Effect of 6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride (Voluven®) on complications after subarachnoid hemorrhage: a retrospective analysis.
6% Hydroxyethyl Starch 130/0.4 in 0.9% Sodium Chloride (Voluven®; 6% HES 130/0.4) is a colloid often used for fluid resuscitation in patients with subarachnoid hemorrhage (SAH), despite a lack of safety data for this use. The purpose of our study was to evaluate the effect of 6% HES 130/0.4 on major complications associated with SAH. Medical records of all patients presenting between May 2010 and September 2012 with aneurysmal SAH were analyzed. Patients were divided in two groups based on the administration of 6% HES 130/0.4; HES group (n=57) and Non-HES group (n=72). The primary outcome included a composite of three major complications associated with SAH: Delayed Cerebral Ischemia (DCI), Hydrocephalus (HCP) requiring cerebrospinal fluid (CSF) shunting, and Rebleeding. The study groups were similar with respect to most characteristics except the incidences of hypertension, ischemic heart disease, Fisher grade and lowest hemoglobin during stay. The odds of developing the primary composite outcome was higher in the HES group [OR= 3.1(1.30-7.36), p=0.01]. The patients in the HES group had a significantly longer median duration of hospital (19 vs 14 days) and Neurointensive Care Unit stay (14 vs 10 days) compared to the Non HES group. We observed increased complications after SAH with 6% HES 130/0.4 (Voluven®) administration. An adequately powered prospective randomized controlled trial into the safety of 6% HES 130/0.4 in this patient population is warranted.


Nanobeads highly loaded with superparamagnetic nanoparticles prepared by emulsification and seeded-emulsion polymerization.
Functional superparamagnetic colloids possessing high saturation magnetization are prepared by emulsification of superparamagnetic nanoparticles (SPM NPs) and heterogeneous polymerization. The colloids consist of a core of densely packed NPs encapsulated within a thin polymer shell. The cores are made by emulsifying SPM NPs and toluene into an aqueous surfactant solution, and subsequently condensing the emulsion droplets by removal of the solvent generating clusters of SPM NPs. By tuning the emulsification condition, this approach allows for control over the size of the clusters from approximately 40 to 200 nm. The polymer shells encapsulating the clusters are made by using seeded-emulsion polymerization concepts. Control over the thickness of the shell and the incorporation of functional groups to the colloid is achieved. Characterization by thermogravimetric analysis (TGA) and magnetometry shows that these colloids have 66 wt % of magnetic material and saturation magnetization of 47 emu/g, confirming that this route generates colloids with a high loading of SPM NPs and high saturation magnetizations.


Platelet activation and aggregation during cardiopulmonary bypass.
Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets are activated during extracorporeal circulation. Subsequent circulation of these activated platelets may be responsible for the ubiquitous platelet dysfunction associated with cardiopulmonary bypass. Using flow cytometry and a monoclonal antibody directed against an alpha-granule membrane protein, granule membrane protein 140 (GMP-140), which is expressed on the platelet surface membrane after activation, we directly measured the percentage of circulating activated platelets in 41 patients before, during, and after cardiopulmonary bypass. In addition, we compared the GMP-140 expression with platelet aggregation in response to adenosine diphosphate (ADP). Cardiopulmonary bypass produced a significant increase in the percentage of GMP-140-positive platelets persisting in the circulation; the percentage peaked at a mean of 29% (range 10-58%) before separation from extracorporeal circulation. A significant percentage of these activated platelets continued to circulate in the early postoperative period. Simultaneous measurement of platelet aggregation in response to ADP demonstrated an aggregation defect that had a time course distinct from platelet activation and whose magnitude did not correlate with the degree of platelet activation in individual patients. We conclude that cardiopulmonary bypass causes a complex constellation of platelet defects, which include alpha-granule release, prolonged circulation of activated, "spent" platelets, and impaired platelet aggregation.


[Clinical indications for resistance testing HIV infection].
Treatment of HIV infection currently presents a number of problems such as: a) Capacity choice of antiretrovirals used (classic and new), b) study of the emergence of resistance to them (molecular mechanisms of emergence of mutations agains treverse transcriptase, protease, integrase and CCR5 antagonists), c) high cost of drugs, as well as analytical testing or hospital incarnation, so palpable that expensive treatment; d) Information clinical application of tests of resistance, ie to whom and when tobe performed; e) Interpretation of genotype resistance, good clinical type (internal, external and cross), the fuzzy rules and fuzzy rules mathematics, neural networks (net neurat Works) or the different cohorts of resistance based on the development of databases.


Mixed methods for telehealth research.
Mixed methods research is important to health services research because the integrated qualitative and quantitative investigation can give a more comprehensive understanding of complex interventions such as telehealth than can a single-method study. Further, mixed methods research is applicable to translational research and program evaluation. Study designs relevant to telehealth research are described and supported by examples. Quality assessment tools, frameworks to assist in the reporting and review of mixed methods research, and related methodologies are also discussed.


Coccidioidomycosis mimicking ovarian cancer.
Dissemination of coccidioidomycosis to the abdominal cavity is rare. No previous case of peritoneal coccidioidomycosis has presented as an adnexal mass. We report a case of peritoneal coccidioidomycosis mimicking ovarian carcinoma. The patient presented with a complex ovarian mass, ascites, omental caking, and an elevated CA 125. The ultimate diagnosis was not made until frozen section histopathology was performed at staging laparotomy. Peritoneal coccidioidomycosis can present with the clinical, radiographic, and serologic features of ovarian cancer. Although essential for diagnosis and staging, radiographic studies and tumor markers have limited specificity. Coccidioidomycosis now joins other benign conditions that comprise the differential diagnosis of patients who present with what seems to be advanced ovarian carcinoma. Infectious diseases consultation is recommended for the management of peritoneal coccidioidomycosis.


Determination of available phenolic compounds in soils by liquid chromatography with solid-phase extraction.
A fast, selective, and sensitive liquid chromatographic (LC) method was developed for determination of derivatives of benzoic and cinnamic acids (gallic, protocatechuic, 2,3,4-trihydroxybenzoic, 4-hydroxybenzoic, vanillic, caffeic, syringic, 4-coumaric, ferulic, sinapic, benzoic, 2-coumaric, cinnamic acids, and 4-hydroxybenzaldehyde and vanillin) in soil samples. The method for sample pretreatment is based on temperature-controlled extraction with water (pH 5.6) for 60 min. Extracts were preconcentrated and purified by solid-phase extraction on OASIS HLB sorbent, with subsequent separation and quantification of individual substances by LC with UV diode-array detection. Limits of detection (3 signal-to-noise LODs) better than 65 ng/g (dry weight) and recoveries from 88 to 99% were found for each compound at absorbance 280 nm. The method was used for determination of bioavailable phenolic compounds in different soil samples.


Botulinum toxin injection techniques for the management of adult spasticity.
Spasticity is often experienced by individuals with injury or illness of the central nervous system from etiologies such as stroke, spinal cord injury, brain injury, multiple sclerosis, or other neurologic conditions. Although spasticity may provide benefits in some patients, it more often leads to complications negatively impacting the patient. Nonpharmacologic treatment options often do not provide long-term reduction of spasticity, and systemic interventions, such as oral medications, can have intolerable side effects. The use of botulinum neurotoxin injections is one option for management of focal spasticity. Several localization techniques are available to physicians that allow for identification of the selected target muscles. These methods include anatomic localization in isolation or in conjunction with electromyography guidance, electrical stimulation guidance, or ultrasound guidance. This article will focus on further description of each of these techniques in relation to the treatment of adult spasticity and will discuss the advantages and disadvantages of each technique, as well as review the literature comparing the techniques.


Asymmetric unimodal maps at the edge of chaos.
We numerically investigate the sensitivity to initial conditions of asymmetric unimodal maps x(t+1)=1-a/x(t)/(z(i)) (i=1,2 correspond to x(t)>0 and x(t)<0, respectively, z(i)>1, 0<a< or =2, t=0,1,2,...) at the edge of chaos. We employ three distinct algorithms to characterize the power-law sensitivity to initial conditions at the edge of chaos, namely: direct measure of the divergence of initially nearby trajectories, the computation of the rate of increase of generalized non-extensive entropies S(q), and multi-fractal analysis. The first two methods provide consistent estimates for the exponent governing the power-law sensitivity. In addition to this, we verify that the multi-fractal analysis does not provide precise estimates of the singularity spectrum f(alpha), especially near its extremal points. Such feature prevents to perform a fine check of the accuracy of the scaling relation between f(alpha) and the entropic index q, thus restricting the applicability of the multi-fractal analysis for studying the sensitivity to initial conditions in this class of asymmetric maps.


Relationship between foal daily gain, suckling behavior, and the distance between foals and their mares in the first 40 days of life of Hokkaido native horses kept outdoors year-round.
In this study, we investigated suckling behavior and the distance between a foal and its mare as indicators of foal growth in Hokkaido native horses (HKD) during the first 40 days of life. Direct observations were made of 22 mare and foal pairs from two consecutive days 1 and 2, 5 and 6, 10 and 11, 20 and 21, 30 and 31, and 40 and 41 after birth by focal animal sampling for 3 h per day. Suckling behavior was continuously recorded, along with the terminator. The distance between the foal and its mare was determined using the instantaneous sampling method (1 min), and the percentage was calculated within 4 m while the foal was recumbent (DPW4FR). In the first week after birth, the duration and frequency of suckling terminated by the foal were negatively correlated with foal daily gains (duration, -0.49, p = 0.028; frequency, -0.53, p = 0.017). The DPW4FR and daily gain during 10-40 days after birth showed significant negative correlation (-0.47, p = 0.031). It is suggested that in HKD reproduction systems, suckling behavior termination by the foal and the distance between the foal and mare may be indicators of early foal growth.


Catering to chondrocytes.
An innovative strategy for delivering drugs to chondrocytes in situ offers new avenues for treating osteoarthritis (Geiger et al, this issue).


Ubiquitination of substrates by esterification.
Post-translational modification by ubiquitination determines intracellular location and fate of numerous proteins, thus impacting a diverse array of physiologic functions. Past dogma has been that ubiquitin was only coupled to substrates by isopeptide bonds to internal lysine residues or less frequently peptide bonds to the N-terminus. Enigmatically, however, several proteins lacking lysines had been reported to retain ubiquitin-dependent fates. Resolution of this paradox was afforded by recent observations that ubiquitination of substrates can also occur on cysteine or serine and threonine residues by thio- or oxy-ester bond formation, respectively (collectively called esterification). Although chemically possible, these bonds were considered too labile to be of physiological relevance. In this review we discuss recent evidence for the ubiquitination of protein substrates by esterification and speculate on its mechanism and its physiological importance.


Increase in family allowances, 1988.
As of 1 January 1988, the monthly rate of family allowances in Morocco was increased from DH 36 to DH 54 per child for the first three children. The allowance remains at DH 36 per child for further children.


Association between Educational Level and Physical Activity in Chronic Disease Patients of Eastern Slovakia.
This study aimed to investigate selected chronic diseases patients with different educational attainment regarding their awareness of and compliance with recommended physical activity. This cross-sectional study was conducted from October 2018 to February 2019 in cooperation with chronic diseases clinics in eastern Slovakia. The study involved 893 patients. People with higher education apparently recognise to a greater extent the importance of nutrition, diet, and the role of physical activity in treating their disease. Moreover, they have knowledge of physical exercises appropriate for their disease. Conversely, a noticeably higher number of less educated patients reported receiving general, respectively detailed information about the importance of physical activity in treating their disease. Differences in awareness of appropriate exercises and their implementation were not statistically significant. The results fail to prove educational attainment being a key determinant of chronic diseases. However, it can be reasonably argued that lower educational attainment may be a reliable risk signal of chronic diseases in later life.


Regulation of insulin-like growth factor II P3 promotor by p53: a potential mechanism for tumorigenesis.
Human insulin-like growth factor (IGF)-II mRNA has been shown to be expressed at high levels in a variety of tumors, including rhabdomyosarcomas. In addition, many tumors have alterations in p53 expression. To investigate whether p53 regulates IGF-II gene expression, we transfected wild-type p53 expression vectors and luciferase constructs driven by IGF-II P3 promotors into multiple cell lines. We found that p53 reduced, in a dose-dependent manner, both endogenous IGF-II P3 transcripts and transfected P3 luciferase expression. The inhibition of P3 luciferase expression by p53 was more pronounced in the two cell lines that expressed mutant p53 protein, RD, and HTB114. The element responsible for this inhibition was mapped to the minimal promoter region. We also transfected an HPV-16 E6 expression plasmid into CCL13 cells containing functional p53 and found that E6 up-regulated IGF-II P3 activity. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein to the TATA motif of P3, although both could directly associate with human TATA-binding protein. Our results suggest that p53 may play a role in regulation of IGF-II gene expression.


Interfacial Properties of Bamboo Fiber-Reinforced High-Density Polyethylene Composites by Different Methods for Adding Nano Calcium Carbonate.
The focus of this study was to observe the effect of nano calcium carbonate (CaCO₃) modification methods on bamboo fiber (BF) used in BF-reinforced high-density polyethylene (HDPE) composites manufactured by extrusion molding. Two methods were used to introduce the nano CaCO₃ into the BF for modification; the first was blending modification (BM) and the second was impregnation modification (IM). In order to determine the effects of the modification methods, the water absorption, surface free energy and interfacial properties of the unmodified composites were compared to those of the composites made from the two modification methods. The results revealed that the percentage increase in the weight of the composite treated by nano CaCO₃ decreased and that of the IMBF/HDPE composite was the lowest over the seven months of time. The results obtained by the acid-base model according to the Lewis and Owens-Wendt- Rabel-Kaelble (OWRK) equations indicated that the surface energy of the composites was between 40 and 50 mJ/m². When compared to the control sample, the maximum storage modulus (E'max) of the BMBF/HDPE and IMBF/HDPE composites increased 1.43- and 1.53-fold, respectively. The values of the phase-to-phase interaction parameter B and the k value of the modified composites were higher than those of the unmodified composites, while the apparent activation energy Ea and interface parameter A were lower in the modified composites. It can be concluded that nano CaCO3 had an effect on the interfacial properties of BF-reinforced HDPE composites, and the interface bonding between IMBF and HDPE was greatest among the composites.


Labour force activity after 65: what explain recent trends in Denmark, Germany and Sweden?
In most OECD member countries labour force attachment, has increased in recent years not only in the age groups 60-64 years but also among people 65 years and older. Focus in this paper is on the trend in older workers' labour force participation in Denmark, Germany and Sweden since 2004. Main emphasis is given to people aged 65-69 years eligible for social security retirement programs from age 65. The gender aspect is included to accommodate different trends for women and men. To explain country differences in trends, the importance of changes in retirement policies of relevance for this age group and cohort relevant changes in education and health is examined and discussed. Further, country differences in the impact from education and health is examined. Results show that the largest increase in labour force participation among people aged 65-69 years has taken place in Sweden following by Germany, while the increase in Denmark is rather small. While the increase in Germany mainly seems to be a result of policy reforms, the increase in Sweden appear to be a result of a combination of policy changes and an increasing educational level. Financial incentives seem most important in Germany and only of minor importance in Denmark, where policy changes directed towards individuals above the age of 65 appear to have been too small so far to affect retirement behaviour significantly.


Advancing non-communicable diseases research in Ghana: key stakeholders' recommendations from a symposium.
There has been a growing increase in the prevalence of non-communicable diseases (NCDs) globally with reports suggesting that the fastest increase in NCD deaths in the world will occur in sub-Saharan Africa (SSA) over the next 5 to 15 years. Despite the projected increase in NCD-related deaths, there is little coordinated research in many West African nations, including Ghana, to quantify and study this burden and to translate the research findings into policy and practice. To address these challenges, the Noguchi Memorial Institute for Medical Research and the Navrongo Health Research Centre, both in Ghana, with support from the Wits NCD Research Leadership Training Program organized a two-day symposium to discuss the advancement of NCD research in the West African sub-region. The aim was to propose the way forward for strengthening applied research that can inform the development of health policies and programs focused on NCDs. Participants were drawn from academia, research and health institutions, early career researchers and postdoctoral fellows. We present the key themes that emerged from the symposium and some strategies for advancing NCD research in West Africa. These include interdisciplinary collaboration between NCD researchers in the region, generation of accurate data on disease burden and strengthening stakeholder and public engagement on NCDs. Funding for the symposium was provided by NIH Fogarty International Center-Grant number D43TW008330, under the Wits Non-Communicable Disease Research Leadership Training Program.


Spinopelvic Parameters among Healthy Volunteers in Iran.
Recently, in approach to spinal pathologies, the whole spine should be considered as a biomechanical unit. Studies have shown the great importance of sagittal and coronal balance and the relationship between the various parts of spine together and pelvis. Former studies have shown a close relationship between spinopelvic parameters and sagittal balance. A complete understanding of sagittal balance basics is needed to achieve the best outcome and avoiding future complications after treatment of spinal deformities. In this study, the normal range of spinopelvic parameters among healthy volunteers in Iran has been evaluated. This cross-sectional study was conducted on healthy volunteers in 2017. The lateral whole-spine X-ray was obtained under the standard conditions. Two spine surgeons measured the parameters including pelvic incidence, pelvic tilt, sacral slope and lumbar lordosis. In this study 100 volunteers were studied; out of whom, 41 participants were male and the mean age was 47.5±11.7 years. The average pelvic incidence, pelvic tilt, and sacral slope were 51.5±10.9, 17.4±9.9, and 34.8±8.8 degrees, respectively. The pelvic tilt was significantly lower in women. It was found that with increasing age, the pelvic incidence and pelvic tilt increases while lumbar lordosis decreases (P<0.05). This study is the first study on the normal range of spinopelvic parameters in healthy individuals in Iran.. Our data showed that PT and PI-LL are significantly lower in women, while, PT, PI and PI-LL increase and LL decreases in older ages.


In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues.
Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma.


Cholesterol testing by general practitioners in Grampian: patterns and outcomes.
Initiation, distribution, concomitants and follow-up of cholesterol testing were studied in Grampian. Data were examined for 4979 patients, representing all patients in one year from those general practices who made exclusive use of the clinical chemistry laboratory for cholesterol testing. A random sample of 215 patients was studied in further detail. Age and sex distribution, results of cholesterol tests and their follow-up, nature and results of associated biochemical tests, test initiation, testing rates by practice, and prescription rates of lipid lowering agents by practice were measured. Cholesterol testing was mostly in line with current knowledge of cardiovascular risk, and associated with further cardiovascular and biochemical assessment. There was a 90-fold range in practice cholesterol testing rates, and a similarly wide range in prescription rates of lipid lowering agents; there was a significant correlation between these. Rates and results of follow-up testing suggests a "rule of halves" for cholesterol testing.


Increased QRS duration and dispersion are associated with mechanical dyssynchrony in patients with permanent right ventricular apical pacing.
Permanent right ventricular apical pacing may have negative effects on ventricular function and contribute to development of heart failure. We aimed to assess intra- and interventricular mechanical dyssynchrony in patients with permanent right ventricular apical pacing, and to establish electrocardiographic markers of dyssynchrony. 84 patients (46:38 male:female) who required permanent pacing were studied. Pacing was done from right ventricular apex in all patients. We measured QRS duration and dispersion on standard 12-lead ECG. Intra- and interventricular mechanical dyssynchrony and left ventricular ejection fraction were assessed by transthoracic echocardiography. Patients were followed-up for 24 months. Results: Six months after implantation, QRS duration increased from 128.02 ms to 132.40 ms, p≤0.05. At 24 months, QRS dispersion increased from 43.26 ms to 46.13 ms, p≤0.05. Intra- and interventricular dyssynchrony increased and left ventricular ejection fraction decreased during follow-up. A QRS dispersion of 47 ms predicted left ventricular dysfunction and long-term electromechanical dyssynchrony with a sensitivity of 80% and a specificity of 76%. Conclusion: In patients with permanent right ventricular apical pacing there is an increased duration and dispersion of QRS related to dyssynchrony and decreased left ventricular ejection fraction. This study shows that QRS dispersion could be a better predictive variable than QRS duration for identifying left ventricular ejection fraction worsening in patients with permanent right ventricular apical pacing. The electrocardiogram is a simple tool for predicting systolic function worsening in these patients and can be used at the bedside for early diagnosis in the absence of clinical symptoms, allowing adjustments of medical treatment to prevent progression of heart failure and improve the patient's quality of life.


A feature-based data association method for multiple acoustic source localization in a distributed microphone array.
Multisource localization using time difference of arrival (TDOA) is challenging because the correct combination of TDOA estimates across different microphone pairs, corresponding to the same source, is usually unknown, which is termed as the data association problem. Moreover, many existing multisource localization techniques are originally demonstrated in two dimensions, and their extensions to three dimensions (3D) are not straightforward and would lead to much higher computational complexity. In this paper, we propose an efficient, feature-based approach to tackle the data association problem and achieve multisource localization in 3D in a distributed microphone array. The features are generated by using interchannel phase difference (IPD) information, which indicates the number of times each frequency bin across all time frames has been assigned to sources. Based on such features, the data association problem is addressed by correlating most similar features across different microphone pairs, which is executed by solving a two-dimensional assignment problem successively. Thereafter, the locations of multiple sources can be obtained by imposing a single-source location estimator on the resulting TDOA combinations. The proposed approach is evaluated using both simulated data and real-world recordings.


Cochlear transduction: from models to molecules and back again.
The strides made over the last few years towards understanding many details of cochlear function still leave a number of issues unresolved. Integrating the information from molecular, genetic and, increasingly, genomic sources requires models that provide close matching between data and theory. For both theoretical and experimental reasons, the difficult area in cochlear physiology has been to understand how sensory transduction operates at the basal end of the mammalian cochlea. The identification of candidate motor proteins in outer hair cells (OHCs) draws attention to the question of whether we understand cochlear tuning. Nevertheless, the association of the cloned motor protein 'prestin' with an anion transporter superfamily provides clues about the molecular nature of the OHC motor in the basolateral membrane, the utilisation of chloride in hair cells and the long-term stability of small basal turn cochlear hair cells.


Owner controlled data exchange in nutrigenomic collaborations: the NuGO information network.
New 'omics' technologies are changing nutritional sciences research. They enable to tackle increasingly complex questions but also increase the need for collaboration between research groups. An important challenge for successful collaboration is the management and structured exchange of information that accompanies data-intense technologies. NuGO, the European Nutrigenomics Organization, the major collaborating network in molecular nutritional sciences, is supporting the application of modern information technologies in this area. We have developed and implemented a concept for data management and computing infrastructure that supports collaboration between nutrigenomics researchers. The system fills the gap between "private" storing with occasional file sharing by email and the use of centralized databases. It provides flexible tools to share data, also during experiments, while preserving ownership. The NuGO Information Network is a decentral, distributed system for data exchange based on standard web technology. Secure access to data, maintained by the individual researcher, is enabled by web services based on the the BioMoby framework. A central directory provides information about available web services. The flexibility of the infrastructure allows a wide variety of services for data processing and integration by combining several web services, including public services. Therefore, this integrated information system is suited for other research collaborations.


Designing Electrophilic and Nucleophilic Dual Centers in the ReS2 Plane toward Efficient Bifunctional Catalysts for Li-CO2 Batteries.
Two-dimensional transition metal dichalcogenides (TMDCs) show great potential as efficient catalysts for Li-CO2 batteries. However, the basal plane engineering on TMDCs toward bifunctional catalysts for Li-CO2 batteries is still poorly understood. In this work, density functional theory calculations reveal that nucleophilic N dopants and electrophilic S vacancies in the ReS2 plane tailor the interactions with Li atoms and C/O atoms in intermediates, respectively. The electrophilic and nucleophilic dual centers show suitable adsorption with all intermediates during discharge and charge, resulting in a small energy barrier for the rate-determining step. Thus, an efficient bifunctional catalyst is produced toward Li-CO2 batteries. As a result, the optimal catalyst achieves an ultrasmall voltage gap of 0.66 V and an ultrahigh energy efficiency of 81.1% at 20 μA cm-2, which is superior to those of previous catalysts under similar conditions. The introduction of electrophilic and nucleophilic dual centers provides new avenues for designing excellent bifunctional catalysts for Li-CO2 batteries.


[Research on effects of taurine on the transplanted tumor of mice].
With the same forage to the mice, three experiments were done. The control group took water and experimental group took 1% taurine. 1. After the mice were vaccinated with S180 sarcoma, every group was further divided into two groups, one treated with cytoxan (CTX), another one treated with nothing. The survival period, weight of the tumor and the tumor inhibition rate were investigated. The result shows: The survival period of the group fed with taurine was (35.75 +/- 23.7) days longer than that of the control group (18.7 +/- 5.6) days, and the tumor inhibition rate was 42.26%. The mice fed with taurine and treated with CTX survived to 61 days with no death, and no tumor could be seen grossly, so the tumor inhibition rate is 100%. The survival period and weight of the tumor were not different between the CTX treated and control groups. 2. Tumor cell membrane fluidity was observed after the mice were vaccinated with Erlish ascitic tumor. The result shows: in the taurine group, the fluorescence polarization (p) is 0.108 +/- 0.020, the viscosity (eta) is 0.618 +/- 0.140 and in the control group p is 0.139 +/- 0.20, eta is 0.874 +/- 0.150, respectively. Thus the cell membrane fluidity of the taurine group is also obviously better than that of the control group (P < 0.01). 3. The immune functions of the two groups were determined by carbon clearance test and capacity of serum hemolysin. The immune function of the taurine group is also obviously higher than that of control group (P < 0.01). All the results described above show:taurine is functioning for tumor inhibition, and has obvious synergic effect while treated with CTX as chemotherophy. It is considered that the tumor inhibit function of taurine may be related to its effects of immune enhancing and membrane profecting.


Anxiety and the colposcopy experience.
The purpose of this study was to explore the anxiety of an abnormal Papanicolaou (Pap) result, the need for colposcopy, and the colposcopic examination experienced by first-time colposcopy clients. Spielberger's State-Trait Anxiety Inventory (STAI) and a Woman's Profile were administered to 149 women who had abnormal Pap smears necessitating colposcopy. The results confirm that this experience evokes anxiety. Younger women who knew less and had concurrent stressors in their lives were most anxious. Women identified ways that health professionals could be more helpful in alleviating their anxiety. Their suggestions included the provision of more information and an opportunity for personal contact with a health professional.


Anemia management and chronic renal failure progression.
Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.


Preparation of Heterobimetallic Ketimido-Actinide-Molybdenum Complexes.
During our attempts to prepare paddlewheel actinide-molybdenum complexes of the type [(X)An(MesNPR2)3Mo(CO)3] (Mes= 2,4,6-trimethylphenyl; X = Cl or I; An = U or Th; R = iPr or Ph) we have found that under certain conditions acetonitrile insertion reactions occur to give the heterobimetallic bridging ketimido species [ClAn(μ-MesNPiPr2)2(μ-MesNPiPr2{μ-NCMe})Mo(CO)3] (An = U, 1; Th, 2), [ClAn(μ-MesNPPh2)2(μ-MesNPPh2{μ-NCMe})Mo(CO)3] (An = U, 3; An = Th, 4), and [IAn(η2-MesNPiPr2)(μ-MesNPiPr2){μ-NC(Me)N(Mes)PiPr2}Mo(CO)3] (An = U, 5; Th, 6). Structural and spectroscopic data confirm the assignment of a ketimido ligand bridging An(IV) and Mo(0) centers. The isolation of 1-6 is in contrast to our previously reported preparations of [(X)An(MesNPPh2)3Mo(CO)3] (An = U or Th; X= Cl or I; Chem. Commun. 2018, 54, 13515-13518) with the difference in reactivity being attributable to a combination of ancillary phosphino-amide, reaction solvent, and temperature variation. Complexes 1-5 represent the first examples of structurally characterized ketimido-bridged actinide-transition metal linkages and demonstrate the profound differences in reaction outcomes that can occur from relatively minor experimental changes.


Self medication practices.
A recently published study observes that lay people control not only decision-making about the health professionals they consult and whether or not they accept the advice they receive, but also about their own care, i.e., self-medication. The authors state that self-medication, which they and others term "folk medicine" is increasing in prominence in relation to its counterpart, professional medicine. Reasons for this shift include, among others, changing disease patterns, shortages of health personnel, and greater public interest in and knowledge about matters of health.The study also stated that the average household had almost 30 different medications on hand, only five of which were likely to be prescriptions. Two-thirds of all purchases of medications were self-determined. There was, as expected, considerable variation in who motivates such purchases according to types of illness involved. If the feasibility study serves no other purpose, its primary value lies in suggesting the areas in which health education and information may be required.


Early PET/CT after radiofrequency ablation in colorectal cancer liver metastases: is it useful?
Morphologic imaging after radiofrequency ablation (RFA) of liver metastases is hampered by an inflammatory response in the ablation margin, making the identification of local tumor progression (LTP) difficult. The aim of this study was to evaluate the efficacy of early (18)F-FDG PET/CT scanning to monitor the effectiveness of RFA in colorectal liver metastases. Twelve patients with 20 metastases were treated with RFA for colorectal liver metastases. They underwent PET/CT within 2 weeks before RFA and within 24 hours after RFA (so termed "early PET/CT"). PET/CT was repeated at 1, 3, and 6 months, and then every 6 months after ablation. The standard of reference was based on available clinical and radiological follow-up data. Early PET/CT revealed total photopenia in 16 RFA-treated metastases, which were found to be without residual tumor on the final PET/CT scan. Three RFA-treated metastases with focal uptake were identified as local tumor progression, which necessitated further treatment. One RFA-treated metastasis with rim-shaped uptake was regarded as inflammation. The results of the early PET/CT scanning were consistent with the findings of the final follow-up. PET/CT performed within 24 hours after RFA can effectively detect whether residual tumor exists for colorectal cancer liver metastases. The results can guide further treatment, and may improve the efficacy of RFA.


Influence of the Sodium Precursor on the Cubic-to-Hexagonal Phase Transformation and Controlled Preparation of Uniform NaNdF4 Nanoparticles.
NaLnF4 nanoparticles (NPs) with lighter lanthanides (where Ln = La, Ce, Nd, or Pr) are more difficult to prepare than those with heavier lanthanides [Naduviledathu et al. Chem Mater., 2014, 26, 5689]. Our knowledge is weakest for NaLnF4 NPs with the lowest atomic mass lanthanides (Yan's group 1: La to Nd) and more advanced for group 2 (Sm to Tb) NaLnF4 NPs [Mai et al., J. Am. Chem. Soc., 2006, 128, 6426]. Here we focus on the synthesis of NaNdF4 NPs. We employed the high-temperature chemical coprecipitation method and explored the influence of a wide range of synthesis parameters (e.g., reaction time and temperature, precursor ratios (Na+/Nd3+ and F-/Nd3+), choice of a sodium precursor (Na-oleate or NaOH), and the amount of oleic acid) on the size and uniformity of the NPs obtained. We tried to identify "sweet spots" in the reaction space that led to uniform NaNdF4 NPs with sizes appropriate for mass tag applications in mass cytometry. We were able to obtain NPs with a variety of sizes in the range of 5-38 nm with several different shapes (e.g., polyhedra, spheres, and rods). XRD patterns recorded for aliquots collected at different reaction time intervals revealed that NaNdF4 nucleated in the cubic phase (α) and then transformed to the hexagonal phase (β) as the reaction progressed up to 2 h. A very striking observation was that the NPs synthesized using NaOH as a reactant preferred to remain in the α-phase, and for a lower reaction temperature (285 °C), did not undergo a phase transformation to the β-phase over 2 h of reaction time. Under similar experimental conditions, NPs prepared using Na-oleate exhibited an α → β phase transformation. Nevertheless, NaNdF4 NPs prepared at a higher temperature (315 °C) using either of the Na+ precursors exhibited the α → β phase transformation over time. This transition, however, appeared to be faster in the case of the NPs synthesized using Na-oleate. We found that, in many instances, syntheses carried out using Na-oleate produced more uniform NPs compared to those synthesized using NaOH. Under the conditions we employed for the Na-oleate precursor, the NPs initially formed were polydisperse spheres that evolved into irregular polyhedra and eventually formed more uniform rod-shaped NPs. The aspect ratio of the final NPs depended on the Na+/Nd3+ precursor ratio. High-resolution transmission electron micrographs and corresponding fast Fourier transform of the data provided information about the preferred growth direction of the NaNdF4 nanorods.


Variable colonial phenotypic expression and comparison to nuclei number in Blastomyces dermatitidis.
We examined colonial phenotypes of five isolates of Blastomyces dermatitidis at 33, 35 and 37 degrees C on four growth media. Three different colony types were identified: yeast, mycelial, and a mixed type consisting of both yeast and mycelia. Each isolate varied in its ability to grow on the different media and at different temperatures, and in the types of colonies it produced in the various temperature-media combinations. Quantification of the number of nuclei per yeast cell by fluorescent staining revealed no correlation between the number of nuclei per cell and the colonial phenotype. These results indicate that the colonial phenotype of B. dermatitidis varies with the isolate as well as with temperature and culture medium, but is not correlated with the number of nuclei per yeast. These findings could provide a start towards typing B. dermatitidis isolates.


Dual-trap optical tweezers with real-time force clamp control.
Single molecule force clamp experiments are widely used to investigate how enzymes, molecular motors, and other molecular mechanisms work. We developed a dual-trap optical tweezers instrument with real-time (200 kHz update rate) force clamp control that can exert 0-100 pN forces on trapped beads. A model for force clamp experiments in the dumbbell-geometry is presented. We observe good agreement between predicted and observed power spectra of bead position and force fluctuations. The model can be used to predict and optimize the dynamics of real-time force clamp optical tweezers instruments. The results from a proof-of-principle experiment in which lambda exonuclease converts a double-stranded DNA tether, held at constant tension, into its single-stranded form, show that the developed instrument is suitable for experiments in single molecule biology.


Multiple feature-based portal vein classification for liver segment extraction.
The liver segments divided by Couinaud classification method are used to understand the functional anatomy of liver, which is significant in hepatic resection surgery. In Couinaud classification method, each third-order branch of the portal vein (PV) defines the supplied territory of a corresponding liver segment. However, the accuracies of the reconstruction and classification of PV are affected by the complicated structure of the vein. The purpose of this paper is to develop a separation and classification method that can accurately extract the liver segments. In this paper, a multiple feature-based method is proposed to obtain liver segments. Because the portal and hepatic veins usually connect in the vessel segmentation result, the PV is first completely separated based on the different strategies for minimal node cut using fused features of topology and appearance. Meanwhile, all bifurcation nodes of PV are detected. The bifurcation nodes are initial ordered through their linkages to classify the branches. Then, the feature of the vascular topology is used to refine the orders of bifurcation nodes. The bifurcation nodes with the refined orders classify the branches between them, and the third-order branches of PV are obtained. The liver segments are eventually obtained through the third-order branches. The separation and classification in the proposed method are evaluated on the CT and MR datasets. The average values of Dice, Jaccard, Recall, and Precision obtained by the proposed method are 93.00%, 87.90%, 93.47%, and 93.19%, respectively. Compared with the state-of-the-art methods, the separation results obtained by the proposed method are more accurate. The branches of PV are classified based on the separation result. According to the third-order branches, eight liver segments correspond to the different functional areas are precisely extracted. The proposed method achieves a high accuracy for the liver segment extraction. And the extracted liver segments are significant for the preplanning of resection surgery.


Electrical stimulation of dorsal root entry zone attenuates wide-dynamic-range neuronal activity in rats.
Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. We conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 msec, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1). The elevated spontaneous activity rate of WDR neurons in SNL rats (n = 25; data combined from post-SNL groups at days 14-16 [n = 15] and days 45-75 [n = 10]) was significantly decreased from the prestimulation level (p < 0.01) at 0-15 min and 30-45 min post-stimulation. In both sham-operated (n = 8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not the A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1-10 mA, 2 msec) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a form of brief neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0-15 min in all groups (p < 0.05). Attenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain.


Aggressive angiomyxoma of the vagina: Case report and review of the literature.
To present the case of a patient diagnosed with aggressive angiomyxoma of the vagina and to conduct a review of the diagnosis, treatment and prognosis of this disease condition. A 46-year old female patient complaining of dysuria and vaginal mass sensation. Physical exploration and imaging studies revealed a tumor extending into the pelvic cavity. The mass was resected through a vaginal approach and pathology of the surgical specimen showed an aggressive angiomyxoma of the vagina. New retrorectar surgery was performed three months after the initial resection because of recurrence. A search was conducted in the Medline via PubMed, Lilacs, Scielo and Google Scholar databases using the terms "Angiomyxoma," "Aggressive" and "Vagina." The search included review articles, case reports and case series published in English and Spanish since 1995. The information extracted included diagnosis, symptoms, signs, immunohistochemistry and imaging studies used, type of treatment surgical or other - and prognosis. Findings are described in narrative form. Overall, 23 titles were identified, of which 14 case reports, 2 clinical case series and 1 review article met the inclusion criteria. Sixty-five per cent of the patients were between 30 and 50 years of age. Diagnosis was made by immunohistochemistry in 8 cases, and diagnostic imaging was used in 12 cases. Computed tomography showed sharper contours of the lesions. Surgical treatment was applied in all reports, supplemented by hormonal therapy in 4 cases. There was follow-up in 14 of the 17 cases reported. Aggressive angiomyxoma of the vagina is rare. Assessment of the role of various immunohistochemical tests is needed in cases identified as aggressive angiomyxoma on histopathology. Evaluation of hormonal treatment as an adjunct to surgery is required. Prognosis is good.


Maximizing vocational outcome after brain injury: integration of medical and vocational hospital-based services.
To describe a medical and vocational case-management system that has been implemented at the Mayo Medical Center in Rochester, Minnesota, to decrease the time between onset of brain injury and successful community reintegration. Barriers to employment are identified and targeted as part of a system that integrates medical center- and community-based services. The success of the project will be determined by several sources, including the Mayo-Portland Adaptability Inventory, a vocational rating scale, and traditional measures of vocational success (for example, level of independent living, job type and setting, rate of pay, and the type and cost of vocational supports being used). Overall study outcomes will be compared against benchmarks derived from the literature on vocational outcome after brain injury. Preliminary data are encouraging that project goals are attainable. The medical case-management system has decreased the amount of time between injury and initiation of vocational and other rehabilitation services. During the first year, 67 persons with brain injury began receiving vocational services through the project, and 34% are in community-based nonsheltered work or training programs. Second-year data will reveal whether the goal of 70% placement within 9 months after admission to the project can be maintained.


Association between postnatal second-hand smoke exposure and ADHD in children: a systematic review and meta-analysis.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder which is caused by the interplay of genetic and environmental risk factors such as second-hand smoke (SHS). The association between postnatal exposure to SHS and ADHD risk in children was still inconclusive. We performed a systematic review and meta-analysis to explore the definite association. We searched for relevant studies from PubMed, Embase, Ovid, and Web of Science databases up to January 2020. We used random effect models to calculate pooled odds ratio (OR) with 95% confidence interval (CI). Subgroup analyses and sensitive analyses were also performed to solve the heterogeneity. According to our inclusion criteria, 9 studies including 6 cross-sectional studies, 2 cohort studies, and 1 case-control study were included in the final analysis. Postnatal exposure to SHS increased the risk of ADHD in children (OR: 1.60; 95% CI: 1.37-1.87). Children who exposed to SHS were found a slight risk for conduct problems (OR: 1.33, 95% CI: 1.00-1.77). Among the studies which used cotinine as a biomarker for SHS exposure, a lower pooled OR (OR = 1.16, 95%CI = 1.01, 1.33) was observed between cotinine and ADHD in children. Our meta-analysis results suggested that SHS exposure may be a risk factor for ADHD. We also found that SHS exposure may be associated with some adverse behavioral outcomes. More prospective studies should be conducted to confirm the relationship between SHS exposure and ADHD in children.


Enactments: an evolving dyadic concept of acting out.
Unspoken actions between the therapist and the patient have major and often unconscious influences on the psychotherapeutic situation. Mutual transferences can bring about acting-out behaviors that portray transference wishes and defenses within both parties. Such actions tend to replace or overshadow verbalizing intrapsychic strife and in that sense can function as formidable resistance to therapeutic introspection. They also may represent behavioral attempts to communicate significant earlier experiences. Reflection on this dyadic interplay has led to contemporary treatment concepts. Enactment, actualization, and treatment misalliances are behavioral manifestations of urges, conflicts, and identifications and they appear most frequently during regressive periods in psychotherapy. Initially an enactment may include a component of the therapist's reciprocal behavior as a necessary feature of the process, prior to a fuller dynamic understanding and eventual definitive interpretation. Collusion by the therapist, through mutual and continuing acting out or through attempts to re-parent, will encourage antitherapeutic misalliances that can lead to continuing symptomatic behaviors and boundary violations. Continuing self-inquiry is essential to facilitate therapeutic change and we need to be aware that the principal analyzing device available to bring about positive change in our patients, is to be found within ourselves.


Basic considerations in the use of coded excitation for color flow imaging applications.
Coded excitation is now a well-established technique in medical ultrasound for B-mode imaging applications. It enables a gain in depth of penetration, without sacrificing the spatial resolution and maintaining an acceptable peak intensity for patient safety. The rationale of this technique for velocity estimation applications still has to be formulated in more precise terms. In particular, differences in the situation that arise in color flow imaging (CFI) applications from typical B-mode imaging conditions, such as signal-to-noise ratio conditions, pulsing strategy, and safety requirements, need to be specifically addressed to assess more quantitatively the potential of this technique. This paper discusses the potential improvement in sensitivity, resolution, and statistical performance provided by coded excitation for CFI applications from theoretical considerations and simulations.


OrganoCat Fractionation of Empty Fruit Bunches from Palm Trees into Lignin, Sugars, and Cellulose-Enriched Pulp.
The palm oil industry produces large amounts of empty fruit bunches (EFB) as waste. EFB are very recalcitrant toward further processing, although their valorization could create novel incentives and bio-economic opportunities for the industries involved. Herein, EFB have been successfully subjected to the OrganoCat pretreatment-using 2,5-furandicarboxylic acid as the biogenic catalyst-to fractionate and separate this lignocellulosic material into its main components in a single step. The pretreatment of EFB leads to the deacetylation and depolymerization of noncellulosic polysaccharides and to the partial delignification of the cellulosic fiber. The OrganoCat processing of EFB yielded 45 ± 0.5 wt % cellulose-enriched pulp, 20 ± 0.7 wt % extracted lignin, 3.8 ± 0.2 wt % furfural, and 11 ± 0.6 wt % hydrolyzed sugars. The obtained EFB-pulp showed high accessibility to cellulases, resulting in a glucan conversion of 73 ± 2% after 72 h (15 ± 2% after 1 h) with commercial cellulase cocktail (Accellerase 1500). Overall, the results suggest that the treatment of the EFB material using OrganoCat may create promising paths for the full valorization of EFBs.


Development and Evaluation of an Intravenous Infusion Sequence Annotation System.
The sequence of intravenous infusions may impact the efficacy, safety, and cost of intravenous medications. The study describes and assesses a computerized clinical decision support annotation system capable of analyzing the sequence of intravenous infusions. All intravenous medications on the hospital formulary were analyzed based on factors that impact intravenous infusion sequence. Eight pharmacy infusion knowledge databases were constructed based on Hospital Infusion Standards. These databases were incorporated into the computerized sequence annotation module within the electronic health record system. The annotation process was changed from pharmacists' manual annotation (phase 1) to computer-aided pharmacist manual annotation (phase 2) to automated computer annotation (phase 3). Comparing phase 2 to phase 1, there were significant differences in sequence annotation with regards to the percentage of hospital wards annotated (100% vs. 4.65%, chi-square = 180.95, p < 0.001), percentage of patients annotated (64.18% vs. 0.52%, chi-square = 90.46, p < 0.001), percentage of intravenous orders annotated (75.67% vs. 0.77%, chi-square = 118.78, p < 0.001), and the number of tubing flushes per ward per day (118.51 vs. 2,115.00, p < 0.001). Compared with phase 1, there were significant cost savings in tubing flushes in phase 2 and phase 3. Compared with phase 1, there was significant difference in the time nurses spent on tubing flushes in phase 2 and phase 3 (1,244.94 vs. 21,684.8 minutes, p < 0.001; 1,369.51 vs. 21,684.8 minutes, p < 0.001). Compared with phase 1, significantly less time was required for pharmacist annotation in phase 2 and phase 3 (90.6 vs. 4,753.57 minutes, p < 0.001; 0.05 vs. 4,753.57 minutes, p < 0.001). A computerized infusion annotation system is efficient in sequence annotation and significant savings in tubing flushes can be achieved as a result.


Prognostic significance of admission levels of cardiac indicators in patients with acute ischaemic stroke: prospective observational study.
The performance of cardiac indicators as determinants of stroke outcomes remains debatable, therefore the present study focused on the short-term prognostic value of cardiac indicators in patients who had experienced acute ischaemic stroke. Consecutive patients with acute ischaemic stroke were enrolled in a prospective stroke registry. Data on demographics, clinical characteristics and cardiac indicator levels (including troponin I, creatine kinase-MB, myoglobin and brain natriuretic peptide) were prospectively collected. Receiver operating characteristic curves and binary logistic regression models were used to examine the performance of variables in predicting poor functional outcomes (modified Rankin Scale score 2-6). Out of 337 patients with acute ischaemic stroke, myoglobin had the greatest power for predicting poor outcomes among the cardiac indicators. Forward stepwise multivariate logistic regression analysis revealed that myoglobin could independently predict short-term outcomes. Spearman's rank correlation tests indicated a positive correlation between myoglobin levels and stroke severity. Among cardiac indicators, myoglobin may be an independent predictor of short-term outcomes in patients with acute ischaemic stroke.


Long-term potentiation in the dentate gyrus of the rat hippocampus is accompanied by brain-derived neurotrophic factor-induced activation of TrkB.
A role for neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF), in modulating synaptic plasticity in the adult brain has been described in recent years by several laboratories. A great deal of emphasis has been placed on establishing its precise role in the expression of long-term potentiation (LTP) in the hippocampus. Here we attempt to address this question by investigating, first, its release following induction of LTP in perforant path-granule cell synapses and, second, the signalling events which follow activation of the BDNF receptor, TrkB, in the presynaptic terminal. We report that BDNF release is increased from slices of dentate gyrus following tetanic stimulation of the perforant path and that TrkB activation is increased in synaptosomes prepared from tetanized dentate gyrus. These changes are accompanied by increased activation of one member of the family of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK) and the data indicate that these events play a role in modulating release of glutamate from perforant path-granule cell synapses, because the Trk inhibitor K252a and the ERK inhibitor, UO126, both inhibited the BDNF-induced enhancement of release. We propose that the increase in phosphorylation of the transcription factor cAMP response element binding protein and in protein synthesis might underlie the more persistent components of LTP in dentate gyrus.


Studies of singlet Rydberg series of LiH derived from Li(nl) + H(1s), with n ≤ 6 and l ≤ 4.
The 50 singlet states of LiH composed of 49 Rydberg states and one non-Rydberg ionic state derivable from Li(nl) + H(1s), with n ≤ 6 and l ≤ 4, are studied using the multi-reference configuration interaction method combined with the Stuttgart/Köln group's effective core potential/core polarization potential method. Basis functions that can yield energy levels up to the 6g orbital of Li have been developed, and they are used with a huge number of universal Kaufmann basis functions for Rydberg states. The systematics and regularities of the physical properties such as potential energies, quantum defects, permanent dipole moments, transition dipole moments, and nonadiabatic coupling matrix elements of the Rydberg series are studied. The behaviors of potential energy curves and quantum defect curves are explained using the Fermi approximation. The permanent dipole moments of the Rydberg series reveal that they are determined by the sizes of the Rydberg orbitals, which are proportional to n(2). Interesting mirror relationships of the dipole moments are observed between l-mixed Rydberg series, with the rule Δl = ±1, except for s-d mixing, which is also accompanied by n-mixing. The members of the l-mixed Rydberg series have dipole moments with opposite directions. The first derivatives of the dipole moment curves, which show the charge-transfer component, clearly show not only mirror relationships in terms of direction but also oscillations. The transition dipole moment matrix elements of the Rydberg series are determined by the small-r region, with two consequences. One is that the transition dipole moment matrix elements show n(-3/2) dependence. The other is that the magnitudes of the transition dipole moment matrix elements decrease rapidly as l increases.


Intraspinal epidural sarcoidosis: case report.
A rare case of lumbar intraspinal epidural sarcoidosis is identified. The rarity of this condition and its clinical presentation are stressed. A young Caucasian man presented with the progressive onset of cauda equina syndrome as a result of an expanding mass in the lumbar epidural space compromising the lumbar dural tube from L1 to S1. The patient presented with motor, sensory, and sphincteric dysfunction as a result of this large intraspinal epidural mass. No evidence of systemic illness was noted concomitant with the patient's onset of neurological symptomatology. The patient underwent surgical extirpation of a lumbar intraspinal epidural mass, which was identified histopathologically as sarcoid granuloma. The postoperative work-up included the identification of a mediastinal adenopathy, which was subsequently biopsied and confirmed the diagnosis of sarcoid disease. The patient was treated postoperatively with oral prednisone over a 4-month period. At 7 months postoperatively, the patient had regained gainful employment, the results of his neurological examination were normal, and he was pain-free. The patient underwent a multilevel bilateral lumbar laminectomy with facet preservation, extending from L1 to S1, allowing for a gross total removal of the epidural mass. Postoperative oral prednisone was administered as adjuvant therapy for the treatment of multisystem sarcoid disease. Aggressive surgical management involving the removal of an extensive epidural mass of the lumbar canal, which was diagnosed as sarcoid disease, coupled with the adjuvant use of oral prednisone has resulted in an excellent outcome for the patient. The results of his clinical examination are now normal, and postoperative radiological imaging reveals no evidence of recurrent or residual disease in the lumbar epidural space. In the unusual case of intraspinal epidural sarcoidosis, the surgical resection of accessible intraspinal epidural masses is recommended, as is the use of oral prednisone postoperatively.


Effect of ketotifen on the methyltransferase activity of asthmatic patients.
The results of this study have revealed that asthmatic individuals have less methyltransferase activity, compared to healthy individuals. This is reflected in a less fluidity of the plasmatic membrane and thus, presents with less beta-receptors compared to healthy subjects. Ketotifen is capable of partially reversing this situation where it stimulates methyltransferase activity of asthmatic individuals approaching the enzyme activity to healthy individuals.


Non-functional neuroendocrine carcinoma of the pancreas: incidence, tumor biology, and outcomes in 2,158 patients.
Pancreatic neuroendocrine cancer is a rare, indolent malignancy with no effective systemic therapy currently available. This population-based analysis evaluated the hypothesis that long-term survival benefit is greater with aggressive, rather than limited, surgical therapy. Non-functional pancreatic neuroendocrine carcinoma (NF-pNEC) cases diagnosed from 1973 to 2004 were retrieved from the SEER database. A total of 2,158 patients with NF-pNEC were identified, representing 2% of all pancreatic malignancies. The annual incidence increased from 1.4 to 3.0 per million during the study period. On average, tumors measured 59 +/- 35 mm (median 50), and age at diagnosis was 59 +/- 15 years; 29% of patients were younger than 50. Nodal (44%) and systemic metastases (60%) were common. Overall the 5-, 10-, and 20-year survival rates were 33%, 17%, and 10%, respectively. Removal of the primary tumor significantly prolonged survival in the entire cohort (median 1.2 vs. 8.4 years; p < 0.001) and among those with metastases (median 1.0 vs. 4.8 years; p < 0.001). No survival difference was seen between enucleation and resection of the primary tumor (median 10.2 versus 9.2 years, p = 0.456). This study suggests that surgical therapy improves survival among patients with localized, as well as metastatic, NF-pNEC. Enucleation may be oncologically equivalent to resection.


Something going on in Milan: a review of the 4th International PhD Student Cancer Conference.
The 4th International PhD Student Cancer Conference was held at the IFOM-IEO-Campus in Milan from 19-21 May 2010 http://www.semm.it/events_researchPast.phpThe Conference covered many topics related to cancer, from basic biology to clinical aspects of the disease. All attendees presented their research, by either giving a talk or presenting a poster. This conference is an opportunity to introduce PhD students to top cancer research institutes across Europe.THE CORE PARTICIPANTING INSTITUTES INCLUDED: European School of Molecular Medicine (SEMM)-IFOM-IEO Campus, MilanBeatson Institute for Cancer Research (BICR), GlasgowCambridge Research Institute (CRI), Cambridge, UKMRC Gray Institute of Radiation Biology (GIROB), OxfordLondon Research Institute (LRI), LondonPaterson Institute for Cancer Research (PICR), ManchesterThe Netherlands Cancer Institute (NKI), Amsterdam'You organizers have crushed all my prejudices towards Italians. Congratulations, I enjoyed the conference immensely!' Even if it might have sounded like rudeness for sure this was supposed to be a genuine compliment (at least, that's how we took it), also considering that it was told by a guy who himself was the fusion of two usually antithetical concepts: fashion style and English nationality.The year 2010 has marked an important event for Italian research in the international scientific panorama: the European School of Molecular Medicine (SEMM) had the honour to host the 4th International PhD Student Cancer Conference, which was held from 19-21 May 2010 at the IFOM-IEO-Campus (http://www.semm.it/events_researchPast.php) in Milan.The conference was attended by more than one hundred students, coming from a selection of cutting edge European institutes devoted to cancer research. The rationale behind it is the promotion of cooperation among young scientists across Europe to debate about science and to exchange ideas and experiences. But that is not all, it is also designed for PhD students to get in touch with other prestigious research centres and to create connections for future post docs or job experiences. And last but not least, it is a golden chance for penniless PhD students to spend a couple of extra days visiting a foreign country (this motivation will of course never be voiced to supervisors).The network of participating institutes has a three-nation core, made up of the Netherlands Cancer Institute, the Italian European School of Molecular Medicine (SEMM) and five UK Cancer Research Institutes (The London Research Institute, The Cambridge Research Institute, The Beatson Institute for Cancer Research in Glasgow, The Patterson Institute for Cancer Research in Manchester and the MRC Gray Institute for Radiation Oncology and Biology in Oxford).The conference is hosted and organised every year by one of the core institutes; the first was in Cambridge in 2007, Amsterdam in 2008 and London in 2009, this year was the turn of Milan.In addition to the core institutes, PhD students from several other high-profile institutes are invited to attend the conference. This year participants applied from the Spanish National Cancer Centre (CNIO, Madrid), the German Cancer Research Centre (DKFZ, Heidelberg), the European Molecular Biology Labs (EMBL, Heidelberg) and the San Raffaele Institute (HSR, Milan). Moreover four 'special guests' from the National Centre for Biological Sciences of Bangalore (India) attended the conference in Milan. This represents a first step in widening the horizons beyond Europe into a global worldwide network of talented PhD students in life sciences.The conference spread over two and a half days (Wednesday 19th to Friday 21st May) and touched on a broad spectrum of topics: from basic biology to development, from cancer therapies to modelling and top-down new generation global approaches. The final selection of presentations has been a tough task for us organisers (Chiara Segré, Federica Castellucci, Francesca Milanesi, Gianluca Varetti and Gian Maria Sarra Ferraris), due to the high scientific level of the abstracts submitted. In the end, 26 top students were chosen to give a 15-min oral presentation in one of eight sessions: Development & Differentiation, Cell Migration, Immunology & Cancer, Modelling & Large Scale approaches, Genome Instability, Signal Transduction, Cancer Genetics & Drug Resistance, Stem Cells in Biology and Cancer.The scientific programme was further enriched by two scientific special sessions, held by Professor Pier Paolo di Fiore and Dr Giuseppe Testa, Principal Investigators at the IFOM-IEO-Campus and by a bioethical round table on human embryonic stem cell research moderated by Silvia Camporesi, a senior PhD student in the SEMM PhD Programme 'Foundation of Life Science and their Bioethical Consequences'.ON TOP OF EVERYTHING, WE HAD THE PLEASURE OF INVITING, AS KEYNOTE SPEAKERS, TWO LEADING EUROPEAN SCIENTISTS IN THE FIELDS OF CANCER INVASION AND BIOLOGY OF STEM CELLS, RESPECTIVELY: Dr Peter Friedl from The Nijmegen Centre for Molecular Life (The Netherlands) and Professor Andreas Trumpp from The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (Heidelberg).All the student talks have distinguished themselves for the impressive quality of the science; an encouraging evidence of the high profile level of research carried out in Europe. It would be beyond the purposes of this report to summarise all 26 talks, which touched many different and specific topics. For further information, the Conference Abstract book with all the scientific content is available on the conference Web site (http://www.semm.it/events_researchPast.php). In what follows, the special sessions and the keynote lectures will be discussed in detail.


Long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect the histamine H1 blocker terfenadine-induced torsades de pointes arrhythmias.
Although a second-generation histamine H(1) blocker terfenadine induced torsades de pointes (TdP) arrhythmias in patients via the blockade of a rapid component of delayed rectifier K(+) current (I(Kr)), such action of terfenadine has not been detected in previous animal models. We analysed the potential of the canine persistent atrioventricular block heart, a new in vivo proarrhythmia model, to detect a torsadogenic effect of terfenadine of an oral dose of 3 or 30 mg kg(-1). The doses can provide therapeutic to supra-therapeutic plasma concentrations as an anti-histamine. In 2 weeks of bradycardiac heart model, there were no significant changes in any of the electrocardiogram parameters after the administration of both doses of terfenadine. In 4-6 weeks of bradycardiac heart model, the low dose of terfenadine hardly affected any of the electrocardiogram parameters except that it induced TdP in one out of six animals. The high dose significantly decreased the atrial rate and ventricular rate, prolonged the QT interval, and induced TdP in five out of six animals. Moreover, temporal variability of repolarization increased after the high-dose administration. These results suggest that long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect terfenadine-induced TdP.


Achieving the Goals of the National HIV/AIDS Strategy: Declining HIV Diagnoses, Improving Clinical Outcomes, and Diminishing Racial/Ethnic Disparities in King County, WA (2004-2013).
The US National HIV/AIDS Strategy defines national objectives related to HIV prevention and care. The extent to which US cities are meeting those objectives is uncertain. We analyzed King County, WA, HIV surveillance data collected between 2004 and 2013. The study population included 9539 persons diagnosed as having and living with HIV infection and 3779 persons with newly diagnosed HIV infection. Between 2004 and 2013, the rate of new HIV diagnosis decreased from 18.4 to 13.2 per 100,000 residents (decline of 28%); AIDS diagnosis rates declined 42% from 12 to 7 per 100,000; and age-adjusted death rates decreased from 27 to 15 per 1000 persons living with HIV/AIDS (decline of 42%; P<0.0001 for all 3 trends). The rate of new HIV diagnosis declined 26% among men who have sex with men (MSM; P=0.0002), with the largest decline occurring in black MSM (44%). Among 8679 individuals with laboratory results reported to National HIV Surveillance System from 2006 through 2013, viral suppression (viral load<200 copies/mL) increased from 45% to 86% (P<0.0001), with all racial/ethnic groups achieving greater than 80% viral suppression in 2013. The rates of new HIV diagnosis, AIDS diagnoses, and mortality in persons living with HIV in King County, WA, have significantly declined over the last decade. These changes have occurred concurrent with a dramatic increase in HIV viral suppression and have affected diverse populations, including MSM and African American MSM. These findings demonstrate substantial local success in achieving the goals of the National HIV/AIDS Strategy.


A Central Bioactive Region of LTBP-2 Stimulates the Expression of TGF-β1 in Fibroblasts via Akt and p38 Signalling Pathways.
Latent transforming growth factor-β-1 binding protein-2 (LTBP-2) belongs to the LTBP-fibrillin superfamily of extracellular proteins. Unlike other LTBPs, LTBP-2 does not covalently bind transforming growth factor-β1 (TGF-β1) but appears to be implicated in the regulation of TGF-β1 bioactivity, although the mechanisms are largely unknown. In experiments originally designed to study the displacement of latent TGF-β1 complexes from matrix storage, we found that the addition of exogenous LTBP-2 to cultured human MSU-1.1 fibroblasts caused an increase in TGF-β1 levels in the medium. However, the TGF-β1 increase was due to an upregulation of TGF-β1 expression and secretion rather than a displacement of matrix-stored TGF-β1. The secreted TGF-β1 was mainly in an inactive form, and its concentration peaked around 15 h after addition of LTBP-2. Using a series of recombinant LTBP-2 fragments, the bioactivity was identified to a small region of LTBP-2 consisting of an 8-Cys motif flanked by four epidermal growth factor (EGF)-like repeats. The LTBP-2 stimulation of TGF-β expression involved the phosphorylation of both Akt and p38 mitogen-activated protein kinase (MAPK) signalling proteins, and specific inactivation of each protein individually blocked TGF-β1 increase. The search for the cell surface receptor mediating this LTBP-2 activity proved inconclusive. Inhibitory antibodies to integrins β1 and αVβ5 showed no reduction of LTBP-2 stimulation of TGF-β1. However, TGF-β1 upregulation was partially inhibited by anti-αVβ3 integrin antibodies, suggestive of a direct or indirect role for this integrin. Overall, the study indicates that LTBP-2 can directly upregulate cellular TGF-β1 expression and secretion by interaction with cells via a short central bioactive region. This may be significant in connective tissue disorders involving aberrant TGF-β1 signalling.


Sleep in restrictive lung disease.
Restrictive lung disease patients exhibit a wide range of breathing and oxygenation abnormalities during sleep. The combination of degree of restriction, whether it is intrapulmonary or extrapulmonary, and confounding factors, such as obesity, age, and sex, will ultimately determine the degree of disturbed nocturnal physiology. The sleep literature is still sparse in most restrictive diseases. For patients with interstitial lung disease, the role of nocturnal oxygen in chronic established fibrosis, and also in acute alveolitis (e.g., farmer's lung, bird fancier's lung, etc.), has not been addressed. As fibrotic lung disease progresses, the degree of nocturnal desaturation and breathing dysrhythmias will progress. Changes in sleep architecture are likely related to the progression of the disease, but this is not known with certainty. Long-term evaluation of sleep and breathing in interstitial lung disease will give further insight into whether or not sleep changes are primary or secondary events. For kyphoscoliosis patients, again, we need more information on sleep as the thoracic deformity changes. In addition, the use of drugs (acetazolomide, medroxyprogesterone, and almitrine) and/or nasal CPAP to treat nocturnal desaturation needs to be assessed in a controlled fashion. In neuromuscular disease, the dynamics of gas exchange and sleep structure need to be defined in a larger group of patients. Factors such as degree of muscle weakness, degree of underlying lung diseases, and medications must be taken into consideration. Nocturnal hypoxemia may cause muscle weakness and fatigue, which in time, could cause more nocturnal hypoventilation and further hypoxemia. Supplemental nocturnal oxygen should be evaluated in this population.


[Prenatal care attention in the view of a group of women who use the supplementary subsector].
This qualitative approach study, aimed at understanding the perception of women who went through the Prenatal Care Attention (PCA), on the context of the Supplementary Subsector (SS), in relation to the quality of this attention. Data were collected through semi-structured interviews and analyzed by descriptive categorization. For the interviews, the PCA was considered of good quality, meeting the women's needs and exzpectations. Receptivity, bonding with the expert the consequently transmitted safety feeling and the duration of the appointments were the prominent criteria in this evaluation. Their'experiences suggest that the PCA performed in the SS partially meets the recommendations of the Brazilian Ministry of Health (MH) and the World Health Organization (WHO). The appointments' frequency and the orientation provided also meet the recommendations. However, the data suggest that the PCA does not meet the orientations of the MH and the WHO regarding avoiding the extended use of hard technology, such as obstetric sonography.


Colony-stimulating factor-1 receptor protein expression is a specific marker for goldfish (Carassius auratus L.) macrophage progenitors and their differentiated cell types.
Signaling through the colony-stimulating factor-1 receptor (CSF-1R) mediates the proliferation, differentiation, and activation of macrophages and their progenitors. In this study we report on the use of an anti-goldfish CSF-1R antibody to specifically recognize a population of CSF-1R positive cells from goldfish tissues. Furthermore, using our previously characterized primary kidney macrophage culture system, we show that CSF-1R positive cells include monocytes, macrophages, and their progenitor cells. Freshly isolated progenitor cells had a higher median florescent intensity ratio than those progenitor cells cultured for up to four days. The decrease in CSF-1R expression on the progenitor cells coincides with the appearance and development of monocytes and macrophages. Monocytes were consistently CSF-1R+ and maintained the high level of CSF-1R expression as they developed into macrophages. Like that of mammalian systems, CSF-1R is expressed on all macrophage sub-populations (progenitors, monocytes, macrophages), and CSF-1R expression increases with macrophage development in teleosts.


Adult-onset nemaline myopathy: a case report and review of the literature.
Nemaline (rod) myopathy is a congenital muscle disease with a wide spectrum of phenotypes, ranging from forms with neonatal onset and fatal outcome to asymptomatic forms. An adult-onset variant is characterized by large numbers of rod-containing myofibers, numerous rods per affected myofiber, and the absence of specific structural abnormalities typical of other muscle diseases. Few cases fulfilling these criteria have been described in the literature. Rare cases have had an associated inflammatory component, and the majority of these have occurred in patients with an underlying immunologic disorder. We present an unusual case of an immunologically competent 65-year-old man with late-onset nemaline myopathy, who was previously diagnosed with an inflammatory myopathy based on a muscle biopsy that contained chronic inflammation. His symptoms consisted of a 2-year history of progressive proximal muscle weakness; his family history was unremarkable. A neurologic examination confirmed the presence of bilateral proximal muscle weakness, normal sensation, and decreased upper and lower extremity reflexes. Creatine kinase levels were normal, and electromyographic findings indicated a myopathic process. A modified trichrome stain of the right biceps muscle revealed granular, basophilic, centrally located rods in the atrophic myofibers. Ultrastructurally, these myofibers contained osmiophilic rectangular structures with a latticelike appearance typical of nemaline myopathy. This case illustrates that adult-onset nemaline myopathy, although rare, should be considered in the differential diagnosis of an inflammatory myopathy.


A reliable Raman-spectroscopy-based approach for diagnosis, classification and follow-up of B-cell acute lymphoblastic leukemia.
Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder that shows high mortality rates due to immature lymphocyte B-cell proliferation. B-ALL diagnosis requires identification and classification of the leukemia cells. Here, we demonstrate the use of Raman spectroscopy to discriminate normal lymphocytic B-cells from three different B-leukemia transformed cell lines (i.e., RS4;11, REH, MN60 cells) based on their biochemical features. In combination with immunofluorescence and Western blotting, we show that these Raman markers reflect the relative changes in the potential biological markers from cell surface antigens, cytoplasmic proteins, and DNA content and correlate with the lymphoblastic B-cell maturation/differentiation stages. Our study demonstrates the potential of this technique for classification of B-leukemia cells into the different differentiation/maturation stages, as well as for the identification of key biochemical changes under chemotherapeutic treatments. Finally, preliminary results from clinical samples indicate high consistency of, and potential applications for, this Raman spectroscopy approach.


An experimental model in calvaria to evaluate bone therapies.
The clinical therapeutic application of experimental strategies requires extensive preclinical experimentation in appropriate animal models. Thus, a valid model must be established. The aim of the present study was to determine the critical size defect (CSD) of rat calvaria that is unable to undergo spontaneous bone regeneration. Forty Sprague Dawley female rats (body weight (bw): 250 +/- 20 g) were distributed in two groups. Circular surgical defects, 3 mm (Group A) and 5 mm (Group B) in diameter, were produced in the parietal bones. The animals were left untreated and sacrificed 1, 2, 3 and 6 weeks after surgery. Group A showed bone formation at the experimental site, increasing from 1 week (4.5%) to 6 weeks (46%). However, Group B showed scarce bone formation (less than 10%) throughout the experimental period. We may conclude that a defect 5 mm in diameter is a critical size defect (CSD) because it is the minimum bone defect size that requires treatment to heal. Thus, a circular defect 5 mm in diameter in rat calvaria would be an appropriate experimental model to study bone therapies.


Role of DnaA protein during replication of plasmid pBR322 in Escherichia coli.
The in vivo role of the Escherichia coli protein DnaA in the replication of plasmid pBR322 was investigated, using a plasmid derivative carrying an inducible dnaA+ gene. In LB medium without inducer, the replication of this plasmid, like that of pBR322, was inhibited by heat inactivation of chromosomal DnaA46 protein so that plasmid accumulation ceased 1 to 2 h after the temperature shift. This inhibition did not occur when the plasmid dnaA+ gene was expressed in the presence of the inducer isopropyl-1-thio-beta-D-galactopyranoside (IPTG). Inhibition was also not observed in glycerol minimal medium or in the presence of low concentrations of rifampicin or chloramphenicol. Deletion of the DnaA binding site and the primosome assembly sites (pas, rri) downstream of the replication origin did not affect the plasmid copy number during exponential growth at 30 degrees C, or after inactivation of DnaA by a shift to 42 degrees C in a dnaA46 host, or after oversupply of DnaA, indicating that these sites are not involved in a rate-limiting step for replication in vivo. The accumulation of the replication inhibitor, RNAI, was independent of DnaA activity, ruling out the possibility that DnaA acts as a repressor of RNAI synthesis, as has been suggested in the literature. Changes in the rate of plasmid replication in response to changes in DnaA activity (in LB medium) could be resolved into an early, rom-dependent, and a late, rom-independent component. Rom- plasmids show only the late effect. After heat inactivation of DnaC, plasmid replication ceased immediately.(ABSTRACT TRUNCATED AT 250 WORDS)


Area and contrast effects upon perceptual and imagery acuity.
We measured the size of visual fields within which actual and imagined circular patterns could be resolved, as the patterns varied in both area and relative contrast. As pattern area increased, imagery fields increased in size at the same rate as perceptual fields. However, as the relative contrast between parts of the patterns was reduced, perceptual fields diminished in size, while imagery fields did not. for all variations of pattern area and contrast, fields in imagery were roughly the same shape as fields in perception. A control experiment provided no support for the possible criticism that these results might be explained on the basis of subjects' expectations for the size and shape of the imagery fields, especially since control subjects falsely believed that reductions in contrast would reduce considerably the size of these fields. Although these findings suggest that images and physical objects are functionally equivalent at pattern-processing levels of the visual system, they demonstrate that images and objects are not functionally equivalent at certain levels of the visual system where information about relative contrast is processed.


Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients.
Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer's disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the 'real-world' arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic. We reviewed the presenting clinical features, the pre-API and post-API investigations, diagnosis and outcomes for the first 100 patients who had API as part of their routine work-up at the Imperial Memory Centre, a tertiary referral clinic in the UK National Health Service. API was primarily used to investigate patients with atypical clinical features (56 cases) or those that were young at onset (42 cases). MRI features of AD did not always predict positive API (67%), and 6 of 23 patients with MRIs reported as normal were amyloid-PET positive. There were significantly more cases categorised as non-AD dementia post-API (from 11 to 23). Patients investigated when API was initially available had fewer overall investigations and all patients had significantly fewer investigations in total post-API. API has a clear impact on the investigation of young-onset or complex dementia while reducing the overall burden of investigations. It was most useful in younger patients, atypical presentations or individuals with multiple possible causes of cognitive impairment.


Life-threatening complications associated with the tyrosine kinase inhibitor sunitinib malate.
Adverse events associated with sunitinib, such as cardiac toxicities, renal damage, and hemostatic complications, are well known. The authors report 3 cases in which patients experienced severe life-threatening complications after commencing sunitinib treatment. One patient developed heart failure with dilation of the left ventricle and decrease in the ejection fraction after one cycle of sunitinib and required treatment with an angiotensin-converting enzyme inhibitor, loop diuretics, and dobutamine. Another patient developed coronary artery stenosis after one cycle of sunitinib and was managed through percutaneous coronary intervention. Although follow-on coronary angiography revealed normal findings after 6 further cycles of sunitinib, this patient eventually expired due to multi-organ failure. The third patient had chronic renal failure before sunitinib treatment and required hemodialysis due to acute-on-chronic renal failure after commencing sunitinib treatment.


[Is autologous chondrocyte implantation a technology suitable for ambulatory health care?].
Statutory ambulatory health care services provided by physicians in Germany are specified by a joint committee of physicians and sickness funds, the Federal Committee of Physicians and Sickness Funds. To ensure that only effective interventions are covered, new medical technologies must demonstrate evidence of clinical effectiveness, cost-effectiveness and medical necessity. Due to increasing demands for reimbursement of autologous chondrocyte implantation, the Committee recently assessed this procedure. Autologous chondrocyte implantation (ACI) is a surgical procedure to reestablish the chondral layer in the knee following trauma. Such injuries may subsequently lead to osteoarthritis, and may eventually require joint replacement. Although the U.S. Food and Drug Administration (FDA) approval of ACI limits its usage to treatment of specific knee defects, other indications, such as for chondromalacia patellae, are promoted by proponents of the technology. The Committee conducted a thorough literature review and examined the status of ACI in other health care systems. Reimbursement of this technology was declined for the following reasons: the effectiveness of ACI has not yet been established in long term, comparative studies, and the procedure involves a type of operation not suitable for the ambulatory health care sector. Other public health insurance systems, such as in Switzerland and Canada, have not yet introduced funding for ACI, and an assessment is currently being conducted by the UK National Institute for Clinical Excellence (NICE). Autologous chondrocyte implantation is a technology that will compete with various other new interventions to correct chondral defects of the knee. It is essential that the treatment effect of ACI be demonstrated in clinically sound, comparative trials before this technology is introduced into the public health care system.


CLINICAL CASE OF NEUROMYELITIS OPTICA SPECTRUM DISORDERS IN YOUNG WOMAN TREATED WITH RITUXIMAB.
We report a case of a 28-year-old female who had the clinical manifestation of Neuromyelitis optica spectrum disorders with the area postrema syndrome at 24 years old. The patient presented with decreased vision due to acute optic neuritis, gait impairment, tetraplegia, sensory, and bladder disturbances. Magnetic resonance imaging of the spinal cord showed longitudinal high-intensity signals on a T2-weighted image in cervical and thoracic parts. Her serum and cerebrospinal fluid were positive for the anti-AQP4 antibody. The patient received high-dose methylprednisolone, plasmapheresis, but she remained free from relapses only after prescribing Rituximab. Prophylactic treatment of Neuromyelitis optica spectrum disorders recurrence must be immediately performed when it is identified because the progression of disability is related to the severity of attacks.


Magnetic resonance imaging findings of fibroepithelial polyp of the vulva: radiological-pathological correlation.
We describe the magnetic resonance (MR) imaging findings in a 20-year-old woman with a fibroepithelial polyp of the vulva. Within the lesion, abundant fibrous tissue was visualized as stratiform hypointense areas on T2-weighted magnetic resonance imaging (MRI) scans. At the center of the attachment site, clustered fatty tissue was revealed as linear hyperintense areas on T1-weighted MRI. A mild degree of edematous stroma including less fibrosis and cellularity was demonstrated as hyperintense areas on T2-weighted MRI and hypointense areas on T1-weighted MRI. Although the MRI findings of fibroepithelial polyps of the vulva are often similar to those of aggressive angiomyxoma, angiomyofibroblastoma, and cellular angiofibroma, a fibroepithelial polyp should be considered when radiological images demonstrate the following features: stratiform hypointense areas surrounded by patchy hyperintense areas on T2-weighted MRI and hyperintense areas on T1-weighted MRI.


What Do We Know About Treating Recalcitrant Auricular Keloids? A Systematic Review and Meta-Analysis.
Recalcitrant auricular keloids are keloids that have recurred after any previous treatment. They have been shown to have an increased likelihood of recurrence. There is no consensus on how best to treat recalcitrant auricular keloids. Here, we perform the first systematic review and meta-analysis investigating the evidence for treating recalcitrant auricular keloids. We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews using specific keywords. Prespecified inclusion and exclusion criteria were used to assess article eligibility. Data were extracted for number of recalcitrant keloids, treatment modality, recurrence, and minimum follow-up time. Included articles were stratified by treatment and assigned a level of evidence (LOE) based on the Oxford Centre for Evidence-Based Medicine guidelines. A meta-analysis was performed to estimate recurrence rates with 95% confidence intervals for each treatment modality. A total of 887 unique articles were identified and 13 included. Eleven were LOE III and 2 were LOE IV. Recurrence rates were found to be 9% (95% CI: 3%-25%) for excision with adjuvant brachytherapy, 14% (95% CI: 12%-17%) for excision with adjuvant compression therapy, 17% (95% CI: 3%-56%) for excision with adjuvant external beam radiation, and 18% (95% CI: 4%-53%) for excision with adjuvant steroid injections. No statistical significant difference was found. Data for treatment of auricular keloids are heterogeneous with few high-quality studies. Excision with adjuvant brachytherapy has the lowest recurrence rate in our analysis. Narrow confidence intervals reported here for brachytherapy and compression therapy may help surgeons more confidently recommend either of these treatment modalities to patients.


DNA and RNA within the nucleus: how much sequence-specific spatial organization?
Spatial organization of various nuclear components is often proposed as a means by which nuclei more efficiently carry out their various tasks. Such functional compartmentalization may involve a sequence-specific packaging and placement of DNA and RNA. Here we review recent insights, allowed primarily by advances in fluorescent in situ hybridization methodology, into the organization of nucleic acids within individual nuclei.