Effect of genetic polymorphisms on smoking cessation: a trial of bupropion in Korean male smokers.
Even though bupropion is first-line pharmacological agent for smoking cessation, not all the smokers successfully quit smoking by bupropion. It means other factors like genetic predisposition could contribute to the therapeutic outcome. The aim of this study is to elucidate the question of whether the abstinence rates by bupropion trial would be different depending on the genotypes. Six candidate genes, thought to be involved in the interaction of nicotine and bupropion (for example, the dopamine receptor type 2, dopamine transporter, norepinephrine transporter, serotonin transporter, catecholamine-O-methyltransferase), and the clinical outcomes of smoking behavior were investigated. The participants were 225 male smokers to whom 150 mg of bupropion SR was administered for 4 weeks. The abstinence rates of specific genotypes were also compared. The results are as follows: (a) the frequencies of the A1/A2 genotype of the dopamine receptor type 2 TaqI A gene and SLC6A3-9 genotype of the dopamine transporter 1 gene were higher in the nonabstinence group than in the abstinence group (chi2=20.40, P<0.01 for A1/A2, chi2=7.76, P=0.01 for SLC6A3-9). The frequencies of the COMTH/COMTH and A/G genotypes of the norepinephrine transporter gene were higher in the abstinence group than in the nonabstinence group (chi2=8.12,P=0.02 for COMTH/COMTH, chi2=3.04, P<0.01 for A/G). (b) Participants having specific genotypes such as homozygotes (A1/A1 or A2/A2) of DRD2 TaqI A, COMTH/COMTH, AG of NET-8, and LL of 5-HTTLPR showed a higher abstinence rate than the other participants. It can be concluded that genetic diversity might determine the effects of bupropion on smoking cessation.


Firing rate propagation through neuronal-astrocytic network.
Understanding the underlying mechanism of the propagation of neuronal activities within the brain is a fundamental issue in neuroscience. Traditionally, communication and information processing have been exclusively considered as the province of synaptic coupling between neurons. Astrocytes, however, have recently been acknowledged as active partners in neuronal information processing. So, it is more reasonable and accurate to study the nature of neuronal signal propagation with the participation of astrocytes. In this paper, we first propose a feedforward neuronal-astrocytic network (FNAsN), which includes the mutual neuron-astrocyte interaction. Besides, we also consider the unreliability of both the synaptic transmission between neurons and the coupling between neurons and astrocytes. Then, the performance of firing rate propagation through the proposed FNAsN is studied through a series of simulations. Results show that the astrocytes can mediate neuronal activities, and consequently improve the performance of firing rate propagation, especially in a weak and noisy environment. From this point of view, astrocytes can be regarded as a realistic internal source of noise, which collaborates with an externally applied weak noise to prevent synchronous neuron firing within the same layer and thus to ensure reliable transmission.


Contribution of fungal loline alkaloids to protection from aphids in a grass-endophyte mutualism.
Fungal endophytes provide grasses with enhanced protection from herbivory, drought, and pathogens. The loline alkaloids (saturated 1-aminopyrrolizidines with an oxygen bridge) are fungal metabolites often present in grasses with fungal endophytes of the genera Epichloë or Neotyphodium. We conducted a Mendelian genetic analysis to test for activity of lolines produced in plants against aphids feeding on those plants. Though most loline-producing endophytes are asexual, we found that a recently described sexual endophyte, Epichloë festucae, had heritable variation for loline alkaloid expression (Lol+) or nonexpression (Lol-). By analyzing segregation of these phenotypes and of linked DNA polymorphisms in crosses, we identified a single genetic locus controlling loline alkaloid expression in those E. festucae parents. We then tested segregating Lol+ and Lol- full-sibling fungal progeny for their ability to protect host plants from two aphid species, and observed that alkaloid expression cosegregated with activity against these insects. The in planta loline alkaloid levels correlated with levels of anti-aphid activity. These results suggested a key role of the loline alkaloids in protection of host plants from certain aphids, and represent, to our knowledge, the first Mendelian analysis demonstrating how a fungal factor contributes protection to plant-fungus mutualism.


Ribozyme-targeting reveals the rate-limiting role of pleiotrophin in glioblastoma.
Glioblastomas (GBMs) are the most frequent malignant brain tumors with very limited treatment options and nearly all GBM patients dying within 1 year. Pleiotrophin (PTN, HB-GAM, HBNF, OSF-1) is a secreted growth factor that shows mitogenic, chemotactic and transforming activity. While PTN expression is tightly regulated during embryogenesis and very limited in normal adult tissues, a marked PTN upregulation is seen in tumors including glioblastomas. Targeting of the PTN receptors, ALK and RPTP-zeta, indicates a contribution of PTN-activated signaling pathways in glioblastomas. However, the relevance of PTN expression itself is unknown especially since, besides PTN, at least one more growth factor, midkine (MK), signals through ALK and is expressed in glioblastoma. Here we demonstrate the biologic relevance of PTN in 2 glioblastoma cell lines in vitro and in vivo. We show that stable ribozyme-targeting leads to a robust reduction of PTN mRNA and protein levels. This results in decreased cell proliferation, cell migration and soft agar colony formation in vitro. Comparing clonal ribozyme-transfected cells with different residual PTN levels, we establish a PTN gene-dose effect of glioblastoma cell proliferation. In a subcutaneous tumor xenograft mouse model, in vivo growth is markedly reduced upon PTN depletion, which is paralleled by decreased PTN serum levels. Furthermore, the immunohistochemical analysis of the tumors shows reduced angiogenesis in PTN-depleted tumors. We conclude that PTN is a rate-limiting growth factor in glioblastoma. Since PTN is overexpressed in glioblastomas but rarely found in normal tissue, PTN may represent an attractive therapeutic target.


Assay of serum inorganic phosphate without deproteinisation: automated and manual micromethods.
Several current techniques for the determination of serum inorganic phosphate in the presence of proteins are shown to have important disadvantages. An improved manual micromethod is described in which proteins are kept in solution by the use of sodium lauryl sulphate and the phosphate determined by the molybdenum blue reaction. The procedure has been adapted for the Technicon AutoAnalyzer and the Vickers D-300 and M-300, and has been shown to give very good precision in routine use.


Optical nonlinearities in As2Se3 chalcogenide glasses doped with Cu and Ag for pulse durations on the order of nanoseconds.
We investigate the dependence of the nonlinear optical properties of Cu-doped and Ag-doped As(2)Se(3) glasses on the incident pulse-width at 1.064 microm using the Z-scan technique. In this work, 11.5-ns optical pulses from a Nd:YAG laser were compressed up to 1.6 ns by using stimulated Brillouin scattering in heavy fluorocarbon liquid. The measurement of the pulse-width dependence of the optical nonlinearities leads to the separation of an ultrafast Kerr nonlinearity and a slow (cumulative) nonlinearity such as a thermal nonlinearity. The measured values of the nonlinear refractive index and the nonlinear absorption coefficient of 4 at.% Cu-doped As(2)Se(3) glass (where the normal photodarkening effect is sufficiently suppressed) and 4 at.% Ag-doped As(2)Se(3) glass were proportional to the pulse width, showing that the cumulative nonlinearity is present in these two glasses. The cumulative nonlinearity of these doped glasses is larger than one of the undoped glass. The origin of such slow nonlinearity is presumably attributed to the photostructural changes inherent in chalcogenide glasses and is directly independent of one of photodarkening.


[Complications and correction of augmentation-plasty with cadaver adipose tissue implantation].
The most common complications after augmentation mammoplasty with homologous fat implants could be demonstrated in one patient. We show our subsequent surgical procedure and the experiences of other authors to achieve an immediately acceptable cosmetic result.


Circadian motor activity affected by stimulant medication in children with attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder occurring in approximately 3-5% of school-aged children. The core symptoms of ADHD are effectively treated with stimulant medications such as methylphenidate; however, there are also negative side effects, including insomnia. It has been suggested that administration of stimulant medication may alter the timing or regularity of circadian motor activity levels. This study aimed to investigate the impact of stimulant medication on the strength and timing of circadian rhythms in 16 stimulant medication-naïve children with ADHD. Participants were monitored for changes in motor activity during a 3-week blinded placebo-controlled medication trial to examine the impact of immediate-release methylphenidate hydrochloride. Motor activity was measured by actigraphy, and 24-h activity profiles were analysed using cosinor analyses to identify measurable changes in circadian rhythms. The children in this sample demonstrated significant increases in motor activity during the sleep-onset latency period. They also showed a significant reduction in relative circadian amplitude and a phase-delay in the timing of the daily rhythm. Clinicians and parents of children being treated with stimulant medication for ADHD should be aware that stimulant medication may cause disruption of sleep/circadian rhythms. Behavioural strategies to improve sleep may be useful for children experiencing these negative effects from medication.


Nanoparticle-driven orientation transition and soft-shear alignment in diblock copolymer films via dynamic thermal gradient field.
Sharp dynamic thermal gradient (∇T ≈ 45 °C mm(-1)) field-driven assembly of cylinder-forming block copolymer (c-BCP) films filled with PS-coated gold nanoparticles (AuNPs; dNP ≈ 3.6 nm, φNP ≈ 0-0.1) is studied. The influence of increasing AuNP loading fraction on dispersion and assembly of AuNPs within c-BCP (PS-PMMA) films is investigated via both static and dynamic thermal gradient fields. With φNP increasing, a sharp transition from vertical to random in-plane horizontal cylinder orientation is observed due to enrichment of AuNPs at the substrate side and favorable interaction of PMMA chains with gold cores. Furthermore, a detachable capping elastomer layer can self-align these random oriented PMMA microdomains into unidirectional hybrid AuNP/c-BCP nanolines, quantified with an alignment order parameter, S.


Ironic capture: top-down expectations exacerbate distraction in visual search.
Ironic processing refers to the phenomenon where attempting to resist doing something results in a person doing that very thing. Here, we report three experiments investigating the role of ironic processing in visual search. In Experiment 1, we informed observers that they could predict the location of a salient color singleton in a visual search task and found that response times were slower in that condition than in a condition where the singleton's location was random. Experiment 2 used the same experimental design but did not inform participants of the color singleton's behavior. Experiment 3 showed that the cost in the predictable condition was not due to dual task costs or block order effects and participants attempting to use the strategy showed a larger cost in the predictable condition than those who abandoned using that location foreknowledge. In this case, responses in the predictable color singleton condition were equivalent with the random color singleton condition. This suggests that having more knowledge about an upcoming, salient distractor ironically increases its interfering influence on performance.


Effects of the progesterone antagonist RU486 on myometrial activity in vivo in early pregnant and pseudopregnant rats.
Myometrial activity in vivo was quantified by video-laparoscopy in early pregnant rats given doses of RU486 which caused embryo abortion and blocked the action of progesterone on the vagina. All treatments diminished the frequency of circular contractions and abolished the curling movements of the uterus which are characteristic of pregnant, pseudopregnant and progestin-treated rats. The effects of RU486 on circular contractions were similar in pseudopregnant rats, i.e. they were not a consequence of embryo abortion. These results support the thesis that increased myometrial circular contractions in early pregnancy and pseudopregnancy are induced by increasing levels of progesterone. Effects of RU486 on longitudinal contractions were more complex: the highest dose inhibited longitudinal contractions on Day 5 of pregnancy and pseudopregnancy, but increased their frequency on Day 6. The acute inhibition of longitudinal contractions by RU486 was unexpected and the mechanism remains to be elucidated. The later increase in the frequency of longitudinal contractions appears to be due to antagonism of progesterone by RU486. The frequency of caudal longitudinal contractions on Day 6 in mated rats given RU486 was similar to that in unmated oestrous rats, but the frequency of cranial longitudinal contractions was significantly higher. These results support the hypothesis that stimuli received during copulation may have long-term effects on myometrial activity, by increasing pacemaker activity at the cervix.


Computational simulation study on the anion recognition properties of functionalized tetraphenyl porphyrins.
The anion recognitions of tetra-(2-formamido) phenyl porphyrin (APP), tetra-(2-ureido) phenyl porphyrin (UPP), and their zinc derivatives (ZnAPP and ZnUPP) to three anions (Cl(-), H2PO4 (-), CH3COO(-)) were studied using quantum mechanical calculations (QM) and molecular dynamics (MD) simulations. The density functional theory (DFT) calculations at M06-2X/6-31G (d, p) level indicated that the anion recognition ability of ZnAPP was better than that of APP, and the anion selectivity was in the order Cl(-) < H2PO4 (-) < CH3COO(-). The selectivity trends for ZnUPP and UPP were found to be H2PO4 (-) < Cl(-) < CH3COO(-). The structures, thermodynamic properties, and recognition mechanisms were discussed in detail. The 2 ns MD simulations were then carried out for anion@ZnAPP and anion@ZnUPP complexes in mixed solvent DMSO/water. The MD simulation results showed that anion@ZnUPP complexes exhibited higher stability than anion@ZnAPP, which was in good agreement with QM results. H-bonds formed between the anions and the side-chains of receptors, and zinc coordination bonds with anions contributed significantly to the stability of complexes. The anion selectivity of ZnAPP and ZnUPP in the solvent phase were also discussed and compared with those in the gas phase.


[The heritage of anaphylaxis].
This text resumes the steps in Immunology that have followed the discovery of anaphylaxis in 1902 by P. Portier and C. Richet. Anaphylaxis was difficult to explain at the beginning of the 20th century where "phylactic" thinking predominated in Immunology. About one hundred years of research were necessary to identify the serum factor, IgE, the cellular actors with their IgE receptors as well as their activation mechanisms and to obtain an atomic view of the interaction between IgE and its receptor. Its also after one century that arrives the first treatment derived from biotechnological research that aims allergies which is the most commonly known expression of an anaphylactic reaction.


Quantitative immunocytochemical studies of endogenous albumin in rat aortic endothelial and mesothelial cells.
Endogenous albumin was revealed over cellular structures of rat ascendent aorta endothelia and mesothelium, with high resolution and specificity, by applying the protein A-gold immunocytochemical approach. This approach allows albumin distribution to be studied under steady-state conditions. The cellular layers evaluated were the aortic endothelium, the capillary endothelium (vasa vasorum), and the mesothelium externally lining the aorta at this level. Gold particles, revealing albumin antigenic sites, were preferentially located over plasmalemmal vesicles and intercellular clefts of endothelial and mesothelial cells, though with different labeling intensities. The interstitial space was also labeled. Morphometrical evaluation of plasmalemmal vesicles demonstrated a higher surface density for these structures in capillary endothelial cells (12%) compared with those in aortic endothelial (5%) and mesothelial cells (2%). Quantitation of gold labeling intensities over these structures revealed a higher labeling over plasmalemmal vesicles of capillary endothelium than over those of aortic endothelium and mesothelium. This result, together with the higher surface density of plasmalemmal vesicles found in capillary endothelium, suggest an important role of these structures in the transendothelial passage of endogenous albumin, particularly for capillary endothelium. On the other hand, labeling densities over mesothelial clefts were found to be higher than those of capillary and aortic endothelia. Results from this study concur with the proposal of a differential passage of albumin according to the cell lining considered, and suggest to a role for mesothelial intercellular clefts in contributing to the presence of albumin in interstitial spaces.


Reconstitution of Organismal Liver Clock Function Requires Light.
Recently Koronowski et al. (Cell, 2019) showed that reconstitution of the liver circadian clock in otherwise genetically arrhythmic mice revives the daily program of the nicotinamide adenine dinucleotide salvage pathway and glycogenesis in vivo. This liver-autonomous metabolic cycling cannot be sustained under constant darkness, revealing the importance of the daily light cycle to restore liver function.


Previous coronary stents do not increase early and long-term adverse outcomes in patients undergoing off-pump coronary artery bypass grafting: a propensity-matched comparison.
The aim of our study was to compare the early and long-term outcomes of patients undergoing off-pump coronary artery bypass grafting (CABG) with and without previous coronary stents. Between September 2004 and September 2011, 269 patients with previous stents underwent first-time isolated off-pump CABG. These patients were compared with 897 patients without previous stent. A propensity score-matching analysis was performed to compare early and late outcomes between the groups. Mean follow-up time was 43.4 months after surgery. Patients with previous stents were more likely to be men (85.9% in the stent group vs 79.4% in the no-stent group; P=.022) and more likely to have prior myocardial infarction (60.2% vs 36.8%; P<.001). Mean number of anastomoses was lower in patients with previous stents than in patients without previous stents (4.0 vs 4.2; P=.037). There was no difference in the use of bilateral internal thoracic artery graft between the groups (88.8% vs 89.1%; P>.999). After propensity adjustment for preoperative characteristics, both operative death (0.7% vs 1.5%; P=.414) and the major complications rates (7.8% vs 7.5%; P=.869) were similar between the groups. The actuarial survival rate at 7 years was not different between the groups (87.2%±3.2% vs 84.8%±2.9%; P=.470). Furthermore, freedom from major adverse cardiac and cerebrovascular events at 7 years were similar between the groups (78.9%±3.8% vs 77.6%±3.3%; P=.811). Previous coronary stents do not increase early and long-term morbidity or mortality in patients undergoing off-pump CABG.


Intraoperative techniques to prevent air leaks.
Persistent air leaks prolong chest tube duration and hospital stay after lung surgery. Air leaks also may lead to life-threatening empyemas. Preventing postoperative air leaks and BPFs is the best treatment for air-leak complications. Meticulous closure of parenchymal, pleural, and bronchial defects is the mainstay of air-leak control. The reinforcement of parenchymal suture and staple lines, pleural apposition, and well-vascularized tissue-flap coverage of bronchial suture and staple lines further reduce the incidence of prolonged air leaks and BPFs.


The recurring problem of retained swabs and instruments.
Patient safety is one of the most pressing challenges in health care. The promotion of safety requires that all those involved in healthcare realise that the potential for errors exists, and that teamwork and communication are essential for preventing errors. Incidents compromising patient safety, such as unintended retention of swabs or instruments, are regarded as 'never events'. These incidents are considered 'unacceptable and eminently preventable', as pointed out by the Department of Health 'never events list' 2012/2013. One estimate says that one case of a retained item occurs at least once a year in a major hospital where 8000 to 18,000 major cases are carried out each year. All healthcare organisations should take appropriate measures to prevent retention of foreign bodies by consistent application of reliable and standardised processes of care. In this review, we explore the risks and complications associated with retained swabs and instruments, and different ways to prevent such risks to patients.


Acute, genetic and sub-chronic toxicities of flaxseed derived Maillard reaction products.
In present study, the acute, genetic, and sub-chronic toxicities of flaxseed derived Maillard reaction products (MRPs) were investigated. Acute toxicity results showed that the 50% lethal dose (LD50) of MRPs in rats was >15.0 g/kg body weight (BW); whereas, the 50% effective dose (ED50) of MRPs was 12.3 g/kg BW. Ames test demonstrated that the back-mutation colonies for MRPs addition of 5,000 μg/dish was positive, which displayed certain mutagenicity. There were no significant differences in micronucleus rate and sperm deformity rate among different dose groups. The sub-chronic toxicity confirmed that less than 0.75 gMRPs/kg BW intake did not affect weight, food intake, mortality, gross pathology, histology, hematology, and serum biochemistry. The obtained results can provide an imperative reference on the safety of a meat flavoring agents.


"Vitamin E" fortified parenteral lipid emulsions: Plackett-Burman screening of primary process and composition parameters.
The objective of this study was to screen the effect of eight formulations and process parameters on the physical attributes and stability of "Vitamin E"-rich parenteral lipid emulsions. Screening was performed using a 12-run, 8-factor, 2-level Plackett-Burman design. This design was employed to construct polynomial equations that identified the magnitude and direction of the linear effect of homogenization pressure, number of homogenization cycles, primary and secondary emulsifiers, pre-homogenization temperature, oil loading, and ratio of vitamin E to medium-chain triglycerides (MCT) in the oil phase on particle size, polydispersity index, short-term stability, and outlet temperature of manufactured emulsions. The viscosity of vitamin E was reduced from 3700 (100%) to 64 mPa.s (30%) by MCT addition. As viscosity is critical for efficient emulsification, vitamin/MCT ratio was the most significant contributor for the stability of emulsions. Particle size increased from 236 to 388 nm, and percentage vitamin remaining emulsified after 48 h dropped from 100 to 73% with increase in vitamin/MCT ratio from 30/70 to 70/30. Significant decrease in particle size and PI, and an increase in outlet temperature were also observed with increase in homogenization pressure and number of homogenization cycles. Emulsifiers and oil loading, however, had insignificant effect on the responses. Overall, stable submicron emulsions at vitamin/MCT ratio of 30/70 could be prepared at 25,000 psi and 25 cycles in ambient conditions. The identification of these parameters by a well-constructed design demonstrated the utility of screening studies in the "Quality by Design" approach to pharmaceutical product development.


Luminance-dependent hue shift in protanopes.
For normal trichromats, the hue of a light can change as its luminance varies. This Bezold-Brücke (B-B) hue shift is commonly attributed to nonlinearity in the blue-yellow opponent system. In the present study, we questioned whether protanopes experience analogous changes. Two protanopes (Ps) viewed spectral lights at six luminance levels across three log steps. Two normal trichromats (NTs) were tested for comparison. A variant of the color-naming method was used, with an additional "white" term. To overcome the difficulty of Ps' idiosyncratic color naming, we converted color-naming functions into individual color spaces, by way of interstimulus similarities and multidimensional scaling (MDS). The color spaces describe each stimulus in terms of spatial coordinates, so that hue shifts are measured geometrically, as displacements along specific dimensions. For the NTs, a B-B shift derived through MDS agreed well with values obtained directly by matching color-naming functions. A change in color appearance was also observed for the Ps, distinct from that in perceived brightness. This change was about twice as large as the B-B shift for NTs and combined what the latter would distinguish as hue and saturation shifts. The protanopic analogue of the B-B shift indicates that the blue-yellow nonlinearity persists in the absence of a red-green signal. In addition, at mesopic levels (< or = 38 td), the Ps' MDS solution was two dimensional at longer wavelengths, suggesting rod input. Conversely, at higher luminance levels (76 td-760 td) the MDS solution was essentially one dimensional, placing a lower limit on S-cone input at longer wavelengths.


Sparsity regularization in dynamic elastography.
We consider the inverse problem of continuum mechanics with the tissue deformation described by a mixed displacement-pressure finite element formulation. The mixed formulation is used to model nearly incompressible materials by simultaneously solving for both elasticity and pressure distributions. To improve numerical conditioning, a common solution to this problem is to use regularization to constrain the solutions of the inverse problem. We present a sparsity regularization technique that uses the discrete cosine transform to transform the elasticity and pressure fields to a sparse domain in which a smaller number of unknowns is required to represent the original field. We evaluate the approach by solving the dynamic elastography problem for synthetic data using such a mixed finite element technique, assuming time harmonic motion, and linear, isotropic and elastic behavior for the tissue. We compare our simulation results to those obtained using the more common Tikhonov regularization. We show that the sparsity regularization is less dependent on boundary conditions, less influenced by noise, requires no parameter tuning and is computationally faster. The algorithm has been tested on magnetic resonance elastography data captured from a CIRS elastography phantom with similar results as the simulation.


Association of exposure to neighborhood drug activity, neurobehavioral traits, and marijuana use among at-risk African American females.
Theories of relative deprivation suggest African Americans in disadvantaged communities are at increased risk for drug use. This increased risk may be due, in part, to exposure to drugs and drug subcultures. Given the significance of the prefrontal cortex (PFC) functioning in yielding behavior that is strategically guided rather than reactive to environmental demands, it is important to examine the relationship between PFC functioning, neighborhood drug activity and substance use among African Americans residing in high risk communities. A sample of 120 young adult African American females was recruited from high-risk neighborhoods. Each completed the modified version of the neighborhood environment scale, a neurobehavioral assessment designed to measure apathy, behavioral disinhibition and executive dysfunction, and provided a urine sample that was tested for the presence of psychoactive drugs. Logistic regression analyses indicated that females with higher scores on behavioral disinhibition were 2.6 times more likely to test positive for marijuana (95%CI = 1.02, 6.57). Neither apathy nor executive dysfunction was related to marijuana use. No relationship emerged between neighborhood drug activity and marijuana use. Among the neurobehavioral traits considered only behavioral disinhibition was associated with marijuana use, suggesting that different neurobehavioral domains may be uniquely related to marijuana use. For females living in high risk environments, the extent to which they are able to control impulses may provide some protection against marijuana use. Future studies focused on the moderating effects of behavioral disinhibition on the association of exposure to risk environments and marijuana use may prove beneficial. Further, the study adds to the small base of literature supporting the Frontal Systems Behavior Scale as a brief assessment to evaluate frontally-mediated neurobehavioral traits relevant to substance use. However, future studies aimed at examining the influence of neighborhood drug activity might benefit from more precise measures of exposure to neighborhood drug activity. More research to replicate and expand on the present findings is warranted.


Predictors and moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS).
To identify predictors and moderators of response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive-behavioral therapy (CBT), both fluoxetine and CBT, or clinical management with pill placebo in the Treatment for Adolescents With Depression Study (TADS). Potential baseline predictors and moderators were identified by a literature review. The outcome measure was a week 12 predicted score derived from the Children's Depression Rating Scale-Revised (CDRS-R). For each candidate moderator or predictor, a general linear model was conducted to examine main and interactive effects of treatment and the candidate variable on the CDRS-R predicted scores. Adolescents who were younger, less chronically depressed, higher functioning, and less hopeless with less suicidal ideation, fewer melancholic features or comorbid diagnoses, and greater expectations for improvement were more likely to benefit acutely than their counterparts. Combined treatment, under no condition less effective than monotherapy, was more effective than fluoxetine for mild to moderate depression and for depression with high levels of cognitive distortion, but not for severe depression or depression with low levels of cognitive distortion. Adolescents from high-income families were as likely to benefit from CBT alone as from combined treatment. Younger and less severely impaired adolescents are likely to respond better to acute treatment than older, more impaired, or multiply comorbid adolescents. Family income level, cognitive distortions, and severity of depression may help clinicians to choose among acute interventions, but combined treatment proved robust in the presence of moderators.


Prevalence of childhood overweight/obesity in Spain 1993-2011 and associated risk factors in 2011 Prevalencia de sobrepeso y obesidad infa.
Childhood obesity is a recognized public health problem. The present work reports the changing prevalence of childhood overweight/obesity in Spanish boys and girls over the period 1993-2011, and examines the risk factors apparent in 2011. Children with a body mass index (BMI) of ≥ 25 were deemed overweight, and those with a BMI of ≥ 30 were deemed obese. Overweight and obesity was consistently more common among boys than among girls. The prevalence of overweight and obesity in Spain increased over the study period. CONCLUSIONS: According to the 2011 data, children who undertook no physical activity, or whose parents/guardians had a low level of education, showed the highest prevalence of obesity.


Simulation as More Than a Treatment-Planning Tool: A Systematic Review of the Literature on Radiation Oncology Simulation-Based Medical Education.
Simulation-based medical education (SBME) is gaining prominence as a tool to meet Accreditation Council for Graduate Medical Education-mandated competency-based assessment educational goals. SBME is used in radiation oncology, although the type and extent are not clear. This study reports a systematic literature review designed to clarify the type and extent of radiation oncology SBME. The systematic review focused on radiation oncology SBME literature. The methods followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria were identified according to the PICOS (population, intervention, comparison, outcome, and setting) framework. The population included undergraduate, graduate, and continuing medical education learners. Studies were limited to English-language studies published on or after January 1, 1990, in peer-reviewed journals. PubMed, MedEdPORTAL, and in-press articles were searched. The PubMed search was conducted using predefined search terms. References and similar articles were examined. Medical Subject Headings terms in selected articles were reviewed to ensure relevant terms were included. Fifty-four SBME publications met the inclusion criteria. Only 9 of 54 studies (17%) self-identified as SBME. SBME types included screen-based simulators (56%), simulated environments (13%), virtual reality and haptic systems (13%), simulated patients (11%), part-task trainers (6%), and computer-based systems with mannequins (2%). A variety of radiation oncology skill sets were addressed, including contouring (54%), treatment planning (20%), clinical decision making (17%), anatomy and/or radiology (13%), radiation biology and/or physics (13%), communication skills and/or patient education (13%), brachytherapy (13%), and immobilization (11%). A target learning population was defined in 47 studies, including residents (53%), attending physicians (36%), medical students (21%), medical physicists (11%), radiation therapists (9%), nurses (6%), administrative staff (4%), and dosimetrists (4%). Learner feedback was reported in 32 studies. Overall, this systematic literature review provides context and guidance for future radiation oncology SBME development. Appropriately framing SBME reports in the radiation oncology literature will facilitate development, implementation, and evaluation of SBME interventions. SBME resources should be centralized to facilitate dissemination and share resources.


Avoidance of copper contamination by field populations of Daphnia longispina.
Almost all terrestrial and aquatic assays that are accepted as standardized, or that have been proposed, involve the exposure of confined organisms to toxicants. If avoidance (sensu evasion, displacement) of contaminants occurs in real situations, then bioassays involving forced exposure severely underestimate pernicious effects of contamination. Two main objectives were achieved in this study: To verify the occurrence of avoidance of copper by cladocerans; to determine the association between avoidance and other toxicity endpoints (lethality and feeding depression), and therefore, to ascertain if fully acclimated individuals from a reference field population exhibited a genetically determined avoidance markedly different from those belonging to a historically metal-stressed population. Twelve cloned lineages of the cladoceran Daphnia longispina, collected from two field populations, were selected according to their lethal sensitivity to copper and acclimated to controlled conditions for more than 30 generations. A 1.1-m test chamber with five compartments was built, allowing the establishment of a dissolved toxicant gradient and the free movement of individuals. In the absence of any toxicant, juveniles from each cloned lineage distributed themselves randomly along the test chamber and furthermore, no significant differences were observed between the two replicates, attesting the repeatability of this novel assay. All lineages showed significant avoidance to copper when exposed to a gradient from 3 to 87 microg/L. The most sensitive lineages to lethal levels of copper began avoiding this metal earlier than resistant ones. An intense association was observed between other endpoints and avoidance; furthermore, avoidance was determined to be much more sensitive than lethality. Therefore, avoidance assays should be recommended as a complementary tool in ecological risk assessments and effluent biomonitoring because such assays can provide cost-effective and ecologically relevant information.


Pleasant music improves visual attention in patients with unilateral neglect after stroke.
To investigate whether listening to pleasant music improves visual attention to and awareness of contralesional stimuli in patients with unilateral neglect after stroke. A within-subject design was used with 19 participants with unilateral neglect following a right hemisphere stroke. Participants were tested in three conditions (pleasant music, unpleasant music and white noise) within 1 week. All musical pieces were chosen by the participants. In each condition, participants were asked to complete three sub-tests of the Behavioural Inattention Test (the Star Cancellation Test, the Line Bisection Test and the Picture Scanning test) and a visual exploration task with everyday scenes. Eye movements in the visual exploration task were recorded simultaneously. Mood and arousal induced by different auditory stimuli were assessed using visual analogue scales, heart rate and galvanic skin response. Compared with unpleasant music and white noise, participants rated their moods as more positive and arousal as higher with pleasant music, but also showed significant improvement on all tasks and eye movement data, except the Line Bisection Test. The findings suggest that pleasant music can improve visual attention in patients with unilateral neglect after stroke. Additional research using randomized controlled trials is required to validate these findings.


Polymers for use in controlled release systems: the effect of surfactants on their swelling properties.
The effect of an ampholytic surfactant on the swelling properties of polymeric materials was studied, using various swelling liquids. Tablets were prepared consisting of hydroxypropyl methylcellulose, poly(oxyethylene) and sodium alginate. Tego betain was the non-ionic surfactant used as an additive in a series of samples made of the above polymers. Those tablets were immersed in distilled water, phosphate buffer and 0.1 N HCl, and their weight uptake was recorded as a function of time, in order to assess the swelling process. Measurements of the contact angle of the above systems were also carried out for estimating their wetting properties. The results of this study showed a selectivity among polymers, surfactant and surrounding liquid. Clearly, an enhancement of the swelling capacity of hydroxypropyl methylcellulose tablets due to the surfactant was recorded. An unclear effect was observed in the case of poly(oxyethylene), whereas for sodium alginate, the dominant factor is its water solubility that controls swelling behaviour.


[Itinerant and established oculists of the 18th century].
The formation of scientific surgery in the 18th century was associated by the development of ophthalmology as a special branch of medicine and accompanied with a large number of more or less qualified oculists. A lot of them travelled practising throughout Europe, propagating their profession by handbills, announcements and booklets. In 1748 Frederick II of Prussia appointed Joseph Hillmer (born about 1720) from Vienna, who was a contemporary of John Taylor (1703-1772) as oculist and charlatan, an ordinary professor for ophthalmiatrics at the Berlin Collegium Medico-Chirurgicum. In 1752 C. E. Eschenbach, in the course of critizing Taylor's charlatanism, had called his century the "Okulisten-seculum". By the way many documents on travelling oculists have been delivered, first of all as to the English oculist, but the most important in medical and historical view concerning Hillmer. Researches on 25 oculist, based on documents and newspapers from 1558 to 1806 (especially concentrated upon Berlin as Hillmer's residence) reveal the transformation of the ancient ophthalmiatry into ophthalmology. There have been resident oculists before the 18th century; their small number corresponded to the poor demographical situation at the time. For the last reason they practised partially travelling. Local medical authorities reglemented them by permission for practising within a given time. Many propagandistic publications about oculistic charlatans, mainly from their own hand, might make us believe, above all the early ophthalmology would have been characterized by travelling oculists, because their respectable and resident colleagues are documented less impressive, for the reason that they have not made as much propaganda, as charlatans made.


DNA-damage induction by eight metal compounds in TK6 human lymphoblastoid cells: results obtained with the alkaline Comet assay.
Metal compounds are long-lived and can react with different macromolecules, producing a wide range of biological effects, including DNA damage. Since their reactivity is associated with their chemical structure, it is important to obtain information on more than one compound from the same metal. In this study, the DNA-damaging potential of two mercury compounds (mercury chloride and methyl mercury chloride), two nickel compounds (nickel chloride and potassium hexafluoronickelate), two palladium compounds (ammonium tetrachloropalladate and ammonium hexachloropalladate), and two tellurium compounds (sodium tellurite and sodium tellurate) was evaluated in human lymphoblastoid TK6 cells by use of the alkaline version of the Comet assay. As the use of computerized image-analysis systems to collect comet data has increased, the metric used for quantifying DNA damage was the Olive tail moment. Treatments lasted for 3h and the range of concentrations tested was different for each metal compound, depending on its toxicity. Both mercury agents produced DNA damage in TK6 cells, with mercury chloride producing considerably more DNA damage than methyl mercury chloride. Of the two nickel compounds, only nickel chloride (a Ni(II) compound) induced DNA breaks. Similarly, of the two palladium compounds, only the Pd(II) compound (ammonium tetrachloropalladate) was positive in the assay. Sodium tellurite was clearly positive, producing concentration-related increases in DNA damage, while sodium tellurate gave a negative response. In conclusion, the ability of inducing DNA damage by the selected metal compounds in human TK6 cells, when measured with the Comet assay, was dependent on the chemical form and, in general, compounds containing the metal in the lower valence state displayed the greater DNA-damaging ability.


Means-Tested Public Assistance Programs and Adolescent Political Socialization.
In recent years, scholars have pointed to the politically demobilizing effects of means-tested assistance programs on recipients. In this study, we bridge the insights from policy feedback literature and adolescent political socialization research to examine how receiving means-tested programs shapes parent influence on adolescent political participation. We argue that there are differences in pathways to political participation through parent political socialization and youth internal efficacy beliefs for adolescents from households that do or do not receive means-tested assistance. Using data from a nationally representative sample of 536 Black, Latino, and White adolescents (50.8% female), we find that adolescents from means-tested assistance households report less parent political socialization and political participation. For all youth, parent political socialization predicts adolescent political participation. Internal political efficacy is a stronger predictor of political participation for youth from a non-means-tested assistance household than it is for youth from a household receiving means-tested assistance. These findings provide some evidence of differential paths to youth political participation via exposure to means-tested programs.


gamma-Glutamyl transpeptidase acylation with peptidic substrates: free energy relationships measured by an HPLC kinetic assay.
gamma-Glutamyl transpeptidase (GGT, EC 2.3.2.2) is a highly glycosylated heterodimeric enzyme linked to the external cellular membrane that catalyzes the hydrolysis of glutathione as well as the transfer of its gamma-glutamyl group to amino acids and dipeptides in a transpeptidation reaction. The measurement of both the hydrolytic and transpeptidation activity of this important enzyme is a challenge, since its native substrates are not highly chromogenic. We have developed an HPLC-based method for the quantitative photometric detection of numerous enzyme substrates and products, after their pre-column derivation with dabsyl chloride. The broad applicability of this method was demonstrated in the kinetic investigation of transpeptidation reactions of rat kidney GGT with glutathione, its native substrate, as well as a series of pertinent glutathione analogues. The pH-rate profile constructed for glutathione confirmed the dependence on the ionisation state of at least two residues. Analysis of the free-energy relationships in the series of synthetic peptidic substrate analogues revealed the importance of enzyme-substrate interactions unrelated to amine leaving group basicity during the acylation step. These results are further interpreted in the context of the recently published structure for a similar GGT.


Be vigilant for patients with coeliac disease.
Recent population studies show that coeliac disease affects around 1 in 100 people. The estimated ratio of diagnosed to undiagnosed individuals is 1:8, and the average delay in diagnosis is reported to be 11 years. The contemporary coeliac patient is diagnosed between the ages of 40 and 60, has normal or even high BMI, and subtle symptoms. Patients are often identified in screening groups which would include those with type 1 diabetes, autoimmune thyroid disease, or a first-degree relative with coeliac disease. The presence of relevant symptoms is not essential for a diagnosis of coeliac disease. Additionally, positive serological testing alone is not sufficient to confirm the diagnosis. Endomysial antibody (EMA) and tissue transglutaminase (TTG) have a combined sensitivity and specificity of > 90% when used in combination in selected populations. However, false positives occur in conditions such as inflammatory bowel disease, and autoimmune disease. Conversely antibody-negative disease accounts for around 9% of cases. IgA deficiency is a cause of false negatives and levels should be checked at the same time as EMA and TTG. Patients must consume a gluten-containing diet for six weeks before serological testing and biopsy if necessary. All those with positive serological tests, and those for whom clinical suspicion is high even if seronegative, should be referred to a gastroenterologist for a duodenal biopsy to confirm or exclude coeliac disease. Diagnosis requires the demonstration of villous atrophy in the small bowel which improves when gluten is withdrawn.


LCP metaphyseal plate fixation for fractures of the distal third humeral shaft using brachialis splitting approach.
The authors retrospectively studied the clinical and radiographic outcomes of locking compressive plate (LCP) metaphyseal plate fixation through the anterolateral approach in patients treated surgically for unstable distal third humeral shaft fractures. Twenty seven patients were treated surgically with LCP metaphyseal plate using brachialis splitting methods through the anterolateral approach. The mean arc of elbow motion was 132.4° with a mean flexion of 133.5° and mean flexion contracture of 1.1°. Three patients had a slight elbow flexion contracture with loss of 5° (n=1), 10° (n=1), and 15° (n=1) of extension. The mean American Shoulder and Elbow Surgeons score was 92.6 points, which corresponded to excellent results in 26 shoulders and a good result in one. The mean Mayo Elbow Performance Score was 90.7 points, which corresponded to excellent results in 24 elbows, a good result in 2, and a fair result in 1. Treatment of distal third humeral shaft fracture using LCP metaphyseal plate through the anterolateral approach is an acceptable and alternative method that can provide good results.


Cedrelopsis grevei induced hypotension and improved endothelial vasodilatation through an increase of Cu/Zn SOD protein expression.
This study was designed to investigate the cardiovascular consequences of oral administration of Cedrelopsis grevei (CG) in normotensive rats. Experiments were designed to investigate hemodynamic parameters in vivo as well as the consequences of CG treatment on the vasoconstriction response to norepinephrine and the vasorelaxant response to ACh ex vivo in isolated aortas and small mesenteric arteries (SMA). Treatment of male Wistar rats with 80 mg/kg CG for 4 wk induced a progressive decrease in systolic blood pressure. In the aorta, CG did not significantly alter the response to norepinephrine despite the participation of extraendothelial nitric oxide (NO)-induced hyporeactivity. In the SMA, contraction to norepinephrine was not modified by CG treatment even though it enhanced the participation of endothelial NO. Endothelium-dependent relaxation to ACh was increased in both the aorta and SMA from CG-treated rats. In the aorta from CG-treated rats, the mechanism involved superoxide dismutase (SOD)- and catalase-sensitive free radical production. The latter was associated with enhanced expression of Cu/Zn SOD and endothelial NO synthase. These results suggest that oral administration of CG produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with enhanced endothelium-dependent relaxation and an induction of Cu/Zn SOD and endothelial NO synthase expressions in the vessel wall. They also show subtle mechanisms that compensate for the increased participation of NO to maintain unchanged agonist-induced contractility. These data provide a pharmacological basis for the empirical use of CG against cardiovascular diseases.


Apple four in human blood coagulation factor XI mediates dimer formation.
Human blood coagulation factor XI is a dimer composed of two identical subunits. Each subunit contains four apple domains as tandem repeats followed by a serine protease region. A disulfide bridge between Cys321 of each fourth apple domain links the subunits together. The role of Cys321 in the dimerization of factor XI was examined by mutagenesis followed by expression of its cDNA in baby hamster kidney cells. The recombinant proteins were then purified from the tissue culture medium and shown to have full biological activity. Normal recombinant factor XI was secreted as a dimer as determined by SDS-PAGE, while recombinant factor XI-Cys321 Ser migrated as a monomer under these conditions. Gel filtration studies, however, revealed that each protein existed as a dimer under native conditions, indicating that the disulfide bond between Cys321 of each factor XI monomer was not necessary for dimer formation. The fourth apple domain (apple4) of factor XI was then introduced into tissue plasminogen activator (tPA) to investigate its role in the dimerization of other polypeptide chains. The fusion protein, containing apple4 (apple4-tPA), formed dimers as detected by SDS-PAGE and gel filtration. Furthermore, dimerization was specific to apple4, while apple3 had no effect on dimerization. These data further indicated that the apple4 domain of factor XI mediates dimerization of the two subunits and the interchain disulfide bond involving Cys321 was not essential for dimer formation.


Feeding hydrogenated fatty acids and triglycerides to lactating dairy cows.
Effects of feeding hydrogenated tallow fatty acids and triglycerides to lactating dairy cows were studied using five primiparous Holstein cows in a 5 x 5 Latin square design. A control diet with no supplemental fat and diets containing either hydrogenated tallow fatty acids or triglycerides at 2 and 5% levels were fed for ad libitum intake. Diets were isonitrogenous but not isocaloric. Each treatment period consisted of 28 d; the last 14 d were used for data collection. Fat-supplemented diets had no effects on DM intake, milk fat percentage, milk protein percentage, and BW compared with the control diet. Energy intake and milk yields were higher for cows fed fat-supplemented diets. Adding fatty acids to diets increased milk fat percentage above that in milk from cows fed triglyceride diets. Apparent digestibilities of DM and OM were lowered by the addition of fat, mainly in response to fatty acid additions. Feeding fatty acids reduced ash digestibility compared with feeding triglycerides, and NDF digestibility also tended to be lower for cows fed fatty acid diets. Fat addition to diets reduced fatty acid digestibility; digestibility of added fat averaged 37.7%. Although of similar saturation, the triglyceride supplement was more ruminally inert than the fatty acid supplement. Esterification and degree of saturation are features of importance when processing tallow for use in ruminant diets.


Neonatal thrombosis and its treatment.
Thromboembolic disease (TE) has been described as the new epidemic of tertiary paediatrics, and no where is this more evident than in the neonatal population. As survival of premature and sick newborns has improved, the frequency of complications associated with intensive supportive therapy and monitoring has increased. Clinically significant thrombosis is emerging as one of the more common complications associated with improved neonatal outcome. The long-term implications of neonatal thrombosis are only just being realised. This systematic review will consider the epidemiology, diagnostic strategies, and outcome for both arterial and venous TE in neonates. The role of inherited thrombophilic abnormalities, and the evidence for anticoagulation therapy will also be considered. The lack of high level evidence in determining optimum therapy is obvious. Further research regarding diagnostic strategies, and optimal therapies is urgently needed.


[The expression of fetuin-A and its pathological significance in fulminant hepatic failure in mice].
To explore the dynamic changes of fetuin-A expression and the influences of the changes on liver damage, hepatocyte apoptosis and inflammation in a mouse fulminant hepatic failure (FHF) model. The changes of fetuin-A expression were investigated by semi-quantitative RT-PCR and Western blot. Immunohistochemical staining was used in TNFa and fetuin-A detection. Hepatocyte apoptosis was detected by TUNEL. Fetuin-A mRNA expression decreased after the FHF model was established for 3 hours (compared with the normal group, P less than 0.01), while the protein expression decreased after nine hours (compared with the normal group, P less than 0.01). Fetuin-A expressions were negatively correlated with the liver pathological scores and TNFa levels. In our mouse FHF model, fetuin-A is a possible protective factor for liver damage.


Synthesis and Characterization of a Brønsted Pair Functionalized Shape-Persistent Macrocycle.
The first shape-persistent macrocycle 1 offering a Brønsted pair functionalized interior is described. Via postcyclization transformation, this heterosequenced compound can be obtained from its corresponding ester 2. The macrocycles differ dramatically in their characteristics such as solubility and appearance. Theoretical investigations suggest that those contrasts might originate from conformational changes due to the formation of a strong O-H-N hydrogen bond in 1.


[A stand for measuring hand grip power and manipulation strength during simultaneous and symmetrical work of both hands].
The measurement system in which a stand for tensometric measurement of working grips power during simultaneous and symmetrical work of both hands is enclosed has been described.


Spontaneous conceptions following successful ART are not associated with premature referral.
What is the rate of spontaneous live births after successful IVF treatment in a cost-free environment, and were couples who achieved a spontaneous live birth referred prematurely? Despite unlimited IVF treatments offered free of charge, the spontaneous live birth rate following successful IVF remained unchanged compared with that cited in previous literature. Couples were not referred prematurely to IVF before fully utilizing other less invasive treatments. A significant number of infertile couples, who achieve their first live birth through assisted reproductive technology (ART), subsequently achieve a second live birth spontaneously. As IVF has become more widely available, it is used in less severe cases of infertility, perhaps explaining a rise in the subsequent spontaneous live birth rate after successful treatments. This retrospective cohort study was performed at a university-based tertiary medical center. The study population included women aged <35 years, with primary infertility, referred for their first IVF treatment to the Sheba Medical Center IVF unit between 2001 and 2002 and followed up for 7 years. The primary outcome was spontaneous live birth rate following successful ART. Relevant data were obtained from the patient files and supplemented by a standardized telephone questionnaire. Of the 171 couples who met the study inclusion criteria, 6 refused to participate in the questionnaire and 31 couples were lost to follow-up. Of the 134 couples who participated, 109 achieved a first live birth with ART. After achieving their first live birth with ART, seven couples who began using contraception or separated or divorced were excluded. Of 102 couples who continued unprotected intercourse after successful ART, 22 subsequently achieved their second live birth spontaneously (21.6%). The women who achieved a second birth spontaneously were not referred earlier to IVF, and actually performed a higher number of ovulation induction cycles before initiating IVF, compared with women who did not conceive spontaneously. This is a retrospective cohort study, and findings should be reaffirmed with a larger prospective randomized study comparing retreatment to achieve a second pregnancy with attempting to conceive spontaneously. Our data suggests that young patients (<35 years), who previously conceived with IVF, without utilizing ICSI and with no known tubal pathology, should consider attempting to conceive spontaneously. No funding was obtained for this study and the authors have no competing interests.


Growth velocity in children in rural Khartoum, Sudan.
The results of a mixed cross-sectional and longitudinal anthropometric survey of Sudanese children up to the age of sixteen years are reported. Weight velocity, height velocity, mid arm circumference velocity, and mid arm muscle circumference velocity, and the age at which 50% of females have reached menarche have been calculated. Growth velocities are lower than for English children and the puberty growth spurts occurs about one year later in Sudanese than in English children


Construction and characterization of herpes simplex virus type 1 mutants with defined lesions in immediate early gene 1.
Transcription from the early and late classes of the herpes simplex virus type 1 (HSV-1) promoters requires prior immediate early (IE) gene expression. Although the product of IE gene 1, Vmw110, is not absolutely essential for virus growth in tissue culture, transfection experiments have demonstrated that Vmw110 can activate gene expression both by itself and in a synergistic manner with the product of IE gene 3, Vmw175. This paper describes the construction of 10 mutant HSV-1 viruses with deletion and insertion mutations in Vmw110. The mutant viruses were then studied in single-step growth curve experiments, by assaying for plaques in a variety of cell types and by analysis of viral polypeptide synthesis during productive infection at high and low multiplicities. The results show that mutations in Vmw110 reduce the efficiency of plaque formation by HSV-1; the extent of this reduction depends on cell type and the position of the mutation in the polypeptide. In particular, a potential zinc finger domain is crucial for Vmw110 function. The patterns and amounts of viral polypeptide synthesis during high multiplicity infections with mutant and wild-type viruses were similar in all cell types. At low multiplicity, mutations in Vmw110 reduced viral gene expression in the least permissive cell type. The data suggest that the role of Vmw110 during virus infection in tissue culture is at a very early stage of low multiplicity infections; its inactivity leads to the failure to express viral genes so that the virus does not enter the lytic cycle.


Laparoscopic cholecystectomy using 2-mm instruments.
Today, laparoscopic cholecystectomy is the method of choice for treatment of symptomatic gallbladder disorders. It minimizes effects of the operation that are independent of the gallbladder, such as trauma to the abdominal wall and other soft tissue. The surgical wounds were even smaller when 2-mm trocars were used. Laparoscopic cholecystectomy using 2-mm instruments was performed in a consecutive series of 14 patients with symptomatic gallstones. The procedure was completed in 12 cases, with conversion to open surgery in two cases. Intraoperative cholangiography was always performed. The postoperative course was always uneventful. The cosmetic effect was highly satisfactory. The procedure using 2-mm instruments could be indicated in selected patients with uncomplicated gallstone disease.


Conformational analysis of xylan chains.
The present study provides a theoretical description of the different levels of structural organization that characterize the xylan polysaccharide in its native and hydrophobic lauroyl esterified forms. The goal of this study was to ascertain the role played by the hydroxyl or lauroyl side groups on the conformational flexibility of the xylan chain backbone. The results reported provide a detailed description of the low-energy conformers of the dimer segments, a complete characterization of the helical structures, an insight into the disordered state of the polysaccharide chains and an estimation of the cohesion of the amorphous solids. Esterification of xylan hydroxyl groups by lauric acid has a large effect on the conformational properties of the glycosidic bonds linking two repeat units. Both the location and the relative energies of the low energy areas of the potential energy surfaces strongly differ: extended and coiled conformations are preferred for the native and hydrophobic forms, respectively. Consequently, the predicted unperturbed polymer chain extension strongly depends on the structure, predicted Lp of the native xylan of 35 A compares favourably well with the experimental ones, this characteristic dramatically decreases to 9A for the hydrophobically modified chain. Curiously, only extended 2(1) and left-handed 3(1) helical structures are calculated stable for both polymers. The estimated cohesive parameters of amorphous bulks reveal that inter-chain interactions are stronger for the xylan chain than that for modified one, the former being stabilized by hydrogen bonds whereas hydrophobic interactions play a determinant role for the latter.


[Mechanisms of the Effects of Probiotics on Symbiotic Digestion].
The published data and our own data on the mechanisms of the influence of microbial probiotics, prebiotics, and their combinations on the processes of symbiotic digestion have been considered and generalized. It is shown that the effects on an organism are associated with the enhanced metabolic activity of intestinal bacteria: stimulation of bacterial fermentation of carbohydrates and formation of short-chained fatty acids, an increase in the blotting capacity of the intestines due to elongation of villi and deepening of crypts, and a decrease in secretion of toxic proteolytic products (ammonia, phenols, thiols, indoles, etc.). It has been shown that a combination of probiotics and prebiotic enhances the biological efficiency of a complex preparation, which contributes to activation of carbohydrate, protein, and mineral metabolism.


Risk behaviour, parental background, and wealth: a cluster analysis among Swedish boys and girls in the HBSC study.
To analyse how health risk behaviours (HRB) are clustered and associated with parental background and family wealth among Swedish boys and girls. Data were collected from Health Behaviour in School-aged Children (HBSC), a global cross-sectional survey for 1997/98, 2001/02, and 2005/06. A total of 11,972 boys and girls in grades 5, 7, and 9 participated in the study. The pupils were categorised in subgroups according to parental background: Swedish (80.0%), mixed (10.6%), and foreign (9.4%). Cluster analyses were used to identify HRB profiles. Multinomial logistic regression analysis was used to estimate associations between cluster allocation, parental background, and family affluence. In total 11,232 pupils were identified and allocated to five cluster profiles, half of them in the cluster profile of low-risk behaviour. The most disadvantaged cluster was multiple HRB, which was characterised by high prevalence of smoking, drunkenness, low physical activity, and high soft-drink consumption. The cluster profile of multiple HRB was associated with both mixed background and foreign background in girls and with mixed background in boys. The cluster profile of inadequate tooth brushing was associated with foreign background in both boys and girls. The cluster profiles of multiple HRB and inadequate tooth brushing were associated with low family affluence in girls. The cluster profiles of multiple HRB and inadequate tooth brushing were associated with parental foreign extraction in boys and girls and with low family affluence in girls. Prevention programmes based on identified clusters of HRB, including consideration of impact of socio-demographic indicators, are needed.


Inflammatory markers and lipid profile in patients of coronary artery disease.
Coronary artery diseases encompass a spectrum of disorders ranging from angina to fatal myocardial infarctions with the main underlying pathology being identified as atherosclerosis. The level of inflammatory markers, C-reactive protein and fibrinogen was determined in hundred patients with established coronary artery disease and correlated with lipid profile which included serum cholesterol, high density lipoprotein (HDL), low density lipoprotein and triglycerides. The results showed a positive correlation between Inflammatory Marker CRP with LDL and serum cholesterol in patients with coronary artery disease. While no significant correlation of CRP was seen with high density lipoprotein (HDL) and triglyceride. Fibrinogen did not show any significant correlation with lipid profile parameters. Although the inflammatory markers were found to have weak positive correlation with the levels of serum lipids, determining both of these parameters together may help in the early detection and treatment of individuals who are at a high risk for cardiac events.


Dissociation of feeding and hoarding after bilateral destruction of lateral septal nuclei in rats.
The interrelationship between Feeding and Hoarding of food pellets was observed to be disrupted following bilateral destruction of lateral septal nuclei in adult male albino rats. The significance of forebrain areas and neuro-endocrinal connection to hypothalamus is discussed.


Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. I. Substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vivo and in vitro.
The ability of substance P (SP) to regulate peak benzyl-penicilloyl (BPO)-specific IgE antibody-forming cell (AFC) responses in vivo and the ability of SP and other neuropeptides to regulate BPO-specific memory IgE AFC responses induced in vitro was determined. SP injected subcutaneously into BPO-keyhole limpet hemocyanin (BPO-KLH)-sensitized mice at the time of peak IgE responses suppressed these responses within 48 h (> 90%). The suppression obtained was IgE isotype-specific, dose-dependent, and transient. When spleen cells from immunized mice were cultured for 5 days with BPO-KLH, peak memory IgE AFC responses were induced in vitro. Inclusion of either SP or vasoactive intestinal peptide (VIP), but not neurotensin, serotonin, somatostatin, or gastrin, in cultures suppressed these responses in isotype-specific, dose-dependent fashion (approximately 70%). SP-, but not VIP-mediated suppression of IgE responses was abrogated by inclusion of anti-IFN gamma culture.


Microporous manganese formate: a simple metal-organic porous material with high framework stability and highly selective gas sorption properties.
Novel microporous metal-organic framework material composed of Mn(II) and formate ions displays permanent porosity, high thermal stability, and size-selective gas sorption behavior. The framework is stable enough to maintain single crystallinity after the complete guest removal at 150 degrees C under a reduced pressure. Most importantly, it selectively adsorbs H2 and CO2 but not N2 and other gases with larger kinetic diameters, which appears to be due to the small aperture of the channels. Despite a moderate H2 storage capacity, which is however still higher than that of any zeolite, its H2 surface coverage is one of the highest among the known microporous materials. Thus this new zeolite-like material made of a simple organic building block may find useful applications in gas separation and sensor.


Analysis of polyamines and acetyl derivatives by a single automated amino acid analyzer technique.
In a single, rapid and precise analysis, monoacetylputrescine, N8-acetylspermidine, N1-acetylspermidine, putrescine, spermidine, and spermine can be separated using a five-buffer system on an automatic amino acid analyzer. This method allows, for the first time, the separation of all the known acetyl derivatives of putrescine and spermidine as well as the parent compounds in urine and tissues with a single automated procedure. The method has been applied to the analysis of biological samples from normal volunteers, cancer patients and a rat liver supernatant. Mass spectral confirmation was obtained for each compound.


House keeping genes and gene expression analysis in transplant recipients: a note of caution.
House keeping genes are often used as a means of standardising results obtained in gene expression investigations. This study was performed to investigate whether beta-actin, beta2-microglobulin (two genes frequently quoted as house keeping genes) and/or transferrin receptor would be suitable house keeping genes for use in gene expression analysis of renal transplant recipients. Sequential expression of all three genes was measured in the peripheral blood mononuclear cells of 13 living donors and 45 renal transplant recipients, pre-operatively and then daily for up to 2 weeks. Fifteen of the recipients experienced an episode of biopsy proven acute rejection. Gene expression measurement was performed using quantitative real time 'TaqMan' PCR technology. Gene expression of all three genes was unchanged in the living donor cohort. However, in the transplant recipients there were significant increases in expression following transplantation in the non-rejectors, and preceding the diagnosis of acute rejection. In the latter group, levels returned to pre-transplant values after the commencement of anti-rejection therapy. Beta-actin, beta2-microglobulin and transferrin receptor gene expression, although not influenced by surgery, is influenced by transplantation, acute rejection and anti-rejection therapy making these genes unsuitable as house keeping genes following renal transplantation. These findings may cast doubt on the results of some studies that used these genes for the purposes of standardisation when looking at cDNA measurement. We suggest that any group wishing to use a house keeping gene ensure that its expression is independent of study parameters prior to the start of the study.


Effect of mouse submaxillary gland and NGF preparations on competent chick ectodermin vitro, studied by the immunofluorescence method.
The submaxillary gland of the male mouse, but not the female, was shown to act strongly neuralizing on competent chick ectoderm, recorded as frequency of neural antigen producing cultures. NGF preparations from mouse submaxillary gland were shown to cause a high frequency of neural antigen producing cultures. The effect of the NGF preparations diminished with time and ceased after storage at -90° C for 17 days. The possible role of NGF in the present system is discussed; but the possibility could not be excluded that factors other than NGF present in the submaxillary gland and the NGF preparations cause the competent ectoderm to neuralize.


Retrobulbar hemodynamic parameters in pseudoexfoliation syndrome and pseudoexfoliative glaucoma.
To compare the hemodynamic parameters in the retrobulbar vessels in pseudoexfoliative syndrome (PXS), pseudoexfoliative glaucoma (PXG), and age-matched healthy subjects by using color Doppler imaging (CDI). 72 eyes from 72 patients with PXS, 70 eyes from 70 patients with PXG, and 66 eyes from 66 age-matched healthy subjects who met the inclusion/exclusion criteria were included in this prospective cross-sectional study. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and Pourcelot resistance index (RI) were assessed in the ophthalmic artery (OA), central retinal artery (CRA), and temporal short-posterior ciliary arteries (SPCA). Visual function was assessed using the 24-2 Swedish Interactive Threshold Algorithm (SITA). The main outcomes of the study were PSV, EDV and RI in the OA, SPCA, and CRA. The EDV in the OA, SPCA and the CRA was decreased significantly (p < 0.001, <0.001, and 0.003 respectively) in the eyes of PXG patients compared with controls and PSX respectively. The RI in the OA, SPCA, and the CRA was significantly higher (p = 0.022, 0.005, and 0.007 respectively) in the eyes of PXG patients compared with healthy controls and PSX patients respectively. The mean difference in mean EDV in the OA between the control group and the PXS was 0.18 cm/s, 95% confidence interval (CI) -0.60 to 0.95, p = 0.661. The mean difference in mean EDV in the SPCA between the control healthy subjects and the pseudoexfoliative subjects was -0.18 cm/s, 95% CI -0.45 to 0.08, p = 0.176. Multivariate regression analysis showed that in the PXG patients the PSV and EDV in the CRA were significantly positively correlated with the mean defect (p = 0.006 and 0.002 respectively). The RI in the CRA was significantly negatively correlated with the mean defect in PXG patients, p = 0.009. The results of this study showed that the retrobulbar hemodynamics might be disturbed in patients with PXG, especially in the central retinal artery. Our results have found no significant differences in the retrobulbar hemodynamic parameters between pseudoexfoliative syndrome patients and age-matched healthy subjects.


Leakiness of termination codons in mitochondrial mutants of the yeast Saccharomyces cerevisiae.
Seven mutants in exon 1 of the mitochondrial cob gene in yeast are described with respect to their translation products, RNA pattern, and deoxyribonucleotide sequence alteration(s). Sequence analysis of the mutations, which previously were shown to cause premature termination of apocytochrome b, revealed that two of them directly transform sense codons to chain-termination codons, whereas the other four are frame-shift mutations (+1/-1, insertions/deletions). Only the latter mutants are found to be leaky in that (a) RNA splicing occurs, and (b) in three of them, to a minor degree an apocytochrome b homologue is synthesized, which, however, does not lead to respiratory competence. Both require translation through exon 1 into downstream introns to produce 'RNA maturases' necessary for splicing the primary transcript (Lazowska et al. 1980; Weiss-Brummer et al. 1982). These and other previously published data show that mitochondrial frame-shift mutants tend to be leaky to a variable degree. Several possible mechanisms of 'frame-shift suppression' are discussed.


Partially resorbable acrylic bone cements based on self-curing acrylic/phosphate glass formulations.
Partially resorbable self-curing cements based on poly(methyl methacrylate)/phosphate glasses were prepared by mixing methyl methacrylate monomer with poly(methyl methacrylate) powder in different proportions (20-60 wt-%) of phosphate glass (BV11) in the system 44.5-P2 O5 , 44.5-CaO, 11-Na2 O (mol-%). The curing of these formulations showed a reduction of 10 degrees C in the maximum temperature and an increase of 10 minutes in the setting time although the content of residual monomer in the cured materials was unaltered. The presence of the inorganic particles did not significantly change the glass transition temperature of the cement. Static mechanical properties were evaluated in compression. The compressive yield strength of PM-MA/BV11 cements were in the range 110-118 MPa, superior to those of the control for dry specimens. When the test was conducted with wet specimens, a decrease in strength was observed due to the dissolution of the glasses in the medium, but the composites prepared with 20 or 40 wt-% BV11 had the compressive yield strengths required by the international standard for acrylic bone cements (ISO 5833). The dynamic mechanical properties of the formulation containing 60 wt-% BV11 and the corresponding control were evaluated through a fatigue crack propagation test. The results showed that both formulations followed a Paris-Erdogan model in the stable crack propagation, with no significant differences in the value of the exponent m of the mentioned law. Finally, the presence of the phosphate glasses in the acrylic composite did not change the wear damage of the pair UHMWPE/Ti6Al4V produced by the PMMA formulations. (Journal of Applied Biomaterials & Biomechanics 2003; 1: 48-57).


Ultrastructural variability in the locomotor cortex of the ciliated protozoa, Mytilophilus pacificae.
Mytilophilus pacificae is an endocommensal ciliate found in the mantle cavity of the Pacific Coast mussel Mytilus californianus. In this paper we report our findings on pellicular organization of this species. Transmission and scanning electron microscope examination of the somatic cortex revealed that a number of different types of kinetids, i.e. monokinetids, dikinetids, and polykinetids are found in the locomotor cortex. The type and distribution of the kinetids are described. Surprisingly, the locomotor region was found to be highly variable among individuals with respect to its kinetid distribution; each cell appears to have its own characteristic kinetid pattern. Some cells have mostly monokinetids and dikinetids in their locomotor cortex, while others may have dikinetids and polykinetids but very few monokinetids. In contrast to the locomotor region, the thigmotactic field (a region specialized for attachment) is exclusively composed of dikinetids and shows no heterogeneity. The finding of ultrastructural variability in the locomotor cortex was unexpected since, in the view of the structural conservatism hypothesis, the somatic cortex is seen as a "stable" element. These observations raise new questions with regard to cortical pattern formation in this organism.


Effects of intraruminal infusions of sodium acetate and sodium chloride on silage intake by lactating cows.
Lactating dairy cows prepared with rumen fistulas were fed on grass silage and concentrates and used in two experiments to compare the effects of sodium acetate and sodium chloride infused over 3 h into the rumen on the voluntary intake of silage. Silage intake was depressed in an approximately linear manner by increasing amounts (6-15 mol) of sodium acetate (NaOAc) and 15 mol NaCl had an effect similar to that of 12 mol NaOAc. Sodium in rumen fluid was significantly correlated with intake as was osmolality. 5.5, 7.4 or 9.1 mol of NaOAc significantly depressed silage intake, while 7.4 and 9.1 mol NaCl had significant effects. There were significant negative relationships between intake and the level of NaOAc or NaCl. It is concluded that the major effect of either salt was via the elevation of osmolality of rumen fluid and the relevance to normal control of feeding is discussed.


Metabolism of the TMA group of antigens during the growth cycle of mycobacteria.
The TMA (thermostable macromolecular antigens) group includes A60 of Mycobacterium tuberculosis and A7 of M. leprae, active components of tuberculin and lepromin. We have previously described the purification and composition of A60, and its ability to elicit immune reactions of humoral and cellular type. In the present work, the intracellular and extracellular distribution and composition of A60 have been traced, as a function of the replication cycle, in static surface cultures of M. bovis. In exponentially-growing mycobacteria, most A60 was present in the cytoplasm and had a high protein/polysaccharide ratio: this ratio, as well as the level of cytoplasmic A60, decreased after cessation of cell proliferation. The A60 fraction located within the cell wall increased during the stationary phase, but its protein/polysaccharide ratio underwent minor changes. A release of cellular polypeptides and polysaccharides into the extracellular fluid occurred during the declining and lysing phases: a fraction of it was represented by A60. This explains the practice of old tuberculin preparation by autoclaving filtrates of autolysed mycobacterial cultures. The pattern of an A60-like antigen in shaken homogeneous cultures of M. smegmatis was similar (most antigen present in cytoplasm during growth, increase of the wall fraction in stationary phase, and extracellular release during the declining phase).


Cryotherapy for Barrett's esophagus: Who, how, and why?
Cryotherapy is a noncontact ablation method that has long been used clinically in the treatment of a wide variety of malignant and premalignant diseases. The relative ease of use and unique mechanisms of cellular destruction make cryotherapy particularly attractive for the eradication of dysplastic Barrett's esophagus. Currently, liquid nitrogen and carbon dioxide are the most common cryogens used. Preliminary data with these agents have shown high efficacy in the reversal of dysplastic Barrett mucosa and excellent safety profiles. Intense investigation on cryotherapy ablation of Barrett's esophagus is ongoing.


Xanthogranulomas associated with hematologic malignancy in adulthood.
Although xanthogranulomatosis (XG), defined as multiple xanthogranulomas occurring simultaneously, was originally described in infants and children, a number of adult cases have been reported. Adult XG, which generally presents in the absence of hyperlipidemia, has many similarities to the childhood variant. Among the similarities are reports of the simultaneous development of XG and hematologic disorders. Herein we report a case of XG in a 45-year-old man with B-cell acute lymphoblastic leukemia and review the literature regarding the association of XG and hematologic disorders in adults. We propose that xanthogranulomas seen in children and adults bear many similarities, clinically and histopathologically, and share an association with hematologic malignancies.


Adult intrasellar teratoid tumor.
Intracranial teratomas rarely occur in adults. The most common sites are the pineal followed by the suprasellar or hypothalamic areas. Infrequently, teratomas can arise within the sella turcica and mimic a pituitary adenoma or craniopharyngioma. Teratoid tumors contain tissue arising from only two of the three primitive germ layers, whereas teratomas have elements of all three. The following case illustrates the unusual occurrence of an intrasellar teratoid tumor in a 33-year-old man.


Diabetic cardiomyopathy and oxidative stress: role of antioxidants.
Diabetes has emerged as a major threat to worldwide health. The increasing incidence of diabetes in young individuals is particularly worrisome given that the disease is likely to evolve over a period of years. In 1972, the existence of a diabetic cardiomyopathy was proposed based on the experience with four adult diabetic patients who suffered from congestive heart failure in the absence of discernible coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholism. The exact mechanisms underlying the disease are unknown; however, there is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Hyperglycemiainduced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, which results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. In this review, we provide the emergence of experimental evidence supporting antioxidant supplementation as a cardioprotective intervention in the setting of diabetic cardiomyopathy.


Microcirculation of the fingers in Raynaud's syndrome: (99m)Tc-DTPA imaging.
We investigated the circulatory characteristics of patients suffering of primary and secondary Raynaud's syndrome. We examined 106 patients presenting with the classical symptoms of Raynaud's syndrom (47 primary, 59 secondary) by hand perfusion scintigraphy developed by our Department of Nuclear Medicine. After visual evaluation we analyzed the images semiquantitatively, using the finger to palm ratio. We statistically compared the patients with primary and those with secondary Raynaud's syndrome. By visual evaluation we constated regional perfusion disturbances in 42 from 59 patients with secondary Raynaud's syndrome. However, this was observed in only 3 from 47 patients with the primary form of this disease. This difference was statistically significant (p<0.001). Semiquantitative analysis showed that the finger/palm ratios (FPR) were significantly lower (p<0.05) for the patients with primary Raynaud's syndrome. No differences in the FPR values concerning sex or right and left side. The hand perfusion scintigraphy with (99m)Tc-DTPA is a noninvasive, cost effective diagnostic tool, which objectively reflects the global and regional microcirculatory abnormalities of the hands, and provides quantitative data for follow-up.


Reported practice variation in pediatric pain management: a survey of Canadian pediatric emergency physicians.
To describe pediatric emergency medicine (PEM) physicians' reported pain management practices across Canada and explore factors that facilitate or hinder pain management. This study was a prospective survey of Canadian pediatric emergency physicians. The Pediatric Emergency Research Canada physician database was used to identify participants, and a modified Dillman's Total Design Survey Method was used for recruitment. The survey response rate was 68% (139 of 206). Most physicians were 31 to 50 years old (82%) with PEM training (56%) and had been in practice for less than 10 years (55%). Almost all pain screening in emergency departments (EDs) occurred at triage (97%). Twenty-four percent of physicians noted institutionally mandated pain score documentation. Ibuprofen and acetaminophen were commonly prescribed in the ED for mild to moderate pain (88% and 83%, respectively). Over half of urinary catheterizations (60%) and intravenous (53%) starts were performed without any analgesia. The most common nonpharmacologic interventions used for infants and children were pacifiers and distraction, respectively. Training background and gender of physicians affected the likelihood of using nonpharmacologic interventions. Physicians noted time restraints to be the greatest barrier to optimal pain management (55%) and desired improved access to pain medications (32%), better policies and procedures (30%), and further education (25%). When analgesia was reported as provided, ibuprofen and acetaminophen were most commonly used. Both procedural and presenting pain remained suboptimally managed. There is a substantial evidence practice gap in children's ED pain management, highlighting the need for further knowledge translation strategies and policies to support optimal treatment.


Peritubular capillary C4d deposition in lupus nephritis different from antibody-mediated renal rejection.
C4d deposition in peritubular capillaries (PTC) has been used as a marker of antibody-mediated rejection (AMR). However, PTC C4d deposition is not described in patients with lupus nephritis (LN). C4d deposition in PTC was detected in 455 patients with biopsy proven LN in the present study. Renal tissues from 21 cases of acute AMR served as controls. C4d deposition in PTC was found in 31 patients (6.81%) with LN. Patients with PTC C4d positive showed higher SLEDAI score and higher frequency of hypocomplementemia as compared to C4d negative. The prevalence of ANA, anti-dsDNA, anti-Sm and ACA were higher in C4d positive group, and most of these patients showed the diffuse proliferative glomerular lesion. In contrast with acute AMR, the staining pattern of C4d was granular deposition and the detection of C4d along PTC was accompanied by deposition of IgG and C1q or C3. Electron dense deposition on PTC was observed in most of LN patients. In conclusion, C4d deposition in PTC could be found in a small part of patients with LN. Our study suggested for the first time that C4d positive deposition were close relation with the higher disease activity of LN, and that immune complex formation might be involved in PTC C4d deposition in LN patients, Such PTC C4d deposition is distinct from that of AMR.


Rectangular-shaped expanded phthalocyanines with two central metal atoms.
Expanded phthalocyanine (Pc) congeners with two Mo or W central metal ions and four isoindole ring moieties have been synthesized using normal Pc formation conditions in the presence of urea. The products have been characterized by electrochemistry; mass spectrometry (MS); IR, electron paramagnetic resonance (EPR), NMR, electronic absorption, and magnetic circular dichroism (MCD) spectroscopies; and X-ray analysis. The X-ray structures have rectangular C(2v) symmetry and provide evidence that the central Mo atoms are linked by a single bond and coordinated by two isoindole nitrogen atoms and two nitrogen atoms from the amine moieties. The electronic absorption bands extend into the 1200-1500 nm region. This can be explained using Gouterman's four-orbital theory. The experimental NMR data and theoretical calculations provide evidence for a heteroaromatic 22-π-electron conjugation system for the ring-expanded Pc system, which satisfies Hückel's (4n + 2)π aromaticity.


Virtual reality, telemedicine, web and data processing innovations in medical and psychiatric education and clinical care.
This article highlights technology innovations in psychiatric and medical education, including applications from other fields. The authors review the literature and poll educators and informatics faculty for novel programs relevant to psychiatric education. The introduction of new technologies requires skill at implementation and evaluation to assess the pros and cons. There is a significant body of literature regarding virtual reality and simulation, including assessment of outcomes, but other innovations are not well studied. Innovations, like other uses of technology, require collaboration between parties and integration within the educational framework of an institution.


Visual processes in a hemialexic patient with posterior callosal section.
A patient with surgical section of the splenium and, probably, the posterior end of the truncus of the corpus callosum was studied 9-13 yr after the operation. His reading aloud, reading comprehension and word-matching abilities were moderately disturbed only in the left hemifield. These three disturbances were equally disturbed. The disturbances were not the result of visual disturbances such as tachistoscopic hemiamblyopia or tachistoscopic hemineglect since Landolt's ring matching was intact in the left hemifield as well as in the right. The disturbances were also not due to the disturbance of tachistoscopic word perception since the patient correctly performed same-different judgment of pairs of words in each hemifield. In his reading aloud and reading comprehension disturbances, ideogram words were less impaired than phonogram words, even when the number of letters in the words was the same. His picture naming ability was not disturbed in each hemifield.


Automated selection of the most epithelium-rich areas in gynecologic tumor sections.
The paper describes an image analysis technique for automated selection of the epithelium-rich areas in standard paraffin tissue sections of ovarian and endometrial premalignancies and malignancies. Two staining procedures were evaluated, Feulgen (pararosanilin) and CAM 5.2, demonstrating the presence of cytokeratin 8 and 18; both were counterstained with naphthol yellow. The technique is based on the corresponding image processing method of automated estimation of the percentage of epithelium in interactively selected microscope fields. With the technique, one image is recorded with a filter to demonstrate where epithelium and stroma lie. This filter is chosen according to the type of staining: it is yellow (lambda = 552 nm) for Feulgen and blue (lambda = 470 nm) for anticytokeratin CAM 5.2. When stroma cannot be distinguished from lumina with the green filter or from epithelium with the blue filter, a second image is recorded from the same microscope field, with a blue filter (lambda = 420 nm) for Feulgen and a yellow filter (lambda = 576 nm) for anticytokeratin CAM 5.2. Discrimination between epithelium and stroma is based on the image contrast range and the packing of nuclei in the yellow image and on the automated classification of the gray value histogram peaks in the blue image. For Feulgen stain the method was evaluated on 30 ovarian tumors of the common epithelial types (8 borderline tumors and 22 carcinomas with various degrees of differentiation) and 30 endometrial carcinomas of different grades.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidermal growth factor treatment switches δ-opioid receptor-stimulated extracellular signal-regulated kinases 1 and 2 signaling from an epidermal growth factor to an insulin-like growth factor-1 receptor-dependent mechanism.
δ-Opioid receptor (DOR)-induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) is mediated by the transactivation of epidermal growth factor (EGF) receptors. Here we demonstrate that in stably DOR-expressing human embryonic kidney (HEK) 293 (HEK/DOR) cells, down-regulation of EGF receptors by long-term EGF (0.1 μg for 18 h) treatment, but not by small interfering RNA, results in functional desensitization of EGF (10 ng/ml)-stimulated ERK1/2 signaling. In EGF receptor-desensitized (HEK/DOR(-EGFR)) cells, however, [d-Ala²,d-Leu⁵]enkephalin (1 μM) and etorphine (0.1 μM) retained their ability to stimulate ERK1/2 activation. The newly acquired signal transduction mechanism is insensitive to the EGF receptor blockers 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) and N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-butynamide (CL-387,785), does not involve DOR internalization and activation of the focal adhesion kinase pp125FAK, but requires matrix metalloproteinase-dependent release of soluble growth factors. A supernatant transfer assay in which conditioned growth media of opioid-treated HEK/DOR and HEK/DOR(-EGFR) "donor" cells are used to stimulate ERK1/2 activity in DOR-lacking HEK293 wild type and HEK293(-EGFR) "acceptor" cells revealed that long-term EGF treatment produces a switch in the receptor tyrosine kinase (RTK) system transactivated by opioids. Using microfluidic electrophoresis, chemical inhibitors, phosphorylation-specific antibodies, and EGF receptor-deficient Chinese hamster ovary-K1 cells, we identified the release of an insulin-like growth factor-1 (IGF-1)-like peptide and activation of IGF-1 receptors in HEK/DOR(-EGFR) cells after DOR activation. A similar switch from a neurotrophic tyrosine kinase receptor type 1 to an IGF-1 receptor-dependent ERK1/2 signaling was observed for chronically nerve growth factor-treated neuroblastoma × glioma (NG108-15) cells. These results indicate that transactivation of the dominant RTK system in a given cellular setting may represent a general feature of opioids to maintain mitogenic signaling.


Early treatment of facial trauma.
Early local care of maxillofacial trauma involves identification and diagnosis of the injuries and early consultation with the appropriate specialists (ie, plastic surgeon, ophthalmologist, otolaryngologist, oral and maxillofacial surgeon). Treatment of the injuries should proceed from the inside mucosal surface toward the cutaneous surface of the face, after occlusal patterns have been established and preliminary fixation of maxillary and mandibular fractures has been effected. Closure of through-and-through lacerations from the inside out and establishment of the mandible as a stable plane against which the remainder of the face may be oriented (the "inside out and bottom up" approach) provide an excellent basis for later definitive rehabilitation.