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Scanning electron microscopy of collecting lymphatic vessels and their comparison to arteries and veins. The morphology of canine thoracic duct and peripheral collecting lymphatics was determined using light microscopy together with scanning and transmission electron microscopy (SEM and TEM). The thoracic duct was compared to the thoracic aorta and to the vena cava. Luminal surface detail was determined using the secondary imaging mode of the SEM. Subsurface nuclear and connective tissue detail was determined using back-scattered electron imagining combined with Willard's modification of Gomori's Methenamine Silver Stain. Central and peripheral lymphatic vessels have surface morphology distinct from either arteries or veins. The endothelial cell density in lymphatic vessels is less than in arteries or veins. The nuclear chromatin of lymphatic endothelial cells is coarsely granular and evenly distributed. This contrasts with nuclei from arteries or veins in which the chromatin is segmented. The distribution and orientation of lymphatic subsurface connective tissue fibers also differs from that seen in arteries and veins. It is concluded that canine lymphatic vessels have a unique surface and subsurface morphology and can be unequivocally identified by SEM.

Evaluation of the anticonvulsant activity of the essential oil of Eugenia caryophyllata in male mice. In this study, the effect of an essential oil of Eugenia caryophyllata (Myrtaceae), an antiepileptic remedy in Iranian folk medicine, against seizures induced by maximal electroshock (MES) or pentylenetetrazole (PTZ) in male mice was studied. The essential oil exhibited anticonvulsant activity against tonic seizures induced by MES. Although it was not effective against clonic convulsions induced by intraperitoneal administration of PTZ, the seizure threshold which was determined by an increase in the dose of intravenously infused PTZ required to induce clonus, was elevated by the essential oil. In addition, at some anticonvulsant doses, the essential oil produced motor impairment on the rotarod.

Double balloon enteroscopy: a 2 year experience. Double balloon enteroscopy is a new technique that enables deep intubation of the endoscope into the small bowel lumen. Through a channel in the endoscope, invasive procedures such as biopsy, polypectomy and hemostasis can be performed, avoiding the need for surgery. To prospectively analyze our results of the first 124 DBEs performed since February 2007. The study group comprised all patients who underwent DBE at the Sheba Medical Center between February 2007 and February 2009. Recorded were the patients' demographic data, comorbidities, indications for the examination, results of previous non-invasive small bowel imaging (computed tomography enterography, capsule endoscopy, etc), investigation time, and results of the procedure including findings, endoscopic interventions, complications and pathological report. A total of 124 procedures were performed in 109 patients. Of the 124 examinations, 57 (46%) were normal and 67 (54%) showed pathology. The main pathologies detected on DBE were polyps (14%), vascular lesions (17.6%) and inflammation (12%). Endoscopic biopsies and therapeutic interventions were required in 58 examinations (46%). A new diagnosis was established in 15% of patients, diagnosis was confirmed in 29% and excluded or corrected in 12%. One complication was observed: a post-polypectomy syndrome that was treated conservatively. DBE is a safe procedure and has a high diagnostic and therapeutic yield. Most of the examinations were performed under conscious sedation, and only a minority of patients required deeper sedation.

CNS drug targeting: have we travelled in right path? Brain disorders, their prevalence and central nervous system (CNS) targeting are now at the rise. However, complexities of blood brain barrier (BBB) have limited the success of CNS targeting. Basic criteria necessary for passive diffusion were believed to influence the CNS drug delivery. However, often, BBB transportation has differed from the dogma of basic criteria. This communication resets the extent to which basic criteria influence the brain delivery, through commanding examples. Further, it appraises the intervention of ABC transporters in BBB transportation, with a special emphasis on P-glycoprotein; and also brings forth the successful CNS transportation of therapeutics achieved through chimeric peptide technology. As a right path to travel, it flickers light on the novel CNS molecular drug targets/biomarkers which are specially expressed by diseased cells. Screening for right molecular target is of great importance for cost and time effective drug discovery process. The principle of chimeric peptide technology should be applied for CNS targeting; and every diseased cell should be screened for its biomarker. Thanks to glycan/lectin arrays technique which scans expression pattern of transporter and their possible ligands, and paves way for a new dimensional research.

Characterization of the human cytochrome P450 forms involved in metabolism of tamoxifen to its alpha-hydroxy and alpha,4-dihydroxy derivatives. Tamoxifen is a known hepatocarcinogen in rats and is associated with an increased incidence of endometrial cancer in patients. One mechanism for these actions is via bioactivation, where reactive metabolites are generated that are capable of binding to DNA or protein. Several metabolites of tamoxifen have been identified that appear to predispose to adduct formation. These include alpha-hydroxytamoxifen, alpha,4-dihydroxytamoxifen, and alpha-hydroxy-N-desmethyltamoxifen. Previous studies have shown that cytochrome P450 (P450) enzymes play an important role in the biotransformation of tamoxifen. The aim of our work was to determine which P450 enzymes were capable of producing alpha-hydroxylated metabolites from tamoxifen. When tamoxifen (18 or 250 microM) was used as the substrate, P450 3A4, and to a lesser extent, P450 2D6, P450 2B6, P450 3A5, P450 2C9, and P450 2C19 all produced a metabolite with the same HPLC retention time as alpha-hydroxytamoxifen at either substrate concentration tested. This peak was well-separated from 4-hydroxy-N-desmethyltamoxifen, which eluted substantially later under the chromatographic conditions used. No alpha,4-dihydroxytamoxifen was detected in incubations with any of the forms with tamoxifen as substrate. However, when 4-hydroxytamoxifen (100 microM) was used as the substrate, P450 2B6, P450 3A4, P450 3A5, P450 1B1, P450 1A1, and P450 2D6 all produced detectable concentrations of alpha,4-dihydroxytamoxifen. These studies demonstrate that multiple human P450s, including forms found in the endometrium, may generate reactive metabolites in women undergoing tamoxifen therapy, which could subsequently play a role in the development of endometrial cancer.

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system. The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. Diabetic myocardium showed a significant increase in protein expression (170 +/- 16% of control) and median mRNA expression (186% of control) of the AT1 receptor. The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89 +/- 5.5% vs 29 +/- 1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

Limited diagnostic value of laryngopharyngeal lesions in patients with gastroesophageal reflux during routine upper gastrointestinal endoscopy. There is growing evidence that gastroesophageal reflux disease (GERD) may cause typical laryngeal/pharyngeal lesions secondary to tissue irritation. The prevalence of those lesions in GERD patients is not well established. The aim of this study was to evaluate the prevalence of GERD signs in the laryngopharyngeal area during routine upper gastrointestinal endoscopy. Between July 2000 and July 2001, 1,209 patients underwent 1,311 upper gastrointestinal endoscopies and were enrolled in this study. The structured examination of the laryngopharyngeal area during upper gastrointestinal endoscopy was videotaped for review by three gastroenterologists and one otorhinolaryngologist, blinded to the endoscopic esophageal findings. From the 1,209 patients enrolled in this prospective study, all patients (group I, N = 132) with typical endoscopical esophageal findings of GERD (Savary-Miller I-IV) were selected. The sex- and age-matched control group II (N = 132) underwent upper gastrointestinal endoscopy for different reasons, had no reflux symptoms, and had normal esophagoscopy. In the two groups of patients, we found no difference in the prevalence of abnormal interarytenoid bar findings (32%vs 32%), arytenoid medial wall erythema (47%vs 43%), posterior commissure changes (36%vs 34%), or posterior cricoid wall edema (1%vs 3%). The only difference was noted in the posterior pharyngeal wall cobblestoning (66%vs 50%, P= 0.004). The results of this large systematic investigation challenge the diagnostic specificity of laryngopharyngeal findings attributed to gastroesophageal reflux.

Kurt Goldstein and his nonlocationist thoughts on aphasia-a pioneer of early network theories at the beginning of the twentieth century? In between Carl Wernicke's locationist aphasia concept from 1874 and Norman Geschwind's new connectionist model of human brain functions in 1965, little notice was taken of the historical debate on aphasia and brain plasticity. Interestingly, Kurt Goldstein made long-forgotten, but highly relevant remarks on the connectionist model and thereby served as an important connecting link between Wernicke and Geschwind. With the original contributions of Goldstein and contemporary authors, we analyzed the historical background of the aphasia debate in the time period between Wernicke and Geschwind, which still influences current aphasia concepts and neurosurgical practice of today.

Effect of intranasal administration of Lactobacillus fermentum CJL-112 on horizontal transmission of influenza virus in chickens. The aim of this study was to determine whether intranasal administration of Lactobacillus sp. could prevent horizontal transmission of H9N2 avian influenza virus (AIV) in specific-pathogen-free chickens. Three-week-old chickens received 500 μL of 1.5 × 10(9) cfu of Lactobacillus fermentum CJL-112 strain (CJL) intranasally for 7 d before and 14 d after a challenge. Challenged chickens, each inoculated with H9N2 AIV, were kept in either direct or indirect contact with naive chickens, and morbidity and viral shedding were monitored. We demonstrated that the intranasal administration of CJL significantly decreased the number of chickens with viral shedding from the gastrointestinal tract in the indirect contact chickens (P < 0.001) and also significantly reduced viral shedding from the respiratory tract in the challenged (P < 0.05) and the direct contact chickens (P < 0.001) than those in the control group. Hence, the use of this lactobacilli strain may constitute a novel and effectively plausible alternative to prevent and control H9N2 AIV infection in chickens.

Solving chemical problems with pattern recognition. Pattern Recognition is becoming established as a general data analysis tool which has widespread applications in chemistry. Whenever something must be learned from objects (elements, compounds, and mixtures) and a chemical/physical theory has not been sufficiently developed, pattern recognition may provide a solution. Materials production problems, screening applications, source identification and structure analysis are important areas of current interest. It is expected that many more areas of application will open up in the years to come. In short, the "educated guess" is being supported by the computer; at least that is our educated guess.

Assessing hydroxychloroquine toxicity by the multifocal ERG. Twenty patients on Plaquenil treatment were evaluated for retinal toxicity using the (EOG) and the mfERG. Group 1 comprises 15 patients (30 eyes) with normal EOG. From these patients 11 (22 eyes) showed normal RRD of mfERG in area 1 and area 2. The rest four patients (8 eyes) the RRD were reduced. Six months after interruption of HC, the mfERG improved in three cases. Group 2 comprises 5 patients (10 eyes) with subnormal EOG. Four (8 eyes) of these showed a decrease of RRD of the mfERG in area 1 and 2. In the rest one (2 eyes) the RRD were normal. Six months after interruption of HC the mfERG and the EOG improved in 2 cases. These results postulate that the mfERG may be used as an alternative method, perhaps more sensitive, for the detection of the HC retinopathy and the follow up of the patients on hydroxychloroquine.

Carbon quantum dots encapsulated in super small platinum nanocrystals core-shell architecture/nitrogen doped graphene hybrid nanocomposite for electrochemical biosensing of DNA damage biomarker-8-hydroxy-2'-deoxyguanosine. In this work, carbon quantum dots (CQD) encapsulated in super small platinum nanocrystals core-shell architecture/nitrogen doped graphene hybrid nanocomposite (CQD@PDA@PtNCs-NGR) was design synthesized. Without using any capping reagent, stabilizer and surfactant, very small CQD was served as template and anchoring point for the synthesis of Pt NCs with a super small size (2.25 nm) and a uniform distribution. Meanwhile, dopamine (DA) was used as bridging agent, positioning agent and weak reducing agent to make Pt2+ grow on the CQD. Combine the high dispersed Pt NCs with high specific surface area and high conductivity of NGR, the CQD@PDA@PtNCs-NGR shows excellent electrocatalytic performance towards the biosensing of DNA damage biomarker- 8-Hydroxy-2'-deoxyguanosine (8-OH-dG). A very low detection limit of 0.45 nM and 0.85 nM (S/N = 3), a wide linear range of 0.013 μM-109.78 μM and a high sensitivity of 7.912 μA μM-1cm-2 and 4.190 μA μM-1cm-2 were obtained. The fabricated CQD@PDA@PtNCs-NGR realized the detection of 8-OH-dG in human urine practical sample. Furthermore, CQD@PDA@PtNCs-NGR was applied for the determination of 8-OH-dG generated from damaged DNA and damaged guanine (G), respectively. This work effectively combines the electrochemical signal of 8-OH-dG with DNA damage, confirms the mechanism of DNA damage, which might pave a new way to establish the associations between degree of DNA damage and 8-OH-dG.

Stimulatory effects of Euphorbia cheiradenia on cell mediated immunity and humoral antibody synthesis. Studies have demonstrated that plant extracts possess various biological characteristics including immunomodulatory activity. Euphorbia cheiradenia Boiss et Hohen (Euphorbiaceae), a medicinal herb native to Iran was investigated for its immunomodulatory effects. The methanolic extract of the plant was prepared and added to mitogen-induced human peripheral blood lymphocyte cultures at different concentrations. Effect of E. cheiradenia on in vivo cell-mediated immunity was measured by delayed type hypersensitivity (DTH) reaction. The effect of the extract on humoral antibody synthesis was also measured in immunized mice treated with different extract concentrations. The stimulation index (SI) for cultures treated with 0.01 to 200 microg/ml of the extract ranged from 1.3+/-0.04 to 2.4+/-0.06, (p<0.01) showing a significant stimulatory effect of E. cheiradenia on the lymphocytes. IL-2 secreted from lymphocytes treated with the extract was significantly higher than that from the non-treated cells (p<0.001). Cell cycle analysis on mitogen-treated lymphocytes exposed to different concentrations of the extract showed an increase in the percentage of cells at G2M phase with increases in the concentration of the extract, but the results was not significant. In DTH skin test, the mean footpad thickness of all mice groups treated with 1, 50 and 100 mg/kg of the extract at 24 hours after immunization with antigen was 3.5+/-0.6 mm compared to 2.5+/-0.5 mm for the non-treated group (p=0.005). Moreover, an increase in production of specific antibody in mice immunized with different extract concentrations was also demonstrated. Results of this study showed the ability of the E. cheiradenia extract to induce proliferation of lymphocytes and enhance both cellular and humoral specific immune responses.

Three-dimensional knee motion before and after high tibial osteotomy for medial knee osteoarthritis. High tibial osteotomy (HTO) is an established surgical option for treating medial knee osteoarthritis. HTO moves the mechanical load on the knee joint from the medial compartment to the lateral compartment by changing the leg alignment, but the effects of the operation remain unclear. The purpose of this study was to evaluate the change in three-dimensional knee motion before and after HTO, focusing on lateral thrust and screw home movement, and to investigate the relationship between the change in knee motion and the clinical results. A series of 19 patients with medial knee osteoarthritis who had undergone HTO were evaluated. We performed a clinical assessment, radiological evaluation, and motion analysis at 2.4 years postoperatively. The clinical assessment was performed using the Japanese Orthopaedic Association knee score. The score was significantly improved in all patients after operation. Motion analysis revealed that lateral thrust, which was observed in 18 of the 20 knees before operation, was reduced to 7 knees after operation. Regarding active terminal extension of the knee, three patterns of rotational movement were observed before operation: screw home movement (external rotation), reverse screw home movement (internal rotation), and no rotation. By contrast, after operation, only reverse screw home movement and no rotation were observed; the screw home movement disappeared in all patients. In the knees with reverse screw home movement after operation, the preoperative score was significantly lower than those in the knees with no rotation after operation. Kinetically, HTO was useful for suppressing lateral thrust in medial knee osteoarthritis, although the rotational movement of the knee joint was unchanged.

Minimally invasive thoracotomy for myocardial revascularisation. A study of 32 cases. This study aimed to evaluate the advantages offered by a myocardial revascularisation technique proposed by Kolessov in 1967: minimally invasive thoracotomy for myocardial revascularisation. The aim was to assess its short and medium-term benefits. During the course of the 1980s, the problems linked to extracorporeal circulation (ECC) and the contraindications for traditional myocardial revascularisation led to a renewed popularity of "beating heart" revascularisation techniques. The largest and most extensive series of patients in the literature undergoing myocardial revascularisation during left mini-thoracotomy was reported by Calafiore et al. In this study we report the series treated by our centre which, albeit involving only 32 cases, obtained good results in the short and medium term. This surgical procedure can only be applied to patients presenting monovasal obstructive coronary disease affecting the anterior interventricular artery (IVA) which must not present small calibre, calcified walls or a lateralised or intramyocardial anatomic position. Invasive and non-invasive instrumental tests carried out to control the distal anastomoses of the left internal mammary artery (IMA) did not reveal angulations and/or stenosing tractions before the anastomosis of IMA to a significant extent also for treatment, when isolating IMA, able to obtain the longest possible length and the best mobility. No infection of surgical wounds was reported postoperatively, as sometimes occurs in median longitudinal sternotomy. The 2-year follow-up showed the resolution of angina in 100% of the patients studied, as well as a satisfactory and rapid renewal of social relations.

Characterization of nonpoint source microbial contamination in an urbanizing watershed serving as a municipal water supply. Inland watersheds in the southeastern United States are transitioning from agricultural and forested land uses to urban and exurban uses at a rate greater than the national average. This study sampled creeks representing a variety of land use factors in a rapidly urbanizing watershed that also serves as a drinking water supply. Samples were collected bimonthly under dry-weather conditions and four times during each of three storm events and assessed for microbial indicators of water quality. Concentrations of fecal indicator bacteria (FIB) including fecal coliforms and Escherichia coli were measured using standard membrane filtration techniques. Results showed that FIB concentrations varied between 10(0) and 10(4) colony forming units (CFU) per 100 mL. An analysis of variance (ANOVA) showed that FIB were generally higher in more developed watersheds (p < 0.01). Concentrations were also significantly greater during storm events than during dry-weather conditions (p < 0.02), although concentrations demonstrated both intra and inter-storm variability. These results indicate that the magnitude of microbial contamination is influenced by intensity of watershed development, streamflow and antecedent precipitation. Dry-weather FIB loads showed considerable seasonal variation, but the average storm event delivered contaminant loads equivalent to months of dry-weather loading. Analysis of intra-storm loading patterns provided little evidence to support "first-flush" loading of either FIB, results that are consistent with environmental reservoirs of FIB. These findings demonstrate that single sampling monitoring efforts are inadequate to capture the variability of microbial contaminants in a watershed, particularly if sampling is conducted during dry weather. This study also helps to identify timing and conditions for public health vulnerabilities, and for effective management interventions.

Effect of ethnicity and age or menopause on the structure and geometry of iliac bone. We measured indices of bone volume (cancellous, cortical) and bone surface (cancellous, endocortical, and intracortical) in intact full-thickness transiliac bone biopsies obtained from 144 healthy women aged 20-74 (35 black and 109 white, 62 premenopausal and 82 postmenopausal). The data were analyzed by two-way analysis of variance of the four groups defined by age/menopause and ethnicity and by linear regression of major variables on age. None of the interaction terms was significant, and none of the regression slopes on age differed between blacks and whites, indicating that the effects of ethnicity and of age/menopause were independent. Accordingly, the data were also analyzed separately for the effects of ethnicity (pre- and postmenopausal combined) and age/menopause (blacks and whites combined). The analyses led to the following conclusions. (1) Blacks have more cancellous and cortical bone than whites in the ilium; the difference was due to thicker trabeculae and thicker cortices with no difference in trabecular number or cortical porosity. (2) The magnitude of the black/white differences was the same throughout the age range covered by the study, indicating differences in peak adult values, not in rates of loss with age. (3) As the result of age/menopause, there were significant reductions in all indices of the amount and structure of bone except for trabecular thickness; the magnitude of the reductions was the same in blacks and whites. (4) Cancellous bone loss was mainly the result of the complete removal of some trabecular elements with increased separation between remaining elements. Cortical bone loss was due to thinning from the endocortical surface with a small but significant contribution from increased cortical porosity, due to an increased number of intracortical canals. These patterns of bone loss were the same in blacks and whites. (5) Although the percentage losses of bone with age/menopause were higher for cancellous than for cortical bone, the absolute amounts of bone lost were about the same for cortical as for cancellous bone. (6) The ratio of surface to tissue volume decreased with age/menopause in cancellous bone but increased in cortical bone; rates of bone loss would change in the same manner if the loss per unit of surface remained constant. (7) The total extent of bone surface in the ilium did not change with age/menopause, so that the surface/volume ratio for the entire bone increased; volumetric bone turnover would increase and bone age decrease if remodeling activity per unit of surface remained constant.

Intracellular barriers to non-viral gene transfer. Non-viral vector mediated gene transfer, compared to viral vector mediated one, is a promising tool for the safe delivery of therapeutic DNA in genetic and acquired human diseases. Although the lack of specific immune response favor the clinical application of non-viral vectors, comprising of an expression cassette complexed to cationic liposome or cationic polymer, the limited efficacy and short duration of transgene expression impose major hurdles in the widespread application of non-viral gene therapy. The trafficking of transgene, complexed with chemical vectors, has been the subject of intensive investigations to improve our understanding of cellular and extracellular barriers impeding gene delivery. Here, we review those physical and metabolic impediments that account, at least in part, for the inefficient translocation of transgene into the nucleus of target cells. Following the internalization of the DNA-polycation complex by endocytosis, a large fraction is targeted to the lysosomal compartment by default. Since the cytosolic release of heterelogous DNA is a prerequisite for nuclear translocation, entrapment and degradation of plasmid DNA in endo-lysosomes constitute a major impediment to efficient gene transfer. Only a small fraction of internalized plasmid DNA penetrates the cytoplasm. Plasmid DNA encounters the diffusional and metabolic barriers of the cytoplasm, further decreasing the number of intact plasmid molecules reaching the nuclear pore complex (NPC), the gateway of nucleosol. Nuclear translocation of DNA requires either the disassembly of the nuclear envelope or active nuclear transport via the NPC. Comparison of viral and plasmid DNA cellular trafficking should reveal strategies that viruses have developed to overcome those cellular barriers that impede non-viral DNA delivery in gene therapy attempts.

Important factors for pain during photodynamic therapy for actinic keratosis. Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin.

Effectiveness of an anti-inflammatory drug, loxoprofen, for patients with nocturia. There is increasing evidence that non-steroidal anti-inflammatory drugs are effective for the treatment of nocturia. In this study, we attempted to investigate the role of loxoprofen sodium (loxoprofen) in the therapeutic management of patients with nocturia. Fifteen benign protastatic hyperplasia and/or overactive bladder patients (13 males and 2 females, 71.1 +/- 1.5 years old) with three or more voids per night were involved. These patients had received standard drug therapy. Although these patients had received standard drug therapy for more than half a year, they had still three or more episodes of nocturia. The patients took a single dose of 60 mg of loxoprofen at night prior to sleep. Before and 1 week after the initiation of this therapy, the effects of this treatment were assessed by frequency volume chart and a questionnaire. In the questionnaire, seven patients answered as excellent, six patients demonstrated improvement of their symptoms, two patients did not show a significant change in their symptoms and no patients demonstrated a deterioration in the symptoms. In frequency volume chart, total void per day, total void per night, total urine volume per day, total night urine volume per day and single voided volume in the night before and after this treatment were 9.97 +/- 0.81 and 8.99 +/- 0.74 per day, 3.82 +/- 0.25 and 1.82 +/- 0.27 per night, 1349 +/- 81 and 1258 +/- 91 mL per day, 567 +/- 46 and 325 +/- 51 mL per night, and 143 +/- 13 and 149 +/- 10 mL, respectively. Loxoprofen can be effective and useful for patients with nocturia. Our data suggest that the main mechanism of this effect is to decrease urine production during a night's sleep.

Experimental primary and secondary infections of domestic dogs with Ehrlichia ewingii. In this study, the infection dynamics of Ehrlichia ewingii, causative agent of granulocytotropic ehrlichiosis in dogs and humans, was examined in experimentally infected dogs by using a combination of physical examination, hematologic and biochemical analyses, and molecular and serologic assays. For the experimental trials, blood from an E. ewingii-infected dog was inoculated intravenously into two naïve dogs and two dogs with prior experimental exposure to E. ewingii (both were negative for E. ewingii DNA by polymerase chain reaction (PCR) assay, but seropositive from initial infection 8 and 10 months prior to challenge). A negative control dog was inoculated with blood from a negative dog. The two primary infection dogs were positive for E. ewingii DNA on DPI 4, remained consistently positive until DPI 60, and were intermittently positive until the end of the study (DPI 144). The two primary infection dogs developed antibodies reactive to E. ewingii by DPI 28 and remained seropositive for the duration of the study. Primary infected dogs had intermittent fever, thrombocytopenia, and leukopenia and some dogs were hyperphosphatemic and/or had elevated ALP levels. The two challenge dogs were positive for E. ewingii DNA on DPI 4 and 18, which was similar to the primary infection dogs, but the duration of E. ewingii DNA detection was shorter. Also, the two challenged dogs did not develop pyrexia or show any hematologic or biochemical abnormalities. E. ewingii was successfully transmitted between dogs by Amblyomma americanum, but not Rhipicephalus sanguineus. This study provides data on the infection dynamics of E. ewingii in dogs during primary and challenge infections and suggests that prior exposure may lessen clinical disease during subsequent infections.

Spatial perception errors do not predict pointing errors by individuals with brain lesions. We examined the relationship between errors in sensorimotor transformations (SMT) for reaching to external targets and visual and kinesthetic spatial perception of those targets by participants with damage to the posterior parietal lobule (PPL) and adjacent areas. A total of 12 participants had focal PPL lesions, 7 had with brain lesions outside the PPL, and 10 had no brain lesions. Brain lesions were due to stroke (12) or surgical resection (7). Participants made visually and kinesthetically guided pointing movements to 16 targets with the ipsilesional hand (to minimize effects of motor deficits). Head and eye movements were unrestricted. When full vision was allowed, all participants pointed accurately to visually specified targets. However, participants with PPL lesions made larger vertical plane errors than did neurologically intact control participants in visual and kinesthetic perceptual tasks and in SMT tasks (in which participants reached without vision to targets that had been visually presented). However, across all 29 participants, the size and direction of SMT errors showed low correlation with visual and kinesthetic perceptual errors. Moreover, participants with PPL lesions who made large visual and/or kinesthetic perceptual errors to individual targets also showed weak correlations with SMT errors to those targets. The results are compatible with theories that different neural pathways support perception and action for both the visual and the kinesthetic systems.

Aerosol deposition and airway obstruction. Intrapulmonary deposition of 1-mum-diameter particles of dioctyl sebacate was studied in 58 working coalminers. Total deposition was found to be significantly correlated with lung function measurements characterizing airway obstruction. The closest relationship was between deposition and the mean maximal flow rate in the third quarter of a forced expiration. The shape of the exhaled aerosol recovery curve was also found to be related to the degree of airway obstruction; 3 basic types are described. The concave type was more common in smokers, in whom deposition was significantly greater. The presence of simple pneumoconiosis was not associated with the degree of aerosol deposition. The significance of the findings of aerosol deposition and its recovery pattern are discussed in relation to the pathogenesis of lung disease.

Initial oxygen saturation values can predict the need to hospitalise children with mild wheezing. Mild wheezing during respiratory infections is a common cause of paediatric hospital admissions. This study aimed to identify factors predicting this condition in children over six months of age. We reviewed the medical records of 539 children, aged 6 months to 16 years, who visited the emergency department because of wheezing during respiratory infection. Mild disease was defined as hospital stays of less than 48 h and severe disease was staying at least 48 h or being treated in intensive care. Patients with an initial oxygen saturation value (SaO2 ) below 90% were analysed separately. Most (87%) of the 539 patients had mild disease, 6% had a severe disease and 7% had an initial SaO2 below 90%. The area under the receiver operating characteristic (ROC) curve for the initial SaO2 predicting mild disease was 0.75 (95% CI 0.53-0.97), and the optimal cut-off value was 93%. An initial SaO2 >93% had a negative predictive value of 93%. Although 270 patients (50%) were hospitalised, only 140 (26%) would have been admitted using an optimal cut-off of SaO2 ≤93%. An initial SaO2 >93% reflects a mild course of acute wheezing and using this cut-off point could have almost halved hospital admissions.

Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma with endometrium. From 1975 to 1992, 54 patients with clinical Stage I and II endometrioid carcinoma of the endometrium, representing 3.5% of all such patients, were deemed medically inoperable and exclusively received radiation therapy. A cohort of 108 operable patients adjusted for age, clinical stage, and grade served as a control group. The 5-year actuarial cancer-specific survivals for patients with Stage I inoperable, Stage 11 inoperable, Stage I operable, and Stage II operable disease were 80, 85, 98, and 100%. The corresponding 5-year overall survival rates were 30, 24, 88, and 85%. Inoperable patients had a median disease-free interval of 36 months for clinical Stage I and 50 months for Stage II disease versus 74.5 and 77 months for the operable patients (P = 0.001). Inoperable patients with Stage I disease had a median survival of 37 months versus 50 months for Stage II (P = NS), with only 7 (13%) of these patients dying with endometrial cancer. Operable patients had a median survival of 75 and 79 months in Stage I and II, respectively, with 14 patients dying with endometrial carcinoma (13%). Stage I and II inoperable patients had significantly shorter survival than operable patients (P < 0.0001). More deaths from intercurrent disease occurred within the inoperable Stage I group than with the operable group (28 of 32 vs 3 of 15, P < 0.0001). Inoperable patients had a significantly shorter overall survival and more deaths due to intercurrent disease than operable patients (P < 0.0001). However, inoperable patients who did not die from intercurrent disease had a median 5-year survival which approaches that of operable patients. Our study demonstrates that exclusive radiation therapy is a well-tolerated and effective treatment for medically inoperable patients.

Iatrogenic Wernicke encephalopathy in a patient with severe hyperemesis gravidarum. Hyperemesis gravidarum complicates 0.5-2.0% of pregnancies and may lead to substantial nutritional deficiencies. Total parenteral nutrition can be used in severe cases in an attempt to avoid such deficiencies. Rarely, thiamine deficiency resulting in Wernicke encephalopathy occurs, with significant maternal morbidity. We present the case of a 30-year-old woman with hyperemesis gravidarum at 13 4/7 weeks of gestation treated with prolonged total parenteral nutrition that lacked thiamine supplementation, resulting in iatrogenic Wernicke encephalopathy. After high-dose intravenous thiamine repletion, she experienced slow resolution of her symptoms. Pregnancies complicated by hyperemesis gravidarum treated with total parenteral nutrition represent potential high-risk clinical scenarios for thiamine deficiency. Compositions of total parenteral nutrition are not standardized. Thus, physicians must confirm repletion of all essential components to avoid significant morbidity.

Heterologous biosynthesis and manipulation of alkanes in Escherichia coli. Biosynthesis of alkanes in microbial foundries offers a sustainable and green supplement to traditional fossil fuels. The dynamic equilibrium of fatty aldehydes, key intermediates, played a critical role in microbial alkanes production, due to the poor catalytic capability of aldehyde deformylating oxygenase (ADO). In our study, exploration of competitive pathway together with multi-modular optimization was utilized to improve fatty aldehydes balance and consequently enhance alkanes formation in Escherichia coli. Endogenous fatty alcohol formation was supposed to be competitive with alkane production, since both of the two routes consumed the same intermediate-fatty aldehyde. Nevertheless, in our case, alkanes production in E. coli was enhanced from trace amount to 58.8mg/L by the facilitation of moderate fatty alcohol biosynthesis, which was validated by deletion of endogenous aldehyde reductase (AHR), overexpression of fatty alcohol oxidase (FAO) and consequent transcriptional assay of aar, ado and adhP genes. Moreover, alkanes production was further improved to 81.8mg/L, 86.6mg/L or 101.7mg/L by manipulation of fatty acid biosynthesis, lipids degradation or electron transfer system modules, which directly referenced to fatty aldehydes dynamic pools. A titer of 1.31g/L alkanes was achieved in 2.5L fed-batch fermentation, which was the highest reported titer in E. coli. Our research has offered a reference for chemical overproduction in microbial cell factories facilitated by exploring competitive pathway.

Pvclust: an R package for assessing the uncertainty in hierarchical clustering. Pvclust is an add-on package for a statistical software R to assess the uncertainty in hierarchical cluster analysis. Pvclust can be used easily for general statistical problems, such as DNA microarray analysis, to perform the bootstrap analysis of clustering, which has been popular in phylogenetic analysis. Pvclust calculates probability values (p-values) for each cluster using bootstrap resampling techniques. Two types of p-values are available: approximately unbiased (AU) p-value and bootstrap probability (BP) value. Multiscale bootstrap resampling is used for the calculation of AU p-value, which has superiority in bias over BP value calculated by the ordinary bootstrap resampling. In addition the computation time can be enormously decreased with parallel computing option.

Note: Localization based on estimated source energy homogeneity. Acoustic signal localization is a complex problem with a wide range of industrial and academic applications. Herein, we propose a localization method based on energy attenuation and inverted source amplitude comparison (termed estimated source energy homogeneity, or ESEH). This inversion is tested on both synthetic (numerical) data using a Lamb wave propagation model and experimental 2D plate data (recorded with 4 accelerometers sensitive up to 26 kHz). We compare the performance of this technique with classic source localization algorithms: arrival time localization, time reversal localization, and localization based on energy amplitude. Our technique is highly versatile and out-performs the conventional techniques in terms of error minimization and cost (both computational and financial).

Signaling pathways coordinating the alkaline pH response confer resistance to the hevein-type plant antimicrobial peptide Pn-AMP1 in Saccharomyces cerevisiae. Genome-wide screening of Saccharomyces cerevisiae revealed that signaling pathways related to the alkaline pH stress contribute to resistance to plant antimicrobial peptide, Pn-AMP1. Plant antimicrobial peptides (AMPs) are considered to be promising candidates for controlling phytopathogens. Pn-AMP1 is a hevein-type plant AMP that shows potent and broad-spectrum antifungal activity. Genome-wide chemogenomic screening was performed using heterozygous and homozygous diploid deletion pools of Saccharomyces cerevisiae as a chemogenetic model system to identify genes whose deletion conferred enhanced sensitivity to Pn-AMP1. This assay identified 44 deletion strains with fitness defects in the presence of Pn-AMP1. Strong fitness defects were observed in strains with deletions of genes encoding components of several pathways and complex known to participate in the adaptive response to alkaline pH stress, including the cell wall integrity (CWI), calcineurin/Crz1, Rim101, SNF1 pathways and endosomal sorting complex required for transport (ESCRT complex). Gene ontology (GO) enrichment analysis of these genes revealed that the most highly overrepresented GO term was "cellular response to alkaline pH". We found that 32 of the 44 deletion strains tested (72 %) showed significant growth defects compared with their wild type at alkaline pH. Furthermore, 9 deletion strains (20 %) exhibited enhanced sensitivity to Pn-AMP1 at ambient pH compared to acidic pH. Although several hundred plant AMPs have been reported, their modes of action remain largely uncharacterized. This study demonstrates that the signaling pathways that coordinate the adaptive response to alkaline pH also confer resistance to a hevein-type plant AMP in S. cerevisiae. Our findings have broad implications for the design of novel and potent antifungal agents.

N-acetylation phenotyping with sulphadimidine in a Turkish population. The distribution of acetylator phenotypes was studied in 244 unrelated Turkish subjects. Sulphadimidine and its acetylated metabolite were measured in 6 h plasma and 0-6 h urine samples after an oral dose of 10 mg/kg. Subjects with 37.5% or less acetylsulphadimidine in plasma were regarded as slow acetylators and the others as rapid acetylators. The mean plasma concentration of acetylsulphadimidine was about 2.5-times lower in slow acetylators. Urinary excretion of total sulphadimidine (free + acetylated) was also significantly lower in slow acetylators compared to rapid acetylators. The frequency of slow acetylators was 60.7% in the population (95% confidence interval 54.3% to 66.8%). Sulphadimidine acetylation showed no variation due to sex, age, body weight or pre-existing disease.

Anesthetic management of a pregnant living related liver donor. Pregnancy is often considered a contraindication to living related liver donation. There are serious medical and ethical considerations if a pregnant woman insists on undergoing partial hepatectomy to save her sick child. Herein we report a case of living related liver donation from a pregnant woman at 18 weeks of gestation to her 1-year-old child with decompensated cirrhosis due to biliary atresia. The left lateral segment of the liver was harvested for donation. Meticulous surgical technique and anesthetic management were mandatory in assuring a successful outcome. While this isolated case demonstrated that living related liver donation can be performed successfully with a pregnant donor, it should be undertaken only when there is absolutely no other donor and the recipient is in urgent need.

[Experimental study of Qiyeling Decoction inducing apoptosis of transplanted human lung adenocarcinoma cells A549 in nude mice]. To study the function of Qiyeling Decoction in inducing apoptosis of transplanted human lung adenocarcinoma cells A549 in nude mice. Nude mice with transplanted A549 tumor were randomly divided into the untreated control group (group A), chemotherapy treated group (group B), chemotherapy plus Qiyeling Decoction treated group (group C), Qiyeling Decoction treated group (group D) and managed correspondingly. The tumor volume was measured and calculated into tumor weight. The apoptosis of tumor cells were examined using in situ cell apoptosis detection kit. The tumor weight was lower obviously in groups B, C and D than that in group A (P<0.05). The apoptosis of tumor cells was lower obviously in groups B, and C than that in group D (P<0.05). Cells in group A appeared perfect differentiation during the early stage and apoptosis later. Qiyeling Decoction can induce A549 cell apoptosis in nude mice.

A prospective randomized comparison of 270 degrees fusions to 360 degrees fusions (circumferential fusions). Prospective randomized comparison of anterior lumbar interbody fusion (ALIF) plus transpedicular instrumentation plus posterolateral fusion (PLF) (360 degrees fusion) to ALIF plus transpedicular instrumentation without PLF (270 degrees fusion). To compare the clinical outcomes, costs, and utilization of health resources of 360 degrees versus 270 degrees fusions. The 360 degrees fusion is effective, but its costs and utilization of health resources are high. The PLF often resorbs and may not be necessary. Before and after surgery pain was measured by the Numerical Rating Scale (NRS), and function was measured by the Oswestry Low Back Disability Index (OSI). Costs were calculated by billing records. Operating times, blood loss, and hospital stays were measured at the time of hospital discharge. There were 48 patients: 21 women and 27 men. Mean age was 42 years. Follow-up averaged 35 months (range 24-45 months). In both 360 degrees and 270 degrees fusions, there were significant improvements in NRS and OSI, and the percentage of solid ALIF was high. Only 14% of PLF appeared solid bilaterally and 18% appeared solid on one side only. There were no significant differences in changes in NRS, changes in OSI, or percentage solid ALIF between the 360 degrees and 270 degrees fusions. However, the 270 degrees fusion group had significantly less blood loss, shorter operative times, shorter hospital stays, and lower professional fees, and although hospital charges were lower, this difference was not significant. Both the 360 degrees and 270 degrees fusions significantly reduce pain and improve function, and there are no significant clinical differences between them. However, there were shorter operating times, less blood loss, lower costs, and less utilization of health care resources associated with the 270 degrees fusions.

Tumoral markers in tumors of the pineal region. In cases of pineal tumors, a germ cell tumor should always be suspected. As some of them are secreting tumors, tumoral markers (AFP and/or hGC) are an important part of the diagnostic process. Their positivity either in the serum and/or in the cerebrospinal fluid may lead to an accurate diagnosis, avoiding a potentially dangerous surgical biopsy. Follow-up of tumoral markers is useful during and after treatment in order to monitor response to chemotherapy or a remission status.

Administration of Cripto in GRP78 overexpressed human MSCs enhances stem cell viability and angiogenesis during human MSC transplantation therapy. The purpose of this study was to explore the effectiveness of concurrent GRP78 overexpression combined with Cripto on hMSC proliferation and migration both in vitro and in vivo. Specifically, we explored whether the treatment enhances effectiveness of hMSC transplantation in ischaemic tissue. Human MSCs obtained from human adipose tissue were cultured in α-minimum essential medium (Hyclone, Logan, UT, USA) supplemented with 10% (v/v) foetal bovine serum (Hyclone), 100 U mL-1 penicillin and 100 μg mL-1 streptomycin. Murine hindlimb ischaemic model was generated with 8-week-old male nude BALB/c mice (Biogenomics, Seoul, Korea) maintained under a 12-h light/dark cycle following the established protocol with minor modification. Cellular injection was performed no later than 3 hour after surgery. Lipofectamine transfection, single-cell cultivation assay, transwell assay, scratch wound-healing migration assay, immunohistochemistry and western blotting assays were performed. Overexpression of GRP78 along with Cripto enhanced hMSC proliferation, migration and invasion. It increased interaction of surface GRP78 receptor with Cripto via JAK2/STAT3 pathway. We confirmed our proposed mechanism by showing that treatment with GRP78 antibody blocks the enhancement in vitro. In vivo, we observed that Cripto induced by the hypoxic environment in hindlimb ischaemic model interacts with the overexpressed GRP78 and increases hMSC proliferation, migration and invasion potentials as well as angiogenesis around transplanted ischaemic site via cytokine secretions. These results demonstrate supporting evidences that GRP78-Cripto combination technique offers novel strategy to enhance MSC proliferation, migration and invasion potentials as well as angiogenesis around ischaemic site, ultimately facilitating MSC-based transplantation therapy in ischaemic conditions.

Histone Variants and Disease. In eukaryotes, the genome is organized into a complex nucleoprotein structure called chromatin. Despite the simplicity of its monomer, DNA and two copies of four histones, the existence of histone variants opens possibilities of multiple chromatin landscapes and fine-tune regulation of molecular mechanisms for the regulation of gene expression and maintenance of genome stability. However, any defects in these combinations may contribute to disease development and/or progression. Here, I review human histone variants and their chaperones, and discuss how they contribute to pathological conditions.

Phase sensitive amplification based on quadratic cascading in a periodically poled lithium niobate waveguide. We propose and demonstrate phase-sensitive amplification based on cascaded second harmonic generation and difference frequency generation within a periodically poled lithium niobate waveguide. Excellent agreement between our numerical simulations and proof-of-principle experiments using a 3-cm waveguide device operating at wavelengths around 1550 nm is obtained. Our experiments confirm the validity and practicality of the approach and illustrate the broad gain bandwidths achievable. Additional simulation results show that the maximum gain/attenuation factor increases quadratically with input pump power, reaching a value of +/- 19.0 dB at input pump powers of 33 dBm for a 3 cm-long waveguide. Increased gains/reduced powers for a fixed gain could be achieved using longer crystals.

Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. We evaluated the protective activity (expressed as ED50 values in mg/kg of phenobarbital (PB, 120 min before testing) and valproate (30 min) alone or combined with caffeine in male mice with seizures induced by maximal electroshock (MES). Both antiepileptic drugs (AEDs) were administered by intraperitoneal (i.p.) injection in a single dose to mice receiving intraperitoneal caffeine either in a single dose 30 min before the test or as pretreatment every 12 h for 3 and 14 days. In addition, we determined the ED50 values of the AEDs 24 and 72 h after 14-day treatment with caffeine. Finally, we studied the influence of a challenge dose of caffeine, injected in mice 24 and 72 h after 14 days of treatment with caffeine, on the protective activity of PB or VPA. Caffeine in a single dose of 23.1 mg/kg reduced the anticonvulsant effect of PB. Its protective activity was further impaired after 3 and 14 days of caffeine treatment. The ED50 for VPA was significantly increased both by the single dose of caffeine and by chronic treatment. The anticonvulsant activity of PB and VPA measured 24 and 72 h after 14-day treatment with caffeine did not differ from control values, but a challenge dose of caffeine injected 24 or 72 h after daily injections for 14 days resulted in a significant reduction in the protective activity of both AEDs. Measurement of the total plasma levels of caffeine, VPA, and PB did not suggest pharmacokinetic interactions as an explanation for our results. Our results indicate that chronic caffeine exposure may progressively reduce the antiepileptic potency of VPA and PB.

Dual use of an amplatzer device in the transcatheter embolization of a large high-flow renal arteriovenous fistula. Embolization procedures are now considered the first-line therapy in the treatment of renal arteriovenous fistulas (AVFs). However, a risk posed by the use of these minimally invasive techniques is the migration of occluding agents into the venous and pulmonary circulations. The risk is of particular importance for larger, high-flow fistulas. The authors describe a case in which an Amplatzer Vascular Plug (AVP) was opened upstream of a renal AVF in the dilated feeding artery and used as a filter and a buttress during coil embolization to prevent coil migration during the treatment of the large, high-flow renal AVF. It was then removed and used again as the final embolic device in the renal artery, performing a dual role in the closure of the renal AVF.

Predictive factors for bile leakage after hepatectomy for hepatic tumors: a retrospective multicenter study with 631 cases at Yokohama Clinical Oncology Group (YCOG). International Study Group of Liver Surgery (ISGLS) proposed the standardized definition for bile leakage (BL) after hepatectomy (Hx) at 2011 to precisely perceive incidence and predictive factors of this critical condition. We conducted a multicenter retrospective study using the ISGLS definition of BL after Hx. Perioperative data regarding 631 patients undergoing elective Hx for hepatic tumors without biliary reconstruction performed between January 2009 and December 2011 were analyzed. BL was observed in 30 patients (4.8%). (Grade A, 8 (1.3%); B, 21(3.3%); C, 1 (0.2%)). Five independent predictors (diagnosis of liver metastases, prolonged operation, high risk procedures defined as Hx with broad exposure of the hilar Glissonean sheath, low platelet count and high serum total bilirubin on postoperative day 1) for grade B/C BL were elucidated by the multivariate analysis. When the study cohorts were divided into groups by number of accompanying these predictors, the more the accompanying independent predictors, the higher the incidence of BL. Notably, incidence of BL exceeded 40% in patients with four or more of these predictors. Risk stratification for BL after Hx can be achievable using independent predictors clarified in this study. However, proper management for high risk patients remains to be elucidated.

Off-Label Prescribing and Polypharmacy: Minimizing the Risks. Off-label prescribing and polypharmacy are commonplace in today's health care environment. Patients are treated with multiple medications obtained through multiple providers, and all too frequently, there is no collaboration amongst professionals. Nurses can address these issues by educating themselves and their patients regarding medication indications and uses, side effects, risks, and benefits. By exploring a patient's medication reconciliation, including over-the-counter agents, and identifying the U.S. Food and Drug Administration-approved indications, as well as potential off-label uses and overlapping side effects of the medications prescribed, nurses can facilitate collaboration among prescribers to reduce polypharmacy, minimize medication side effects, and alleviate drug-drug interactions, while improving patient outcomes and quality of life. [Journal of Psychosocial Nursing and Mental Health Services, 55(2), 17-22.].

The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome. Autonomic modulation, particularly high vagal tone, plays an important role in the occurrence of ventricular tachyarrhythmias in the Brugada syndrome. Food intake modulates vagal activity. We assessed the usefulness of a novel diagnostic technique, the "full stomach test," for identifying a high-risk group in patients with a Brugada-type electrocardiogram (ECG). In 35 patients with a Brugada-type ECG, we assessed 12-lead ECGs before and after a large meal, a pilsicainide pharmacological test, spontaneous ST-segment change, late potentials by signal-averaged ECG, microvolt T-wave alternans, and four other ECG parameters. These patients were divided into two groups (i.e., high-risk group [n = 17] and indeterminate risk group [n = 18]). The full stomach test was defined as positive when augmentation of characteristic ECG abnormalities was observed after meals. Thirteen patients had a prior history of life-threatening events such as aborted sudden death and syncope, with a total of 30 episodes. These episodes had a circadian pattern, at night and after meals. The full stomach test was positive in 17 of the study patients (49%). A positive test outcome was characterized by a higher incidence of a history of life-threatening events than a negative test outcome (P = 0.015, odds ratio = 7.1). In comparison between the two groups, the incidence (82%) of positive outcomes in the high-risk group was significantly higher than that (17%) in the indeterminate risk group (P = 0.0002). Characteristic ECG changes diagnostic of Brugada syndrome are augmented by a large meal. These data are associated with a history of life-threatening events in Brugada syndrome.

[Contraception and Gardnerella vaginalis. First study of the Italian population]. The association between contraception and Gardnerella vaginalis was studied in the population of L'Aquila. This research was conducted in the cytocolposcopic Center of the Obstetrics and Gynaecology Clinic, and the Department of Biotechnology and Biometry at L'Aquila University on 1212 females. Of the examined patients, 178 (14.7%) employed a prophylactic method and of these 104 (58.4%) used barrier-systems, while 74 (41.6%) used estroprogestins. Gardnerella vaginalis was isolated in 63 females (6.1%) that used no contraceptive and 19 (10.7%) that employed one.

Wortmannin inhibition of forskolin-stimulated chloride secretion by T84 cells. The time- and dose-dependent effects of wortmannin on transepithelial electrical resistance (Rte) and forskolin-stimulated chloride secretion in T84 monolayer cultures were studied. In both instances, maximal effects developed over 2 h and were stable thereafter. Inhibition of forskolin-stimulated chloride secretion, as measured by the short-circuit current (Isc) technique, had an IC50 of 200-500 nM, which is 100-fold higher than for inhibition of phosphatidylinositol 3-kinase (PI3K), but similar to the IC50 for inhibition of myosin light chain kinase (MLCK) and mitogen-activated protein kinases (MAPK). Previous work demonstrated that 500 nM wortmannin did not inhibit the cAMP activation of apical membrane chloride channels. We show here that 500 nM wortmannin has no affect on basolateral Na/K/2Cl-cotransporter activity, but inhibits basolateral membrane Na/K-ATPase activity significantly. The MLCK inhibitors ML-7 and KT5926 were without affect on forskolin-stimulated Isc. Similarly, the p38- and MEK-specific MAPK inhibitors SB203580 and PD98059 did not reduce forskolin-stimulated Isc. In contrast, the non-specific MAPK inhibitor apigenin reduced forskolin-stimulated Isc and basolateral membrane Na/K-ATPase activity similar to wortmannin. In isolated membranes from T84 cells, wortmannin did not inhibit Na/K-ATPase enzymatic activity directly. We conclude that one or more MAPK may regulate the functional expression of basolateral membrane Na/K-ATPase by controlling the abundance of enzyme molecules in the plasma membrane.

Optimal white light control of the negative to neutral to positive charge transition (NeNePo) in the electronic manifold of the silver trimer. Control over the electronic state of the Ag(3) cluster is approached via a progression of ultrafast photoinduced transitions within the full electronic manifold of the negative to the neutral and finally the cationic state of the system. High-bandwidth supercontinuum laser pulses ranging from 500 to 950 nm are employed for addressing the wide range of electronic resonance conditions associated with the ladder climbing process of a tandem photoelectron detachment and a resonance enhanced multiphoton ionization (REMPI). With the control of the phase over the full spectral envelope of the supercontinuum in a pulse shaper arrangement, pulse forms are generated with the aim of synchronizing ultrashort subpulse sequences to the characteristic dynamics of the system during charge reversal. Pulse forms ranging over several hundred femtoseconds in total duration and subpulse structures down to 15 fs duration with a variable spectral composition can be obtained for this purpose. A free optimization based on a closed-loop genetic algorithm is employed for ordering the subpulse sequences to match the structural evolution of the system. The effective control attainable in this scenario is evaluated in view of maintaining a defined sequence of electronic transitions within the complex dynamic response of the system during the photoexcitation. Further emphasis is made on analyzing the degree of control attainable in the nonlinear regime of multiphoton excitation at supercontinuum bandwidths.

Receptor-based design of cytokine therapeutics. Cytokines hold huge potential for the treatment of disease due to their often fundamental roles in development and homeostasis. However, it is this same primary biological function that can both cause disease through dysregulation as well as prevent their therapeutic use due to systemic consequences arising from this inherent pleiotropy. Molecularly, this can be explained through an understanding of the receptor system specific to each cytokine and the cells on which they are expressed. This knowledge has been exploited to yield muteins (mutated proteins) that exhibit selective, and sometimes novel, biological properties dependent upon receptor subunit usage. In some cases, these muteins have been evaluated in clinical trials and have been approved for clinical use; in most instances, however, these muteins are not suitable for therapeutic application due to intrinsic characteristics of the muteins themselves or the cellular and receptor system to which they are directed. Ultimately, molecular insight to the biological processes governing disease pathology underlies the successful application of mutein-based therapy. The clinical success enjoyed by a subset of these proteins signals the advent of a new mode of therapeutic protein development.

Improvement of response time with an additional bias beam in a BaTiO(3) self-pumped phase-conjugate mirror. Improvement of the response time of the BaTiO(3) self-pumped phase-conjugate mirror is demonstrated with a simple configuration. It is based on beam amplification in the crystal driven by an additional bias beam.

Mucosal immunity: overcoming the barrier for induction of proximal responses. Vaccination represents one of the most efficacious and cost-effective medical interventions. It is the only medical intervention proven to eliminate disease at a global level. Many of the pathogens against which we most require adequate vaccines infect via the highly exposed mucosal surfaces. For this reason the mucosa is often considered the first, and sometimes only, line of defense. Therefore, responses that protect the local mucosa are vital. In this review, we first explore the immunological mechanisms that protect the mucosa. We then review the literature of mucosal vaccines within the principles of antigenic composition, dose, and danger, highlighting the need and niche for the next generation of mucosal vaccines.

Circulating zinc-α2-glycoprotein is reduced in women with polycystic ovary syndrome, but can be increased by exenatide or metformin treatment. The study was to investigate circulating zinc-α2-glycoprotein (ZAG) concentrations in women with PCOS, and changes in ZAG levels after exenatide or metformin treatment. One hundred eighty-two women with polycystic ovary syndrome (PCOS) who met the 2003 Rotterdam diagnostic criteria and 150 controls without PCOS were recruited. We partitioned women with PCOS into groups according to body mass index or blood glucose concentrations, determined serum ZAG, anthropometric parameters, metabolic and endocrine indicators, and inflammatory markers, and statistically analyzed the results. Eighty-two overweight/obese subjects of the recruited women with PCOS were then randomly assigned to groups administered either 12 weeks of exenatide injection (10 μg b.i.d.) or oral metformin (1,000 mg b.i.d.). Circulating ZAG levels were determined after 12 weeks of treatment. The results showed that circulating ZAG was significantly lower in PCOS women than in healthy women (p < 0.01). Overweight/obese women and those with higher blood glucose levels had lower circulating ZAG. After 12 weeks of exenatide or metformin treatment, there were significant increases (p < 0.01) in circulating ZAG in both treatment groups (the exenatide baseline level was 46.54 ± 2.38 ng/mL vs. 56.41 ± 2.02 ng/mL after treatment, p < 0.01; metformin baseline was 47.81 ± 2.14 ng/mL vs. 55.67 ± 2.01 ng/mL after treatment, p < 0.01), however there was no statistical difference between the 2 treatments (p > 0.05). Circulating ZAG is closely related to PCOS and could be an important adipokine involved in the occurrence and development of PCOS. ZAG might possibly be applicable as a new observational indicator in the treatment of PCOS.

Nonimmune complexed HCV RNA titer in serum as a predictor of interferon response in patients with chronic hepatitis C. Hepatitis C virus (HCV) has been reported to exist in the circulation of patients in various forms such as free virions, immune complexes, and nucleocapsids. To clarify the clinical significance of serum HCV titers according to the forms of virus particles, we evaluated the immune complexed (IC) and nonimmune complexed (NIC) HCV RNA titers in 77 chronic hepatitis patients treated with interferon (IFN). IC and NIC forms in pretreatment serum were separated by immunoprecipitation using antihuman immunoglobulin antibody, and quantified by reverse transcription polymerase chain reaction. Serum titers of NIC HCV RNA were correlated with those of whole serum HCV RNA (r = 0.96, p < 0.01) and IC HCV RNA (r = 0.98, p < 0.01), but they were not with the aminotransferase levels, gamma-globulin concentration, and grading or staging of liver histology. Nonresponders to IFN had significantly high NIC HCV RNA titers compared with sustained responders (10(4.93 +/- 0.81) copies/ml vs 10(4.06 +/- 0.69) copies/ml, p < 0.01). It is noteworthy that the relative amount of NIC HCV RNA to whole serum HCV RNA was also significantly higher in nonresponders than in sustained responders (0.66 +/- 0.10 vs 0.50 +/- 0.11, p < 0.0001). Multivariate analysis showed that low NIC HCV RNA titer (p < 0.01) and genotype 2 (p = 0.02) were independent variables contributing to sustained response to IFN, but the whole serum HCV RNA titer was not. Pretreatment NIC HCV RNA titer is a more reliable predictive marker than genotype or whole serum HCV RNA of a sustained response to IFN monotherapy. This finding suggests that humoral immunity may affect the response to IFN.

Rat jejunal absorptive function after intestinal transplantation. Effects of extrinsic denervation. Jejunal absorptive function was evaluated following small intestinal transplantation to determine the effects of extrinsic denervation. In particular, water and sodium absorption were measured following transplantation (denervated) and compared to a control group (Thiry-Vella). Water flow was initially secretory two days after transplantation (-41 +/- 27 microliters/min/g dry tissue weight) but became absorptive at day 8 (25 +/- 25). Water flow in the Thiry-Vella group was not significantly different (P > 0.05) from the transplant group at days 8 (17 +/- 7) and 10 (47 +/- 42). Sodium flows were also initially secretory in the transplant group and became absorptive. This study refutes previous claims that small bowel transplants have a deficiency of water absorption due to extrinsic denervation of the bowel and suggests normal absorptive function of water, electrolytes, and protein.

Leukocyte adhesion in local versus hemorrhage-induced ischemia. The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia-reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion.

Ablative facial resurfacing. Ablative resurfacing is a powerful tool for rejuvenation of the aging face and for the treatment of a wide array of skin lesions. In the proper hands, it is a safe and effective way to treat many of the problems of photodamaged skin that surgery or nonablative methods cannot address. This article discusses the three most common modalities used in ablative facial resurfacing: chemical peels, dermabrasion, and laser resurfacing. Indications, mechanism of action, techniques, results, and complications all are reviewed.

Influence of HLA-DR phenotype and myopia on the risk of nonproliferative and proliferative diabetic retinopathy. The relationship between HLA-DR phenotype, refractive error, and risk of both nonproliferative and proliferative diabetic retinopathy was studied among 227 insulin-dependent diabetics participating in a case-control study of diabetic retinopathy. In the absence of myopia, risk of both proliferative and nonproliferative diabetic retinopathy was increased for HLA-DR phenotypes 4/0, 3/0, and X/X (HLA susceptible) compared to HLA-DR phenotypes 3/4, 3/X, and 4/X (HLA nonsusceptible). Odds ratios equalled 11.8 and 7.4 respectively. In the presence of myopia this increased risk associated with HLA status was abolished. Myopia decreased the risk of proliferative and nonproliferative diabetic retinopathy among HLA-susceptible individuals, odds ratio equalled .09 and .09, but had no protective influence among HLA-nonsusceptible individuals.

The development of adaptive skills in young people with Down syndrome. To help children with Down syndrome reach optimum levels of adaptive behaviour, caretakers need to know how and to what extent children with Down syndrome acquire adaptive skills. The adaptive levels of motor, daily living, communicative and social behavioural skills were determined in a group of 984 Dutch children with Down syndrome, aged between 0 and 12 years, and compared with the adaptive levels of typically developing children using a Dutch version of the Vineland Screener. Children with Down syndrome acquire their adaptive skills at a slower pace and reach their ceiling scores at about the age of 12 years, at a substantially lower level than a reference group of typically developing children. Down children seem to acquire skills in a similar sequence and according to a similar trajectory. Development of adaptive skills varies greatly between participants with Down syndrome. For that reason, cohort studies on the development of individuals with Down syndrome over a prolonged period of time are needed.

Detection of HSV and EBV in esophageal carcinomas from a high-incidence area in Shantou China. An association between viral infection, particularly the human papillomavirus, and the development of esophageal carcinoma (EC) has been reported. However, reports concerning the relationship between herpes simplex virus (HSV) and Epstein-Barr virus (EBV) with EC are few. There are geographic variations in infection rates. This study was aimed to determine the co-incidence of infection of the two viruses' with esophageal carcinoma and the differentiation of cancer tissues and lymphocytes infiltration in the tumor stroma of the high-incidence area of Shantou China. To determine the association between viral infection (HSV and EBV) and EC, we applied in situ hybridization (ISH) and immunohistochemistry (IHC) in 164 esophageal carcinoma surgical specimens from the high-incidence area of Shantou China. HSV DNA and HSVI, II protein expression were found in 52 (31.7%) of the 164 tumors; EBV EBER and LMP-1 proteins were identified in only 10 (6.1%) carcinoma specimens by in situ hybridization and immunohistochemistry. In histopathology analysis, the positive cases of HSV appeared to be more predominant in well and moderately differentiated squamous cell carcinomas, and the positive cases of EBV were found in poorly differentiated squamous cell carcinomas or undifferentiated carcinomas with intense lymphoid infiltration. Our results confirm the involvement of HSV and EBV in esophageal carcinomas and the relationship between HSV and EBV infection and esophageal carcinoma cell differentiation with lymphocyte infiltration in the tumor stroma. However, the two herpes viruses, HSV and EBV, particularly the human HSV may be one of the etiological factors in development of this malignancy among the high-incidence population of Shantou China.

Two syntheses of 3-amino-3-deoxy-alpha-D-altropyranosyl 3-amino-3-deoxy-alpha-D-altropyranoside, a new analog of alpha,alpha-trehalose, involving reduction of a diazide and reductive amination of a diketone. A new diamino sugar, 3-amino-3-deoxy-alpha-D-altropyranosyl 3-amino-3-deoxy-alpha-D-altropyranoside (5) was synthesized by two routes starting from alpha,alpha-trehalose. The first route involved reduction and deprotection of a previously described, benzylidenated diazido analog. The second approach proceeded from the known 2,2'-di-O-benzyl-4,6;4',6'-bis-O-benzylidene derivative of alpha-D-altropyranosyl alpha-D-altropyranoside, to the corresponding 3,3'-diketone, which was subjected to reductive amination with sodium cyanoborohydride and ammonium acetate. The major product, separated in 39% yield from by-products after N-acetylation, was deprotected to give 5. Four by-products were isolated in low yields and determined to be monoaminated analogs which comprise two epimeric, 3'-hydroxy structures and two 3'-epimeric, 3'-cyano-3'-hydroxy structures in their non-aminated residues. A number of observations concerning the 13C- and 1H-n.m.r. spectra of the products are discussed, especially with regard to chemical-shift dependencies for certain ring and substituent protons, and attention is drawn to some inter-residue shielding phenomena.

The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis. The relationship between symptom improvement (SI) and acceleration of gastric emptying (GE) for different drugs used in the treatment of idiopathic and diabetic gastroparesis is uncertain. In this paper we examined the study-specific correlations between SI and GE, and we performed a meta-regression analysis of the association across multiple studies. The MEDLINE database (1,946 to present) was searched, and only controlled trials or trials with an established effective comparator that compared both SI and GE were included. Studies were identified for metoclopramide (n=6), domperidone (n=6), cisapride (n=14), erythromycin (n=3), botulinum toxin (n=2), and levosulpiride (n=3). Even though most drugs concomitantly improved symptoms and accelerated GE, no study reported a significant correlation between SI and GE. Moreover, a correlation analysis over all studies using meta-regression did not show a significant relationship between SI and GE. Our findings need to be qualified by inconsistencies in study methods, which is a limitation but also suggests that our findings are robust to methodological factors. In this review, no evidence of a relationship between SI and GE was identified for different drugs used for the treatment of gastroparesis. This finding questions the use of GE measurement to direct drug development for gastroparesis.

[Chronic thallium poisoning (author's transl)]. A rare case of criminal, chronic thallium poisoning is described. In spite of the general prohibition of the cosmetics, drugs and rodent exterminators containing thallium thallium intoxications are still observed occasionally. In the reported case typical symptoms as initial pain, dryness of the skin, constipation and insomnia were missing. The clinical picture was dominated by a polyneuropathy more pronounced in the lower extremities, a lesion of the optic nerve and the psychic symptoms of organic damage. A particular feature was the early loss of sensitivity of the anterior rami of the intercostal nerves.

[Capacity of Caragana microphylla shrub on counteracting snow movement and its influence on snow morphology in the Xilinhot Steppe, China.] The aim of this study was to examine the impacts of characteristics of the shrub (shrub height, shrub width on the windward side, shrub length on the downwind side) on the snow morphology (snow height, snow width, and snow tail length) in the typical steppe of Xilinhot, China. The relationship between shrub height and parameters of snow morphology showed significant quadratic polynomial regression. The relationship between shrub width on the windward side, length on the downwind side and parameters of snow morphology showed significant power function (exponent was less than 1). The morphology and development characteristics of shrub snow were affected by the shrub characteristic parameters. Shrub height had the greatest influence on snow height. Shrub width at the windward side had the greatest influence on snow width and snow tail length. The snow morphology developed faster when the shrub was small, and then tended to be stable. The two-dimensional snow retention range model of shrub directly reflected the disturbance range of shrub to wind and the potential range of snow, indirectly reflected the capacity of shrub to retard snow movement. The three-dimensional snow blocking volume model of shrub snow directly reflected the snow resistance capacity of shrub under certain snow sources and wind conditions. Both models established here would provide a theoretical basis for estimating snow resources and preventing snow disaster in the wind blown snow area of typical steppe.

Correlation between lung perfusion blood volume and SPECT images in patients with chronic thromboembolic pulmonary hypertension by balloon pulmonary angioplasty. We evaluated the reperfusion by balloon pulmonary angioplasty (BPA) in lung PBV and SPECT images. In total, 17 patients and 57 sessions were evaluated. Pre-BPA and post-BPA lung PBV and SPECT/CT images, based on both anatomical segments and physiologic regions (upper/middle/lower) were compared. BPA had a positive effect on most hypoperfused/unperfused segments/regions. There was generally a high rate of agreement between PBV measurements and SPECT/CT. BPA shows promise as a treatment modality for CTEPH patients. SPECT/CT, and, to a lesser extent, PBV, were useful in indicating areas in need of balloon angioplasty.

The pleiotropic effects of erythropoietin in the central nervous system. Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases.

Mitral annular displacement by Doppler tissue imaging may identify coronary occlusion and predict mortality in patients with non-ST-elevation myocardial infarction. Mitral annular displacement (MAD) is a simple marker of left ventricular (LV) systolic function. The aim of this study was to test the hypothesis that MAD can distinguish patients with non-ST-segment elevation myocardial infarctions (NSTEMIs) from those with significant coronary artery disease without infarctions, identify coronary occlusion, and predict mortality in patients with NSTEMIs. MAD was compared with established indices of LV function. In this retrospective study, 167 patients with confirmed NSTEMIs were included at two Scandinavian centers. Forty patients with significant coronary artery disease but without myocardial infarctions were included as controls. Doppler tissue imaging was performed at the mitral level of the left ventricle in the three apical planes, and velocities were integrated over time to acquire MAD. LV ejection fraction, global longitudinal strain (GLS), and wall motion score index were assessed according to guidelines. MAD and GLS could accurately distinguish patients with NSTEMIs from controls. During 48.6 ± 12.1 months of follow-up, 22 of 167 died (13%). MAD, LV ejection fraction, and GLS were reduced and wall motion score index was increased among those who died compared with those who survived (P < .001, P < .001, P < .001, and P = .02, respectively). Multivariate Cox proportional-hazards analyses revealed that MAD was an independent predictor of death (hazard ratio, 1.36; 95% confidence interval, 1.07-1.73; P = .01). MAD and GLS were reduced and wall motion score index was increased in patients with coronary artery occlusion compared with those without occlusion (P = .006, P = .001, and P = .02), while LV ejection fraction did not differ (P = .20). MAD accurately identified patients with NSTEMIs, predicted mortality, and identified coronary occlusion in patients with NSTEMIs.

Ethnic dependent differences in diagnostic accuracy of glycated hemoglobin (HbA1c) in Canadian adults. Previous studies have shown varying sensitivity and specificity of hemoglobin A1c (HbA1c) to identify diabetes and prediabetes, compared to 2-h oral glucose tolerance testing (OGTT) and fasting plasma glucose (FPG), in different ethnic groups. Within the Canadian population, the ability of HbA1c to identify prediabetes and diabetes in First Nations, Métis and Inuit, East and South Asian ethnic groups has yet to be determined. We collected demographic, lifestyle information, biochemical results of glycemic status (FPG, OGTT, and HbA1c) from an ethnically diverse Canadian population sample, which included a purposeful sampling of First Nations, Métis, Inuit, South Asian and East Asian participants. Sensitivity and specificity using Canadian Diabetes Association (CDA) recommended cut-points varied between ethnic groups, with greater variability for identification of prediabetes than diabetes. Dysglycemia (prediabetes and diabetes) was identified with a sensitivity and specificity ranging from 47.1% to 87.5%, respectively in Caucasians to 24.1% and 88.8% in Inuit. Optimal HbA1c ethnic-specific cut-points for dysglycemia and diabetes were determined by receiver operating characteristic (ROC) curve analysis. Our sample showed broad differences in the ability of HbA1c to identify dysglycemia or diabetes in different ethnic groups. Optimal cut-points for dysglycemia or diabetes in all ethnic groups were substantially lower than CDA recommendations. Utilization of HbA1c as the sole biochemical diagnostic marker may produce varying degrees of false negative results depending on the ethnicity of screened individuals. Further research is necessary to identify and validate optimal ethnic specific cut-points used for diabetic screening in the Canadian population.

Comparison of real waste (MSW and MPW) pyrolysis in batch reactor over different catalysts. Part II: contaminants, char and pyrolysis oil properties. Pyrolysis of real wastes (MPW and MSW) has been investigated at 500°C, 550°C and 600°C using Y-zeolite, β-zeolite, equilibrium FCC, MoO3, Ni-Mo-catalyst, HZSM-5 and Al(OH)3 as catalysts. The viscosity of pyrolysis oils could be decreased by the using of catalysts, especially by β-zeolite and MoO3. Both carbon frame and double bound isomerization was found in case of thermo-catalytic pyrolysis. Char morphology and texture analysis showed more coke deposits on the catalyst surface using MSW raw material. Pyrolysis oils had K, S, P Cl, Ca, Zn, Fe, Cr, Br and Sb as contaminants; and the concentrations of K, S, P, Cl and Br could be decreased by the using of catalysts.

Anaphylaxis in the monkey: hemodynamics and blood flow distribution. Aggregate anaphylaxis was induced in eight ovalbumin-sensitized monkeys (Macaca irus). Hemodynamics, blood flow distribution and myocardial performance were studied. Following challenge, severe circulatory shock developed. Systemic arterial and left atrial pressures decreased and pulmonary arterial and right atrial pressures increased. There was a tenfold increase in pulmonary vascular resistance, and cardiac output was markedly reduced (-75%). A redistribution of the blood flow to vital organs (brain, heart and liver) occurred, at the expense of flow to other regions (muscles, kidneys, pancreas and spleen). There was also a redistribution of the blood flow within the myocardium, resulting in an unchanged right ventricular blood flow, despite a decrease in total myocardial blood flow. Right ventricular stroke work was reduced in spite of high filling pressures, whereas the decrease in left ventricular stroke work coincided with low filling pressures. It is concluded that the initial main cause of the low outflow state was an increased resistance in the pulmonary circulation followed by acute right heart failure.

Sternal resection for metastasis from thyroid carcinoma and reconstruction with the sandwiched Marlex and stainless steel mesh. A case of 69-year-old woman with a solitary sternal bone metastasis from thyroid carcinoma undergoing surgical therapy was reported here. On admission, most part of the body of the sternum was destroyed by tumor. Subtotal sternectomy was performed and a part of the major pectoral muscles adherent to the sternal tumor was also resected. The chest wall defect was reconstructed with a sandwiched Marlex and stainless steel mesh. Pathological examination of the resected specimen revealed metastatic papillary carcinoma of the thyroid. Her postoperative course was uneventful. The reconstruction with Marlex and stainless steel mesh seemed to be an appropriate procedure to prevent paradoxical movement of the thorax and protect the intrathoracic organs. Stainless steel mesh compensated for limited resiliency of Marlex mesh and remained rigid in all directions.

Insulin induced reversibility of altered responsiveness in femoral arterial bed of diabetic dogs. The altered reactivities of femoral arterial bed to noradrenaline, phenylephrine, adenosine and prostacyclin were compared in 18, clinically manifest but aketotic, alloxan diabetic mongrel dogs. Alloxan treatment markedly increased the vasoconstrictor responses to noradrenaline and phenylephrine, as well as the adenosine-induced vasodilation in the femoral vasculature. These changes were prevented or normalized, respectively, in the early or late insulin-treated alloxan diabetic animals. In the case of noradrenaline not only a normalization but also an explicit overcompensation could be observed by insulin treatment. The altered reactivity to prostacyclin could not be influenced by insulin therapy. These results indicate a significant difference in the effect of insulin treatment on the altered diabetic vascular responsiveness to catecholamines and adenosine or to prostacyclin.

Congenital spinal tuberculosis associated with asymptomatic endometrial tuberculosis: A rare case report. Spinal tuberculosis constitutes 50% of all musculoskeletal tuberculosis. However, literature regarding congenital spinal tuberculosis is very scanty. Congenital spinal tuberculosis was diagnosed in a two-month-old child on the basis of age at presentation (gibbus since three weeks of age), hepatomegaly, raised ESR, radiological destruction of D10-D11 vertebrae, asymptomatic maternal endometrial tuberculosis and tuberculous histopathology from CT guided biopsy specimen from D10 vertebra. Both child and mother were treated by antitubercular treatment. Child improved symptomatically, gibbus became less prominent and ESR became normal at the end of one year of treatment. Patient had no recurrence during last two years of follow-up. This is the first case of congenital tuberculosis of spine with a documented source of infection from asymptomatic maternal endometrial tuberculosis. CT guided core biopsy from vertebra/aspiration from the paravertebral abscess help in early diagnosis and treatment to reduce neurological morbidity and mortality. Endometrial biopsy help in establishing the diagnosis of congenital tuberculosis and adequate antitubercular treatment in such cases may provide protection to fetus in subsequent pregnancy.

Neonatal presentation of Prader Willi sindrome. Personal records. Prader Willi Syndrome (PWS) is characterized by typical appearance, obesity, short stature, hypothalamic hypogonadism, cryptorchidism, hypotonia, behavioural abnormalities and mental retardation. It is considered as a continuous genes syndrome with different genotypes: microdeletion of the region 15q11-q13 with paternal imprinting; maternal uniparental disomy (UPD) of chromosome 15; chromosomal rearrangement. Clinical manifestations evolve with age from newborn (hypotonia, poor sucking, hypoplastic external genitalia) to childhood (delay in psychomotor development, hyperphagia, obesity, acromicria and craniofacial dysmorphisms). We present five newborns who received an early diagnosis, based on clinical presentation. The early treatment and follow-up can in fact improve the natural evolution of the syndrome in order to prevent respiratory tract diseases and obesity, and to improve growth.

Arachnoid cysts in adults: long-term follow-up of patients treated with internal shunts to the subdural compartment. We have previously presented an alternative method for surgical decompression of intracranial arachnoid cysts. This minimally invasive method, with insertion of an internal shunt from the cyst to the subdural compartment, seemed to be an efficient and simple, and hence promising technique. The aim of the present study was to investigate the long-term results of this procedure. This study is a questionnaire-based retrospective study that includes 31 adult patients (>18 years) who were operated on in our department for an arachnoid cyst in the temporal fossa or overlying the frontal convexity with the internal shunt technique between April 1990 and October 2003. Follow-up ranged from 15 months to 14.8 years (mean = 8.2 years). Of the patients, 83% were asymptomatic or had insignificant complaints at follow-up. A total of 17% reported no reduction of the preoperative complaints. No patient experienced worsening of the symptoms. The cyst was no longer visible on postoperative radiologic examinations in 37% of the patients. In 37%, the postoperative fluid volume was less than 50% of the original volume. In 13%, the cyst volume was reduced but the postoperative volume was greater than 50% of the original cyst volume. Thus, the cyst was unchanged in only 13% of the patients. There was no correlation between volume reduction and clinical improvement. A complication (subdural hygroma or hematoma) occurred in 7 patients, all with temporal cysts, leading to reoperation in 4. None of the complications caused permanent neurologic deficits or invalidity. Seven patients were reoperated on because of suspected or established treatment failure. The internal shunt technique is a relatively simple, safe, and efficient alternative method for treatment of arachnoid cysts. It should be considered a valuable alternative in the treatment of arachnoid cysts.

Toxic effects of unresolved complex mixtures of aromatic hydrocarbons accumulated by mussels, Mytilus edulis, from contaminated field sites. Exposure of marine mussels (Mytilus edulis) to an unresolved complex mixture (UCM) of aromatic hydrocarbons isolated from a crude oil has been shown to reduce their feeding rate by 40%. The present study was undertaken to determine whether UCMs bioaccumulated by mussels in the field are also toxic. The feeding rate of mussels derived from polluted sites increased when they were placed in clean water, pointing to a loss of toxic agents from the tissues. At the end of the depuration period, water in which mussels from an oil-polluted site had been held contained a UCM. Steam-distillation extracts of the tissues of mussels taken from several polluted sites were shown to be highly toxic to the feeding activity of juvenile mussels. The tissues of mussels from these sites contained UCMs. Nontoxic steam distillates from clean mussels did not. Steam-distillation extracts of mussels from an oil-polluted site were fractionated by normal-phase high-performance liquid chromatography. A fraction, largely comprising a "monoaromatic" UCM, reduced the feeding rate of juvenile mussels by 70%. Two later-eluting fractions containing aromatic UCMs also produced smaller depressions in feeding rate. These results support our contention that some aromatic UCM hydrocarbons constitute a forgotten pollutant burden in the marine environment.

Cytoskeletal actin: the influence of major burns on neutrophil structure and function. It has been noted that major trauma and burns patients who survive beyond 48 h most frequently succumb to sepsis and multiple organ failure. Furthermore, such patients are usually markedly hypermetabolic and in negative nitrogen balance at the time of their demise. Along with many other systemic and immune dysfunctions, the polymorphonuclear white blood cells in this setting become functionally impaired. Given that the motile white blood cells contain significant proportions of the contractile protein, actin, we speculated that the leucocyte dysfunction might in part be related to the overall systemic catabolism of actin stores. Accordingly, this hypothesis was explored by comparing the functions and cytoskeletal structure of neutrophilic leucocytes from normal control adults and victims of fresh, major thermal injuries. On days 1 and 7 after a burn of > 25 per cent of total body surface area, peripheral blood was drawn from 10 patients (mean age 33 years, mean burn area 44.2 per cent), and seven unburned controls (mean age 35.2 years). Neutrophils isolated from these specimens were tested for stimulated chemotactic rate, efficacy of intracellular killing as determined by superoxide production rate, and the levels of soluble and insoluble intracellular actin. In addition, both light microscopy and scanning electron microscopy were used to visualize the actin cytoskeleton. The results indicated that both chemotactic rate (12 mu/min vs. 38 mu/min--P < 0.05) and superoxide production rate (9 vs 43 mumol/ml10E6 cells--P < 0.05), were significantly reduced in the burn patients by day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimizing independent finger flexion with zone V flexor repairs using the Massachusetts General Hospital flexor tenorrhaphy and early protected active motion. Independent FDS action has been cited to be problematic with repair of multiple tendons in zone V owing to adhesion formation between the flexor digitorum superficialis (FDS) and the flexor digitorum profundus (FDP) tendons. Of the several described flexor repair techniques the ideal tendon repair should be strong enough to allow for early active motion to minimize adhesion formation and maximize tendon healing. Biomechanical studies have proven the Massachusetts General Hospital (MGH) repair to be strong enough to allow for early active motion. The purpose of this study was to examine the use of the MGH technique for zone V flexor tendon injuries to allow for early protected active motion to achieve independent finger flexion through better differential gliding of the tendons. We performed a retrospective review 168 zone V finger flexor tendon repairs for 29 patients performed consecutively over 4 years when early active motion was not contraindicated. The same early protected active motion protocol was used for all of these patients. We reviewed total active motion, independent flexion, rupture, and need for tenolysis. These injuries involved 103 FDS and 65 FDP tendons to 103 fingers. The median follow-up period was 24 weeks. Of these 29 patients 19 were men and 10 were women. The average patient age was 28 years. The total active motion for these zone V repairs was 236 degrees +/- 5 degrees Overall 97 of 103 digits attained good to excellent function and 88 of 103 developed some differential glide. One of these patients required a tenolysis. Three repairs ruptured in 1 patient owing to suture breakage that was associated with noncompliance with the dorsal extension block splint. Our retrospective review of 168 consecutive flexor tendon repairs showed that the MGH technique allowed for early protected active motion, which provided good to excellent functional outcomes with 88 of 103 developing independent finger flexion at an acceptably low complication risk.

[Resistance to tumor specific therapy with imatinib by clonal selection of mutated cells]. A 60-year-old woman presented with night-sweats and increasing weakness. Physical examination revealed no abnormalities. For 27 years she had been treated for Philadelphia-positive chronic myeloid leukemia (CML). Because of progressive disease treatment with the tyrosine kinase inhibitor imatinib (STI571, Glivec (R)) had been started 9 months before. She had achieved complete hematological remission within 8 weeks, but not a cytogenetic response. Elevated WBC count (26.7/nl) with a differential displaying typical features of acceleration in bone marrow aspirate confirmed CML in accelerated phase. Sequencing of the ATP binding site of the BCR-ABL gene, which - at protein level - is the target for imatinib, revealed the clonal selection of cells harboring a point mutation leading to the exchange of amino acid 253 from tyrosine to histidine. This was considered to be the cause of resistance to imatinib. Dose increase of imatinib up to 600 mg daily and administration of cytarabine did not overcome resistance. Imatinib therapy was discontinued; hematologic remission was induced by oral therapy with hydroxyurea and mercaptopurine. In the course of the following 6 months a gradual decrease of the resistant clone from 100 % down to lower than the detection limit of the method was demonstrated. Clonal mutations are often the cause of resistance to imatinib therapy. They can be detected by sequencing of the ATP binding site of BCR-ABL in specialized laboratories. This case shows that discontinuation of imatinib therapy can significantly reduce the mutated (resistant) clone and thereby restore sensitivity to imatinib.

Erythrocyte sedimentation rate and C-reactive protein levels are poorly correlated with clinical measures of disease activity in rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis patients. To determine the patterns and correlation of elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels with outcome measures in rheumatoid arthritis (RA), and compare it to systemic lupus erythematosus (SLE) and osteoarthritis (OA) patients. Brooklyn Outcomes Arthritis Registry Database (BOARD) was analyzed to determine both first visit and mean values of ESR and CRP, along with disease activity measures in each patient. Data were analyzed with descriptive statistics and correlations. Among all patients half of all (n=377) ESR results were elevated. In RA patients the proportions of having both ESR and CRP elevated, both within normal levels, and only one elevated and the other normal were similar. For all diagnosis, both ESR and CRP have weak positive correlations with disease activity measures measured at first visits. ESR and CRP have a modest positive correlation with each other across all three disease groups. In this cohort of RA, SLE and OA patients, ESR and CRP values were modestly correlated with each other and they were weakly correlated with disease activity measures. These data suggest that another look at the role of ESR and CRP as markers of inflammation in RA patients seen in routine care may be in order.

Electrospinning of sodium alginate-pectin ultrafine fibers. In this study, we investigated the electrospinning process of sodium alginate-pectin fibers intended to be used as a carrier for stabilizing folic acid. Fiber-forming solutions containing 0.01% (w/w) folic acid were prepared by blending low- or medium-viscosity sodium alginate with pectin in a 70 : 30 ratio to form LSAP and MSAP solutions, respectively. Similar to other polysaccharide polymers reported previously, these solutions could not be electrospun. However, the incorporation of poly(ethylene oxide) (PEO) effectively enabled the electrospinning process. Electrospun fibers of different morphologies, ranging from fiber to fiber-bead, were obtained, depending on the blend ratio, concentration, and viscosity of the polymer-PEO solution used. Fibers electrospun from 3% MSAP/PEO (80%/20% w/w) had the smallest diameter (about 40 nm), whereas fibers containing higher PEO contents were larger in diameter. Bead-free fibers were formed when 4% LSAP/PEO (50/50) and 5% LSAP/PEO (80/20 to 50/50) were electrospun. The electrical conductivity and surface tension lowering effects of PEO on the polymer solution were likely the contributing factors for the observed electrospinning behaviors. By adjusting the formulation of the polymer solution, fibers of various morphologies may be obtained to suit different end-use applications. A study is currently ongoing to investigate the effectiveness of these fibers for stabilizing folic acid.

Initial planning benefits complex prospective memory at a cost. The effect of initial planning on complex prospective memory was investigated using a virtual environment and a sample of healthy young adults (N = 34). Participants were assigned to either an initial planning or a control condition and were asked to complete a series of time- and event-based prospective memory tasks. The planning group completed the tasks more quickly and accurately than the control group. However, the total time spent, including both planning and task execution, was comparable for the two groups. Within the planning group, tasks that were planned were more likely to be completed than unplanned tasks, but inclusion of overly detailed information in the plans resulted in poorer performance. These results suggest that although initial planning can be beneficial to task completion, the complexity of a plan may contribute to decrements in performance.

The Landau-Kleffner syndrome or 'acquired aphasia with convulsive disorder'. Long-term follow-up of six children and a review of the recent literature. We present six patients with acquired aphasia with convulsive disorder (Landau-Kleffner syndrome) and distill the main clinical features from a review of the recent literature. Our series showed that the clinical picture can vary at onset, as well as during the course of the illness, and that the long-term outcome of the aphasia is quite unpredictable, despite the fact that epilepsy and electroencephalographic abnormalities usually regress or disappear with the years. We also call attention to the electroencephalographic phenomenon of electrical status epilepticus during slow sleep, and we suggest that the course of the aphasia may well be linked to the appearance and disappearance of electrical status epilepticus during slow sleep. Therefore, we recommend a sleep electroencephalogram in all children with Landau-Kleffner syndrome. Finally, our findings did not demonstrate the beneficial effect of treatment with anticonvulsants on the aphasia, but recent studies have shown that treatment with corticosteroids, whether combined with anticonvulsants, is effective.

Ontogenetic variation in the chemical defenses of cane toads (Bufo marinus): toxin profiles and effects on predators. We conducted a quantitative and qualitative chemical analysis of cane toad bufadienolides--the cardioactive steroids that are believed to be the principal cane toad toxins. We found complex shifts in toxin composition through toad ontogeny: (1) eggs contain at least 28 dominant bufadienolides, 17 of which are not detected in any other ontogenetic stage; (2) tadpoles present a simpler chemical profile with two to eight dominant bufadienolides; and (3) toxin diversity decreases during tadpole life but increases again after metamorphosis (larger metamorph/juvenile toads display five major bufadienolides). Total bufadienolide concentrations are highest in eggs (2.64 +/- 0.56 micromol/mg), decreasing during tadpole life stages (0.084 +/- 0.060 micromol/mg) before rising again after metamorphosis (2.35 +/- 0.45 micromol/mg). These variations in total bufadienolide levels correlate with toxicity to Australian frog species. For example, consumption of cane toad eggs killed tadpoles of two Australian frog species (Limnodynastes convexiusculus and Litoria rothii), whereas no tadpoles died after consuming late-stage cane toad tadpoles or small metamorphs. The high toxicity of toad eggs reflects components in the egg itself, not the surrounding jelly coat. Our results suggest a dramatic ontogenetic shift in the danger that toads pose to native predators, reflecting rapid changes in the types and amounts of toxins during toad development.

[Delayed primary anastomosis for esophageal atresia]. The aim of study is to review patients with esophageal atresia, treated by means of delayed primary esophageal anastomosis at Vilnius University Children's Hospital. Study was performed by retrospective analysis of medical records including period of 1992-2002, and clinical evaluation of late results. There were 97 patients with esophageal atresia, and 17 (17.5%) of them were selected for delayed primary esophageal anastomosis. This method was introduced in year 1993. Out of 17 patients selected for delayed primary esophageal anastomosis; 4 died from septic complications. Early complications included leakage of the anastomosis for six patients; four of them recovered after conservative treatment. Esophageal stricture occurred in 5 patients, and was resolved by bouggienage. The follow-up of 13 survivors at present is from 2 to 10 years. Gastroesophageal reflux was diagnosed in 4 patients, one of them was cured with Nissen fundoplication; others received medication. All at present are developing normally. None of them suffer from dysphagia. They do not need esophageal dilatation. We have found that in this group of patients elongation of esophageal segments and delayed primary esophageal anastomosis is effective and esophagus saving procedure.

Assessment of competency in clinical measurement: comparison of two forms of sequential test and sensitivity of test error rates to parameter choice. To assess clinical measurement competency by two sequential test formulations [resetting sequential probability ratio test (R-SPRT) and learning curve cumulative summation (LC-CUSUM)]. Numerical simulation and retrospective observational study. Obstetric ultrasound department. Cohorts of 10,000 simulated trainees and 62 obstetric sonographers training in nuchal translucency (NT) measurement at the 11-14-week pregnancy scan with limited case availability. Application of LC-CUSUM and R-SPRT to clinical measurement training. Proportions of real trainees achieving competency by LC-CUSUM and R-SPRT, proportions of simulated competent trainees not achieving competency (Type I error), proportions of simulated incompetent trainees achieving competency (Type II error), distribution of case number required to achieve competency (run length) and frequency of resets. For simulated cohorts, significant differences in run-length distribution and true test error rates were found between the R-SPRT and LC-CUSUM tests with equivalent parameters. Increasing the cases available to each trainee reduced the Type I error rate but increased the Type II error rate for both sequential tests for all choices of unacceptable failure rate. Discontinuities in the proportion of trainees expected to be test competent were found at critical values of unacceptable failure rate. With equivalent parameters, the R-SPRT and LC-CUSUM formulations of sequential tests produced different outcomes, demonstrating that the choice of test method, as well as the choice of parameters, is important in designing a training scheme. The R-SPRT detects incompetence as well as competence and may indicate need for further training. Simulations are valuable in estimating the proportions of trainees expected to be assessed as competent.

[Optimizing palliative therapy in pancreatic carcinoma]. Only an interdisciplinary approach between surgeon, medical oncologist and radiologist may allow the optimisation of palliative treatment for pancreatic carcinoma. If imaging diagnostics do not allow to decide about the resectability of a tumour, an explorative laparotomy should be performed, unless this is precluded by comorbidity. Due to similar morbidity and mortality, but better long-term results, a choloedocho-jejunostomy should be performed for intra-operatively unresectable tumors in favour of a cholecysto-jejunostomy. In selected patients a gastro-enterostomy may be indicated. However, this is not justified prophylactically. If imaging diagnostics show definite signs of unresectability in the absence of a gastric outlet obstruction, the treatment depends on the general condition of the patient: Insertion of a pigtail-catheter is sufficient for patients in poor general condition and a short life expectancy; metal wallstents should be preferred for patients in good general condition and a life expectancy in excess of six months, due to better results regarding quality of life. Chemoablation of the celiac plexus is an useful method to control the sever pain, which is common in these patients; radiotherapy or analgesic therapy may be used alternatively.

Quantitative drug interactions prediction system (Q-DIPS): a dynamic computer-based method to assist in the choice of clinically relevant in vivo studies. Metabolic drug interactions are a major source of clinical problems, but their investigation during drug development is often incomplete and poorly specific. In vitro studies give very accurate data on the interactions of drugs with selective cytochrome P450 (CYP) isozymes, but their interpretation in the clinical context is difficult. On the other hand, the design of in vivo studies is sometimes poor (choice of prototype substrate, doses, schedule of administration, number of volunteers), with the risk of minimising the real potential for interaction. To link in vitro and in vivo studies, several authors have suggested using extrapolation techniques, based on the comparison of in vitro inhibition data with the active in vivo concentrations of the inhibitor. However, the lack of knowledge of one or several important parameters (role of metabolites, intrahepatocyte accumulation) often limits the possibility for safe and accurate predictions. In consequence, these methods are useful to complement in vitro studies and help design clinically relevant in vivo studies, but they will not totally replace in vivo investigation in the future. We have developed a computerised application, the quantitative drug interactions prediction system (Q-DIPS), to make both qualitative deductions and quantitative predictions on the basis of a database containing updated information on CYP substrates, inhibitors and inducers, as well as pharmacokinetic parameters. We also propose a global approach to drug interactions problems--'good interactions practice--to help design rational drug interaction investigations, sequentially associating in vitro studies, in vitrolin vivo extrapolation and finally well-designed in vivo clinical studies.

Modeling the epidermal growth factor -- epidermal growth factor receptor l2 domain interaction: implications for the ligand binding process. Signaling from the epidermal growth factor (EGF) receptor is triggered by the binding of ligands such as EGF or transforming growth factor alpha (TGF-alpha) and subsequent receptor dimerization. An understanding of these processes has been hindered by the lack of structural information about the ligand-bound, dimerized EGF receptor. Using an NMR-derived structure of EGF and a homology model of the major ligand binding domain of the EGF receptor and experimental data, we modeled the binding of EGF to this EGF receptor fragment. In this low resolution model of the complex, EGF sits across the second face of the EGF receptor L2 domain and EGF residues 10-16, 36-37, 40-47 bind to this face. The structural model is largely consistent with previously published NMR data describing the residues of TGF-alpha which interact strongly with the EGF receptor. Other EGF residues implicated in receptor binding are accounted by our proposal that the ligand binding is a two-step process with the EGF binding to at least one other site of the receptor. This three-dimensional model is expected to be useful in the design of ligand-based antagonists of the receptor.

Dual role of DNA intrinsic curvature and flexibility in determining nucleosome stability. A statistical mechanistic approach to evaluate the sequence-dependent thermodynamic stability of nucleosomes is proposed. The model is based on the calculation of the DNA intrinsic curvature, obtained by integrating the nucleotide step deviations from the canonical B-DNA structure, and on the evaluation of the first order elastic distortion energy to reach the nucleosomal superstructure. Literature data on the free energy of nucleosome formation as obtained by competitive nucleosome reconstitution of a significant pool of different DNA sequences were compared with the theoretical results, and a satisfactorily good correlation was found. A striking result of the comparison is the emergence of two opposite roles of the DNA intrinsic curvature and flexibility in determining nucleosome stability. Finally, the obtained results suggest that the curvature-dependent DNA hydration should play a relevant role in the sequence-dependent nucleosome stability.

Spintronics in antiferromagnets. Magnetic domains and the walls between are the subject of great interest because of the role they play in determining the electrical properties of ferromagnetic materials and as a means of manipulating electron spin in spintronic devices. However, much less attention has been paid to these effects in antiferromagnets, primarily because there is less awareness of their existence in antiferromagnets, and in addition they are hard to probe since they exhibit no net magnetic moment. In this paper, we discuss the electrical properties of chromium, which is the only elemental antiferromagnet and how they depend on the subtle arrangement of the antiferromagnetically ordered spins. X-ray measurement of the modulation wavevector Q of the incommensurate antiferromagnetic spin-density wave shows thermal hysteresis, with the corresponding wavelength being larger during cooling than during warming. The thermal hysteresis in the Q vector is accompanied with a thermal hysteresis in both the longitudinal and Hall resistivity. During cooling, we measure a larger longitudinal and Hall resistivity compared with when warming, which indicates that a larger wavelength at a given temperature corresponds to a smaller carrier density or equivalently a larger antiferromagnetic ordering parameter compared to a smaller wavelength. This shows that the arrangement of the antiferromagnetic spins directly influences the transport properties. In thin films, the sign of the thermal hysteresis for Q is the same as in thick films, but a distinct aspect is that Q is quantized.

[A case of skeletal muscle metastasis on the left thigh after esophagectomy for esophageal adenocarcinoma in Barrett' s esophagus]. We report the case of a 45-year-old man with advanced esophageal adenocarcinoma in Barrett's esophagus. After neoadjuvant chemotherapy using S-1, docetaxel, and cisplatin, the patient underwent thoracoscopic esophagectomy with a two-field lymph node dissection and reconstruction with a gastric tube through the posterior mediastinal route. The pathological stage was CT-pT4 (diaphragm), ly2, v1, CT-pN1, CT-pStage IVa. Fourteen months after the operation, the patient complained of pain in his left thigh with a palpable indurated mass that was increasing in size. Needle biopsy specimens revealed skeletal muscle metastasis of the adenocarcinoma. The metastastic lesion was resected and local control was achieved successfully for 13 months, after which the patient died because of intrabronchial bleeding.

Centrifugal cytology of nipple aspirate cells. Two improvements in the methodology for obtaining and preparing nipple aspirates from nonlactating women are reported. The first is the development and use of a new breast pump with a controllable vacuum and cups of various sizes. The second is the use of centrifugal cytology to prepare the dispersions. Twenty-one of 24 breasts of patients in the age range 30 to 49 years produced cellular dispersions which contained foam cells; of them, 13 contained ductal cells. A comparison of glutaraldehyde and ethanol fixation indicated that the cells appeared substantially the same.

Synthesis and Semiconducting Characteristics of the BF2 Complexes of Bisbenzothiophene-Fused Azadipyrromethenes. A novel type of dibenzothiophene [b]-fused core-expanded azaBODIPYs were obtained through an efficient post-functionalization of tetrabrominated azadipyrromethenes, using CuI-catalyzed cyclization, followed by BF2 complexation. These dyes show nearly planar skeletons, strong NIR absorption with maximum peaks up to 733 nm, and remarkable low-lying LUMO level of -4.15 eV. The field-effect transistor based on 1b exhibits bipolar transport properties, with the highest electron and hole mobilities up to 0.012 and 0.046 cm2 V-1 s-1, respectively.

[An experimental infection of Hyalomma asiaticum and Ornithodoros papillipes ticks with a single and combined infection with Coxiella burnetii and Dermacentroxenus sibericus]. Experimental infection of H. asiaticum and O. papillipes with Coxiella burnetii and R. (D.) sibericus in different succession and individual study of these arthropods by means of the fluorescent antibodies method, ordinary microscopy and titration on laboratory animals have revealed an ambiguous outcome of the development of combined rickettsial infection in these ticks. The first agent obtained by the vector either prevents utterly the reproduction of the heterologous agent or inhibits its activity. At the concurrent infection of the ticks with two species of rickettsiae the reproduction of the both agents takes place but against a background of intersuppression of their reproduction. The development of the combined rickettsial infection in ticks is an example of "irregular competition" of species as one of the types of competitive relationships.

Onset of diradical character in small nanosized graphene patches. A family of small graphene patches, i.e., rectangular polyaromatic hydrocarbons (PAHs), that have both zigzag and armchair edges is investigated to establish their ground state electronic structure. Broken symmetry density functional theory (DFT) and plane wave DFT were used to characterize the onset of diradical character via relative energies of open-shell and closed-shell singlet states. The perfect pairing (PP) active space approximation of coupled cluster theory was used to characterize diradical character on the basis of promotion of electrons from occupied to unoccupied molecular orbitals. The role of zigzag and armchair edges in the formation of open-shell singlet states is elucidated. In particular, it is found that elongation of the zigzag edge results in an increase of diradical character whereas elongation of the arm chair edge leads to a decrease of diradical character. Analysis of orbitals from PP calculations suggests that diradical states are formally Mobius aromatic multiconfigurational systems.

[Lid reconstruction: functional and aesthetic aspects]. There are numerous different procedures for eyelid reconstruction, one of them being the transfer of pedicled full eyelid flaps. With regard to the increasing demands of the patients the so-called sandwich techniques in most cases offer the chance to get the best functional and aesthetic result in a individual situation. Some of these techniques are presented here.

Two ways of estimating the euro value of the illicit market for cannabis in France. The most recent health surveys in general population are used in order to estimate the annual market size for cannabis in France in 2005. Two methods for arriving at an estimate are proposed: the first based on reported consumption, the other on reported expenditure on cannabis. The annual sales figure for cannabis in France is between 746 and 832 million euro. Men's expenditure accounts for between 80 and 85% of total expenditure and those aged between 15 and 24 years account for the greatest part of the size of the cannabis market, between 57 and 60%, depending upon the method. According to these estimates, consumers' average annual expenditure on cannabis is around euro 202 in France, compared to estimates obtained for New Zealand and Holland (euro 124) and the United States (euro 362).

Whole Genome DNA Methylation Analysis Using Next-Generation Sequencing (BS-seq). Plant methylation is widely evident and has played crucial roles ranging in defining the epi-genome variations during abiotic and biotic stress. Variations in epi-genomic level has observed not only in the symmetrical as well as the non-symmetrical sequences. Plethora of these epi-genomic variations have been widely also demonstrated at the flowering, tissue-specific, and also at developmental stages revealing a strong association of the observed epi-alleles to the physiological state. In the present chapter, epi-genomic analysis of the s has been described with functional workflow and illustrated methodology.

Adverse health events associated with domestic violence during pregnancy among Brazilian women. domestic violence during pregnancy remains an unsolved and neglected social problem despite the recognised adverse physical and mental health consequences. to examine the association between domestic violence (psychological violence and physical or sexual violence) and health problems self-reported by pregnant women. a cross-sectional analysis from a cohort study of 1,379 pregnant women attending prenatal care in public primary care units in Campinas, São Paulo, Brazil. Data were collected by interviewing women when they enroled for prenatal care. Domestic violence and alcohol abuse were ascertained by validated questionnaires. Referred morbidities, undesirable behaviours and sociodemographic characteristics were also recorded. Univariate analyses were used to estimate prevalence and unadjusted odd ratios. Multivariate logistic regression was used to identify the independent association between psychological violence and physical or sexual violence during pregnancy and women's health outcomes. psychological violence and physical or sexual violence were reported by 19.1% (n=263) and 6.5% (n=89) of the pregnant women, respectively. Psychological violence was significantly associated with obstetric problems [odds ratio (OR) 1.95; 95% confidence interval (CI) 1.39-2.73], premature rupture of membranes (OR 1.64, 95% CI 1.01-2.68), urinary tract infection (OR 1.71, 95% CI 1.19-2.42), headache (OR 1.75, 95% CI 1.25-2.40) and sexual risk behaviours (OR 2.28, 95% CI 1.18-4.41). Physical or sexual violence was significantly associated with: obstetric problems (OR 1.72, 95% CI 1.08-2.75), premature rupture of membranes (OR 2.11, 95% CI 1.14-3.88), urinary tract infection (OR 2.05, 95% CI 1.26-3.34), vaginal bleeding (OR 1.95, 95% CI 1.10-3.43) and lack of sexual desire (OR 3.67, 95% CI 2.23-6.09). domestic violence during pregnancy was associated with adverse clinical and psychological outcomes for women. These results suggest that a well-organised health-care system and trained health professionals, as well as multisectorial social support, are necessary to prevent or address the negative influence of domestic violence on women's health in Brazil.

A novel method for material characterization of reusable products. Product reuse contributes favorably to waste management and resource recovery by diverting products from terminal disposal to second-hand urban markets. Many organizations with social mission incorporate in their activities the process of reuse, thus making valuable products available to second-hand customers through their thrift stores. Data management and product classification are an important aspect of quantitative analysis of second-hand products circulating through reuse organizations. The New York City Center for Materials Reuse has, for the last 10years, organized the reuse activities of most not for profit organizations, and collected valuable information on the strengths and weaknesses of their operations. One such finding is the casual, and inconsistent approach used by these organizations to keep a record of the level and value of the reuse efforts they undertake. This paper describes a novel methodology developed to standardize record keeping and characterize commonly reused post-consumer products by assessing the outgoing product flow from reuse organizations. The approach groups material composition of individual products into main product categories, creating a simplified method to characterize products. Furthermore, by linking product categories and material composition, the method creates a matrix to help identify the material composition of products handled by reuse organizations. As part of the methodology, whenever adequate data are not available about certain types of products, a process identified as "field characterization study" is proposed and incorporated in the implementation to develop meaningful and useful data on the weight and material composition. Finally, the method incorporates the estimation of the environmental impact of reuse using standard models available through the U.S. Environmental Protection Agency and other worldwide entities. The diversified weight and size of products poses a challenge to the statistical significance of the estimated weights. A case study is presented, illustrating how the proposed methodology can be applied to estimate environmental benefits from the sale of second-hand products in reuse organizations.

Assessing Infrastructure to Care for Pediatric Patients in the Prehospital Setting. Pediatric patients represent a small proportion of emergency medical services (EMS) calls, challenging providers in maintaining skills in treating children. Having structural capacity to appropriately diagnose and treat pediatric patients is critical. Our study measured the availability of off-line and on-line medical direction and recommended pediatric equipment at EMS agencies. A Web-based survey was sent to EMS agencies in 2010 and 2013, and results were analyzed to determine availability of medical direction and equipment. Approximately 5000 agencies in 32 states responded, representing over 80% response. Availability of off-line medical direction increased between years (78% in 2010 to 85% in 2013), was lower for basic life support (BLS) (63% and 72%) than advanced life support (ALS) agencies (90% and 93%), and was generally higher in urban than rural or frontier locations. On-line medical direction was consistently available (90% both years) with slight increases for BLS agencies (87% to 90%) and slightly greater availability for urban and rural compared with frontier agencies. The majority of agencies carried most recommended equipment; however, less than one third of agencies reported carrying all equipment. Agencies with off-line medical direction, on-line medical direction, and with both off-line and on-line medical direction were respectively 1.69, 1.31, and 2.21 times more likely to report carrying all recommended equipment. Basic structural capacity exists in EMS for treating children, with improvements seen over time. However, gaps remain, particularly for BLS and nonurban agencies. Continuous attention to infrastructure is necessary, and the recent development of national performance measures should further promote quality emergency care for all children.

Ibrutinib induces multiple functional defects in the neutrophil response against Aspergillus fumigatus. Bruton's tyrosine kinase inhibitor ibrutinib has become a leading therapy against chronic lymphoid leukemia. Recently, ibrutinib has been associated with the occurrence of invasive fungal infections, in particular invasive aspergillosis. The mechanisms underlying the increased susceptibility to fungal infections associated with ibrutinib exposure are currently unknown. Innate immunity, in particular polymorphonuclear neutrophils, represents the cornerstone of anti-Aspergillus immunity however the potential impact of ibrutinib on neutrophils has been little studied. Our study investigated the response to Aspergillus fumigatus and neutrophil function in patients with chronic lymphoid leukemia or lymphoma, who were undergoing ibrutinib therapy. To answer this question, we studied the consequences of ibrutinib exposure on the functions and anti-Aspergillus responses of neutrophils obtained from healthy donors and 63 blood samples collected at different time points amongst 32 patients receiving ibrutinib for lymphoid malignancies. We used both flow cytometry and video-microscopy approaches to analyze neutrophils' cell surface molecule expression, cytokine production, oxidative burst, chemotaxis and killing activity against Aspergillus. Ibrutinib is associated, both in vitro and in patients under treatment, with multiple functional defects in neutrophils, including decreased reactive oxygen species production, impairment of their capacity to engulf Aspergillus and inability to efficiently kill germinating conidia. Our results demonstrate that ibrutinib-exposed neutrophils develop significant functional defects that impair their response against Aspergillus fumigatus, providing a plausible explanation for the emergence of invasive aspergillosis in ibrutinib-treated patients.