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BACs-on-Beads™ (BoBs™) assay for the genetic evaluation of prenatal samples and products of conception. BACs-on-Beads™ (BoBs™) is a new emerging technology, a modification of comparative genomic hybridization that can be used to detect DNA copy number gains and losses. Here, we describe the application of two different types of BoBs™ assays: (1) Prenatal BoBs (CE-IVD) to detect the most frequent syndromes associated with chromosome microdeletions, as well as the trisomy 13, 18 and 21, and (2) KaryoLite BoBs (RUO) which can detect aneuploidy in all chromosomes by quantifying proximal and terminal regions of each chromosomal arm. The interpretation of the results by BoBsoft™ software is also described. Although BoBs™ may not have the breadth and scope to replace chromosomal microarrays (array comparative genomic hybridization and single nucleotide polymorphism array) in the prenatal setting, particularly when a fetal anomaly has been detected, it is a well suited alternative for FISH or QF-PCR because BoBs™ is comparable, if not superior in terms of cost, turnaround time (TAT) and throughput and accuracy. BoBs™ also has the ability to detect significant fetal mosaicism (≥30% with Prenatal BoBs and ≥50% with KaryoLite BoBs). However, perhaps the greatest strength of this new technology is the fact that unlike FISH or QF-PCR, it has the ability to detect common microdeletion syndromes or additional aneuploidies, both of which may be easily missed despite excellent prenatal sonography. Thus, when BoBs™ is applied in the correct clinical setting and run and analyzed in appropriate laboratories this technique can improve and augment best practices with a personalization of prenatal care.

Conformational Change and Epimerization of Diketopiperazines Containing Proline Residue in Water. In water, diketopiperazines cyclo(L-Pro-L-Xxx) and cyclo(L-Pro-D-Xxx) (Xxx=Phe, Tyr) formed an intramolecular hydrophobic interaction between the main skeleton part and their benzene ring, and both cyclo(L-Pro-L-Xxx) and cyclo(L-Pro-D-Xxx) took a folded conformation. The conformational changes from folded to extended conformation by addition of several deuterated organic solvents (acetone-d6, metanol-d4, dimethyl sulfoxide-d6 (DMSO-d6)) and the temperature rise were investigated using 1H-NMR spectra. The results suggested that the intrarmolecular hydrophobic interaction of cyclo(L-Pro-D-Xxx) formed more strongtly than that of cyclo(L-Pro-L-Xxx). Under a basic condition of 1.0×10-1 mol/L potassium deuteroxide, enolization of O1-C1-C9-H9 moiety of cyclo(L-Pro-L-Xxx) occurred, while that of the O4-C4-C3-H3 moiety did not. Cyclo(L-Pro-L-Xxx) epimerized to cyclo(D-Pro-L-Xxx), while cyclo(L-Pro-D-Xxx) did not change.

Online photoionization mass spectrometric evaluation of catalytic co-pyrolysis of cellulose and polyethylene over HZSM-5. The hydrogen-deficient and oxygen-rich nature of lignocellulosic biomass prohibits effective conversions of biomass to fuels and chemicals via catalytic pyrolysis due to significant coking of the catalysts. Co-feeding of biomass feedstock with hydrogen-rich and oxygen-deficient thermoplastics could improve the process. Herein, thermal and catalytic co-pyrolysis of cellulose and polyethylene (PE) was studied via thermogravimetry combined with an online photoionization time-of-flight mass spectrometry (PI-TOF-MS). No notable synergetic effect was found in the thermal co-pyrolysis process while a considerable synergetic effect was observed during the catalytic co-pyrolysis. In the case of catalytic pyrolysis, co-feeding of cellulose with PE significantly improved the aromatic formation. Detailed reaction intermediates and products were detected by PI-TOF-MS and the process of aromatization could be ascribed to aromatization of small oxygenates and olefins, as well as Diels-Alder reaction and dehydration by HZSM-5. Moreover, this study provides a reliable tool for screening and optimizing of catalytic co-pyrolysis.

Identification of key recombinants in multiplex SMA families. Recent reports have provided evidence that a major gene for autosomal recessive proximal spinal muscular atrophy (SMA) resides in a small genetic interval in bands q12-q13 of chromosome 5, a 4-cM region proximally flanked by D5S125 (EF(TG/AG)n) and distally by MAP1B/D5S112 or a 0.7-cM interval (range 0.1-2.1 cM) flanked by D5S435 proximally and MAP1B/D5S112 distally. We present the identification of key recombinants between SMA and the closest flanking DNA-markers in an analysis of Dutch and Italian SMA families. These crossovers may serve as reference points for new markers in this region and may thus be instrumental in a further refined mapping of the SMA gene. Two markers, D5S351 (I105) and D5S357 (Mfd151), could be mapped distally to SMA in the interval SMA-D5S112.

Does telaprevir possess a direct antidiabetic effect? Hepatitis C virus (HCV) induces insulin resistance, which improves upon viral clearance. Telaprevir is a protease inhibitor effective against HCV genotype 1. We reported a case, whose history suggests that telaprevir may induce some antidiabetic effect independently of its suppression of HCV. A 56-year-old woman with obesity, type 2 diabetes treated with sitagliptin and metformin, and HCV-related cirrhosis was given triple therapy with pegylated interferon-alpha, ribavirin and telaprevir. After 2 weeks of treatment, HCV RNA was no longer detectable but the patient described a pronounced drop in the capillary glucose levels and episodes of hypoglycaemia that compelled her to stop all antidiabetic treatment. One month after stopping telaprevir, she had to resume her antidiabetic treatment, despite a persisting virological response. Despite reaching a sustained virological response, her diabetes progressed. Although the suppression of HCV replication may have played a role in reducing glucose intolerance, the fact that this patient resumed her prior antidiabetic treatment upon completing the telaprevir treatment, while still aviremic, suggests that telaprevir may have an additional antidiabetic effect. Further evidence about the possible role and mechanisms of telaprevir as antidiabetic agent is warranted.

A cure Weibull gamma-frailty survival model and its application to exploring the prognosis factors of neuroblastoma. The log rank test and the Cox regression, or modifications thereof, emphasize the effect of covariates on survival rate parameter. In some cases, cured individuals, i.e., individuals who may not experience the event of interest may exist in the population of interest. In this situation, we may wish to examine the effect of covariates on both survival rate and cured fraction parameters. Motivated by the Japanese neuroblastoma dataset, we consider a cure model that accounted for the effect of covariates on both of the abovementioned parameters. To deal with heterogeneity that is not explained by covariates, as well as individual random heterogeneity, we perform a frailty variable. Moreover, some nested models are fitted to deal with the principle of parsimony. The effect of covariates was then evaluated by the best nested model. From a statistical point of view, we found that the model of analysis is flexible and adequate to describe the abovementioned dataset. From a medical point of view, we confirmed AGE and STAGE to be the most dominant prognosis factor of neuroblastoma. We also conclude that NMYC and FERRITIN are the other most important prognosis factors. The analysis designated that some of the prognosis factors of neuroblastoma probably just affected the median life of patients and some others are the fatal prognosis factor indicated by their effect which significance on both of survival rate and cured fraction parameters. The present model of analysis is also potentially extendable to facilitate other aspects of inferences.

New organo- and amidozinc derivatives of primary amines. Five new zinc derivatives of primary amines [R'ZnN(H)R]2 [R = SiPh3, R' = Me (1), N(SiMe3)2 (4); R = Si(NMe2)3, R' = Me (2), Et (3), N(SiMe3)2 (5)] have been synthesised by reaction of R'2Zn and H2NR. All five species are dimers in which the N-H groups are disposed in a trans manner about a central Zn2N2 ring. In 1 and 4 the coordination at zinc is trigonal planar, while in 2, 3, 5 the zinc is in a distorted tetrahedral environment due to additional Me2N: → Zn coordination from one SiNMe2 group. 5 was found to be generally resistant to NH deprotonation by bases such as MN(SiMe3)2 (M = Li, K) or Zn[N(SiMe3)2]2, but reacts with Sn[N(SiMe3)2]2 to give the tin-free, tetrameric mixed zinc-imido/amido species, [{(Me3Si)2N}{(Me2N)3SiN(H)}{(Me2N)3SiN}Zn2]2 (6) which can be viewed as part of a hexameric Zn6N6 drum which has lost a Zn2N2 ring.

Sailors' scurvy before and after James Lind--a reassessment. Scurvy is a thousand-year-old stereotypical disease characterized by apathy, weakness, easy bruising with tiny or large skin hemorrhages, friable bleeding gums, and swollen legs. Untreated patients may die. In the last five centuries sailors and some ships' doctors used oranges and lemons to cure and prevent scurvy, yet university-trained European physicians with no experience of either the disease or its cure by citrus fruits persisted in reviews of the extensive but conflicting literature. In the 20(th) century scurvy was shown to be due to a deficiency of the essential food factor ascorbic acid. This vitamin C was synthesized, and in adequate quantities it completely prevents and completely cures the disease, which is now rare. The protagonist of this medical history was James Lind. His report of a prospective controlled therapeutic trial in 1747 preceded by a half-century the British Navy's prevention and cure of scurvy by citrus fruits. After lime-juice was unwittingly substituted for lemon juice in about 1860, the disease returned, especially among sailors on polar explorations. In recent decades revisionist historians have challenged normative accounts, including that of scurvy, and the historicity of Lind's trial. It is therefore timely to reassess systematically the strengths and weaknesses of the canonical saga.

The role of urologists in the care of children with cancer. At most institutions, pediatric urologists play a limited role in the care of children with cancer. Pediatric urologists have a unique experience and skill set to contribute to the care of these patients. Interested pediatric urologists should become experts in pediatric urologic oncology and demonstrate this interest by participating in tumor board and relevant academic activities. They should advocate for a collaborative approach with pediatric general surgeons in the surgical management of children with genitourinary as such an approach benefits patient care, contributes to professional development of all parties, and develops relationships that contribute to programmatic development for the institution in oncology and other areas.

Salmonella in Dairy Cattle. As an infectious, contagious pathogen, Salmonella is probably rivaled by only bovine viral diarrhea virus in its ability to cause clinical disease, such as enteritis, septicemia, pneumonia, and reproductive losses. The increasing prevalence of Salmonella, particularly Salmonella Dublin, on dairies presents new challenges to producers and veterinarians. No current discussion of bovine salmonellosis is complete without acknowledging the increasing public health concern. Increasing antimicrobial resistance among enteric pathogens brings the use of antimicrobials by veterinarians and producers under ever stricter scrutiny. This article provides a comprehensive review of Salmonella etiology, prevalence, pathogenesis, diagnostics, treatment, and control.

Radioactive antigen suicide of an anti-DNP (2,4-dinitrophenyl) clone. I. Recovery and escape from clonal dominance by suicide resistant precursors. An anti-2,4-dinitrophenyl (DNP) clone line, maintained in vivo by serial passage through irradiated syngeneic recipients, was exposed to 125I-labeled dinitrophenylated L-Tyr-L-Glu-L-Lys copolymer antigen of high specific activity. Hapten-specific suicide was obtained, though with more difficulty than for a heterogeneous secondary response. The recovery was followed and was shown to occur either with the same clones or with new clones, depending on conditions. After suicide at a late passage of the clone, recovery by new clones occured very rapidly. This indicated that there was a background heterogeneity in the clone system, normally suppressed by clonal dominance and that some of these new clones were suicide resistant.

Molecular diagnostic techniques for the clinical evaluation of gliomas. Newly developed molecular techniques have been integrated into the routine assessment of gliomas in some laboratories. These tests serve to complement the subjective nature of morphologic analysis. Such strategies add useful information regarding pathogenicity, patient survival, and potential response to treatment. As we learn more about the molecular characteristics of these tumors, this information will provide the basis for the development of specific, targeted therapies. This review will describe the background, methods, clinical utility, and strengths and weaknesses of several molecular approaches, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), loss of heterozygosity (LOH)-testing, and nucleic acid sequencing, that are currently being employed in the diagnosis and evaluation of glial tumors.

Monitoring of Human Uterus Transplantation With Cervical Biopsies: A Provisional Scoring System for Rejection. Until now, absolute uterine factor infertility has been the major untreatable form of female infertility. Uterus transplantation has recently proven to be the first successful treatment for absolute uterine factor infertility, with demonstration of live births. In this study, live donation uterus transplantation was performed in nine women. In total, 163 cervical biopsies (149 protocol, 14 follow-up) were taken to detect histopathological signs of rejection. Based on experience from animal experiments, we used a three-grade scoring system to evaluate biopsies systematically. Nine episodes of rejection were diagnosed in five patients: grade 1 in six episodes, grade 2 in two episodes, and grade 3 in one episode. Treatment decisions were based on histopathology, and all rejection episodes were reversed after treatment. The biopsies were reviewed retrospectively, and immunohistochemistry was performed to characterize the inflammatory infiltrates. A borderline category was introduced to avoid overtreatment of patients. Based on our review of all biopsies, we put forward a simple grading system for monitoring of rejection and to guide immunosuppressive treatment in uterus transplantation.

The leader's use of metaphor in group psychotherapy. This article discusses the leader's use of metaphor in outpatient, psychodynamic group psychotherapy. Four clinical examples are provided that illustrate how the phase of group development informs the leader's use of metaphor. Therapeutic features and uses of metaphor include (1) the development of ego skills that transform passivity into activity and foster the examination of unhealthy norms; (2) the modulation and rechanneling of potentially destructive affect and the intensification of affect that is denied, minimized, or avoided; (3) the creation of a verbal play space in which shared group language evolves; (4) and the provision of various levels of concreteness and abstraction as well as differing perspectives. Abuses of metaphorical interventions are discussed.

Brain excitability and long latency muscular arm responses: non-invasive evaluation in healthy and parkinsonian subjects. Thirty healthy and 35 volunteers affected by Parkinson's disease (PD) were examined. Long latency responses (LLRs) and short latency somatosensory evoked potentials (SEPs) after median nerve stimulation were respectively recorded from forearm flexor muscles, and from 19 scalp electrodes, during relaxation (condition 1), light and maximal muscle contraction (conditions 2 and 3). Linear interpolation of SEPs was performed to produce isopotential colour maps. Latencies and amplitudes of the V1-V2 component in LLR, as well as of parietal, central and frontal scalp SEPs were analysed in the 3 experimental conditions. Highly significant inverse correlation matched the frontal SEP to the LLR V2 component amplitudes, both in healthy and in PD subjects. However, the V2 component--which in the former group was reliably identifiable only in condition 3--was presented in conditions 1 and 2 in a high percentage of PD subjects who also showed an abnormally reduced frontal SEP during complete relaxation. Excitability changes of brain motor areas induced by a sensory input were tested as follows: the motor cortex was transcranially stimulated (TCS) by magnetic pulses with an intensity 10% below (A) or above (B) the threshold for twitch elicitation during complete relaxation of forearm muscles; TCS was randomly preceded (range 14-32 msec) by a shock to the median or ulnar nerve at the elbow with identical characteristics as for LLR elicitation. An initial epoch of 'inhibition' followed by a peak of 'facilitation' of the amplitude of motor responses to TCS was observed when conditioning stimuli to the median nerve preceded TCS by 14-20 and by 24-32 msec, respectively. Contrary to normals, conditioning stimulation of the median nerve did not significantly influence the excitability threshold to TCS in those parkinsonians with depressed frontal N30.

Promoting older adults' well-being through Internet training and use. The purpose of the current research was to test the psychological impact of learning how to use computers and the Internet in old age, hypothesizing that such activities would contribute to seniors' well-being and personal sense of empowerment. Employing a quasi-experimental research design, we offered a course, conducted in small groups, in computer operation and Internet browsing to 22 older adults (mean age of 80) who went to day-care centers for the elderly or resided in nursing homes. A comparison group of 26 participants (similar in all major respects) was engaged in other activities. Both groups were administered measures of physical functioning, life satisfaction, depression, loneliness and self-control at pre- and post-intervention four months later. Individual semi-structured interviews were conducted with participants who finished the computer course. ANCOVA was employed for controlling the effects of control variables and pre-intervention differences on participants who completed the activities. Results showed a significant improvement among participants in the intervention group in all measures except physical functioning, whereas deterioration in all measures was detected in the comparison group. Computer and Internet use seems to contribute to older adults' well-being and sense of empowerment by affecting their interpersonal interactions, promoting their cognitive functioning and contributing to their experience of control and independence.

Fluctuation of serum complement levels in children with neuroblastoma. Serum samples from eleven children with neuroblastoma were drawn at diagnosis and again every 15 days or a month after the beginning of treatment over the course of 17 months observation. Twenty healthy children of the same age with no appreciable clinical manifestation were also studied as controls. Investigations included quantitative serum complement levels (total complement hemolytic activity, C3 and C4), anticomplementary serum activity and urine catecholamine levels (VMA and HVA). Complement levels of tumor patients were significantly higher than those of healthy subjects, but fluctuations were seen at different stages of the disease; patients at admission with active tumors or tumor recurrence had higher complement levels than those of patients in remission. Temporary recurrences of the disease were usually accompanied by fluctuations of urinary catecholamines, serum complement levels (mainly C3) and anticomplementary serum activity. At the terminal phase of the disease a drop in complement levels was usually seen, while urinary catecholamines were progressively increasing.

Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component delta9-tetrahydrocannabinol (delta9-THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats. To determine the effects of pretreatment with delta9-THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of delta9-THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB1 receptor antagonist, SR141716, to reverse the effects of delta9-THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of delta9-THC.or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with delta9-THC (0.25-1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle. delta9-THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own. These results are the first to show that both delta9-THC, which acts on both CB 1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning.

Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry. This study identified variables associated with increased risk of atrial fibrillation in people with type 1 diabetes. We performed a cohort study of people with type 1 diabetes from the Swedish National Diabetes Registry followed up between 1 January 2001 and 31 December 2013. Median follow-up was 9.7 years (interquartile range 5.2-13.0). The association between potential risk factors and incident atrial fibrillation was investigated using adjusted Cox regression. To compare the impact of each risk factor, the gradient of risk per 1 SD was estimated. In this cohort of 36,258 patients with type 1 diabetes, 749 developed atrial fibrillation during follow-up. Older age, male sex, renal complications, increased BMI and HbA1c, coronary artery disease, heart failure, and heart valve disease increased the risk of atrial fibrillation. Age, signs of renal dysfunction with macroalbuminuria, and decreasing estimated glomerular filtration rate were associated with the highest gradient of risk for atrial fibrillation. High blood pressure, severe obesity (BMI >35 kg/m2), and elevated levels of HbA1c (>9.6%) were associated with increased risk, but no associations were found with hyperlipidemia or smoking. The most prominent risk factors for atrial fibrillation in people with type 1 diabetes were older age, cardiovascular comorbidities, and renal complications, while obesity, hypertension, and hyperglycemia had more modest affects.

[The survival indices of patients with stage IV gastric cancer treated by polyplatilen]. The survival indices of patients suffering gastric cancer stage IV in application of cytostatic preparation polyplatilen were studied up. The most expedient mode of treatment was suggested the conduction of no less than 2 courses of monochemotherapy. As a result, one year had survived (22.53 +/- 4.68)% patients, three years--(7.54 +/- 3.16)%, five years--(4.43 +/- 2.46)%.

Numerical study of the effects of Planetary Boundary Layer structure on the pollutant dispersion within built-up areas. The effects of different Planetary Boundary Layer (PBL) structures on pollutant dispersion processes within two idealized street canyon configurations and a realistic urban area were numerically examined by a Computational Fluid Dynamics (CFD) model. The boundary conditions of different PBL structures/conditions were provided by simulations of the Weather Researching and Forecasting model. The simulated results of the idealized 2D and 3D street canyon experiments showed that the increment of PBL instability favored the downward transport of momentum from the upper flow above the roof to the pedestrian level within the street canyon. As a result, the flow and turbulent fields within the street canyon under the more unstable PBL condition are stronger. Therefore, more pollutants within the street canyon would be removed by the stronger advection and turbulent diffusion processes under the unstable PBL condition. On the contrary, more pollutants would be concentrated in the street canyon under the stable PBL condition. In addition, the simulations of the realistic building cluster experiments showed that the density of buildings was a crucial factor determining the dynamic effects of the PBL structure on the flow patterns. The momentum field within a denser building configuration was mostly transported from the upper flow, and was more sensitive to the PBL structures than that of the sparser building configuration. Finally, it was recommended to use the Mellor-Yamada-Nakanishi-Niino (MYNN) PBL scheme, which can explicitly output the needed turbulent variables, to provide the boundary conditions to the CFD simulation.

Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF. Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) are small proteins, which are related both by sequence and by in vitro enzyme activity. Here we show that the gene for DDT in human and mouse is identical in exon structure to MIF. Both genes have two introns that are located at equivalent positions, relative to a twofold repeat in protein structure. Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this superfamily exist in nematodes and a plant, and a related gene in C. elegans shares an intron position with MIF and DDT. In addition to similarities in structure, the genes for DDT and MIF are closely linked on human Chromosome (Chr) 22 and mouse Chr 10.

Studies of plasmacytoid dendritic cell dynamics in simian immunodeficiency virus infection of nonhuman primates provide insights into HIV pathogenesis. Plasmacytoid dendritic cells (pDC) play a key role in antiviral immunity through their immense capacity to produce type I interferons (IFN) and other cytokines and through induction of antigen-specific T cell responses. Several reports have documented decreased numbers and reduced function of pDC in the circulation of HIV patients associated with progression to disease, indicating that pDC are likely to be important in control of HIV infection. The mechanism of pDC loss has not been determined and is difficult to address in natural infection of humans. As highlighted in this brief review, the study of pDC dynamics in simian immunodeficiency virus (SIV) infection of nonhuman primates paves the way to understanding the complex biology of this important innate system cell in HIV and other viral infections.

Diagnosis and treatment of metachronous cancers in the esophagus and the head and neck region. The esophagus and the head and neck region, both having the squamous epithelium, are thought to be subject to the same carcinogenic factors. This report discusses the diagnosis and treatment of secondary cancer detected following the treatment of primary cancer in 21 patients who had metachronous cancer comprising esophageal cancer and head and neck cancer. The secondary cancer was already advanced when detected despite the fact that almost all patients were followed up regularly at the outpatient clinic of the facility where the primary cancer was treated. Although surgical treatment of the secondary cancer was similar to that of the usual primary cancer, the prognosis for the former was poor, indicating that the prognosis tends to be determined by the disease stage of the secondary cancer. Early detection of the secondary cancer requires esophagoscopy using the iodine dye method or close examination of the head and neck region at an otolaryngologic outpatient clinic at the time of treatment of the primary cancer and thereafter at 6- to 12-month intervals.

Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Adrenocorticotropin (ACTH) and cortisol in plasma were measured weekly from early in gestation through delivery in five women whose pregnancies were normal. During the twelfth week of pregnancy, the concentration of ACTH in plasma of blood samples obtained between 0800 and 0900 hours was 23 +/- 4.6 pg/ml (mean and SEM) and rose progressively to 59 +/- 16 pg/ml at 37 weeks. The levels of ACTH in plasma were significantly lower throughout pregnancy than those found in nonpregnant women. During labor and delivery, ACTH levels rose strikingly to values of 301 +/- 137 pg/ml. As pregnancy advanced, the concentration of cortisol in plasma increased progressively from 149 +/- 34 ng/ml (mean and SEM) at 12 weeks to 352 +/- 90 ng/ml at 26 weeks' gestation but changed minimally thereafter until labor commenced, during which values of 706 +/- 148 ng/ml were achieved. ACTH and cortisol secretory patterns over a 24-hour period were also investigated in one subject during each trimester of pregnancy. Diurnal variations were observed that were qualitatively similar to those seen in nonpregnant women. From the results of these studies, we conclude that ACTH levels are suppressed in plasma of normal pregnant women but are higher in late pregnancy than in early pregnancy. The rise in plasma ACTH concentrations, as pregnancy advances, in spite of increasing levels of plasma cortisol, estrogens, and progesterone, is suggestive of the possibility that a source of ACTH exists that is not subject to negative feedback control, that the clearance of free cortisol increases as pregnancy advances, or that there is an alteration in the metabolism of the ACTH precursor protein produced by the pituitary and/or placenta.

Visualization of early events in tumor formation of eGFP-transfected rat colon cancer cells in liver. Colon cancer preferentially metastasizes to the liver. To determine cellular backgrounds of this preference, we generated an enhanced green fluorescent protein (eGFP)-expressing rat adenocarcinoma cell line (CC531s) that forms metastases in rat liver after administration to the portal vein. Intravital videomicroscopy (IVVM) was used to visualize early events in the development of tumors in livers of live animals from the time of injection of the cancer cells up to 4 days afterward. Based on information obtained with IVVM, tissue areas were selected for further analysis using confocal laser scanning microscopy (CLSM), electron microscopy (EM), and electron tomography. It was shown that initial arrest of colon cancer cells in sinusoids of the liver was due to size restriction. Adhesion of cancer cells to endothelial cells was never found. Instead, endothelial cells retracted rapidly and interactions were observed only between cancer cells and hepatocytes. Tumors developed exclusively intravascularly during the first 4 days. In conclusion, initial steps in the classic metastatic cascade such as adhesion to endothelium and extravasation are not essential for colon cancer metastasis in liver.

Proteome analysis of human stomach tissue: separation of soluble proteins by two-dimensional polyacrylamide gel electrophoresis and identification by mass spectrometry. Two-dimensional gel electrophoresis (2-DE) maps for human stomach tissue proteins have been prepared by displaying the protein components of the tissue by 2-DE and identifying them using mass spectrometry. This will enable us to present an overview of the proteins expressed in human stomach tissues and lays the basis for subsequent comparative proteome analysis studies with gastric diseases such as gastric cancer. In this study, 2-DE maps of soluble fraction proteins were prepared on two gel images with partially overlapping pH ranges of 4-7 and 6-9. On the gels covering pH 4-7 and pH 6-9, about 900 and 600 protein spots were detected by silver staining, respectively. For protein identification, proteins spots on micropreparative gels stained with colloidal Coomassie Brilliant Blue G-250 were excised, digested in-gel with trypsin, and analyzed by peptide mass fingerprinting with delayed extraction-matrix assisted laser desorption/ionization-mass spectrometry (DE-MALDI-MS). In all, 243 protein spots (168 spots in acidic map and 75 spots in basic map) corresponding to 136 different proteins were identified. Besides these principal maps, overview maps (displayed on pH 3-10 gels) for total homogenate and soluble fraction, are also presented with some identifications mapped on them. Based on the 2-DE maps presented in this study, a 2-DE database for human stomach tissue proteome has been constructed and is available at http://proteome.gsnu.ac.kr/DB/2DPAGE/Stomach/. The 2-DE maps and the database resulting from this study will serve important resources for subsequent proteomic studies for analyzing the normal protein variability in healthy tissues and specific protein variations in diseased tissues.

[New standards for catecholamine therapy in cardiopulmonary resuscitation? Results of a modified application in a resuscitation model]. Using a standardized porcine CPR-model (3 min of cardiac arrest induced by ventricular fibrillation) the effects of epinephrine (10 micrograms/kg iv, 50 micrograms/kg iv, 100 micrograms/kg endobronchially, eb) and norepinephrine (10 micrograms/kg iv, 100 micrograms/kg eb) on resuscitability and early post-resuscitation haemodynamics were compared. Success rate was 100% after epinephrine 10 micrograms/kg iv and 100 micrograms/kg eb, 75% after epinephrine 50 micrograms/kg iv, 80% after norepinephrine iv and 60% after norepinephrine eb. In an unmedicated control group 50% of all animals were successfully resuscitated. Early post-resuscitation haemodynamics in the high dose epinephrine group were characterized by tachycardia and progredient myocardial failure, while in the norepinephrine groups a low cardiac output was accompanied by small cardiac stroke volumes and an increased vascular resistance. It is concluded that iv or eb epinephrine given in standard doses has still to be considered as the drug therapy of choice after short term cardiac arrest or in the presence of ventricular fibrillation. Before different drugs or dosing strategies can be recommended, further experimental and clinical validation is required.

Disproportionation of thermoelectric bismuth telluride nanowires as a result of the annealing process. P-type thermoelectric bismuth telluride nanowires were fabricated by pulsed electrodeposition in anodic aluminium oxide (AAO) membranes. Subsequently, the nanowires were annealed at 423, 523 and 673 K in an inert atmosphere for 4 h. With increasing temperature, it was observed that the Te compound incongruently sublimates due to its high vapor pressure, leading to disproportionation (from Bi(2)Te(3) to Bi(4)Te(3)via Bi(4)Te(5)). The crystalline structure of the nanowires was then investigated using XRD and SAED, with nanowire compositions investigated using an EDX attached to a TEM. The crystallinity of the nanowires was found to be enhanced with increased annealing temperature, and nanowires annealed at 673 K were stably maintained in the Bi(4)Te(3) phase. Additionally, the Seebeck coefficient was determined and the thermopower of nanowires annealed at a temperature of 423 K was shown to be slightly enhanced. Significantly suppressed Seebeck values for annealing temperatures of 523 K and 673 K were also observed.

Seventy-four defibrillations for sotalol-induced torsades de pointes. We report a patient with sotalol-induced torsades de pointes episodes that did not respond to magnesium and amiodarone. Electrical defibrillation totaling 15,120 joules had to be applied. However, torsades de pointes episodes could be brought under control only after the induction of general anesthesia with pentothal.

[Secreting parathyroid carcinoma. Apropos of a case]. Parathyroid carcinoma is rare and hits diagnosis often difficult. A case is reported, remarkable by the age of the patient (17 years), and the main peculiarities of the disease are reviewed: frequency of complete bone syndrome, palpable tumour of the neck, calcemia more than 140 mg/l, occurrence of recurrent palsy; relapsing course, death being dependent on hypercalcemia rather than metastasis; median survival time about five years, non influenced by chemotherapy. Ultrastructural study, previously realized in about thirty cases, is specially evaluated: it seems able to concur on anatomopathologic diagnosis, when assertion of malignancy is difficult.

People, pigs and parasites in New Guinea: relational contexts and epidemiological possibilities. Within Papua New Guinea the relationship people have with their pigs varies between societies. These differences arise in the earliest phase of rearing piglets and result in domestic animals whose primary attachments are to other pigs, to places or to people. For Papua New Guineans, different pig management regimes fulfill ecological and social needs. In addition, however, the ways in which pigs are raised and managed, and the presence or absence of a local population of wild pigs, have consequences for the exposure of both domestic pigs and people to parasites that they may host. Effective control of disease-inducing parasites should be attentive to society-specific relationships between people and their pigs.

A Highly Stable and Insensitive Fused Triazolo-Triazine Explosive (TTX). A fused-ring conjugated energetic molecule, 4-amino-3,7-dinitro-[1,2,4]triazolo[5,1-c] [1,2,4]triazine (TTX), has been synthesized in good yield in a two-step process starting from the known 5-amino-3-nitro-1H-1,2,4-triazole (ANTA). Characterization of TTX shows that it possesses energetic properties approaching those of 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX), but with a higher thermal stability and lower sensitivity towards impact and friction.

Ineffectiveness of rabies vaccination alone for post-exposure protection against rabies infection in animal models. Most reported vaccination failures among rabies-exposed patients were due to fail to timely co-administer rabies immunoglobulin (RIG). Considering that such protection failure might be caused by low antigen titers in the vaccine, scientists improved antigen titers to 4.0 IU or even higher, yet the failure remained. Therefore, it becomes vital to develop more efficacious vaccine against rabies. In our evaluation of a novel PIKA rabies vaccine, we used multiple animal models (beagles, golden hamsters and Kunming mice) to mimic post-exposure scenarios. All animals were challenged with wild-type rabies virus, followed by vaccination with either rabies vaccines commercially available or PIKA rabies vaccines. As 100% of animals survived after administration of traditional rabies vaccines and rabies immunoglobulin, 80% of animals survived with rabies immunoglobulin alone. Strikingly, animals receiving traditional rabies vaccines alone showed extremely low survival rates, indicating insignificant benefit for exposed animals (p > 0.05, compared to unvaccinated control groups). To the contrary, 40-80% of animals receiving the experimental PIKA rabies vaccines were protected (p < 0.05, compared to unvaccinated control groups). If the above results are fully confirmed, we may conclude that currently as high as 99% of post-exposure patients who are seeking protection against rabies, but only receiving rabies vaccination, could be meaningless.

Varicella in Chimpanzees. Two chimpanzees were inoculated subcutaneously with the wild-type Oka strain of varicellazoster virus (VZV). Viral DNA was detected in peripheral blood mononuclear cells of both animals using the polymerase chain reaction (PCR) shortly after inoculation. Ten days after inoculation both animals developed an erythematous, papular rash near the site of inoculation that extended into the adjacent dermatome. Viral DNA was found by PCR in a skin biopsy from one of the animals at the time of the rash. While only two animals were studied, the development of a mild form of varicella in chimpanzees indicates that these animals might be useful for molecular studies of viral genes involved in virulence or attenuation of VZV.

Secondary prevention through cardiac rehabilitation: from knowledge to implementation. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation. Increasing awareness of the importance of cardiovascular prevention is not yet matched by the resources and actions within health care systems. Recent publication of the European Commission's European Heart Health Charter in 2008 prompts a review of the role of cardiac rehabilitation (CR) to cardiovascular health outcomes. Secondary prevention through exercise-based CR is the intervention with the best scientific evidence to contribute to decrease morbidity and mortality in coronary artery disease, in particular after myocardial infarction but also incorporating cardiac interventions and chronic stable heart failure. The present position paper aims to provide the practical recommendations on the core components and goals of CR intervention in different cardiovascular conditions, to assist in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of CR. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, national or individual centre level, need to consider where and how structured programmes of CR can be delivered to all patients eligible. Thus a novel, disease-oriented document has been generated, where all components of CR for cardiovascular conditions have been revised, presenting both well-established and controversial aspects. A general table applicable to all cardiovascular conditions and specific tables for each clinical disease have been created and commented.

Negative chronotropic and inotropic effects of U-92032, a novel T-type Ca2+ channel blocker, on the isolated, blood-perfused dog atrium. We investigated the effects of U-92032 ((7-((bis-4-fluorophenyl) methyl)-1-piperazinyl)-2-2(2-hydroxyethylamino)-4-(1-methylethyl)- 2,4, 6-cycloheptatrien-1-one), a novel T-type Ca2+ channel blocker, on sinus rate and atrial contractile force in the isolated, blood-perfused atrium of the dog. U-92032 (1 to 300 nmol) induced negative chronotropic and inotropic responses in a dose-dependent manner, and the percentage decrease in sinus rate was less than that in atrial contractile force. Atropine did not affect the negative responses to U-92032. These results suggest that U-92032, a T-type Ca2+ channel blocker, simultaneously decreases the sinus rate and atrial force as do L-type Ca2+ channel blockers in the isolated dog atrium.

Tuning the structure and parameters of a neural network by using hybrid Taguchi-genetic algorithm. In this paper, a hybrid Taguchi-genetic algorithm (HTGA) is applied to solve the problem of tuning both network structure and parameters of a feedforward neural network. The HTGA approach is a method of combining the traditional genetic algorithm (TGA), which has a powerful global exploration capability, with the Taguchi method, which can exploit the optimum offspring. The Taguchi method is inserted between crossover and mutation operations of a TGA. Then, the systematic reasoning ability of the Taguchi method is incorporated in the crossover operations to select the better genes to achieve crossover, and consequently enhance the genetic algorithms. Therefore, the HTGA approach can be more robust, statistically sound, and quickly convergent. First, the authors evaluate the performance of the presented HTGA approach by studying some global numerical optimization problems. Then, the presented HTGA approach is effectively applied to solve three examples on forecasting the sunspot numbers, tuning the associative memory, and solving the XOR problem. The numbers of hidden nodes and the links of the feedforward neural network are chosen by increasing them from small numbers until the learning performance is good enough. As a result, a partially connected feedforward neural network can be obtained after tuning. This implies that the cost of implementation of the neural network can be reduced. In these studied problems of tuning both network structure and parameters of a feedforward neural network, there are many parameters and numerous local optima so that these studied problems are challenging enough for evaluating the performances of any proposed GA-based approaches. The computational experiments show that the presented HTGA approach can obtain better results than the existing method reported recently in the literature.

[Demethylation pattern of PD-1 gene in promoter region is associated with the PD-1 expression on peripheral blood mononuclear cells in chronic hepatitis B patients]. To observe the expression variations and influencing factors of programmed death one (PD-1) and DNA demethylation of PD-1 promoter on peripheral blood mononuclear cells (PBMCs) in chronic hepatitis B (CHB) patients and further investigate the relationship between the demethylation pattern of PD-1 gene in promoter region and the PD-1 expression on PBMC in CHB patients. A total of 162 subjects, including 144 CHB patients and 18 healthy blood donors, were enrolled. The expression of PD-1 on PBMCs was detected by flow cytometry. And the serum HBV markers, HBV DNA load and liver function were also measured. DNA of PBMCs was treated with sodium bisulfite; the PD-1 promoter fragments were amplified by polymerase chain reaction (PCR) and then transformed into Escherichia coli. Positive clones were selected for sequencing and the methylation status of fragments of PD-1 promoter was examined. With the PD-1 expression in normal controls (10.8% ± 4.4%) as a baseline level, the expression of PD-1 in CHB patients significantly increased. In CHB patients, the serum expression of PD-1 in PBMCs from patients with positive HBeAg (27.1% ± 18.4%) was much higher than that from those with negative HBeAg (19.6% ± 15.6%). And the expression level of PD-1 was not correlated with serum HBV DNA load and serum level of alanine aminotransferase. The results of bisulfite genomic sequencing showed that demethylation probability of some CG points in PD-1 promoter region (-601, -553, -538, -483, -463, -317 bp) were significantly correlated with PD-1 expression level (P < 0.05). The demethylation pattern of PD-1 gene in promoter region is associated with the PD-1 expression on PBMC in CHB patients.

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide-38 inhibit IL-10 production in murine T lymphocytes. Vasoactive intestinal peptide (VIP), a neuropeptide present in the peptidergic innervation of lymphoid organs and expressed in thymocytes and peripheral lymphocytes has been previously reported to modulate cytokine expression in T lymphocytes. In this study, we investigated the effects of VIP and of the structurally related neuropeptide PACAP-38 on the expression of IL-10 in murine lymphocyte cultures. Both neuropeptides inhibit IL-10 production by spleen cells or thymocytes activated via the TCR-associated CD3 complex in a similar dose-response manner. The inhibition is specific, presumably mediated through the VIP-R1, and maximum inhibitory levels are achieved within the first 5 to 15 min of exposure to VIP or PACAP-38. CD4+ T cells function as direct cellular targets for the two neuropeptides. The fact that VIP, PACAP-38, and forskolin, all known cAMP inducers, also inhibit IL-10 production, suggests the participation of cAMP in signal transduction. VIP and PACAP-38 regulate transcriptional expression of IL-10, since IL-10 steady state mRNA levels are significantly reduced by treatment with the two neuropeptides. These results expand the range of neuroendocrine-regulated cytokines and support the idea that neuropeptides such as VIP and PACAP, which are released or produced in the local lymphoid microenvironment and specifically modulate the expression of various cytokines, may participate in the intricate cytokine network controlling local immune responses.

Biotransformation of carcinogenic arylamines and arylamides by human placenta. Placental biotransformation reactions may modulate the effect a xenobiotic has on the developing fetus. However, in spite of the critical role the placenta plays in supporting fetal life, little is known about the pharmacology and toxicology of the human placenta. Our laboratory has previously characterized the N-acetylation activity of the human term placenta. This activity is predominantly attributable to the NAT1 form of arylamine N-acetyltransferase (NAT). Although acetylation is generally thought to be a detoxifying reaction, both N-acetylation and deacetylation reactions play an important role in the activation of carcinogenic arylamines to their reactive and toxic forms. In the current study we characterized the activity of human placental NAT and deacetylase toward the carcinogenic arylamine, 2-aminofluorene (AF) and its acetylated metabolite, 2-acetylaminofluorene (AAF). 2-Aminofluorene is a synthetic, prototype carcinogenic arylamine compound, and its metabolism has been extensively studied in the laboratory. Our data show that the affinity (Km = 24.2 +/- 1.66 mumol/L; mean +/- SEM, n = 6) and maximal velocity (Vmax = 4.29 +/- 0.33 nmol/min/mg; mean +/- SEM, n = 6) of AF N-acetylation by human placenta are similar to those in human liver. The deacetylation of AAF to AF by placental microsomes may be catalyzed by a carboxylesterase. However, our studies with inhibitors reveal that the characteristics of human placental deacetylation activity differ from that of human liver.(ABSTRACT TRUNCATED AT 250 WORDS)

IL-12 induces autophagy in human breast cancer cells through AMPK and the PI3K/Akt pathway. Interleukin-12 (IL-12) serves an important role in immune responses and antitumor activity. The study of the association between autophagy and cancer cells remains controversial. The present study aimed to investigate the effect of IL‑12 on autophagy in the human breast cancer cell lines MDA‑MB‑231 and MCF‑7, and the possible molecular mechanism. Breast cancer cells were treated with different concentrations of recombinant IL‑12. The expression of the autophagy-associated protein microtubule‑associated protein light chain 3 (LC3) was determined using western blot analysis, fluorescein isothiocyanate‑labeled LC3 was detected using fluorescence microscopy and autophagosomes were examined using transmission electron microscopy. Alterations in the phosphatidylinositol 3‑kinase/Rac‑α serine/threonine protein kinase (PI3K/Akt) and 5'‑AMP‑activated protein kinase subunit β‑1 (AMPK) pathways, in addition to pathway‑associated proteins, were detected using western blotting, following treatment with IL‑12 and pretreatment with the PI3K/Akt activator insulin‑like growth factor or the AMPK inhibitor compound C. It was observed that IL‑12 was able to upregulate the expression of the autophagy‑associated protein LC3 in a concentration‑ and time‑dependent manner, and induce the formation of autophagosomes in the two cell lines, and that the above effects involved the inhibition of the PI3K/Akt signaling pathway and the activation of the AMPK signaling pathway.

A family with 2 different hereditary diseases leading to early cardiac involvement. Autosomal dominant limb-girdle muscular dystrophy type 1B (LGMD 1B) is caused by mutations in the LMNA gene. The disorder is associated with potentially fatal cardiac arrhythmias. Brugada syndrome (BS) is an autosomal dominant channelopathy linked to mutations in the SCN5A gene. BS is also associated with increased risk of sudden cardiac death. We reported a family in which a novel gene mutation, a missense mutation (c.80C>T) in exon 1 of the LMNA gene causing autosomal dominant LGMD 1B, occurred in association with SCN5A gene mutation causing BS. After the diagnosis of BS, 4 patients received implantable cardioverter-defibrillator therapy. Eight members of the family deceased at early age before the diagnosis. We emphasized the co-occurrence of 2 different conditions predisposing to sudden cardiac death: LGMD 1B caused by a novel mutation and BS.

The use of estimated glomerular filtration rate for dose adjustment of medications in the elderly. Adverse drug effects as a consequence of inappropriate dosage are a common cause of hospitalization among the elderly. Older individuals are at a particular risk of overdosing because their kidney function decreases with advancing age and the elderly are often prescribed several pharmaceutical drugs. In addition, serum creatinine levels decrease owing to a reduction in muscle mass with age. Therefore, drug dosing based on the serum creatinine level only, instead of using assessment of the renal function, may result in overdosing of frail elderly patients. Renal function, i.e., the glomerular filtration rate can, with simple formulas, be estimated from analysis of creatinine and/or plasma cystatin C (eGFR). Such estimations performed with modern and validated formulas, as a rule present renal function normalized to the body surface area (mL/min/1.73 m(2)). A good estimation of how much the normal dosing interval should be prolonged, or the dose reduced, to obtain a desired plasma concentration of drugs that are mainly eliminated by glomerular filtration can be obtained by calculating the ratio between the patient's eGFR and the normal renal function (about 90-125 mL/min/1.73 m(2)). Increased knowledge and use of eGFR by prescribing physicians will reduce the risk of overdosing drugs in the elderly.

rIL-2 in metastatic soft tissue sarcomas refractory to chemotherapy: response and enhancement of further chemosensitivity. Chemotherapy (CT) in advanced and metastatic soft tissue sarcoma (STS) has a reported response rate of 17 to 30%, with a median survival of 30 months. Experimental and clinical studies have demonstrated some response with high-dose intravenous recombinant Interleukin-2 (r-IL2). We report a retrospective analysis of twelve patients with metastatic or locally evolutive STS who received high-dose rIL-2 immunotherapy: all patients were pre-treated with CT and were non responsive. All of these patients developed usual severe toxicity. One patient achieved a partial response with rIL-2 with more than 75% regression of lung metastases. All patients received CT post rIL-2 and 2 of them achieved a further response: 1 of them had a complete response (CR), and one had a partial response (PR). These results suggest that rIL-2 has a relatively low efficacy in patients with STS but that some of these patients can be, after rIL-2, responders to CT despite previous resistance.

Trapping sheep blowflies using bait-bins. A bait-bin designed to attract and kill sheep blowflies is described. It is composed of a garbage bin plus lid, attractant and insecticide-treated offal. Fly entry holes are covered with differentiator wire to increase selectivity of kill. Placing bait-bins in preferred habitats of blowflies to optimise kill is outlined and temporal insecticide strategies to increase effectiveness of kill and reduce blowfly resistance are suggested. Preliminary data supporting the effectiveness of bait-bins in reducing blowfly numbers and flystrike in combination with good management practices to reduce sheep susceptibility to flystrike in the arid zone of New South Wales are presented and cost-effectiveness of bait-bins is analysed.

Dual effect of the adapter growth factor receptor-bound protein 14 (grb14) on insulin action in primary hepatocytes. Tight control of insulin action in liver is a crucial determinant for the regulation of energy homeostasis. Growth factor receptor-bound protein 14 (Grb14) is a molecular adapter, highly expressed in liver, which binds to the activated insulin receptor and inhibits its tyrosine kinase activity. The physiological role of Grb14 in liver metabolism was unexplored. In this study we used RNA interference to investigate the consequences of Grb14 decrease on insulin-regulated intracellular signaling, and on glucose and lipid metabolism in mouse primary cultured hepatocytes. In Grb14-depleted hepatocytes, insulin-induced phosphorylation of Akt, and of its substrates glycogen synthase kinase 3 and fork-head box protein 1, was increased. These effects on insulin signaling are in agreement with the selective inhibitory effect of Grb14 on the receptor kinase. However, the metabolic and genic effects of insulin were differentially regulated after Grb14 down-regulation. Indeed, the insulin-mediated inhibition of hepatic glucose production and gluconeogenic gene expression was slightly increased. Surprisingly, despite the improved Akt pathway, the induction by insulin of sterol regulatory element binding protein-1c maturation was totally blunted. As a result, in the absence of Grb14, glycogen synthesis as well as glycolytic and lipogenic gene expression were not responsive to the stimulatory effect of insulin. This study provides evidence that Grb14 exerts a dual role on the regulation by insulin of hepatic metabolism. It inhibits insulin receptor catalytic activity, and acts also at a more distal step, i.e. sterol regulatory element binding protein-1c maturation, which effect is predominant under short-term inhibition of Grb14 expression.

[Titanium miniplate fixation in head and neck cancer surgery]. To evaluate the rigid fixation with miniplates in head and neck cancer surgery. A consecutive series of 40 patients with head and neck tumor underwent rigid fixation with the Martin titanium miniplates system in a 6 years period. The miniplates were used to fix bone graft reconstruction following mandible resection (n = 14), mandibulotomies for oral and oropharyngeal surgical access (n = 12), maxilla swinging for nasopharyngeal access (n = 11) and other purposes (n = 3). Twenty-three of all cases(57.5%) received perioperative radiotherapy with average doses of 60Gy at the osteotomy site. Eleven of the 40 patient (22%) developed plate related complication which included 5 infections, 3 mandibular osteonecroses, 1 plate exposure, 1 screw loose and 1 nonunion. Complications were more likely to occur in patients with perioperative radiation than patients without (39.1% versus 11.8%, P = 0.079). Except one case, All the uncomplicated dentulous patients demonstrated stable and good occlusion. Oral feeding usually started on the 3-4th day after surgery. There was no need for intermaxillary fixation. The miniplate provided stable mandibular or maxillary fixation and accurate repositioning, eliminated the need for intermaxillary fixation. The malleability and versatility of miniplate make it unique in bone graft shaping for mandibular reconstruction. Complication seems to be related to perioperative radiotherapy. Median or paramedian mandibular osteotomy, which is non-radiated region in most radiotherapy cases, is advocated.

Apolipoproteins a-I and B as components of metabolic syndrome with respect to diabetes status: a factor analysis. The aim of the current study was to elucidate the clustering pattern of metabolic syndrome components along with apolipoproteins (Apo) A-I and B in diabetic and nondiabetic subjects. Factor analysis of conventional variables of metabolic syndrome [i.e., waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and systolic blood pressure (SBP)] with or without addition of Apo A-I and B was performed on 567 and 327 diabetic and nondiabetic subjects, respectively. Thereafter, analyses were repeated after substitution of TG and HDL-C by the TG-to-HDL-C ratio (TG/HDL-C). Regarding conventional variables of metabolic syndrome, one or two underlying factors were identified, depending on whether lipid measures were entered as two distinct variables or as a composite measure. Apolipoproteins were consistent with a one-factor structure model of metabolic syndrome and did not change the loading pattern remarkably in nondiabetics. TG and HDL-C tended to cluster with Apo B and A-I, respectively, in different models. The current study confirms that addition of Apo A-I and B is consistent with the one-factor model of metabolic syndrome and does not modify the loading pattern remarkably in nondiabetic subjects.

Analyzing the stimulus properties of objects used in stereotyped behavior. Ten severely retarded children who engaged in object stereotypies were observed during 10, 1-hour sessions in various contexts of their living and school environments. The percentage of object stereotypies performed and the nature of the objects manipulated were described. For the children as a group, context did not affect the level of object stereotypies, but other stereotypies were performed most often during music sessions. In Study 2 the objects manipulated in a stereotyped manner were presented to six people who were asked to describe the physical dimensions of the object when it was moved. Judges found that most children appeared to respond to flexibility, whereas some children appeared to respond to other feedback. Study 3 was designed to validate the dimensions selected by the judges. Each dimension agreed on by five of the judges in Study 2 was used to construct sets of five objects that varied with respect to that dimension. The children were presented with the set of objects and differential manipulation along the dimension was assessed. The judges' selections were partially validated.

Page Kidney Following a Nonepisode Protocol Renal Allograft Biopsy: A Case Report. Page kidney refers to a clinical condition that is characterized by the acute onset of hypertension and renal dysfunction owing to external compression of the kidney by a hematoma, tumor, lymphocele, or urinoma. We report a case in which Page kidney occurred after a nonepisode protocol renal allograft biopsy. A 31-year-old man with end-stage renal disease received a living related kidney transplant from his father. One year later, a nonepisode protocol renal allograft biopsy was performed. A day later, the patient's serum creatinine level increased to 4.23 mg/dL, and a subcapsular renal hematoma was detected using ultrasonography and computed tomography. Page kidney was diagnosed, and immediate surgical removal of the hematoma was performed. Nine days after the operation, the patient's serum creatinine level had improved to 1.89 mg/dL. Page kidney is a serious but treatable complication of renal allograft biopsies, and clinicians should pay attention to such complications, even in the setting of nonepisode protocol renal allograft biopsies.

Polycystic ovary syndrome: implications of metabolic dysfunction. To determine the prevalence of metabolic syndrome (MS) and its clinical interrelations in polycystic ovary syndrome (PCOS). This was a cross-sectional, prospective study with 100 patients with diagnosed PCOS based on the consensus of Rotterdam (2003). We investigated the interrelationships of MS, with intrinsic PCOS data. Dermatological profile was analyzed, in addition to acanthosis nigricans (AN) in the presence of hirsutism and acne. The use of HOMA-IR (homeostatic model assessment of insulin resistance) aimed at the correlation with MS in order to establish the metabolic dysfunction with the state of insulin resistance. The mean and standard deviations corresponding figures for age, body mass index and waist circumference were, respectively, 25.72 (± 4.87), 30.63 (± 9.31) and 92.09 (± 18.73). The prevalence of MS was 36% and significantly correlated with BMI, AN, and in 51% of patients the state of insulin resistance (HOMA-IR). Regarding skin profile, only AN significant correlation with MS. We propose the routine inspection of metabolic components related to severe PCOS. These parameters configure the cardiovascular risk and such conduct is of undoubted importance to public health.

Rayleigh instability of the inverted one-cell amphibian embryo. The one-cell amphibian embryo is modeled as a rigid spherical shell containing equal volumes of two immiscible fluids with different densities and viscosities and a surface tension between them. The fluids represent denser yolk in the bottom hemisphere and clearer cytoplasm and the germinal vesicle in the top hemisphere. The unstable equilibrium configuration of the inverted system (the heavier fluid on top) depends on the value of the contact angle. The theoretically calculated normal modes of perturbation and the instability of each mode are in agreement with the results from ComFlo computational fluid dynamic simulations of the same system. The two dominant types of modes of perturbation give rise to axisymmetric and asymmetric sloshing of the cytoplasm of the inverted embryos, respectively. This work quantifies our hypothesis that the axisymmetric mode corresponds to failure of development, and the asymmetric sloshing mode corresponds to development proceeding normally, but with reversed pigmentation, for inverted embryos.

Analysis of the catalytic and binding residues of the diadenosine tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans by site-directed mutagenesis. The contributions to substrate binding and catalysis of 13 amino acid residues of the Caenorhabditis elegans diadenosine tetraphosphate pyrophosphohydrolase (Ap(4)A hydrolase) predicted from the crystal structure of an enzyme-inhibitor complex have been investigated by site-directed mutagenesis. Sixteen glutathione S-transferase-Ap(4)A hydrolase fusion proteins were expressed and their k(cat) and K(m) values determined after removal of the glutathione S-transferase domain. As expected for a Nudix hydrolase, the wild type k(cat) of 23 s(-1) was reduced by 10(5)-, 10(3)-, and 30-fold, respectively, by replacement of the conserved P(4)-phosphate-binding catalytic residues Glu(56), Glu(52), and Glu(103) by Gln. K(m) values were not affected, indicating a lack of importance for substrate binding. In contrast, mutating His(31) to Val or Ala and Lys(83) to Met produced 10- and 16-fold increases in K(m) compared with the wild type value of 8.8 microm. These residues stabilize the P(1)-phosphate. H31V and H31A had a normal k(cat) but K83M showed a 37-fold reduction in k(cat). Lys(36) also stabilizes the P(1)-phosphate and a K36M mutant had a 10-fold reduced k(cat) but a relatively normal K(m). Thus both Lys(36) and Lys(83) may play a role in catalysis. The previously suggested roles of Tyr(27), His(38), Lys(79), and Lys(81) in stabilizing the P(2) and P(3)-phosphates were not confirmed by mutagenesis, indicating the absence of phosphate-specific binding contacts in this region. Also, mutating both Tyr(76) and Tyr(121), which clamp one substrate adenosine moiety between them in the crystal structure, to Ala only increased K(m) 4-fold. It is concluded that interactions with the P(1)- and P(4)-phosphates are minimum and sufficient requirements for substrate binding by this class of enzyme, indicating that it may have a much wider substrate range then previously believed.

Alterations of nucleic acid and protein syntheses in vivo in the chick embryo mediated by captan. 1. The objective of this investigation was to measure the effects of captan on DNA, RNA and protein biosyntheses in limbs of developing chick embryo, in vivo. 2. Captan (12p.p.m.) was injected into the egg on day 4 of incubation and macromolecular syntheses were measured on days 8--14. 3. Total DNA content was unaffected by captan, but incorporation of [3H]thymidine was inhibited over the entire time range; the period of peak specific activity (day 11) was inhibited in treated samples to 67% of control. 4. Total RNA content was reduced in the earlier days but returned to normal by day 14, whereas incorporation of [3H]uridine was lowered throughout the period. The timing of peak specific activity for RNA synthesis was delayed by 2 days in treated eggs and was inhibited by 32% when peak days were compared. 5. Total protein concentration was slightly lowered by captan treatment in the mid-range of the days measured and the incorporation of [3H]valine was retarded in the early days; peak periods of synthesis were similar in magnitude but were shifted from days 9--10 in control to day 11 in treated embryos.

Rehydration of air-dried cervical smears: a feasible alternative to conventional wet fixation. To evaluate the effect of rehydration of air-dried cervical smears on staining quality and to find out whether rehydration techniques can be adopted as an alternative method, especially in high-volume, resource-limited settings. A total of 950 paired wet-fixed and air-dried-rehydrated cervical smears collected by paramedical workers from an urban slum of Delhi, India, were compared for staining quality by assessing different cytoplasmic and nuclear parameters. The staining quality in air-dried-rehydrated smears was satisfactory and comparable to wet-fixed smears (61.3% versus 63.6%). The staining was superior in rehydrated smears in 26.5%, as compared with 15.4% in wet-fixed ones (P <.001). Unsatisfactory staining was observed in 12.2% of rehydrated smears, as compared with 21% of wet-fixed smears. The smear background was cleaner in rehydrated smears. Red blood cells were observed in only 3% of rehydrated smears, in comparison to 12% in wet-fixed ones (P <.001). Rehydration of air-dried cervical smears is a suitable alternative to wet-fixed smears. The staining quality is either the same as or better than wet-fixed smears, and the unsatisfactory rate is lower. This technique is simple and can be conveniently adopted in resource-limited settings.

Study of receptor-stimulated phosphatidylinositol hydrolysis in intact, perfused rat hearts. 1. Phosphatidylinositol turnover has been measured in intact, perfused rat hearts by measuring generation of inositol phosphates following [3H]-inositol labelling. Stimulation of accumulations of inositol monophosphate, inositol bisphosphate and inositol trisphosphate were observed during perfusion with either noradrenaline (3 X 10(-5) mol/l) or carbachol (10(-3) mol/l). 2. Stimulation by noradrenaline was antagonized by prazosin (10(-7) mol/l) but not by propranolol (10(-7) mol/l), indicating mediation via alpha 1-adrenoceptors. Stimulation by carbachol was antagonized by atropine (10(-7) mol/l). 3. Transmural electrical stimulation of the hearts failed to increase inositol phosphate accumulation through alpha 1-adrenoceptors. A small stimulation mediated by muscarinic receptors was observed. Therefore alpha 1-adrenoceptors which stimulate phosphatidylinositol turnover probably do not have a synaptic localization in heart. 4. The development of methods for the study of phosphatidylinositol turnover in intact hearts will facilitate an investigation of relationships between this signal transduction pathway and cardiac function.

Disturbance suppression for quadrotor UAV using sliding-mode-observer-based equivalent-input-disturbance approach. This paper presents a new control scheme for quadrotor unmanned aerial vehicle attitude control and disturbance suppression. A quadrotor dynamic model is divided into two subsystems: fully-actuated and under-actuated. While the PID method is used to control the fully-actuated subsystem, a sliding-mode-observer-based equivalent-input-disturbance approach is used to control the under-actuated subsystem. The system design is simple, and it is globally uniformly ultimately bounded. Simulations and comparisons demonstrate the effectiveness of the method.

An adsorptive stripping voltammetry procedure for ultra-trace determination of U(VI) using double accumulation step on two lead-film working electrodes. We report a very sensitive stripping voltammetric procedure for determination of ultra-trace quantity of U(VI) in water samples. A very low detection limit was achieved owing to the application of a new construction of the voltammetric electrode cell with two built-in working electrodes that differed significantly in their surface area. The procedure was based on the double adsorptive accumulation of the U(VI)-cupferron complex onto two lead film working electrodes. Under optimal conditions the detection limit for accumulation time of 120 s for the big electrode and 120 s for the small electrode was about 3.1 × 10(-11) mol L(-1), whereas for accumulation time of 480 s for the big electrode and 240 s for the small electrode it was about 1.1 × 10(-11) mol L(-1). The proposed method was successfully validated using certified reference material seawater NASS-5.

Evaluation of functional recovery by motor functional independence measure test of elderly after hip fracture in Serbia. The aim of the study was to evaluate motor functional status measured by motor Functional Independence Measure (mFIM) test in population above 65 years of age after the hip fracture. We evaluated 203 patients after hip fracture by mFIM test on 3 occasions: at admission (Period-1), at discharge (Period-2) and 3 months after discharge (Period-3); 3 age groups: Group(65-74), Group(75-84) and Group(85-up) and 2 groups concerning Severity Index (SI): group 0-1.99 (SI1) and group ≥ 2 (SI2). In same SI group there is significant increase in mFIM values for Period-2 and Period-3 for both genders and in first two age groups, while for those above 85 years of age with higher SI we found non-significant change in mFIM values between discharge and 3 months post discharge period. The most significant improvement is obtained for women in first and third age groups and with higher SI. Gender is not significant predictor for motor functional recovery measured by mFIM test in patients with hip fracture, although the admittance mFIM is a good indicator for mFIM capacity recovery in women of certain age groups (first and third age groups).

Brief physician advice for alcohol problems in older adults: a randomized community-based trial. Alcohol use in older adults is common. It is associated with depression, hypertension, diabetes, drug interactions, accidents, and increased rates of emergency department visits and hospitalizations. A controlled clinical trial (Project GOAL--Guiding Older Adult Lifestyles) tested the efficacy of brief physician advice in reducing the alcohol use and use of health care services of older adult problem drinkers. Twenty-four community-based primary care practices in Wisconsin (43 family physicians and internists) participated in the trial. Of the 6073 patients screened, 105 men and 53 women met inclusion criteria and were randomized into a control group (n = 71) or an intervention group (n = 87). Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions that included advice, education, and contracting using a scripted workbook. A total of 146 patients (92.4%) participated in the 12-month follow-up procedure. No significant differences were found between the control and intervention groups at baseline in alcohol use, age, socioeconomic status, depression, onset of alcohol use, smoking status, activity level, or use of mood-altering drugs. The older adults who received the physician intervention demonstrated a significant reduction in 7-day alcohol use, episodes of binge drinking, and frequency of excessive drinking (P <.005) compared with the control group at 3, 6, and 12 months after the intervention. There was a 34% reduction in 7-day alcohol use, 74% reduction in mean number of binge-drinking episodes, and 62% reduction in the percentage of older adults drinking more than 21 drinks per week in the intervention group compared with the control group. There were no significant changes in health status. Patterns of health care utilization were not extensively analyzed because of the small number of events. This study provides the first direct evidence that brief physician advice can decrease alcohol use by older adults in community-based primary care practices.

Bioavailability of copper, cadmium, zinc, and lead in tropical savanna soils assessed by diffusive gradient in thin films (DGT) and ion exchange resin membranes. The technique of diffusion gradient in thin films (DGT) for assessing bioavailable metals has not been tested under field conditions. We assessed the relationships of DGT- and cation exchange resin-membrane-measured concentrations of Cd, Cu, Pb, and Zn with plant uptake of the metals under greenhouse and field conditions. In the greenhouse, the effective concentrations of Cu, Pb, and Zn by DGT correlated significantly with uptake by sorghum (Sorghum bicolor), but cation exchange resin-membrane-measured concentrations of Cd, Pb, and Zn did not correlate with sorghum uptake. In the field, the DGT-measured concentrations of Cd, Pb, and Zn were not linearly related to uptake Cd, Pb, and Zn by lettuce (Lactuca sativa) except for Cu uptake (r = 0.87, p < 0.05). Similarly, it was only the resin-membrane-extractable Pb that correlated with Pb uptake by lettuce (r = 0.77; p < 0.05). However, fitting non-linear regression models improved the plant metal uptake predictions by DGT-measured bioavailable Cd, Cu, Pb, and Zn under field conditions. In conclusion, the DGT technique was fairly predictive of bioavailability in the greenhouse, but not in the field.

Salvage of avascular bone from frostbite with free tissue transfer. Traditional management of frostbite injury of the hands and fingers has been to allow demarcation to occur between viable and nonviable tissues, corresponding to the level of amputation required. In this case report, phalangeal length in mummified digits was maintained with free tissue transfer followed by evidence of bony revascularization on bone scan. Rather than waiting for tissue demarcation to occur, the authors propose that consideration be given to debridement of soft tissues in the frostbitten fingers followed by free tissue transfer to salvage length and function in the digital bony skeleton.

Synthesis and Characterization of Copper(II), Zinc(II), and Potassium Complexes of a Highly Fluorinated Bis(pyrazolyl)borate Ligand. Highly fluorinated, dihydridobis(3,5-bis(trifluoromethyl)pyrazolyl)borate ligand, [H(2)B(3,5-(CF(3))(2)Pz)(2)](-) has been synthesized and characterized as its potassium salt. The copper(II) and zinc(II) complexes, [H(2)B(3,5-(CF(3))(2)Pz)(2)](2)Cu and [H(2)B(3,5-(CF(3))(2)Pz)(2)](2)Zn, have been prepared by metathesis of [H(2)B(3,5-(CF(3))(2)Pz)(2)]K with Cu(OTf)(2) and Zn(OTf)(2), respectively. All the new metal adducts have been characterized by X-ray diffraction. The potassium salt is polymeric and shows several K.F interactions. The Cu center of [H(2)B(3,5-(CF(3))(2)Pz)(2)](2)Cu adopts a square planar geometry, whereas the Zn atom in [H(2)B(3,5-(CF(3))(2)Pz)(2)](2)Zn displays a tetrahedral coordination. Bis(pyrazolyl)borate ligands in the Zn adduct show a significantly distorted boat conformation. The nature and extent of this distortion is similar to that observed for the methylated analog, [H(2)B(3,5-(CH(3))(2)Pz)(2)](2)Zn. This ligand allows a comparison of electronic effects of bis(pyrazolyl)borate ligands with similar steric properties. Crystallographic data for [H(2)B(3,5-(CF(3))(2)Pz)(2)]K: triclinic, space group P&onemacr;, with a = 8.385(1) Å, b = 10.097(2) Å, c = 10.317(1) Å, alpha = 104.193(9) degrees, beta = 104.366(6) degrees, gamma = 91.733(9) degrees, V = 816.5(3) Å(3), and Z = 2. [H(2)B(3,5-(CF(3))(2)Pz)(2)](2)Cu is monoclinic, space group C2/c with a = 25.632(3) Å, b = 9.197(1) Å, c = 17.342(2) Å, beta = 129.292(5) degrees, V = 3164.0(6) Å(3), and Z = 4. [H(2)B(3,5-(CF(3))(2)Pz)(2)](2)Zn is triclinic, space group P&onemacr;, with a = 9.104(1) Å, b = 9.278(1) Å, c = 18.700(2) Å, alpha = 83.560(6) degrees, beta = 88.200(10) degrees, gamma = 78.637(9) degrees, V = 1538.8(3) Å(3), and Z = 2. [H(2)B(3,5-(CH(3))(2)Pz)(2)](2)Zn is monoclinic, space group C2/c with a = 8.445(1) Å, b = 14.514(2) Å, c = 19.983(3) Å, beta = 90.831(8) degrees, V = 2449.1(6) Å(3), and Z = 4.

Paroxetine in the treatment of depressed patients with haematological malignancy: an open-label study. The efficacy and tolerability of paroxetine in the treatment of depressive disorders is well known, however, its efficacy and safety for the treatment of depression in patients with cancer has been poorly studied. Therefore this study was aimed at evaluating the efficacy and tolerability of paroxetine in the treatment of depressed patients with haematological malignancy (HM). Fifty-two patients with major depressive disorder (MDD) based on DSM-IV criteria along with comorbid HM were allotted to an 8 week trial with a flexible-dose regime of paroxetine in combination with their chemotherapy or supportive pharmacotherapy. The treatment response was assessed at baseline, week 2, week 4 and week 8 with the 17-item Hamilton rating scale for depression (HAM-D17), the Montgomery Asberg depression rating scale (MADRS) and the clinical global impression-severity (CGI-S). Side effects were collected with reported adverse events and laboratory tests throughout the study period. 44.2% of 52 patients completed the 8 week trial. Scores on the HAM-D17, MADRS and CGI-s (last observation carried forward, LOCF) at baseline were significantly reduced with a mean reduction of 30.5%, 32.8% and 39.1%, respectively, after 8 weeks treatment with paroxetine. In this preliminary study, paroxetine was found to be effective and moderately tolerated in the treatment of depressed patients with HM, and the present study calls for a controlled study in this field to extend and form a framework on the psychopharmacological data in this field.

[Music-Acoustic Signals Controlled by Subject's Brain Potentials in the Correction of Unfavorable Functional States]. Literature review and the results of own studies on the development and experimental testing of musical EEG neurofeedback technology are presented. The technology is based on exposure of subjects to music or music-like signals that are organized in strict accordance with the current values of brain potentials of the patient. The main attention is paid to the analysis of the effectiveness of several versions of the technology, using specific and meaningful for the individual narrow-frequency EEG oscillators during the correction of unfavorable changes of the functional state.

Involvement of P-gp in the process of apoptosis in peripheral blood mononuclear cells. Multidrug resistance mediated by the drug-efflux protein P (P-gp) is one of mechanisms that cells use to escape death induced by drugs and other agents. The aim of the study was to evaluate the effect of P-gp inhibition on apoptosis of PHA-activated peripheral blood mononuclear cells (MNC) as well as apoptosis induced by methotrexate (MTX), dexamethasone (DEX), methylprednisolone (MP) and cortisone (COR). Apoptosis was quantified by flow cytometry using Annexin V/PI and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL). P-gp expression was inhibited using verapamil (VER) and P-gp specific monoclonal antibodies (mAb). VER and mAb enhanced the apoptosis of PHA-activated MNC. Moreover these agents significantly increased the apoptosis induced by MTX, DEX, MP and COR. The results of this study suggest that P-gp is involved in the process of apoptosis in peripheral blood mononuclear cells.

Stochastic model for outcome prediction in acute illness. The aims were to apply a stochastic model to predict outcome early in acute emergencies and to evaluate the effectiveness of various therapies in a consecutively monitored series of severely injured patients with noninvasive hemodynamic monitoring. The survival probabilities were calculated beginning shortly after admission to the emergency department (ED) and at subsequent intervals during their hospitalization. Cardiac function was evaluated by cardiac output (CI), heart rate (HR), and mean arterial blood pressure (MAP), pulmonary function by pulse oximetry (SapO(2)), and tissue perfusion function by transcutaneous oxygen indexed to FiO(2),(PtcO(2)/FiO(2)), and carbon dioxide (PtcCO(2)) tension. The survival probability (SP) of survivors averaged 81.5+/-1.1% (SEM) and for nonsurvivors 57.7+/-2.3% (p<0.001) in the first 24-hour period of resuscitation and subsequent management. The CI, SapO(2),PtcO(2)/FiO(2) and MAP were significantly higher in survivors than in nonsurvivors during the initial resuscitation, while HR and PtcCO(2) tensions were higher in the nonsurvivors. Predictions made during the initial resuscitation period in the first 24-hours after admission were compared with the actual outcome at hospital discharge, which were usually several weeks later; misclassifications were 9.6% (16/167). The therapeutic decision support system objectively evaluated the responses of alternative therapies based on responses of patients with similar clinical-hemodynamic states.

[The cell micro-encapsulation techniques and its advancement in the field of gene therapy]. It is no doubt that the gene therapy using recombinant engineering cells provides a novel approach to many refractory diseases. However, the transplant rejection from the host's immune system against heterogeneous cells has been the main handicap of its clinical application. The modern cell micro-encapsulation technique with good immune isolation makes it possible to overcome this problem and has shown potential application foreground in clinical therapies for a lot of diseases such as Parkinson's disease and Hemophiliac disease. This article reviews mainly the relative materials and techniques in processing micro-encapsulation, the host cells used to construct the recombinant genetic engineering cells and application of cell micro-encapsulation technique in the field of gene therapy.

Annual cycles in plasma testosterone and thyroxine in the male aspic viper Vipera aspis L., (Reptilia, Viperidae), in relation to the sexual cycle and hibernation. Blood samples were taken monthly from males of Vipera aspis kept in outdoor terraria. Plasma testosterone was estimated by radioimmunoassay and plasma thyroxine by the technique of isotopic competition, between October 1979 and September 1985. Plasma testosterone showed an annual bimodal profile. The highest peak was observed from February 15 to the end of March. 2 to 5 weeks after the first emergence from hibernation. Values then decreased greatly, to reach a minimum level when the vernal spermiogenesis was at its maximum. The secondary peak of plasma testosterone was lower and less well marked. It occurred at the end of summer, during the strongest spermiogenesis, and preceded the autumnal facultative mating period. Plasma thyroxine was at a maximum concentration from February to March after which levels decreased markedly. The seasonal profile of plasma thyroxine was clearly marked during the period of hibernation. From September to October, 2 months before the beginning of hibernation, thyroxine levels began to decrease, and they reached a minimum in November-December. Endocrine reactivation of the thyroid appeared at the end of hibernation. However, in contrast to the plasma testosterone, endocrine activity of the thyroid began 2 to 3 weeks before the end of hibernation. Mechanisms of reactivation for testicular and thyroidal endocrine structures are discussed.

Electrocardiographic Monitoring of Psychiatric In-patients Taking Antipsychotic Medications. To assess the adherence to guidelines for electrocardiographic (ECG) monitoring in Hong Kong psychiatric in-patients who have been prescribed antipsychotic medications. In-patients who had been prescribed antipsychotic drugs on hospital admission during the baseline audit period of 15 April 2015 to 16 July 2015 and the re-audit period of 28 January 2016 to 30 April 2016 were included. Quality improvement interventions were delivered after the baseline audit. ECG monitoring adherence was categorised as full adherence (ECG before taking antipsychotics), partial adherence (ECG after taking antipsychotics), or non-adherence (no ECG during hospital stay). Overall compliance was defined as full adherence plus partial adherence. The baseline audit and re-audit included 378 and 422 patients, respectively. Overall compliance with ECG monitoring increased significantly from the baseline audit to re-audit (40.2% vs. 69.9%; p < 0.001). Case-doctors having the grade of resident was associated with stronger adherence to ECG monitoring in both audits. Adherence to ECG monitoring guidelines for in-patients who are prescribed antipsychotic drugs is low in Hong Kong, and junior doctors (residents) demonstrate stronger adherence than moresenior doctors.

Narrowing down the region of the Vf locus for scab resistance in apple using AFLP-derived SCARs. A narrow-down strategy to restrict the Vf region, which controls resistance to the fungal disease apple scab in apple, to a genetic distance of 0.4 cM is presented. Using 11 AFLP-derived SCARs and three RAPD-derived SCARs, all linked to the Vf gene, we subjected 1,412 scab-resistant individuals from 16 mapping populations to genotype analysis. Eleven recombinant individuals were identified within a genetic distance of 0.9 cM around the Vf gene. Using these 11 recombinants, we achieved fine-resolution of several AFLP-derived SCAR markers surrounding the Vf gene, resulting in the following genetic linkage map: ACS-6 and ACS are located left of the Vf gene at genetic distances of 0.2 cM and 0.1 cM, respectively; ACS-7 and ACS-9 are inseparable from the Vf gene; ACS-8, ACS-10, and ACS-4 are located to the right of the Vf gene at genetic distances of 0.1 cM, 0.4 cM, and 0.5 cM, respectively; the remaining five SCARs-ACS-11, ACS-5, ACS-2, ACS-1, and AL07-are inseparable and are located right of the Vf gene at a genetic distance of 0.7 cM. By integrating this linkage data with our previous physical map, we generated a revised map of the narrowed-down region of Vf.

Serum levels of β-catenin as a potential marker for genotype 4/hepatitis C-associated hepatocellular carcinoma. The global rising incidence of hepatocellular carcinoma (HCC), which parallels the increase of hepatitis C virus (HCV) prevalence, has sparked a renewed interest in discovering additional HCC serum markers. In this study, we investigated the clinical use of serum E-cadherin, ICAM, MMP-2, VEGF, OPN and β-catenin as potential diagnostic makers for HCV/genotype 4-associated HCC. Twenty cases of healthy subjects, 11 cases with asymptomatic HCV/genotype 4 carriers (ASC), 28 chronic hepatitis (CH) cases and 32 patients with HCC were enrolled in this study. Serum levels of proteins were measured by a sandwich-enzyme-linked (ELISA) assay. The diagnostic accuracy of each candidate marker was evaluated using receiver-operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). We demonstrated that serum β-catenin levels were significantly elevated in patients with HCC compared to those with CH, ASC and healthy controls. Among the six studied markers, β-catenin was also found to be the only marker that can significantly discriminate between patients with HCC and those with CH; therefore, β-catenin could be considered as a potential marker for early diagnosis of HCV-associated HCC in patients infected with HCV genotype 4.

Links between the detritivore and the herbivore system: effects of earthworms and Collembola on plant growth and aphid development. Effects of Collembola (Heteromurus nitidus and Onychiurus scotarius) and earthworms (Aporrectodea caliginosa and Octolasion tyrtaeum) on the growth of two plant species from different functional groups (Poa annua and Trifolium repens), and on the development of aphids (Myzus persicae) were investigated in a laboratory experiment lasting 20 weeks. Using soil from a fallow site which had been set aside for about 15 years, we expected that nitrogen would be of limited supply to plants and hypothesized that the soil animals studied, particularly earthworms, would increase nutrient availability to plants and thereby also modify aphid reproduction and development. Plant growth was modified strongly by the presence of soil animals. Earthworms caused a more than twofold increase in shoot and root mass of P. annua but increased that of T. repens by only 18% and 6%, respectively. However, earthworms neither affected plant shoot/root ratio nor the nitrogen concentration in plant tissue. In contrast, the presence of Collembola caused a reduction in plant biomass particularly that of P. annua roots, but plant tissue nitrogen concentration was increased, although only slightly. Aphid reproduction on T. repens was lowered in the presence of Collembola on average by 45% but on P. annua increased by a factor of about 3. It is concluded that Collembola decrease aphid reproduction on more palatable host plants like T. repens but increase that on less palatable ones like P. annua. Earthworm presence also affected aphid reproduction but the effect was less consistent than that of Collembola. In the presence of earthworms, aphid reproduction was in one experimental period increased by some 70%. Earthworms also modified the numbers of Collembola and their vertical distribution in experimental chambers. Exploitation of deeper soil layers by H. nitidus was increased but, generally, O. scotarius numbers were reduced whereas those of H. nitidus increased in earthworm treatments. The presence of Collembola also influenced earthworm body mass during the experiment. In general it declined, but in the presence of Collembola loss of body mass of A. caliginosa was more pronounced. We conclude that inhibiting effects between Collembola and earthworms resulted from the use of a common resource, litter material rich in nitrogen. This is supported by the higher C/N ratio of the litter material in the presence of earthworms and Collembola by the end of the experiment. Effects of soil invertebrates like Collembola and earthworms on plant performance and aphid development are assumed to be modified by complex direct and indirect interactions among soil animal groups.

An analysis of lymphocyte subsets in the regional lymph nodes of patients with papillary thyroid carcinoma. Lymphocyte subsets in the lymph nodes regional to papillary thyroid carcinoma were determined using flow cytometry to ascertain the differences in local immunological responses between elderly and young patients. Lymph nodes from age-matched patients with benign thyroid tumors were used as controls. No significant alterations in lymphocyte subsets were observed in the lymph nodes from the young patients regardless of whether metastasis was present, whereas those from the elderly patients showed significant decreases in pan T cell (CD2+, CD3+) and cytotoxic T cell (CD8+, CD8+CD11b-) populations, and a significant increase in B cells (CD19+) compared with those from both the young patients and the age-matched controls. These results indicate that local immunological alterations occur in elderly patients with papillary thyroid carcinoma, and we believe that immunological changes are one of the clinical characteristics of this tumor.

In vivo investigation of the distribution and the local speciation of selenium in Allium cepa L. by means of microscopic X-ray absorption near-edge structure spectroscopy and confocal microscopic X-ray fluorescence analysis. In this work, microscopic X-ray absorption near-edge structure spectroscopy (mu-XANES) and confocal microscopic X-ray fluorescence analysis (mu-XRF) were used for the in vivo determination of the distribution of total selenium and for the local speciation of selenium in roots and leaves of onion. Selected Allium cepa L. plants were grown hydroponically in a standard medium containing inorganic selenium compounds (selenite or selenate). The measurements were performed in vivo, that is, on living plants without the need for any form of sampling or sample pretreatment and without the necessity for cutting plant tissues into pieces. Distinct energy differences of the XANES spectra of various selenium reference compounds having different oxidation states allow adjusting the excitation energies used for mu-XRF mapping in such a manner that the distribution of selenium in various oxidation states is obtained with a spatial resolution of a few tens of micrometers within the virtual cross section of the onion tissues. We find that the ratio of inorganic to amino acid selenium compounds differs in various subparts of the plant. Detailed in vivo investigation of the distribution of various selenium species in virtual cross sections of root tips and green leaf shows that the selenium transport takes place via different mechanisms, depending on the nature of the selenium compounds originally taken up.

Multichannel Fourier-transform interferometry for fast signals. Multichannel Fourier transform interferometry to measure the spectrum of arbitrarily short pulses and of fast time-varying signals was achieved using a micro/nanomanufactured multimirror array. We describe the performance of a demonstrator FTIR that works in the mid-infrared (MIR) range of 700-1400 cm(-1) and reaches a spectral resolution of 10 cm(-1) taking into account apodization. Spectral measurements down to pulse lengths of 319 µs were carried out using a mechanical camera shutter. Arbitrarily short pulses are expected feasible provided the source can deliver enough photons to overcome the noise equivalent number of photons.

A comparison of rural and urban Emergency Medical System (EMS) personnel: a Texas study. In treating accident victims, actions by the Emergency Medical Personnel (EMP) at the scene may be the difference between life or death, full recovery or permanent disability. Development of selected profiles based on locale of services, tenure, and paramedic certification will provide valuable insight into the diversity within the Emergency Medical Services (EMS) profession. Not only will these profiles enable administrators to improve their recruitment, training, and retention of the emergency medical workforce, it potentially could enhance the quality of health care in the community. Emergency medical personnel attending a statewide conference in Texas in late 1996 (n = 425). 1) There is no difference between the profiles of urban and rural EMP; 2) There is no difference between the profiles of urban EMP with < 9 years of experience and those with > or = 9 years of experience; 3) There is no differences between the profiles of rural EMP with < 9 years of experience and those with > or = 9 years of experience. 4) There is no difference between the profiles of urban EMP with paramedic certification and those without certification; and 5) There is no difference between the profiles of rural EMP with paramedic certification and those without certification. EMP attending the conference completed 425 survey instruments measuring five demographic features, five work-related features, and two psychological features. Survey instruments were included in each registrant's conference package. Completed surveys were deposited anonymously in labeled receptacles throughout the statewide conference site. Data collection ceased at the end of the conference. Discriminant analysis identified distinct profiles for the urban and rural EMP. The urban EMP, more than rural subjects, was younger (mean = 36 years), more likely to be compensated 100% for their services, had a higher level of education (mean = 13.8 years), and reported a lower level of burnout. Urban EMP with < 9 years of experience tended to be younger, male, married, and reported less burnout. Urban paramedics were more likely to be compensated 100% for their services, and had achieved a higher level of education. The rural EMP with < 9 years of experience were less likely to be paramedic, reported lower burnout scores, and was younger. The rural EMP without paramedic certification was more likely to be a volunteer, and have had fewer years of service. In Texas, locale of service (urban or rural), length of tenure as an EMP (> or = 9 years), and paramedic certification appear to be significant factors that define the EMP population in Texas.

The transobturator sling: newest tension-free suburethral sling for treatment of stress urinary incontinence. T his innovative sling system places the sling between the obturator foramens using a perineal approach while preserving an intact retropubic space. Potential complications associated with tension-free sling systems that use needle-carrier placement through the retropubic space, such as the tension-free vaginal tape (TVT, Gynecare, Ethicon, Somerville, NJ, USA), are eliminated and routine cystoscopy is not required. The procedure is effective and safe for the primary treatment of stress urinary incontinence in patients with urethral hypermobility, intrinsic sphincter deficiency, or both. It is equally efficient in treatment of recurrent and mixed urinary incontinence. Short-term results are similar to those of the retropubic tension-free slings.

Nigella sativa oil for prevention of chronic cyclosporine nephrotoxicity: an experimental model. Nephrotoxicity is the main secondary effect of cyclosporine A (CsA) treatment. The antioxidant action of Nigella sativa oil (NSO) may explain the protective effect of these agents against various hepatotoxic and nephrotoxic models in vivo and in vitro. This study was designed to investigate the possible protective effects of NSO, in prevention of chronic CsA-induced nephrotoxicity in rats. Animals were randomly divided into four experimental groups: the control group received sunflower oil, the other groups were treated with CsA (25 mg/kg/day b.w. orally) or NSO (2 ml/kg orally) or CsA + NSO, respectively. Urine and serum creatinine levels, tissue superoxide dismutase, glutathione peroxidase and catalase enzyme activities, and nitric oxide and malondialdehyde levels were measured, and histological examination was performed. In our study, CsA caused a significant deterioration in the renal function, morphology and gave rise to severe oxidative stress in the kidney. NSO significantly improved the functional and histological parameters and attenuated the oxidative stress induced by CsA. In conclusion, our study demonstrated for the first time that NSO protects kidney tissue against oxygen free radicals, preventing renal dysfunction and morphological abnormalities associated with chronic CsA administration.

Hepatitis risk: a clinical perspective. Clinical guidelines are outlined that will minimize the risk of professional personnel treating patients with hepatitis B. Following these procedures is emphasized as the history of the patient is not a reliable tool in screening this disease.

The importance of prevention of sinusoidal endothelial cell injury during cold preservation of liver graft. We investigated adenosine triphosphate (ATP) synthesis, lipid peroxidation, and activities of radical scavenging enzymes in mitochondria, as well as the ultrastructural morphological changes during cold preservation of swine liver grafts (n = 6) with either Euro Collins (EC) or University of Wisconsin (UW) solutions. The liver, harvested by a standard procedure, was preserved in one of the solutions at 4 degrees C. The values of the total adenine nucleotide and mitochondrial respiratory control ratio (RCR), an index of ATP synthesis, decreased gradually for up to 24 hr during preservation with either of the two solutions and there was no statistical difference between them. Chemiluminescence of mitochondria, an index of lipid peroxidation, in the graft preserved with EC solution or UW solution decreased, and after 24 hr there was no significant difference between the two solutions. Activities of radical scavenging enzymes were well maintained in any of the two solutions. Transmission electron microscopy (TEM) findings showed that the sinusoidal endothelial cells were preserved much better with UW solution than with EC solution even after 12 hr preservation. We concluded that UW solution, more effective for the protection against injuries of the sinusoidal endothelial cells during cold preservation, leads to better results in clinical transplantation, but this solution has no protective effects on energy production, nor radical scavenging enzyme activities of mitochondria. In the maintenance of liver graft viability, protection of the sinusoidal microcirculatory disturbance is more important than that of the mitochondrial function.

Radiation affects the responsiveness of bone marrow to G-CSF. In this study, we investigated the response of irradiated bone marrow cells to granulocyte colony-stimulating factor (G-CSF). Freshly harvested bone marrow cells were treated with either saline (vehicle control) or 20 ng/ml of G-CSF. Thereafter, cells were separated into nonirradiated (no-IR) and irradiated (IR, 0.5 Gy) groups. IR cells exhibited a higher proliferation rate in response to G-CSF, as compared to the no-IR cells. Reduced levels of reactive oxygen species indicated that G-CSF-treated IR cells produced fewer free radicals, as compared to the no-IR cells. The G-CSF-treated IR cells also had a lower apoptotic rate than their no-IR counterparts. Furthermore, G-CSF-treated IR cells exhibited less alteration of mitochondrial membrane potential, as compared to the no-IR cells. Finally, the mitochondrial number increased in the G-CSF-treated IR cells. The radiation-induced increase in plasma IL-6 in vivo could be enhanced by the administration of G-CSF. The data suggest that radiation potentiates the response of bone marrow cells to G-CSF treatment.

Modeling carbon dioxide adsorption on polyethylenimine-functionalized TUD-1 mesoporous silica. Samples of porous, foam-like TUD (Technische Universität Delft)-1 mesoporous silica were functionalized with polyethylenimine and were used as a substrate for CO(2) adsorption. Produced solids were characterized by means of electron microscopy, thermogravimetric analysis, and N(2) adsorption/desorption at 77K, in order to prove that polymer chains efficiently filled the pores of functionalized samples. CO(2) adsorption isotherms on polyethylenimine-containing TUD-1 were evaluated at T=298, 313, 328, and 348 K for pressures up to 100 kPa by means of a volumetric technique. The CO(2) adsorption capacity proved to be significantly dependent on temperature, with the highest capacity encountered at T=348 K. The experimental data for CO(2) adsorption were satisfactorily described by means of the Langmuir isotherm, and the dependence of the isosteric heat on the fractional coverage of the adsorbent was evaluated by means of the van't Hoff equation, showing values in the order of 80 kJ/mol for a fractional coverage of about 50%.

'Not waving but drowning': a study of the experiences and concerns of midwives and other health professionals caring for obese childbearing women. to explore the experiences and concerns of health professionals who care for childbearing women who are obese. obesity is increasing nationally and internationally and has been described as an epidemic. A number of studies have highlighted the risks associated with obesity during childbirth, yet few studies have investigated the experiences and concerns of midwives and other health professionals in providing care to these women. a descriptive qualitative study using focus groups and face-to-face interviews to collect data. Interviews were audio recorded and transcribed verbatim. Data were analysed using thematic analysis. three maternity units in New South Wales, Australia. participants included 34 midwives and three other health professionals. three major themes emerged from the data analysis: 'a creeping normality', 'feeling in the dark' and 'the runaway train'. The findings highlight a number of tensions or contradictions experienced by health professionals when caring for childbearing women who are obese. These include, on the one hand, an increasing acceptance of obesity ('a creeping normality'), and on the other, the continuing stigma associated with obesity; the challenges of how to communicate effectively with pregnant women about their weight and the lack of resources, equipment and facilities ('feeling in the dark') to adequately care for obese childbearing women. Participants expressed concerns about how quickly the obesity epidemic appears to have impacted on maternity services ('the runaway train') and how services to meet the needs of these women are limited or generally not available. it was clear in this study that participants felt that they were 'not waving but drowning'. There was concern over the fact that the issue of obesity had moved faster than the health response to it. There were also concerns about how to communicate with obese women without altering the relationship. Continuity of care, training and skills development for health professionals, and expansion of limited services and facilities for these women are urgently needed.

Congenital absence of superior vena cava: unusual anomaly of superior systemic veins complicating pacemaker placement. Congenital anomalies of the superior systemic veins can complicate placement of transvenous pacemaker electrode leads. Persistent left superior vena cava is the most common congenital anomaly; in this paper, we describe the case of a patient who had congenital absence of both superior venae cavae, which has not been reported previously. The superior systemic veins drained into persistent double azygos veins subdiaphragmatically. The anomaly was verified by venography. Temporary cardiac pacing was established by passing the electrode lead through the femoral vein, and a permanent epicardial pacemaker lead was placed thereafter. This appears to be the first recorded case of such an anomaly.

Mapping a nucleolar targeting sequence of an RNA binding nucleolar protein, Nop25. Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of lysine and arginine residues in the subdomain resulted in the loss of Nop25 nucleolar localization. These results suggest that the lysine and arginine residue-enriched peptide is the most prominent nucleolar targeting sequence of Nop25 and that the long stretch of basic residues might play an important role in the nucleolar localization of Nop25. Although Nop25 contained putative SUMOylation, phosphorylation and glycosylation sites, the amino acid substitution in these sites had no effect on the nucleolar localization, thus suggesting that these post-translational modifications did not contribute to the localization of Nop25 in the nucleolus. The treatment of the cells, which expressed a GFP-fusion protein with a nucleolar targeting sequence of Nop25, with RNase A resulted in a complete dislocation of the protein from the nucleolus. These data suggested that the nucleolar targeting sequence might therefore play an important role in the binding of Nop25 to RNA molecules and that the RNA binding of Nop25 might be essential for the nucleolar localization of Nop25.

[Two cases of Richter's syndrome]. Two cases of Richter's syndrome were observed by the authors between April and August 1987. The patients were treated previously because of chronic lymphoid leukemia. The histological findings indicated in both cases immunoblast transformation of CLL. The patients were non-respondent to intensive chemotherapy and died within a short time.

Structures, Bonding, and Energetics of Potential Triatomic Circumstellar Molecules Containing Group 15 and 16 Elements. The recent discovery of PN in the oxygen-rich shell of the supergiant star VY Canis Majoris points to the formation of several triatomic molecules involving oxygen, nitrogen, and phosphorus; these are also intriguing targets for main-group synthetic inorganic chemistry. In this research, high-level ab initio electronic structure computations were conducted on the potential circumstellar molecule OPN and several of its heavier group 15 and 16 congeners (SPN, SePN, TePN, OPP, OPAs, and OPSb). For each congener, four isomers were examined. Optimized geometries were obtained with coupled cluster theory [CCSD(T)] using large Dunning basis sets [aug-cc-pVQZ, aug-cc-pV(Q+d)Z, and aug-cc-pVQZ-PP], and relative energies were determined at the complete basis set limit of CCSDT(Q) from focal point analyses. The linear phosphorus-centered molecules were consistently the lowest in energy of the group 15 congeners by at least 6 kcal mol(-1), resulting from double-triple and single-double bond resonances within the molecule. The linear nitrogen-centered molecules were consistently the lowest in energy of the group 16 congeners by at least 5 kcal mol(-1), due to the electronegative central nitrogen atom encouraging electron delocalization throughout the molecule. For OPN, OPP, and SPN, anharmonic vibrational frequencies and vibrationally corrected rotational constants are predicted; good agreement with available experimental data is observed.

Effect of ischemia preconditioning and leech therapy on cutaneous pedicle flaps subjected to prolonged ischemia in a mouse model. We sought to determine the effect of ischemic preconditioning (IPC) and hirudotherapy (leech therapy) on cutaneous pedicle flaps after they underwent prolonged ischemia (global ischemia) in a mouse model. Twenty cutaneous pedicle flaps were elevated in 20 mice, and the animals were randomized into four groups: sham, control, IPC and leech (5 flaps in each group). Except in the sham group, all flaps were subjected to global ischemia for 5 h via pedicle clamping. The control group did not receive any treatment before or after global ischemia. In the IPC group, global ischemia was preceded by three 10-min episodes of ischemia, each followed by 10 min of reperfusion. In the leech therapy group, after global ischemia, hirudotherapy was performed. Flap survival area and histopathological changes were evaluated on the 10th day after surgery. Flap survival areas were significantly higher in both the IPC and leech groups than in the control group and were significantly higher in the leech group than in the IPC group (p < 0.05). In conclusion IPC and hirudotherapy had definite effects on the survival area of cutaneous pedicle flaps that underwent prolonged ischemia in a mouse model.

High-performance liquid chromatographic assay for the measurement of atovaquone in plasma. A rapid and efficient isocratic high-performance liquid chromatographic assay for the measurement of atovaquone in plasma has been developed and validated. The drug was extracted from plasma with organic solvents, assayed on a C1 column with a mobile phase of methanol-0.1% acetic acid (70:30, v/v), and detected by ultraviolet absorbance at 254 nm. Recovery of atovaquone from plasma was greater than 85%. Intra- and inter-assay variability were less than 8%, and the average accuracy of the assay (expressed as % bias) ranged from -7.4 to + 2.2%. The upper and lower limits of quantitation were 100 and 0.25 microgram/ml, respectively. Measurement of atovaquone in spiked plasma control samples during routine runs of clinical trial samples confirmed the reliability of the assay.

International Perinatal Nephrology Symposium, 20-21 June 2001, Lausanne, Switzerland. The 5th International Symposium on Prenatal Nephrology returned this year to Lausanne, Switzerland, after being held in the 2 previous years across the border in France (Strasbourg 1999 and Dijon 2000). The main topics presented for discussion to the approximately 80 participants (from 13 countries) dealt this year -- in English and in French -- with several aspects of acute renal failure (ARF) in the newborn. Indeed lively, friendly and interesting discussions again characterized this very constructive meeting held in ideal warm weather beside Lac Léman.

Iron Deficiency Anemia in Adolescents Who Present with Heavy Menstrual Bleeding. To assess the clinical severity and initial treatment of iron deficiency anemia (IDA) in female adolescents with heavy menstrual bleeding (HMB) in our center. Retrospective cohort study of electronic medical records via search of administrative records using International Classification of Diseases Ninth Revision codes for IDA or unspecified anemia and disorders of menstruation. Children's Medical Center in Dallas, Texas. One hundred seven patients with HMB and concomitant IDA (median age, 14.4 years) who presented to the outpatient, emergency department, and/or inpatient settings. The median initial hemoglobin concentration for all patients (n = 107) was 7.4 g/dL, and most (74%, n = 79) presented to the emergency department or via inpatient transfer. Symptomatic IDA was treated with blood transfusion in 46 (43%, n = 46). Ferrous sulfate was the most commonly prescribed oral iron therapy. Seven patients received intravenous iron therapy either initially or after oral iron treatment failure. Combined oral contraceptives were commonly prescribed for abnormal uterine bleeding, yet 10% of patients (n = 11) received no hormonal therapy during their initial management. Evaluation for underlying bleeding disorders was inconsistent. Severe anemia because of IDA and HMB resulting in urgent medical care, including hospitalization and blood transfusion, is a common but underemphasized problem in adolescent girls. In addition to prevention and early diagnosis, meaningful efforts to improve initial management of adolescents with severe HMB and IDA are necessary.

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes. Chemokines and their receptors are essential for leukocyte trafficking, and also implicated in cancer metastasis to specific organs. We have recently demonstrated that CXCR3 plays a critical role in metastasis of mouse melanoma cells to lymph nodes. Here, we show that some human colon cancer cell lines express CXCR3 constitutively. We constructed cells that expressed CXCR3 cDNA ('DLD-1-CXCR3'), and compared with nonexpressing controls by rectal transplantation in nude mice. Although both cell lines disseminated to lymph nodes at similar frequencies at 2 weeks, DLD-1-CXCR3 expanded more rapidly than the control in 4 weeks. In 6 weeks, 59% of mice inoculated with DLD1-CXCR3 showed macroscopic metastasis in para-aortic lymph nodes, whereas only 14% of those with the control (P<0.05). In contrast, metastasis to the liver or lung was rare, and unaffected by CXCR3 expression. In clinical colon cancer samples, we found expression of CXCR3 in 34% cases, most of which had lymph node metastasis. Importantly, patients with CXCR3-positive cancer showed significantly poorer prognosis than those without CXCR3, or those expressing CXCR4 or CCR7. These results indicate that activation of CXCR3 with its ligands stimulates colon cancer metastasis preferentially to the draining lymph nodes with poorer prognosis.

Relations between force-velocity characteristics of the knee-hip extension movement and vertical jump performance. Relations between force-velocity characteristics of the multijoint movement of the lower limbs and vertical jump performance were investigated. A total of 67 untrained subjects (age: 19.54 +/- 2.38 years; height: 166.88 +/- 8.53 cm; body mass: 59.14 +/- 10.82 kg, mean +/- SD) performed isometric and isotonic knee-hip extension movements on a servo-controlled dynamometer, and the force-velocity relations were determined. Also, vertical jump (VJ) performance was measured with a jump gauge. The force-velocity relation was described with a linear function so that the maximum isometric force (Fmax) and the maximum unloaded velocity (Vmax) for the knee-hip extension movement were estimated by extrapolation. Maximum isometric force coincided with maximum isometric force, F(0) (F(0)/Fmax = 1.03 +/- 0.24). Maximum isometric force, Vmax, and maximum power output (Pmax) were positively correlated with VJ (r = 0.48, 0.68, and 0.76, respectively; p < 0.001). However, when Fmax, Vmax, and Pmax were normalized with body mass (BM), leg length (LL), and BM, respectively, no correlation was seen between Fmax/BM and VJ (r = 0.24, p > 0.05), and significant correlations were seen between Vmax/LL and VJ (r = 0.56, p < 0.001) and between Pmax/BM and VJ (r = 0.65, p < 0.001). On the other hand, Fmax and Vmax (r = 0.12, p > 0.05) and Fmax/BM and Vmax/LL (r = 0.05, p > 0.05) were not significantly correlated, indicating that Fmax and Vmax were independent variables. The present estimates of Fmax, Vmax, and Pmax can be useful for evaluating the actual performance of multijoint movement of the lower limbs. It is suggested that, although in untrained individuals the speed of movement might be a more important determinant of jump performance, jump performance ability has a potential to improve with increases in strength of the lower limb.

Undiscovered Pulsar in the Local Bubble as an Explanation of the Local High Energy Cosmic Ray All-Electron Spectrum. Cosmic ray electrons and positrons are tracers of particle propagation in the interstellar medium (ISM). A recent measurement performed using the High Energy Stereoscopic System extends the all-electron (electron+positron) spectrum up to 20 TeV, probing very local sources and transport due to the ∼10 kyr cooling time of these particles. An additional key local measurement was the recent estimation of the ISM diffusion coefficient around Geminga performed using the High-Altitude Water Cherenkov Observatory. The inferred diffusion coefficient is much lower than typically assumed values. It has been argued that if this diffusion coefficient is representative of the local ISM, pulsars would not be able to account for the all-electron spectrum measured at Earth. Here we show that a low diffusion coefficient in the local ISM is compatible with a pulsar wind nebula origin of the highest energy electrons, if a so-far-undiscovered pulsar with spin-down power ∼10^{33-34} erg/s exists within 30-80 pc of Earth. The existence of such a pulsar is broadly consistent with the known population and may be detected in near future survey observations.

The fixation of anti-HBsAg on plastic surfaces. Serum samples were found to be capable of desorbing as much as 40% of the antibody to hepatitis B surface antigen (anti-HBsAg) adsorbed to plastic surfaces. This previously unreported loss could affect the accuracy of the assay, so chemical fixation was examined as a means for preventing antibody desorption during a 'sandwich' radioimmunoassay for HBsAg. Methods for fixing the anti-HBsAg were developed with glutaraldehyde and ethylchloroformate. Both methods prevented antibody desorption from polyvinylchloride and polystyrene without affecting immunoreactivity in radioimmunoassay. A combined glutaraldehyde-ethylchloroformate method resulted in stronger fixation that fully resisted the sera that caused the greatest desorption. It was found that only polymerized glutaraldehyde fixed anti-HBsAg to plastic; the monomer was ineffective. Anti-HBsAg fixed microtiter plates could be stored for at least 4 weeks without loss of sensitivity in radioimmunoassays. These methods could be adapted for use in other assays where the prevention of protein desorption from the solid phase is an important consideration.

Exposing the "myth" of ABC, "anything but chrysotile": a critique of the Canadian asbestos mining industry and McGill University chrysotile studies. Beginning in the 1930s, the Canadian asbestos industry created and advanced the idea that chrysotile asbestos is safer than asbestos of other fiber types. We critically evaluate published and unpublished studies funded by the Quebec Asbestos Mining Association (QAMA) and performed by researchers at McGill University. QAMA-funded researchers put forth several myths purporting that Quebec-mined chrysotile was harmless, and contended that the contamination of chrysotile with oils, tremolite, or crocidolite was the source of occupational health risk. In addition, QAMA-funded researchers manipulated data and used unsound sampling and analysis techniques to back up their contention that chrysotile was "essentially innocuous." These studies were used to promote the marketing and sales of asbestos, and have had a substantial effect on policy and occupational health litigation. Asbestos manufacturing companies and the Canadian government continue to use them to promote the use of asbestos in Europe and in developing countries. Am. J. Ind. Med. 44:540-557, 2003.

An immobilized fork as a termination of replication intermediate in Bacillus subtilis. The structure of a DNA intermediate associated with termination of chromosome replication in Bacillus subtilis and derived from a unique BamHI 24.8 X 10(3) base-pair (bp) region of the chromosome has been investigated. The intermediate has properties expected for a forked structure. Gel electrophoresis followed by Southern transfer and hybridization to cloned DNA has shown it to comprise single strands of 15.4 X 10(3) bp and 24.8 X 10(3) bp, in approximately equimolar amounts. After purification away from the bulk of chromosomal DNA, electron microscopy of the intermediate established that 15% of the DNA was present as branched molecules and a significant proportion (11 of 31) of these contained two arms of matching length. The average dimensions (best estimates) of this unique class of Y-shaped molecule were 9.5(+/- 0.3) X 10(3), 15.1(+/- 0.4) X 10(3) and 24.6 24.6(+/- 0.6) X 10(3) bp for the stem, arms and end-to-end length, respectively. These values are consistent with the single strand composition of the intermediate as found. Furthermore, hybridization of the single strands to DNA from known locations within the BamHI 24.8 X 10(3) bp region has established the orientation of the forked intermediate relative to the genetic map. The intermediate presumably reflects the immobilization of the clockwise replication fork within the 24.8 X 10(3) bp region, at a location approximately 15.4 X 10(3) bp from the right end.

[Effects of controlled-release N and K fertilizers on N, P, and K use efficiency of mauls (Manlus robusta)]. A pot experiment was conducted to study the effects of controlled-release N and K fertilizers on mauls seedlings growth, their P and K use efficiency, and the N balance in soil-plant system. The results showed that the nutrient release from controlled-release fertilizers accorded well with the nutrient requirement of mauls seedlings. Controlled-release N fertilizer significantly increased the K use efficiency, and controlled-release K fertilizer significantly increased the N use efficiency. Under the same K application rate, the plant height and stem diameter under the application of controlled-release N fertilizer (CN) and controlled-release N and K fertilizers (NK) had no significant difference, while those under the application of common fertilizer (SF) were all higher. The plant dry mass and the P and K use efficiency were in the order of NK>CN>SF. Under the application of NK, the application rate of K had no significant effects on the plant height and stem diameter, but significantly affected the plant dry mass. The P use efficiency increased with increasing application rate of controlled-release K fertilizer, but was less affected by application rate common K fertilizer. The K use efficiency decreased with increasing application rate of K. The N use efficiency was in the order of NK>CN>SF, while the N loss rate was in adverse. The residual rate of NK and CN had no significant difference, but was higher than that of SF. The application rate of controlled-release K fertilizer had significant effects on the N use efficiency and N loss rate, but no significant effects on N residual rate.