Caspase-dependent and -independent cell death induced by 3-nitropropionic acid in rat cortical neurons.
Mitochondria play a critical role in cell death by releasing apoptogenic factors, such as cytochrome c and apoptosis-inducing factor (AIF), from the intermembrane space into the cytoplasm. Because mitochondrial dysfunction has been shown to be involved in several neurodegenerative diseases, mitochondrial toxins are largely used to model these disorders. These include 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, which has been used to model Huntington's disease and was previously reported by us to induce apoptotic cell death through caspase activation. In the present study, we evaluated the involvement of caspase-independent neuronal cell death induced by 3-NP (1 mM) and the effect of z-VDVAD-fmk, an inhibitor of caspase-2, using cortical neurons in culture. Our results highly suggest that 3-NP induces both caspase-dependent and -independent cell death. We showed that z-VDVAD-fmk prevented both caspase-2 and -3-like activities evoked by 3-NP, but only partly prevented chromatin fragmentation/condensation. However, z-VDVAD-fmk did not avoid 3-NP-induced release of cytochrome c or AIF from mitochondria nor did it affect the levels of mitochondrial Bax. Furthermore, 3-NP-mediated decrease in plasma membrane integrity was not affected by z-VDVAD-fmk. Under these conditions, the inhibitor prevented the caspase-dependent cell death.


Selected Topics in the Molecular Pathology of Endometrial Carcinoma.
In the developed world, endometrial carcinoma is the most common malignant tumor of the female gynecologic tract. Numerous epidemiologic studies indicate that exposure to unopposed estrogen is a significant risk factor for developing endometrial cancer, particularly endometrioid-type endometrial carcinoma; however, a number of other molecular pathways and mechanisms are also important in endometrial cancer. In this review, the authors highlight some of the more interesting molecular pathways in endometrial cancer, such as the PTEN/PI3K/AKT pathway, microsatellite instability, and molecular mediators of epithelial-to-mesenchymal transition.


Clinical impact of transesophageal echocardiography in the diagnosis and management of infective endocarditis.
Transesophageal echocardiography (TEE) has assumed a prominent role in the diagnosis and management of infective endocarditis (IE). The impact of negative TEE findings on the management of patients suspected of having IE is not clear. To better understand how a negative TEE examination would influence patient management, the medical records of 93 consecutive patients undergoing TEE to evaluate for IE were examined. The influence of TEE was assessed based on changes in diagnosis, antibiotic therapy, or the need for surgical intervention during hospitalization. The negative predictive value of TEE was found to be 100% in native valves and 90% in prosthetic valves. The overall impact of negative TEE findings was significant in terms of final diagnosis and duration of antibiotic therapy (a negative TEE resulted in 60% reduction in antibiotic duration, p = 0.0001). These findings suggest that in patients with native heart valves, a negative TEE examination virtually excludes IE. In patients with prosthetic valves, a negative TEE significantly decreases the likelihood of IE but does not completely exclude the diagnosis; therefore, in this setting, a negative finding should be closely correlated with the clinical course.


Serum paraoxonase 1 (PON1) activity and lipid metabolism parameters changes in different production cycle periods of Holstein-Friesian, Polish Red and Norwegian breeds.
We investigated the measurement of paraoxonase 1 (PON1), as a potential marker of redox state changes in dairy cows, its involvement in lipid metabolism and compared it with superoxide dismutase (SOD) activity changes. We also evaluated lipid metabolism parameters associated with dairy production. PON1 paraoxonase and arylesterase acitvities, SOD activity, beta-hydroxybutyrate (BHB), uric acid (UA), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol and triglyceride concentrations were measured in Holstein-Friesian, Polish Red and Norwegian breeds serum in two production cycles. Our data showed a significant postpartum depletion in PON1 activity and lipoprotein and lipid products concentrations, with elevated BHB values. However, there were no significant changes in SOD activity and uric acid concentrations in Holstein-Friesian and Polish Red breeds after calving. At lactation peak there was a significant SOD activity decrease correlated with standardized PON1 activity depletion in all examined breeds. The results suggest that PON1 might be a better parameter for minimal redox state changes in serum, shortly after labour in the examined breeds.


Cytokine induction by pyrogens: comparison of whole blood, mononuclear cells, and TLR-transfectants.
Given the shortcomings in the measurement of pyrogenic contamination of pharmaceuticals and/or test substances by means of the rabbit pyrogen test and the Limulus amoebocyte lysate (LAL) test, several in vitro pyrogen tests have been developed based on the measurement of cytokine production by monocytes. In this study we measured cytokine production (IL-6, IL-8, IL-1beta, and TNF) in diluted whole blood (WB), mononuclear cells (MNC), and HEK cells stably transfected with CD14 and Toll-like Receptor-2 (TLR2) or TLR4, after stimulation with both standard pyrogens and contaminated substances. Our study demonstrated that in MNC, IL-6 production was more sensitive to pyrogen stimulation than IL-1beta and TNF production. The sensitivity of WB IL-8 production for pyrogens was comparable with that of MNC IL-6 production, but higher than WB IL-6 production. MNC IL-8 production as readout for pyrogenic stimulation was not useful due to high background IL-8 production. Surprisingly, contaminated culture media potently stimulated WB IL-8 production, but not MNC IL-6 production. Finally, the value of TLR-transfected HEK cells in the detection of pyrogenic contamination as well as the role of IL-10 in interindividual differences in cytokine production, is discussed. To summarize, the results presented herein together with literature data indicate that the measurement of WB IL-8 production may represent an advantageous alternative to the measurement of MNC IL-6 production, for the detection of pyrogenic contamination of pharmaceuticals.


Thermal modeling of snake infrared reception: evidence for limited detection range.
For more than 40 years, information has circulated with regard to the sensitivity of infrared pit organs in both boid and crotaline snakes (pythons and pit vipers, respectively). The most often quoted sensitivity is 0.003 degrees C and this value is based on the work of Bullock and co-workers (1956). Missing from previous work was a quantitative model of radiation transfer that would report sensitivity not in terms of degrees Celsius, but rather sensing distance. Since prey detection is often cited as the function of the infrared pit organ, quantification of this sensing distance seemed to be an important value that was missing from the literature. In this paper, we model the radiation transfer process from a 37 degrees C object, i.e. warm-blooded prey, to an infrared pit organ. The model tries to answer a very basic question-at what distance does the thermal signature of a 37 degrees C object blend into the background for a non-imaging biological infrared sensor? The output of the model, the sensing distance, is of particular interest in comparing biological infrared sensors to current semiconductor-based infrared (IR) detectors-largely because of inappropriate comparisons between the temperature sensitivity of IR snake reception and imaging IR cameras. The purpose of the presented work to make more appropriate comparisons, i.e. sensing distance. This sensing distance output indicates an extremely short detection distance (<5 cm)-contradictory to what is observed experimentally. This dichotomy raises further questions regarding how the biological system amplifies this weak signal.


[Use of the MS2 automated system in the determination of the activity of 5 antiseptic drugs: quality control].
The study of growth curves of Klebsiella pneumoniae and Staphylococcus aureus in presence of five antiseptics, established using a MS2 Abbott system is presented. From our results, the advantages of automation after the adaptation of the method for the determination of bactericidal properties are examined. This technique may be proposed for the quality control of such drugs.


Heat conduction in a two-dimensional harmonic crystal with disorder.
We study the problem of heat conduction in a mass-disordered two-dimensional harmonic crystal. Using two different stochastic heat baths, we perform simulations to determine the system size (L) dependence of the heat current (J). For white noise heat baths we find that J approximately 1/L(alpha) with alpha approximately equal to 0.59, while correlated noise heat baths give alpha approximately equal to 0.51. A special case with correlated disorder is studied analytically and gives alpha=3/2, which agrees also with results from exact numerics.


In vivo acylation of triglycerides and phosphoglycerides of liver subcellular fractions with palmitate-1-14C in rats fed vitamin A.
Incorporation of palmitate-1-14C into liver and its mitochondrial, and microsomal triglycerides and phosphoglycerides of rats fed 100000 I.U. of vitamin A for two days has been studied. Feeding of vitamin A significantly increased triglycerides in liver and its mitochondrial, microsomal and supernatant fractions as compared to the controls. A significant increase in total phospholipids and phosphatidyl choline was noted in liver mitochondrial and microsomal fractions of vitamin A fed rats. The incorporation of palmitate-1-14C (counts/min/liver) into triglycerides of liver mitochondrial, microsomal and supernatant fractions of vitamin A fed rats was significantly higher, whereas in phosphatidyl ethanolamine and phosphatidyl choline it was not significantly different from the controls.


The surface structure seen on gonococci after treatment with CMP-NANA is due to sialylation of surface lipopolysaccharide previously described as a 'capsule'.
Phenotypic serum resistance of gonococci in urethral exudates is due to sialylation of lipopolysaccharide (LPS) by host cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). A surface structure was visible on gonococci [strain BS4 (agar)] that had been stained with ruthenium red after incubation with CMP-NANA. This structure was not visible after neuraminidase treatment, which released sialic acid but not LPS. The LPS profiles of strain BS4 (agar) had another in vivo-selected strain Gc40 (variant D1), were similar. A monoclonal antibody (mAb) which recognises epitope C on the LPS of 'capsulated' gonococci was shown by immunoblotting to react with several LPS components, including one of about 4.5 kDa which contains the probable site of sialylation by CMP-NANA. The reactions with the mAb were not affected by growing the strains with CMP-NANA nor by neuraminidase treatment of the sialylated LPS. The mAb also gold-labelled the surface of both strains before and after treatment with CMP-NANA. These data indicate that sialylation by CMP-NANA and staining with ruthenium red renders more visible the surface LPS which, sometimes in the past, has been seen as a 'capsule'.


Embolic event in the puerperium with tragic end.
To present a case of a patient with embolic event in the puerperium at the surgery for residual trophoblastic tissue. Case report. Department of Obstertics and Gynaecology, Hospital Rakovník. We present the 33-year-old second-graders case of three weeks of labor at 40th weeks, which was operated at our workplace for residual trophoblastic tissue. The gynecological surgery took place without complications, however, after the operation, breathing and circulation arrest. Thrombolysis was given for suspicion of embolization etiology. In spite of an intense urgent CPR and multidisciplinary collaboration, there is a failure in the life and death of the patient. In presenting this serious case of an embolic event, the author want to emphasize the need for proper diagnosis, an indication of the surgical performance or the conservative procedure for placental remnants in the puerperium.


The protein-tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signaling.
In this study we have investigated the down-regulation of epidermal growth factor (EGF) receptor signaling by protein-tyrosine phosphatases (PTPs) in COS1 cells. The 45-kDa variant of the PTP TCPTP (TC45) exits the nucleus upon EGF receptor activation and recognizes the EGF receptor as a cellular substrate. We report that TC45 inhibits the EGF-dependent activation of the c-Jun N-terminal kinase, but does not alter the activation of extracellular signal-regulated kinase 2. These data demonstrate that TC45 can regulate selectively mitogen-activated protein kinase signaling pathways emanating from the EGF receptor. In EGF receptor-mediated signaling, the protein kinase PKB/Akt and the mitogen-activated protein kinase c-Jun N-terminal kinase, but not extracellular signal-regulated kinase 2, function downstream of phosphatidylinositol 3-kinase (PI 3-kinase). We have found that TC45 and the TC45-D182A mutant, which is capable of forming stable complexes with TC45 substrates, inhibit almost completely the EGF-dependent activation of PI 3-kinase and PKB/Akt. TC45 and TC45-D182A act upstream of PI 3-kinase, most likely by inhibiting the recruitment of the p85 regulatory subunit of PI 3-kinase by the EGF receptor. Recent studies have indicated that the EGF receptor can be activated in the absence of EGF following integrin ligation. We find that the integrin-mediated activation of PKB/Akt in COS1 cells is abrogated by the specific EGF receptor protein-tyrosine kinase inhibitor tyrphostin AG1478, and that TC45 and TC45-D182A can inhibit activation of PKB/Akt following the attachment of COS1 cells to fibronectin. Thus, TC45 may serve as a negative regulator of growth factor or integrin-induced, EGF receptor-mediated PI 3-kinase signaling.


Biomechanical analysis of maxillary expansion in CLP patients.
To carry out a comparative biomechanical analysis of maxillary low force expansion using the quadhelix appliance in cleft and noncleft patients. We also intended to determine whether a sufficient transverse skeletal effect could be achieved among cleft patients using the quadhelix appliance. Three finite element models of the viscerocranium and neurocranium were established in which a transverse expansion of the maxilla using a quadhelix (transverse force of 2 N) was simulated. The skeletal effects at the anatomic structures of the midface and the cranial base were far more marked in the simulation models with clefts compared to the morphologically normal state. The highest expansions were measured for bilateral cleft palates. Thus, the expansion measured at the supraorbital margin was 4.7 mustrain with a bilateral cleft, 2.1 mustrain with a unilateral cleft, and only 0.2 mustrain with the morphologically normal state. For bilateral and also for unilateral bone clefts, the skeletal effect of a maxillary low force expansion with a quadhelix on the anatomical structures of the viscerocranium and neurocranium is very much larger than is the case for individuals without clefts. In the presence of a continuous cleft in the jaw and palate area, orthodontic forces (quadhelix) are apparently already sufficient to allow a skeletal expansion of the maxilla. Maxillary expansion using the quadhelix appliance represents a reasonable alternative to using conventional rapid maxillary expansion appliances among cleft patients.


Vasoactive intestinal peptide-containing nerves in Peyer's patches.
Vasoactive intestinal peptide (VIP) is a neuropeptide that is well represented in the gut tract. Previous work has demonstrated that murine T lymphocytes have high-affinity specific receptors for VIP and has implicated their interaction with VIP in the control of T-cell migration into Peyer's patches in vivo. It was postulated that this effect was mediated by interactions in the vicinity of the specialized endothelium of the postcapillary venules of Peyer's patches. We report the localization of VIP-like immunoreactivity in mouse Peyer's patches. Immunohistochemical staining was performed with heterologous antiserum against VIP using the avidin-biotin-peroxidase complex technique. VIP positivity was present near vessels of various sizes and in close proximity to small caliber vessels lined with specialized polygonal endothelial cells. These findings provide an anatomical basis for the concept that VIP may be available as a local neurophysiological signal during the migration of lymphocytes from the blood into Peyer's patches.


Reflex vascular defects in the orthostatic tachycardia syndrome of adolescents.
Dependent pooling occurs in postural orthostatic tachycardia syndrome (POTS) related to defective vasoconstriction. Increased venous pressure (Pv) >20 mmHg occurs in some patients (high Pv) but not others (normal Pv). We compared 22 patients, aged 12-18 yr, with 13 normal controls. Continuous blood pressure and strain-gauge plethysmography were used to measure supine forearm and calf blood flow, resistance, venous compliance, and microvascular filtration, and blood flow and swelling during 70 degrees head-up tilt. Supine, high Pv had normal resistance in arms (26 +/- 2 mmHg x ml(-1) x 100 ml x min) and legs (34 +/- 3 mmHg x ml(-1) x 100 ml x min) but low leg blood flow (1.5 +/- 0.4 ml x 100 ml(-1) x min(-1)). Supine leg Pv (30 +/- 2 vs. 13 +/- 1 mmHg in control) exceeded the threshold for edema (isovolumetric pressure = 19 +/- 3 mmHg). Supine, normal Pv had high blood flow in arms (4.1 +/- 0.2 vs. 3.5 +/- 0.2 ml x 100 ml(-1) x min(-1) in control) and legs (3.8 +/- 0.4 vs. 2.7 +/- 0.3 ml x 100 ml(-1) x min(-1) in control) with low resistance. With tilt, calf blood flow increased steadily in POTS with high Pv and transiently increased in normal Pv. Calf volume increased in all POTS patients. Arm blood flow increased in normal Pv only with forearm maintained at heart level. These data suggest that there are (at least) two subgroups of POTS characterized by high Pv and low flow or normal Pv and high flow. These may correspond to abnormalities in local or baroreceptor-mediated vasoconstriction, respectively.


Working smarter: the use of priorities and a model in designing nursing research.
It is imperative to maximize our limited resources conducting nursing research through targeting studies in priority areas and structuring projects to foster comprehensiveness and generalizability. This paper reviews priorities for nursing research and presents a model for research, detailing its component domains and the relationships among these domains. It further applies the model to a specific research project concerned with comparing the outcomes of two intensive community-based service programs for children with serious emotional disturbances and discusses the implications of applying this model.


LPS-induced ROS generation and changes in glutathione level and their relation to the maturation of human monocyte-derived dendritic cells.
Lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation and the concomitant decline in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) were demonstrated in human monocyte-derived dendritic cells (DC). Further, their relation to the maturation of DC, characterized by the production of cytokines, up-regulation of cell surface molecules and allo-stimulatory capacity, was examined. The LPS-induced ROS generation was demonstrated using electron paramagnetic resonance spectroscopy in intact cells, and was also confirmed using laser scanning confocal microscopy. The GSH/GSSG was assesed using a glutathione assay kit. When the DC were treated with alpha-phenyl-tert-butylnitrone, the ROS generation was attenuated, but the declined GSH/GSSG was not attenuated, and only cytokine production was suppressed among the above-mentioned maturation characteristics. When the DC were treated with glutathione monoethyl ester, both the ROS generation and the declined GSH/GSSG were attenuated, and the maturation characteristics were all suppressed. These findings suggest that the LPS-induced ROS generation and the concomitant decline in GSH/GSSG occur in human monocyte-derived DC and that the former is involved in cytokine production, while the latter is involved in the up-regulation of cell surface molecules and allo-stimulatory capacity. Since the cytokine production and the allo-stimulatory capacity of DC play an important role in inflammatory and immune responses, differential regulation of the ROS generation and the declined GSH/GSSG may be useful as therapeutic tools in diseases where both responses become entangled, such as sepsis and graft-versus-host disease.


Imaging of a pediatric abdominal mass.
The approach to the child with an abdominal mass will be aided by careful consideration of the radiographic imaging modalities available at an institution. The relative advantages, disadvantages, costs, and radiation of each modality are presented. The recommended workup of a pediatric abdominal mass, as well as the most common masses and their differential diagnosis, are outlined.


Sleep-Disordered Breathing and Cardiac Arrhythmias.
Over the past few years sleep-disordered breathing has been identified as an important factor in arrhythmogenesis and a potential target of therapy to prevent cardiac arrhythmias in selected patients. In this review we highlight the role of obstructive sleep apnea and Cheyne-Stokes respiration in the pathophysiology of arrhythmias, address their clinical effect in supraventricular and ventricular tachyarrhythmias, and in conduction disturbances, and address the role of current treatment options for sleep-disordered breathing in the primary and secondary prevention of arrhythmic events.


Laparoscopic subcapsular nephrectomy.
A 26-year-old patient with end-stage renal disease secondary to vesicoureteral reflux and recurrent pyelonephritis was referred for bilateral native nephrectomy. A transperitoneal laparoscopic approach was used. Extremely dense fibrosis was encountered around the left kidney during the dissection. A left laparoscopic subcapsular nephrectomy and a right extracapsular nephrectomy were performed. The indications and surgical technique for laparoscopic subcapsular nephrectomy are discussed.


[Advances on the immunotoxicity of airborne fine particulate matter (PM2.5)].
Exposure to airborne fine particulate matter (PM2.5) is an health risk factor, and immune system is one of the target tissues. Fine particulate matter had an effect on the host specific immune and nonspecific immune. The immune effect has two side, it can cause the damage to body, on the other hand it can also clean up the particulate matter. Immunotoxicity of PM2.5 is also associated with the other biological effect such as genotoxicity. Damage of fine particulate is through oxidant stress, inflammation and neurogenic inflammation and so on, but the detail of the mechanism for them is lacking. This review describes the immunotoxicity of PM2.5 from different aspects and levels.


Activation of N-sulfonyl oxaziridines using copper(II) catalysts: aminohydroxylations of styrenes and 1,3-dienes.
N-Sulfonyl oxaziridines are susceptible to electrophilic activation using copper(II) catalysts and react with styrenes under these conditions to provide 1,3-oxazolidines in a formal aminohydroxylation of the alkene. We propose a two-step mechanism involving a cationic intermediate to account for the rate differences and regioselectivities observed using a variety of styrenes. In accord with our hypothesis, aminohydroxylations of a range of substrates bearing electron-stabilizing groups are successful, and 1,3-dienes are particularly good substrates for copper(II)-catalyzed aminohydroxylation. Reactions of unsymmetrical dienes provide good to excellent olefin selectivity, the sense and magnitude of which can be rationalized upon consideration of the stability of the cationic intermediates suggested by our mechanism. Diastereoselective synthesis of a diverse range of densely functionalized structures can be achieved by polyfunctionalization of dienes using aminohydroxylation as a key complexity-increasing step.


On the suppression mechanism of the pseudo-Jahn-Teller effect in middle E6 (E = P, As, Sb) rings of triple-decker sandwich complexes.
Quantum chemical calculations of the CpMoE(6)MoCp (E = P, As, Sb) triple-decker sandwich complexes showed that E(6) fragments in the central decks of the complexes are planar. Analysis of molecular orbitals involved in vibrational coupling demonstrated that filling the unoccupied molecular orbitals involved in vibronic coupling with electron pairs of Mo atoms suppresses the PJT effect in the CpMoE(6)MoCp (E = P, As, Sb) sandwich, with the E(6) ring becoming planar (D(6h)) upon complex formation. The AdNDP analysis revealed that bonding between C(5)H(5)(-) units and Mo atoms has a significant ionic contribution, while bonding between Mo atoms and E(6) fragment becomes appreciably covalent through the δ-type M → L back-donation mechanism.


Testicular extramedullary myeloid cell tumor in a patient with myelodysplastic syndrome.
We report herein a case of extramedullary myeloid tumor arising bilaterally in the testes of a 66-year-old man, who had previously been diagnosed with myelodysplastic syndrome. Light microscopy of the testicular neoplasm demonstrated a tumor composed of large, slightly polygonal cells with pale blue to weakly eosinophilic cytoplasm. The tumor cells were immunoreactive for CD45, myeloperoxidase, lysozyme, CD43, and MB2. Many of the cells also expressed chloroacetate esterase. Peripheral blood and bone marrow findings were consistent with chronic myelomonocytic leukemia (FAB-CMML), particularly in the most recent material, which showed clear cellular dysplasia and an increase in the percentage of blasts in the bone marrow (15% to 20% of all nucleated cells). This case of extramedullary myeloid tumor is unusual in view of the patient's age and the testicular location. It emphasizes the importance of including extramedullary myeloid tumor in the differential diagnosis of histologically undifferentiated large-cell tumors, as well as a need to use a broad panel of immunohistochemical stains in such cases.


Endovascular therapy of acute ischemic stroke.
Intravenous fibrinolysis is the only proven treatment for acute ischemic stroke (AIS), but a limited therapeutic time window and risk of systemic hemorrhagic limit its real-world effectiveness. Minimally invasive endovascular therapies may provide opportunities to expand the AIS treatment window and enhance clinical outcomes. Current and future endovascular techniques that aim to address the hemodynamic, neuroanatomic and neurovascular complexities of acute cerebral ischemia are discussed. Scales for measuring relevant angiographic and clinical end points are also covered. Procedural timing and optimal patient selection using various imaging modalities are mentioned. Previous and ongoing clinical trials in AIS are discussed as well as emerging approaches. Endovascular therapy has opened up new horizons for treatment of AIS. It offers multiple new and promising therapeutic approaches that are not limited to one specific device or method, but could conceivably be additive and also individualized based upon each patient's characteristics.


Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation, Blood Cell Count, and IGF-1 Levels in Spinal Cord Injury-Induced Rats.
Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective effect of the oral administration of selenium nanoparticles in rats with spinal cord injury (SCI). Forty adult female rats were randomly assigned to two equal groups as experimental and control. Under general inhalation anesthesia, in both groups, SCI was created, at the T9-10 level of the column. On the third day after the operation, a supplement of selenium nanoparticle was administered to the experimental group at 0.2 mg/kg per day. The histology of the site of injury, IGF-1 serum concentrations, and changes in the white blood cells were examined in both groups at different pre-surgical and post-surgical times. The results of the current study showed a significant decrease in the total white blood cells, including lymphocyte, neutrophil, and monocyte in the experimental group compared to the control group. Histological evaluation showed that the inflammatory responses reduced significantly in the experimental group compared to the control group. In conclusion, we speculate that the decrease in the number of inflammatory cells after oral administration of the selenium nanoparticles is due to the neuroprotective effects of this nanoparticle.


Brain, emotion and decision making: the paradigmatic example of regret.
Human decisions cannot be explained solely by rational imperatives but are strongly influenced by emotion. Theoretical and behavioral studies provide a sound empirical basis to the impact of the emotion of regret in guiding choice behavior. Recent neuropsychological and neuroimaging data have stressed the fundamental role of the orbitofrontal cortex in mediating the experience of regret. Functional magnetic resonance imaging data indicate that reactivation of activity within the orbitofrontal cortex and amygdala occurring during the phase of choice, when the brain is anticipating possible future consequences of decisions, characterizes the anticipation of regret. In turn, these patterns reflect learning based on cumulative emotional experience. Moreover, affective consequences can induce specific mechanisms of cognitive control of the choice processes, involving reinforcement or avoidance of the experienced behavior.


Comparison of methods for magnetic resonance-guided [18-F]fluorodeoxyglucose positron emission tomography in human carotid arteries: reproducibility, partial volume correction, and correlation between methods.
Inflammation is a major risk factor for atherosclerotic plaque rupture and clinical events. Previous studies have shown that plaque [(18)F]fluorodeoxyglucose (FDG) uptake correlates with macrophage content. In this study we examined the reproducibility of 3 methods of quantifying plaque FDG uptake in the carotid arteries using positron emission tomography (PET). The correlation between 2 simplified uptake parameters (standardized uptake value [SUV], vessel wall-to-blood ratio [VBR]) and a gold standard technique (influx rate [K(i)]) was also determined. We used MRI to correct carotid plaque FDG uptake for partial volume error. Seven patients with a recent carotid territory transient ischemic attack underwent imaging twice within 8 days using MR and FDG-PET. MR coregistered to PET was used to delineate regions of interest, and to facilitate partial volume correction (PVC). SUV was the most reproducible parameter irrespective of whether it was normalized by body surface area (BSA), lean body mass, or weight (intraclass correlation coefficient=0.85, 0.88, and 0.90, respectively). VBR correlated better to K(i) than SUV (r=0.58 VBR, r=0.46 SUV(BSA)). PVC improved these correlations to r=0.81 VBR and r=0.76 SUV(BSA), and only slightly degraded the reproducibility of SUV (intraclass correlation coefficient=0.83-0.85). MR-guided FDG-PET is a highly reproducible technique in the carotid artery and the excellent anatomic detail provided by MR facilitates PVC. Of the methods examined, SUV(BSA)(PVC) appears to represent the best compromise between reproducible and accurate determination of FDG metabolism in carotid artery vessel wall.


Inhibition of PMA-induced human T cell proliferation by bryostatin is associated with enhanced degradation of conventional protein kinase C (cPKC): Ca2+ signals restore mitogenic activity without abrogating enhanced cPKC degradation.
Protein kinase C (PKC)-activating tumor promoters, such as PMA, are mitogenic to human T lymphocytes but, in contrast to many physiological mitogenic agonists, PMA does not operate via a receptor-coupled, IL-2-dependent signaling pathway. Bryostatin, another PKC activator, is not mitogenic to human T cells and, moreover, it inhibits the PMA-induced mitogenic response. Inhibition of the PMA-induced human T cell proliferation by bryostatin correlates with the bryostatin-induced increased degradation rate of conventional PKC (cPKC) isoenzymes. Nevertheless, bryostatin synergizes with suboptimal doses of various T cell mitogens operating via a Ca(2+)-dependent signaling pathway to induce a strong IL-2-dependent proliferative response. Our findings indicate that Ca2+ signals do not abolish the bryostatin-induced enhanced degradation rate of cPKC observed in human T cells. The results suggest that transient activation of cPKC by bryostatin induces some irreversible biochemical events that, by themselves, are not sufficient for the induction of cell proliferation, but that can be complemented by a Ca(2+)-mediated signal(s) leading to IL-2-dependent T cell proliferation. In contrast, PMA-induced IL-2-independent proliferation of human T cells appears to be dependent on the continuous presence of cPKC (that may mediate some critical events at late stages of the response) and, therefore, is inhibited by bryostatin, that induces a rapid degradation of potentially active cPKC.


Developing the knowledge base about carers and personalisation: contributions made by an exploration of carers' perspectives on personal budgets and the carer-service user relationship.
This qualitative study aimed to explore an under-researched issue within the emerging body of research about carers and personalisation - the carer-service user relationship. It was carried out across 11 English local authorities between 2011 and 2012 and focused on the impact of a change in the service user's social care arrangements to a personal budget on this relationship. Using purposive sampling and explicit inclusion criteria, data were gathered through semi-structured in-depth interviews with 23 carers in long-term dyadic relationships with an adult in receipt of social care who had changed to a personal budget. The interviews explored carers' perceptions of the carer-service user relationship before and after the advent of the personal budget and changes that had occurred. The findings were thematically analysed and reflect the fact that in addition to the effects of the move to a personal budget on the carer-service user relationship, the interviewees talked at length about a range of other effects of this move. Just over half of those interviewed felt that the personal budget had enhanced the carer-service user relationship. The other effects were both positive and negative. Three quarters reported positive outcomes, such as feeling happier, healthier and having more control over their lives. Although two thirds experienced negative feelings about having less involvement in the service user's care, these feelings eased over time and if they had confidence in the quality of the care. Over half found administering the personal budget stressful. Further analysis of these findings showed the study contributes not only to existing knowledge about the carer-service user relationship within personalisation but also to knowledge about the effects of personalisation on carers more generally. It therefore simultaneously develops the emergent knowledge base about carers and personalisation. Recommendations based on this analysis are made about future practice and research.


[Comparative estimation of a new empirical formula for the calculation of the focal power of intraocular lenses in the short anteroposterior axis of the eye].
This comparative clinical study has indicated the importance of correctly choosing a formula to calculate the focal power of an intraocular lens (IOL) in the short ocular anteroposterior axis (APA). The most accurate and comparable formulas SRK II and SRK/T at the mean ocular APA values have significant errors at an APA of less than 21 mm. The new empirical formula allows the accuracy of calculation of the focal power of IOL to be increased in the short ocular APA as compared with other currently used formulas.


Effects of vimentin disruption on the mechanoresponses of articular chondrocyte.
Human articular cartilage is subjected to repetitive mechanical loading during life time. As the only cellular component of articular cartilage, chondrocytes play a key role in the mechanotransduction within this tissue. The mechanoresponses of chondrocytes are largely determined by the cytoskeleton. Vimentin intermediate filaments, one of the major cytoskeletal components, have been shown to regulate chondrocyte phenotype. However, the contribution of vimentin in chondrocyte mechanoresponses remains less studied. In this study, we seeded goat articular chondrocytes on a soft polyacrylamide gel, and disrupted the vimentin cytoskeleton using acrylamide. Then we applied a transient stretch or compression to the cells, and measured the changes of cellular stiffness and traction forces using Optical Magnetic Twisting Cytometry and Traction Force Microscopy, respectively. In addition, to study the effects of vimentin disruption on the intracellular force generation, we treated the cells with a variety of reagents that are known to increase or decrease cytoskeletal tension. We found that, after a compression, the contractile moment and cellular stiffness were not affected in untreated chondrocytes, but were decreased in vimentin-disrupted chondrocytes; after a stretch, vimentin-disrupted chondrocytes showed a lower level of fluidization-resolidification response compared to untreated cells. Moreover, vimentin-disrupted chondrocytes didn't show much difference to control cells in responding to reagents that target actin and ROCK pathway, but showed a weaker response to histamine and isoproterenol. These findings confirmed chondrocyte vimentin as a major contributor in withstanding compressive loading, and its minor role in regulating cytoskeletal tension.


Child sexual abuse. The suspects, the suspicions and the background.
In a study of suspected cases of child sexual abuse, 22 persons (21 men and one woman) were identified as probable perpetrators according to the child psychiatric evaluation. Eight perpetrators admitted abuse, although denying certain aspects of the allegations, and two persons made what was categorized as partial confirmations. Nine cases led to a charge and eight of these to a conviction. Disease, addiction, sexual frustration, unwanted separation, ageing and adolescence were identified as factors which in individual cases seemed to have influenced a person's predisposition to abuse children sexually.


[Animal model of addiction].
Animal models are a valuable tool in the investigation of the nervous system. Many similarities between animal and human dependency behaviours have been observed. Animal model based on the self-administration response has contributed to understanding of the neurobiological basis of particular stages of the dependence process. Animals are used also to study the mechanism of alcohol dependence. Working out an animals model of addiction should include references to the clinically important phenomena related to psychological dependence which has not been displayed. This situation get us to consider the latest findings and theories about evolution of the wise human.


Use of smokeless tobacco by Mexican-American high school students.
A survey of 208 girls and 191 boys attending a public high school in southwestern New Mexico was conducted to examine students' use of smokeless tobacco products. One Mexican-American girl identified herself as a user of chewing tobacco. Of the boys 8% (17) indicated that they used chewing tobacco and 7% (15) reported that they dipped snuff. 6% (12) indicated use of both snuff and chewing tobacco. The boys included 153 Mexican-Americans of whom 7% used smokeless tobacco and 26 Anglo-Americans of whom 34% were users.


Cutting edge: a critical role of nitric [corrected] oxide in preventing inflammation upon apoptotic cell clearance.
Apoptotic cells are removed by phagocytes without causing inflammation. It remains largely unresolved whether anti-inflammatory mediators prevent neutrophil infiltration upon apoptotic cell clearance in vivo. In this study, we showed that, upon induction of apoptosis in the thymus by x-ray, inducible NO synthase knockout (KO) mice exhibited higher levels of neutrophil infiltration and production of MIP-2 and keratinocyte-derived chemokine (KC) in the thymus than wild-type (WT) mice. Furthermore, administration of NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, to x-irradiated WT mice increased the level of neutrophil infiltration to that of KO mice by the augmentation of MIP-2 and KC production. Additionally, thymic macrophages isolated from x-irradiated KO mice produced more MIP-2 and KC than those from WT mice. Thus, although apoptosis is believed to be noninflammatory, this is actually achieved by the production of immunosuppressive signals such as NO that counteract proinflammatory chemokines such as MIP-2 and KC.


The Role of Academic Partnership in Disaster Risk Management: A Systematic Review.
ABSTRACTObjective:The aim of this systematic review is to investigate the community-based academic partnership roles in disaster risk management. The assessment of the documents was conducted by reviewing abstracts and full papers of the available studies, which provided considerable background and promoted knowledge in academic interventional roles in disaster risk management. The articles were searched with a wide range of key words related to the research topic. The studies included the research available between 2000 and September 2017 in the English language. The selection of articles was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Of 997 articles, we selected 12 full-text articles that met the criteria for the final review based on the study objective. The results show that, although universities can play multidirectional roles in disaster risk management phases, the development of the academic partnership potential and collaboration for disaster risk management and disaster risk reduction for stakeholders is necessary. The universities' potential in providing sufficient disaster health literacy is not currently considered important enough in communities.Therefore, the proper context-bound models of development based on a community's skills and universities' potential should receive more attention.


Update on cardiovascular prevention in clinical practice: A position paper of the European Association of Preventive Cardiology of the European Society of Cardiology.
European guidelines on cardiovascular prevention in clinical practice were first published in 1994 and have been regularly updated, most recently in 2016, by the Sixth European Joint Task Force. Given the amount of new information that has become available since then, components from the task force and experts from the European Association of Preventive Cardiology of the European Society of Cardiology were invited to provide a summary and critical review of the most important new studies and evidence since the latest guidelines were published. The structure of the document follows that of the previous document and has six parts: Introduction (epidemiology and cost effectiveness); Cardiovascular risk; How to intervene at the population level; How to intervene at the individual level; Disease-specific interventions; and Settings: where to intervene? In fact, in keeping with the guidelines, greater emphasis has been put on a population-based approach and on disease-specific interventions, avoiding re-interpretation of information already and previously considered. Finally, the presence of several gaps in the knowledge is highlighted.


Malaria outbreak in a tribal area of Gujarat state, India.
Malaria incidence in Gujarat state had been on a general decline since 1989. However in some tribal villages in forested areas of Valsad district, southern Gujarat, there was an outbreak of malaria in September 1995. Five children died in Ashlona village. During investigation conducted in October 1995 in affected villages, the malaria parasite rate was 26% (217/833) with >91% infections due to P. falciparum. A high proportion of P. falciparum infections had ring stages suggesting active transmission. Against a minimum norm of 10% annual blood examination rate, there was a major breakdown of active surveillance for malaria. In the absence of health agencies in or near affected villages, the malaria parasite load continued to build up leading to an outbreak towards the end of monsoon season. Indoor residual spraying with deltamethrin caused significant reduction in densities of malaria vector An. culicifacies. Measures to prevent malaria outbreaks in inaccessible areas have been discussed.


Phytoremediation of polycyclic aromatic hydrocarbons in soil: part I. Dissipation of target contaminants.
Phytoremediation has been demonstrated to be a viable cleanup alternative for soils contaminated with petroleum products. This study evaluated the application of phytoremediation to soil from a manufactured gas plant (MGP) site with high concentrations of recalcitrant, polycyclic aromatic hydrocarbons (PAHs). Two greenhouse studies investigated the potential dissipation and plant translocation of PAHs by fescue (Festuca arundinacea) and switchgrass (Panicum virgatum) in the first experiment and zucchini (Curcubita pepo Raven) in the second. The MGP soil was highly hydrophobic and initially inhibited plant growth. Two unplanted controls were established with and without fertilization. In the first experiment, concentrations of PAHs decreased significantly in all treatments after 12 mo. Plant biomass and microbial numbers were statistically equivalent among plant species. PAH concentrations in plant biomass were negligible for fescue and switchgrass. In the second experiment, zucchini enhanced the dissipation of several PAHs after 90 d of treatment when compared to the unvegetated soil. Plant tissue concentrations of PAHs were not elevated in the zucchini roots and shoots, and PAHs were not detectable in the fruit.


Efficient surface enhanced Raman scattering on confeito-like gold nanoparticle-adsorbed self-assembled monolayers.
Confeito-like gold nanoparticles (AuNPs; average diameter = 80 nm) exhibiting a plasmon absorption band at 590 nm were adsorbed through immersion-adsorption on two self-assembled monolayers (SAMs) of 3-aminopropyltriethoxysilane (APTES-SAM) and polystyrene spheres coated with amine-terminated poly(amido amine) dendrimers (DEN/PS-SAM). The surface enhanced Raman scattering (SERS) effect on the SAM substrates was examined using the molecules of a probe dye, rhodamine 6G (R6G). The Raman scattering was strongly intensified on both substrates, but the enhancement factor (>10,000) of the AuNP/DEN/PS-SAM hierarchy substrate was 5-10 times higher than that of the AuNP/APTES-SAM substrate. This strong enhancement is attributed to the large surface area of the substrate and the presence of hot spots. Furthermore, analyzing the R6G concentration dependence of SERS suggested that the enhancement mechanism effectively excited the R6G molecules in the first layer on the hot spots and invoked the strong SERS effect. These results indicate that the SERS activity of confeito-like AuNPs on SAM substrates has high potential in molecular electronic devices and ultrasensitive analyses.


Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis.
To contrast the effect of the burden of vasculitis activity with the burden of adverse events on 1-year mortality of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study assessed the outcome and adverse events in patients prospectively recruited to four European AAV clinical trials. Data on 524 patients with newly diagnosed AAV were included. The burden of adverse events was quantified using a severity score for leucopenia, infection and other adverse events, with an additional weighting for follow-up duration. A 'combined burden of events' (CBOE) score was generated for each patient by summing the individual scores. Vasculitis severity was quantified using the Birmingham vasculitis activity score and glomerular filtration rate (GFR). 1-year mortality probability was 11.1%; 59% and 14% of deaths were caused by therapy-associated adverse events and active vasculitis, respectively. Using Cox regression analysis, infection score (p<0.001), adverse event score (p<0.001), leucopenia score (p<0.001) and GFR (p=0.002) were independently associated with mortality. The risk of 1-year mortality remained low (5%) with CBOE scores less than 7, but increased dramatically with scores above this. Hazard ratio for death with a CBOE greater than 7 was 14.4 (95% CI 8.4 to 24.8). Age and GFR were independent predictors of CBOE score. The greatest threat to patients with AAV in the first year of therapy is from adverse events rather than active vasculitis. The accumulation of adverse events, monitored using this scoring method, should prompt increased awareness that the patient is at high risk of death.


Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations.
While the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time. Here, we critically review exactly what DES can tell us about cerebral function. First, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms. In brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.


Pediatric cholangiopathies: diseases of the gallbladder and biliary tract.
Pediatric gallbladder and bile duct disease encompasses a broad spectrum of processes, from congenital to developmental to neoplastic. We describe normal pediatric biliary anatomy and summarize the most common pathologic entities, with a focus on non-invasive imaging techniques and findings. Ultrasound is the first-line imaging modality in children with suspected biliary pathology based on its widespread availability, cost effectiveness, and lack of ionizing radiation. MRI and MRCP are often used for further evaluation in cases of diagnostic uncertainty and for surgical planning.


Is there any correlation between the elevated plasma levels and gene variations of factor VIII in Turkish thrombosis patients?
We investigated factor VIII (FVIII) gene mutations in 20 thrombosis patients with high level of FVIII and 20 control healthy participants. Blood samples were used for the determination of FVIII levels using static timing analyze (STA) kits. Informed consent forms were collected from all participants. Factor VIII level was 237 ± 46 IU/dL in patients group; however, it was 122 ± 38 IU/dL in healthy control participants. Isolated genomic DNAs were screened using 37 pairs of primers covering promoter region and 26 exons of FVIII gene. Single-strand conformation analysis (SSCA) technique was performed for polymorphism/mutation analyses. We observed polymorph patterns in exon 6, exon 13, exon 14F, exon 19, and exon 25 regions. However, we found no evidence of an association between observed single nucleotide polymorphisms and high thrombosis levels. In conclusion, observed exons polymorphisms do not seem to be associated with a venous thromboembolism.


The relationship between women's mental health and domestic violence in semirural areas: a study in Turkey.
The authors examine the relationship between emotional disorders and domestic violence (DV) in 395 women of different ethnicities in Turkey. PRIME MD (Primary Care Evaluation of Mental Disorders) was used for diagnosis. This is a cross-sectional and epidemiological research. showed that the prevalence of emotional disorders, anxiety, and somatoform disorders was 22.8%, 24.8%, and 16.9%, respectively. The mean DV score was 2.98±1.32 over 10.00. DV scores were higher when women did not want to get married or did not have their family's blessing for marriage. Observed scores were also high for civil marriage cases, or when women had a job, had low income, or were afraid of their husbands (P<.05). The number of comorbid diagnoses increased with increase in DV scores (P<.001). Mean DV scores were higher for women diagnosed with major depression, partial remission or recurrence of major depression, panic disorder, and common anxiety (P<.05). The authors recommend that if physicians suspect any emotional disorders in women in primary care, they should evaluate for DV.


Endobronchial inflammatory polyp associated with a foreign body. Successful treatment with corticosteroids.
We describe a case of endobronchial polyp associated with a foreign body. To our knowledge, this is the first report of such an occurrence. The polyp was successfully treated with steroids. This is only the third report of steroid treatment of endobronchial polyps.


[Quantification of oxygen-induced retinopathy in the mouse].
To establish a quantifying model of retinal neovascularization suitable for examining pathogenesis and therapeutic intervention for the retinal neovascularization. Sixty 7-day-old C57BL/6J mice were divided into oxygen-induced retinopathy group and control group. In oxygen-induced retinopathy group, 32 mice were exposed to (75 +/- 2)% oxygen for 5 days and then to room air; in control group, 32 mice were raised in room air. The retinal frozen sections were stained with griffonia simplicifolia lectin B4 (GSA) which selectively stained vascular cells; or the retinal preparation perfused with fluorescein-dextran were used to test the areas of the retinal neovascularization. After 5 days of exposure to hyperoxia at postnatal day 12 (P12), the larger central radial vessels became tortuous and constricted and central perfusion became obviously decreased. After returning to room air for 2 days at P14, neovascularization was seen. This response was maximal at P17. The reproducible and quantifiable mouse model of retinal neovascularization is useful for the study of pathogenesis of retinal neovascularization and therapeutic intervention.


Brunkow exercises and low back pain.
Brunkow exercises starting with dynamic contraction of hands and feet with fixed point on the wrist or/and heal. Dynamic contraction from the beginning, transferring through kinetic chain, leads to isometric contraction of the group of muscles, which has to be included in the exercise. Starting positions determine the group of muscles to be trained. The purpose of this study is to investigate influence of Brunkow exercises on spinal motion improvement and pain relief and to evaluate use of Brunkow exercises, as a routine method for lower back pain in Physical Medicine and Rehabilitation Centres. Thirty-four patients with symptoms of low back pain were included in study. Patients received a mean of 14.9 treatments with standard deviation of 8.96. All patients were assessed before and after the treatment for spinal mobility and flexibility as well as pain intensity. All parameters for spinal movements showed statistically significant improvement in patients with low back pain who practiced Brunkow exercise program at the end of treatment in relations to pre-treatment values, with significant difference of p<0.01 for all motions. Pain was reduced on VAS for X=1.,7 with S.D. 1.97. Difference Test was t=6.020 with significant difference p<0.01. Flexibility of spine increased, so average difference in values before and after treatment for Shober test was 0.5 cm with SD 0.65. Difference test was t=3.794 with significant difference p<0.01. Brunkow exercises for low back pain are beneficial treatment for increasing flexibility and mobility of spine and improving the pain.


Expression of FOXL2 and RSPO1 in Hen Ovarian Follicles and Implication of Exogenous Leptin in Modulating Their mRNA Expression in In Vitro Cultured Granulosa Cells.
In this study, using a laying hen model, we determined the expression of FOXL2 and RSPO1 in different central and peripheral tissue and ovarian follicles at different stages of development. At the same time, mRNA expression of both genes in granulosa and theca cells harvested from follicles at different stages of folliculogenesis was also evaluated. Finally, we assessed the effect of leptin treatment on expression of FOXL2 and RSPO1 in in vitro cultured granulosa cells harvested from 1-5 mm to F3-F1 follicles. Our RT-qPCR results revealed that a comparatively higher expression of FOXL2 and RSPO1 was observed in ovary, hypothalamus, and pituitary. Abundant mRNA expression of FOXL2 was observed in small prehierarchical follicles (1-1.9 and 2-2.9 mm follicles; p < 0.05), whereas mRNA expression of RSPO1 showed an increasing trend in large hierarchical follicles (F5-F1), and its abundant expression was observed in post-ovulatory follicles. FOXL2 mRNA expression was stable in granulosa cells harvested from 3-5 mm to F4 follicles, and exhibited a significantly higher expression in large hierarchical follicles. Conversely, relatively low mRNA expression of FOXL2 was observed in theca cells. RSPO1 mRNA expression was relatively lower in granulosa cells; however, theca cells exhibited a significantly higher mRNA expression of RSPO1 in F4 to F1 follicles. In the next experiment, we treated the in vitro cultured granulosa cells with different concentrations (1, 10, 100, and 1000 ng/mL) of exogenous leptin. Compared to the control group, a significant increase in the expression of FOXL2 was observed in groups treated with 1, 10, and 100 ng/mL leptin, whereas expression of RSPO1 was increased in all leptin-treated groups. When treated with 100 ng/mL leptin, FOXL2 and RSPO1 expression was upregulated in cultured granulosa cells harvested from both large hierarchical (F3-F1) and small prehierarchical follicles (1-5 mm). Based on these findings and evidence from mainstream literature, we envisage that FOXL2 and RSPO1 genes (in connection with hypothalamic-hypophysis axis) and leptin (via modulation of FOXL2 and RSPO1 expression) might have significant physiological roles, at least in part, in modulating the ovarian mechanisms, such as follicle development, selection, and steroidogenesis in laying hens.


[Clinical application of universal spine system in reconstruction of lumbar sacrum joint after resection of sacrum tumor].
To investigate the operative indications and techniques of the universal spine system (USS) in reconstruction of the stability of the lumbar-sacrum joint after resection of sacrum tumor. Nine patients were treated with USS after resection of sacrum tumor. Among them, there were 6 males and 3 females, aged from 34-60 years. The operation could be divided into four main procedures: 1. to resect sacrum tumor; 2. to insert the pedicle screw into the normal pedicle (L3 or L4 or L5) above the region of laminectomy; 3. to insert the lower screw into the iliac plate; 4. to put the rods, bone graft and links. There was no recurrence of sacrum tumor by MRI examination during 7-17 month follow-up. The pains of the lumbar-sacrum joint and the spinal nerve root were relieved obviously. The patients could stand and walked normally. There was no loose screw and no fracture of the screw and the rod. There was no appearance of the enlarged screw passage, the lessened pelvis and lowed L5 spine. Reconstruction of the lumbar-sacrum joint by the USS after resection of sacrum tumor is a practical operation clinically. It is characterized by the easy manipulation, few complication and stable fixation.


Redox regulation of lung inflammation: role of NADPH oxidase and NF-kappaB signalling.
Regulation of reduction/oxidation (redox) state is critical for cell viability, activation, proliferation and organ function, and imbalance of oxidant/antioxidant balance is implicated in various chronic respiratory inflammatory diseases, such as asthma, pulmonary fibrosis and chronic obstructive pulmonary disease. CS (cigarette smoke) is a complex mixture of various noxious gases and condensed tar particles. These components elicit oxidative stress in lungs by continuous generation of ROS (reactive oxygen species) and various inflammatory mediators. In the present review, we have discussed the role of oxidative stress in triggering the inflammatory response in the lungs in response to CS by demonstrating the role of NADPH oxidase, redox-sensitive transcription factors, such as pro-inflammatory NF-kappaB (nuclear factor kappaB) and antioxidant Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), as well as HDAC (histone deacetylase) in pro-inflammatory cytokine release by disruption of HDAC-RelA/p65 NF-kappaB complex.


Follow-up after treatment of cervical intraepithelial neoplasia by human papillomavirus genotyping.
To assess the use of human papillomavirus genotyping in cervical intraepithelial neoplasia posttreatment follow-up. Prospective observational study. Ninety women underwent cytologic testing and human papillomavirus genotyping at the follow-up visit after conization. Cones were retrospectively genotyped. A second cytologic follow-up was performed. Margin status and presence of cervical intraepithelial neoplasia 3+ in the cone were poor predictors of treatment outcome (sensitivity, < 50%; diagnostic odds ratio, <or= 2.5). Presence of high-/intermediate-risk human papillomavirus types predicted 100% of residual high-grade squamous intraepithelial lesion/cervical intraepithelial 2+ at a specificity of 73%. Testing only 13 high-risk types showed equal sensitivity but higher specificity (86%; P < .01). Persistent high-risk human papillomavirus infection (13 types) detected high-grade residual disease with a sensitivity of 60% at a very high specificity (95%), resulting in a positive predictive value of 43%, which exceeded the positive predictive values of all other criteria. Testing for high-risk human papillomavirus identified all recurrent/residual high-grade cervical intraepithelial neoplasia. Focusing on women with persistent human papillomavirus types through genotyping substantially increased positive predictive value but at a loss in sensitivity.


Laryngeal pyogenic granulomas do not express oestrogen or progesterone receptors.
The objective of this study was to determine the presence of oestrogen and/or progesterone receptors in laryngeal pyogenic granulomas and the impact of these receptors on recurrence of pyogenic granulomas. Twenty-two consecutive patients who underwent microlaryngoscopy and removal of pyogenic granulomas were studied retrospectively. The indications for surgery were airway compromise, failure of medical therapy and suspicion of malignancy. Twelve of these patients' granulomas were analysed for oestrogen and progesterone receptors. Charts were analysed for age, sex, location of the lesion, history of trauma, intubation or gastroesophageal reflux disease (GORD), airway symptoms and recurrence. Oestrogen/progesterone receptors were analysed following deparaffinization of specimens and immunostaining with prediluted anti-oestrogen receptor monoclonal antibody and anti-progesterone receptor monoclonal antibody. No sample expressed oestrogen or progesterone receptors. There were too few recurrences to detect if lack of these receptors played any role in determining outcome in this group. Most of the patients had a history of GORD, intubation or laryngeal surgery. There were 12 recurrences in four patients. All of the recurrences improved on prolonged courses of omeprazole. Pyogenic granulomas do not possess oestrogen or progesterone receptors and are unlikely to respond to hormonal therapy. Patients who have, or are being operated on for, laryngeal pyogenic granulomas should be placed on proton pump inhibitors to decrease the likelihood of recurrence.


An Alternative Method to Treat Ankyloglossia.
Ankyloglossia entails short lingual frenum, impairing satisfactory tongue movement and leading to problems related to deglutition, feeding and diction. This clinical report uses laser technology, rather than traditional surgical procedure with scalpel, to perform a lingual frenulotomy on a 9-year old child diagnosed with ankyloglossia, aiming to investigate more conservative and less traumatic dental procedures. Due to the many advantages of the laser device, such as bloodless surgical field, absence of sutures, minimal swelling and post-surgical pain, the high intensity diode laser is a viable alternative technique in soft tissue surgeries.


Domestic violence is associated with environmental suppression of IQ in young children.
Research suggests that exposure to extreme stress in childhood, such as domestic violence, affects children's neurocognitive development, leading to lower intelligence. But studies have been unable to account for genetic influences that might confound the association between domestic violence and lower intelligence. This twin study tested whether domestic violence had environmentally mediated effects on young children's intelligence. Children's IQs were assessed for a population sample of 1116 monozygotic and dizygotic 5-year-old twin pairs in England. Mothers reported their experience of domestic violence in the previous 5 years. Ordinary least squares regression showed that domestic violence was uniquely associated with IQ suppression in a dose-response relationship. Children exposed to high levels of domestic violence had IQs that were, on average, 8 points lower than unexposed children. Structural equation models showed that adult domestic violence accounted for 4% of the variation, on average, in child IQ, independent of latent genetic influences. The findings are consistent with animal experiments and human correlational studies documenting the harmful effects of extreme stress on brain development Programs that successfully reduce domestic violence should also have beneficial effects on children's cognitive development.


Synthesis of 1-aminoisoquinolines via Rh(III)-catalyzed oxidative coupling.
[RhCp*Cl(2)](2) can catalyze the oxidative coupling of N-aryl and N-alkyl benzamidines with alkynes to give N-substituted 1-aminoisoquinolines in high selectivity.


The influence of general and case-related experience on primary care treatment decision making.
In an effort to examine how general vs case-related clinical experience influenced physicians' treatment decisions, four clinical case vignettes (rheumatoid arthritis, fever of undetermined origin, exercise-induced asthma, and cor pulmonale) were presented to 387 primary care physicians. For each case, physicians indicated (1) their willingness to proceed with treatment without seeking additional information, (2) their preferences for sources of supplementary information, and (3) their preferences for continued care responsibility. The results indicated that the nature of the particular vignette had a major impact on how physicians made treatment decisions. Also, having greater case-related experience and being younger led to greater willingness to proceed with treatment and preferences for continued care responsibility. Preferences for information sources were largely independent of either form of experience. Treatment decision making appears to be quite dependent on experience with similar problems and being up-to-date on current treatment procedures.


Real-time monitoring of propofol in expired air in humans undergoing total intravenous anesthesia.
The physicochemical properties of propofol could allow diffusion across the alveolocapillary membrane and a measurable degree of pulmonary propofol elimination. The authors tested this hypothesis and showed that propofol can be quantified in expiratory air and that propofol breath concentrations reflect blood concentrations. This could allow real-time monitoring of relative changes in the propofol concentration in arterial blood during total intravenous anesthesia. The authors measured gas-phase propofol using a mass spectrometry system based on ion-molecule reactions coupled with quadrupole mass spectrometry which provides a highly sensitive method for on-line and off-line measurements of organic and inorganic compounds in gases. In a first sequence of experiments, the authors sampled blood from neurosurgery patients undergoing total intravenous anesthesia and performed propofol headspace determination above the blood sample using an auto-sampler connected to the mass spectrometry system. In a second set of experiments, the mass spectrometry system was connected directly to neurosurgery patients undergoing target-controlled infusion via a T piece inserted between the endotracheal tube and the Y connector of the anesthesia machine, and end-expiratory propofol concentrations were measured on-line. A close correlation between propofol whole blood concentration and propofol headspace was found (range of Pearson r, 0.846-0.957; P < 0.01; n = 6). End-expiratory propofol signals mirrored whole blood values with close intraindividual correlations between both parameters (range of Pearson r, 0.784-0.985; n = 11). Ion-molecule reaction mass spectrometry may allow the continuous and noninvasive monitoring of expiratory propofol levels in patients undergoing general anesthesia.


Genetic determinants of autism in individuals with deletions of 18q.
Previous research has suggested that individuals with constitutional hemizygosity of 18q have a higher risk of autistic-like behaviors. We sought to identify genomic factors located on chromosome 18 as well as other loci that correlate with autistic behaviors. One hundred and five individuals with 18q- were assessed by high-resolution oligo aCGH and by parental ratings of behavior on the Gilliam Autism Rating Scale. Forty-five individuals (43%) had scores within the "possibly" or "very likely" categories of risk for an autism diagnosis. We searched for genetic determinants of autism by (1) identifying additional chromosome copy number changes (2) Identifying common regions of hemizygosity on 18q, and (3) evaluating four regions containing candidate genes located on 18q (MBD1, TCF4, NETO1, FBXO15). Three individuals with a "very likely" probability of autism had a captured 17p telomere in addition to the 18q deletion suggesting a possible synergy between hemizygosity of 18q and trigosity of 17p. In addition, two of the individuals with an 18q deletion and a "very likely" probability of autism rating had a duplication of the entire short arm of chromosome 18. Although no common region of hemizygosity on 18q was identified, analysis of four regions containing candidate genes suggested that individuals were significantly more likely to exhibit autistic-like behaviors if their region of hemizygosity included TCF4, NETO1, and FBXO15 than if they had any other combination of hemizygosity of the candidate genes. Taken together, these findings identify several new potential candidate genes or regions for autistic behaviors.


Acute and repeated vapor exposure toxicology of 3-(methylthio)propionaldehyde.
Because of its vapor pressure (0.6 torr at 20 C) there is a potential for vapor exposure to 3-(methylthio)propionaldehyde (3-MTP) vapor. Liquid 3-MTP may contain trace amounts of acrolein (up to 0.1%), and therefore acrolein vapor may also be present. Acute exposure (24 min to 4 h) of rats to substantially saturated atmospheres of 3-MTP generated statically (measured concentrations of 261-951 ppm) resulted in marked ocular and respiratory irritancy followed by death. Deaths occurred either during exposure or a few days postexposure, depending on exposure time. Measured acrolein vapor concentrations in these static studies were 16.7-216 ppm. In contrast, when substantially saturated vapor atmospheres were generated dynamically (277-320 ppm 3-MTP) only minor transient signs of irritancy were present, and only 1/40 exposed animals died. Acrolein vapor concentrations ranged 0-6.8 ppm. These findings indicate that the toxicity associated with acute static exposures to 3-MTP vapor was due to accumulated acrolein vapor, and that 3-MTP per se has a low order of acute vapor inhalation toxicity. In a first 9-d repeated vapor exposure study (6 h/d) rats were exposed to 0, 23.6, 96.8 or 246.2 ppm 3-MTP vapor; the mean acrolein concentration was 1.34 ppm (range 1.08-1.72 ppm). There were no mortalities, but exposure concentration-related indications of toxicity were present. These included reduced body weights, hematology (increased lymphocytes), serum chemistry (reduced total protein and globulin), and respiratory tract histopathology. The latter consisted mainly of squamous metaplasia in the anterior nasal passages at all concentrations, being minimal at 23.6 ppm. At the high concentration there was also olfactory atrophy and squamous metaplasia in the larynx, trachea, and larger bronchi; 23.6 ppm was a threshold effect level. The respiratory tract histopathology was compatible with exposure to acrolein vapor. In a second 9-d study, rats were exposed to 0, 0.47, 4.99 or 50.5 ppm (6 h/d); no acrolein could be detected in the chamber air samples. There were no differences between the controls (air alone) and 3-MTP exposed animals with respect to signs, body weights, food consumption, hematology, serum chemistry, urinalysis, and gross and microscopic pathology. Without detectable acrolein vapor, 50.5 ppm 3-MTP was a no observable effects level.


[Research progress in telemonitoring systems and automatic analysis methods of ambulatory ECG signals].
This paper reviews the research progress in telemonitoring systems and automatic analysis of ECG signals. The key problems, urgently to be solved, about the automatic analysis in ECG telemonitoring systems are discussed.


Retroperitoneal sacrocolpopexy for correction of prolapse of vaginal vault.
The problem of prolapse of vaginal vault has a clearly defined anatomic basis and so does it surgical restoration. Herein, we present our experience with a technique that is a modification of the abdominal sacrocolpopexy of Randall and Nichols. Our procedure is characterized by the use of a segment of Teflon (polytetrafluoroethylene) vascular prosthesis placed in the retroperitoneum at the sacral concavity to fasten the vaginal vault to the promontory. We have obtained excellent results with its application in 18 patients, who had a return to normal sexual activity and no recurrences during a follow-up period of 36 months.


Undiagnosed diabetes mellitus and metabolic control assessed by HbA(1c) among residents of nursing homes.
Diabetes prevalence and diabetes care in residents of nursing homes is a neglected area of research although the growing number of elderly people with diabetes represents a growing challenge for health care in most countries. In this study, we used HbA(1c) measurement to estimate the percentage of residents with undiagnosed diabetes and the quality of metabolic control of subjects with known diabetes in nursing homes. All 41 nursing homes in the county of Heinsberg in Northrhine-Westfalia were asked to complete a structured questionnaire on the prevalence of known diabetes among all residents. In addition, all residents were offered measurement of glycated haemoglobin A1c (HbA(1c)) from a capillary blood sample. Undiagnosed diabetes was defined by a HbA(1c) level greater than 6.0%. 39 nursing homes participated in the study comprising 99.6% of all residents. Among the 1936 residents 507 (26.2%) were known to suffer from diabetes. Among the latter 37.0% were under insulin treatment. Blood samples for the determination of HbA(1c) were obtained from 979 subjects from 20 nursing homes. Among those 60 years old or above (n = 843) the mean level of HbA(1c) in those with known diabetes was 7.3 +/- 1.5% and in those without 6.1 +/- 0.9%. Only 16.7% of the subjects with known diabetes had a HbA(1c) greater than 8.5% indicating poor metabolic control. Among the residents previously not known to have diabetes 47.2% had a HbA(1c) equal to or greater than 6.1%, but among those only 8.5% had a HbA(1c) greater than 7.0%. Although the prevalence of undiagnosed diabetes mellitus defined by HbA(1c) above the normal range in elderly nursing home residents is high, only few may require treatment. The quality of metabolic control among those with known diabetes mellitus is better than expected.


Ultrasonic irradiation of dichlorvos: decomposition mechanism.
The sonochemical degradation of dichlorvos in a batch reactor is investigated. Dichlorvos was irradiated with 500 kHz ultrasound at input powers ranging from 86 to 161 W. Acoustic power and sparge gas are two factors which greatly affect sonochemical degradation efficiency. Increasing total acoustic power input from 86 to 161 W resulted in a change in the rate constant from 0.018 +/- 0.001 min-1 to 0.037 +/- 0.002 min-1. The change in rate constant due to sparge gas (Argon, Oxygen, and Argon/Oxygen (60/40% v/v) mixture) at a power of 161 W is also investigated, with the Argon/Oxygen mixture giving the highest rate constant (0.079 +/- 0.005 min-1). Total organic carbon and ion chromatographic analyses are employed to determine and quantify major degradation products, including dimethyl phosphate, formate, carbon dioxide, chloride, and phosphate. The extent of mineralization, indicated by a decrease in the total organic carbon, and the formation of the various intermediates and products, varies with saturating gas. A pathway for dichlorvos decomposition is proposed, based upon formation rates of the various intermediates and products and the rate of decrease of the total organic carbon in the system. The limiting steps in the mineralization pathway appear to be transformation of dimethyl phosphate and formate.


Expression of cell-adhesion molecules in the salivary gland microenvironment of Sjögren's syndrome.
The potential role of cell adhesion molecules in the pathogenesis of Sjögren's syndrome (SS) was assessed by examining their expression in salivary gland (SGL) tissue. Intercellular adhesion molecule type 1 (ICAM-1), lymphocyte function-associated antigen type 1 (LFA-1), LFA-3, CD2, and CD44 expression were determined using indirect immunofluorescence techniques. In inflamed labial SGL tissue, ICAM-1 expression was evident on infiltrating LFA-1+/CD2+/LFA-3+ mononuclear cells, and to a limited extent on SGL acinar epithelial cells adjacent to sites of intense inflammation. In SS, the SGL microenvironment is characterized by only a modest up-regulation of ICAM-1 expression on epithelial cells, despite the presence of T cells bearing an activated phenotype.


Epidemiology and risk factors of brucellosis in Alexandria governorate.
This study aimed to describe the trend and to identify possible risk factors for brucellosis in Alexandria in northern Egypt. We enrolled 72 confirmed cases of brucellosis and 144 age-matched controls in this study. Participants were interviewed at home using a structured questionnaire. Working with animals, breeding goats and eating ice cream bought from street vendors were significantly associated (P < 0.05) with brucellosis by univariate and multivariate analysis. Contact with infected animals and their products was the most important method of transmission.


[A comparison between radiologic and endoscopic examinations of early cancer of the stomach (author's transl)].
Comparison between radiologic and endoscopic-bioptic examinations shows that, in early cancer, great demands are made on the radiologic technique and experience of the examiner. An integrated technique using relief- and double-contrast with additional induced hypotony can achieve demonstration of circumscribed shallow changes of less than 2 cm diameter in all segments of the stomach. With this technique over 80% of early cancers can be detected radiologically.


Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide.
Our objective was to investigate the effect of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of gliclazide, a sulfonylurea antidiabetic drug. In a randomized 2-way crossover study with a 4-week washout period, 9 healthy Korean subjects were treated once daily for 6 days with 600 mg rifampin or with placebo. On day 7, a single dose of 80 mg gliclazide was administered orally. Plasma gliclazide, blood glucose, and insulin concentrations were measured. Rifampin decreased the mean area under the plasma concentration-time curve for gliclazide by 70% (P <.001) and the mean elimination half-life from 9.5 to 3.3 hours (P <.05). The apparent oral clearance of gliclazide increased about 4-fold after rifampin treatment (P <.001). A significant difference in the blood glucose response to gliclazide was observed between the placebo and rifampin phases. The effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide suggests that rifampin affects the disposition of gliclazide in humans, possibly by the induction of cytochrome P450 2C9. Concomitant use of rifampin with gliclazide can considerably reduce the glucose-lowering effects of gliclazide.


Highly Functionalized Ring B Labdane Synthesis as Key Intermediate in the Route to Forskolin.
Sclareol has been employed as starting material for the synthesis of several advanced intermediates towards the synthesis of highly ring B oxygenated labdanes. Dinorlabdanes 6,7,8,9-tetraoxygenated with 6,7-dioxygenated functionalities with a-cis or O-cis dispositions, have been prepared and can be used for forskolin or analogues synthesis.


Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center.
To better understand the feasibility of using imatinib, a tyrosine kinase inhibitor, to treat active diffuse cutaneous systemic sclerosis (dcSSc). We performed a 6-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study of imatinib in patients with active dcSSc. Data on safety, modified Rodnan skin thickness scores (MRSS), Health Assessment Questionnaire (HAQ) scores, patient's and physician's global assessments (100-mm visual analog scale), and biomarkers in serum and skin biopsy samples were collected. We used a 4:1 randomization strategy (imatinib 200 mg administered twice a day versus placebo), stratifying according to current use of methotrexate. The plan was to enroll 20 dcSSc patients. After enrolling 10 patients (9 receiving active drug and 1 receiving placebo), we found poor tolerability and high rates of adverse events with imatinib, and study enrollment was discontinued. There was no significant difference in the mean MRSS in all patients who took imatinib (31.1 at baseline versus 29.4 at 6 months) or in only those who completed 6 months of imatinib (31.0 at baseline versus 30.3 at 6 months), and there was no difference in the C-reactive protein level, erythrocyte sedimentation rate, physician's global assessment, patient's global assessment, response to the Health Transition query, or the HAQ scores between those who did and those who did not complete 6 months of therapy. Side effects were edema, fluid retention, fatigue, nausea, cramps/myalgias, diarrhea, alopecia, and anemia. Most side effects occurred within the first week of treatment, and even when imatinib was reintroduced at a lower dosage (200 mg daily), it was poorly tolerated. Two patients were hospitalized because of side effects of the medication. In general, biomarker levels in plasma and skin did not change. Imatinib was poorly tolerated, and this could limit its application in SSc. The study was too small to form conclusions about the efficacy of imatinib in SSc.


General view of vestibular disorders.
The role of the labyrinthine receptors is to transduce the forces associated with head acceleration into a biological signal. Vestibular centres in the brain use this signal, in cooperation with visual and somatosensory signals, to detect the motion of the head and its position relative to gravity vector and to produce motor reflexes to maintain equilibrium and accurate vision during head movements. The evaluation of vestibular function is the mainstay of the general otoneurological examination and relies upon testing for static and dynamic imbalance in the vestibular system, positional testing, eye movement testing and testing for visual-vestibular interaction. The more recent aspects of two conditions, benign paroxysmal positional vertigo and ocular tilt reaction, are discussed. Their pathophysiological mechanisms are reinterpreted and re-evaluated on the basis of present knowledge of vestibulo-oculomotor function.


Body composition of mice following exposure to 4300 and 6100 meters.
Male Swiss mice were exposed for 3 and 7 d to simulated altitudes of 4300 and 6100 m. Body weight losses were enhanced at the higher elevation and after longer exposure at each elevation. Carcass analyses showed the weight losses to be attributable to decrements in body water and fat content. The water decrements were a little greater than the fat decrements after all exposure conditions. At both elevations, however, fat loss increased significantly as exposure was extended from 3 to 7 d whereas water loss remained unchanged.


IPF patients are limited by mechanical and not pulmonary-vascular factors - results of a derivation-validation cohort study.
During cardiopulmonary exercise testing (CPET), Idiopathic Pulmonary Fibrosis (IPF) patients do not reach their direct maximum voluntary ventilation (MVV) and have deranged gas exchange. Their exercise limitation is therefore attributed to a pulmonary vascular mechanism. We studied two cohorts (derivation and validation) of IPF patients with lung function testing and CPET. Maximal ventilation at exercise (VEpeak) was compared to direct MVV by Bland-Altman analysis. In the derivation cohort (n = 101), direct MVV over-estimated VEpeak by a factor of 1.51, driven by respiratory rate during MVV that was 1.99 times higher at rest as compared to VEpeak at exercise. The formula (FEV1 × 20.1) + 15.4 was shown to predict VEpeak (r2 = 0.56) in the derivation cohort. In the validation cohort of 78 patients, VEpeak was within a factor of 1.27 (6.8 l/min) of predicted according to the novel formula. According to the novel prediction formula the majority of patients (58%) in the entire cohort have VEpeak within 85% of their predicted MVV, which would indicate a mechanical respiratory limitation to exercise. Estimation of direct MVV performed at rest leads to significant over-estimation of the breathing reserve in IPF patients. This may lead to over-diagnosis of pulmonary vascular limitation in these patients. Expected maximal ventilation at exercise may be accurately predicted indirectly by an IPF-specific formula.


Dobutamine stress echocardiography and the resting but not exercise electrocardiograph predict severe coronary artery disease in renal transplant candidates.
After renal transplantation half of all deaths are cardiac, so prior detection and treatment of severe coronary artery disease (CAD) is advocated. The aim of this study was to identify non-invasive predictors of severe CAD in a group of renal transplant candidates. One hundred and twenty-five renal transplant candidates (mean age 52+/-12 years, 80 male, mean creatinine 608+/-272 micromol/l) were studied. All had coronary angiography, dobutamine stress echocardiography, and resting and exercise electrocardiograph (ECG). Severe CAD was defined as luminal stenosis >70% by visual estimation in at least one epicardial artery. The resting ECG was recorded as abnormal if there was evidence of pathological Q waves, left ventricular hypertrophy, ST depression or elevation > or=1 mm, T wave inversion or bundle branch block. Total exercise time, maximal ST segment change, maximal heart rate and systolic blood pressure, limiting symptoms and Duke score were calculated during the exercise ECG test. Of the patients, 36 (29%) had severe CAD, 55% were on dialysis and 39% were diabetic. Patients with severe CAD were significantly older (P<0.001), had higher total cholesterol (P = 0.05), higher CRP level (P = 0.05), larger left ventricular (LV), end systolic and end diastolic diameter (P = 0.007 for each), and lower LV ejection fraction (P = 0.01). A significantly higher percentage were diabetic (P = 0.05), had previous graft failure (P = 0.05), mitral annular calcification (P = 0.04), an abnormal resting ECG (P = 0.001) and positive stress echo result (P<0.001). Cardiac symptoms and exercise ECG parameters were not significantly different in the two groups. Stepwise logistic regression identified an abnormal resting ECG (OR 7, 95% CI 2, 34, P = 0.013) and positive stress echo result (OR 23, 95% CI 6, 88, P<0.001) as independent predictors of severe CAD. In selecting which potential renal transplant candidates should undergo coronary angiography, resting ECG and dobutamine stress echocardiography are the best predictors of severe CAD.


Complete synthesis and transcription in vitro of a gene coding for human ribosomal 5S RNA.
The gene coding for the major human ribosomal 5S RNA was chemically synthesized and cloned into a pUC13 vector. This approach was taken, because attempts to isolate the human 5S gene have thus far yielded either pseudogenes or variant 5S genes of unknown function. The synthetic human gene was transcribed by RNA polymerase III either in a crude HeLa cell extract or in a system reconstituted from partially purified transcription factors. Comparative studies with the Xenopus laevis somatic 5S gene show that the human gene is transcribed with similar fidelity and an efficiency of about 80% under optimal conditions. The time-course of transcription and optimal concentrations of template and transcription factors were found to be similar for both genes studied. The synthetic gene described may prove useful to study its interaction with human transcription factors in a homologous system.


A theoretical study of dihydrogen bonds in small protonated rings: aziridine and azetidine cations.
B3LYP/6-311++G(d,p) calculations were used to predict some molecular properties of the C2H6N+...BeH2, C2H6N...MgH2, C3H8N...BeH2 and C3H8N+...MgH2 dihydrogen-bonded complexes. In these systems, it was demonstrated that the C2H6N+ and C3H8N+ protonated rings are potential candidates to bind with protonic hydrogens derived from alkaline earth metal compounds, BeH2 and MgH2. In terms of structural parameters and quantification of the dihydrogen bond energies, we should mention that the C2H6N+ three-membered ring provides the formation of stronger bound systems, which are 4.0 kJ mol-1 more stables than C3H8N+ four-membered ones. As complement, the analysis of the infrared spectrum indicated that red-shifts and blue-shifts are occurring in the N-H bonds of both C2H6N+ and C3H8N+ cationic rings. However, these two vibrational shifts were also verified on BeH2 and MgH2, what lead us to affirm that cationic compounds derived from small nitrogen rings and earth alkaline molecules are able to form unusual dihydrogen-bonded complexes by means of distinct spectroscopic phenomena, the red-shits and blue-shifts.


Sensitivity of the properties of ruthenium "blue dimer" to method, basis set, and continuum model.
The ruthenium "blue dimer" [(bpy)(2)Ru(III)OH(2)](2)O(4+) is best known as the first well-defined molecular catalyst for water oxidation. It has been subject to numerous computational studies primarily employing density functional theory. However, those studies have been limited in the functionals, basis sets, and continuum models employed. The controversy in the calculated electronic structure and the reaction energetics of this catalyst highlights the necessity of benchmark calculations that explore the role of density functionals, basis sets, and continuum models upon the essential features of blue-dimer reactivity. In this paper, we report Kohn-Sham complete basis set (KS-CBS) limit extrapolations of the electronic structure of "blue dimer" using GGA (BPW91 and BP86), hybrid-GGA (B3LYP), and meta-GGA (M06-L) density functionals. The dependence of solvation free energy corrections on the different cavity types (UFF, UA0, UAHF, UAKS, Bondi, and Pauling) within polarizable and conductor-like polarizable continuum model has also been investigated. The most common basis sets of double-zeta quality are shown to yield results close to the KS-CBS limit; however, large variations are observed in the reaction energetics as a function of density functional and continuum cavity model employed.


The zebrafish genome: a review and msx gene case study.
Zebrafish is one of several important teleost models for understanding principles of vertebrate developmental, molecular, organismal, genetic, evolutionary, and genomic biology. Efficient investigation of the molecular genetic basis of induced mutations depends on knowledge of the zebrafish genome. Principles of zebrafish genomic analysis, including gene mapping, ortholog identification, conservation of syntenies, genome duplication, and evolution of duplicate gene function are discussed here using as a case study the zebrafish msxa, msxb, msxc, msxd, and msxe genes, which together constitute zebrafish orthologs of tetrapod Msx1, Msx2, and Msx3. Genomic analysis suggests orthologs for this difficult to understand group of paralogs.


Microchimerism after liver transplantation: prevalence and methodological aspects of detection.
Microchimerism after liver transplantation is a readily observed phenomenon. The immunological implications, however, remain unclear. Moreover, methodological approaches and their detection limits in the study of allogeneic microchimerism have not been studied in detail. Therefore, the aim of this study was to evaluate the single-step and nested formats of the polymerase chain reaction/sequence-specific priming (PCR-SSP) approach under standardized conditions. For that purpose, a panel of recombinant plasmid clones was generated by PCR cloning. The panel contained the allelic sequences of the second exon of DRB1 covering all DR specificities on a low-resolution level. Using this panel, limiting dilution assays for various DR sequences in the presence and absence of competitor DNA were carried out to determine the minimal number of copies required for detection by single-step and nested PCR-SSP. Subsequently, 22 liver transplant recipients were analyzed in a retrospective study for the presence of allogeneic microchimerism by nested PCR-SSP. Although at least 10 copies of template DNA could be detected by nested PCR-SSP overall, single-step PCR-SSP was on average 10(2) to 10(3) times less sensitive. Upon the addition of human competitor DNA, the detection limits decreased on average by a factor of 10. In addition, sequence-specific differences in amplification efficiency could be appreciated. Using nested PCR-SSP, peripheral blood allogeneic microchimerism could be observed in 17 of 22 HLA-DR-mismatched liver recipients. Recombinants representing recipient DRB1 specificities were used to exclude false-positive results by lack of cross-reactivities of the donor-specific primers and to evaluate negative results due to sample-related reduced amplification efficiencies in microchimerism-negative recipients. In donor/recipient combinations that differed by at least one DR specificity, allogeneic microchimerism was seen in 87.5% of the cases. In five chimerism-negative cases, sample-related problems were detected in two cases. The optimization and standardization of the detection of genomic HLA sequences at low copy number may be greatly facilitated using a clonal reference system. Furthermore, a clonal reference system may be used to conduct cross-priming experiments to exclude false-positive results and may allow the determination of sample-specific detection limits for donor-derived HLA-DR specificities in chimerism-negative patients. Our evaluation of the PCR-SSP approach for the study of allogeneic microchimerism indicated that nested PCR-SSP provides the most sensitive format when HLA sequences are targeted. Yet, the detection sensitivity may vary between individual alleles and specificities. Allogeneic microchimerism in liver recipients can be observed in the majority of patients. However, the detection may be subject to the degree of mismatching, the HLA-DR alleles involved, and sample-related impaired PCR amplification efficiency.


Efficacy of antibiotics against influenza-like illness in an influenza epidemic.
To determine if an antibiotic reduces the incidence of complications associated with influenza-like illness during an influenza epidemic. During the outbreak of influenza in Kobe in 1998, 85 patients suffering from an influenza-like illness were randomly assigned to two groups. Patients received placebo or sultamicillin orally for 4 days. The incidence of complications of influenza-like illness were compared and statistically assessed. There was no difference in the duration of fever or the incidence of acute otitis media. However, the incidence of pneumonia was significantly lower in the sultamicillin group than the placebo group (2.4 vs 16.3%, P < 0.05). Sultamicillin reduced the incidence of pneumonia associated with influenza-like illness during the influenza epidemic. This result suggests that antibiotics can reduce the rate of pneumonia associated with influenza.