Colchicine antimitosis causes progression of S-(1,2-dichlorovinyl)-L-cysteine-induced injury leading to acute renal failure and death in mice.
Objective of the present study was to test the importance of tissue repair in the final outcome of S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced nephrotoxicity using colchicine (CLC) intervention. Male Swiss Webster (SW) mice were administered a normally nonlethal dose of DCVC (30 mg/kg, i.p.) on day 0 and CLC (2 mg/kg, i.p.) at 42 and 66 h after administration of DCVC. The mice were observed for mortality and various renal injury and repair parameters were studied during a time course of 0-14 days. Administration of 30 mg DCVC/kg led to loss of renal architecture by day 1, which sustained until day 5, and regressed thereafter to reach normal architecture by day 10 resulting in 100% survival. Renal dysfunction as assessed by increases in plasma BUN and creatinine levels was concordant during this time course. Urinary volume increased significantly between days 10 and 14 with significant increases in urinary glucose concentrations on days 1-4. Calpain leakage increased from day 1 and remained so until day 5 before declining at later time points. In contrast, CLC intervention led to marked inhibition of S-phase DNA synthesis and 100% mortality by 120 h. H&E sections of kidneys revealed loss of renal architecture on day 1 which progressively worsened from day 2 to 4. Polyuria and glycosuria were evident during the first 2 and 3 days, respectively. Calpain immunohistochemistry revealed progressive leakage of calpain in the extracellular space during 2-4 days which lead to increased renal injury as evident from significant increases in calpain specific breakdown products (CSBPs) of alpha-fodrin during the same period of time. The group of mice receiving 2 mg CLC/kg alone showed a significant increase in urinary creatinine concentration on day 5. Neither the expression nor localization of aquaporin 1 was altered in any of the treatment groups. These results show that antimitotic intervention after DCVC-initiated renal injury leads to expansion and progression of that injury, which appears to be due to proteolytic destruction of neighboring cells mediated by calpain leaking out of necrosed renal tubular epithelial cells.


The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage.
A long-standing challenge in the biomechanics of connective tissues (e.g., articular cartilage, ligament, tendon) has been the reported disparities between their tensile and compressive properties. In general, the intrinsic tensile properties of the solid matrices of these tissues are dictated by the collagen content and microstructural architecture, and the intrinsic compressive properties are dictated by their proteoglycan content and molecular organization as well as water content. These distinct materials give rise to a pronounced and experimentally well-documented nonlinear tension-compression stress-strain responses, as well as biphasic or intrinsic extracellular matrix viscoelastic responses. While many constitutive models of articular cartilage have captured one or more of these experimental responses, no single constitutive law has successfully described the uniaxial tensile and compressive responses of cartilage within the same framework. The objective of this study was to combine two previously proposed extensions of the biphasic theory of Mow et al. [1980, ASME J. Biomech. Eng., 102, pp. 73-84] to incorporate tension-compression nonlinearity as well as intrinsic viscoelasticity of the solid matrix of cartilage. The biphasic-conewise linear elastic model proposed by Soltz and Ateshian [2000, ASME J. Biomech. Eng., 122, pp. 576-586] and based on the bimodular stress-strain constitutive law introduced by Curnier et al. [1995, J. Elasticity, 37, pp. 1-38], as well as the biphasic poroviscoelastic model of Mak [1986, ASME J. Biomech. Eng., 108, pp. 123-130], which employs the quasi-linear viscoelastic model of Fung [1981, Biomechanics: Mechanical Properties of Living Tissues, Springer-Verlag, New York], were combined in a single model to analyze the response of cartilage to standard testing configurations. Results were compared to experimental data from the literature and it was found that a simultaneous prediction of compression and tension experiments of articular cartilage, under stress-relaxation and dynamic loading, can be achieved when properly taking into account both flow-dependent and flow-independent viscoelasticity effects, as well as tension-compression nonlinearity.


[Investigation on serious diarrhea].
We made an etiologic and epidemiologic investigation on 92 cases of serious diarrhea patients treated at hospitals of different level in Longhai county in 1986. From 63 patients, pathogenic organisms were isolated with the case positive rate of 64.48%; There are totally 75 isolates with the strain positive rate of 81.52%, among which 50 strains were ETEC (66.67%). High incidence was in August and September, during which there were 77 cases accounting for 83.69% of total cases and pathogen isolation rate was the highest. The main pathogen was ETEC, most of them were ST-producing strains, whose toxigenic ability is stronger there was only 19.70% whose ratio of intestinal weight to body weight was less than 0.1000 and the rest 80.30% more than 0.1000 in baby mice test.


Differing photo-oxidation mechanisms: electron transfer in TiO2 versus iron-doped TiO2.
Low-level iron doping has been found to alter the photo-oxidation mechanism of TiO(2) by efficiently activating molecular oxygen. In the absence of iron, TiO(2) either reduces water or stores the electron. Quantitatively, 0.5% Fe-TiO(2) is nearly three times as efficient as undoped TiO(2); 0.1% Fe-TiO(2) is twice as efficient. It is found that the efficiency boost primarily results from a more effective use of the absorbed UV photons. Extension of absorption into the visible region due to iron doping increases the efficiency by a factor of only 1.03 compared with UV-only irradiation. Characterization of these small particles reveals that particle size, crystal structure (anatase in all cases), and exposed faces are all insensitive to iron doping. Iron modifies the electronic states of TiO(2) by introducing an interband state and enhancing population of a newly identified state at +1.48 eV that acts as an efficient electron-hole recombination site. Activation of molecular oxygen effectively competes with electron-hole pair recombination.


Serum concentrations of apoptosis-associated molecules in septic children with leukemia, neutropenia and fever.
It has been shown that Fas, Fas-L, TNF and TNFR-1 display high serum concentrations in subjects with sepsis. This suggests that these are potential severity markers. However, the serum concentration of these molecules in children with leukemia and suspected sepsis has to be established before proposing their use as diagnostic biomarkers. We included children <17 years of age diagnosed with acute lymphoblastic leukemia with neutropenia and fever (NF). The subjects were divided into two groups: (1) leukemia and NF with sepsis, (2) leukemia and NF without sepsis. Determination of serum levels of TNF-α, TNFR-1, Fas and Fas-L was performed using ELISA tests, and apoptosis percentage using flow cytometry. Seventy-two subjects with ALL and NF were included in the two groups. The highest serum levels of TNF-α (35.2 ± 7.6 pg/ml) and TNF-R1 (4102 ± 2440) and the lowest levels of Fas-L (19.4 ± 7.3 pg/ml) were found in group 2: however, the difference in comparison with patients without sepsis was not statistically significant. Low levels of Fas-L and low percentage of apoptotic cells are observed in septic subjects. This pattern may reflect the presence of sepsis among subjects with NF secondary to leukemia.


Applicability of the.Lorentzian peak method to analyze leaky and lossy optical waveguides.
Several conclusions concerning the applicability of the Lorentzian peak method to compute the complex propagation constant of leaky and lossy waveguide modes are established.


Lateral Inhibition is a Neural Mechanism Underlying Mismatch Negativity.
The human auditory change detection response known as mismatch negativity (MMN) is an auditory event-related potential that has been extensively used to investigate various aspects of human brain function and dysfunction. However, two competing views of the neural mechanism that underlie MMN have been a subject of debate for decades. The sensory memory hypothesis claims that the MMN reflects sensory memory-based change detection. The adaptation hypothesis argues that neural adaptation and lateral inhibition can fully explain the MMN. To date, there remains a lack of empirical evidence exploring whether lateral inhibition underlies MMN, which is a critical assumption of the adaptation hypothesis. In this study, an oddball paradigm was developed in which tone-pairs composed of two sinusoidal tones were presented as standards and deviants (e.g., a 330 Hz-392 Hz tone-pair was presented as standard, and a 392 Hz-330 Hz tone-pair was presented as deviant). The paradigm expected that two successive MMNs would be elicited by the two successive acoustic deviations in the deviant tone pairs, but when the two tones composing the tone-pairs were close in frequency, the first MMN would be attenuated in amplitude due to lateral inhibition. The results demonstrate that only one (the second) MMN was observed when the two tones were close in frequency (330 Hz and 392 Hz), but two MMNs were observed when the two tones were distant in frequency (330 Hz and 3135 Hz). These results suggest that lateral inhibition is a neural mechanism that underlies the MMN response.


Understanding the arousal of anger: a patient-centred approach.
The aim of this article is to enable reflection on practice by exploring a nurse-patient scenario and identifying what factors trigger anger and aggressive behaviour. It recommends strategies that can be used to tackle anger among patients, and emphasises the importance of the therapeutic relationship. Anger management, which usually refers to cognitive behavioural therapy designed to enable people to manage anger, is not explored.


Gastric intramural pH as indicator of early allograft viability in orthotopic liver transplantation.
The determination of the viability of OLT grafts has relied upon metabolic tests of the liver, which take several hours to evaluate and therefore are only conclusive in most patients well into the postoperative period. Earlier diagnosis of graft failure or nonfunction would allow intraoperative reassessment of surgical technique and, in the case of graft failure, earlier planning for retransplantation. Since gastrointestinal mucosal ischemia is one of the earliest manifestations of impaired core tissue in the critically ill, a tonometric nasogastric tube (Tonomitor) was used in our patients to measure intramucosal gastric pH (pHi) during the preanhepatic (stage I), anhepatic (stage II), and neohepatic (stage III) phases of OLT in 35 patients as an indicator of graft liver function and viability. Based on the results of the pHi measurement 30 min after reperfusion during stage III, patients were divided into 2 groups using a pHi of 7.30 as the dividing point. Patients with a pHi equal or higher than 7.30 were assigned to group 1 (n = 24) and patients with a pHi lower than 7.30 were assigned to group 2 (n = 11). The pHi in group 1 patients averaged 7.37 +/- 0.5 30 min after reperfusion and throughout surgery. The pHi in group 2 patients was lower than that of the group 1 patients 30 min after reperfusion, 7.23 +/- 0.04 (P < 0.001). The pHi in 10 group 2 patients returned to normal within 3 hr after reperfusion and the pHi values for these patients were not significantly different from those of group 1 at 3 hr after reperfusion. The pHi in 1 group 2 patient remained lower than 7.30 and never returned to normal; this patient underwent retransplantation the following day. Utilizing the tonometric nasogastric tube to sample intramucosal pH allowed early detection of graft function and intermittent trending of pHi in patients with questionable graft function during the operative period. It also provided a means of assessing graft function independent of enzymatic criteria, which provide little information in the early phase of transplantation.


Preparative isolation of immune complexes from serum by sucrose gradient ultracentrifugation.
Immune complexes were isolated by ultracentrifugation in sucrose gradients (20-65% (w/w]. the centrifugation procedure was demonstrated to be isopycnic. The banding density of the complexes was influenced by the chemical nature and molecular size of the antigen and by the antigen to antibody ratio. The method was applied for preparative isolation of immune complexes from patients with systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and uncomplicated psoriasis.


[Unusual "lipid cysts" in the acetabular labrum of patients with hip joint osteoarthrosis].
Diagnostic pathological examination of surgical specimens from patients with hip joint osteoarthrosis occasionally exhibits as yet undescribed pseudocysts consisting of folded granular membranes in necrotic or chondroid tissues. When stained with Sudan red, the content of these cysts indicates the presence of lipid substances. The presence of S100 protein-positive cells with intracytoplasmic fat vacuoles as well as such cells in the walls indicate that they develop from fat inclusions occurring in the chondroid cells of the labrum. Two different wall structures were detected by electron microscopy. The first type exhibited small walls of a granular material similar to the endoplasmic reticulum that surrounds intracytoplasmic fat globules. The second type consisted of broad layers of very tiny granules indicating a more advanced stage of the development of these cysts. The reason for the occurrence of these "chondrocytogenic lipid cysts" remains unknown-it may be assumed that they are due to mechanical labrum destruction that occurs in osteoarthrosis.


Reliability of a repeated-sprint test for field-hockey.
The purpose of this study was to assess the reliability of a repeated-sprint test, specifically designed for field-hockey, as it was based directly on the time-motion analysis of elite level competition. The test consisted of 6 x 30-m over-ground sprints departing on 25s, with an active recovery (approximately 3.1-3.3 ms(-1)) between sprints. Ten highly trained, male, field-hockey players (mean+/-S.D.: age, 23+/-3 years; body mass, 78.1+/-7.1 kg) participated in this study. Following familiarisation, the subjects performed the repeated-sprint test on two occasions, 7 days apart. The reliability of the test variables was assessed by the typical error of measurement (TE). The total sprint time was very reliable (T(1): 26.79+/-0.76 s versus T2: 26.83+/-0.74 s), as the TE was 0.7% (95% CL, 0.5-1.2%). However, the percent sprint decrement was less reliable (T1: 5.6+/-0.9% versus T2: 5.8+/-1.0%), with the TE being 14.9% (95% CL, 10.8-31.3%). In summary, it is suggested that this field-hockey-specific, repeated-sprint test is very reliable when the results are presented as the total sprint time.


Inhibition of peroxisome proliferator-activated receptor gamma activity in esophageal carcinoma cells results in a drastic decrease of invasive properties.
Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARgamma is a nuclear receptor superfamily member that is expressed in many cancers. PPARgamma expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARgamma antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (< 10 mM). A high concentration of antagonists (50 microM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARgamma antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK-MAPK pathway, and this was independent of apoptosis. These results suggested that PPARgamma plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer.


Optimization and statistical evaluation of dissolution tests for indinavir sulfate capsules.
An optimization, statistically based on t-student test, to set up dissolution test conditions for indinavir sulfate capsules is presented. Three dissolution media, including that reported in United States Pharmacopeial Forum, and two apparatus, paddle and basket, were applied. Two different indinavir sulfate capsules, products A and B, were evaluated. For a reliable statistical analysis eighteen capsules were assayed in each condition based on the combination of dissolution medium and apparatus. All tested media were statistically equivalent (P > 0.05) for both drug products when paddle apparatus was employed at the stirring speed of 50 rpm. The use of basket apparatus at the stirring speed of 50 rpm caused significant decrease in the drug release percent for the product B (P < 0.05). The best dissolution conditions tested, for products A and B, were applied to evaluate capsules dissolution profiles. Twelve dosage units were assayed and dissolution efficiency concept was used, for each condition, to obtain results with statistical significance (P > 0.05). Optimal conditions to carry out the dissolution test were 900 ml of 0.1 M hydrochloric acid as dissolution medium, basket at 100 rpm stirring speed and 260 nm ultraviolet detection.


Degenerative lumbar scoliosis.
In adults, symptomatic scoliosis is usually a de novo primary degenerative deformity that develops in the fifth or sixth decade or an unrecognized or untreated idiopathic deformity with superimposed degeneration. The evaluation and treatment of adult scoliosis must focus on addressing patient symptoms while limiting the consequences of the treatment. The presence of neurological deficits, the flexibility of the deformity, the coronal and sagittal balance, and status of spinal segments outside of the main deformity are all important considerations when planning surgery. The complication rate of deformity surgery in adults is potentially high; but excellent functional outcome and patient satisfaction can occur with thorough preoperative patient education and meticulous surgical technique.


[Sudden cardiac death in giant cell arteritis].
The autopsy findings of a 74-year-old women who unexpectedly died are presented. She had suffered from polymyalgia but typical symptoms of temporal arteritis had been absent and tentative treatment with prednisone had not improved the polymyalgic pain. The autopsy revealed a generalized giant cell arteritis involving the left temporal artery, the left common carotid artery, the ascending aorta, a submucosal artery of the ileum and the left anterior descending branch of the coronary arteries. Histology showed typical granulomatous infiltrates including giant cells, followed by thrombotical occlusion of the coronary artery branch and subsequent myocardial infarction. Giant cell arteritis is a systemic vasculitis of aged subjects with predominant localisation in the cranial arteries, but occasional involvement of any type of visceral and peripheral arteries. Coronary involvement with sudden cardiac death is not a commen complication of giant cell arteritis but has occasionally been described in the literature.


Involvement of CesA4, CesA7-A/B and CesA8-A/B in secondary wall formation in Populus trichocarpa wood.
Cellulose synthase A genes (CesAs) are responsible for cellulose biosynthesis in plant cell walls. In this study, functions of secondary wall cellulose synthases PtrCesA4, PtrCesA7-A/B and PtrCesA8-A/B were characterized during wood formation in Populus trichocarpa (Torr. & Gray). CesA RNAi knockdown transgenic plants exhibited stunted growth, narrow leaves, early necrosis, reduced stature, collapsed vessels, thinner fiber cell walls and extended fiber lumen diameters. In the RNAi knockdown transgenics, stems exhibited reduced mechanical strength, with reduced modulus of rupture (MOR) and modulus of elasticity (MOE). The reduced mechanical strength may be due to thinner fiber cell walls. Vessels in the xylem of the transgenics were collapsed, indicating that water transport in xylem may be affected and thus causing early necrosis in leaves. A dramatic decrease in cellulose content was observed in the RNAi knockdown transgenics. Compared with wildtype, the cellulose content was significantly decreased in the PtrCesA4, PtrCesA7 and PtrCesA8 RNAi knockdown transgenics. As a result, lignin and xylem contents were proportionally increased. The wood composition changes were confirmed by solid-state NMR, two-dimensional solution-state NMR and sum-frequency-generation vibration (SFG) analyses. Both solid-state nuclear magnetic resonance (NMR) and SFG analyses demonstrated that knockdown of PtrCesAs did not affect cellulose crystallinity index. Our results provided the evidence for the involvement of PtrCesA4, PtrCesA7-A/B and PtrCesA8-A/B in secondary cell wall formation in wood and demonstrated the pleiotropic effects of their perturbations on wood formation.


[Dermatology].
Many significant advances in dermatology were published during 2009, focussing on infectious diseases, inflammatory disorders and oncology. Molecular medicine, as a result of the human genome project, also modifies the field of dermatology. Bioinformatics and biotechnology revolutionize the daily clinical practice in dermatology. A change of paradigm occurs notably in infectious diseases.


Hyperbaric oxygen treatment ameliorates gentamicin-induced nephrotoxicity and expression of kidney injury molecule 1 in the rat model.
In recent years hyperbaric oxygen (HBO2) therapy has been considered as an effective method for the treatment of gentamicin (GM)-induced renal toxicity. However, the findings related to the use of HBO2 for GM toxicity are limited and contradictory. The aim of this study is to investigate the protective role of HBO2 on GM-induced nephrotoxicity. For this purpose, Wistar albino rats (n=28) were randomly divided into four equal groups: C, HBO2, GM and GM+HBO2. GM (100 mg/kg, ip) and HBO2 were applied over seven days. On the eighth day blood and kidney tissue samples were harvested. The albumin, creatinine, and urea levels were determined from serum samples. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) values were analyzed spectrophotometrically. The relative expression level of TNF-α, IL-1β and Kim-1 gene were determined by qRT-PCR assays; histopathologic investigation was completed in kidney tissue samples. Serum urea, albumin and creatinine levels significantly increased in the GM group compared to the GM+HBO2 group. For antioxidant parameters the GM+HBO2 group was not statistically different from the C group but was significantly different compared with the GM group. TNF-α, IL-1β and Kim-1 gene expression levels in the GM group were statistically increased compared to the GM+HBO2 group (p=0.015, p=0.024, p=0.004) respectively. Severe tubular necrosis, epithelial desquamation and mild peritubular hemorrhage were observed in the GM-administrated group, while HBO2 exposure ameliorated these alterations. In conclusion, HBO2 exposure may be defined as a potential method for the prevention of GM-induced renal toxicity.


Determinants of coronary blood flow following primary angioplasty for acute myocardial infarction.
The aim of this study was to evaluate determinants of coronary blood flow following primary angioplasty (PA) in acute myocardial infarction (AMI). The corrected TIMI (thrombolysis in myocardial infarction) frame count and the TIMI flow grade were used as indexes of coronary blood flow, and its determinants were examined in 115 consecutive AMI patients who underwent PA (pain onset </= 12 hr). The following were validated as univariate predictors of slower corrected TIMI frame count: a lower pressure-derived farctional collateral flow (PDCF) index (P < 0.01), poor angiographic collaterals (P < 0.01), TIMI flow 0, 1 before PA (P < 0.05), and the presence of heavy thrombi (P < 0.01). The PDCF index and the presence of heavy thrombi were independent predictors of the corrected TIMI frame count. Likewise, the PDCF index (chi(2) = 12.9; P < 0.01) and the presence of heavy thombi (chi(2) = 11.4; P < 0.01) were independent predictors of TIMI 3 flow. In conclusion, collateral flow and the presence of thrombi are major determinants of coronary blood flow after PA in AMI.


Development of the cardiac conduction system: a matter of chamber development.
Within one day after the formation of the linear heart an adult type of electrocardiogram (ECG) can be monitored, reflecting the development of coordinated activation of the heart. The possibility that during evolution and ontogenesis of the heat, this development is achieved by localized growth of cardiac chambers rather than of a conduction system is discussed here.


Effect of Hybrid stage 1 procedure on ventricular function in infants with hypoplastic left heart syndrome.
The effect of Hybrid stage 1 palliation for hypoplastic left heart syndrome on right ventricular function is unknown. We sought to compare right ventricular function in normal neonates and those with hypoplastic left heart syndrome before Hybrid palliation and to assess the effect of Hybrid palliation on right ventricular function, using the right ventricular myocardial performance index and the ratio of systolic and diastolic durations. We carried out a retrospective review of echocardiographic data on 23 infants with hypoplastic left heart syndrome who underwent Hybrid palliation and 35 normal controls. Data were acquired before Hybrid and after Hybrid palliation - post 1, 0-4 days; post 2, 1 week; post 3, 2-3 weeks; post 4, 1-1.5 months following Hybrid palliation. Myocardial performance index and ratio of systolic and diastolic durations were higher in the pre-Hybrid hypoplastic left heart syndrome group (n=23) - 0.47±0.16 versus 0.25±0.07, p<0.001; 1.59±0.44 versus 1.09±0.14, p<0.0001 - compared with controls (n=35). There was no significant change in the myocardial performance index at any of the post-Hybrid time points. Ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid - post 3: 2.08±0.62 and post 4: 2.21±0.45 versus pre: 1.59±0.44, p=0.043 and 0.003. There were no significant differences in parameters between sub-groups of infants who died (n=10) and survivors (n=13). Right ventricular myocardial performance index and ratio of systolic and diastolic durations were significantly higher in infants with hypoplastic left heart syndrome before intervention compared with controls. The ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid palliation. Our data suggest that infants with hypoplastic left heart syndrome have right ventricular dysfunction before intervention, which worsens over 2 weeks after Hybrid palliation.


[Factors associated with postpartum weight retention based on the generalized estimation equation in Kaifu Districtin Changsha].
To investigate the current status of the postpartum weight retention (PPWR) in Kaifu District of Changsha, and explore the influential factors with PPWR based on the generalized estimating equation model. Methods: A cluster sampling method was applied to select women who gave birth at the health service centers of 3 street communities in Kaifu District of Changsha during 2015. According to the inclusion and exclusion criteria, 783 cases were finally included in the study. Data on PPWR were collected prospectively by using the self-made questionnaire at 1, 3, 6 and 8 months after childbirth. Analysis were performed to investigate the associations between PPWR and its potential factors with generalized estimation equation model. Results: The mean PPWR of women was gradually decreased with the increase of postpartum time, and 34.6% of them have returned to the pre-pregnancy weight in the 8 months postpartum. Our findings revealed that gestation weight gain (GWG), pre-pregnancy body mass index, feeding patterns, and delivery mode were significantly associated with maternal PPWR (P<0.05). In contrast, maternal age, educational level, per capita income of family, parity and postpartum depression were not contributed to PPWR (P>0.05). Conclusion: GWG is one of the most important predictors for PPWR. The key to reducing PPWR is to control GWG systematically. Early targeted interventions and health education should be taken to prevent women from excessive PPWR at the first-year postpartum, in particular to the women who underwent cesarean deliveries and breastfed their infants. It is conducive to reduce the risks of overweight or obesity caused by PPWR.


A new radiometric assay for the quantitation of surface-bound IgG on sensitized erythrocytes.
We have developed a sensitive, straightforward method for the quantitation of surface-bound IgG on sensitized erythrocytes. The assay is based on the consumption by sensitized cells of anti-IgG antiserum. The remaining anti-IgG is quantitated in a second incubation by precipitation with 125I-IgG in the presence of polyethylene glycol. Calibration curves for this assay were constructed using known amounts of unlabeled IgG. The method can be performed in microtitre plates and eliminates the use of purified anti-erythrocyte antibodies, or highly purified specific anti-IgG antisera. The results were completely consistent with those of immunofluorescence assays, but our method was much more sensitive, less than 500 molecules of IgG per cell being detected reproducibly. The technique is not laborious and takes much less time than previously described methods with similar sensitivity. As an example of the applicability of this test, the implications of ligand density for the detection by EA rosetting of Fc receptors on human monocytes are shown. The results suggest that a large variation exists in the affinity of the different types of Fc receptors for their ligands.


In vitro antimicrobial activity of tioconazole and its concentrations in vaginal fluids following topical (vagistat-1 6.5%) application.
In vitro assays demonstrated that clinical yeasts were significantly more inhibited by tioconazole (MIC50, < or = 0.5 microgram/ml) than by fluconazole (MIC50, 8 micrograms/ml). Tioconazole also exhibited high potency against most molds (Alterneria spp. and Acremonium spp.). All Candida tropicalis isolates had MICs of 8 micrograms/ml, four-fold greater than any other Candida spp. Generally Gram-negative bacteria were less susceptible to tioconazole. Moraxella catarrhalis (MIC90, 2 micrograms/ml) was the most susceptible Gram-negative species. Staphylococci and enterococci were the most susceptible to tioconazole Gram-positive species (MIC50s, 1-8 micrograms/ml). Bacterial species associated with vaginosis. [Gardnerella vaginalis (MIC90, 16 micrograms/ml), Mobiluncus spp. (MIC90, 16 micrograms/ml) and Prevotella biviadisiens (MIC90, 64 micrograms/ml)] were inhibited by tioconazole. Isolates of Lactobacillus spp. were most resistant (MIC90, > or = 256 micrograms/ml) to tioconazole. Vaginal fluid levels of tioconazole (mean, 91.4 micrograms/ml) persisted above the MIC90 levels (1-64 micrograms/ml) for most fungal and bacterial pathogens for 72 h in 19 evaluable female human subjects receiving 300 mg tioconazole in an intravaginal ointment.


Noncontrast multidetector CT of the kidneys: utility of 2D MPR and 3D rendering to elucidate genitourinary pathology.
To encourage routine use of 2D multiplanar reconstructions (MRPs) and 3D renderings when interpreting noncontrast computed tomography (CT) of the kidney, as this practice can unveil findings related to the kidney or its vasculature that are not apparent on axial sections. Inspecting the kidneys or characterizing CT findings with both axial sections and MPRs may facilitate identification of vascular and neoplastic pathology.


The role of tumor necrosis factor alpha in chemical-induced hepatotoxicity.
Only recently have toxicologists come to understand the role of inflammation, and TNFalpha specifically, in classical toxicological processes. This relationship appears fairly complex, as inflammation and proliferation may well be only one facet of a time- and dose-dependent continuum of toxicological and repair processes. Not surprisingly, considerable efforts are being undertaken using our newly found understanding of molecular control to develop specific and safe chemical, biological, and molecular regulators of TNFalpha for potential therapeutic use. Their effectiveness in controlling environmental or occupational diseases has yet to be established.


An interface phase transition: complete to partial wetting.
When two fluid phases are near a critical point, one of them will be excluded from contact with any third phase that happens to be present by a wetting film of the other critical phase. A simple and quite general strategy that may be used to induce a phase transition from complete wetting of the third phase to incomplete wetting is to add a new component to the fluid phases chosen to drive the two phases away from their critical point. This strategy is illustrated for methanol-cyclohexane mixtures.


In vivo BMP-7 (OP-1) enhancement of osteoporotic vertebral bodies in an ovine model.
Prevention of osteoporotic vertebral fractures could help at-risk individuals avoid the pain and morbidity associated with these fractures. Currently, patients with osteoporosis are treated with systemic medications to reduce fracture risk. Although effective, these therapies do not eliminate fractures and also tend to have a gradual time-dependent effect on fracture risk. The mechanism of action of the bone morphogenetic protein (BMP) family theoretically makes these molecules candidates for rapidly enhancing local bone structure. An in vivo study analyzing the effects of BMP-7 (osteogenic protein 1 [OP-1]) treatment on osteopenic ovine vertebral architecture and biomechanics. We tested the hypothesis that local injection of OP-1 into osteopenic ovine vertebrae will improve bone mass and trabecular distribution, thereby reducing bone fragility and fracture risk. We specifically evaluated compressive biomechanics and morphology of osteopenic ovine vertebral bodies 6 months after local OP-1 treatment. In vivo animal study. Skeletally mature sheep (n=24) underwent ovariectomy and were placed on low cation relative to anion diet. These interventions reduce bone density and induce skeletal fragility. After 6 months, sheep were randomly assigned to six treatment groups based on OP-1 dose (370 mg or 0 mg) and carrier with 4 animals/treatment group. Carriers A and B were poly-L-glycolic acid (PLGA) biospheres with different release kinetics (B allowing sustained BMP release); Carrier C was carboxymethylcellulose. After creating an 8-mm-diameter defect in the midvertebral body, sheep underwent intravertebral body implantation at two nonadjacent levels. Animals were euthanized 6 months after implantation and bone mineral density (BMD), biomechanics, and histomorphometry were assessed. Two-way analysis of variance was used to determine effects of OP-1 (alpha=0.05). An 81.9%, 333.2%, and 39.9% increase in stiffness was seen for OP-1 treated vertebra with Carriers A, B, and C respectively. Although these effects did not reach statistical significance, trends toward improvement were evident. Histology showed varied degrees of bony healing in the injection sites. Histomorphometrically, OP-1 treated vertebrae showed improvements in percent bone of up to 38% and star volume of up to 55% (with Carrier B). Improvements in whole vertebral body BMD were not detected for any treatment. In this study, local OP-1 treatment showed a positive trend in improving mechanical strength and histomorphometric parameters of osteopenic vertebra, despite the absence of consistent change in BMD. Controlled slow release of OP-1 using PLGA microspheres appeared to be the most effective method of protein delivery. In conclusion, we feel that the pilot data suggest that the use of OP-1 in the treatment of vertebral osteoporosis in an attempt to enhance bone strength merits further study.


[Study of drug allergies with special reference to skin manifestations].
One hundred and forty four patients, with dermal reactions to different drugs, were chosen from our clinic. The selection criteria was based on a detailed and careful anamnesis in order to be certain of the specific drug responsible for the reaction. We tried to establish a drug-specific reaction pattern for each of the drugs studied. Intradermal skin tests were performed with all drugs to be studied, except with pyrazolones and aspirin, for which patch tests were applied. The drug concentrations were established prior to the tests in order to avoid unwanted unspecific reactions. In every case, immediate and delayed reaction readings were carried out. A three crosses reaction (+++) was considered positive. The skin tests were positive in 44% of the cases, a value higher than those referred to by most authors. The delayed reactions to skin tests and the chloramphenicol-mediated delayed-type "dermatitis-like" manifestations are compared. It is noteworthy to mention that positive delayed reactions were observed more frequently with chloramphenicol than with any of the other studied drugs. The same applies for those patients with a positive history to chloramphenicol. The most common reaction pattern to penicillin and streptomycin in our series (20%) were urticaria and Quincke's edema. Penicillin, pyrazolones and streptomycin were the most common drugs responsible for urticarial patterns, being the pyrazolones related to fixed erythema in many cases. The age group 25-50 was the most frequently involved. No sex predominance was observed. The value of the classic skin tests is discussed, so are history recording and the in vitro tests.


Change in disability follows inpatient treatment for late life depression.
The objective of this study was to examine the relationship between functional disability and improvement in late life depression after acute inpatient treatment. The study was a longitudinal assessment of depression and disability. Patients were assessed during an initial inpatient hospitalization and then 3 months postdischarge. All patients were evaluated initially after admission to one of 71 inpatient psychiatric treatment facilities. The study comprised of 2572 patients older than age 60 who were relatively cognitively intact and experiencing significant depressive symptoms. Depressive symptoms were measured using the Geriatric Depression Scale. Disability was measured using the Instrumental Activities of Daily Living Scale and the Medical Outcomes SF-36. Depressive symptoms improved in the majority of patients. Moreover, improvement in depressive symptomatology was significantly related to improvement in instrumental activities of daily living (IADLs) and to health-related quality of life as measured by the SF-36. This relationship was strongest among those who initially presented with some disability in IADLs. This work underscores further the disabling nature of depression. Moreover, findings from this study suggest that treatment focused on depression can lead to significant improvements in both depressive symptoms and functional abilities. However, the results also suggest that the relationship between depression and disability is complex and that the effect of treating depression is not the only factor in the reversal of disability.


Production, stabilisation and characterisation of silver nanoparticles coated with bioactive polymers pluronic F68, PVP and PVA.
The increasing and alarming panorama of bacterial infections and associated morbidities that occur during medical and hospital procedures makes the development of technologies that aid in controlling such bacterial infections of utmost importance. Recent studies have shown that formulations with metal nanoparticles exhibit good antibacterial properties against a broad spectrum of microorganisms. Moreover, it was demonstrated that some biologically active polymeric materials, when applied in combination with chemical antimicrobial agents, enhance the therapeutic action of the latter. The research effort entertained herein aimed at the physico-chemical characterisation of silver nanoparticles obtained by chemical reduction, stabilised by bioactive polymers polyvinyl alcohol and polyvinylpyrrolidone, and further co-stabilised by pluronic F68. Scanning electron microscopy images of the nanoparticles produced, coated with different stabilisers, have shown that the chemical nature of the stabilisation effect promoted incorporation of pluronic in the nanoparticles and was closely related to an increase in the silver concentration in the nanoparticle samples obtained via energy-dispersive X-ray spectroscopy. The study described herein also shows that the nature of the stabiliser favours the interaction of pluronic F68 with samples containing silver nanoparticles.


[Effect of adenosine on endothelin-1 in the infarcted reflow and no-reflow myocardium of mini-swine].
To evaluate the effect of adenosine on endothelin-1 (ET-1) after acute myocardial infarction (AMI) and reperfusion and explore the possible mechanism of no-reflow. Twenty-four mini-swine were randomized into three study groups: control group (n=8), adenosine treated group (n=8), and sham-operated group (n=8). The mini-swine in the groups were subjected to 3 hours of coronary occlusion, followed by 60 minutes of reperfusion except those in the sham-operated group. The levels of ET-1 in blood sample, normal, infracted reflow and no-reflow myocardium were evaluated by radioimmuno-assay (RIA). The gene expressions of ET-1 in normal, infracted reflow and no-reflow myocardium were quantified by reverse transcription-polymerase chain reaction. In both control group and adenosine group, compared with that at the baseline, ET-1 in blood sample significantly increased at 5 minutes and 180 minutes of left anterior descending coronary artery occlusion, as well as 5 and 60 minutes of reperfusion (all P < 0.01). In adenosine group, the levels of ET-1 were significantly lower than those in the control group (P < 0.05, P < 0.01). In both control group and adenosine group, compared with that in normal myocardium, ET-1 levels in both infarcted reflow and no-reflow myocardium significantly increased (both P < 0.01), with the level of ET-1 in no-reflow myocardium significantly higher than that in infarcted reflow myocardium (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01). In both control and adenosine groups, compared with that in normal myocardium, the gene expression of ET-1 in infarcted reflow myocardium was significantly up-regulated (P < 0.01), while that of ET-1 in. no-reflow myocardium significantly down-regulated (P < 0.01). In adenosine group, the level of ET-1 in infarcted reflow myocardium was significantly lower than that in the control group (P < 0.01). The endothelium injury may be one of the important mechanisms for no-reflow phenomenon. Adenosine cay prevent endothelium from injury to reduce no-reflow.


Clinimetric concepts in outcome assessment: the OMERACT filter.
Validation is the process by which the clinical measurement (clinimetric) properties of an assessment procedure are formally evaluated. In the case of outcome measures, this process traditionally establishes the reliability, validity, and responsiveness of the measurement technique. Although the statistical methods used are diverse, the principles to be followed have been well established and are generally accepted. The basic issues are similar and transcend outcome measurement in different medical conditions. In addition to fulfilling clinimetric requirements, outcome measures are required to be practical in their application. The OMERACT group have recently proposed a novel user-friendly paradigm to capture the essential elements of truth, discrimination, and feasibility. This paradigm is termed the OMERACT filter.


Structural characterization of the unligated and choline-bound forms of the major pneumococcal autolysin LytA amidase. Conformational transitions induced by temperature.
The secondary and tertiary structures of the choline-dependent major pneumococcal autolysin LytA amidase and of its COOH-terminal domain, C-LytA, have been investigated by circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Deconvolution analysis shows that the far-UV CD spectrum of both proteins is governed by chiral contributions, ascribed to aromatic residue clusters contained in the COOH-terminal module. The secondary structure of LytA, determined from the FTIR spectral features of the amide I' band, results in 19% of alpha-helix and tight loops, 47% of beta-sheets, 23% of turns, and 11% of irregular structures. Similar values are obtained for C-LytA. The addition of choline significantly modifies the far- and near-UV CD spectra of LytA and C-LytA. These changes are attributed to alterations in the environment of their aromatic clusters, since the FTIR spectra indicate that the secondary structure is essentially unaffected. CD choline titration curves at different wavelengths show the existence of two types of binding sites/subunit. Data analysis assuming protein dimerization upon saturation of the high affinity sites reveals positive cooperativity between the low affinity sites. Thermal denaturation of both proteins occurs with the formation of unfolding intermediates and the presence of residual secondary structure in the final denatured state. The irreversibility of the thermal denaturation of LytA and C-LytA results from the collapse of the polypeptide chain into intermolecular extended structures. At saturating concentrations, choline prevents the formation of these structures in the isolated COOH-terminal module.


Assessment of pulmonary arterial hypertension in patients with systemic sclerosis: comparison of noninvasive tests with results of right-heart catheterization.
Pulmonary hypertension (PH) is an ominous complication in patients with scleroderma (systemic sclerosis, SSc). We compared noninvasive assessment of PH with pulmonary artery (PA) pressures obtained by right-heart catheterization (RHC). Forty-nine patients with SSc were evaluated for suspected PH based on clinical findings, progressive dyspnea, and pulmonary function tests (PFT). PH was defined as mean PA pressure > or = 25 mm Hg, or > or = 30 mm Hg after exercise, with normal pulmonary capillary wedge pressure (PCW). Doppler echocardiography (echo) and cardiac magnetic resonance imaging (MRI) were performed within 4 hours of RHC, and the predictive accuracy of the tests was compared. RHC identified 24/49 (49%) patients with PH. The noninvasive cutpoints were: estimated right ventricular systolic pressure > 47 mm Hg by echo; diameter of the main PA > 28 mm by MRI; and the ratio of forced vital capacity to diffusion capacity (%FVC/%DLCO) > 2.0 by PFT. Echo classified 38 subjects correctly (14/24 with and 24/25 without PH; sensitivity 58%, specificity 96%). The area under receiver-operating characteristic curve (AUC) was 0.84 for echo. MRI measurement of PA diameter had a sensitivity of 68% and specificity 71% (AUC 0.78). PFT evaluation had a sensitivity of 71% and specificity of 72% (AUC 0.76). In evaluation of SSc with suspected PH, echo appeared to be the most useful among the noninvasive tests, mainly due to the high specificity, high positive predictive value, and highest AUC. However, due to the low sensitivity of noninvasive testing, RHC should remain the gold standard.


The effect of age and sex on metabolism and urinary excretion of antipyrine.
Drug-metabolizing capacity is generally reduced in the elderly. The purpose of this investigation was to study antipyrine clearance and metabolite excretion in old subjects of both sexes. Saliva clearance of antipyrine and the production clearances of antipyrine metabolites were studied in young and elderly volunteers of both sexes. Seventy-six elderly subjects (mean age 81 years) were compared with a group of 24 young subjects (mean age 29 years). After oral administration, salivary antipyrine clearance declined with age in both males and females, whether or not this variable was corrected for weight, and antipyrine half-life was significantly prolonged in elderly groups of either sex. The percentage urinary excretion of the antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) was reduced at 48 h in the elderly compared to young subjects by 23%, 31%, and 10%, respectively, in males, and by 41%, 41%, and 24%, respectively, in females. The formation clearance of HMA was reduced by 47% in males and by 52% in females. NORA clearance declined by 42 and 56%, respectively, in males and females. A decrease of 30% in males and 44% in females was observed in OHA clearance. The findings suggest that aging leads to altered disposition of antipyrine in both males and females and that the main metabolic pathways of the compound are not different in the elderly.


Antimicrobial susceptibility of well-characterised multiresistant CTX-M-producing Escherichia coli: failure of automated systems to detect resistance to piperacillin/tazobactam.
This study was designed to determine the in vitro activities of several antimicrobial agents against well-characterised CTX-M-producing Escherichia coli strains isolated from clinical specimens. Minimum inhibitory concentrations (MICs) were determined for 202 extended-spectrum beta-lactamase (ESBL)-producing E. coli using microbroth dilution and Vitek methods according to Clinical and Laboratory Standards Institute criteria. Molecular characterisation was performed using isoelectric focusing and polymerase chain reaction (PCR) with sequencing, whilst strain relatedness was determined by pulsed-field gel electrophoresis (PFGE) using XbaI. Of the 202 ESBL-producing E. coli, 2 produced VEB-1, 12 produced TEM-52, 32 produced SHV types (including SHV-2 and -12) and 156 produced CTX-M types (including CTX-M-2, -3, -14, -15, -24, -27 and -30). The MIC(50) and MIC(90) (MIC for 50% and 90% of the organisms, respectively) for the antimicrobial agents tested were, respectively: piperacillin/tazobactam (TZP), 32mg/L and >256mg/L; ciprofloxacin, 16mg/L and 32mg/L; gentamicin, 8mg/L and 128mg/L; amikacin, 2mg/L and 16mg/L; ertapenem, 0.03mg/L and 0.12mg/L; imipenem, 0.03mg/L and 0.12mg/L; meropenem, 0.03mg/L and 0.03mg/L; and tigecycline 0.12mg/L and 0.5mg/L. Vitek Legacy and Vitek 2 failed to detect TZP resistance in 91 (90%) and 75 (74%) of 101 TZP-resistant ESBL-producing strains, respectively, especially CTX-M-15-producing isolates that co-produced OXA-1. The carbapenems, amikacin and tigecycline had good in vitro activities against multiresistant CTX-M-producing E. coli. We recommend that laboratories using Vitek should employ alternative susceptibility testing methods for TZP before reporting the activity of this agent against ESBL-producing E. coli.


Time-of-flight atom probe measurements on Ni3Al and Co3W.
In this study, a VG FIM100 was taken into operation, consisting of a field-ion microscope (FIM), a time-of-flight atom probe (TOFAP) and an imaging atom probe. A tungsten specimen was used to calibrate the conversion of flight times to m/n values. The resulting relative mass resolution of the TOFAP was calculated to be m/Deltam approximately 500 FWHM. In time-of-flight measurements of homemade boron-doped Ni-rich Ni(3)Al, a so-called ladder diagram was constructed from the evaporation data of a <001> pole. This ladder diagram revealed a very high degree of ordering in the alternating pure Ni and mixed Ni/Al planes: only 0.4% of the detected Al atoms were located on pure Ni planes. The number of null pulses to start a new plane was found to be much higher for Ni/Al planes (5 x 10(2)) than for Ni planes (1 x 10(2)). Moreover, the ladder diagram showed that boron was uniformly distributed through the matrix with nearly all boron found on pure Ni-planes. The suggestion that boron preferentially settles on these planes would be supported by reports of a strong Ni-B bond, since on Ni planes, B atoms can be accommodated on octahedral interstitial sites surrounded by only Ni atoms. Finally, we performed time-of-flight measurements on Co(3)W. The ion species observed in these measurements included a wide variety of WN(n)(2+) ions, with 0</=n</=9. Especially, the ions with odd n prevailed in this ion group.


Practical management of functional abdominal pain in children.
Functional abdominal pain (FAP) is common in childhood, but is not often caused by disease. It is often the impact of the pain rather than the pain itself that results in referral to the clinician. In this review, we will summarise the currently available evidence and discuss the functional dimensions of the presentation, within the framework of commonly expressed parental questions. Using the Rome III criteria, we discuss how to classify the functional symptoms, investigate appropriately, provide reassurance regarding parental worries of chronic disease. We outline how to explain the functional symptoms to parents and an individualised strategy to help restore function.


Comparative aspects of oxidative metabolism of neutrophils from human blood and guinea pig peritonea: magnitude of the respiratory burst, dependence upon stimulating agents, and localization of the oxidases.
We have compared the subcellular sites of H2O2 and presumably also superoxide-(O2-) production, and certain aspects of metabolic responses (O2 consumption, O2- production) of stimulated neutrophils from human blood and those elicited into guinea pig peritonea. Stimulation was accomplished with either opsonized zymosan or phorbol-12-myristate-13-acetate (PMA). Striking quantitative differences were observed between these cell types with regard to the increased respiration and O2- production observed during stimulation. These differences were most apparent when opsonized zymosan served as the stimulating agent. They were minimized when the soluble stimulating agent, PMA, was used. With either stimulus, the subcellular sites of H2O2 production were the same for both types of neutrophils, i.e., the plasmalemma and phagosomal membranes. No H2O2 production could be detected cytochemically in the absence of stimulation. Treatment of both unstimulated human blood and elicited guinea pig peritoneal neutrophils with the nonpenetrating, covalently linking reagent, p-diazobenzenesulfonic acid, failed to diminish O2- production upon subsequent stimulation, in contrast to a previous report. These data are discussed in terms of the possible cytological arrangements of the respiratory enzyme(s), and the different modes of stimulation of neutrophil metabolism by various agents. Ancillary data on elicited mouse peritoneal neutrophils are presented.


On risking risk assessment of delinquent juveniles: some questions concerning the role of psychopathy.
In recent years much research effort has been directed at assessing psychopathic personality disorder in juveniles and at devising structured assessment procedures for recidivism risk. Clinicians, however, are often reluctant to incorporate this recent research into their practice. While accepting the importance of a better understanding of the development of psychopathic personality disorder, we discuss three arguments against the uncritical application of current research findings concerning the disorder and its clinical value as a risk factor. We briefly review empirical evidence for the role of the disorder in risk assessment. A developmental psychopathology argument against current thinking about juvenile psychopathic personality disorder, and a criminological argument against risk assessment but in favor of a desistance approach to delinquency are discussed.


The interactive effects of perceived peer drinking and personality profiles on adolescent drinking: a prospective cohort study.
(1) To classify Australian adolescents according to their alcohol consumption trajectories; and (2) to assess the direct and interactive effects of perceived peer drinking (PPD) and personality on adolescent drinking. Prospective cohort study comprising secondary analysis of six waves of prospective data (collected between 2014 and 2016) from the control arm of the Climate Schools Combined Study. Nineteen schools across three Australian states. A total of 1492 socio-demographically diverse students (mean age at baseline: 13.47; 68% female; 82% born in Australia). Alcohol consumption trajectories were assessed using self-reported sipping of alcohol, full standard drink consumption, binge drinking and quantity and frequency of alcohol consumption. One item assessed PPD and personality was assessed using the Substance Use Risk Profile Scale. Eight hundred and sixty-four (58%) adolescents consumed alcohol across the study period. Four drinking trajectories were identified: abstaining (n = 513; reference group); onset (n = 361; initiated after baseline); persistent (n = 531; initiated prior to baseline); and decreasing (n = 50; consumed alcohol at baseline but ceased or decreased thereafter). A significant PPD × anxiety sensitivity (AS) interaction affected probability of belonging to the onset (P < 0.001) and persistent (P = 0.003) trajectories. The effect of PPD on probability of belonging to the onset trajectory was only significant when adolescents reported low [95% confidence interval (CI) = 1.464-2.646, P < 0.001], but not high AS. The effect of PPD on probability of belonging to the persistent drinking trajectory was stronger at low (95% CI = 2.144-3.283, P < 0.001), compared with high (95% CI = 1.440-2.308, P < 0.001) AS. In Australian adolescents, self-reported drinking onset and persistent drinking appear to be more strongly associated with perceived peer drinking in those with low anxiety sensitivity than those with high anxiety sensitivity.


Expectation and futurity: The remarkable success of genetic determinism.
Genetic determinism is nowadays largely questioned and widely criticized. However, if we look at the history of biology in the last one hundred years, we realize that genetic determinism has always been controversial. Why, then, did it acquire such relevance in the past despite facing longstanding criticism? Through the analysis of some of the ambitious expectations of future scientific applications, this article explores the possibility that part of the historical success of genetic determinism lies in the powerful rhetorical strategies that have connected the germinal matter with alluring bio-technological visions. Indeed, in drawing on the recent perspectives of "expectation studies" in science and technology, it will be shown that there has been an interesting historical relationship between reductionist notions of the gene as a hereditary unit, coded information or functional DNA segment, and startling prophecies of what controlling such an entity might achieve. It will also be suggested that the well-known promissory nature of genomics is far older than the emergence of biotechnology in the 1970s. At least from the time of the bio-utopias predicted by J.B.S. Haldane and J. S. Huxley, the gene has often been surrounded by what I call the "rhetoric of futurity": a promissory rhetoric that, despite momentous changes in the life sciences throughout the 20th century, has remained relatively consistent over time.


Is it time for personalized cardiac resynchronization therapy.


[An efficient method for screening effective siRNAs using dual-luciferase reporter assay system].
To establish an efficient method for screening effective small interference RNA (siRNA) using dual-luciferase reporter assay system. Based on the siRNA expression vector pSilencer-4.1, 3 candidate green fluorescence protein (GFP) gene siRNA expression plasmids, namely pSi-GFPsiRNA1, pSi-GFPsiRNA2, and pSi-GFPsiRNA3, along with the negative control pSi-Negative, were constructed. Using the pGL3-promoter vector, the GFP-luciferase (GFP-LUC) expression plasmid pGL3-GFPf was constructed with the same Kozak consensus translation initiation site and start codon ATG for GFP-LUC coding sequence. The GFP fragment containing the target sequences of 3 GFP siRNAs was introduced into the 3' untranslate region of LUC in the modified pGL3-promoter vector to construct the plasmid pGL3-GFPp. The GFP siRNAs expression plasmids and Renilla luciferase reporter vector pRL-TK were co-transfected with pGL3-GFPf or pGL3-GFPp into the HEK293 cells, respectively. The luciferase activities were determined by dual-luciferase reporter assay, and the GFP mRNA expressions were detected by real-time quantitative PCR. In the groups cotransfected with GFP siRNAs expression plasmids and pGL3-GFPf, the luciferase activities were reduced obviously, and the reduction was more significant in cells transfected with GFPsiRNA1 compared with the control cells (P<0.01).GFP mRNA levels were also markedly lowered in cells transfected with GFPsiRNA1 as shown by real-time PCR (P<0.01). In addition, the results of dual-luciferase reporter assay and real-time PCR showed that among the groups cotransfected with GFP siRNAs expression plasmids and pGL3-GFPp, the GFP expression was inhibited most obviously by GFPsiRNA1 (P<0.01). The dual-luciferase reporter assay system provides a useful method for screening effective siRNAs targeting specific genes.


Sentinel lymph node biopsy in patients with thin melanoma: occurrence of nodal metastases and its prognostic value.
We identified the proportion of positive sentinel lymph node biopsies (SNBs) in patients treated for thin melanoma (Breslow thickness <or= 1.0 mm). Breslow thickness is compared to the American Joint Committee of Cancer (AJCC) stage as a predictor for sentinel node involvement, and the prognostic value of the SNB in thin melanoma is analysed.Our prospective database of 248 patients, treated for melanoma between January 1994 and August 2007, was reviewed and completed. In 78 patients, SNB was performed for a thin melanoma. Overall, 23.8% of the SNBs were positive; in thin melanoma 6.4% were positive. All those nodal metastases were found in the group with a Breslow thickness of 0.76-1.0 mm, resulting in 12.8% of positive SNBs in this subgroup (X(2) p = 0.02). In AJCC stage 1a, 4.3% had a positive SNB, in AJCC stage 1b the SNB positive proportion was 9.4% (X(2) p = 0.38). Disease free survival in the node positive group was 100%. Breslow thickness only appears to be a practical tool in predicting lymph node involvement. SNB can be omitted in melanoma patients with a Breslow thickness <or= 0.75 mm. The prognostic value of SNB might be different in thin melanoma patients. Further research is warranted to asses the value of SNB in this subgroup of patients.


The Humanities in Medical Education: Ways of Knowing, Doing and Being.
The personhood of the physician is a crucial element in accomplishing the goals of medicine. We review claims made on behalf of the humanities in guiding professional identity formation. We explore the dichotomy that has evolved, since the Renaissance, between the humanities and the natural sciences. The result of this evolution is an historic misconstrual, preoccupying educators and diverting them from the moral development of physicians. We propose a curricular framework based on the recovery of Aristotelian concepts that bridge identity and activity. The humanities and the natural sciences, jointly and severally, can fulfill developmental, characterological and instrumental purposes.


In vivo biotinylated proteins as targets for phage-display selection experiments.
Screening phage-displayed combinatorial libraries represents an attractive method for identifying affinity reagents to target proteins. Two critical components of a successful selection experiment are having a pure target protein and its immobilization in a native conformation. To achieve both of these requirements in a single step, we have devised cytoplasmic expression vectors for expression of proteins that are tagged at the amino- or carboxy-terminus (pMCSG16 and 15) via the AviTag, which is biotinylated in vivo with concurrent expression of the BirA biotin ligase. To facilitate implementation in high-throughput applications, the engineered vectors, pMCSG15 and pMCSG16, also contain a ligase-independent cloning site (LIC), which permits up to 100% cloning efficiency. The expressed protein can be purified from bacterial cell lysates with immobilized metal affinity chromatography or streptavidin-coated magnetic beads, and the beads used directly to select phage from combinatorial libraries. From selections using the N-terminally biotinylated version of one target protein, a peptide ligand (Kd= 9 microM) was recovered that bound in a format-dependent manner. To demonstrate the utility of pMCSG16, a set of 192 open reading frames were cloned, and protein was expressed and immobilized for use in high-throughput selections of phage-display libraries.


Intra-cavity cryogenic optical refrigeration using high power vertical external-cavity surface-emitting lasers (VECSELs).
A 7% Yb:YLF crystal is laser cooled to 131 ± 1 K from room temperature by placing it inside the external cavity of a high power InGaAs/GaAs VECSEL operating at 1020 nm with 0.15 nm linewidth. This is the lowest temperature achieved in the intracavity geometry to date and presents major progress towards realizing an all-solid-state compact optical cryocooler.


An rpoB signature sequence provides unique resolution for the molecular typing of cyanobacteria.
The use of morphological characters for the classification of cyanobacteria has often led to ambiguous strain assignment. In the past two decades, the availability of sequences, such as those of the 16S rRNA, nif, cpc and rpoC1 genes, and the use of metagenomics, has steadily increased and has made the reconstruction of evolutionary relationships of some cyanobacterial groups possible in addition to improving strain assignment. Conserved indels (insertions/deletions) are present in all cyanobacterial RpoB (β subunit of RNA polymerase) sequences presently available in public databases. These indels are located in the Rpb2_6 domain of RpoB, which is involved in DNA binding and DNA-directed RNA polymerase activity. They are variable in length (6-44 aa) and sequence, and form part of what appears to be a longer signature sequence (43-81 aa). Indeed, a number of these sequences turn out to be distinctive among several strains of a given genus and even among strains of a given species. These signature sequences can thus be used to identify cyanobacteria at a subgenus level and can be useful molecular markers to establish the taxonomic positions of cyanobacterial isolates in laboratory cultures, and/or to assess cyanobacterial biodiversity in space and time in natural ecosystems.


Case report: granulocytic sarcoma (chloroma) presenting as a cerebellopontine angle mass.
Granulocytic sarcomas (chloromas) are rare, solid extramedullary tumours composed of granulocyte precursors occurring in association with granulocytic leukaemia. A cerebellopontine angle granulocytic sarcoma in a 4-year-old child presenting with unilateral facial palsy is reported. The computed tomographic (CT) findings are described, with a review of the literature, and the significance of early diagnosis is discussed.


Fetal loss in BALB/C mice infected with Neospora caninum.
The suitability of mice as a model for reproductive loss due to Neospora caninum infection was investigated. Groups of mice were infected with 2 x 10(6) N. caninum before pregnancy (10 days) and during pregnancy (days 5 and 10 of gestation). In mice infected before and during early pregnancy, fetal loss was evaluated throughout gestation, and pregnancy loss was evaluated by enumeration of fetal resorptions and total fetuses. In mice infected before pregnancy, no difference was present in resorptions between infected and control mice, although litter size was decreased in the infected mice (P < 0.05). In mice infected during early pregnancy (day 5 gestation) and examined temporally throughout gestation, resorptions were increased in the infected mice compared to the control mice (P < 0.05). In mice infected at 5 days gestation and examined at one time point (day 14 of gestation), the resorption rate for infected mice was 33% and 12% for controls (P < 0.05). Routine histopathologic examination and immunohistochemistry using N. caninum-specific antisera did not identify tachyzoites in placental and fetal tissues during the pre- and early pregnancy infections. In mice infected late midgestation (day 10), N. caninum tachyzoites were identified in placenta and fetal muscle and neural tissue. In the placenta, there was multifocal necrosis and hemorrhage with intralesional tachyzoites. Tachyzoites in fetal tissues were not associated with pathologic changes. No reproductive loss was associated with mice infected late in gestation. These data demonstrate that mice can be used as a model for the study of fetal resorption and congenital infection associated with N. caninum.


Kinetic properties of arachidonoyl-coenzyme A synthetase in rat brain microsomes.
Free arachidonic acid is released rapidly in the brain at the onset of ischemia and during convulsions. The transient nature of this phenomenon indicates the existence of an active reacylation system for this fatty acid, likely an arachidonoyl-CoA synthetase-arachidonoyl transferase. The first of these enzymatic activities in brain microsomes was studied and it was found that [1-14C]arachidonic acid is rapidly activated and shows an absolute requirement for ATP and CoA. MgCl2 enhances this activity 10-fold. The optimum pH is 8.5, and the apparent Km values for the radiolabeled substrate, ATP, CoA, and MgCl2 are 36, 154, 8, and 182 microM, respectively. The apparent Vmax is 32.4 nmol/min/mg protein for arachidonic acid. The presence of Triton X-100 (0.1%) in the assay medium caused a significant reduction in apparent Km (9.4 microM) and Vmax (25.7 nmol/min/mg protein) values. The enzymatic activity is thermolabile with a T1/2 of less than 1 min at 45 degrees C and a maximal activity at 40 degrees C. The breaking point or transition temperature is 25 degrees C in an Arrhenius plot. The activation energies were 95 kJ/mol from 0 to 25 degrees C and 30 kJ/mol from 25 to 40 degrees C. Fatty acid competition studies showed inhibition by unlabeled docosahexaenoic and arachidonic acids with a Ki of 31 and 37 microM, respectively, in the absence and 18 and 7.7 microM in the presence of Triton X-100. Palmitic acid and oleic acid slightly inhibited the reaction whereas linoleic acid inhibited it to a moderate extent. It is concluded that this very active enzyme can activate arachidonic acid as well as docosahexaenoic acid in brain microsomes. In addition, this reaction may be involved in regulating the pool size of these free fatty acids in brain by rapid removal through activation, thus limiting eicosanoid formation. Moreover, the rapid formation of polyenoic acyl-coenzyme A may participate in the retention of essential fatty acids in the central nervous system.


Trends in the prevalence and distribution of teacher-identified special health-care needs across three successive population cohorts.
Some children's special health-care needs (SHCN) are formalised at the start of schooling (established SHCN), but a larger proportion start with difficulties that are milder or not yet diagnosed (emerging SHCN). This study explores whether: (i) the prevalence of teacher-identified SHCN (both overall and according to type of needs) and (ii) distribution across disadvantaged communities have changed over three successive population cohorts of Australian children. We draw on repeated cross-sectional data from the Australian Early Development Census, a teacher-reported checklist completed on full populations of Australian school entrants in 2009, 2012 and 2015. It includes a measure of SHCN, as well as demographic information. The proportion of children with emerging and established needs was mostly stable from 2009 to 2015 (emerging needs: 17.1-18.9%; established needs: 4.4-4.9%). Change over time was observed in the prevalence of some specific types of impairment. Speech impairment rose by 14.7% for children with emerging needs, and emotional problems rose by 13.7% for children with established needs. Children living in the most disadvantaged neighbourhoods had higher odds of SHCN in all years (e.g. emerging needs relative risk ratio 1.65 (99% confidence interval 1.55-1.75) in 2015; established needs relative risk ratio 1.88 (99% confidence interval 1.71-2.06) in 2015). A large proportion of children starting school each year have SHCN. The types of SHCN that children present with increasingly reflect complex difficulties that require input from both the health and education sectors. Effective responses also need to consider the added impact of disadvantage.


Characterization of phosphorus forms in lake macrophytes and algae by solution (31)P nuclear magnetic resonance spectroscopy.
Debris from aquatic macrophytes and algae are important recycling sources of phosphorus (P), which can result in continuing blooms of algae by recycling bioavailable P in the eutrophic lakes. However, knowledge of forms of P in aquatic macrophytes and algae and their contribution to internal loads of P in lakes is limited. Without such knowledge, it is difficult to develop appropriate strategies to remediate and or restore aquatic ecosystems that have become eutrophic. Therefore, in this work, P was extracted from six types of aquatic macrophytes and algae collected from Tai Lake of China and characterized by use of solution (31)P-nuclear magnetic resonance (NMR) spectroscopy. When extracted by 0.5 M NaOH-25 mM EDTA, extraction recovery of total P(TP) and organic P(Po) exceeded 90 %. Concentrations of Po in algae and aquatic macrophytes were 5552 mg kg(-1) and 1005 mg kg(-1) and accounted for 56.0 and 47.2 % of TP, respectively. When Po, including condensed P, was characterized by solution (31)P-NMR Po in algae included orthophosphate monoesters (79.8 %), pyrophosphate (18.2 %), and orthophosphate diester (2.0 %), and Po in aquatic macrophytes included orthophosphate monoesters (90.3 %), pyrophosphate (4.2 %), and orthophosphate diester (5.5 %). Additionally, orthophosphate monoesters in algal debris mainly included β-glycerophosphate (44.1 %), α-glycerophosphate (13.5 %), and glucose 6-phosphate (13.5 %). Orthophosphate monoesters in aquatic macrophytes mainly included β-glycerophosphate (27.9 %), α-glycerophosphate (24.6 %), and adenosine 5' monophosphate (8.2 %). Results derived from this study will be useful in better understanding nutrient cycling, relevant eutrophication processes, and pollution control for freshwater lakes.


Focus issue: plant communication.
This week's issues of Science and Science's STKE focus on plant signaling with an emphasis on volatile organic compounds. Science emphasizes the chemistry of and information encoded by plant volatiles and how plants, plant pathogens, or humans utilize this aromatic information. Articles and resources at STKE highlight the evolution of olfactory signal transduction, describe the biosynthetic and signaling pathways of the plant hormone jasmonate, and provide an animated overview of how the plant hormone auxin regulates gene expression.


Infection and inflammation and the coagulation system.
Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). Systemic inflammation results in activation of coagulation, due to tissue factor-mediated thrombin generation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Pro-inflammatory cytokines play a central role in the differential effects on the coagulation and fibrinolysis pathways. Vice-versa, activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms. Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The relevance of the cross-talk between inflammation and coagulation is underlined by the promising results in the treatment of severe systemic infection with modulators of coagulation and inflammation.


Reduction of intraspecific aggression in adult rats by neonatal treatment with a selective serotonin reuptake inhibitor.
Most studies suggest that serotonin exerts an inhibitory control on the aggression process. According to experimental evidence, this amine also influences growth and development of the nervous tissue including serotoninergic neurons. Thus, the possibility exists that increased serotonin availability in young animals facilitates a long-lasting effect on aggressive responses. The present study aimed to investigate the aggressive behavior of adult rats (90-120 days) treated from the 1st to the 19th postnatal day with citalopram (CIT), a selective serotonin reuptake inhibitor (20 mg/kg, s.c., every 3 days). Aggressive behavior was induced by placing a pair of rats (matched by weight) in a box (20 x 20 x 20 cm), and submitting them to a 20-min session of electric footshocks (five 1.6-mA - 2-s current pulses, separated by a 4-min intershock interval). When compared to the control group (rats treated for the same period with equivalent volumes of saline solution), the CIT group presented a 41.4% reduction in the duration of aggressive response. The results indicate that the repeated administration of CIT early in life reduces the aggressive behavior in adulthood and suggest that the increased brain serotoninergic activity could play a role in this effect.


Combined therapy with tiotropium and formoterol in chronic obstructive pulmonary disease: effect on the 6-minute walk test.
Combined therapy with tiotropium and long-acting beta 2 agonists confers additional improvement in symptoms, lung function and aspects of health-related quality of life (QOL) compared with each drug alone in patients with COPD. However, the efficacy of combined therapy on walking distance, a surrogate measure of daily functional activity and morbidity remains unclear. The aim was, therefore, to quantify the benefit of this therapy on the six minute walk test. Secondary outcomes included change in lung function, symptoms, the BODE index and QOL. In a double-blind, crossover study, 38 participants with moderate to severe COPD on tiotropium were randomised to receive either formoterol or placebo for 6 weeks. Following a 2-week washout period, participants crossed over to the alternate arm of therapy for a further 6 weeks. Thirty-six participants, with an average age of 64.3 years and FEV1 predicted of 53%, completed the study. Combined therapy improved walking distance by a mean of 36 metres [95% CI: 2.4, 70.1; p = 0.04] compared with tiotropium. FEV1 increased in both groups (160 mL combination therapy versus 30 mL tiotropium) with a mean difference of 110 mL (95% CI: -100, 320; p = 0.07) between groups, These findings further support the emerging advantages of combined therapy in COPD. Australian New Zealand Clinical Trials.


Quantitative assessment of the bone morphogenetic protein expression from alternate bone graft harvesting sites.
Bone morphogenetic proteins (BMPs) play important roles in the stimulation of osteogenesis and osteoinduction during bone fracture healing and their expression levels may be important for bone graft efficacy. The objective of this study was to determine if there are variations in the expression of BMPs and their receptors in various bone graft harvesting sites. We analyzed autogenous marrow aspirates obtained from three different graft sites for the mRNA levels of BMPs and their receptors. Using real-time polymerase chain reaction, we analyzed the mRNA levels of BMPs and their receptors in autogenous bone marrow aspirates obtained from three different bone graft sites of 10 different human subjects. Collection of autogenous bone marrow from the iliac crest, the proximal humerus, and the proximal tibia was performed using standard sterile techniques in the operating room as part of surgery to treat an established fracture nonunion. The mRNA levels of BMP-2 and BMP-5 were the highest in the bone marrow aspirates from the three different sites, whereas the mRNA levels of the other osteoinductive BMPs (BMP-4, -5, -6, -7, -8, and -9) were lower. The mRNA levels of BMP-3, an inhibitor of osteogenesis, were the lowest in the bone marrow aspirates of all three different sites. There were no statistical significant differences in the mRNA levels of any of the BMPs or their receptors investigated in this study in the bone marrow of the three different sites. Because no statistical significant differences in the mRNA levels of the BMPs and their receptors were detected in the bone marrow aspirates from the three different sites, our findings suggest that potential differences of various graft sites in the augmentation of bone healing does not result from different expression levels of BMPs.


Lectin-binding glycoproteins in the developing and adult snail CNS.
Glycoproteins are complex molecules of the cell surface and the extracellular matrix (ECM) playing a fundamental role in the migration, guidance and synapse formation of neurons. In the present study, the glycosylated protein composition and localization were investigated in the adult and developing CNS of an aquatic (Lymnaea stagnalis) and a terrestrial (Helix pomatia) snail species, applying lectin histochemistry and blotting. Lectin probes that are specific for N-acetyl-glucosamine (GlcNAc) oligomers frequently appeared in anatomically different regions of the adult ganglia of both species, such as, the periganglionic sheath, the interperikaryonal space and the neuropil. Different GlcNAc residues were found to intensively glycosylate five, high-molecular weight proteins characteristic for the ECM of Lymnaea CNS and localized mainly in the interperikaryonal space. N-acetyl-galactosamine oligomers were less pronounced in the adult snail ganglia, they were detected only in the periganglionic sheath and the attached basement lamina. Apart from some similarities, the glycosylation pattern of proteins and the distribution of glycoproteins in the neuropil displayed significant differences in Lymnaea and Helix. All continuous and increasing level of and also transient presence of glycoproteins were detected during Lymnaea CNS development. Our results indicate a rich glycosylated pattern of specific proteins in the snail CNS, displaying remarkable species- and age-dependent changes which suggest the wide importance of protein glycosylation in the CNS of invertebrates.


Optimization of k-space trajectories for compressed sensing by Bayesian experimental design.
The optimization of k-space sampling for nonlinear sparse MRI reconstruction is phrased as a Bayesian experimental design problem. Bayesian inference is approximated by a novel relaxation to standard signal processing primitives, resulting in an efficient optimization algorithm for Cartesian and spiral trajectories. On clinical resolution brain image data from a Siemens 3T scanner, automatically optimized trajectories lead to significantly improved images, compared to standard low-pass, equispaced, or variable density randomized designs. Insights into the nonlinear design optimization problem for MRI are given.


AAEM minimonograph #43: neuromuscular problems in the performing arts.
Over the past 10-15 years, there has been increasing interest in the health problems of performing artists. In this review, I will discuss the major playing-related disorders seen in instrumental musicians. Among the 672 instrumentalists evaluated, the major diagnoses identified included musculoskeletal disorders in 64%, peripheral nerve problems in 22.5%, and focal dystonia in 7%. Sixty percent of instrumentalists were female although males predominate in the group with focal dystonia. The average age of those evaluated was 32 years. Among musculoskeletal disorders overuse syndrome is the most common. Frequent peripheral nerve disorders include thoracic outlet syndrome, carpal tunnel syndrome, and ulnar neuropathy. A characteristic distribution of symptoms and signs is identified for each instrument group. Electrodiagnostic studies are an important part of the evaluation of these disorders. With carefully designed treatment, the majority of instrumental musicians can be returned to full and pain-free playing activities. The success rate is highest in some entrapment neuropathies but remains low in focal dystonia.


Examining young children's social competence using functional ability profiles.
To explore the use of International Classification of Functioning, Disability, and Health for Children and Youth (ICF-CY) based profiles of children's functional abilities in relation to their social competence. Subgroups based on shared profiles of functional ability were investigated as an alternative or complement to subgroups defined by disability categories. Secondary analysis of a nationally representative data set of young children identified for special education services in the United States was used for the present study. Using five subgroups of children with shared profiles of functional ability, derived from latent class analysis in previous work, regression analyses were used to examine the relationships between social competence and functional abilities profile subgroup membership. Differences among the subgroups were examined using standardized effect sizes. R2 values were used to examine explained variance in social competence in relation to subgroup membership, disability category, and these variables in combination. Functional ability profile subgroup membership was moderately related to children's social competence outcomes: social skills and problem behaviors. Effect sizes showed significant differences between subgroups. Subgroup membership accounted for more variance in social competence outcomes than disability category. The results provide empirical support for the importance of functional ability profiles when examining social competence within a population of young children with disabilities. Implications for Rehabilitation The extent to which children with disabilities experience difficulty with social competence varies by their functional characteristics. Functional ability profiles can provide practitioners and researchers working young children with disabilities important tools to examine social competence and to inform interventions.


Bipolar Electrode Array Embedded in a Polymer Light-Emitting Electrochemical Cell.
A linear array of aluminum discs is deposited between the driving electrodes of an extremely large planar polymer light-emitting electrochemical cell (PLEC). The planar PLEC is then operated at a constant bias voltage of 100 V. This promotes in situ electrochemical doping of the luminescent polymer from both the driving electrodes and the aluminum discs. These aluminum discs function as discrete bipolar electrodes (BPEs) that can drive redox reactions at their extremities. Time-lapse fluorescence imaging reveals that p- and n-doping that originated from neighboring BPEs can interact to form multiple light-emitting p-n junctions in series. This provides direct evidence of the working principle of bulk homojunction PLECs. The propagation of p-doping is faster from the BPEs than from the positive driving electrode due to electric field enhancement at the extremities of BPEs. The effect of field enhancement and the fact that the doping fronts only need to travel the distance between the neighboring BPEs to form a light-emitting junction greatly reduce the response time for electroluminescence in the region containing the BPE array. The near simultaneous formation of multiple light-emitting p-n junctions in series causes a measurable increase in cell current. This indicates that the region containing a BPE is much more conductive than the rest of the planar cell despite the latter's greater width. The p- and n-doping originating from the BPEs is initially highly confined. Significant expansion and divergence of doping occurred when the region containing the BPE array became more conductive. The shape and direction of expanded doping strongly suggest that the multiple light-emitting p-n junctions, formed between and connected by the array of metal BPEs, have functioned as a single rod-shaped BPE. This represents a new type of BPE that is formed in situ and as a combination of metal, doped polymers, and forward-biased p-n junctions connected in series.


A mixed alkanethiol based immunosensor for surface plasmon field-enhanced fluorescence spectroscopy in serum.
This paper describes a simple and sensitive immuno-based biosensor for interference-reduced detection of C-reactive protein (CRP) in serum. The detection was performed by using a non-competitive sandwich immunoassay in combination with surface plasmon field-enhanced fluorescence spectroscopy (SPFS). CRP is an important marker for the diagnosis of inflammatory processes and cardiovascular diseases (CVD). It is nowadays detected by high-sensitivity enzyme-linked immunosorbent assays (ELISA) in blood serum. CRP was used as a model analyte in this work because it is well-characterized. However, interfering effects of matrix components affect the limit of detection (LOD) and quantification (LOQ) in general. Therefore, the availability of fast, sensitive and robust analytical methods is of major interest. A number of biosensor approaches have been described already, but only a few have demonstrated their usefulness in authentic samples such as serum. Thus our aim was to develop a simple and sensitive immunoassay-based biosensor for an interference-reduced detection of CRP in serum with surface plasmon enhanced fluorescence spectroscopy (SPFS). LODs and LOQs were experimentally determined both for CRP spiked buffer and serum. SPFS in combination with our biosensor allows sensitive analysis of CRP, achieving in buffer a LOD of 0.016 μg mL(-1) and a LOQ of 0.049 μg mL(-1). In serum the accomplished LOD was 0.026 μg mL(-1) and the LOQ was found to be 0.08 μg mL(-1). These low LODs and LOQs demonstrate the applicability of the designed biosensor for qualitative and semi-quantitative analysis of trace amounts of substances in very small sample volumes of body fluids.


7-O-[4-methyl piperazine-1-(2-acetyl)]-2H-1-benzopyran-2-one: a novel antifilarial lead compound.
In preliminary studies we found that benzopyrones (coumarins), which are known to exert many biological activities including anti-inflammatory effect, possess promising macrofilaricidal action as well. In order to explore the possibility of combining such a macrofilaricidal activity with the microfilaricidal potential of the known piperazine pharmacophore, we synthesized a series of compounds and evaluated their antifilarial effect. In the present study, one of these compounds, 7-O-[4-methyl piperazine-1-(2-acetyl)]-2H-1-benzopyran-2-one (2), which has shown promising macrofilaricidal action against rodent filariid Litomosoides carinii in cotton rats, was evaluated against infection with Brugia malayi in Mastomys coucha and jird (Meriones unguiculatus). In the B. malayi-M. coucha system, the compound at a dose of 300 mg/kg, oral (p.o.) x5 days showed 53.6% adulticidal and 46.0% microfilaricidal activity along with 46.3% sterilization effect on the female worms. In addition, the compound interfered with the establishment of infective larvae (L(3))-induced infection to an extent of 50% at the same dose level. At 1 microM concentration it inhibited protease activity of B. malayi to 82%. The compound thus provides a novel lead for further synthesis and development of antifilarial agents with macrofilaricidal, microfilaricidal, female-sterilizing and possible larvicidal efficacy.


Expression of thyroid-specific transcription factors in thyroid carcinoma, contralateral thyroid lobe and healthy thyroid gland in dogs.
Thyrotropin receptor (TSH-R), thyroglobulin (Tg), thyroperoxidase (TPO), thyroid specific transcription factor-1 (TTF-1), paired box 8 transcription factor (PAX-8), insulin like growth factor-1 (IGF-1) and estrogen receptor alpha (ERα) transcripts were determined by real-time PCR in follicular carcinoma and contralateral (CL) lobes, and healthy thyroid canine glands. Concentrations of TSH-R, PAX-8, and ERα mRNA were not different among groups; the carcinoma group had lower Tg and TPO mRNA than healthy and CL groups, while no differences were found between the two latter groups, suggesting that the carcinoma tissue presents an altered capacity to synthesize thyroid hormones. The transcription factor that promotes thyrocytes proliferation, TTF-1 as well as IGF-1, presented a greater mRNA expression in the CL group, suggesting that the CL lobe may function in a compensatory state.


Key elements for the education and counselling of patients treated with oral anticancer drugs.
The process of education and counselling of patients treated with oral anticancer drugs, aimed to achieve adequate self-management, involves different stakeholders (i.e. physicians, oncology nurses, pharmacists) from primary and secondary care. However, currently no guiding principles exist on how to organize and perform education and counselling for these patients. Therefore, the purpose of this study was to develop and build consensus on key elements for the education and counselling in patients on oral anticancer drugs. A multi-method approach combining a literature search, semi-structured interviews with patients and healthcare professionals, and input from experts were used to develop an initial list of key elements. Subsequently, consensus was built in a two-round Delphi-study, involving patients and healthcare professionals from primary and secondary care. Key elements were retained if at least 80% of respondents in all groups considered the element as important or if in at least one group 90% consensus was reached. The initial list contained 110 key elements, divided in 7 themes: coordination of care, patient contacts: style and content, medication counselling at the start of the treatment and during follow-up, psychosocial support, and involvement of family and friends. After the first Delphi round, 80% consensus was reached for 23 elements; 6 new key elements were added. After the second round, 80% consensus was reached for 51 out of 116 elements; 31 elements were added following the 90%-rule, yielding a list of 82 elements. The final list of 82 key elements, obtained in this study, could be used to develop clinical pathways that guide adequate education and counselling of patients on oral anticancer drugs. Due to the open description, the implementation of these elements can be adapted to the specific context and composition of the oncology team.


VISUAL FUNCTION CORRELATES OF FOVEAL SLOPE CHANGES ON OPTICAL COHERENCE TOMOGRAPHY IN MACULAR TELANGIECTASIA TYPE 2.
To evaluate changes in foveal and parafoveal thickness measured using optical coherence tomography across five stages of macular telangiectasia 2 (MacTel 2) and to correlate the foveal slope angle with best-corrected visual acuity (BCVA). A multicentered, cross-sectional study of 90 patients with bilateral MacTel 2 was carried out. We reviewed medical records of patients who had undergone optical coherence tomography. Mean retinal thickness foveal and subfoveal were noted from ETDRS (Early Treatment Diabetic Retinopathy Study) mapping and later used for calculating foveal slope angle. The change in retinal thickness and foveal angle across five stages of MacTel 2 was assessed. Central foveal thickness and foveal slope angle were correlated with BCVA. The foveal slope angles were calculated quadrantwise and stagewise. The mean slope angle was minimum in temporal quadrant (6.29°) followed by inferior (7.13°), superior (7.54°), and nasal (7.93°). The slope angles were 9.27°, 7.95°, 6.70°, 6.10°, and 6.31° in Stages 1, 2, 3, 4, and 5, respectively. Statistically significant correlation noted between the temporal, superior, inferior slope angles and BCVA (in logarithm of the minimum angle of resolution) with r = -0.18, -0.19, and -0.25, respectively (P < 0.05). No statistically significant correlation was noted between central retinal thickness and BCVA. The BCVA correlates better with slope angles than central retinal thickness. This implies that, change in both foveal and parafoveal regions accounts for vision change. Greater the foveal slope angle, the better the vision.


Dysgenetic hypoplastic kidney simulating metastatic lung carcinoma.
We describe a 57-year-old male with prior history of an absent right kidney and kidney transplant who was found to have lung cancer. Integrated positron emission tomography (PET) and computerized tomography (CT) scan was done for staging and showed uptake in the right upper lung primary and right renal fossae region which was suggestive of metastatic disease. An excisional biopsy of the right renal fossae mass showed that it was a hypoplastic kidney simulating a metastatic focus on PET scan. The patient eventually underwent a left upper lobectomy with a final pathological stage of T2N0M0. Positive PET scan areas should be biopsied to confirm the presence of metastatic disease before excluding patients from surgical treatment.