Transmucosal delivery of oxytocin to rabbits using a mucoadhesive buccal patch.
A biocompatible, mucoadhesive buccal patch was evaluated in rabbits for transmucosal delivery of peptides. Oxytocin (OT) was incorporated into custom coformulations of Carbopol 974P and silicone polymer and the resulting plasma OT concentration versus time profiles determined following patch application. For comparative purposes, the mean values determined for the elimination half-life (t1/2), volume of distribution (Vd), and the total body clearance (CL) following intravenous injection of OT were 2.9 +/- 0.2 min, 85.3 +/- 6.7 ml, and 20.4 +/- 2.03 ml/min, respectively. Following application of oxytocin-loaded mucoadhesive patches, plasma OT concentrations remained 20- to 28-fold greater from 0.5 to 3.0 hr than control animals administered placebo patches. The steady-state plasma OT concentration (Css) following application of the buccal patches was 80.6 +/- 15.9 pg/ml. The lag-time associated with attainment of the Css was 0.45 +/- 0.18 hr. Steady-state flux (Jss) of oxytocin in vivo was 139 +/- 36.8 ng/hr/cm2. Based on the amount of OT remaining in the patches following removal, the average dose of OT released in vivo was 0.27 +/- 0.024 mg with a bioavailability of 0.1%. No significant alterations in mucosal histology were observed when underlying mucosa to which OT patches had been applied were compared to either control (no patch) mucosa or mucosa underneath placebo patches. The mucoadhesive buccal patches were easy to apply and remove, nonirritating to tissue, and able to continuously deliver a nonapeptide over 3 hr. Based on these preliminary studies, the mucoadhesive buccal patches evaluated may represent an improved transmucosal drug delivery system for peptides and conventional drug substances.


Artificial UV-B induced changes in pigmentation of marine diatom Coscinodiscus gigas.
In vitro studies in marine diatom Coscinodiscus gigas revealed that artificial UV-B radiation (313 nm) at a dose level of 0.4W m(-2) for a continuous period of 3 hours in a UV treatment chamber caused disbursement of chromatophores from their normal loci and resulted in clumping / aggregation of chromatophores exhibiting a phenomenon called UV-B induced syntrophism. It is also understood that such clumping could cause only insignificant reduction in photosynthetic oxygen release.


Thinking inside the box: the health cube paradigm for health and wellness program evaluation and design.
Appropriately constructed health promotions can improve population health. The authors developed a practical model for designing, evaluating, and improving initiatives to provide optimal value. Three independent model dimensions (impact, engagement, and sustainability) and the resultant three-dimensional paradigm were described using hypothetical case studies, including a walking challenge, a health risk assessment survey, and an individual condition management program. The 3-dimensional model is illustrated and the dimensions are defined. Calculation of a 3-dimensional score for program comparisons, refinements, and measurement is explained. Program 1, the walking challenge, had high engagement and impact, but limited sustainability. Program 2, the health risk assessment survey, had high engagement and sustainability but limited impact. Program 3, the on-site condition management program, had measurable impact and sustainability but limited engagement, because of a lack of program capacity. Each initiative, though successful in 2 dimensions, lacked sufficient evolution along the third axis for optimal value. Calculation of a 3-dimensional score is useful for health promotion program development comparison and refinements, and overall measurement of program success.


Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced Parkinson's disease in mice.
Paeonol is a major phenolic compound of the Chinese herb, Cortex Moutan, and is known for its antioxidant, anti-inflammatory and antitumor properties. The present study was designed to investigate the therapeutic potential and underlying mechanisms of paeonol on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of Parkinson's disease (PD). MPTP (25 mg/kg), followed by probenecid (250 mg/kg), was administered via i.p. injection for five consecutive days to induce the mouse model of PD. Paeonol (20 mg/kg) was administrated orally for 21 days. Behavior was assessed using the rotarod performance and open‑field tests. Additionally, the levels of tyrosine hydroxylase (TH), microglia, interleukin‑1β (IL‑1β), and brain‑derived neurotrophic factor (BDNF) in the substantia nigra pars compacta (SNpc) were evaluated by immunohistochemical staining. MPTP/p‑induced motor deficits were observed to be significantly improved following long‑term treatment with paeonol. Paeonol treatment decreased MPTP/p‑induced oxidative stress, as determined by evaluating the activity levels of superoxide dismutase, catalase and glutathione. Additionally, MPTP/p‑induced neuroinflammation was assessed by examining the levels of microglia and IL‑1β, which were significantly decreased following paeonol treatment. Paeonol treatment improved the MPTP/p‑induced dopaminergic neurodegeneration, as measured by observing the increased TH level in the SNpc. Furthermore, the BDNF level was significantly elevated in the paeonol treatment group compared with mice treated with MPTP/p only. In conclusion, paeonol exerted therapeutic effects in the MPTP/p‑induced mouse model of PD, possibly by decreasing the damage from oxidative stress and neuroinflammation, and by enhancing the neurotrophic effect on dopaminergic neurons. The results demonstrate paeonol as a potential novel treatment for PD.


Dynamic contrast-enhanced MRI in the differentiation of posttreatment fibrosis from recurrent carcinoma of the head and neck.
The aim of this study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (MRI) in the differentiation of posttreatment fibrosis from recurrent carcinoma, by comparing the dynamic contrast-enhancement characteristics of the lesions. Twenty-six patients with previously treated carcinoma of the head and neck are studied by conventional and dynamic contrast-enhanced MRI at least 6 months after treatment by radiotherapy and/or surgery. Patients are divided into tumor-positive or -negative groups according to the radiological and clinical follow-up and biopsy. Lesion enhancement ratios at each dynamic sequence are calculated. The tumor-positive group consisted of 11 patients, while the tumor-negative group included 15 patients. Between the two groups, lesion enhancement ratios are found to be significantly different (P<.05). Dynamic contrast-enhanced MRI may be a valuable modality in the differentiation of recurrent tumor from posttreatment fibrotic changes of the head and neck.


Immune reconstitution inflammatory syndrome in a patient with HIV presenting as severe mixed haemolytic anaemia.
A patient with a delayed diagnosis of vertically transmitted HIV presented with a rare form of severe warm and cold (mixed) autoimmune haemolytic anaemia, six months after starting antiretroviral therapy. The CD4 count had responded rapidly to introduction of antiretroviral therapy, rising from 5 cells/µL to 93 cells/µL over the course of six months. The haemolysis was resistant to immunoglobulin therapy, eventually responding to corticosteroids. On careful scrutiny of the case, we found the features to be in keeping with immune reconstitution inflammatory syndrome; thorough investigations revealed no other trigger for haemolysis in this case.


Development and validation of a liquid chromatography with tandem mass spectrometry method for the determination of isomangiferin in rat plasma with application to a preclinical pharmacokinetic study.
A sensitive and specific liquid chromatography with tandem mass spectrometry method was firstly developed for the measurement of isomangiferin in rat plasma. Chloramphenicol was selected as the internal standard. Sample preparation was carried out through a simple one-step protein precipitation procedure with methanol. Negative electrospray ionization was performed using multiple reaction monitoring mode with transitions of m/z 421.1/301.1 for isomangiferin, and 321.1/151.9 for chloramphenicol. The calibration curve was linear over the range of 0.1-600 ng/mL, with a lower limit of quantification at 0.1 ng/mL. The intra- and interday precisions (relative standard deviation) were no more than 8.2% and accuracies (relative error) were within the range of -8.4 to 2.2%. The recovery, matrix effect and stability under different conditions were all proved acceptable. The validated method has been successfully applied to a preclinical pharmacokinetic study of isomangiferin in rats for the first time.


Basic phenotypic analysis of six novel yeast genes reveals two essential genes and one which affects the growth rate.
Phenotypic analysis was performed on six mutants of Saccharomyces cerevisiae deleted in one of the following open reading frames (ORFs), located on chromosome II: YBR254c, YBR255w, YBR257w, YBR258c, YBR259w and YBR266c. Disruption of the ORFs was carried out in the diploid strain FY1679 using the kanMX4 marker flanked by short sequences homologous to the target locus. Tetrad analysis following sporulation of the heterozygous disruptants showed that YBR254c and YBR257w are essential genes. YBR257w was later characterized and renamed POP4, its gene product being involved in 5.8S rRNA and tRNA processing (Chu et al., 1997). The tetrad analysis performed for the heterozygous disruptant for YBR266c showed that two of the four viable spores gave colonies of smaller size, reflecting a slower growth rate. Growth analysis of the disruptant haploids confirmed this defect at 30 degrees C and also at 15 degrees C. However, complementation tests failed to confirm that the deletion of YBR266c is responsible for this growth defect. Growth analysis of the disruptant haploid ybr255w(delta) showed a slower growth rate on YPD and minimal medium at 15 degrees C. Finally, no phenotypic effect could be detected associated to the disruption of ORFs YBR258c and YBR259w.


The nature and organization of satellite DNAs in Petunia hybrida, related, and ancestral genomes.
The garden petunia, Petunia hybrida (Solanaceae) is a fertile, diploid, annual hybrid species (2n=14) originating from P. axillaris and P. inflata 200 years ago. To understand the recent evolution of the P. hybrida genome, we examined tandemly repeated or satellite sequences using bioinformatic and molecular cytogenetic analysis. Raw reads from available genomic assemblies and survey sequences of P. axillaris N (PaxiN), P. inflata S6, (PinfS6), P. hybrida (PhybR27) and the here sequenced P. parodii S7 (PparS7) were used for graph and k-mer based cluster analysis of TAREAN and RepeatExplorer. Analysis of repeat specific monomer lengths and sequence heterogeneity of the major tandem repeat families with more than 0.01% genome proportion were complemented by fluorescent in situ hybridization (FISH) using consensus sequences as probes to chromosomes of all four species. Seven repeat families, PSAT1, PSAT3, PSAT4, PSAT5 PSAT6, PSAT7 and PSAT8, shared high consensus sequence similarity and organisation between the four genomes. Additionally, many degenerate copies were present. FISH in P. hybrida and in the three wild petunias confirmed the bioinformatics data and gave corresponding signals on all or some chromosomes. PSAT1 is located at the ends of all chromosomes except the 45S rDNA bearing short arms of chromosomes II and III, and we classify it as a telomere associated sequence (TAS). It is the most abundant satellite repeat with over 300,000 copies, 0.2% of the genomes. PSAT3 and the variant PSAT7 are located adjacent to the centromere or mid-arm of one to three chromosome pairs. PSAT5 has a strong signal at the end of the short arm of chromosome III in P. axillaris and P.inflata, while in P. hybrida additional interstitial sites were present. PSAT6 is located at the centromeres of chromosomes II and III. PSAT4 and PSAT8 were found with only short arrays. These results demonstrate that (i) repeat families occupy distinct niches within chromosomes, (ii) they differ in the copy number, cluster organization and homogenization events, and that (iii) the recent genome hybridization in breeding P. hybrida preserved the chromosomal position of repeats but affected the copy number of repetitive DNA.


The Role of the Medical Profession in Victorian Assisted Dying Law Reform.
The Voluntary Assisted Dying Act Vic will commence operation on 19 June 2019. Doctors were highly visible in the debate which informed the recent law reform process, and Victorian legislators relied considerably on the diverse views of the medical profession. It is important to pay attention to the role played by doctors in the legalisation of assisted dying in Victoria, not only because the current political environment suggests that further reforms may be likely in other Australian jurisdictions, but also because doctors' knowledge and expertise visibly contributed to the outcome of that process in Victoria. This article aims to map the participation of doctors in the recent law reform process to analyse how their professional attributes positioned them in the Victorian assisted dying space. It is suggested that doctors were afforded a place in law reform because of the routine acceptance of doctors as knowledge keepers in matters of life and death and an acknowledgment of the integral role of medical expertise in the legislation. A textual analysis of the Hansard record of the Victorian debate reflects that individual practitioner advocacy for legalisation prevailed over opposition by the national branch of the Australian Medical Association in the deliberations of parliamentarians.


Chemical and Sensory Characterization of Oxidative Changes in Roasted Almonds Undergoing Accelerated Shelf Life.
In almonds, there is no standard method for detecting oxidative changes and little data correlating consumer perception with chemical markers of rancidity. To address this, we measured peroxide values (PV), free fatty acid values (FFAs), conjugated dienes, tocopherols, headspace volatiles, and consumer hedonic response in light roasted (LR) and dark roasted (DR) almonds stored under conditions that promote rancidity development over 12 months. Results demonstrate that, although rancidity develops at different rates in LR and DR almonds, consumer liking was not significantly different between LR and DR almonds. Average hedonic ratings of almonds were found to fall below a designated acceptable score of 5 ("neither like nor dislike") by 6 months of storage. This did not correspond with recommended industry rejection standard of PV < 5 mequiv peroxide/kg oil and FFA < 1.5% oleic. FFAs remain well below <1.5% oleic during storage, indicating that FFAs are not a good marker of rancidity in roasted almonds stored in low humidity environments. Regression of consumer liking to concentration of rancidity indicators revealed that selected headspace volatiles, including heptanal, octanal, nonanal, 2-octenal, 2-heptanone, 2-pentylfuran, hexanal, and pentanal, had a better correlation with liking than did nonvolatile indicators.


Characteristics and surgical outcome of HCC patients with low platelet count.
Hepatocellular carcinoma (HCC) patients often have low platelet count (LPC). The aim of this study was to determine unique features of HCC patients with LPC. HCC patients who underwent surgery were divided into two groups: LPC group (platelet count ≤100,000/mm³, n=84) and control group (platelet count >100,000/mm³, n=240). Surgical outcomes, risk factors for postoperative complications and prognostic factors were retrospectively compared. HCC patients with LPC had poorer liver function, smaller tumors, less anatomical resection and more frequent postoperative liver failure than control group patients. Postoperative survival was not different between the two groups. Tumor invasion to the main branch or trunk of portal vein (Vp3, 4) was the only risk factor for postoperative substantial complications in the LPC group. Postoperative survival was worse in patients with tumor diameter ≥4 cm or multiple tumors and in those who underwent preoperative transcatheter arterial chemoembolization (TACE) in the LPC group by multivariate analysis. Among them, preoperative TACE were not prognostic factors in the control group. In HCC patients with LPC, Vp3, 4 patients should be carefully monitored after surgery and preoperative TACE is not recommended for long-term postoperative survival.


Trichromatic Concept at SPring-8 RIKEN Beamline I.
SPring-8 RIKEN beamline I has been designed and developed for structural biology research by the Institute of Physical and Chemical Research (RIKEN). The beamline consists of two experimental stations for protein crystallography and small-angle X-ray scattering. Both types of experiments can be carried out simultaneously, with dichromatic synchrotron radiation emitted from two coaxial undulators with vertical polarization. The branched beams are generated by a transparent diamond crystal. With synchrotron radiation, the multiple-wavelength anomalous-dispersion (MAD) method, which gives phases from a single anomalous scatterer, has been developed. Anomalous scattering contributes a small proportion of the diffraction intensity so that the accuracy of intensity data is important. The protein crystallography branch of RIKEN beamline I has been designed based on a 'trichromatic concept' to optimize MAD data collection. This concept requires the quasi-simultaneous collection, by use of a 'trichromator', of three intensity data sets at three different wavelengths from a single protein crystal without changing any settings. The main feature of the concept is the minimization of systematic errors in the measurement of anomalous diffraction for the MAD method. Initial commissioning of the beamline has provided three different monochromated undulator beams, which were successfully observed on the phosphor screen located at the near end of the trichromator.


Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.
Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner.


Conditional activation defect of a human Gsalpha mutant.
Hormonal signals activate trimeric G proteins by promoting exchange of GTP for GDP bound to the G protein's alpha subunit (Galpha). Here we describe a point mutation that impairs this activation mechanism in the alpha subunit of Gs, producing an inherited disorder of hormone responsiveness. Biochemical analysis reveals an activation defect that is paradoxically intensified by hormonal and other stimuli. By substituting histidine for a conserved arginine residue, the mutation removes an internal salt bridge (to a conserved glutamate) that normally acts as an intramolecular hasp to maintain tight binding of the gamma-phosphate of GTP. In its basal, unperturbed state, the mutant alphas binds guanosine 5'-[gamma-thio]triphosphate (GTP[gammaS]), a GTP analog, slightly less tightly than does normal alphas, but (in the GTP[gammaS]-bound form) can stimulate adenylyl cyclase. The activation defect becomes prominent only under conditions that destabilize binding of guanine nucleotide (receptor stimulation) or impair the ability of alphas to bind the gamma-phosphate of GTP (cholera toxin, AlF4- ion). Although GDP release is usually the rate-limiting step in nucleotide exchange, the biochemical phenotype of this mutant alphas indicates that efficient G protein activation by receptors and other stimuli depends on the ability of Galpha to clasp tightly the GTP molecule that enters the binding site.


Proteomic analysis reveals differential protein expression by Bacillus cereus during biofilm formation.
Bacillus cereus, a dairy-associated toxigenic bacterium, readily forms biofilms on various surfaces and was used to gain a better understanding of biofilm development by gram-positive aerobic rods. B. cereus DL5 was shown to readily adapt to an attached mode of growth, with dense biofilm structures developing within 18 h after inoculation when glass wool was used as a surface. Two-dimensional gel electrophoresis (2DE) revealed distinct and reproducible phenotypic differences between 2- and 18-h-old biofilm and planktonic cells (grown both in the presence and in the absence of glass wool). Whereas the 2-h-old biofilm proteome indicated expression of 15 unique proteins, the 18-h-old biofilm proteome contained 7 uniquely expressed proteins. Differences between the microcolony (2-h) proteome and the more developed biofilm (18-h) proteome were largely due to up- and down-regulation of the expression of a multitude of proteins. Selected protein spots excised from 2DE gels were subjected to N-terminal sequencing and identified with high confidence. Among the proteins were catabolic ornithine carbamoyltransferase and L-lactate dehydrogenase. Interestingly, increased levels of YhbH, a member of the sigma 54 modulation protein family which is strongly induced in response to environmental stresses and energy depletion via both sigma(B) and sigma(H), could be observed within 2 h in both attached cells and planktonic cultures growing in the presence of glass wool, indicating that this protein plays an important role in regulation of the biofilm phenotype. Distinct band differences were also found between the extracellular proteins of 18-h-old cultures grown in the presence and in the absence of glass wool.


Comparison of Cavum Septum Pellucidum Size in Euploid and Aneuploid Fetuses.
The aim of the present study is to compare the cavum septum pellucidi (CSP) z-score in euploid and aneuploid fetuses and to investigate the performance of the CSP width/length and CSP width/biparietal diameter (BPD) ratios as a diagnostic marker in aneuploidy. A total of 54 patients, 20 aneuploid and 35 euploid fetuses, between 18 and 37 weeks of gestation, were included in this retrospective study. The CSP width z-score was compared between the two groups. Receiver operating characteristic (ROC) curves were calculated for the CSP width/length and CSP width/BPD ratios to predict aneuploidy. The median CSP width was 4.8 mm (range, 1.8 to 8.5 mm) in the euploid group, and 5.4 mm (range 3.1 to 8.4 mm) in the aneuploid group. Cavum septum pellucidi width z-score, CSP width/length ratio, and CSP width/BPD ratio were significantly higher in fetuses with aneuploidy than in fetuses with normal karyotype (p = 0.001; p = 0.013; p = 0.028). In the ROC analysis, the CSP width/length ratio had the optimal cutoff value of 0.59, with 72.0% sensitivity and 58.0% specificity, and for the CSP width/BPD ratio, the cutoff value was 0.081 with 83.0% sensitivity and 61.0% specificity for detection of aneuploidy. CSP width z-score was found to be increased in aneuploid fetuses. The CSP width /BPD ratio can be used as a new marker for predicting aneuploidy.


An 11-Year-Old Male With Vertebral Osteomyelitis and a Paraspinal Abscess.
We report the case of an 11-year-old immunocompetent patient presenting with a 2-week history of upper back pain, diagnosed with thoracic vertebral osteomyelitis and a paraspinal abscess caused by Bartonella henselae. He was treated with gentamicin and doxycycline followed by oral rifampicin and doxycycline with favorable outcome.


Encountering deception in virtual spaces: guidelines for virtual ethnography.
This Perspective Essay draws from an experience of deception in virtual fieldwork and considers implications for those designing methodologies for virtual ethnographies. As qualitative field work increasingly takes place within virtual spaces and through virtual means, researchers are faced with critical dilemmas in the processes of data gathering and verification. One of these dilemmas concerns ensuring data validity and facticity if encountered with research subjects who are deceptive about their identity, experiences, or relationship to the field of research. This Perspective Essay offers specific guidelines concerning articulating the nature and possibilities of deception in virtual spaces, identifying deceptive data, and what to do with deceptive data in order to maintain data validity and transparency.


Bioethanol production from wheat straw by phosphoric acid plus hydrogen peroxide (PHP) pretreatment via simultaneous saccharification and fermentation (SSF) at high solid loadings.
Phosphoric acid plus hydrogen peroxide (PHP) pretreatment was employed on wheat straw for ethanol conversion by simultaneous saccharification and fermentation (SSF) at high loadings. Results showed solid loading of PHP-pretreated wheat straw can be greatly promoted to 20%. Although more enzyme input improved ethanol conversion significantly, it still can be potentially reduced to 10-20 mg protein/g cellulose. Increasing yeast input also promoted ethanol conversion, however, the responses were not significant. Response surface method was employed to optimize SSF conditions with the strategy of maximizing ethanol conversion and concentration and minimizing enzyme and yeast input. Results indicated that ethanol conversion of 88.2% and concentration of 69.9 g/L were obtained after 120 h SSF at solid loading of 15.3%, and CTec2 enzyme and yeast were in lower input of 13.2 mg protein/g cellulose and 1.0 g/L, respectively. Consequently, 15.5 g ethanol was harvested from 100 g wheat straw in the optimal conditions.


Course types in schizophrenia: an analysis of European and American studies.
There have only been a dozen studies in the world literature which have followed patients across decades after their first admissions. Persistent findings of wide heterogeneity in long-term outcome functioning have broadened and challenged the pessimistic view of outcome held by many clinicians with short-term and narrowly defined caseloads. This report compares and contrasts three very long-term followup studies completed in the past 15 years which have also documented course as well as outcome. Ciompi's schematic representation of longitudinal courses has been augmented by data from the Vermont and Burghölzli studies and sheds new light on the underlying hidden heterogeneity within samples. Two case studies present vivid portraits of very different trajectories taken over time and illuminate the processes under scrutiny.


Emulsion electrospinning of polycaprolactone: influence of surfactant type towards the scaffold properties.
Producing uniform nanofibers in high quality by electrospinning remains a huge challenge, especially using low concentrated polymer solutions. However, emulsion electrospinning assists to produce nanofibers from less concentrated polymer solutions compared to the traditional electrospinning process. The influence of individual surfactants towards the morphology of the emulsion electrospun poly (ɛ-caprolactone)/bovine serum albumin (PCL/BSA) nanofibers were investigated by using (i) non-ionic surfactant sorbitane monooleate (Span80); (ii) anionic sodium dodecyl sulfate (SDS); and (iii) cationic benzyltriethylammonium chloride, and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer Pluronic F108 of different concentrations. The morphology, along with the chemical and mechanical properties of the fibers, was evaluated by field emission scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimetry, water contact angle, and tensile tester. With the addition of surfactants, the electrospinnability of dilute PCL solution was enhanced, with either branched or uniform fibers were obtained. Electrospinning of an emulsion containing 0.4% (w/v) SDS produced the smallest and the most uniform nanofibers (167 ± 39 nm), which was attributed to the high conductivity of the solution. Analysis revealed that the emulsion electrospun nanofibers containing different surfactants and surfactant concentrations differ in fiber morphology and mechanical properties. Results suggest that surfactants have the ability to modulate the fiber morphology via electrostatic and hydrogen bonding, depending on their chemical structure.


Communication: Influence of external static and alternating electric fields on water from long-time non-equilibrium ab initio molecular dynamics.
The response of water to externally applied electric fields is of central relevance in the modern world, where many extraneous electric fields are ubiquitous. Historically, the application of external fields in non-equilibrium molecular dynamics has been restricted, by and large, to relatively inexpensive, more or less sophisticated, empirical models. Here, we report long-time non-equilibrium ab initio molecular dynamics in both static and oscillating (time-dependent) external electric fields, therefore opening up a new vista in rigorous studies of electric-field effects on dynamical systems with the full arsenal of electronic-structure methods. In so doing, we apply this to liquid water with state-of-the-art non-local treatment of dispersion, and we compute a range of field effects on structural and dynamical properties, such as diffusivities and hydrogen-bond kinetics.


Graves' Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature.
In the last few years, immune checkpoint inhibitors (ICPis) have become a common treatment of cancer. ICPis are associated with peculiar immune side effects, termed immune-related adverse events (irAEs). Thyroid disfunction is a common irAE, but clinical manifestation, severity, and pathogenesis can be variable. While destructive thyroiditis and hypothyroidism are the most common thyroid irAEs induced by ICPis, autoimmune hyperthyroidism (Graves' disease) is rare. We describe a case of a Graves' disease induced by anti-PD-1 therapy and we review the previous reports on this issue. A 51-year-old man developed an overt autoimmune hyperthyroidism 2 months after he had started nivolumab (anti-PD-1) therapy for a metastatic non-small cell lung cancer. Although TSH-receptor autoantibodies (TRAb) were negative, the persistence of hyperthyroidism, the hypervascular pattern at thyroid ultrasound, and the high uptake at thyroid scintigraphy were all features suggestive of Graves' disease. Methimazole was started with the prompt restoration of euthyroidism. TRAb remained undetectable during the entire follow-up. Autoimmune hyperthyroidism can be induced by anti-PD-1 treatment. TRAb were negative in both cases of nivolumab-induced Graves' disease described to date. A correct differential diagnosis between destructive thyroiditis and autoimmune hyperthyroidism is crucial for the appropriate treatment.


An Efficient, Versatile, and Safe Access to Supported Metallic Nanoparticles on Porous Silicon with Ionic Liquids.
The metallization of porous silicon (PSi) is generally realized through physical vapor deposition (PVD) or electrochemical processes using aqueous solutions. The former uses a strong vacuum and does not allow for a conformal deposition into the pores. In the latter, the water used as solvent causes oxidation of the silicon during the reduction of the salt precursors. Moreover, as PSi is hydrophobic, the metal penetration into the pores is restricted to the near-surface region. Using a solution of organometallic (OM) precursors in ionic liquid (IL), we have developed an easy and efficient way to fully metallize the pores throughout the several-µm-thick porous Si. This process affords supported metallic nanoparticles characterized by a narrow size distribution. This process is demonstrated for different metals (Pt, Pd, Cu, and Ru) and can probably be extended to other metals. Moreover, as no reducing agent is necessary (the decomposition in an argon atmosphere at 50 °C is fostered by surface silicon hydride groups borne by PSi), the safety and the cost of the process are improved.


Luteal phase support in fresh and frozen embryo transfer cycles.
Nearly 5 million babies have been delivered following assisted conception (IVF/ICSI) and the demand is increasing. Meticulous ovarian stimulation and well programmed luteal phase support are the landmarks of treatment success. Although the importance of luteal phase support in IVF/ICSI cycles is well established, the optimal route, dose and duration of this support is still a matter of debate. Regardless of the ovarian stimulation, parenteral and vaginal progesterone has been one of the most common routes. However, oral or subcutaneous routes are also well-investigated and reveal satisfactory clinical outcomes. It is obviously critical to choose a progesterone with adequate clinical efficacy and patient tolerability as well. Moreover, fresh and frozen embryo transfer cycles markedly different from each other in terms of physiological changes and luteal support concept should be modified accordingly. The aim of this narrative review is to provide evidence-based take home messages for the luteal phase support in either fresh or frozen embryo transfer cycles in the context of a recent scientific evidence.


Successful recruitment for medical device clinical studies.
Inadequate subject enrollment represents a significant obstacle during a medical device clinical investigation. It can lead to costly delays and jeopardise the success of an entire device development project. This article discusses the importance of devising an effective subject recruitment strategy so that clinical and regulatory requirements can be met.


Efficient quantum circuits for dense circulant and circulant like operators.
Circulant matrices are an important family of operators, which have a wide range of applications in science and engineering-related fields. They are, in general, non-sparse and non-unitary. In this paper, we present efficient quantum circuits to implement circulant operators using fewer resources and with lower complexity than existing methods. Moreover, our quantum circuits can be readily extended to the implementation of Toeplitz, Hankel and block circulant matrices. Efficient quantum algorithms to implement the inverses and products of circulant operators are also provided, and an example application in solving the equation of motion for cyclic systems is discussed.


Delayed Onset of Subclavian Artery Pseudoaneurysm With Brachial Plexus Compression Following Gunshot Wound Injury.
Early diagnosis of brachial plexus injuries is crucial to prevent long-term morbidity and improve outcomes. We present a unique case of delayed onset of brachial plexus compression two months following a traumatic gunshot injury causing multiple injuries including a T1 vertebral body comminuted fracture and pneumothorax. The patient experienced significant pain and progressive neurological examination changes during follow-up visits, and thus duplex ultrasound and computed tomography (CT) angiography were performed, which demonstrated a left subclavian artery pseudoaneurysm. This was managed operatively by evacuation and interposition bypass. Injuries to the cervical and upper thoracic spine are complex, and when patients present with new-onset neurological findings, axillary swelling, or significant uncontrolled postoperative pain, secondary complications should be suspected. Patients at a high risk of vascular reinjury should be routinely monitored at follow-up to prevent the development of progressive neurological damage to the brachial plexus.


Amoebic liver abscess.
Sonography is a major advance in the diagnosis of ALA. Identification of amoebic antigen in the pus is a specific immunodiagnostic test. Medical therapy with a single drug (metronidazole) is adequate in most instances. Routine needle aspiration or surgical drainage are not indicated. The abscess cavity may take up to 18 months for resolution and demonstration of such a lesion does not warrant repeated therapy unless clinical evidence of recurrence is present. Recurrences are rare. Clinical and laboratory evidences of poor prognosis are being identified, and may guide the treatment modality to be selected.


10 m/25 Gbps LiFi transmission system based on a two-stage injection-locked 680 nm VCSEL transmitter.
A 10 m/25 Gbps light-based WiFi (LiFi) transmission system based on a two-stage injection-locked 680 nm vertical-cavity surface-emitting laser (VCSEL) transmitter is proposed. A LiFi transmission system with a data rate of 25 Gbps is experimentally demonstrated over a 10 m free-space link. To the best of our knowledge, it is the first time a two-stage injection-locked 680 nm VCSEL transmitter in a 10 m/25 Gbps LiFi transmission system has been employed. Impressive bit error rate performance and a clear eye diagram are achieved in the proposed systems. Such a 10 m/25 Gbps LiFi transmission system provides the advantage of a communication link for higher data rates that could accelerate the deployment of visible laser light communication.


Tubal ectopic pregnancy in acute abdominal presentation: A case control analysis.
The aim of the study was to evaluate the demographic data, clinical findings, ectopic pregnancy (EP) localization (left or right-sided), and treatments versus clinical presentation of tubal pregnancies (TP) with or without acute abdomen. Pregnants with a diagnosis of TP, selected for acute abdomen or not, were evaluated and compared, concerning EP local-ization (right/left), age, parity, symptoms (menstrual delay, vaginal bleeding, and groin pain), initial β-hCG value, endometrial thickness, presence of rupture, and treatment type (methotrexate and surgery). On a total of 122 pregnants with TP, 32 showed acute abdomen, 45 had a TP located in the right tube and 32 in the left tube. In the acute abdomen group, parity, initial β-hCG level, and endometrial thickness were greater than non-acute abdomen group. In addition to this, the frequency of bleeding complaints, right-sided TP, rupture, and need for surgery were higher, than to the non-acute abdomen group. The frequency of the previous EP and methotrexate treatment was higher in those with the left-sided TP compared to those with the right-sided TP. EP rate, in patients with TP who applied to the emergency department with acute abdominal symptoms, was mostly located in the right tube with greater frequency of salpingectomy in open surgery.


Evaluation of cholinesterase level in an endemic population exposed to malathion suspension formulation as a vector control measure.
The manuscript describes a study on the blood cholinesterase (ChE) level in an exposed population at different interval of time after spraying with malathion suspension (SRES) use for kala-azar vector control in an endemic area of Bihar, India. The toxicity of a 5% malathion formulation in the form of a slow release emulsified suspension (SRES) was assessed by measuring serum ChE levels in spraymen and in the exposed population. The study showed a significant decrease in ChE levels in the spraymen (p < 0.01) after one week of spraying and in exposed population one week and one month after of spraying (p < 0.01), but was still within the normal range of ChE concentration, one year after spraying, the ChE concentration in the exposed population was the same as prior to spraying (p > 0.01). On no occasion was the decrease in ChE level alarming. A parallel examination of the clinical status also showed the absence of any over toxicity or any behavioural changes in the exposed population. Hence, it may be concluded that 5% malathion slow release formulation, SRES, is a safe insecticide for use as a vector control measure in endemic areas of kala-azar in Bihar, India so long as good personal protection for spraymen is provided to minimize absorption and it can substitute the presently used traditional DDT spray.


Reconstructions of corticogeniculate axons in the cat.
The terminal arbors of corticofugal axons to the dorsal lateral geniculate nucleus in the cat were filled with horseradish peroxidase and then partially reconstructed through serial sections. The results demonstrate that these arbors are far more complex than was suspected from previous studies of axon segments in individual sections. These axons branch profusely and spread widely within the nucleus. Within laminae A and A1 the terminal arbor of a single axon can be more than 800 micron wide compared with retinogeniculate axons whose terminal arbors range in width from 100 to 410 micron (Sur and Sherman, '82).


Text entry rate of access interfaces used by people with physical disabilities: A systematic review.
This study systematically reviewed the research on assistive technology (AT) access interfaces used for text entry, and conducted a quantitative synthesis of text entry rates (TER) associated with common interfaces. We searched 10 databases and included studies in which: typing speed was reported in words per minute (WPM) or equivalent; the access interface was available for public use; and individuals with physical impairments were in the study population. For quantitative synthesis, we used only the TER reported for individuals with physical impairments. Studies also had to report the sample size, and the average and standard deviation for the TER data. Thirty-nine studies met the criteria for quantitative synthesis. Studies involved seven interface types: standard keyboard typing, on-screen keyboard (OSK) with cursor selection, OSK with scanning selection, automatic speech recognition (ASR), Morse code, brain-computer interface (BCI), and other. ASR, standard keyboard, cursor OSK, and scanning OSK had at least four studies and 30 subjects, with TER averaging 15.4, 12.5, 4.2, and 1.7 WPM, respectively. When combined with measurements of a particular client's text entry performance, the TER from this review can be used within an evidence-based decision-making process for selecting control interfaces.


CD40 ligand exerts differential effects on the expression of I gamma transcripts in subclones of an IgM+ human B cell lymphoma line.
The CD40:CD40 ligand (CD40L) interaction plays a critical role in T cell-dependent isotype switching. To elucidate the role of CD40 signaling in the activation of gamma germline transcription and as an extension, in targeting Cgamma regions for isotype switching, an IgM+ Burkitt lymphoma cell line (Ramos 2G6) was assayed for the up-regulation of germline gamma transcripts after CD40L stimulation. Independent Ramos 2G6 subclones that either expressed (Igamma+) or did not express (Igamma-) basal levels of Igamma transcripts were assessed for their transcriptional response to CD40L signaling by contact with either a Jurkat T cell line (D1.1) or a transfected CD40L-expressing epithelial cell line (293/CD40L) in the presence or absence of IL-4. Both Igamma- and Igamma+ Ramos 2G6 subclones cultured with IL-4 and CD40L markedly up-regulated germline transcription predominantly from the gamma1, gamma2, and gamma3 subclasses over levels obtained with IL-4 alone. In addition, these two signals were required to obtain de novo switch recombination. However, incubation with CD40L alone resulted in a substantial increase in germline transcription only in the Igamma+ and not the Igamma- subclones. Observed basal transcription at the gamma1 locus also correlated with the ability of not only the gamma1 locus, but also the gamma2 and gamma3 loci, to up-regulate germline transcripts in response to CD40 signaling. These data are consistent with CD40:CD40L contact up-regulating germline transcription only after the B cell has received a signal that alters the transcriptional state of the heavy chain locus.


Quaternary interactions and supercoiling modulate the cooperative DNA binding of AGT.
Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein-protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ωave. We found that while nearest-neighbor contacts were significant, long-range interactions dominated cooperativity and this pattern held true whether the DNA was single-stranded or duplex. Experiments with single plasmid topoisomers showed that the average cooperativity was sensitive to DNA twist, and was strongest when the DNA was slightly underwound. This suggests that AGT proteins are optimally juxtaposed when the DNA is near its torsionally-relaxed state. Most striking was the decline of binding stoichiometry with linking number. As stoichiometry and affinity differences were not correlated, we interpret this as evidence that supercoiling occludes AGT binding sites. These features suggest that AGT's lesion-search distributes preferentially to sites containing torsionally-relaxed DNA, in vivo.


On the origins of diastereofacial selectivity of [4 + 2] cycloadditions in cage- annulated and polycarbocyclic diene/dienophile systems.
pi-Facial diastereoselectivities in Diels-Alder reactions that involve pi-facially differentiated cyclohexa-1,3-dienes, i.e., 3-substituted or 3-10-disubstituted hexacyclo-[10.2.1.0.(2,11)0.(4,9)0.(4,14)0(9,13)]pentadeca-5,7-dienes have been investigated. Two types of reactions have been examined experimentally and theoretically: (i) reactions of cage-annulated, pi-facially differentiated cyclohexa-1,3-dienes with pi-facially symmetric dienophiles and (ii) reactions of pi-facially symmetric dienes with cage-annulated, pi-facially differentiated dienophiles.


Place of death and associated factors among patients with amyotrophic lateral sclerosis in Madrid (Spain).
Our objectives were to analyse the place of death, its temporal trend and associated sociodemographic factors among patients with amyotrophic lateral sclerosis (ALS) resident in the Autonomous Community of Madrid. This was a population based cross-sectional study of deaths from ALS (ICD-10 code G12.2) from 2003 to 2011, included in regional death statistics. The sociodemographic variables were age, gender, marital status, place of residence and socioeconomic level. Logistic regressions were performed to identify factors associated with death in hospital, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Joinpoint models were used to analyse annual trends for death in hospital. Of 1035 patients who died of ALS, 56.1% died in a hospital, 30.4% at home, 8.3% in a residential home and it was unknown for 5.1%. The percentage of deaths in hospital was lower in older and in single people than in married ones (55.0% and 61.9%, respectively; ORa 0.74, 95% CI 0.57-0.97). This percentage increased progressively as socioeconomic level fell (66.3% in Q5 compared to 49.6% in Q1, ORa 2.03, 95% CI 1.36-3.02). A significant increase in the percentage of deaths in hospital was observed. In conclusion, factors such as age, marital status or socioeconomic level play a part in the place of death of those with ALS.


Lessons Learned: Creation and Testing of a New Instrument (Sex Offenders Grooming Assessment) for Measuring Sex Offenders' Perceptions of Their Grooming Behaviors.
Grooming is a process whereby an individual who plans to commit a sexual crime uses deception with the victim as well as the people in the environment (such as the victim's family members, the offender's family, etc.) so that the crime goes undetected. Despite the overwhelming presence of grooming in sexual crimes, there is a dearth of research on sex offenders' perceptions of their own grooming behaviors. This paper describes the psychometrics and lessons learned in the pilot study of testing and revising a new instrument for measuring sex offenders' perceptions of their grooming behaviors (Sex Offenders Grooming Assessment; SOGA), with a sample (n = 50) of convicted male sex offenders in community based specialized therapy. Analyses suggest that using behaviorally-specific questions yielded more reliable results than general categorical grooming questions. Understanding how sex offenders perceive and report their grooming behavior provides valuable insight critical to treatment and assessment.


Demographic characteristics of Australian health consumers who were early registrants for opt-in personally controlled electronic health records.
Differential uptake of, or access to, personal electronic health records (PEHRs) has the potential to impact on health disparities among certain social groups. In 2012, the Australian Government introduced the Personally Controlled Electronic Health Record (PCEHR), an opt-in system operated by the then National E-Health Transition Authority (NEHTA). In July 2016, the My Health Record (MyHR), an opt-out model, operated by the Australian Digital Health Agency replaced the PCEHR, providing additional support for consumers. This research was carried out between 2012 and 2015, covering the opt-in PCEHR phase. The aim of the study was to explore demographic characteristics of Australian health consumers who were first to register for a PEHR, and to identify the age and gender populations less likely to register for a PEHR in the opt-in format. The study aimed to provide early data on registrants and potential methods to encourage individuals to register for a PEHR. A cross-sectional study investigated differences in registrations for PEHRs from 2012 to 2015 by age and sex. Results revealed that males were less likely to register than females, and adolescents of both sexes were the least likely to register when compared with any other age group. Similarly, middle-aged males had among the lowest reported registrations, as did older females. While e-health has the potential to improve health outcomes and PEHRs the potential to empower consumers to better manage their health and improve their access health services, evidence from this study suggested that some population groups that experience health inequalities (e.g. older people) were underrepresented among registrants for PEHRs. As income, ethnicity and education are major drivers for health disparities in Australia, future research should focus on uptake and use of PEHRs (now the MyHR) from the perspective of these variables.


Management and outcome of pediatric metastatic Wilms' tumor at the National Cancer Institute, Egypt.
Wilms' tumor (WT) is the most common renal malignant tumor of childhood. Metastatic WT has a worse prognosis than localized disease. This study aims to assess the clinical outcome and different prognostic factors that influence treatment outcome of pediatric metastatic WT cases treated at National Cancer Institute (NCI), Egypt, between January 2008 and December 2015. Medical records were retrospectively reviewed for clinical, radiological and histopathological data, treatment received, and survival outcome. In the specified study period, 24/103 (23.3%) patients with WT were metastatic at presentation. The mean age was 5.25 ± 2.87 years (range 2.0-12.7). Abdominal swelling/mass was the commonest presentation (70.8%). Only 3 patients (12.5%) had combined lung and liver metastases while 21 patients (87.5%) had pulmonary-only metastases. All patients had favorable histology tumors with no anaplasia. Nine patients (37.5%) underwent upfront nephrectomy. Majority of patients (91.7%) had local stage III disease. Surgical complications were reported in 4 patients; 3 of them had up-front nephrectomy. Only 7/21 patients achieved rapid complete response of pulmonary nodules after 6 weeks of chemotherapy (CTH), and they had a better survival outcome. Patients were followed up till December 2017. Thirteen patients (54.1%) experienced events during the study period including 5 relapses, 6 cases with disease progression, and 2 patients died out of sepsis. The 3-year event-free and overall survival rates were 48.2% and 54.2%, respectively. Neo-adjuvant CTH followed by delayed nephrectomy seems more suitable approach in our institute. Pulmonary response to neo-adjuvant CTH appears to be a strong predictor for outcome.


Coexistence of cholinergic and somatostatin receptors on astrocytes of rat CNS.
Electrophysiological studies have shown that somatostatin (SOM; 10(-8) and 10(-7) M) causes a hyperpolarization of the majority of astrocytes in explant cultures of rat spinal cord and cortex. When SOM and the cholinergic agonists muscarine and nicotine (10(-6) M) were tested on the same cell, all three compounds produced hyperpolarizations, suggesting a colocalization of functional cholinergic and SOM receptors on the glial membrane. Combined immunohistochemical and autoradiographic binding studies demonstrating that almost all astrocytes which were immunostained by the monoclonal muscarinic or nicotinic antibodies were also intensely labelled by 125I-SOM, provide further evidence for the coexistence of cholinergic and SOM receptors on astrocytes.


Drug transfer into cerebrospinal fluid after simultaneous administration of ampicillin with ceftriaxone or ceftazidime in rabbits with Staphylococcus aureus meningitis.
Meningitis was induced in white rabbits with a non beta-lactamase producing strain of Staphylococcus aureus. There was no significant difference in the CSF level of ceftazidime after simultaneous administration of ceftazidime with ampicillin or after ceftazidime alone. In contrast the percentage CSF penetration of ampicillin decreased from 8.81% after administration of ampicillin alone to 2.77% after the simultaneous administration of ampicillin with ceftazidime. The ratio of AUC in CSF and serum was 19.4% after ampicillin alone and 7.71% after simultaneous administration with ceftazidime. When ceftriaxone was combined with ampicillin there was no effect on the CSF penetration of either drug. Cephalosporins have unpredictable effects on the CSF concentration of ampicillin, probably due to variable effects on the penetration of ampicillin from blood to CSF.


The miR9863 family regulates distinct Mla alleles in barley to attenuate NLR receptor-triggered disease resistance and cell-death signaling.
Barley (Hordeum vulgare L.) Mla alleles encode coiled-coil (CC), nucleotide binding, leucine-rich repeat (NB-LRR) receptors that trigger isolate-specific immune responses against the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). How Mla or NB-LRR genes in grass species are regulated at post-transcriptional level is not clear. The microRNA family, miR9863, comprises four members that differentially regulate distinct Mla alleles in barley. We show that miR9863 members guide the cleavage of Mla1 transcripts in barley, and block or reduce the accumulation of MLA1 protein in the heterologous Nicotiana benthamiana expression system. Regulation specificity is determined by variation in a unique single-nucleotide-polymorphism (SNP) in mature miR9863 family members and two SNPs in the Mla miR9863-binding site that separates these alleles into three groups. Further, we demonstrate that 22-nt miR9863s trigger the biogenesis of 21-nt phased siRNAs (phasiRNAs) and together these sRNAs form a feed-forward regulation network for repressing the expression of group I Mla alleles. Overexpression of miR9863 members specifically attenuates MLA1, but not MLA10-triggered disease resistance and cell-death signaling. We propose a key role of the miR9863 family in dampening immune response signaling triggered by a group of MLA immune receptors in barley.


Deep brain stimulation of the ventral striatal area for poststroke pain syndrome: a magnetoencephalography study.
Poststroke pain syndrome (PSPS) is an often intractable disorder characterized by hemiparesis associated with unrelenting chronic pain. Although traditional analgesics have largely failed, integrative approaches targeting affective-cognitive spheres have started to show promise. Recently, we demonstrated that deep brain stimulation (DBS) of the ventral striatal area significantly improved the affective sphere of pain in patients with PSPS. In the present study, we examined whether electrophysiological correlates of pain anticipation were modulated by DBS that could serve as signatures of treatment effects. We recorded event-related fields (ERFs) of pain anticipation using magnetoencephalography (MEG) in 10 patients with PSPS preoperatively and postoperatively in DBS OFF and ON states. Simple visual cues evoked anticipation as patients awaited a painful (PS) or nonpainful stimulus (NPS) to the nonaffected or affected extremity. Preoperatively, ERFs showed no difference between PS and NPS anticipation to the affected extremity, possibly due to loss of salience in a network saturated by pain experience. DBS significantly modulated the early N1, consistent with improvements in affective networks involving restoration of salience and discrimination capacity. Additionally, DBS suppressed the posterior P2 (aberrant anticipatory anxiety) while enhancing the anterior N1 (cognitive and emotional regulation) in responders. DBS-induced changes in ERFs could potentially serve as signatures for clinical outcomes. NEW & NOTEWORTHY We examined the electrophysiological correlates of pain affect in poststroke pain patients who underwent deep brain stimulation (DBS) targeting the ventral striatal area under a randomized, controlled trial. DBS significantly modulated early event-related components, particularly N1 and P2, measured with magnetoencephalography during a pain anticipatory task, compared with baseline and the DBS-OFF condition, pointing to possible mechanisms of action. DBS-induced changes in event-related fields could potentially serve as biomarkers for clinical outcomes.


Short-term fasting promotes insulin expression in rat hypothalamus.
In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6-h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular.


Knowledge of stroke among a Brazilian urban population.
Knowledge of the population in regards to stroke has clinical and epidemiological importance. Prompt identification of the symptoms means efficient medical attendance within the window of therapeutic opportunities reducing significantly the morbidity-mortality. Our aim was to evaluate the level of knowledge of the population of Teresina (PI) concerning factors of risk, symptoms and treatment of stroke. The door-to-door study was carried out by means of a standardized application of questionnaire on risk factors, symptoms and attitude when faced with a stroke victim. 991 forms were selected. Factors of risk more cited were hypertension identified by 416 [42.0%] and hyperlipidemia 284 [28.7%]. The most remembered symptoms were headache 277 [28.0%] and hemiplegia 219 [22.1%]. 375 (37.8%) respondents were unable to identify any risk factors and and 410 (41.4%) any symptom. The lack of knowledge of the population of Teresina in relation to stroke reflects the need for intervention through public and professional educational campaigns.


A highly functionalized ferrocenylpyrazolo[2,3-a]pyridine.
The crystal structure of [2-(4-bromophenyl)-4-cyano-5-ferrocenylpyrazolo[2,3-a]pyridin-7-yl]acetonitrile, C(26)H(17)N(4)FeBr or [Fe(C(5)H(5))(C(21)H(12)BrN(4))], shows that the pyrazolopyridine ring system (PP), the bromophenyl ring (BP) and the cyclopentadiene ring (Cp) are nearly planar. The PP ring system is twisted out of the plane of the BP and Cp rings by about 20 degrees.


Rituximab in lymphomatoid granulomatosis.
Lymphomatoid granulomatosis (LG) is an Epstein-Barr virus-associated, multisystemic disease that combines a granulomatous inflammatory process with lymphoproliferative potential. It is a rare disorder with a variable clinical presentation ranging from an indolent process to an aggressive B-cell lymphoma. Outcome is unpredictable, and a standard treatment has not yet been established. Cases treated with rituximab, an anti-CD20 monoclonal antibody, have been reported with variable results. We report on 2 children with LG treated with rituximab and review the literature. The first patient had good response but the second did not. Rituximab is a treatment option for LG.


Field distribution of compound muscle action potentials of the calf muscles in rabbits.
The purpose of this study is to verify that compound muscle action potentials (CMAPs) generated a stationary potential and to examine extension of the CMAPs away from the stimulated muscle. A referential derivation and/or bipolar derivation to record the stationary potentials were carried out following tibial nerve stimulation at the popliteal fossa in 10 rabbits. After recording a bipolar and/or referential derivation, wave changes were monitored before and after severing the tibial nerve. The change of the wave by compressing or direct electrical stimulation to the calf muscle was also monitored. In referential derivatives, the stationary waves were observed on top of the skull in all the rabbits examined with the peak latency of the potentials from 3.78 msec to 5.04 msec. In bipolar derivations, the upper limits of the stationary waves recorded were the trunks. The peak latencies were from 2.35 msec to 5.46 msec with an average of 4.12 msec. By analyzing the results from severing the tibial nerves, compressing the calf muscles, and direct electrical stimulation of the calf muscle, the origin of these stationary potentials was determined to be CMAPs of the calf muscles. These findings suggest contamination of the stationary potentials originated by CMAPs for recording of any evoked potentials when motor nerves are stimulated.


[Benthic macrofauna associated to Thalassia testudinum in Bahía de Mochima, Sucre, Venezuela].
Diversity and abundance of benthic macrofauna associated to Thalassia testudinum were studied at Ensenada de Reyes, Mochima Bay, in the northeastern coast of Venezuela. Samples were taken monthly in six stations, three at 1 m in depth and three at 6 m, between December 1992 and February 1994, using a quadrat of 0.25 m2 for collecting plants and sediment; each sample was washed with seawater through a 1 mm sieve. The specimens were fixed in 6% formaldehyde. A total of 1722 organisms (6 888 ind x m2) and 127 species of macroinvertebrates were collected. Mollusks dominated with 53 species, followed by polychaetes (40), crustaceans (18) and echinoderms (8). Remaining groups were represented by 1-2 species. The highest abundance was in October (214 specimens), and the lowest in December 1993 (79 specimens). Specific richness was between 47 species in October and 18 in May 1993. Mean species diversity was 2.79-1.36 bits/ind. There were differences (ANOVA p<0.01) in number of specimens at the two depths but not throughout the 15 month study period (p>0.05). There were more specimens and species at the lowest depth and in stations with higher Thalassia testudinum biomass.


Construction of chimeric plasmids containing histone H5 cDNA from hen erythrocyte. DNA sequence of a fragment derived from the 5' region of H5 mRNA.
We report that construction and characterization of chicken erythrocyte histone H5 cDNA recombinant plasmids. cDNA was synthesized from poly(A)+ polysomal RNA enriched in H5 mRNA and inserted into the PstI site of pBR322. Several clones containing H5 cDNA sequences were obtained and one of them (p541), expressing H5 antigenic determinants, was sequenced. The DNA insert of p541 contains 118 nucleotides from the 5' non-translated region of H5 mRNA and sequences coding for up to residue 46 of the N-terminus of the arginine (position 15) H5 variant. There is a strikingly high number of repeated sequences both in the leader and coding region; among these, the octanucleotide 5' GCG GCG GC 3' is found five times along the sequence. Although the H5 mRNA 5' leader is GC-rich (66%), there is an AT-rich region, about 16 nucleotides long, which shares strong homology with the leaders of sea urchin histone H1 mRNAs.


The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a community-based analysis.
The effectiveness of upper endoscopy in unselected patients with upper gastrointestinal hemorrhage has not been well studied. This study was undertaken to identify factors associated with the performance of early endoscopy (ie, within 1 day of hospitalization) and, after adjusting for these factors, to determine associations between early endoscopy and in-hospital mortality, length of stay, and performance of surgery. Subjects in this observational cohort study were 3,801 consecutive admissions with upper gastrointestinal hemorrhage to 30 hospitals in a large metropolitan region. Demographic and clinical data were abstracted from hospital records. A multivariable model based on factors that potentially could relate to the decision to perform endoscopy was developed to determine the propensity (0 to 100%) for early endoscopy in each patient. Early endoscopy was performed in 2,240 patients (59%), and although it was not associated with mortality after adjusting for severity of illness among all patients, it was associated with a higher risk of death for patients in the lowest propensity group. Early endoscopy was associated with a lower likelihood of upper gastrointestinal surgery in all patients and in the two highest propensity groups and with a shorter length of stay in the entire cohort and in all subgroups. In the absence of specific contraindications, early endoscopy should be considered because of associated reductions in length of stay and surgical intervention. Further studies are needed to identify subgroups in whom the procedure may be associated with adverse effects on survival.


Verbal and spatial working memory in school-age children: developmental differences in susceptibility to interference.
The development of verbal and spatial working memory was investigated with an interference paradigm. Memory spans were obtained from 3 groups (8-, 10-, and 19-year-olds) under 6 different conditions: Two primary memory tasks (1 verbal, 1 spatial) were administered in isolation and in conjunction with 2 versions of a secondary task. The primary tasks required recalling a series of visually presented digits and recalling the locations of Xs in a series of visually presented grids. The secondary tasks required reporting the color of the stimuli as they were presented using either a verbal or a spatial response. Analyses revealed that all age groups showed domain-specific interference (i.e., interference by a secondary task from the same domain as the primary task), but only the 8-year-olds also showed nonspecific interference (i.e., interference by a secondary task from a domain different than the primary memory task), suggesting that at least some executive functions do not reach adult levels of efficiency until approximately age 10.


Tissue Regeneration with Hydrogel Encapsulation: A Review of Developments in Plants and Animals.
Hydrogel encapsulation has been widely utilized in the study of fundamental cellular mechanisms and has been shown to provide a better representation of the complex in vivo microenvironment in natural biological conditions of mammalian cells. In this review, we provide a background into the adoption of hydrogel encapsulation methods in the study of mammalian cells, highlight some key findings that may aid with the adoption of similar methods for the study of plant cells, including the potential challenges and considerations, and discuss key findings of studies that have utilized these methods in plant sciences.


Specificity and stoichiometry of subunit interactions in the human telomerase holoenzyme assembled in vivo.
The H/ACA motif of human telomerase RNA (hTR) directs specific pathways of endogenous telomerase holoenzyme assembly, function, and regulation. Similarities between hTR and other H/ACA RNAs have been established, but differences have not been explored even though unique features of hTR H/ACA RNP assembly give rise to telomerase deficiency in human disease. Here, we define hTR H/ACA RNA and RNP architecture using RNA accumulation, RNP affinity purification, and primer extension activity assays. First, we evaluate alternative folding models for the hTR H/ACA motif 5' hairpin. Second, we demonstrate an unanticipated and surprisingly general asymmetry of 5' and 3' hairpin requirements for H/ACA RNA accumulation. Third, we establish that hTR assembles not one but two sets of all four of the H/ACA RNP core proteins, dyskerin, NOP10, NHP2, and GAR1. Fourth, we address a difference in predicted specificities of hTR association with the holoenzyme subunit WDR79/TCAB1. Together, these results complete the analysis of hTR elements required for active RNP biogenesis and define the interaction specificities and stoichiometries of all functionally essential human telomerase holoenzyme subunits. This study uncovers unexpected similarities but also differences between telomerase and other H/ACA RNPs that allow a unique specificity of telomerase biogenesis and regulation.


[Principles of complex treatment of suppurative surgical diseases in children].
The authors describe their experiences with the treatment of 174 children with purulent diseases of the skin and subcutaneous fat, staphylococcal destruction of lungs, acute hematogenic osteomyelitis. The intensive infusion therapy for desintoxication is shown to be necessary as well as immune therapy, antibacterial and desensitizing preparations.


Hypertension in Bo, Sierra Leone.
To identify the prevalence of hypertension among adults in Bo, Sierra Leone. Hypertension data were extracted from outpatient clinic records. Mercy Hospital in urban Bo, Sierra Leone. All nonpregnant outpatients aged -15 years seen at the outpatient clinic in 2009. Prevalence of hypertension, defined as a systolic blood pressure > or = 140 mm Hg and/or a diastolic blood pressure > or = 90 mm Hg. Data from 3944 individuals were analyzed (mean age 38.7 years). The overall prevalence of hypertension among those aged > or = 15 years was 25.2%, with an age-adjusted prevalence of 19.6%. The prevalence of hypertension for participants aged > or = 20 years was 27.1%, with an age-adjusted prevalence of 23.6%. There were no significant differences in blood pressure by sex. The prevalence of hypertension increased significantly with age for both males and females (P < .001). The prevalence of hypertension in Sierra Leone is consistent with the rates of hypertension observed in other parts of West Africa.


Familial association of keratoconus and granular corneal dystrophy: The familial case series.
The aim of the present study was to evaluate the coexistence of bilateral keratoconus and granular corneal dystrophy (GCD) in the members of a family. A total of 22 patients were examined in four generations of the family tree in this family screening study. Visual acuity test, biomicroscopic examination, and fundus examination were performed in all patients. The diagnosis of granular dystrophy was based on biomicroscopic examination findings. Corneal topography was performed on the patients diagnosed with granular dystrophy and other family members aged >5 years with normal examination findings. Corneal photographs were obtained from all patients with granular dystrophy except one case. Keratoconus or subclinical keratoconus was detected in seven cases. In addition, GCD type 1 was found in six of the seven cases. All patients diagnosed with keratoconus and granular dystrophy were females. On the other hand, there was no ophthalmologic problem in the men of the family tree. Although an autosomal dominant inheritance was found, the onset of the disease only in women suggests that there may be a variant expression. The present study showed an association of GCD and keratoconus in four generations of a family. More research is required to further explain this association.


Who Is Ordering MRIs in Newly Diagnosed Breast Cancer Patients?
The role of MRI in the workup of newly diagnosed breast cancer patients remains controversial. Breast MRI detects additional disease, but this has not translated into improved outcomes. In light of a dramatic rise in MRI use, we investigated patterns of MRI ordering for newly diagnosed breast cancer. All newly diagnosed breast cancer cases presenting for surgical management to a specialized breast center from 2011 to 2013 were reviewed. Patients who had an MRI ordered by their operating surgeon were compared with those who had an MRI completed previously. Of 1037 patients, 504 (49%) with newly diagnosed breast cancer underwent MRI as part of their preoperative evaluation. Variables associated with MRI use included commercial insurance, increased breast density, genetic testing, mamographically occult disease, and lobular pathology. Of women who presented to our center with an MRI already completed, 63 per cent were ordered by a primary care provider. Of the 504 patients, 233 (44%) who had an MRI underwent an additional biopsy, and 166 (33%) had a resultant change in management. There was no significant difference in MRI-directed change in patient care depending on ordering provider. Further research is needed to develop evidence-based guidelines for preoperative MRI evaluation to optimize patient outcomes.


Sudden cardiac death: what is inside our genes?
Although sudden cardiac death in youths is generally rare, it is estimated that 10% to 20% of these deaths occur in previously healthy infants, children, adolescents and young adults without any findings on autopsy and with devastating consequences on the family. The majority of these deaths are caused by inherited arrhythmia syndromes, the so-called 'channelopathies'. In the present paper, the recent advances in the clinical and genetic background of long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome and the overlapping phenotypes are reviewed, and the recently established connections between these syndromes and idiopathic ventricular fibrillation and sudden infant death syndrome are discussed.


Reversible pH-induced fluorescence colour change of gold nanoclusters based on pH-regulated surface interactions.
To prepare water-dispersible, biocompatible, ratiometric pH nanosensors is challenging. We report here for the first time that the emission colour of NAD+-capped AuNCs responds to the mono-/bidentate anchoring of the phosphoric groups of the ligand. The AuNCs exhibit a high luminescence (21% quantum yield) and an outstanding performance as fluorescent ratiometric pH sensors over a broad pH range.


Predicting Adolescent Substance Use in a Child Welfare Sample: A Multi-Indicator Algorithm.
Given the risk of substance use (SU) among adolescents in the child welfare system, identification of risk for prospective impairing SU behaviors is a significant public health priority. We sought to quantify the incremental validity of routine multi-informant assessments of adolescent psychological distress (i.e., the Child Behavior Checklist and Youth Self-Report) and a commonly used SU screening protocol (i.e., the CRAFFT) to predict SU at 18 and 36 months after baseline in a nationally representative child welfare sample (N = 1,054; Mage = 13.72). We used receiver operator characteristics and reclassification analyses to develop our algorithms. We found that a battery consisting of baseline CRAFFT scores, self-reported delinquent behavior, and parent-reported rule-breaking behavior provided an incrementally valid prediction model for SU behavior among females, while baseline CRAFFT scores and self-reported delinquent behavior incrementally predicted SU for males. Results suggest that leveraging existing assessments within the child welfare system can improve forecasting of SU risk for this population.


Virulence of Bacteria Colonizing Vascular Bundles in Ischemic Lower Limbs.
We documented previously the presence of bacterial flora in vascular bundles, lymphatics, and lymph nodes of ischemic lower limbs amputated because of multifocal atheromatic changes that made them unsuitable for reconstructive surgery and discussed their potential role in tissue destruction. The question arose why bacterial strains inhabiting lower limb skin and considered to be saprophytes become pathogenic once they colonize deep tissues. Bacterial pathogenicity is evoked by activation of multiple virulence factors encoded by groups of genes. We identified virulence genes in bacteria cultured from deep tissue of ischemic legs of 50 patients using a polymerase chain reaction technique. The staphylococcal virulence genes fnbA (fibronectin-binding protein A), cna (collagen adhesin precursor), and ica (intercellular adhesion) were present in bacteria isolated from both arteries and, to a lesser extent, skin. The IS256 gene, whose product is responsible for biofilm formation, was more frequent in bacteria retrieved from the arteries than skin bacteria. Among the virulence genes of Staphylococcus epidermidis encoding autolysin atlE, icaAB (intercellular adhesion), and biofilm insert IS256, only the latter was detected in arterial specimens. Bacteria cultured from the lymphatics did not reveal expression of eta and IS256 in arteries. The Enterococcus faecalis asa 373 (aggregation substance) and cylA (cytolysin activator) frequency was greater in arteries than in skin bacteria, as were the E. faecium cyl A genes. All Pseudomonas aeruginosa virulence genes were present in bacteria cultured from both the skin and arteries. Staphylococci colonizing arterial bundles and transported to tissues via ischemic limb lymphatics expressed virulence genes at greater frequency than did those dwelling on the skin surface. Moreover, enterococci and Pseudomonas isolated from arterial bundles expressed many virulence genes. These findings may add to the understanding of the mechanism of development of destructive changes in lower limb ischemic tissues by the patient's, but not hospital-acquired, bacteria, as well as the generally unsatisfactory results of antibiotic administration in these cases. More aggressive antibiotic therapy targeted at the virulent species should be applied.


Precipitating and agglutinating activity in duck anti-soluble protein immune sera.
Ducks were inoculated parenterally, up to 4 times, with bovine serum albumin (BSA), B gamma globulin (BGG), or horse gamma globulin (HGG). Their sera were tested in immunodiffusion tests for precipitins. Only BSA and BGG induced precipitins. Only 7 of 443 sera tested, obtained from 3 of 62 inoculated ducks, developed a precipitin line with homologous antigen. All 7 sera were obtained from the earliest bleeding (7 days) after inoculation. Sera were also tested for agglutinins in direct passive hemagglutination (DPHA) and direct red-cell-linked antigen tests (DRCLAT) and for nonagglutinating antibodies in indirect red-cell-linked antigen tests (IRCLAT). No duck had a passive-hemagglutination-demonstrable primary immune response. Demonstrable DPHA titers after subsequent inoculations were very low compared with responses to these antigens of other species noted by other workers. Duck immune response was greatly diversified: all inoculation regimens that induced agglutinins in some ducks left others completely unstimulated. Precipitins and agglutinins of the same ducks correlated well: those 7 sera that had precipitins also had the highest DPHA titers for the 3 donor ducks. However, hemagglutinating titer and presence of precipitins in sera of different ducks correlated poorly. Increasing the age of the ducks at the first inoculation from 6 to 10 weeks increased the number of responders and DPHA titers of their sera. Non-agglutinating antibodies were demonstrated in anti-BSA sera: in IRCLAT, the sera had titers 2-to-256-fold higher than the sera in DPHA or DRCLAT had. Duck immunoglobulins were deficient in those immunological reactions (precipitation and agglutination) that require functional bivalency.


Divergent responses of plant functional traits and biomass allocation to slope aspects in four perennial herbs of the alpine meadow ecosystem.
Slope aspect can cause environmental heterogeneity over relatively short distances, which in turn affects plant distribution, community structure, and ecosystem function. However, the response and adaptation strategies of plants to slope aspects via regulating their physiological and morphological properties still remain poorly understood, especially in alpine ecosystems. Here, we selected four common species, including Bistorta macrophylla, Bistorta vivipara, Cremanthodium discoideum, and Deschampsia littoralis, to test how biomass allocation and functional traits of height, individual leaf area, individual leaf mass, and specific leaf area (SLA) respond to variation in slope aspect in the Minshan Mountain, eastern Tibetan Plateau. We found that the slope aspect affected SLA and stem, flower mass fraction with higher values at southwest slope aspect, which is potentially related to light environment. The low-temperature environment caused by the slope aspect facilitates the accumulation of root biomass especially at the northeast slope aspect. Cremanthodium discoideum and D. littoralis invested more in belowground biomass in southeast and southwest slope aspects, although a large number of significant isometric allocations were found in B. macrophylla and B. vivipara. Finally, we found that both biotic and abiotic factors are responsible for the variation in total biomass with contrasting effects across different species. These results suggest that slope aspect, as an important topographic variable, strongly influences plant survival, growth, and propagation. Therefore, habitat heterogeneity stemming from topographic factors (slope aspect) can prevent biotic homogenization and thus contribute to the improvement of diverse ecosystem functioning.


The role of anesthesia and catecholamines in the renal response to mild hemorrhage.
The role of the sympathoadrenal system in the renal response to mild hemorrhage was investigated in animals anesthetized with either sodium pentobarbital (Group I) or alpha-chloralose (Group II). Significantly greater decreases in renal blood flow (RBF) and increases in renal vascular resistance (RVR) were seen after hemorrhage in Group II than in Group I. Concomitant with these changes were increases both in circulating catecholamines and plasma renin activities. In Group II, however, the rise in plasma epinephrine was also significantly higher than in Group I. Additional studies were performed in pentobarbital anesthetized dogs either chemically denervated with 6-hydroxydopamine (Group III) or treated with the prostaglandin synthetase inhibitor indomethacin (Group IV). In Group III, following hemorrhage, changes in renal hemodynamics and circulating catecholamines were similar to those of Group I. In Group IV, although blood pressure was better maintained during hemorrhage than in the other groups, RVR increased to the same extent as in Group II, although increases in circulating catecholamines were comparable to those observed in Group I. Whereas pentobarbital anesthesia attenuated the sympathoadrenal response to mild hemorrhage, indomethacin appeared to sensitize the animals to adrenergic discharge by removing the modulatory effect of the prostaglandin system.


Climate change--how ready are you?
In an article that first appeared in Canadian Healthcare Facilities magazine, Kent Waddington, communications director, and Linda Varangu, Executive Director, at the Canadian Coalition for Green Health Care, and Peter Berry, senior policy analyst, and Jaclyn Paterson, environmental health specialist, at Health Canada, examine, in the light of the increasing frequency of extreme weather events, some of the latest thinking on the topic in Canada, and reflect on the initiatives taken by a number of the country's healthcare facilities to prepare for such incidents, and mitigate their impact.


Ovarian function following targeted anti-angiogenic therapy with bevacizumab.
Improvements in cancer therapy have enabled further insight into the long-term effects of treatment, including the highly prevalent gonadal failure. The focus of treatment has been shifted to the preservation of fertility, which may be achieved by preventing ovarian toxicity. To this end, new molecular-targeted agents, including monoclonal antibodies, have been developed and used in a standard procedure for managing different cancers. However, the prolonged antitumor activity of these drugs may cause the emergence of new toxic effects. The aim of the present review was to discuss the leading toxic effect of the anti-angiogenic agent bevacizumab on ovarian function in female patients of reproductive age, which may be observed and expected during in clinical practice. The majority of bevacizumab-induced side effects are expected to be transient and eliminated within the anticipated drug clearance time frame; however, fundamental investigations on these effects are required for generating more evidence-based practice guidelines.


Barycentric extension of generalized matching.
In most studies of choice under concurrent schedules of reinforcement, two physically identical operanda are provided. In the "real world," however, more than two choice alternatives are often available and biases are common. This paper describes a method for studying choices among an indefinite number of alternatives when large biases are present. Twenty rats were rewarded for choosing among five operanda with reinforcers scheduled probabilistically and concurrently. Large biases were generated by differences among the operanda: two were levers and three were pigeon keys. The results showed that when reinforcer frequencies were systematically varied, an extension of Baum's (1974) Generalized Matching Model, referred to as the Barycentric Matching Model, provided an excellent description of the data, including individual bias values for each of the operanda and a single exponent indicating sensitivity to reinforcer ratios.


Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs early cardiac gene activity.
Herein, the restricted expression of serum response factors (SRF) closely overlapped with Nkx2-5 and GATA4 transcripts in early chick embryos coinciding with the earliest appearance of cardiac alpha-actin (alphaCA) transcripts and nascent myocardial cells. The combinatorial expression of SRF, a MADS box factor Nkx2-5 (a NK4 homeodomain), and/or GATA4, a dual C4 zinc finger protein, in heterologous CV1 fibroblasts and Schneider 2 insect cells demonstrated synergistic induction of alphaCA promoter activity. These three factors induced endogenous alphaCA mRNA over a 100-fold in murine embryonic stem cells. In addition, the DNA-binding defective mutant Nkx2-5pm efficiently coactivated the alphaCA promoter in the presence of SRF and GATA4 in the presence of all four SREs and was substantially weakened when individual SREs were mutated and or serially deleted. In contrast, the introduction of SRFpm, a SRF DNA-binding mutant, blocked the activation with all of the alphaCA promoter constructions. These assays indicated a dependence upon cooperative SRF binding for facilitating the recruitment of Nkx2-5 and GATA4 to the alphaCA promoter. Furthermore, the recruitment of Nkx2-5 and GATA4 by SRF was observed to strongly enhance SRF DNA binding affinity. This mechanism allowed for the formation of higher ordered alphaCA promoter DNA binding complexes, led to a model of SRF physical association with Nkx2-5 and GATA4.


Spontaneous rupture of choledochal cyst: an unusual cause of acute abdomen in children.
Rupture is one of the rare complications of choledochal cysts. The cause of rupture is unknown in many cases and is considered to be spontaneous. Two patients admitted to the hospital with acute abdominal picture were initially thought to have postoperative abscess and appendicitis. However, the presence of bilelike fluid suggested a bile tract pathology, and evaluation showed rupture choledochal cysts. Although spontaneous rupture of a choledochal cyst is a rare complication, and can sometimes be the initial manifestation of a choledochal cyst, it should be considered in the presence of bilelike fluid and differentiated from spontaneous perforation of the bile tract. In spontaneous rupture of choledochal cyst, cystectomy, cholecystectomy, and Roux-Y hepaticoportoenterostomy is the treatment of choice.


First observation of the decays B(0) → D(+)K(-)π(+)π(-) and B(-) → D(0)K(-)π(+)π(-).
First observations of the Cabibbo-suppressed decays B(0) → D(+)K(-)π(+)π(-) and B(-) → D(0)K(-)π(+)π(-) are reported using 35 pb(-1) of data collected with the LHCb detector. Their branching fractions are measured with respect to the corresponding Cabibbo-favored decays, from which we obtain B(B(0) → D(+)K(-)π(+)π(-))/B(B(0) → D(+)π(-)π(+)π(-))=(5.9±1.1±0.5)×10(-2) and B(B(-) → D(0)K(-)π(+)π(-))/B(B(-) → D(0)π(-)π(+)π(-))=(9.4±1.3±0.9)×10(-2), where the uncertainties are statistical and systematic, respectively. The B(-) → D(0)K(-)π(+)π(-) decay is particularly interesting, as it can be used in a similar way to B(-) → D(0)K(-) to measure the Cabibbo-Kobayashi-Maskawa phase γ.


Bacterial translocation from the gastrointestinal tracts of rats receiving thermal injury.
Rats receiving nonlethal thermal burns over 20 or 40% of their total body surface area were tested at various intervals for the translocation of indigenous bacteria from their gastrointestinal tracts to their mesenteric lymph nodes, peritoneal cavities, and bloodstreams. No indigenous bacteria were cultured from these organs of control rats or from rats receiving 20% burns. However, 44% of the rats receiving 40% burns exhibited viable Escherichia coli, Proteus mirabilis, Staphylococcus sp. and Clostridium sp. in their mesenteric lymph nodes 2 days after thermal injury. Bacterial translocation after burn stress also was tested in antibiotic-decontaminated rats monoassociated with E. coli. E. coli attained population levels in these animals of 10(8) to 10(9) per g cecum. E. coli translocated to 100% of the mesenteric lymph nodes of both the control and 40% burned rats. However, E. coli translocated at a greater incidence to the spleens, livers, and peritoneal cavities of the burned rats compared with translocation to these organs in control rats. The numbers of E. coli translocating to the mesenteric lymph nodes, spleens, and livers also were greater in the 40% burned rats than in control rats. By 14 days after thermal injury, the rats were able to clear E. coli from their spleens and livers, and the infection remained localized in the mesenteric lymph nodes. These results support the concept that the indigenous gastrointestinal flora or exogenous organisms colonizing the gastrointestinal tract are potential sources of septicemia after thermal injury.


Methanolic extract of Woodfordia fruticosa Kurz flowers ameliorates carbon tetrachloride-induced chronic hepatic fibrosis in rats.
Hepatic fibrosis, characterized by extracellular matrix accumulation, is the common cause of chronic liver failure and is a leading cause of morbidity and mortality worldwide. The aim of the present study was to evaluate the effect of dried flowers of Woodfordia fruticosa on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rat model. Hepatic fibrosis was induced in male Wistar rats by CCl4 administration (150 μl/100 g rat weight, oral) twice a week for 10 weeks. In preventive model, administration of daily doses of methanolic extract of W. fruticosa (MEWF) at two different doses (100 mg/kg, body weight (b.w.) and 200 mg/kg, b.w.) was started 1 week before the onset of CCl4 administration and continued for 10 weeks. In curative model, MEWF at 100 and 200 mg/kg were given for last 2 weeks after the establishment of fibrosis. MEWF at a dose of 200 mg/kg was able to exert a more pronounced effect as evidenced histologically by significant reduction in fibrotic septa formation in liver tissue, immunohistochemically by abridged expression of collagen III, and also biochemically by serum and tissue antioxidant status, lipid peroxidation, and hydroxyproline level. Liquid chromatography-mass spectrometry analysis revealed the presence of confertin, quercetin methyl ether, ellagic acid, and stigmasterol in MEWF, which could be responsible for its antifibrotic activity. These results indicate the effective protection exerted by MEWF against CCl4-induced hepatic fibrosis in a dose-dependent manner.


Psychotherapeutic strategies for bulimia nervosa.
Psychotherapeutic strategies for bulimia nervosa have included behavioral, cognitive-behavioral, psychodynamic, and educational treatments used in individual, family, and group settings. Controlled studies have demonstrated the efficacy of behavioral and cognitive-behavioral approaches for these disorders, and extensive clinical experience suggests a role for individual psychodynamic and family approaches as well, particularly in the treatment of frequently encountered complex clinical conditions in which bulimia nervosa coexists with other mood, anxiety, personality, and interpersonal disorders. Guidelines for clinical management have emerged from both research studies and the cumulative experiences of specialists.


[Influence of nasal continuous positive airway pressure on response to exercise in patients with obstructive sleep apnea syndrome].
Obstructive sleep apnea syndrome (OSAS) patients are at risk of cardiovascular complications. The aim of this study was to assess the effect of treatment with continuous positive airway pressure (CPAP) on the response to symptom limited exercise test. twenty nine OSAS patients (1 F, 28 M), mean age 50.7+/-9.7 yrs with body mass index of 32.6+/-4.5 kg/m2 participated in the study. OSAS was diagnosed by overnight polysomnography. Incremental cardiopulmonary exercise test (CPET) on a treadmill was performed twice: before and after 2-3 weeks of regular treatment with CPAP. mean apnea + hypopnea index (AHI) before therapy was 57.6+/-12 h(-1). CPAP treatment did not change peak oxygen consumption (VO2max) (38.3+/-9.0 vs. 38.9+/-6.9 mlO2/kg/min, p=ns) or peak heart rate (153.4+/-21 min- vs. 155.5+/-22 min(-1), p=ns). There were no significant changes in ventilation or gas exchange variables. However, a decrease in peak systolic blood pressure from 194.5+/-24 mmHg to 186.7+/-27.9 mmHg (p<0.05) with CPAP treatment was found. During recovery a decrease in heart rate (at 1st minute and minutes 3 - 6) and mean arterial pressure (MAP) (minutes 4-7) with CPAP treatment was observed. Significant correlations between VO2max and AHI (r=-0,38, p<0,05); MAP at peak exercise and: AHI, mean oxygen saturation (SaO2) during sleep, minutes of sleep with SaO2<90% (T90); MAP at recovery (minutes 3-8) and T90 before CPAP treatment were also noted. OSAS patients are not limited on exercise. Treatment with nasal CPAP attenuates circulatory response to incremental exercise on a treadmill.


Functional analysis of leptin receptor activation using a Janus kinase/signal transducer and activator of transcription complementation assay.
The leptin receptor (LR), a member of the class I cytokine receptor family, is composed of a single subunit. Its extracellular domain consists of two so-called cytokine receptor homology domains, separated by an Ig-like domain, and two additional fibronectin type III modules. Requirements for LR activation were examined using a complementation strategy. Two LR mutants, LR-FFY-Deltabox 1 and LR-F3, deficient in Janus kinase or signal transducer and activator of transcription (STAT) activation, respectively, were only able to generate a STAT3-dependent signal when coexpressed. Based on the requirements for Janus kinase/STAT signaling, and on the lack of complementation with similar receptor constructs, but containing the extracellular domain of the homodimeric erythropoietin receptor, this observation can be explained only by higher order LR clustering. Using a panel of deletion mutants we were able to define a role for the cytokine receptor homology 1 and Ig-like domains in leptin signaling. Moreover, we demonstrate a nonredundant function for the individual receptor chains within the homomeric LR complex. Based on these data, we propose a possible model for LR clustering.