on the superficial epigastric vessels was raised in 42 rats. Blood cell flux in the flap was recorded continuously with a laser Doppler flux meter. The feeding artery was pinched to induce vasospasm, and different concentrations of calcitonin gene-related peptide (10(-7), 10(-8), 10(-9), 10(-10) mol) or a control of sodium chloride 0.9% was applied topically to relieve the ischemia. Results showed that calcitonin gene-related peptide at a concentration of 10(-7) mol significantly shortened the time to reach 50% of the original blood cell flux values (270 +/- 123 seconds) and significantly increased the number of flaps in which the blood cell flux values were restored to prestress levels within 30 minutes. The data support the conclusion that, in this model, topical calcitonin gene-related peptide at the concentration of 10(-7) mol was effective in promoting recovery of the microcirculation after mechanically induced ischemia, without the adverse effects associated with other commonly used vasodilators.


Systemic diseases in elderly dental patients.
Systemic diseases, blood pressure and pulse rate, were investigated in 1012 elderly patients who consulted the gerodontic clinic of Tokyo Medical and Dental University Hospital. One or more systemic diseases was found in 64.2 per cent of the subjects. Hypertension was the most frequent systemic disease, occurring in 30.9 per cent of the subjects, and was followed by angina pectoris, diabetes, arrhythmias, digestive diseases, cerebrovascular diseases and myocardial infarction, respectively. Nearly 17 per cent of the patients had two or more diseases. Among these diseases, hypertension was frequently combined with angina pectoris, myocardial infarction, arrhythmia, and cerebrovascular diseases. Patients with systemic diseases are at a greater risk during dental treatment. Psychosomatic stress and vasoconstrictors in local anaesthesia possibly induce the exacerbation of systemic diseases or unexpected cardiovascular reactions. Isolated systolic hypertension (systolic blood pressure of 160 mm Hg or more) was noted in 14.3 per cent of the patients. Among these patients, 6.3 per cent of patients were hypertensive patients who had both above 160 mm Hg systolic pressure and 95 mm Hg diastolic pressure. Elderly dental patients have various systemic diseases. Accordingly, it is very important for the dentist to identify systemic diseases of patients and to understand systemic conditions before treatment commences.


[Basic tenets for quality circles in North Rhine Medical Service of Public Health Insurance].
The Medical Advisory Service of the Health Insurance in the area of the Northern Rhine (MDK Nordrhein) has set up an internal concept for quality management since 1998. This concept includes the installation and performance of quality circles. Staff members were internally qualified as "presenters". They worked out principles for quality circles of the MDK North Rhine which were implemented as binding basic rules by the managing conference of the MDK. The principles will be presented in detail.


Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS.
We studied alterations in the mRNA expression levels of BCL2 (Bcl-2), BCL2L12, BAX, FAS and CASPASE-9 genes in the MCF-7 breast cancer cell line in response to treatment with two anticancer drugs. Cell toxicity was evaluated by the MTT method, trypan blue staining and DNA laddering, whereas the expression levels of the apoptosis-related genes were analysed by RT-PCR using gene-specific primers. In the case of etoposide, down-regulation of the BCL2L12-A gene variant and of CASPASE-9, as well as upregulation of BAX, was observed, whereas treatment of MCF-7 cells with taxol led to down-regulation of the mRNA levels of all genes examined. Our results support the idea that after long-term clinical studies, mRNA expression analysis of BCL2L12 and other members of the BCL2 gene family may serve as useful molecular markers predicting chemotherapy response in breast cancer.


Development and characterization of temperature-controlled microreactors for protein crystallization.
Physico-chemical properties of the crystallization of biological macromolecules are of particular interest for an efficient way to get high-quality crystals. Concept and realization of a novel temperature-controlled microreactor to study these parameters is revealed. The characterization of the device is focussed on the temperature distribution across the reaction chamber, its long-term stability and accuracy as well as the regeneration of the surface inside the chamber after contamination with a hydrophilic protein (rGFP). We conclude that a microreactor for in situ observation of a temperature-controlled batch crystallization is in place.


Change of Direction Assessment Following Anterior Cruciate Ligament Reconstruction: A Review of Current Practice and Considerations to Enhance Practical Application.
Change of direction (CoD) has been indicated as a key mechanism in the occurrence of anterior cruciate ligament (ACL) injury during invasion sports. Despite these associations, assessments of knee function in athletic populations at the time of return to sport following ACL reconstruction (ACLr) have often focused on strength and single-leg hop tests, with a paucity of evidence to describe the CoD characteristics. Therefore, the aim of this narrative review was to describe the movement strategies exhibited following ACLr during CoD tasks and to critically analyze the range of tests that have been used. Specifically, we examined their ability to identify between-limb deficits and individuals who display a heightened risk of secondary injury and/or reductions in their level of pre-injury performance. MEDLINE, PubMed and SPORT Discuss databases were used and 13 articles were identified that met the inclusion criteria. Examination of the available literature indicates that current field-based practices are not representative of relevant sport demands and are unable to effectively assess knee function following ACLr. Laboratory-based studies have identified residual deficits and altered movement strategies at the time of return to sport, and this in part may be related to risk of re-injury. However, these assessments exhibit inherent limitations and are not practically viable for monitoring progress during rehabilitation. Consequently, alternative solutions that are more-aligned with the multitude of factors occurring during CoD maneuvers in chaotic sports environments are warranted to allow practitioners to 'bridge the gap' between the laboratory and the sports field/court. This approach may facilitate a more informed decision-making process with the end goal being, a heightened 'return to performance' and a lower risk of re-injury.


The trajectory of Virgínia Schall: integration of Health, Education, Science and Literature.
This article presents Virgínia Schall's professional career, interrupted very early. It highlights her major role in the integration of the fields of Health, Education and Scientific Dissemination in Brazil. The contextualization of her academic and literary production as a researcher at the Oswaldo Cruz Foundation, demonstrates Virgínia's contribution in strengthening the institution and in the teaching of dozens of researchers and students. With a strong inter- and multidisciplinary approach, she was a pioneer in the field of Health Education, Science Education, and Science Dissemination. Virgínia participated in the implementation of two post graduate courses and regularly worked as consultant for CNPq, CAPES, SVS/MS and the Ministry of Education, consolidating national policies in these areas. Besides being the author of several children's books and educational resources about health, environment and science, Virgínia conceived the Life Museum at Fiocruz-RJ, as a space for integrating science, culture, and society, with focus on science, health, and technology information and education. She was also a poet, member of the Women's Academy of Letters in Minas Gerais, and produced diverse and award-winning poetry and prose literary pieces.


Application of BI-RADS Descriptors in Contrast-Enhanced Dual-Energy Mammography: Comparison with MRI.
Contrast-enhanced (CE) magnetic resonance imaging (MRI) BI-RADS descriptors are used in the evaluation of contrast-enhanced dual-energy mammography (CEDEM) images of mass lesions and are assumed to be applicable. Patients with suspicious mass lesions on mammography (BI-RADS 4 or 5) were included. CEDEM examinations were performed using a modified prototype unit. CE-MRI was performed using a high temporal and high spatial resolution imaging protocol. 2 blinded breast radiologists evaluated all images using criteria related to contrast enhancement intensity and morphology according to the BI-RADS lexicon (5th edition) in 2 sessions. Histopathology was used as the standard of reference. 11 patients with 5 benign and 6 malignant index lesions were included. Enhancement characteristics were similar in the malignant cases. Enhancement of the benign lesions was moderate on CEDEM and strong on MRI. Discrepancies in the BI-RADS descriptors did not influence the final BI-RADS score. Overall, the BI-RADS assessment was almost identical in all cases. 1 malignant lesion was rated BI-RADS 4 with CEDEM and BI-RADS 5 with MRI, and 1 benign was rated BI-RADS 2 and BI-RADS 1, respectively. MRI BI-RADS descriptors of contrast-enhancing lesions can be applied for the morphologic analysis of mass lesions on CEDEM.


Continuous electrocardiogram reveals differences in the short-term cardiotoxic response of Wistar-Kyoto and spontaneously hypertensive rats to doxorubicin.
Electrocardiography (ECG) is one of the standard technologies used to monitor and assess cardiac function, and provide insight into the mechanisms driving myocardial pathology. Increased understanding of the effects of cardiovascular disease on rat ECG may help make ECG assessments in rat toxicology studies routine, thus facilitating continuous measurement of functional decrements associated with cardiotoxicant exposure. These studies seek to test the hypothesis that hypertensive rats are more susceptible to the short-term cardiotoxic effects of doxorubicin (DOX) when compared with normotensive rats with respect to continuously measured ECG endpoints. Male Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats surgically implanted with radiotelemeters were treated once a week for three weeks with either vehicle, 1.25 (low), 2.5 (medium), or 5 (high) mg/kg DOX (i.p.). ECG, heart rate (HR), and core body temperature (T(co)) were continuously monitored during the 1-week baseline and throughout the experimental period until rats were sacrificed 24 h after the third injection. DOX prevented normal body weight gain in both strains and significantly decreased diurnal HR and T(co) of high DOX SH rats. In the ECG, SH rats had prolonged baseline PR intervals and QT(c) when compared with WKY rats. All DOX-treated WKY rats subsequently developed PR interval prolongation; however only those treated with high DOX had increased QT(c). DOX caused an increase in ST interval in SH rats, and resulted in ECG morphology changes. The number of arrhythmias due to DOX was increased in both strains. In conclusion, ECG analysis can reveal underlying cardiovascular disease as a risk factor in the heart's response to toxicant-induced injury in the rat; and be a valuable tool to evaluate baseline vulnerability and assess cardiotoxicity.


Oppositional behavior in children.
Early intervention for children's oppositional behaviors is likely to be more effective than later treatment. The term oppositional includes a variety of noncompliant and aggressive behaviors that can be assessed with clinical interviews, rating scales, direct observation, and self-report measures. Treatment of children's oppositional behaviors is best approached from a parent training perspective. Parent training approaches have produced significant improvements in children's behavior, although far more research has been devoted to discipline than to identifying the more salient features of time-in. Recent advances in assessment and treatment are notable, but continued efforts are needed to determine the optimal treatments that produce the best social and psychological outcomes for children and adolescents.


Fusion activity dissociated from replication ability in feline immunodeficiency virus (FIV) in human cells.
Multinucleated-giant-cell formation followed by cell killing was observed after cocultivation of the feline immunodeficiency virus (FIV)-producing feline T-cell line 3201/FIV with various human cells, including T-cell lines carrying human T-cell lymphotropic virus type I (HTLV-I). The susceptibility to giant cell formation varied with the cell lines tested. Cocultivation of irradiated 3201/FIV cells with MT-2 cells resulted in giant cell formation as early as 2 h in culture, with striking resemblance to that induced by human immunodeficiency virus (HIV). MT-4 cells (HTLV-I positive) and H9 cells (HTLV-I negative) were less susceptible than MT-2 to the induction of syncytia. MOLT-4 cells (HTLV-I negative) had intermediate sensitivity to syncytia formation. No syncytia were observed in the monocytic cell line U-937 (HTLV-I negative). Syncytia formation between 3201/FIV and MT-2 cells was inhibited by polyclonal cat anti-FIV antisera but not polyclonal cat anti-feline leukemia virus (FeLV) antisera, goat anti-FeLV, uninfected specific-pathogen-free cat serum, human anti-HTLV-I antisera, or normal human and goat serum. Concentrated cell-free FIV supernatant from 3201/FIV also induced giant cells of MT-2 cells that were indistinguishable from those induced by cocultivation. Giant cells and extensive cell killing associated with giant cell formation declined and disappeared within 10 days. Surviving cells appeared to be of normal size and grew continuously without expressing FIV antigen or releasing infective virus. Although Southern blot analysis using probes specific for FIV could not detect proviral DNA in any of the five human cell lines cocultured with irradiated 3201/FIV cells, the polymerase chain reaction (PCR) technique detected FIV-specific DNA in MOLT-4 cells. DNA from the FIV-PCR positive MOLT-4 cells was PCR negative for endogenous FeLV-specific sequences, indicating that the MOLT-4 cell DNA was not contaminated with DNA from feline cells (i.e., 3201 cells). The FIV-MOLT-4 cells remained PCR positive for FIV after 40 passages, suggesting stable integration in the human cell line. These findings indicate that FIV is capable of forming proviral DNA in human T-lymphoid cells by cocultivation, although this FIV-carrying human cell line failed to produce replication-competent viruses.


Rapid development of piperidine carboxamides as potent and selective anaplastic lymphoma kinase inhibitors.
Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC(50) = 0.174 μM) during high throughput screening, with selectivity over the related kinase insulin-like growth factor-1 (IGF1R). The X-ray cocrystal structure of 1 with the ALK kinase domain revealed an unusual DFG-shifted conformation, allowing access to an extended hydrophobic pocket. Structure-activity relationship (SAR) studies were focused on the rapid parallel optimization of both the right- and left-hand side of the molecule, culminating in molecules with improved potency and selectivity over IGF1R.


Experimental Hepatotoxicity Produced by Ethinyl estradiol.
Ethinyl oestradiol (EO) is the most commonly used as a component of oral contraceptive and hormonal replacement therapy (HRT) in women. However, its excessive and prolonged use may cause cytotoxicity, including cancer of many organs. Hence, the present study was performed to produce the experimental hepatotoxicity in female albino rats. EO was administered to different groups of rats, respectively @ 250, 500 and 750 μg/kg body weight, orally, weekly for 16 and 20 weeks. One group of rats was administered with saline alone to serve as control. The rats were sacrificed after their respective experimental periods, and the livers were collected and preserved in 10% buffered formalin. Later on, the histopathological study of liver tissues was done. On the 17(th) week, the hepatic tissues showed severe congestion, focal areas of hemorrhage, extreme vacuolation of cytoplasm, distended sinusoids with dilated central veins. Degeneration and necrosis of hepatocytes as evidenced by increased cytoplasmic granularity, and dissolution of nuclear materials were seen. On the 21(st) weeks, these changes were extremely severe and quite conspicuous. Distinct fibrosis was also noticed. EO caused hepatotoxicity, the extent and severity of which were dose and time dependent, indicating that this drug at higher dose after prolonged duration (500 or 750 μg/kg, orally, weekly for 20 weeks) may cause the standard experimental hepatotoxicity in rats.


Phase II study of selumetinib (AZD6244, ARRY-142886) plus irinotecan as second-line therapy in patients with K-RAS mutated colorectal cancer.
More than half of colorectal tumors harbor activating mutations in RAS/RAF proteins. Selumetinib (AZD6244, ARRY-142886) is a small molecule kinase inhibitor targeting MEK kinase, downstream of RAS. We examined the efficacy and safety of selumetinib with irinotecan in second-line therapy. Patients with K-RAS mutated colorectal cancer, progressing on first-line oxaliplatin-based chemotherapy with bevacizumab, were eligible for this multicenter open-label phase I/II trial. In part A, a dose was determined using a standard "3 + 3" design; in part B, efficacy was determined. The primary endpoint was RECIST response rate. Historical data for irinotecan were used as reference. Secondary endpoints included progression-free survival and overall survival. Thirty-two patients entered the study, and 31 were treated. All had K-RAS exon 2 mutated tumors. In phase I, the recommended oral dose of selumetinib was 75 mg twice per day with intravenous (IV) irinotecan, 180 mg/m² every 2 weeks. Three patients (9.7 %) had partial response . Sixteen patients (51.6 %) had stable disease for ≥4 weeks, including three >1 year. The most common grade 3 adverse events included diarrhea, neutropenia, fatigue, anemia, nausea, and dehydration. The study was terminated before a pre-planned accrual of 45 subjects. Despite termination before full accrual, the point estimates of RR and median PFS show promising results, suggesting that further investigations of MEK inhibition in the treatment of metastatic colorectal cancer are warranted. Studies combining MEK inhibitors with cytotoxics or other targeted agents may lead to improved clinical activity based on the emerging preclinical data.


Kinetic stability and crystal structure of the viral capsid protein SHP.
SHP, the capsid-stabilizing protein of lambdoid phage 21, is highly resistant against denaturant-induced unfolding. We demonstrate that this high functional stability of SHP is due to a high kinetic stability with a half-life for unfolding of 25 days at zero denaturant, while the thermodynamic stability is not unusually high. Unfolding experiments demonstrated that the trimeric state (also observed in crystals and present on the phage capsid) of SHP is kinetically stable in solution, while the monomer intermediate unfolds very rapidly. We also determined the crystal structure of trimeric SHP at 1.5A resolution, which was compared to that of its functional homolog gpD. This explains how a tight network of H-bonds rigidifies crucial interpenetrating residues, leading to the observed extremely slow trimer dissociation or denaturation. Taken as a whole, our results provide molecular-level insights into natural strategies to achieve kinetic stability by taking advantage of protein oligomerization. Kinetic stability may be especially needed in phage capsids to allow survival in harsh environments.


A new type of biomaterial for artificial skin: dehydrothermally cross-linked composites of fibrillar and denatured collagens.
A new type of biomaterial for artificial skin was developed as a form of sponge by combining fibrillar collagen (F-collagen) with gelatin. The sponge was physically and metabolically stabilized by introducing dehydrothermal cross links. To get the final product, various conditions in the preparation of sponges were evaluated by in vitro cellular responses and in vivo tissue reactions. Fibroblasts placed on a sponge of gelatin attached themselves to it, migrated well into the sponge, and remained inside it for at least 7 days. However, sponges of gelatin showed structural instability for hydrolytic degradation by the cells. Most fibroblasts appeared not to penetrate into the interior of a sponge of F-collagen but to remain on its surface when fibroblasts were placed on the sponge, suggesting poor attraction of F-collagen toward cells. Implantation experiments of sponges of F-collagen revealed an intense infiltration of neutrophils into the sponge, indicating F-collagen as an inducer of the inflammatory reaction. These aggravating characters of F-collagen sponges were greatly improved by blending gelatin with F-collagen. The new type of collagen-based biomaterials developed in the present study is expected to become a useful matrix substance for artificial skin.


Engagement in community service among college students: is it affected by significant attachment relationships?
This study served as an exploratory analysis of how engagement in community service activities among college students is affected by significant attachment relationships. More specifically, this study investigated the difference between community service and non-service students in terms of their motivation to engage in community service activities as a function of the quality of their attachment to parents and close personal friends. A quantitative approach was used to analyse these issues. The findings revealed that students who had some community service experience evidenced more secure attachments to close personal friends while their attachments to parents were varied. Closer examination of the attachment data revealed that the community service students were more likely to have either very high or very low attachment relationships with their parents. These findings suggest that when incorporating service-learning into the college curriculum, one should examine the influence of other important contexts, (i.e. parents and peers) on community service outcomes.


Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes.
Tissue factor (TF) plays a central role in haemostasis and thrombosis. Following vascular damage, vessel wall TF initiates the extrinsic coagulation cascade. TF can also be exposed by monocytes. Inflammatory or infectious stimuli trigger synthesis of new TF protein by monocytes over the course of hours. It has also been suggested that monocytes can expose TF within minutes when stimulated by activated platelets. Here, we have confirmed that monocytes rapidly expose TF in whole blood and further demonstrate that platelet P-selectin exposure is necessary and sufficient. Monocyte TF exposure increased within five minutes in response to platelet activation by PAR1-AP, PAR4-AP or CRP-XL. PAR1-AP did not trigger TF exposure on isolated monocytes unless platelets were also present. In whole blood, PAR1-AP-triggered TF exposure required P-selectin and PGSL-1. In isolated monocytes, although soluble recombinant P-selectin had no effect, P-selectin coupled to 2 µm beads triggered TF exposure. Cycloheximide did not affect rapid TF exposure, indicating that de novo protein synthesis was not required. These data show that P-selectin on activated platelets rapidly triggers TF exposure on monocytes. This may represent a mechanism by which platelets and monocytes rapidly contribute to intravascular coagulation.


Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database.
To examine changes in temporal trends in breast cancer mortality in women living in 30 European countries. Retrospective trend analysis. Data source WHO mortality database on causes of deaths Subjects reviewed Female deaths from breast cancer from 1989 to 2006 Changes in breast cancer mortality for all women and by age group (<50, 50-69, and >or=70 years) calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in all age mortality began to change. From 1989 to 2006, there was a median reduction in breast cancer mortality of 19%, ranging from a 45% reduction in Iceland to a 17% increase in Romania. Breast cancer mortality decreased by >or=20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1987-9. England and Wales, Northern Ireland, and Scotland had the second, third, and fourth largest decreases of 35%, 29%, and 30%, respectively. In France, Finland, and Sweden, mortality decreased by 11%, 12%, and 16%, respectively. In central European countries mortality did not decline or even increased during the period. Downward mortality trends usually started between 1988 and 1996, and the persistent reduction from 1999 to 2006 indicates that these trends may continue. The median changes in the age groups were -37% (range -76% to -14%) in women aged <50, -21% (-40% to 14%) in 50-69 year olds, and -2% (-42% to 80%) in >or=70 year olds. Changes in breast cancer mortality after 1988 varied widely between European countries, and the UK is among the countries with the largest reductions. Women aged <50 years showed the greatest reductions in mortality, also in countries where screening at that age is uncommon. The increasing mortality in some central European countries reflects avoidable mortality.


[Experimental study of implantation of neurotropin-3 modified olfactory ensheathing cells in experimental allergic encephalomyelitis].
To investigate the therapeutic effect of neurotrophin-3 (NT-3) modified olfactory ensheathing cell (OEC) upon experimental allergic encephalomyelitis (EAE). OEC-NT-3 gene engineering cell, constructed by neurotrophin-3 transinfecting GEC inducted by retrovirus, was transplanted into lateral ventricle. The migration and distribution were observed and compared with control group and OEC transplantation group. Then myelin repairing and axon regeneration were evaluated from conical somatosensory evoked potential (CSEP), function score and ultrastructural morphology. (1) OEC-NT-3 could survive, migrate within axons and spread diffusely away from the focus at Day 28 post-transplantation; (2) as compared with other two groups, more nerve fibers, better myelin repair and more distinct myelin structure were observed in the transgene group; (3) as compared with other two groups, the latent time was obviously shortened and the amplitude higher in the transplantation group (P < 0.05); (4) the transcription level of NT-3mRNA in the transgene group was significantly higher than the GEC group and the contrast group (212.32 +/- 16.14) x 10(-2) vs. (1.98 +/- 0.19) x 10(-2), (1.23 +/- 0.13) x 10(-2) (P < 0.01). OEC-NT-3 cell expresses NT-3 stably and effectively in EAE. It may contribute to the repairing of myelin and the regeneration of axon.


Estrogen replacement and migraine aura.
To assess the association between estrogen replacement therapy and migraine aura. Estrogen replacement therapy is increasingly used by perimenopausal and postmenopausal women for management of menopausal symptoms and for long-term protection against osteoporosis and arterial disease. There are few reports about the effects of estrogen replacement therapy on migraine. Case reports were collected from women developing migraine aura related to use of estrogen replacement therapy. Four patients who developed migraine aura associated with the use of estrogen replacement therapy are described. In all cases, reducing the dose of estrogen or changing the route of delivery was associated with loss of aura. These findings suggest that high levels of estrogen in women using replacement therapy can trigger migraine aura.


Multisite stimulation in refractory heart failure.
Since the early nineties, the employment of DDD pacing from a right ventricular site with a short AV delay in patients with severe heart failure has led to considerable conflicting results, so that the real benefit of this method remains to be defined even in selected patients, such as those with first-degree AV block, QRS duration > 140 ms due to left bundle branch block (LBBB), mitral regurgitation time > or = 450 ms and diastolic filling time < or = 200 ms. Indeed, the asynchronous activation induced by pacing the right apex is the most important limitation to the technique, particularly in patients without an LBBB pattern or in those with an incomplete LBBB pattern. Recent studies have also shown that pacing of the right interventricular septum provides no better results than pacing of the right apex, at least in selected patients with no LBBB pattern and no significant mitral regurgitation. Today, it has been suggested that permanent biventricular pacing could be proposed as a feasible and reliable approach to improving ventricular function through the synchronization of the septum and the apex of the left ventricle, particularly in patients with a marked delay in ventricular activation sequence. This technique may be performed by means of transvenous leads inserted through the coronary sinus into the cardiac veins to stimulate both ventricles simultaneously, starting from the right apex and left lateral wall. Consequently, this approach supplies a strong basis for initiating further studies to examine the chronic effects of left ventricular pacing in patients with severe heart failure. We also suggest that the new tissue Doppler imaging techniques could usefully be applied to accurately select candidates to biventricular pacing.


Structural study on cultured isolated fetal rat pancreatic islets.
To perform a morphometric and structural study of the cultured isolated fetal rat pancreatic islets. Islets of the fetal rat pancreas, aged 22 days were isolated by the standard procedure of collagenase digestion and culture technique. The islets were cultured for 1, 2, 3, 4 and 5 days. The islets were counted under a dissecting microscope and islet diameter and purity were measured under a phase contrast microscope fitted with a calibrated grid. The islet specimens were fixed in buffered neutral formalin, dehydrated in alcohol and embedded in parablast. Sections were stained with hematoxylin and eosin. This study was conducted in King Fahd Medical Research Center, Faculty of Medicine, King Abdul-Aziz University, Kingdom of Saudi Arabia, during 2003 and 2004. The purity of the cultured islets gradually increased with time and was significantly different between the cultured groups. The number of the cultured islets gradually decreased with time. The islet diameter gradually increased with culture period. The islet purity and diameter were significantly different between the cultured groups. Parablast sections stained with hematoxylin and eosin showed that the shape and histological structure of the cultured islets were intact. The results of the present work represent an extensive morphometric structural study of isolated cultured fetal islets. The culture islet diameter and purity showed gradual increase with culture period, while the islet number showed gradual decrease.


Selective separation of structure-related alkaloids in Rhizoma coptidis with "click" binaphthyl stationary phase and their structural elucidation with liquid chromatography-mass spectrometry.
It is a new task to separate structure-related compounds into a fraction according to their structural characteristics in a complex traditional Chinese medicine (TCM). This method makes separation of the components of the sample simple and structural elucidation easy. In this study, selective separation of alkaloids in Rhizoma coptidis was realized on a "click" binaphthyl column possessing a planar conjugate structure. Three kinds of alkaloids, aporphine, tetrahydroprotoberberine and protoberberine in Rhizoma coptidis showed better retention than other compounds by virtue of π-π interactions with the stationary phase. Moreover, the "click" binaphthyl column could distinguish the aporphine and tetrahydroprotoberberine alkaloids possessing two benzene rings from the protoberberine alkaloids possessing three benzene rings. After separating on the "click" binaphthyl column, the fractions containing the alkaloids were collected and then analyzed with liquid chromatography-mass spectrometry (LC-MS). Totally, 23 alkaloids were identified, and among these alkaloids, three tetrahydroprotoberberine, two aporphine and seven protoberberine alkaloids were first found in Rhizoma coptidis. These newly found alkaloids are minor compounds, and they are always neglected without eliminating the interference of compounds in large amounts by pre-separation on the "click" binaphthyl column. The typical fragmentation pathways of each class of alkaloids were summarized to illustrate their structures. In the MS(2) spectrum, the loss of a molecule of dimethylamine ((CH(3))(2)NH) was observed as the characteristic loss of aporphine alkaloids. All the tetrahydroprotoberberine alkaloids would undergo the Retro-Diels-Alder (RDA) fragmentation reaction in the MS(2) fragmentation. For protoberberine alkaloids, different characteristic fragmentations were observed with different skeleton structures.


Parry-Romberg syndrome with multiple intracranial cysts: A rare case report.
Parry-Romberg syndrome (PRS) is a rare, poorly understood degenerative condition characterized by atrophic changes affecting one side of the face. The cause of these changes remains obscure. Migraine and facial pain such as trigeminal neuralgia are the most common neurological symptoms in this patient group. Sometimes, it causes epilepsy and rarely cerebral hemiatrophy, meningeal thickening, cortical dysgenesis, calcified lesions, aneurysms, and intracranial vascular malformations. Herein, the author reports the first case of PRS with multiple large intracranial cysts producing raised intracranial pressure.


Developmental process: family caregivers of demented Japanese.
1. Developmental process of caring for demented elders: the case of family caregivers consists of the beginning process (stage 1 through 4) and the awakening process (stage 5 through 7). 2. In the beginning process, the caregiver is unaware of the interaction between him/her and the demented family member, relies on conventional, general-purpose methods of care and on verbal communication, and consider care in terms of training and discipline of the person cared for. 3. The caregiver in the awakening process has realized that there is interaction between him/her and the demented family member, reflects on the nonverbal signs shown by the elder in order to improve their care, and provide warm and considerate care by making the most of nonverbal communication.