[Cognitive functions and cerebral oxygenation of older patients after general and regional anaesthesia].
The aim of the present study was to show the influence of cerebral oxygenation (regional cerebral oxygen saturation rSO(2) by near infrared spectroscopy) and of the nocturnal arterial oxygen saturation (SatO(2) by pulse oximetry) on the restitution of cognitive functions in patients aged between 40 and 85 years scheduled for elective hip arthroplasty. A total of 40 patients (ASA II) were randomized to be operated either in general anaesthesia or regional anaesthesia. The patients were additionally classified by age (40-64 years and 65-85 years). Cognitive functions were tested 14-16 h pre-operatively (t0), 1.5 h post-operatively (t1) and at the first and third postoperative days (t2 and t3). During testing, as well as during surgery and postoperatively until t1, rSO(2) was continuously measured. SatO(2) was measured in the night before surgery (N0) and for 3 nights after surgery (N1, N2, N3) between 22.00 p.m. and 5.00 a.m. These measurements were divided into interval groups (80-83%, 84-87%, 88-91%, 92-95%, 96-100%). Almost all cognitive functions were significantly reduced at t1 in all groups compared to t0, but recovered up to the third postoperative day (t3). RSO(2) in contrast was significantly reduced in all groups compared to t0 at the third postoperative day (t3). The relative proportion of the intervals compared to the total measurement time for SatO(2) shifted in both anaesthesia procedures: before surgery (N0) the most frequented interval was 96-100%, after surgery (N1, N2) it was 88-91%. There was no correlation between rSO(2), the restitution of the tested cognitive functions and SatO(2). Cognitive functions recovered completely during the first 3 postoperative days in patients scheduled for elective hip surgery under general or regional anaesthesia regardless of age and type of anaesthesia. This restitution of cognition occurred despite a significant decrease of cerebral oxygenation (rSO(2)) and despite an increase of nocturnal hypoxaemic intervals. Changes of the rsO(2) up to 3% below the baseline values (measured by NIRS) do not predict cognitive restitution. A minimal limiting value of the rSO(2) could not be defined.


Myelotoxicity of oral topotecan in relation to treatment duration and dosage: a phase I study.
Oral topotecan has been recently brought into clinical practice at a dose of 2.3 mg/m(2) for 5 days, every 3 weeks. Published data show quite high myelotoxicity. The aim of this trial was to define the daily dose and treatment duration, which permits safe toxicity. The study was designed to begin at a low daily dosage of 1.5 mg/m(2) and was escalated by increasing the topotecan dose and the day-treatment duration. The plan was to end up with 2.3 mg/m(2) daily for 5 days. In cases of tolerability with the last dosage given, we would then continue testing a higher daily dosage. Treatment repetition was planned to be every 21 days. Dosage levels were 1.5, 2.0 and 2.3 mg/m(2) for 3 days, 2.0 and 2.3 mg/m(2) for 4 days, and 2.3 mg/m(2) for 5 days. Toxicity was scored according to the Common Toxicity Criteria. Thirty-two patients (27 male, five female, median age 60 years, range 46-77 years) with small-cell lung cancer were included. The patients on 1.5 and 2 mg/m(2) for 3 days showed no myelotoxicity. Four (25%) patients on 2.3 mg/m(2) 3-day treatment developed grade 3-4 neutropenia. Three of five patients (60%) treated for 4 days at a dose of 2.3 mg/m(2) developed grade 3-4 neutropenia and less than half (two of five, 40%) of these patients had thrombocytopenia. Eight patients (66.7%) on the 5-day treatment presented with serious grade 3-4 myelotoxicity. Two treatment-related deaths were observed in the 5-day group and one in the 4-day group. Granulocyte growth factor was applied in over 60% of the patients. In conclusion, a dose of 2.3 mg/m(2) for 5 days was intolerable. Dose-limiting toxicity was 2.3 mg/m(2) for 4 days without prophylactic granulocyte colony-stimulating factor administration. The safe duration of oral topotecan treatment and the maximum tolerated dose seem to be not longer than 3 days at a dose of 2.3 mg/m(2).


Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation.
Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the heart; however, the function of CHP3 is unclear. Here, we aimed to identify the cardiac functions of CHP3. CHP3 was expressed in hearts at a wide range of developmental stages and was specifically detected in neonatal rat ventricular myocytes (NRVMs) but not in cardiac fibroblasts in culture. Moreover, knockdown of CHP3 expression using adenoviral-based RNA interference in NRVMs resulted in enlargement of cardiomyocyte size, concomitant with increased expression of a pathological hypertrophy marker ANP. This same treatment elevated glycogen synthase kinase (GSK3α/β) phosphorylation, which is known to inhibit GSK3 function. In contrast, CHP3 overexpression blocked the insulin-induced phosphorylation of GSK3α/β without affecting the phosphorylation of Akt, which is an upstream kinase of GSK3α/β, in HEK293 cells, and it inhibited both IGF-1-induced phosphorylation of GSK3β and cardiomyocyte hypertrophy in NRVMs. Co-immunoprecipitation experiments revealed that GSK3β interacted with CHP3. However, a Ca(2+)-binding-defective mutation of CHP3 (CHP3-D123A) also interacted with GSK3β and had the same inhibitory effect on GSK3α/β phosphorylation, suggesting that the action of CHP3 was independent of Ca(2+). These findings suggest that CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3α/β phosphorylation and subsequent enzymatic activation of GSK3α/β.


Using genomics to develop novel antibacterial therapeutics.
As the genomics era matures, the availability of complete microbial genome sequences is facilitating computational approaches to understand bacterial genomes and DNA structure/function relationships. From the genome of pathogens, we can derive invaluable information on potential targets for new antimicrobial agents. Advancements in high-throughput 'omics' technologies and the availability of multiple isolates of the same species have significantly changed the time frame and scope for identifying novel therapeutic targets. This article aims to discuss selected aspects of the bacterial genome, and advocates 'omics'-based techniques to advance the discovery of new therapeutic targets against extracellular bacterial pathogens.


[Balloon pulmonary valvuloplasty, 15-year experience at the Siglo XXI IMSS National Medical Center].
To evaluate 15 years of experience with balloon pulmonary valvuloplasty in a single third level health care center. Hundred-fifty patients underwent the procedure, 73 (48%) men and 77 (52%) women, mean age 10.5 +/- 11.3 years. The initial systolic gradient decreased from 86 +/- 35 to 21.67 +/- 12.20 mm Hg, p < 0.001, whereas the initial right ventricular systolic pressure decreased from 106 +/- 34.8 to 53 +/- 27 mm Hg, p < 0.0001. At the end of the follow-up, 48 +/- 44 months, the systolic gradient was 13.43 +/- 8.73 mm Hg, p < 0.001. Major complications occurred in 9 (6.4%) patients. Immediate technical success was achieved in 111 (74%) patients and failure in 39 (26%). At the end of the follow-up period, successful outcomes were achieved in 104 (89.6%); in contrast, failures were present in 12 (10.4%) patients, p < 0.001. Death occurred in 2 (1.33%) patients. The predictors for failure were age < 1.5 +/- 1-33 years (p < 0.004), dysplastic valve (p < 0.001), high initial systolic gradient (p < 0.002), and high initial systolic right ventricular pressure (p < 0.0001). Balloon pulmonary valvuloplasty is an effective, safe, and first choice treatment for congenital pulmonary valve stenosis.


Effect of gastric myoelectric activity on carbohydrate absorption of fruit juice in children.
Juices have a different rate of gastric emptying than other foods. This may alter the rate of delivery of carbohydrates to the small bowel for absorption. The aim of the study is to demonstrate that faster gastric emptying is associated with greater production of hydrogen through a randomized, crossover study of 39 healthy children. The electrogastrography (indicator of the gastric myoelectric activities) and breath hydrogen tests (indicator of carbohydrate malabsorption) were performed at baseline and after ingestion of 240 to 330 mL of grape or pear juice given in a random order. The cutaneous electrogastrogram was analyzed by running spectral analysis to compute pre- and postprandial period dominant power (PDP) and running spectrum total power (RSTP). Postprandial PDP and RSTP were higher (p < 0.02) in the pear juice group than in the grape juice group, suggesting higher antral myoelectric activities. Twenty three percent of the subjects had significant movement artifacts that suggested discomfort after drinking pear juice compared to 5% after grape juice (p < 0.03). Breath hydrogen test was more frequently positive (increase >20 part per million [ppm] above baseline) after pear juice (52.2%; mean, 36 +/- 33 ppm) than after grape juice (4.3%, 6 +/- 6 ppm). In a multiple regression analysis, the most predictive independent variable of hydrogen concentration was found to be either postprandial PDP (r2 = 0.24; p < 0.002), or RSTP (r2 = 0.37; p < 0.001). Juices affect gastric myoelectric activity. Grape juice induces lower antral myoelectric activities and is better absorbed. The malabsorption of carbohydrates of juices is in part related to their effect on the gastric physiology.


Growth in biomedical publications and scientific institutions in the Emirates (1998-2004): an Arabian renaissance?
The United Arab Emirates is witnessing a rapid development in population and infrastructure, leading to an expansion in the educational field and the health care system, including universities, hospitals and research institutes. One potential outcome of this development is an increase in biomedical research publications. This was examined in this study. Searches were made of three databases; PubMed, Current Contents and embase. All records from these databases related to the Emirates were downloaded and cross-referenced. Duplications were removed as well as erroneous records. A total of 1369 publications during 1998-2004 were obtained. Analysis of these records revealed that the Faculty of Medicine and Health Sciences, located at the federal University, was responsible for 48% of all biomedical publications. All hospitals together accounted for 24%, while other universities and other research institutes accounted for 13 and 14% respectively. Further analysis revealed that there had been no further growth in the number of publications since 1998. This is in contrast to the increasing number of institutions that have been set up in the 1998-2004 period; from 29 to 112. The Emirates are witnessing a rapid development in universities, colleges, hospitals and research centres. The ratio of publications, as yet, has not kept up with this development. The enormous growth in institutes, however, may, in time, herald an Arabian renaissance in scientific activity and related publications.


[Quantitative analysis of the corrosion rates of palladium alloys by isolated polarization].
The corrosion resistance of three palladium alloys and one conventional high noble alloy were examined by isolated polarization. Using this method, isolated plots of the cathodic and anodic reaction can be recorded. The corrosion current is given as the anodic and cathodic plots intercept. The current densities of the palladium alloys were approximately ten times higher than of the high noble alloy. All results were dependent on the acidity of the electrolyte.


Acute blood-brain barrier permeabilization in rats after systemic Phoneutria nigriventer venom.
A highly controlled transport of substances at the interface between blood and brain characterizes the blood-brain barrier (BBB), fundamental for maintenance of the homeostasis of the cerebral milieu. In this study, we investigated the time course (15 min, 1, 2, and 5 h) of BBB opening induced by intravenous (i.v.) injection of Phoneutria nigriventer spider venom (PNV) using quantitative and morphological approaches on cerebellum and hippocampus vessels for assessment of BBB permeability. The results showed vasogenic edema and tracer extravasation faster and severalfold higher in hippocampus than in cerebellum. Reactive astrocytes with swollen perivascular end-feet processes were found only in cerebellum. An immediate and total degradation of laminin in capillaries occurred resulting in the disappearance of the basement membrane. In medium-sized vessels, this effect was less prominent. The changes were transient, with cerebellum in general presenting a faster recovery. However, at 5 h laminin was overexpressed, principally in hippocampus. The rapid and abrupt shift of laminin expression in capillaries (at 15 min) coincided with the immediate and severe signs of intoxication shown by the animals, but not with the peak of leakage of vessels and vasogenic edema, which occurred later (1-2 h). The findings suggest a complex regulatory mechanism, since the extension of BBB impairment caused by PNV depends on the region of the SNC, and on the vessels types. It is suggested that the components of the BBB (gliovascular unit) have a critical role in these differences. P. nigriventer venom can be a useful tool to explore the mechanisms of BBB.


Inductively coupled plasma mass spectrometry as a simple, rapid, and inexpensive method for determination of uranium in urine and fresh water: comparison with LIF.
A simple method, based on inductively coupled plasma mass spectrometry, for determination of uranium in urine at levels that indicate occupational exposure, is presented. Sample preparation involves a fifty-fold dilution of the urine by nitric acid (2% HNO3) and no other chemical treatment or separation. The analysis itself is completed in under 3 min. The analytical procedure is fully automated so that a technician may perform over 100 analyses per day. With proper control of the blank contribution, a lower limit of detection of 3 ng L(-1) in the original urine sample was achieved. Uranium concentrations in the range 6-30 ng L(-1) were found in urine samples of people that are not occupationally exposed. The validity of the results was demonstrated through measurement of standards, controlled uranium addition experiments and, at higher concentrations, by comparison with results obtained by an independent method based on laser induced fluorescence. The laser induced fluorescence technique was found to be sufficient for detection of occupational exposure at an action level of 1.5 microg L(-1). Use of internal standards, indium, and thallium, improved quantification by about 10%, but was not deemed necessary for routine analysis. The inductively coupled plasma mass spectrometry is also ideally suited for monitoring uranium in fresh water and drinking water, as no sample dilution is required and the lower limit of detection is below 0.15 ng L(-1).


Supramolecular Chemistry of Cucurbiturils: Tuning Cooperativity with Multiple Noncovalent Interactions from Positive to Negative.
Rational control of the cooperativity of multiple noncovalent interactions often plays an important role in the design and construction of supramolecular self-assemblies and materials, especially in precision supramolecular engineering. However, it still remains a challenge to control the cooperativity of multiple noncovalent interactions through tuning the hydrophobic effect. In this work, we demonstrate that the binding cooperativity of cucurbit[8]uril(CB[8])-mediated homoternary complexes is strongly influenced by the amphiphilicity of guest molecule side groups on account of an interplay between both classical (entropy-driven) and nonclassical (enthalpy-driven) hydrophobic effects. To this end, we rationally designed and prepared a series of guest molecules bearing a benzyl group as the CB[8] homoternary binding motif with various hydrophilic and hydrophobic side groups for cooperative control. By gradually tuning side groups of the guest molecules from hydrophilic to hydrophobic, we are able to control the binding from positive to negative cooperativity. An advanced molecular recognition process and self-assembling system can be developed by adjusting the positive and negative cooperativity. The ability to regulate and control the binding cooperativity will enrich the field of supramolecular chemistry, and employing cooperativity-controlled multiple noncovalent interactions in precision supramolecular engineering is highly anticipated.


Full Protection of Intensely Luminescent Gold(I)-Silver(I) Cluster by Phosphine Ligands and Inorganic Anions.
An intensely luminescent gold(I)-silver(I) cluster [(C)(AuPPhpy2 )6 Ag6 (CF3 CO2 )3 ](BF4 )5 (PPhpy2 =bis(2-pyridyl)phenylphosphine) (3) is synthesized by the reaction of [(C)(AuPPhpy2 )6 Ag4 ](BF4 )6 with AgCF3 CO2 . All eight faces of the octahedral C@Au6 core in 3 are capped, that is, six faces are capped by silver ions and two by tetrafluoroborates. Cluster 3 is intensely luminescent in solution with a quantum yield of 92 %. Ligation of CF3 CO2- ions is vital for the construction and emission properties of 3, as confirmed by DFT calculations. BF4- ions are involved in the protecting sphere of the metal core, as evidenced by 19 F NMR data. The participation of phosphines, CF3 CO2- , and BF4- ions in the protection of the emissive core and the enhancement of the rigidity of the cluster result in the high emission efficiency. This is the first example of organic ligands and inorganic anions forming a rigid protecting sphere for luminescent coinage-metal clusters.


Mesiotemporal Disconnection and Hypoactivity in Klüver-Bucy Syndrome: Case Series and Literature Review.
Klüver-Bucy syndrome (KBS) is often perceived as rare and limited to cases with bilateral amygdala destruction. In fact, various alternate mechanisms may be involved, warranting exploration of the syndrome's presentation, pathophysiology, prognosis, and management. Clinical management and the electronic medical records were examined for 2 patients diagnosed with partial KBS (ICD-10 F07.0) after experiencing ≥ 3 of the following: placidity, indiscriminate dietary behavior, hyperorality, hypersexuality, visual agnosia, and hypermetamorphosis. A literature search was performed in April 2015 by using the keyword Kluver-Bucy in PubMed and Ovid databases for English language publications since inception. Additionally, the authors reviewed the reference list of these publications in order to identify additional reports. Studies were included if they had information about presentation, pathophysiology, syndrome treatment or management, and course of KBS. Information about our KBS cases was obtained by reviewing electronic medical records and by direct observation of the patients. A total of 186 (PubMed) and 137 (Ovid) publications were identified in each database. We ultimately reviewed 109 articles containing information about KBS, finding 51 publications addressing relevant aspects of this syndrome. The first case demonstrates KBS secondary to mesiotemporal structural atrophy, and the second illustrates transient KBS due to functional, postictal, hypoactivity within such structures. Literature review and discussion regarding both prognosis and treatment of KBS follows. Klüver-Bucy syndrome may be underreported due to a limited understanding of the syndrome as one necessitating bilateral amygdaloid destruction. The syndrome can be seen with damage/hypofunction of the hippocampal-amygdaloid complex and its projections. The prognosis of KBS is variable, and its treatment is based on a combination of environmental and pharmacologic measures.


Statistical monitoring for non-Gaussian processes based on MICA-KDR method.
The focus of the current work attempts to propose a purely data-based model for generating residuals for non-Gaussian process monitoring purposes, the idea of residual generation is borrowed from the field of model-based fault detection and applied in statistical monitoring, the generated residual instead of the measured variables is thus modeled and monitored. The proposed approach first employs the modified independent component analysis (MICA) algorithm to extract independent components (ICs) from a given dataset. Secondly, through assuming but only one variable is missing at one time, the known data regression (KDR) method dealing with missing data problem is then used for estimating the corresponding ICs. The inconsistency between the actual and estimated ICs is called residual and may present much lower level of non-Gaussianity, in contrast to the actual ICs. Thirdly, a principal component analysis based statistical monitoring model can be utilized for online fault detection based on the generated residual. Finally, the superiority and efficiency of the MICA-KDR approach over its counterparts are validated by implementing comparisons on two industrial processes, the proposed MICA-KDR method is demonstrated to be a comparative alternative in monitoring non-Gaussian processes.


Evaluation of minimum interdental threshold ability in dentate female temporomandibular disorder patients.
Minimum interdental threshold is the smallest thickness that can be detected between teeth during an occlusion and has an influence on the occlusal force and on the control of mandibular movements. The aim of this study was to assess the possible association of the signs and symptoms of temporomandibular disorders (TMD) with the ability to detect a minimum interdental threshold. Two hundred women were equally divided into four groups: asymptomatic (control), subjects with masticatory muscle pain, with articular [temporomandibular joint (TMJ)] pain and mixed (muscular and articular pain). Evaluation of the ability to detect a minimum interdental threshold was performed using aluminium foils with 0.010, 0.024, 0.030, 0.050, 0.080 and 0.094 mm of thickness in the premolar region. A total of 20 tests with each thickness for each patient were performed, starting with the thickest foil (0.094 mm) and ending with the thinnest one. The myogenic pain and articular groups presented significantly higher threshold values (0.020 and 0.022 mm, respectively), when compared to the control. Both groups reached the level of certain perceptiveness only at 0.030 mm. No significant correlation was found between minimum interdental threshold and age. These results suggest that discrimination of thicknesses can be disturbed as a consequence of TMD manifestations and not the cause of it. Clinicians should, therefore, be aware that changes on muscles and TMJ can secondarily lead to occlusion changes. The mechanisms involved in this process, however, are not well understood and warrant further investigation.


[Personalizing the reference level: gold standard to evaluate the quality of service perceived].
To know the cutoff point at which in-house Nuclear Medicine Department (MND) customers consider that the quality of service is good (personalized cutoff). We conducted a survey of the professionals who had requested at least 5 tests to the Nuclear Medicine Department. A total of 71 doctors responded (response rate: 30%). A question was added to the questionnaire for the user to establish a cutoff point for which they would consider the quality of service as good. The quality non-conformities, areas of improvement and strong points of the six questions measuring the quality of service (Likert scale 0 to 10) were compared with two different thresholds: personalized cutoff and one proposed by the service itself a priori. Test statistics: binomial and Student's t-test for paired data. A cutoff value of 7 was proposed by the service as a reference while 68.1% of respondents suggested a cutoff above 7 points (mean 7.9 points). The 6 elements of perceived quality were considered strong points with the cutoff proposed by the MND, while there were 3 detected with the personalized threshold. Thirteen percent of the answers were nonconformities with the service cutoff versus 19.2% with the personalized one, the differences being statistically significant (difference 95% CI 6.44%:0,83-12.06). The final image of the perceived quality of an in-house customer is different when using the cutoff established by the Department versus the personalized cutoff given by the respondent.


Development of a modified three-stage methane production process using food wastes.
A modified three-stage system was developed for the rapid production of methane from food wastes. The primary stage was a semianaerobic hydrolysis/acidogenic system, in which approx 4100 mg/L of volatile fatty acids (VFAs) was produced at a hydraulic retention time (HRT) of 2 d. The operation temperature and pH were 30 degrees C and 5.0-5.5, respectively. The non-degraded materials were removed through a hole at the bottom of the reactor. The secondary stage was an anaerobic acidogenic system equipped with an upflow anaerobic sludge blanket (UASB) type of fermentor. VFA was accumulated up to 6100 mg/L by the addition of Clostridium butyricum to the reactor at an HRT of 2 d. The optimum temperature and pH range were 35 degrees C and 5.0-5.5, respectively. The tertiary methanogenic stage produced CH4 and CO2 from the VFA in the UASB reactor. Methane content was 72% of the total gas volume, and the yield was 0.45-0.50 m3/kg of volatile solids at an HRT of 12 d. The operation temperature and pH were 41 degrees C and 7.6-7.9, respectively. The three-stage process exhibited an unusually high total chemical oxygen demand reduction rate up to 95%. Total nitrogen decreased to 96% and < 10 mg/L of total phosphorus remained in the final effluent.


Alpha-1 adrenergic receptor: binding and phosphoinositide breakdown in human myometrium.
Alpha-1 adrenergic receptors were examined in both inner and outer layers of human pregnant myometrium using radioligand binding of [3H]prazosin. [3H]prazosin bound rapidly and reversibly to a single class of high affinity binding sites in myometrial membrane preparations. Scatchard analysis gave similar values of equilibrium dissociation constants in both myometrial layers. In contrast, more alpha-1 adrenergic receptors were detected in the outer layer than in the inner layer. Antagonist inhibited [3H]prazosin binding with an order of potency of prazosin greater than phentolamine greater than idazoxan. Competition experiments have also revealed that a stable guanine nucleotide decreases the apparent affinity of norepinephrine for myometrial [3H]prazosin binding sites. The functional status of these alpha-1 adrenergic receptors was also assessed by measuring the norepinephrine-induced accumulation of inositol phosphates in myometrial tissue. Norepinephrine produced a concentration-dependent accumulation of inositol phosphates in both myometrial layers. However, norepinephrine-induced increases in inositol 1,4,5-triphosphate were only observed in the outer layer. These results indicate that alpha-1 adrenergic receptors in human myometrium at the end of pregnancy are linked to phosphoinositide hydrolysis and that this response occurs mainly in the outer layer.


Risk factors for median sternotomy dehiscence in cardiac surgery.
We retrospectively reviewed several risk factors for median sternotomy dihiscence in our cardiac surgery patients for a recent 18-month period. We studied these factors by univariate and multivariate analysis with respect to sternal dehiscence. Univariate analysis showed several factors to be significant: female sex (P = .03), obesity (P = .002), diabetes (P = .01), and prolonged postoperative ventilation (P = .006). Mammary artery bypass versus saphenous vein bypass only approached significance (14% vs 3%, P = .11). Multivariate analysis showed obesity (P = .002), diabetes (P = .041), and prolonged postoperative ventilation (P = .005) to be important. We conclude that obese diabetic women are at extremely high risk for sternotomy dehiscence, and mammary artery bypass in this high-risk population may be a relative contraindication.


Self-assembly of heme A and heme B in a designed four-helix bundle: implications for a cytochrome c oxidase maquette.
Heme A, a prosthetic group of cytochrome c oxidase [EC 1.9.3.1], has been introduced into two de novo designed four helix bundle proteins, [H10A24](2) and [H10H24](2), known to bind 2-4 equiv of heme B, respectively [Robertson, D. E., Farid, R. S., Moser, C. C., Mulholland, S. E., Pidikiti, R., Lear, J. D., Wand, A., J., DeGrado, W. F., and Dutton, P. L. (1994) Nature 368, 425-432]. [H10A24](2), [Ac-CGGGELWKL x HEELLKK x FEELLKL x AEERLKK x L-CONH(2)](2)(2), binds two heme A molecules per four-helix unit via bis-histidine ligation at the 10,10' positions with measured K(d) values of <0.1 and 5 nM, values much lower than those measured for heme B (K(d) values of 50 and 800 nM). The heme A-protein complex, [heme A-H10A24](2), exhibits well-defined absorption spectra in both the ferric and ferrous states, and an electron paramagnetic resonance spectrum characteristic of a low spin heme in the ferric form. A single midpoint redox potential (E(m8)) was determined for [heme A-H10A24](2) at -45 mV (vs SHE), which is significantly higher than that of the protein bound heme B (-130 and -200 mV). The observation of a single midpoint redox potential for [heme A-H10A24](2) and a pair of midpoints for [heme B-H10A24](2) indicates that the di-alpha-helical monomers are oriented in an anti topology (disulfides on opposite sides of bundle) in the former (lacking heme-heme electrostatic interaction) and syn in the latter. A mixture of global topologies was indicated by the potentiometric titration of the related [heme A-H10H24](2) which possess two distinct reduction potentials of +41 (31%) and -65 mV (69%). Self-assembly of the mixed cofactor heme A-heme B-[H10A24](2) was accomplished by addition of a single equivalent of each heme A and heme B to [H10A24](2). The single midpoint redox potential of heme B, E(m8) = -200 mV, together with the split midpoint redox potential of heme A in heme A-heme B-[H10A24](2), E(m8) = +28 mV (33%) and -65 mV (67%), indicated the existence of both syn and anti topologies of the two di-alpha-helical monomers in this four helix bundle. Synthesis of the mixed cofactor [heme A-heme B-H10H24](2) was accomplished by addition of a 2 equiv of each heme A and heme B to [H10H24](2) and potentiometry indicated the pair of hemes B resided in the 10,10' sites and heme A occupied the 24,24' sites. The results indicate that heme peripheral structure controls the orientation of the di-alpha-helical monomers in the four-helix bundle which are interchangeable between syn and anti topologies. In the reduced form, [heme A-H10A24](2), reacts quantitatively to form [carbonmonoxy-heme A-H10A24](2) as evidenced by optical spectroscopy. The synthetic [heme A-H10A24](2) can be enzymatically reduced by NAD(P)H with natural reductases under anaerobic conditions, and reversibly oxidized by dioxygen to the ferric form.


The impact of nontraditionalism on the malleability of gender stereotypes in Spain and Germany.
Gender stereotypes and inequalities are based on and sustained by people's perception of gender roles. The evolution of these gender roles, however, might be substantially different depending on cultural and social evolution in different countries. In a study, we investigated stereotypes in Germany and Spain, where residents might have different beliefs about gender roles due to their different social evolution after the Second World War and their economic and social advances. Results showed that in both countries people's expectations of differences in masculine characteristics between men and women were less noticeable than perceptions in the past or present. We also demonstrated that people perceive an increase in masculinity in women. This increase is more evident in Spaniards than in Germans. In estimations about the past, present, and future, Spaniards also perceived an increase of gender-stereotypic feminine characteristics more in men than in women. Our results are consistent with the predictions of social role theory, as gender stereotypes can include dynamic aspects and the content of these stereotypes is rooted in social roles.


Impact of a plastid-bearing endocytobiont on apicomplexan genomes.
Both the chromosomal and extrachromosomal components of the apicomplexan genome have been supplemented by genes from a plastid-bearing endocytobiont: probably an algal cell. The sequence of the apicomplexan plastid's vestigial genome indicates that a large number (>100) of genes of endocytobiotic origin must have transferred laterally to the host cell nucleus where they control maintenance of the plastid organelle and supply its functional components by means of post-translational protein trafficking. Should the nuclear genes prove to be less divergent phylogenetically than those left on the plastid genome, they might give better clues than we have at present to the origin of the plastid-bearing endocytobiont. Most of these nuclear genes still await discovery, but the on-going genome sequencing project will reveal the function of the organelle, as well as many "housekeeping" processes of interest on a wider front. The plastid's own protein synthetic machinery, being cyanobacterial in origin, offers conventional targets for antibiotic intervention, and this is discussed here using a structural model of elongation factor Tu. Uncovering the vital function(s) of the plastid organelle will provide new drug targets.


Correlation of Ki-67 and p53 with the new World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia.
The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a "field effect" with occult molecular aberration.


The independent effects of atmospheric pressure and oxygen partial pressure on gas exchange of the chicken embryo.
CO2 production and air cell PCO2 were continuously measured during late development in the chicken egg while acutely exposed from one to three hours to various O2 concentrations ranging from 11 to 39%. A small but significant increase in metabolism, ca. 8%, was found when O2 concentration was above normal values, while a reduction to 70% was observed when O2 concentrations were below normal, and fell to 50% when maintained for three hours. These values were also compared with metabolic rates reported by Lokhorst and Romijn (1965, 1967)) who incubated eggs continuously at reduced O2 concentrations as well as under reduced barometric pressure, and showed that at the same ambient PO2 the metabolism was significantly higher in the eggs at reduced barometric pressure. We attribute this difference to the increased diffusion coefficient of O2 which is inversely related to the barometric pressure. It illustrates that the ambient partial pressure of O2 and ambient atmospheric pressure exert an independent effect upon gas exchange of the avian embryo.


Binding of cationic porphyrin to isolated DNA and nucleoprotein complex: quantitative analysis of binding forms under various experimental conditions.
We studied the complex formation of tetrakis(4-N-methylpyridyl)porphyrin (TMPyP) with double stranded DNAs and T7 phage nucleoprotein complex. We analyzed the effect of base pair composition of DNA, the presence of capsid protein, and the composition of the microenvironment on the distribution of TMPyP between binding forms as determined by the decomposition of porphyrin absorption spectra. No difference was found in the amount of bound TMPyP between DNAs of various base compositions; however, the ratio of TMPyP binding forms depends on the AT/GC ratio. The presence of protein capsid opposes the binding of TMPyP to DNA. This behavior offers a possibility to investigate the protein capsid integrity due to the analysis of porphyrin binding. Increasing ionic strength of monovalent ions decreases the amount of bound porphyrin through the inhibition of intercalation, but does not influence the quantity of groove-binding forms when TMPyP interacts with isolated DNA. In the case of the nucleoprotein complex the groove-binding is also inhibited already at 140 mM ionic strength. The presence of 1 mM divalent cations (Mg(2+), Ca(2+), Cu(2+) and Ni(2+)) in a buffer solution of 70 mM ionic strength does not influence significantly the free to bound ration of TMPyP when it interacts with isolated DNA. The contribution of binding forms is remarkably different in Mg(2+)/Ca(2+) and Cu(2+)/Ni(2+) containing solutions. Transition metals significantly decrease the binding sites for intercalation in both DNA and nucleoprotein complex, but facilitate the groove-binding of TMPyP to isolated DNA.


The kinematics of load carrying in humans and great apes: implications for the evolution of human bipedalism.
We present a comparison of loaded and unloaded carrying kinematics in humans, common chimpanzees (Pan troglodytes), bonobos (Pan paniscus), western lowland gorillas (Gorilla gorilla gorilla) and Bornean and Sumatran orang-utans (Pongo pygmaeus and Pongo abelii). Human hindlimb joint and segment angles were collected during treadmill locomotion using infrared motion analysis cameras. Non-human primate fore- and hindlimb joint and segment angles were collected at zoos during free-ranging locomotion using a standard video camera. In quadrupedal locomotion there were small but potentially important changes associated with load carriage leading to a more upright trunk and a shift in shoulder excursion. These changes were exacerbated as locomotion shifts from quadrupedal to tripedal and bipedal gaits when carrying more awkward loads suggesting a possible adaptive sequence. However, food carrying may favour a highly flexed bent-hip bent-knee bipedal gait since it allows simultaneous foraging and hoarding. In bipedal humans no changes in limb kinematics were seen associated with type of load, although asymmetric loads may lead to lateral postural shifts. Carrying may therefore be an important component of the evolutionary shift to habitual bipedalism, although further work is needed to understand the full biomechanical implications.


Insulin receptor substrate-1 and -2 mediate resistance to glucose-induced caspase-3 activation in human neuroblastoma cells.
Hyperglycemia in patients with type 2 diabetes causes multiple neuronal complications, e.g., diabetic polyneuropathy, cognitive decline, and embryonic neural crest defects due to increased apoptosis. Possible mechanisms of neuronal response to increased glucose burden are still a matter of debate. Insulin and insulin-like growth factor-1 (IGF-1) receptor signaling inhibits glucose-induced caspase-3 activation and apoptotic cell death. The insulin receptor substrates (IRS) are intracellular adapter proteins mediating insulin's and IGF-1's intracellular effects. Even though all IRS proteins have similar function and structure, recent data suggest different actions of IRS-1 and IRS-2 in mediating their anti-apoptotic effects in glucose neurotoxicity. We therefore investigated the role of IRS-1/-2 in glucose-induced caspase-3 activation using human neuroblastoma cells. Overexpression of IRS-1 or IRS-2 caused complete resistance to glucose-induced caspase-3 cleavage. Inhibition of PI3-kinase reversed this protective effect of IRS-1 or IRS-2. However, MAP-kinases inhibition had only minor impact. IRS overexpression increased MnSOD abundance as well as BAD phosphorylation while Bim and BAX levels remained unchanged. Since Akt promotes cell survival at least partially via phosphorylation and inhibition of downstream forkhead box-O (FoxO) transcription factors, we generated neuroblastoma cells stably overexpressing a dominant negative mutant of FoxO1 mimicking activation of the insulin/IGF-1 pathway on FoxO-mediated transcription. Using these cells we showed that FoxO1 is not involved in neuronal protection mediated by increased IRS-1/-2 expression. Thus, overexpression of both IRS-1 and IRS-2 induces complete resistance to glucose-induced caspase-3 activation via PI3-kinase mediated BAD phosphorylation and MnSOD expression independent of FoxO1.


Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis.
To obtain reliable estimates of the relative efficacy and safety of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of patients with venous thromboembolism. A literature search of randomized trials evaluating LMWH and UFH for the period from 1980 to 1994 was conducted to obtain data for a meta-analysis. Studies were classified as level 1 if they were double-blind or if there was blinded assessment of outcome measures, and level 2 if they did not provide assurance of blinded outcome assessment. In level 1 studies, the relative risk (RR) of recurrent venous thromboembolism during the first 15 days and over the entire period of anticoagulant therapy was 0.24 (95% confidence intervals [CI] 0.06 to 0.80, P = 0.02) and 0.39 (95% CI 0.30 to 0.80, P = 0.006), respectively, in favor of LMWH treatment. The RR for major bleeding was 0.42 (95% CI 0.2 to 0.9, P = 0.01), in favor of LMWH. In level 2 studies, no significant differences in the rates of recurrent venous thromboembolism or major bleeding were observed. Pooling level 1 and level 2 studies, the RR for overall mortality and mortality in cancer patients was 0.51 (95% CI 0.2 to 0.9, P = 0.01), and 0.33 (95% CI 0.1 to 0.8, P = 0.01), respectively in favor of LMWH. LMWH are likely to be more effective than UFH in preventing recurrent venous thromboembolism, to produce less major bleeding, and to be associated with a lower mortality rate, particularly in the subgroup of patients with cancer.


[Russian consensus on the diagnosis, treatment, and monitoring of acromegalia (draft)].
Acromegaly is a serious disease of the hypothalamic-pituitary system, caused by chronic overproduction of growth hormone (GH) in individuals with completed physiological growth, affecting mainly people of working age. The disease is characterized by significant disability of patients and a reduction in life expectancy, the main reasons for which are complications caused by prolonged hypersecretion of GH. These include primarily damage to the cardiovascular system, respiratory system, metabolic disorders, malignant neoplasms of the gastrointestinal tract. At the same time, timely diagnosis and adequate treatment can reduce mortality several times, significantly improve the quality of life of patients.Until now, the problem of optimizing the diagnosis of acromegaly, especially the so-called "soft" form, as well as the choice of the most effective and safe treatment method, is relevant all over the world and in our country in particular.At the V Russian Congress of Endocrinology, a draft consensus on the management of patients with acromegaly was discussed. Subject to the provisions of the international agreement and Russian experience, recommendations are offered for the diagnosis, treatment and monitoring of this disease for further discussion, followed by the adoption of a final consensus.


Double dissociation between the contributions of the septal and temporal hippocampus to spatial learning: the role of prior experience.
The mammalian hippocampus is anatomically heterogeneous along its longitudinal axis, and there is evidence that distinct functions are executed by different septotemporal subregions. The best documented example is the dependency of spatial learning on the septal, but not the temporal, hippocampus. Here, we carried out a watermaze memory task in rats with partial lesions of the septal or temporal hippocampus made either before or after training. We then studied memory retention, reversal, and new spatial learning in a novel environment. This resulted in the surprising finding that spatial learning in a new environment is dependent on the temporal hippocampus in rats with preoperative experience of a different pool. Rats with septal hippocampal lesions made after learning not only retained the focused search strategy that was acquired during preoperative training, but were also capable of rapid spatial learning in a second pool. This demonstrates that once spatial information has been acquired in one context, related new learning in a different context can be mediated by the temporal hippocampus, a result that challenges the widely held view that spatial memory is an exclusive function of the septal hippocampus.


Mode conversion in high-definition plasmonic optical nanocircuits.
Symmetric and antisymmetric guided modes on a plasmonic two-wire transmission line have distinct properties and are suitable for different circuit functions. Being able to locally convert the guided modes is important for realizing multifunctional optical nanocircuits. Here, we experimentally demonstrate successful local conversion between the symmetric and the antisymmetric modes in a single-crystalline gold plasmonic nanocircuit with an optimally designed mode converter for optical signals at 194.2 THz. Mode conversion may find applications in controlling nanoscale light-matter interaction.


The in vitro toxicity of cobalt-chrome-molybdenum alloy and its constituent metals.
Cobalt-chrome-molybdenum alloys are widely used in orthopaedic implants. Although they are relatively well tolerated, complications (including loosening and tissue necrosis) still occur and sometimes appear to be due to incomplete biocompatibility of the alloy. To investigate the local effect of the alloy on cells derived from the musculo-skeletal system, primary lines of fibroblastic cells from newborn rats were exposed to powders of cobalt-chrome-molybdenum alloy and its main constituents cobalt, chromium nickel and molybdenum. The toxicity of the metals was determined by counts of total cell number and of abnormal cells at intervals from 2 to 12 d. The alloy was much less toxic than cobalt or nickel and the pattern of toxicity was different for each metal. The results emphasize the difficulty of devising a single tissue culture test of toxicity which will measure the toxicity of any potential implant material.


Indices of obesity and blood pressure in young men followed 32 years.
In order to assess the effects of baseline indices of obesity, lean body mass, blood pressure, and weight change on future blood pressure, 112 former college men were examined 20 and 32 years after initial examination at age 20.5 (+/- 2) yr. Baseline body weight, relative body weight, body mass index and body density all showed similar significant correlations with baseline systolic blood pressure (r = 0.35, 0.31, 0.30 - 0.31) but not baseline diastolic blood pressure (r = 0.13, 0.07, 0.10 - 0.11) or follow-up blood pressure. Changes in body weight, relative body weight, body mass index and sum of skinfolds were significantly correlated with change in both systolic and diastolic blood pressure. Baseline systolic blood pressure was the most powerful predictor of 20- and 32-yr follow-up systolic (r = 0.57, 0.42), but baseline diastolic was a much weaker correlate of follow-up diastolic blood pressure (r = 0.24, 0.18).


Removal of over the scope clips (OTSC) with an Nd:YAG Laser.
Until recently there has been no technique available which reproducibly and safely allows endoscopic closures of penetrating defects within the digestive tract. With the new "over the scope clipping system" (OTSC system), which regarding design and function is similar to a bear-trap, a method is available for the endoscopic closure of fistulas and perforations. The OTSC-systems are designed for permanent placement. However, in the case of misplacement or the need to remove the clip after healing of the defect, a technique for destroying and removing the clip should be available. We demonstrate for the first time the successful removal of the deeply penetrating OTSC system by using the Nd:YAG-Laser in 3 cases: (i) after closure of an oesophageal fistula, (ii) after closure of a perforation of the distal common bile duct in the roof of the papilla and (iii) after clip misplacement in a case of a wide oesophagomediastinal fistula resulting in a severe oesophageal stenosis. Clinically relevant thermal lesions were not observed after the procedure. If clinically necessary, the OTSC-system can be safely removed by the Nd:YAG Laser in centres for interventional endoscopy. Because of the small number of cases the method must still be considered as experimental and requires further validation. This will be possible with the help of a newly established OTSC registry ( www.endodo.de ).


Renal Denervation for Ventricular Arrhythmia in Patients with Implantable Cardioverter Defibrillators.
To investigate the efficacy of renal denervation (RDN) on the recurrence of ventricular arrhythmia (VA) in Asian patients with implantable cardioverter defibrillators (ICDs).Eight ICD patients with recurrent VA episodes underwent RDN using an off-the-shelf saline-irrigated catheter. The pre- and postprocedural VA episodes were counted via ICD interrogation. All patients underwent successful RDN without any complications related to radiofrequency catheter ablation. The median follow-up was 15 months (range 6-30), and the median VA episodes per month were significantly reduced from 3.17 (range 0.33-15.33) to 0.10 (range 0-5.83) after RDN (P < 0.05).RDN is an effective suppressor of VA in Asian patients with ICDs.


Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes.
The management of primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web-based voting. Consensus was achieved with more than 80 per cent agreement; less than 80 per cent agreement indicated low consensus. During conferences held in September 2011 and March 2012, open discussion took place on areas in which there is a low level of consensus. The final consensus document included 51 voted statements, making recommendations on ten key areas of PRC-bTME and RRC. Consensus agreement was achieved on the recommendations of 49 statements, with 34 achieving consensus in over 95 per cent. The lowest level of consensus obtained was 76 per cent. There was clear identification of the need for referral to a specialist multidisciplinary team for diagnosis, assessment and further management. The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority.


Increasing obstetrical care access to the rural poor.
Rising malpractice insurance rates have led to a decrease in the number of physicians who provide rural obstetrical care. North Carolina has responded with the Rural Obstetrical Care Incentive (ROCI) Program, which provides up to $6,500 per year to physicians who provide obstetrical care to the rural poor in conjunction with a local health department. This study finds some evidence that the program has led to an increase in the satisfaction that physician participants feel toward the prenatal care available at the local health department; that participants are increasing their provision of obstetrical care to Medicaid patients compared to other physicians in the state; and that the percentage of women delivering after receiving inadequate prenatal care is decreasing in the original ROCI counties, at a time when other rural counties are experiencing an increase in this measure. Other states should consider the ROCI program as one aspect of a rural health strategy.


Co-axial electrospun polystyrene/polyurethane fibres for oil collection from water surface.
The pollution arising from oil spills is a matter of great concern due to its damaging impacts on the ecological environment, which has created a tremendous need to find more efficient materials for oil spill cleanup. In this work, we reported a sorbent for oil soak-up from a water surface with a high sorption capacity, good selectivity, and excellent reusability based on the hydrophobic-oleophilic fibrous mats that were fabricated via co-axial electrospinning polystyrene (PS) solution as the shell solution and polyurethane (PU) solution as the core solution. The fine structures of as-prepared fibers were regulated by manipulating the spinning voltages, core solution concentrations, and solvent compositions in shell solutions, which were also characterized by field emission scanning electron microscopy, transmission electron microscopy, nitrogen adsorption method, and synchrotron radiation small-angle X-ray scattering. The effects of inter-fiber voids and intra-fiber porosity on oil sorption capacities were well studied. A comparison of oil sorption capacity for the single fiber with different porous structures was also investigated with the help of scanning transmission X-ray microscopy. The results showed that the sorption capacities of the as-prepared sorbent with regards to motor oil and sunflower seed oil can be 64.40 and 47.48 g g(-1), respectively, approximately 2-3 times that of conventional polypropylene (PP) fibers for these two same oils. Even after five sorption cycles, a comparable oil sorption capacity with PP fibers was still maintained, exhibiting an excellent reusability. We believe that the composite PS-PU fibrous mats have a great potential application in wastewater treatment, oil accident remediation and environmental protection.


Volumetric magnetic resonance imaging correlates of the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment neuropsychology protocols.
Vascular cognitive impairment (VCI) refers to the entire spectrum of cognitive dysfunction attributable to vascular changes in the brain. The objective of this study is to evaluate magnetic resonance imaging (MRI) correlates of performance on the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) VCI neuropsychology protocols. Fifty ischemic stroke patients and 50 normal elderly persons completed the VCI protocols and MRI. Relationships between the four cognitive domains (executive/activation, language, visuospatial, and memory) and three protocol (60-, 30-, and 5-min) summary scores with MRI measures of volumes of white matter hyperintensities (WMH) and global brain and hippocampal atrophy were assessed using linear regression. All cognitive domain scores were associated with WMH volume and, with the exception of language domain, with global atrophy. Additional relationships were found between executive/activation and language domains with left hippocampal volume, visuospatial domain with right hippocampal volume, and memory domain with bilateral hippocampal volumes. All protocol summary scores showed comparable relationships with WMH and hippocampal volumes, with additional relationships found between the 60- and 30-min protocols with global brain volume. Performance on the NINDS-CSN VCI protocols reflects underlying volumetric brain changes implicated in cognitive dysfunctions in VCI.


Radioluminescence of some optical fibres.
Measurement of radiation fields with small scintillators as detectors for radiation dose is an attractive method provided that the scintillator luminescence can be discriminated against other unwanted signals. In diagnostic radiology radioluminescence of the optical fibres required for a transmission of the luminescence to an optical detector is the only source for such an impairment of the signal. To find fibres with low radioluminosity a survey of ten commercial fibres including polystyrene (PS), polystyrene wavelength shifting fibres, poly-methylmetacrylate (PMMA) and silica as fibre core material was made. Measurements were made with two photomultipliers of different spectral response and a clinical x-ray unit. Lowest radioluminosity was obtained with PMMA fibres. Depending on spectral sensitivity of the multiplier clear PS fibres give five to ten times the luminescence of PMMA. From the silica fibres only one high-OH fibre gave comparable results for wavelength up to 520 nm. Wavelength shifting fibres and silica fibres with low OH-content show strong fluorescence and are not suitable fibre materials.


Imaging for carotid stenting.
Carotid artery stenting (CAS) using embolic protection devices (EPD) has emerged as a viable alternative to carotid endarterectomy (CEA) in select patients. Imaging plays a critical role in the selection of patients for CAS. Duplex ultrasonography alone is insufficient to assess patients for CAS suitability. Advancements in computed tomography angiography (CTA) and magnetic resonance angiography (MRA) techniques are helping to identify lesions vulnerable to cerebral embolization during carotid interventions - a more prevalent event during CAS in comparison to CEA. Here we review the relevant data on the various imaging techniques available to improve patient selection and minimize neurologic adverse events during carotid artery stenting.


Sex preference for children and its implications for fertility in rural Bangladesh.
In this study, the level and pattern of sex preference for children and its effects on fertility intention, fertility-regulating behavior, and fertility implications for women are investigated. Data are from a 1976 cross-sectional KAP (knowledge, attitude, and practice of family planning) survey and a three-year longitudinal study, conducted between December 1976 and 31 December 1979, of vital events for 860 married women of childbearing age from Companiganj, Bangladesh. The results show that although son preference is very strong in this area, more than 98 percent of women desire at least one daughter. However, women with a higher proportion of sons are less likely to want more children and are more likely to practice contraception and to be sterilized. Although women with a higher proportion of sons have somewhat lower fertility in the prospective follow-up period, the net effect of son preference on fertility is not significant, possibly because of the low level of contraceptive use in the population.


Deep vein thrombosis in a patient with lepromatous leprosy receiving thalidomide to treat leprosy reaction.
Thalidomide is the treatment of choice for severe or recurrent erythema nodosum leprosum. Its use has been associated with deep vein thrombosis in patients with blood disorders, however, particularly when used in combination with corticosteroids or chemotherapy. We describe a case of deep vein thrombosis in a 43-year-old man with lepromatous leprosy who was being treated with thalidomide and prednisone for a type 2 leprosy reaction (erythema nodosum leprosum); the patient also had transiently positive antiphospholipid antibody results. We stress the importance of considering deep vein thrombosis, a potentially fatal complication, in dermatology patients treated with thalidomide.


Little chameleons: The development of social mimicry during early childhood.
Adults use behavioral mimicry to blend in with (or stand out from) their social environment. Adopting another's mannerisms and behaviors, or "mimicking", communicates liking and similarity between interaction partners and has been shown to serve as an implicit affiliation mechanism. Given this important social function, it is surprising that so little is known about the development of mimicry. In two studies, we investigated mimicry and its social sensitivity during early childhood. Children of 4 to 6years (Study 1) and 3years (Study 2) first chose a novel group based on their color preference. Following a baseline phase, children observed videos of in-group and out-group models performing behaviors that are typically mimicked in adults. Importantly, the children received neither instructions nor encouragement to copy the behaviors. Both 3-year-olds and 4- to 6-year-olds displayed behavioral mimicry. Furthermore, 4- to 6-year-olds mimicked the in-group model more than the out-group model, and this in-group bias was also evident in their explicit group preferences. Together, these studies present the first evidence for behavioral mimicry and its social sensitivity during early childhood. Placed in the context of social development, the findings provide a necessary contribution to current developmental and psychological theories on mimicry and behavior copying.


Rediscovering peritoneal macrophages in a murine endometriosis model.
What are the features of peritoneal macrophage subgroups and T helper cells in the development of murine endometriosis? During the development of endometriosis in a murine model, large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs) are polarized into M1 and M2 cells, respectively, and the proportions of T helper (Th) 1, Th17 and T regulatory (Treg) cells are increased. Numerous studies investigating the etiology and pathogenesis of endometriosis have focused on the polarization states of peritoneal macrophages in endometriosis models and patients, but the results are inconclusive. Further studies indicate that peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs, although their roles in endometriosis are unknown. This study involves a prospective and randomized experiment. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group) according to the presence or absence of transplantation. The transplant periods are 0.25, 3, 14, 28 and 42 days. C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of allogeneic endometrial segments. Dynamic changes of peritoneal macrophage subsets and polarization profiles were evaluated by flow cytometry (FCM). Macrophage morphology and density were assessed by cell counting under a microscope. Dynamic changes of Th1, Th2, Th17 and Treg cells were estimated by FCM. Peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs. The proportion of SPMs increased immediately after peritoneal injection of endometrial tissues, whereas LPMs showed an opposite trend. Peritoneal macrophages differentiated into both M1 and M2 macrophages. The bidirectional polarization of macrophages was caused by the inverse trends of polarization of LPMs and SPMs. Consistently, the proportions of Th1, Th17 and Treg cells were all increased in mice with endometriosis. N/A. In this study, detection was only performed in a murine endometriosis model. Clinical data and more intervention experiments are required in understanding the roles of LPMs and SPMs in endometriosis. The dramatic changes of LPMs and SPMs in proportion and polarization profiles clarified the varying differentiation states of peritoneal macrophages. In addition, LPMs and SPMs may play different roles in the pathogenesis of endometriosis in different stages of endometriosis. Therefore, the new classification should be included in future relevant basic and clinical studies on endometriosis. This research was supported totally by grant 81270671 from the National Natural Science Foundation of China. The authors report no conflict of interest.


Surface Reconstruction via Fusing Sparse-Sequence of Depth Images.
Handheld scanning using commodity depth cameras provides a flexible and low-cost manner to get 3D models. The existing methods scan a target by densely fusing all the captured depth images, yet most frames are redundant. The jittering frames inevitably embedded in handheld scanning process will cause feature blurring on the reconstructed model and even trigger the scan failure (i.e., camera tracking losing). To address these problems, in this paper, we propose a novel sparse-sequence fusion (SSF) algorithm for handheld scanning using commodity depth cameras. It first extracts related measurements for analyzing camera motion. Then based on these measurements, we progressively construct a supporting subset for the captured depth image sequence to decrease the data redundancy and the interference from jittering frames. Since SSF will reveal the intrinsic heavy noise of the original depth images, our method introduces a refinement process to eliminate the raw noise and recover geometric features for the depth images selected into the supporting subset. We finally obtain the fused result by integrating the refined depth images into the truncated signed distance field (TSDF) of the target. Multiple comparison experiments are conducted and the results verify the feasibility and validity of SSF for handheld scanning with a commodity depth camera.


Effects of gentamicin sulfate on enzyme activities of carbonic anhydrase from human erythrocytes in vitro and from rat erythrocytes in vivo.
The effects of gentamicin sulfate on carbonic anhydrase (CA) enzyme activity in in vitro human and in in vivo rat erythrocytes were investigated. For in vitro study, human carbonic anhydrase-I and -II (HCA-I and HCA-II) were purified by affinity-column chromatography, and rats were used for in vivo study. In vivo and in vitro CA enzyme activity was determined colorimetrically using the CO2-hydration method of Wilbur and Anderson as modified by Rickli et al. Gentamicin sulfate (1.98-9.90 mM) showed in vitro inhibitory effects on HCA-I and HCA-II hydratase activity up to a 2 mM concentration, when determined using the C02-hydratase method. Rat erythrocyte CA activity was significantly inhibited for up to 3 h (p<0.001) following intramuscular administration of gentamicin sulfate to Sprague-Dawley rats (3.2 mg/kg body weight). In conclusion, gentamicin sulfate inhibits CA enzyme activity in vivo and at low concentrations in vitro, but activated it at high concentrations (> or = 4 mM) in vitro.


Contemporary Perioperative Analgesia in Total Knee Arthroplasty: Multimodal Protocols, Regional Anesthesia, and Peripheral Nerve Blockade.
Perioperative care of the total knee arthroplasty (TKA) patient has evolved considerably over the past decade. Among the changes driving this evolution toward shorter hospitalization and accelerated rehabilitation have been regional anesthesia, peripheral nerve blockade, and multimodal analgesia protocols. These complementary techniques are increasingly supported by scientific evidence, though considerable uncertainty persists regarding the optimal combination of strategies. Continued refinement of technique and critical evaluation is trending toward greater characterization of the comparative effectiveness of myriad options. Contemporary interdisciplinary arthroplasty care teams have the opportunity to individualize the TKA patient's perioperative pain control to optimize not only the clinical outcome but also patient satisfaction.


Two-dimensional organization of mono- and bisurea supramolecular polymers studied by scanning tunneling microscopy.
Scanning tunneling microscopy (STM) of mono- and bisurea-functionalized oligo(p-phenylenevinylene)s at solid/liquid interface visualized two-dimensionally-ordered double columnar structures of pi-conjugated segments scaffolded by one-dimensional supramolecular polymerization of urea hydrogen-bonding units. In contrast to a persistent alignment of the bisurea compound supported by twofold intermolecular urea-urea hydrogen-bonding, the building blocks in the monourea double columns shows dynamic fluctuation and defects because of their rotational motion around urea-urea hydrogen-bonding axis and/or adsorption-desorption of the individual molecules from the surface. Self-assembled structures of mono- and bisurea compounds at solid/liquid interface revealed by STM can be related to their gelation abilities in organic solvents.


Effect of polychlorinated biphenyl (Aroclor 1260) on histology of kidney and thyroid of rats.
Gross histological alteration in kidney and thyroid structures were observed in male Wistar rats fed polychlorinated biphenyls (PCBs; Aroclor 1260) at 50 and 100 ppm level in normal commercial diet for 120 days. While the kidney showed glomerulonephritis, degenerative changes in the proximal and distal tubules and increased cellularity of glomeruli, thyroid showed degeneration of follicles, fibrosis of follicles and lymphocytic infiltration followed by thyroiditis.


Changes in the structure of the rat hippocampus after prolonged postnatal hypoxia.
The authors compare the structure of the pyramidal neurones in the CA1 region of the hippocampus in rats repeatedly exposed to aerogenic hypoxia from birth to the age of 17 days and in control animals. In preparations from 18-day-old animals impregnated by the Colgi-Cox method the length of the dendrites and the density of the spines were quantitatively evaluated together with the shape of the spines at various segments of the dendritic tree. After hypoxia the number of dendritic fibres compared with the controls was smaller in the region of the basal dendrites (P less than 0.01) and in the preterminal and terminal branches of the apical dendrites (P less than 0.05). Spine density after hypoxia was lower than in the controls on the basal dendrites (P less than 0.01) and, except for the terminal part, on the apical dendrites (P less than 0.01). The dendritic spines of experimental animals were found to be short, club-shaped and thick, while in the controls they were long, thin and sometimes branched. Prolonged postnatal hypoxia discernibly interfered with the process of formation of the microstructure of the hippocampus. Uneven restriction of the receptive field of the neurones and the suggested alteration in the transmitting characteristics of the spines might be the cause of some of the functional changes previously described in animals after hypoxia.


Effect of phosphodiesterase (1B, 2A, 9A and 10A) inhibitors on central nervous system cyclic nucleotide levels in rats and mice.
Phosphodiesterase (PDE) inhibition has been broadly investigated as a target for a wide variety of indications including central nervous system (CNS) disorders. Cyclic nucleotide (cNT) changes within associated tissues may serve as a biomarker of PDE inhibition. We recently developed robust sample harvesting and bioanalytical methods to quantify cNT levels in rodent brain and cerebrospinal fluid (CSF). Herein, we report on the application of those methods to study rodent species-specific and rodent brain region-specific cNT changes following individual or concomitant PDE inhibitor administration. Male Sprague Dawley (Crl:CD® [SD]) rats were dosed subcutaneously (sc) with a PDE1B inhibitor (DNS-0056), a PDE2A inhibitor (PF-05180999), a PDE9A inhibitor (PF-4447943), and a PDE10A inhibitor (MP10), each at a single dose of 10 or 30 mg/kg, or concomitantly with all 4 inhibitors at 10 mg/kg each. Male Carworth Farms (Crl:CF1 ®[CF-1]) mice were dosed intraperitoneally (ip) with the four individual inhibitors at a single dose of 10 mg/kg or concomitantly with all 4 inhibitors at 10 mg/kg each. The doses studied are generally adequate for affecting measurable cNT levels in the tissues of interest and were thereby chosen for this investigation. Measured 3',5'-cyclic adenosine monophosphate (cAMP) changes were generally statistically insignificant in the brain, striatum and CSF after administration of the aforementioned PDE inhibitors. However, the levels of 3',5'-cyclic guanosine monophosphate (cGMP) increased in both rat and mouse striatum (2.2-, 2.1- and 1.7-fold and 6.4-, 2.8- and 1.7-fold, respectively) after PDE2A, 9A, and 10A inhibitor dosing. In all cases, the cNT changes followed the same trend in the brain, striatum and CSF after PDE inhibitor dosing and dose response was observed in rats. Concomitant treatment with PDE1B, PDE2A, PDE9A and PDE10A inhibitors resulted in a 4.4- and 36.7-fold increase of cGMP in rat and mouse striatum. The drug exposures after concomitant treatment were also higher than in the individual inhibitor-treated animals. cGMP enhancement observed could be due to synergistic effects, though an additive effect of the combined inhibitor concentrations may also contribute.


[Risk factors for 4-year mortality in older adults. Toledo Study].
multiple factors contribute to mortality in older adults. Measures of physical and cognitive function are strong predictors of mortality, but the extent to which function, health-related quality of life and other factors contribute independently to mortality risk is not known. we performed a prospective study of a representative sample of people aged 65 years and older (n=3,214) followed-up for 4 years. Individuals from the sample were interviewed to obtain information about sociodemographic characteristics, comorbidity, functional status, health-related quality of life, and healthcare utilization. The main outcome measure was 4-year mortality. To assess the independent impact of each risk factor on mortality, several multivariate survival models were built using the Cox proportional hazard model. in the 4 years of monitoring, 478 people died (14.9%). The variables independently associated with mortality risk were age 75 years or older (HR = 1.93), male gender (HR = 1.73), heart disease (HR = 1.32), chronic respiratory disease (HR = 1.78), activities of daily living disability (HR = 1.55), instrumental activities of daily living disability (HR = 2.19), cognitive impairment (HR = 1.39), poor health-related quality of life (HR = 1.85) and hospital admission in the year prior to the interview (HR = 1.51). objective measures of physical and cognitive function are independent predictors of 4-year mortality in the elderly. Poor health-related quality of life is associated with mortality. The magnitude of this association is comparable to that of other well-know predictors of mortality. Instruments to measure health-related quality of life can be useful to evaluate health requirements in the elderly.


Unilateral blindness with third cranial nerve palsy and abnormal enhancement of extraocular muscles on magnetic resonance imaging of orbit after the ingestion of methanol.
Methanol is generally known to cause visual impairment and various systemic manifestations. There are a few reported specific findings for methanol intoxication on magnetic resonance imaging (MRI) of the brain. A case is reported of unilateral blindness with third cranial nerve palsy oculus sinister (OS) after the ingestion of methanol. Unilateral damage of the retina and optic nerve were confirmed by fundoscopy, flourescein angiography, visual evoked potential and electroretinogram. The optic nerve and extraocular muscles (superior rectus, medial rectus, inferior rectus and inferior oblique muscle) were enhanced by gadolinium-DTPA on MRI of the orbit. This is the first case report of permanent monocular blindness with confirmed unilateral damage of the retina and optic nerve, combined with third cranial nerve palsy after methanol ingestion.


[BCG sepsis as a fatal complication of BCG vaccination].
Fatal septicemia with Bacillus Calmette-Guérin (BCG) following BCG vaccination is always caused by an underlying defect of immunologic mechanisms. At the Children's Hospital, University of Berne, two cases of BCG septicemia were recently observed. The clinical picture, course, and pathogenesis of the illness are discussed. The harmless complications of BCG vaccination are summarized, and a review of the literature on fatal disseminated BCG infection stresses the different type of immunologic mechanism defect and clinical course. Therapy with antituberculous drugs is ineffective. Other therapeutic measures are mentioned. Immunologic tests must be performed rapidly when fatal disseminated BCG infection is suspected, in order to organize genetic counselling as soon as possible. The question whether newborns should still be vaccinated in spite of the numerous complications is discussed and answered in the affirmative.


Automatic detection of feeding- and drinking-related agonistic behavior and dominance in dairy cows.
Accurate assessments of social behavior and dominance relationships in cattle can be time consuming. We investigated whether replacements at the feed bunk and water trough-one type of agonistic interaction-can be used to automatically assess dominance relationships. Our study set out to (1) validate a replacement detection algorithm using combined data from electronic feed and water bins, and (2) investigate the applicability of this algorithm to identify individual dominance scores and group-level social hierarchy in freestall-housed dairy cows. We used 4 groups of lactating cows kept in different group sizes (11 to 20 cows) located at 2 research facilities. In both facilities, feed and water were provided via automated feeding systems. A trained observer recorded all agonistic interactions in the pen over multiple days using video. Data from the electronic feed and water bins for the same days were analyzed using an algorithm to detect replacements (i.e., visits where a receiver cow was competitively replaced by an actor cow). Most agonistic interactions at the feed bunk were replacements. These replacements were associated with a brief interval between the time the receiver cow left the bin and the actor cow took her place; the optimal threshold to detect these replacements varied from 22 to 27 s between groups, independent of stocking density. The recall and precision of an algorithm based upon this threshold was high (on average >0.8), comparable to that of trained human observers. We improved data preparation by controlling for detection errors and included filtering to reduce false positives. This resulted in a >20% decrease in false positives and an increase in precision of 0.043. The dominance hierarchy based upon algorithm-detected replacements was similar to that based upon total agonistic interactions observed in the pen; the Spearman rank correlation coefficient between these hierarchies varied among the groups from 0.81 to 0.96. We conclude that data from electronic feed and water bins can accurately estimate agonistic behavior and dominance relationships among dairy cows.


Evidence for endocrine disruption in invertebrates.
The issue of endocrine disruption (ED) in invertebrates has generated remarkably little interest in the past compared to research with aquatic vertebrates in this area. However, with more than 95% of all known species in the animal kingdom, invertebrates constitute a very important part of the global biodiversity with key species for the structure and function of aquatic and terrestrial ecosystems. Despite the fact that ED in invertebrates has been investigated on a smaller scale than in vertebrates, invertebrates provide some of the best documented examples for deleterious effects in wildlife populations following an exposure to endocrine-active substances. The article provides an overview of the diversity in endocrine systems of invertebrates. The principal susceptibility of invertebrates to endocrine-active compounds is demonstrated with the case studies of tributyltin effects in mollusks and of insect growth regulators, the latter as purposely synthesized endocrine disrupters. The additional evidence for ED in invertebrates from laboratory and field studies is summarized as an update and amendment of the EDIETA report from 1998. Finally, conclusions about the scale and implications of the observed effects are drawn and research needs are defined.


Rapid identification of Bacillus cereus based on the detection of a 28.5-kilodalton cell surface antigen.
Conventional procedures for the identification of suspect Bacillus cereus isolated on mannitol-egg yolk-polymyxin (MYP) agar may need several days. To facilitate the identification of the bacterium, an enzyme-linked immunosorbent assay (ELISA) was developed. The assay was based on the detection of a 28.5-kDa cell surface antigen of B. cereus. Bacterial colonies grown on MYP agar or nutrient agar were suspended in phosphate-buffered saline (pH 7.2) containing 0.1% Teepol. The cell suspensions were heated at 100 degrees C for 5 min and added to the microtiter plates coated with antibodies against the 28.5-kDa antigen. After washing, the same antibodies labeled with horseradish peroxidase were used as secondary antibodies to reveal the signal of antigen-antibody reaction. For 38 strains of B. cereus and 127 strains of non-B. cereus bacteria (including 79 isolates of Bacillus spp.) tested, the sensitivity and specificity of the ELISA were 100 and 88.2%, respectively. Strains producing false-positive results were members of the B. cereus group (i.e., Bacillus anthracis, Bacillus mycoides, and Bacillus thuringiensis), which are genetically and biochemically similar to B. cereus. Similar ELISA results were obtained by using antibodies against another cell surface antigen with a molecular mass of 20 kDa. If members of the B. cereus group were recognized as a single species, the sensitivity and specificity of the ELISA were 100 and 99.1%, respectively. The ELISA could be used as a rapid method for presumptive identification of B. cereus grown on MYP agar.


[Thymoma and primary Gougerot-Sjögren syndrome progressing to severe bronchiolitis].
The authors report a case of a thymoma associated with Gougerot-Sjögren's syndrome in a patient aged 40 years. The excision of the thymic tumour and complementary radiotherapy lead to a remission in the patient. There was an unfavourable progression of this syndrome from a respiratory stand-point with the development of a predominantly bronchiolitic picture over four years.


Neuromuscular ankle joint stabilisation after 4-weeks WBV training.
Whole body vibration (WBV) training is increasingly implemented in prevention programs as well as in rehabilitation protocols but evidence for beneficial effects of WBV training over several weeks on ankle joint stabilisation is lacking. The purpose of the study was to investigate the effects of 4-weeks WBV training on reflex activity of the long peroneal and tibialis anterior muscles and on the duration of ankle inversion movement in response to an unexpected combined 24 degrees inversion 15 degrees plantar flexion ankle joint motion. Twenty-six healthy subjects were divided into an intervention group (n=16) and a control group (n=10). The intervention group trained thrice weekly for 3 min on a unidirectional oscillating vibration platform (30 Hz, 4 mm amplitude). Pre and post intervention reflex activity were measured and the duration of ankle joint movement was calculated by vertical ground reaction forces. After four weeks of WBV training no significant changes were found in latencies and reflex activity in both muscles in response to ankle sprain simulation. Similar results were observed for the time of ankle inversion motion. Based on the present results, it is unlikely that 4-weeks WBV training has beneficial effects on ankle joint stability in the case of an ankle inversion motion.


New molecular cage clusters of Pb by encapsulation of Mg.
Endohedral clusters formed from the Zintl ions Pb(10) (2-) and Pb(12) (2-) are particularly stable and therefore suitable for the assembly of larger aggregates. We therefore investigate the formation of Mg-doped lead clusters in the gas phase, and demonstrate that a whole series of new molecular cage clusters of lead can be generated by encapsulation of magnesium. Mass spectrometry reveals that some of the cluster compounds, with one and two Mg atoms attached to the lead clusters, display large intensities compared to the pure lead clusters, which indicates that the compound clusters are particularly stable. The magnesium-doped lead-cluster assemblies were further analyzed within a molecular-beam electric deflection experiment. Almost vanishing permanent dipole moments for MgPb(10-16) support the idea that a single Mg atom could be encapsulated within a highly symmetric lead cage, which results in structures with not only enhanced stability but also increased symmetry compared to the pure lead clusters Pb(N).


Oral iron supplementation with Feralgine® in inflammatory bowel disease: a retrospective observational study.
Inflammatory bowel disease (IBD) is a relapsing chronic disease of the gastrointestinal (GI) tract. Among IBD patients, anemia is more frequent than in general population. Recent studies demonstrated a good iron absorption using Feralgine®, a compound of ferrous bysglicinate chelate and alginic acid, oral supplementation with both good compliance rate and efficacy in treating iron deficiency anemia especially due to its high oral bioavailability. In this study we evaluated hemoglobin (Hb) improvement after Feralgine® supplementation in patients with IBD and anemia. This is a retrospective observational study. All data were derived from the patients' registry of the Inflammatory Bowel Disease Center, San Giovanni Antica Sede-Molinette Hospital, Turin, Italy. All IBD patients suffering from anemia and treated with Feralgine® (Tecnofer Plus), 1 capsule daily, were selected. Mean Hb value increased from 11 g/dL (95% confidence interval [CI]: 10.72-11.47) to 12.2 g/dL (95% CI: 11.6-12.52, P=0.0001), after three months of Feralgine® supplementation. While 90% of the patients did not report adverse events, 10% experienced dyspepsia and worsening of diarrhea. Only 6% of patients suspended oral iron supplementation due to GI intolerance (adherence rate 94%). Oral supplementation with Feralgine® induced a significant improvement in Hb levels, suggesting that in IBD patients with mild or moderate anemia, oral iron supplementation could be considered the first line therapy. We suggest further studies on larger cohorts to assess iron, ferritin and transferrin saturation improvement after this treatment.


Host-guest assembly of squaraine dye in cucurbit[8]uril: its implication in fluorescent probe for mercury ions.
The binding interactions between SQ2 squaraine dye and cucurbit[8]uril (CB8) effectively removes the aggregation of SQ2 in aqueous solution by forming a 1 : 1 inclusion complex. The resulting SQ2.CB8 complex exhibits highly selective fluorescence quenching by Hg(2+) ions, as a result of the synergetic binding between CB8, SQ2 and metal cation.


[Reflections about the efficiency criteria for cancer treatments during marketing authorization application].
Although clear and validated recommendations exist concerning the evaluation of cancer treatments at the international level, the criteria retained to obtain the marketing authorization (MA) are multiple and heterogeneous. This qualitative survey explores the opinion related to the assessment of cancer treatment among the several concerned population. By the way of semi-structured interviews, our aim was to elicit perceptions toward the criteria which should be retained during the process of MA, by patients, oncologists, members of the pharmaceutical industry, health decision-makers and general population. Our survey emphasizes the variability of the significations associated with the criteria of efficiency of cancer treatments according to the characteristics of the respondents. We also have observed some common expectations from patients and oncologists toward the economic and political aspect, but also from the whole respondents toward the importance of the comfort of the patients. Lastly, the necessity to define specific criteria related to clinical cases emerges.


Planck's generalised radiation law and its implications for cathodoluminescence spectra.
Cathodoluminescence (CL) is an important analytical technique for probing the optical properties of materials at high spatial resolution. Interpretation of CL spectra is however complicated by the fact that the spectrum depends on the carrier injection density of the incident electron beam. Here a generalised version of Planck's radiation law is used to uncover the evolution of CL spectra with injection under steady-state conditions. The importance of the quasi-Fermi level is highlighted and it is shown that steady-state luminescence is suppressed when the carrier distributions undergo a population inversion. The theory is consistent with some well-known luminescence phenomena, such as the blue shifting of donor-acceptor pair transitions with increased injection, and its predictions are experimentally verified on CdTe and GaN, which are exemplar thin-film solar cell and light emitting diode materials respectively. Furthermore, the discussion is broadened to include pulsed illumination in time resolved CL, where the carrier distribution is dynamically evolving with time.


A proteomic view on the role of glucose in peritoneal dialysis.
Peritoneal dialysis is a frequently used mode of renal replacement therapy although peritoneal dialysis fluid (PDF) acts as stressor for mesothelial cells. In this study, stress response to PDF is investigated by a proteomics approach using Met-5A cell cultures closely resembling mesothelial cells. In a previous work, we identified about 100 proteins as significantly enhanced or diminished in abundance after full-PDF stress (90 mM glucose, pH 5.8, and presence of lactate and glucose degradation products (GDPs)) using two-dimensional electrophoresis (2-DE) and MALDI-MS and MS/MS techniques. In this paper, a functional analysis is presented assigning these proteins to glucose associated pathways according to the KEGG database. To establish the stressor role of high glucose concentration, the up/down regulation of proteins populating these pathways were investigated in a fluorescence-difference gel electrophoresis (DIGE) experiment exposing Met-5A cells to nonphysiologically high glucose conditions only. In this glucose-single stress experiment, the fold-change ratios of the investigated glucose-pathway associated proteins were found much lower than observed in the previous full-PDF stress experiments. This finding supports the hypothesis that cellular response to full-PDF stress is not primarily induced by the high glucose concentration, even when focusing on proteins belonging to the glucose associated pathways.


Mottled permanent incisors in 15-year-old Lagos children.
Mottled permanent incisors were studied in a stratified convenience sample of 206 Lagos schoolchildren aged 15 years. The mouth prevalence of this condition was 32%, and the right-left symmetry of the mottled incisors occurred very approximately in only a third of those persons with mottling. The distribution pattern was similar to that observed in similarly aged children in non-fluoride communities, and also that observed in optimally fluoridated Anglesey, England. The cause of this type of mottling in unknown, but its distribution suggests that endogenous (possibly genetic) factors may be involved.


Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsy--prospective multicenter study.
To compare biopsy performance of two approaches for multiparametric magnetic resonance (MR)-targeted biopsy (TB) with that of extended systematic biopsy (SB) in prostate cancer (PCa) detection. This institutional review board-approved multicenter prospective study (May 2009 to January 2011) included 95 patients with informed consent who were suspected of having PCa, with a suspicious abnormality (target) at prebiopsy MR. Patients underwent 12-core SB and four-core TB with transrectal ultrasonographic (US) guidance, with two cores aimed visually (cognitive TB [TB-COG]) and two cores aimed using transrectal US-MR fusion software (fusion-guided TB [TB-FUS]). SB and TB positivity for cancer and sampling quality (mean longest core cancer length, Gleason score) were compared. Clinically significant PCa was any 3 mm or greater core cancer length or any greater than 3 Gleason pattern for SB or any cancer length for TB. Statistical analysis included t test, paired χ(2) test, and κ statistic. Primary end point (core cancer length) was calculated (paired t test). Among 95 patients (median age, 65 years; mean prostate-specific antigen level, 10.05 ng/mL [10.05 μg/L]), positivity rate for PCa was 59% (n = 56) for SB and 69% (n = 66) for TB (P = .033); rate for clinically significant PCa was 52% (n = 49) for SB and 67% (n = 64) for TB (P = .0011). Cancer was diagnosed through TB in 16 patients (17%) with negative SB results. Mean longest core cancer lengths were 4.6 mm for SB and 7.3 mm for TB (P < .0001). In 12 of 51 (24%) MR imaging targets with positive SB and TB results, TB led to Gleason score upgrading. In 79 MR imaging targets, positivity for cancer was 47% (n = 37) with TB-COG and 53% (n = 42) with TB-FUS (P = .16). Neither technique was superior for Gleason score assessment. Prebiopsy MR imaging combined with transrectal US-guided TB increases biopsy performance in detecting PCa, especially clinically significant PCa. No significant difference was observed between TB-FUS and TB-COG for TB guidance.


Thyroid stimulating hormone receptor antibody levels in Singaporean patients with autoimmune thyroid disease.
Stimulating thyrotrophin receptor antibodies (TRAbs) have been identified as the antibodies responsible for the pathogenesis of Graves' disease (GD) while blocking TRAbs have been implicated as the cause of hypothyroidism in some patients with chronic lymphocytic thyroiditis (CLT). TRAb positivity in patients with other thyroid disorders such as silent thyroiditis, toxic multinodular goitre and subacute thyroiditis has been reported but the role of TRAb in these disorders is unclear. A study was carried out to determine the prevalence of TRAb positivity in Singaporean patients with a spectrum of thyroid diseases. TRAb levels were measured in 181 patients with GD, 54 patients with CLT (37 goitrous and 17 agoitrous), 16 patients with thyroid nodules, 11 patients with subacute thyroiditis, 1 patient with hyperthyroidism due to a human chorionic gonadotrophin (HCG)-secreting tumour, 2 patients with thyroid stimulating hormone-secreting tumours and 2 patients with amiodarone-induced dysthyroidism. Using a cut-off of 10.0 U/L, TRAb levels were found to be positive in 79.0% of GD patients, 9.2% of CLT patients (euthyroid and hypothyroid) and no patients with other thyroid disorders. TRAb was a more sensitive marker of GD than anti-thyroglobulin antibodies (53.2%) but not anti-microsomal (78.3%) antibodies. TRAb levels > 10.0 U/L appear to be highly specific for autoimmune thyroid disease.


Fetal echocardiography--applications and limitations.
Fetal echocardiography has been a useful technique for demonstrating the anatomy of the developing human heart. M-mode echocardiography may be used to provide rhythm diagnosis in the absence of high-fidelity transabdominal fetal electrocardiograms. The information so generated may be applied to plan the management of pregnancy and delivery in a population at "high risk" for structural or functional heart disease and may provide the impetus for developing in utero treatment programs. For this reason, a high degree of sensitivity and specificity must be asked of the technique and of the personnel performing the examination. "Major" malformations which impart marked hemodynamic and structural alterations on the fetal heart may be reliably diagnosed. Diseases which must be identified on the basis of direct recognition of subtle abnormalities of structure, with little impact on fetal flow patterns (e.g. mild semilunar valve stenosis of perimembranous ventricular septal defect) have been more problematic. Before effective screening and treatment programs for the fetal heart can be developed, a cooperative effort between cardiologists and perinatologists is essential in order to gain facility with imaging as well as familiarity with the natural history of these conditions.