Updating the Micro-Tom TILLING platform.
The dwarf tomato variety Micro-Tom is regarded as a model system for functional genomics studies in tomato. Various tomato genomic tools in the genetic background of Micro-Tom have been established, such as mutant collections, genome information and a metabolomic database. Recent advances in tomato genome sequencing have brought about a significant need for reverse genetics tools that are accessible to the larger community, because a great number of gene sequences have become available from public databases. To meet the requests from the tomato research community, we have developed the Micro-Tom Targeting-Induced Local Lesions IN Genomes (TILLING) platform, which is comprised of more than 5000 EMS-mutagenized lines. The platform serves as a reverse genetics tool for efficiently identifying mutant alleles in parallel with the development of Micro-Tom mutant collections. The combination of Micro-Tom mutant libraries and the TILLING approach enables researchers to accelerate the isolation of desirable mutants for unraveling gene function or breeding. To upgrade the genomic tool of Micro-Tom, the development of a new mutagenized population is underway. In this paper, the current status of the Micro-Tom TILLING platform and its future prospects are described.


A complex elder care simulation using improvisational actors.
Complex simulations can facilitate students' synthesis of knowledge. Simulations of cognitively impaired elders provide nursing students the opportunity to use critical thinking and clinical decision-making skills in complex patient care situations. The authors report their experiences in designing, implementing, and evaluating a simulation on cognitive problems in elders using actors. This simulation required third-year baccalaureate nursing students to differentiate delirium from dementia, identify symptoms of heart failure, and address a family member's concerns.


Bopindolol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy.
Bopindolol is a nonselective beta-adrenoceptor antagonist [corrected] with partial agonist activity which is used in the treatment of hypertension. The drug is rapidly metabolised to an active hydrolysed form. The antihypertensive effects of bopindolol 0.5 to 4 mg are sustained for more than 24 hours after once daily dosing, and the drug appears similar in efficacy to propranolol, metoprolol, atenolol, pindolol and slow release nifedipine in the treatment of mild to moderate forms of this disease. In limited trials bopindolol has also successfully reduced symptoms in patients with angina pectoris, anxiety and essential tremor. Thus, bopindolol is an effective and well-tolerated beta-adrenoceptor antagonist.


A zwitterionic viologen disulfonate-hydroquinone charge-transfer crystal: 2,2'-(4,4'-bipyridinium-1,1'-diyl)di(ethanesulfonate)-hydroquinone (1/2).
The structure of the title compound, C(14)H(16)N(2)O(6)S(2).2C(6)H(6)O(2), consists of 2,2'-(4,4'-bipyridinium-1,1'-diyl)di(ethanesulfonate) molecules (with crystallographically imposed twofold symmetry) that are hydrogen bonded to each other, as well as to hydroquinone molecules, in a complex three-dimensional motif. The orange color of the crystals is indicative of the donor-acceptor interaction between the electron-rich hydroquinone pi-donor and the electron-deficient bipyridinium pi-acceptor. The dihedral angle between the bipyridyl planes is 38.31 (11) degrees. The distance from the centroid of one of the hydroquinone molecules to the center of the bipyridinium group is 3.653 (3) A, which is within the range typically observed for molecular complexes exhibiting charge-transfer characteristics.


Stabilizing effects of coenzyme Q10 on potassium ion release, membrane potential and fluidity of rabbit red blood cells.
The effects of coenzyme Q10 (Co Q10) on potassium ion release, membrane potential and fluidity of rabbit red blood cells were studied. Co Q10 inhibited the increased potassium ion release induced by cetylamine or lysolecithin from the cells. Co Q10 slightly decreased the membrane potential monitored by changes in fluorescence intensity of cyanine dye, 3,3'-dipropyl-2,2'-thiodicarbocyanine iodide [diS-C3-(5)], and also slightly decreased the membrane fluidity measured by using 1,6-diphenyl-1,3,5-hexatriene (DPH). These effects of Co Q10 on the membrane are considered to be due to its membrane stabilizing activity by interaction with lipid bilayers of the membrane.


Functional PET Evaluation of the Photosensitive Baboon.
The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes.


[Choledochal cyst as an unexpected intraoperative finding].
In adulthood, choledochal cysts often surprisingly are discovered during cholecystectomy. Abdominal ultrasonography incorrectly identified the cyst as a dilated or septated gallbladder. Once suspected preoperatively, confirmation of the diagnosis is obtained by ultrasonography or computerized axial tomography, which define its relationship to the vascular structures in the porta. The rapidity and accuracy of ultrasonography favour its use as the initial investigative procedure. Direct cholangiography is the preferred modality for accurate definition of the type of choledochal cyst, ductal strictures, intrahepatic ductal configuration, and polypoid filling defects suggesting cholangiocarcinoma. The well known risk of development of ascending cholangitis as well as cystic cancer, mainly in the adult, indicates the excisional operation for preventing these complications. Cyst excision and Roux-en-Y hepaticojejunostomy is the definitive treatment of choice.


Long-term follow up of relapsed/refractory non-Hodgkin lymphoma patients treated with single-agent selinexor - a retrospective, single center study.
Selinexor is a first-in-class, oral therapy that selectively inhibits nuclear export. The drug is active with an overall response rate (ORR) of approximately 30% in relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL). Long-term patient follow-up has not been reported. Thirty-one NHL patients were treated between July 2012 and July 2018; 22 were evaluated for response. ORR was 32% (7/22). Two patients achieved complete remission (CR) and were alive and lymphoma-free at the end of follow-up. Fifteen patients (68%) progressed during treatment, most of them died within 3-10 months. The most common grade 3/4 adverse events were gastrointestinal and hematological. Median follow up was 50 months. Overall survival for the entire cohort was 16%. Selinexor monotherapy for r/r NHL is an active therapy with the potential for long-term disease control. It may serve as a 'bridge' to subsequent therapy. Additional studies are needed to identify predictive biomarkers and to evaluate combination approaches.


The cell surface receptor for immunoglobulin E. Effect of tunicamycin on molecular properties of receptor from rat basophilic leukemia cells.
Cell surface receptors for immunoglobulin E were isolated by repetitive affinity chromatography from rat basophilic leukemia cells biosynthetically labeled with L-[35S]methionine and D-[3H]mannose. Native immunoglobulin E receptor appeared as a very broad band in the 45,000 to 62,000 Mr region in sodium dodecyl sulfate polyacrylamide gels. However, from cells cultured in the presence of tunicamycin, a relatively narrow band with an apparent Mr of 38,000 was isolated. The 38,000 Mr band rebound to immunoglobulin E-Sepharose, was immunoprecipitated with antibodies to immunoglobulin E receptor, shared tryptic peptides with native receptor, and was labeled with L-[35S]methionine but not D-[3H]mannose, and thus appears to be immunoglobulin E receptor lacking N-linked oligosaccharides. It is demonstrated that N-linked oligosaccharides account for much of the apparent heterogeneity of native receptor in sodium dodecyl sulfate polyacrylamide gels and in two-dimensional gel electrophoresis. A receptor-associated protein with apparent Mr = 30,000, prominently labeled with L-[35S]methionine but not with D-[3H]mannose, did not have altered molecular properties when isolated from tunicamycin-cultured cells, and did not share tryptic peptides with receptor.


Sterically stabilized anti-idiotype immunoliposomes improve the therapeutic efficacy of doxorubicin in a murine B-cell lymphoma model.
A liposome containing diverse synthetic lipid derivatives of polyethylene glycol (PEG) results in smaller distribution volume and longer circulation time in blood and, thus, may improve drug targeting. The characteristics and therapeutic efficacy of immunoliposomes with similar liposomal formulation have never been studied in lymphoma models. We have developed immunoliposomes conjugated with S5A8 monoclonal antibody, an anti-idiotype antibody to 38C13 murine B-cell lymphoma, and loaded them with doxorubicin using an ammonium sulfate gradient. Purified antibodies were covalently coupled to the termini of PEG on the surface of small unilamellar liposomes. Cell binding and internalization ability of these immunoliposomes were estimated by a fluorescence assay using a pH-sensitive fluorescent dye (HPTS). The in vitro cytotoxicity of doxorubicin encapsulated in immunoliposomes was greater for idiotype-positive 38C13 cells than for the idiotype-negative variant of this cell line. In syngeneic C3H/HeN mice, doxorubicin encapsulated in immunoliposomes exhibited a long circulation time and was more effective at prolonging survival of mice bearing 38C13 tumor than non-targeted liposomal doxorubicin or free doxorubicin plus empty immunoliposomes. Our results demonstrate the superiority of targeted therapy with these immunoliposomes and its potential in lymphoma treatment.


Clinical applications of molecular biology for infectious diseases.
Molecular biological methods for the detection and characterisation of microorganisms have revolutionised diagnostic microbiology and are now part of routine specimen processing. Polymerase chain reaction (PCR) techniques have led the way into this new era by allowing rapid detection of microorganisms that were previously difficult or impossible to detect by traditional microbiological methods. In addition to detection of fastidious microorganisms, more rapid detection by molecular methods is now possible for pathogens of public health importance. Molecular methods have now progressed beyond identification to detect antimicrobial resistance genes and provide public health information such as strain characterisation by genotyping. Treatment of certain microorganisms has been improved by viral resistance detection and viral load testing for the monitoring of responses to antiviral therapies. With the advent of multiplex PCR, real-time PCR and improvements in efficiency through automation, the costs of molecular methods are decreasing such that the role of molecular methods will further increase. This review will focus on the clinical utility of molecular methods performed in the clinical microbiology laboratory, illustrated with the many examples of how they have changed laboratory diagnosis and therefore the management of infectious diseases.


Sources of motivation, interpersonal conflict management styles, and leadership effectiveness: a structural model.
126 leaders and 624 employees were sampled to test the relationship between sources of motivation and conflict management styles of leaders and how these variables influence effectiveness of leadership. Five sources of motivation measured by the Motivation Sources Inventory were tested-intrinsic process, instrumental, self-concept external, self-concept internal, and goal internalization. These sources of work motivation were associated with Rahim's modes of interpersonal conflict management-dominating, avoiding, obliging, complying, and integrating-and to perceived leadership effectiveness. A structural equation model tested leaders' conflict management styles and leadership effectiveness based upon different sources of work motivation. The model explained variance for obliging (65%), dominating (79%), avoiding (76%), and compromising (68%), but explained little variance for integrating (7%). The model explained only 28% of the variance in leader effectiveness.


Acetylation of Dna2 endonuclease/helicase and flap endonuclease 1 by p300 promotes DNA stability by creating long flap intermediates.
Flap endonuclease 1 (FEN1) and Dna2 endonuclease/helicase (Dna2) sequentially coordinate their nuclease activities for efficient resolution of flap structures that are created during the maturation of Okazaki fragments and repair of DNA damage. Acetylation of FEN1 by p300 inhibits its endonuclease activity, impairing flap cleavage, a seemingly undesirable effect. We now show that p300 also acetylates Dna2, stimulating its 5'-3' endonuclease, the 5'-3' helicase, and DNA-dependent ATPase activities. Furthermore, acetylated Dna2 binds its DNA substrates with higher affinity. Differential regulation of the activities of the two endonucleases by p300 indicates a mechanism in which the acetylase promotes formation of longer flaps in the cell at the same time as ensuring correct processing. Intentional formation of longer flaps mediated by p300 in an active chromatin environment would increase the resynthesis patch size, providing increased opportunity for incorrect nucleotide removal during DNA replication and damaged nucleotide removal during DNA repair. For example, altering the ratio between short and long flap Okazaki fragment processing would be a mechanism for better correction of the error-prone synthesis catalyzed by DNA polymerase alpha.


Relationship between histologic grade and cytofluorometric cellular DNA and RNA content in primary bone tumors.
The diagnosis and grading of bone tumors remains a challenging problem. We studied the relationship between histologic grade and cytofluorometric cellular DNA and RNA content in 108 primary bone tumors. The data included DNA ploidy, mean DNA content (MDC), S-phase fraction (SPF), mean RNA content (MRC) and RNA/DNA ratio (RDR; MRC/MDC) which represents the RNA content normalized for the DNA content. Benign tumors had a diploid stem line with low MDC (mean; 1.04), low SPF (0.9), high MRC (2.41) and high RDR (2.31). Giant cell tumors of bone, which are locally aggressive benign tumors, showed diploidy with relatively higher MDC (1.07, p < 0.01) and SPF (2.6, p < 0.01) and lower MRC (1.81, p < 0.01) and RDR (1.69, p < 0.01). Similar results were obtained in low-grade sarcomas. In high-grade sarcomas, the data depended on the histologic findings. Pleomorphic sarcomas such as osteosarcomas revealed aneuploidy with remarkably higher MDC (1.70 in osteosarcomas, p < 0.01) and SPF (6.5, p < 0.01), but lower RDR (1.70, p < 0.01). In contrast, small cell sarcomas, such as Ewing's sarcomas, showed diploidy with low MDC (1.11 in Ewing's sarcomas, N.S.) and SPF (2.5, p < 0.01) and extremely low RDR (1.34, p < 0.01). The RDR value was higher in well-differentiated tumors than in primitive tumors, rendering it useful in grading bone tumors with a diploid stem line. By combining the RDR value with the MDC value, 96% of diploid sarcomas could be distinguished from benign tumors. These results indicate that cellular DNA and RNA content analysis may be of value in assessing the malignant potential of diploid as well as aneuploid bone sarcomas.


Overtraining and the use of feature and geometric cues for reorientation.
Using a dynamic three-dimensional virtual environment task, we investigated the influence of overtraining of feature and geometric cues on preferential spatial cue use. We trained two groups of human participants to respond to feature and geometric cues in separate enclosures before placing these cues in conflict on a critical test trial. All participants learned to respond to rewarded features located along the principal axis of a rectangular search space and to rewarded geometric cues of a rectangular search space in separate training phases followed by a single test trial. During the test trial, we situated the rewarded features in the unrewarded geometric corners and the unrewarded features in rewarded geometric corners. For one group, participants were overtrained with feature cues compared to geometric cues before experiencing the conflict test; whereas, for another group, participants were overtrained with geometric cues compared to feature cues before experiencing the conflict test. Although both groups learned to respond to both feature and geometric cues at an equivalent rate and to an equivalent level of terminal accuracy, testing results revealed no difference between the groups with respect to their preference for feature or geometric cues. Despite a lack of influence of overtraining on spatial cue preference, participants showed an overall preference for feature cues. We discuss the results with respect to implications for theoretical accounts of spatial learning.


Interspecies Differences in Activation of Peroxisome Proliferator-Activated Receptor γ by Pharmaceutical and Environmental Chemicals.
Endocrine disrupting chemicals (EDCs) are able to deregulate the hormone system, notably through interactions with nuclear receptors (NRs). The mechanisms of action and biological effects of many EDCs have mainly been tested on human and mouse but other species such as zebrafish and xenopus are increasingly used as a model to study the effects of EDCs. Among NRs, peroxisome proliferator-activated receptor γ (PPARγ) is a main target of EDCs, for which most experimental data have been obtained from human and mouse models. To assess interspecies differences, we tested known human PPARγ ligands on reporter cell lines expressing either human, mouse, zebrafish, or xenopus PPARγ. Using these cell lines, we were able to highlight major interspecies differences. Known hPPARγ pharmaceutical ligands modulated hPPARγ and mPPARγ activities in a similar manner, while xPPARγ was less responsive and zfPPARγ was not modulated at all by these compounds. On the contrary, human liver X receptor (hLXR) ligands GW 3965 and WAY-252623 were only active on zfPPARγ. Among environmental compounds, several molecules activated the PPARγ of the four species similarly, e.g., phthalates (MEHP), perfluorinated compounds (PFOA, PFOS), and halogenated derivatives of BPA (TBBPA, TCBPA), but some of them like diclofenac and the organophosphorus compounds tri-o-tolyl phosphate and triphenyl phosphate were most active on zfPPARγ. This study confirms or shows for the first time the h, m, x, and zfPPARγ activities of several chemicals and demonstrates the importance of the use of species-specific models to study endocrine and metabolism disruption by environmental chemicals.


Alkalitolerance: a biological function for a multidrug transporter in pH homeostasis.
MdfA is an Escherichia coli multidrug-resistance transporter. Cells expressing MdfA from a multicopy plasmid exhibit multidrug resistance against a diverse group of toxic compounds. In this article, we show that, in addition to its role in multidrug resistance, MdfA confers extreme alkaline pH resistance and allows the growth of transformed cells under conditions that are close to those used normally by alkaliphiles (up to pH 10) by maintaining a physiological internal pH. MdfA-deleted E. coli cells are sensitive even to mild alkaline conditions, and the wild-type phenotype is restored fully by MdfA expressed from a plasmid. This activity of MdfA requires Na(+) or K(+). Fluorescence studies with inverted membrane vesicles demonstrate that MdfA catalyzes Na(+)- or K(+)-dependent proton transport, and experiments with reconstituted proteoliposomes confirm that MdfA is solely responsible for this phenomenon. Studies with multidrug resistance-defective MdfA mutants and competitive transport assays suggest that these activities of MdfA are related. Together, the results demonstrate that a single protein has an unprecedented capacity to turn E. coli from an obligatory neutrophile into an alkalitolerant bacterium, and they suggest a previously uncharacterized physiological role for MdfA in pH homeostasis.


Tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis on immunosuppressive therapy.
Kaposi sarcoma is a malignant vascular neoplasm uncommonly seen in immunosuppressed patients. Herein we report an unusual case of tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis treated with prednisolone and cyclosporine. The patient presented after 10 months of starting the treatment with a tonsillar mass. Histological examination was typical of monomorphic spindle cell proliferation with slit-like vascular channels. The tumor cells expressed CD34, D2-40 and positive nuclear stain for HHV-8. Kaposi sarcoma is associated with immunosuppression and rarely occurs in the tonsil. Clinicians should be aware of this rare presentation of Kaposi sarcoma.


Rotavirus-Induced Neonatal Epileptic Encephalopathy-A Disease Spectrum Illustrated by Monochorionic Twins.
Rotavirus has been associated with neonatal seizures and specific white matter magnetic resonance imaging (MRI) abnormalities. We describe monochorionic twins who not only tested positive for rotavirus with these white matter MRI abnormalities but who also showed an electroencephalogram (EEG) pattern characteristic of early infantile epileptic encephalopathy (EIEE), which has so far solely been described in epileptic encephalopathies with a poor prognosis. This report suggests that rotavirus infection must be added to the list of causes of EIEE EEG, and that the outcome then is likely more favorable. As MRI and EEG signs of rotavirus encephalopathy were present in one twin with only subtle neurologic symptoms, rotavirus may well cause insidious central nervous system complications more often. We suggest considering rotavirus infection in neonates presenting with seizures, and to add rotavirus infection to the differential diagnosis of EIEE.


Riboswitch-Mediated Gene Regulation: Novel RNA Architectures Dictate Gene Expression Responses.
Riboswitches are RNA elements that act on the mRNA with which they are cotranscribed to modulate expression of that mRNA. These elements are widely found in bacteria, where they have a broad impact on gene expression. The defining feature of riboswitches is that they directly recognize a physiological signal, and the resulting shift in RNA structure affects gene regulation. The majority of riboswitches respond to cellular metabolites, often in a feedback loop to repress synthesis of the enzymes used to produce the metabolite. Related elements respond to the aminoacylation status of a specific tRNA or to a physical parameter, such as temperature or pH. Recent studies have identified new classes of riboswitches and have revealed new insights into the molecular mechanisms of signal recognition and gene regulation. Application of structural and biophysical approaches has complemented previous genetic and biochemical studies, yielding new information about how different riboswitches operate.


Some singular properties of bacterial flagella, with special reference to monotrichous forms.
Roberts, F. F., Jr. (University of Maryland, College Park), and R. N. Doetsch. Some singular properties of bacterial flagella, with special reference to monotrichous forms. J. Bacteriol. 91:414-421. 1966.-Heat (60 C for 30 min), 10 m acetamide, and 8 m urea all brought about rapid and complete dissolution of flagella from monotrichous bacteria; hence, these flagella respond similarly to those of peritrichous forms. Chloramphenicol (10(3) mug/ml) inhibited regeneration of flagella in all peritrichously flagellated cultures; however, monotrichous forms were able to regenerate their flagella in a concentration 10(2) times that required to inhibit multiplication. Peritrichous bacteria did not synthesize flagella when infected by lytic bacteriophages. In these experiments, the time from infection to lysis was sufficient for uninfected controls to resynthesize their flagella. Monotrichous bacteria, however, in all but one instance, were able to resynthesize their flagella before lysis occurred. A study of flagella resynthesis in a non-nutritive milieu indicated that only a small amount of flagellum precursor is present in any given cell. The effect of temperature on synthesis of flagella indicated that, although some bacteria multiply and are motile at a given temperature, they are unable to resynthesize their flagella at that same temperature. This strongly suggests that initial flagellum synthesis and flagellum regeneration are not necessarily identical processes.


Two-dimensional self-assembly of dendritic amphiphilic molecule with ferroncenyl subsitutuents at the liquid/solid interface.
Two-dimensional self-assembly of dendritic amphiphilic molecule with ferroncenyl subsitutuents (2,3,4-tri-(11-ferroncenyl)undecyloxybenzoic acid, Fc3COOH) on highly oriented pyrolytic graphite surface was investigated by scanning tunneling microscopy at the liquid/solid interface. Fc3COOH molecule formed an ordered molecular nanostructure--an alternating big/small bright dots pattern on the graphite surface extended to several hundred nanometers. On the basis of the simulation and combined with our STM results, it is concluded that the molecular adsorption conformation has an appreciable effect on the interactions of molecule-molecule and molecule-substrate. The pi-pi interactions between ferrocene groups together with the van der Waals interactions between alkyl chains direct the stacking behavior of Fc3COOH molecules. Due to the steric constraints, no hydrogen bonding between the carboxyl groups was formed during the self-assembly.


Methionine restriction up-regulates the expression of the pi class of glutathione S-transferase partially via the extracellular signal-regulated kinase-activator protein-1 signaling pathway initiated by glutathione depletion.
Understanding the molecular events underlying gene regulation by amino acids has attracted increasing attention. Here, we explored whether the mechanism by which methionine restriction affects the expression of the pi class of glutathione S-transferase (GSTP) is related to oxidative stress initiated by glutathione (GSH) depletion. Rat primary hepatocytes were cultured in an L-15-based medium in the absence or presence of 200 muM L-buthionine sulfoximine (BSO) or in a methionine-restricted L-15 medium supplemented with 20 muM L-methionine up to 72 h. BSO and methionine restriction time-dependently induced GSTP mRNA and protein expression in a similar pattern accompanied by a decrease in the cellular GSH level. The phosphorylation of extracellular signal-regulated kinase (ERK), but not of c-Jun NH(2)-terminal kinase and p38, was stimulated by methionine restriction and BSO. Electromobility gel shift assay showed that the DNA-binding activity of nuclear activator protein-1 (AP-1) increased in cells exposed to methionine restriction or BSO. With the ERK inhibitor FR180204, AP-1 activation and GSTP expression were abolished. Moreover, the induction of GSTP by methionine restriction and BSO was reversed by GSH monoethyl ester and N-acetylcysteine. Our results suggest that methionine restriction up-regulates GSTP gene expression, which appears to be initiated by the ERK-AP-1 signaling pathway through GSH depletion in rat hepatocytes.


[Oxymatrine in the treatment of chronic hepatitis B for one year: a multicenter random double-blind placebo-controlled trial].
To evaluate the efficacy and safety of oxymatrine in the treatment of chronic hepatitis B. A multicenter randomized double-blind placebo-controlled trial was conducted. A total of 144 patients with chronic hepatitis B entered the study for 52 weeks; of them 72 received oxymatrine, and 72 received a placebo. Before and after the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reactions were observed. In 144 patients, 14 were dropped and excluded due to inconsistencies in the included standard. Therefore, the efficacy and safety of 130 patients were analyzed. After being treated for 52 weeks, 70.77% of the patients in the study group had a normal ALT level, and in 43.08% and 33.33% their HBV DNA and HBeAg became negative. In the placebo group, 39.68% had normal ALT level, and 12.31% and 3.33% had their HBV DNA and HBeAg become negative. The rates of complete response and partial response in the oxymatrine group were 23.08% and 58.46%, and in the placebo group they were 3.08% and 44.62%. They were significantly higher in the oxymatrine group than in the placebo group. In the oxymatrine treated patients, 12 weeks after its withdrawal, 60.00% had a normal ALT level, 41.54% and 23.33% had both HBV DNA and HBeAg negative. In the placebo group, 31.75% had a normal ALT level, 3.08% and 1.67% had both HBV DNA and HBeAg negative. The rates of complete response and partial response in the oxymatrine group were 21.54% and 47.69%, and in the placebo group they were 0 and 41.54%. They were significantly higher in the study group than in the placebo group. The adverse reaction rates of oxymatrine in the study and the placebo group were 7.69% and 6.15%, respectively, but there was no statistical significant difference between them. Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.


Alcohol consumption and suicide mortality by age among Finnish men, 1950-1991.
An earlier comparative time series analysis of the connection between per capita alcohol consumption and suicide mortality reported, unexpectedly, a non-significant effect of alcohol on the suicide rate of Finnish men. However, the suicide rate of Finnish men is heterogeneous in regard to age groups. There is also indication that the connection between alcohol and suicides is stronger in younger than in older age groups. Time series data on per capita alcohol consumption and age-specific suicide mortality in 1950-91 were used to scrutinize the relationship. The results indicate that the suicide rate of Finnish men in age groups 15-34 years and 35-49 years is associated with per capita alcohol consumption, while no connection could be established between the suicide rates of men aged 50-69 years and 70+ years and either per capita alcohol consumption or a lagged consumption measure. Real income, divorce rate and unemployment rate were regarded as possible confounding variables.


Probing the kinetics of ligand exchange on colloidal gold nanoparticles by surface-enhanced Raman scattering.
We report a new approach to study the kinetics of ligand exchange on colloidal gold nanoparticles, where the coordination and dissociation of surface ligands could be monitored in situ by surface-enhanced Raman scattering.


EUS-guided pancreatic pseudocyst drainage: review and experience at Harbor-UCLA Medical Center.
Pancreatic pseudocyst, the most common cystic lesion of the pancreas, is a localized collection of fluid rich in amylase within or adjacent to the pancreas and enclosed by a nonepithelialized wall, occurring as a result of acute or chronic pancreatitis, pancreatic trauma, or pancreatic duct obstruction. Currently, at least 3 major forms of therapy are available: percutaneous drainage, surgical intervention, and endoscopic drainage. Controversy exists concerning which of these techniques should be offered to the patient as initial therapy. Three options exist for the surgical management of pancreatic pseudocysts: excision, external drainage, and internal drainage. Surgery, which traditionally was the major treatment approach for pancreatic pseudocysts, has been challenged by newer endoscopic techniques. Given the low complication and mortality rates and the high success rate of endoscopic drainage when compared with surgery, surgical intervention should be reserved only for certain cases. Addition of endoscopic ultrasonography (EUS) for endoscopic drainage is a new and exciting development and may decrease the risks associated with endoscopic drainage. We report our experience of 14 cases of EUS-guided pancreatic pseudocyst drainage and review the literature for advantages and disadvantages of these pancreatic pseudocyst drainage procedures. Complications, recurrence, success, and mortality rates for each procedure are described. Our approach to pancreatic pseudocyst management is described in the form of an algorithm.


Clinical characterisation of a novel paroxysmal dyskinesia in Welsh terrier dogs.
Breed specific paroxysmal dyskinesias are increasingly recognised in veterinary medicine. We aimed to characterise the phenomenology, clinical course and prevalence of a previously unreported paroxysmal dyskinesia in the Welsh terrier breed. Clinical records of five Welsh terriers with paroxysmal episodes were reviewed. Additionally, owners of Welsh terriers were invited to complete a questionnaire with the aim of characterising paroxysmal episodes in the wider breed population. Clinical examinations (n = 5) and diagnostic investigations (n = 3) of affected Welsh terriers were within normal limits, apart from mild-moderate ventriculomegaly on cranial magnetic resonance imaging (n = 3). The survey of Welsh terrier owners revealed episodes consistent with a paroxysmal dyskinesia in 41 (22.8%) of 177 respondents. Median age of onset was 59 months. Episodes were predominantly characterised by sustained hypertonicity with periods of limb flexion, abnormal head and body posture, with preserved consciousness. Episode duration ranged from 30 s to 30 min (median, 3 min 30 s), with frequency varying widely between dogs. Affected dogs demonstrated a stable to improving clinical course in most cases. This study investigated a previously unreported paroxysmal dyskinesia in Welsh terriers. Similar clinical signs within the breed were potentially consistent with an inherited cause, worthy of further investigation.


In silico carbon molecular beam epitaxial growth of graphene on the h-BN substrate: carbon source effect on van der Waals epitaxy.
Against the presumption that hexagonal boron-nitride (h-BN) should provide an ideal substrate for van der Waals (vdW) epitaxy to grow high quality graphene films, carbon molecular beam epitaxy (CMBE) techniques using solid carbon sublimation have reported relatively poor quality of the graphene. In this article, the CMBE growth of graphene on the h-BN substrate is numerically studied in order to identify the effect of the carbon source on the quality of the graphene film. The carbon molecular beam generated by the sublimation of solid carbon source materials such as graphite and glassy carbon is mostly composed of atomic carbon, carbon dimers and carbon trimers. Therefore, the graphene film growth becomes a complex process involving various deposition characteristics of a multitude of carbon entities. Based on the study of surface adsorption and film growth characteristics of these three major carbon entities comprising graphite vapour, we report that carbon trimers convey strong traits of vdW epitaxy prone to high quality graphene growth, while atomic carbon deposition is a surface-reaction limited process accompanied by strong chemisorption. The vdW epitaxial behaviour of carbon trimers is found to be substantial enough to nucleate and develop into graphene like planar films within a nanosecond of high flux growth simulation, while reactive atomic carbons tend to impair the structural integrity of the crystalline h-BN substrate upon deposition to form an amorphous interface between the substrate and the growing carbon film. The content of reactive atomic carbons in the molecular beam is suspected to be the primary cause of low quality graphene reported in the literature. A possible optimization of the molecular beam composition towards the synthesis of better quality graphene films is suggested.


Self-built supercritical CO2 anti-solvent unit design, construction and operation using carbamazepine.
The purpose of this study was to design and build a supercritical CO(2) anti-solvent (SAS) unit and use it to produce microparticles of the class II drug carbamazepine. The operation conditions of the constructed unit affected the carbamazepine yield. Optimal conditions were: organic solution flow rate of 0.15 mL/min, CO(2) flow rate of 7.5 mL/min, pressure of 4,200 psi, over 3,000 s and at 33 degrees C. The drug solid-state characteristics, morphology and size distribution were examined before and after processing using X-ray powder diffraction and differential scanning calorimetry, scanning electron microscopy and laser diffraction particle size analysis, respectively. The in vitro dissolution of the treated particles was investigated and compared to that of untreated particles. Results revealed a change in the crystalline structure of carbamazepine with different polymorphs co-existing under various operation conditions. Scanning electron micrographs showed a change in the crystalline habit from the prismatic into bundled whiskers, fibers and filaments. The volume weighted diameter was reduced from 209 to 29 mum. Furthermore, the SAS CO(2) process yielded particles with significantly improved in vitro dissolution. Further research is needed to optimize the operation conditions of the self-built unit to maximize the production yield and produce a uniform polymorphic form of carbamazepine.


Prostaglandin (PGF2 alpha)-induced parturition in red deer (Cervus elaphus L.).
Prostaglandin PGF2 alpha seems to act satisfactorily as a birth inducing agent in red deer (Cervus elaphus). The progress of actual delivery and lactation in the experiments of induced parturition corresponds with observations from natural conditions. The pattern of response time to the birth inducing agent agrees with experience from domesticated species, being longest in females with the least developed fetuses. Complications such as those reported from practice with induced parturition in domestic species were not experienced in the three experiments on red deer. Applications of prostaglandin PGF2 alpha prior to approximately 18-20 days preterm probably reduce chances for the offspring to survive. This seemingly being due to ontogenetical immaturity in the fetus, and deficient hormonal development in the mother, necessary for normal lactogenesis.


The Communication Infrastructure as a Social Determinant of Health: Implications for Health Policymaking and Practice.
Policy Points Persistent communication inequalities limit racial/ethnic minority access to life-saving health information and make them more vulnerable to the effects of misinformation. Establishing data collection systems that detect and track acute gaps in the supply and/or access of racial/ethnic minority groups to credible health information is long overdue. Public investments and support for minority-serving media and community outlets are needed to close persistent gaps in access to credible health information.


Automated ejection fraction determination from gated myocardial FDG-PET data.
The aim of this study was to determine the potential of the automated calculation of the left ventricular ejection fraction from gated myocardial positron emission tomography (PET) scans. We retrospectively analyzed the data of 20 patients who underwent both gated fluorine 18 deoxyglucose (FDG)-PET and equilibrium radionuclide angiography (ERNA). Gated PET data were analyzed by 2 independent programs (ie, quantitative gated single photon emission computed tomography [QGS]) originally developed for gated single photon emission computed tomography studies and functional polarmap (FPM) originally developed for the analysis of (functional) dynamic PET studies. ERNA data were used as the gold standard. Both QGS and FPM left ventricular ejection fraction results correlated highly with ERNA (y = 0.90 x x-5.9, r = 0.86, P < .0001; y = 0.80 x x+3.3, r = 0.84, P < .0001, respectively). The correlation between FPM and QGS left ventricular ejection fraction results was even higher (y = 0.89 x x+8.6, r = 0.97, P < .0001). Bland-Altman plots showed systematic differences in the left ventricular ejection fraction of -9.6% +/- 7.5% (QGS vs ERNA), -3.8% +/- 7.8% (FPM vs ERNA), and -5.8% +/- 3.5% (QGS vs FPM). Further comparison of the left ventricular volumes revealed systematic difference between QGS and FPM. Our results indicate that the correlation between the different left ventricular ejection fractions shows little sensitivity to errors in the left ventricular volumes; however, the exact relationship is influenced by these errors. It is concluded that the automated determination of the left ventricular ejection fraction from gated PET data has significant potential; its results are highly and significantly correlated with ERNA. However, the methods presented here require additional calibration before final accuracy and clinical applicability can be determined.


The role of exportin 6 in cytoskeletal-mediated cell death and cell adhesion in human non-small-cell lung carcinoma cells following doxorubicin treatment.
The actin cytoskeleton plays an important role in various cellular processes. The different forms ofactin (G-actin and F-actin) participate in the organization of nuclear structure and its functions. The structure of the actin cytoskeleton is controlled by proteins involved in the translocation of actin between cytoplasm and the nucleus. In this study, we used siRNA method to investigate the role of exportin 6 in the switching between nuclear and cytoplasmic F-actin pools in H1299 cells treated with no, 1.0 or 2.5 μM doxorubicin. We showed that silencing of exportin 6 expression changed the response of H1299 to doxorubicin. Here, we observed increased population of cells affected by doxorubicin-induced necrotic cell death. Furthermore, fluorescence studies showed that downregulation of exportin 6 exerted profound DOX-induced changes in the F-actin cytoskeleton architecture. The F-actin cytoskeleton was seen in the form of small fibers or aggregates after doxorubicin treatment. Additionally, some cells lost cell adhesion properties. Downregulation of exportin 6 influenced also transcriptional activity of the cells. In cells transfected with nontargeting siRNA, we observed a higher level of 5'-fluorouridine fluorescence than in cells with silenced export in 6 expression. In conclusion, we showed that downregulation of exportin 6 induced necrotic cell death. Moreover, the observed alterations of cell adhesion suggest the key role of cytoplasmic F-actin in maintaining intercellular junctional complexes and/or focal adhesion properties and the importance of the balance between nuclear and cytoplasmic F-actin pools.


GATA-3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB.
The zinc finger transcription factor GATA-3 is a master regulator of type 2 T-helper cell development. Interestingly, in GATA-3-/- mice, noradrenaline (NA) deficiency is a proximal cause of embryonic lethality. However, neither the role of GATA-3 nor its target gene(s) in the nervous system were known. Here, we report that forced expression of GATA-3 resulted in an increased number of tyrosine hydroxylase (TH) expressing neurons in primary neural crest stem cell (NCSC) culture. We also found that GATA-3 transactivates the promoter function of TH via specific upstream sequences, a domain of the TH promoter residing at -61 to -39 bp. Surprisingly, this domain does not contain GATA-3 binding sites but possesses a binding motif, a cAMP response element (CRE), for the transcription factor, CREB. In addition, we found that site-directed mutation of this CRE almost completely abolished transactivation of the TH promoter by GATA-3. Furthermore, protein-protein interaction assays showed that GATA-3 is able to physically interact with CREB in vitro as well as in vivo. Based on these results, we propose that GATA-3 may regulate TH gene transcription via a novel and distinct protein-protein interaction, and directly contributes to NA phenotype specification.


Inhibitors of the Fanconi anaemia pathway as potential antitumour agents for ovarian cancer.
The Fanconi anaemia (FA) pathway is an important mechanism for cellular DNA damage repair, which functions to remove toxic DNA interstrand crosslinks. This is particularly relevant in the context of ovarian and other cancers which rely extensively on interstrand cross-link generating platinum chemotherapy as standard of care treatment. These cancers often respond well to initial treatment, but reoccur with resistant disease and upregulation of DNA damage repair pathways. The FA pathway is therefore of great interest as a target for therapies that aim to improve the efficacy of platinum chemotherapies, and reverse tumour resistance to these. In this review, we discuss recent advances in understanding the mechanism of interstrand cross-link repair by the FA pathway, and the potential of the component parts as targets for therapeutic agents. We then focus on the current state of play of inhibitor development, covering both the characterisation of broad spectrum inhibitors and high throughput screening approaches to identify novel small molecule inhibitors. We also consider synthetic lethality between the FA pathway and other DNA damage repair pathways as a therapeutic approach.


Measles in Ghana--1973-1982.
Admissions of children with measles constituted 8.8% of all admissions to the paediatric medical service of the Korle Bu Teaching Hospital, Accra, over the ten-year-period 1973-1982. Measles remains endemic in urban Accra as in the towns of other developing nations. The peak of admissions occurred in the age range seven to 12 months. Complications were frequent, with a high mortality (16.86%). Bronchopneumonia, the commonest complication (63.9%) was also the commonest cause of death in 51.5% of cases. Comparative national case-mortality rates were, however, surprisingly low and should be accepted with caution. There is an urgent need for intensification of immunization efforts through amalgamation of the preventive and curative services of Ghana, especially for children attending health centres for medical care. Vaccination should be administered before the peak age of admission, preferably at six months of age, with a second dose administered as soon after one year of age as possible.


Pre-existing medical conditions as predictors of adverse events in day-case surgery.
We have developed mathematical models to estimate the risk of perioperative adverse events in patients with pre-existing conditions undergoing day-case surgery. We studied 17,638 consecutive day-case surgical patients in a prospective study. Preoperative, intraoperative and postoperative data were collected. Risk modelling was performed with backward stepwise multiple logistic regression and validated on a separate subset of our patients. Eighteen pre-existing conditions were entered into the model. We adjusted for age, sex, and duration and type of surgery. Seven associations between pre-existing medical conditions and perioperative adverse events were statistically significant. Hypertension predicted the occurrence of any intraoperative event and intraoperative cardiovascular events. Obesity predicted intraoperative and postoperative respiratory events, and smoking and asthma predicted postoperative respiratory events. Gastro-oesophageal reflux predicted intubation-related events. The presented models of risk estimation were validated internally and provided a useful tool for accurate risk estimation.


Synthesis of (-)-9,10-epi-stemoamide.
An efficient synthesis of (-)-9,10-epi-stemoamide has been accomplished in nine steps and 13% overall yield. The synthesis features a lithium hydroxide-promoted fragmentation and an intramolecular 7-exo-trig radical cyclization.


Decaffeinated Green Tea Extract Does Not Elicit Hepatotoxic Effects and Modulates the Gut Microbiome in Lean B6C3F₁ Mice.
The main purpose of this study was to investigate the hepatotoxic potential and effects on the gut microbiome of decaffeinated green tea extract (dGTE) in lean B6C3F₁ mice. Gavaging dGTE over a range of 1X-10X mouse equivalent doses (MED) for up to two weeks did not elicit significant histomorphological, physiological, biochemical or molecular alterations in mouse livers. At the same time, administration of dGTE at MED comparable to those consumed by humans resulted in significant modulation of gut microflora, with increases in Akkermansia sp. being most pronounced. Results of this study demonstrate that administration of relevant-to-human-consumption MED of dGTE to non-fasting mice does not lead to hepatotoxicity. Furthermore, dGTE administered to lean mice, caused changes in gut microflora comparable to those observed in obese mice. This study provides further insight into the previously reported weight management properties of dGTE; however, future studies are needed to fully evaluate and understand this effect.


Roles for sigma factors in global circadian regulation of the cyanobacterial genome.
The circadian clock of the unicellular cyanobacterium Synechococcus elongatus PCC 7942 imposes a global rhythm of transcription on promoters throughout the genome. Inactivation of any of the four known group 2 sigma factor genes (rpoD2, rpoD3, rpoD4, and sigC), singly or pairwise, altered circadian expression from the psbAI promoter, changing amplitude, phase angle, waveform, or period. However, only the rpoD2 mutation and the rpoD3 rpoD4 and rpoD2 rpoD3 double mutations affected expression from the kaiB promoter. A striking differential effect was a 2-h lengthening of the circadian period of expression from the promoter of psbAI, but not of those of kaiB or purF, when sigC was inactivated. The data show that separate timing circuits with different periods can coexist in a cell. Overexpression of rpoD2, rpoD3, rpoD4, or sigC also changed the period or abolished the rhythmicity of PpsbAI expression, consistent with a model in which sigma factors work as a consortium to convey circadian information to downstream genes.


Structure of a triple helical DNA with a triplex-duplex junction.
Extended purine sequences on a DNA strand can lead to the formation of triplex DNA in which the third strand runs parallel to the purine strand. Triplex DNA structures have been proposed to play a role in gene expression and recombination and also have potential application as antisense inhibitors of gene expression. Triplex structures have been studied in solution by NMR, but have hitherto resisted attempts at crystallization. Here, we report a novel design of DNA sequences, which allows the first crystallographic study of DNA segment containing triplexes and its junction with a duplex. In the 1.8 A resolution structure, the sugar-phosphate backbone of the third strand is parallel to the purine-rich strand. The bases of the third strand associate with the Watson and Crick duplex via Hoogsteen-type interactions, resulting in three consecutive C(+).GC, BU.ABU (BU = 5-bromouracil), and C(+).GC triplets. The overall conformation of the DNA triplex has some similarity to the B-form, but is distinct from both A- and B-forms. There are large changes in the phosphate backbone torsion angles (particularly gamma) of the purine strand, probably due to the electrostatic interactions between the phosphate groups and the protonated cytosine. These changes narrow the minor groove width of the purine-Hoogsteen strands and may represent sequence-specific structural variations of the DNA triplex.


Electrochemically controlled assembly and logic gates operations of gold nanoparticle arrays.
The reversible assembly of β-cyclodextrin-functionalized gold NPs (β-CD Au NPs) is studied on mixed self-assembled monolayer (SAM), formed by coadsorption of redox-active ferrocenylalkylthiols and n-alkanethiols on gold surfaces. The surface coverage and spatial distribution of the β-CD Au NPs monolayer on the gold substrate are tuned by the self-assembled monolayer composition. The binding and release of β-CD Au NPs to and from the SAMs modified surface are followed by surface plasmon resonance (SPR) spectroscopy. The redox state of the tethered ferrocene in binary SAMs controls the formation of the supramolecular interaction between ferrocene moieties and β-CD-capped Au NPs. As a result, the potential-induced uptake and release of β-CD Au NPs to and from the surface is accomplished. The competitive binding of β-CD Au NPs with guest molecules in solution shifted the equilibrium of the complexation-decomplexation process involving the supramolecular interaction with the Fc-functionalized surface. The dual controlled assembly of β-CD Au NPs on the surface enabled to use two stimuli as inputs for logic gate activation; the coupling between the localized surface plasmon, associated with the Au NP, and the surface plasmon wave, associated with the thin metal surface, is implemented as readout signal for "AND" logic gate operations.


On the properties of input-to-output transformations in neuronal networks.
Information processing in neuronal networks in certain important cases can be considered as maps of binary vectors, where ones (spikes) and zeros (no spikes) of input neurons are transformed into spikes and no spikes of output neurons. A simple but fundamental characteristic of such a map is how it transforms distances between input vectors into distances between output vectors. We advanced earlier known results by finding an exact solution to this problem for McCulloch-Pitts neurons. The obtained explicit formulas allow for detailed analysis of how the network connectivity and neuronal excitability affect the transformation of distances in neurons. As an application, we explored a simple model of information processing in the hippocampus, a brain area critically implicated in learning and memory. We found network connectivity and neuronal excitability parameter values that optimize discrimination between similar and distinct inputs. A decrease of neuronal excitability, which in biological neurons may be associated with decreased inhibition, impaired the optimality of discrimination.


Isolation and culture of human intestinal smooth muscle cells.
Intestinal smooth muscle cells were isolated from human bowel and maintained in culture through several passages. These cells were obtained by enzyme digestion of slices taken from the circular layer of the muscularis propria of human jejunum. When subcultured, they initially flattened out and then began proliferating after 3 days. After 3 weeks in culture, they began aggregating into ridges. Fluorohistochemical staining revealed numerous prominent actin stress fibers. When these cells were exposed to the C-terminal octapeptide of cholecystokinin they contracted in a dose-dependent fashion. The availability of human intestinal smooth muscle cells in culture will considerably enhance our ability to study the contractile, proliferative and connective tissue responses of the smooth muscle of the human gastrointestinal tract.


Interleukin-1 alpha stimulates osteoclast formation from peripheral blood monocytes and increases osteoclastic activity.
Interleukin-1 (IL-1) is produced by monocytes and marrow stromal cells and can stimulate bone resorption in tissue culture. In addition, IL-1 can induce osteoclast-like cell formation in long-term bone marrow culture. However, whether IL-1 can increase osteoclast formation by stimulating fusion of peripheral blood monocytes is not clear. In addition, the precise effect of IL-1 on osteoclastic activity is still not well known. Using the bioassay of osteoclast formation, osteoclast-free fetal calvariae were harvested from 14-day timed-pregnant Sprague-Dawley rats and cultured in BGJb medium for 10 days. On the 10th day, mononuclear cells were obtained from peripheral blood of 8-week-old female Sprague-Dawley rats through cardiac puncture and Ficoll-Paque density gradient separation method and co-cultured with osteoclast-free developing bone explant. On the same day, various concentrations of IL-1 alpha (1,10 or 100 U/ml) were added daily in the experimental dishes while only BGJb medium was added in the controls. In addition, 45Ca release assay and quantitation of nuclei per osteoclast were performed to evaluate the effect of IL-1 alpha on osteoclastic activity. Ten days after adding monocytes, there were 14.25 osteoclasts in the control, without IL-1 alpha; with 1 U of IL-1 alpha, there were 14.75 osteoclasts; with 10 U of IL-1 alpha, there were 18.00 osteoclasts; with 100 U of IL-1 alpha, there were 20.75 osteoclasts. In addition, IL-1 alpha stimulated the release of 45Ca and increased the number of average nuclei per osteoclast dose-dependently, indicating a significant increase in bone resorption. IL-1 alpha could increase osteoclast formation by stimulating the fusion of peripheral blood monocytes. In addition, IL-1 alpha is a potent stimulator of osteoclastic activity.


Headache in 25 consecutive patients with atrial septal defects before and after percutaneous closure--a prospective case series.
In contrast to patent foramen ovale that is highly prevalent in the general population, atrial septal defect (ASD) is a rare congenital heart defect. The effect of ASD closure on headache and migraine remains a matter of controversy. The objectives of our study were (1) to determine headache prevalence in consecutive patients with ASD scheduled for percutaneous closure for cardiologic indications, using the International Classification of Headache Disorders and (2) to compare headache characteristics before and after closure of ASD. In this observational case series no a priori power analysis was performed. Twenty-five consecutive patients were prospectively included over 27 months. Median duration of follow-up was 12 months [interquartile range 0]. Prevalence of active headache seemed to be higher compared with the general population: any headaches 88% (95% confidence interval 70-96), migraine without aura 28% (14-48), migraine with aura 16% (6-35). After ASD closure, we observed a slightly lower headache frequency (median frequency 1.0 [2.6] vs. 0.3 [1.5] headaches per month; P = .067). In patients with ongoing headaches, a significant decrease in headache intensity (median VAS 7 [3] vs. 5 [4]; P = .036) was reported. Three patients reporting migraine with aura before the intervention noted no migraine with aura attacks at follow-up, 2 of them reported ongoing tension-type headache, 1 migraine without aura. In summary, this prospective observational study confirms the high prevalence of headache, particularly migraine, in ASD patients and suggests a possible small beneficial effect of ASD closure.


Adherence to 1997 diabetes screening guidelines in a large ambulatory clinic.
The purpose of this study was to evaluate whether the 1997 American Diabetes Association screening guidelines were being implemented by primary care providers. A retrospective health record review was undertaken in a large midwestern ambulatory care clinic. A master list was developed of clients aged 45 to 54 years who had been given a physical examination between January 1, 1998, and June 30, 1998. A total of 310 records were systematically selected and abstracted. Data were analyzed using descriptive statistics. Although all subjects met the age criterion by design, and a high percent were high risk, only 57.7% were screened for diabetes. Adherence to the 1997 screening guidelines was inadequate in this practice setting; therefore the authors suggest replicating this study in other practice settings. Diabetes educators should continue to promote the practice of screening high-risk individuals of all ages.


Insulin-like growth factors induce apoptosis as well as proliferation in LIM 1215 colon cancer cells.
The insulin-like growth factor (IGF) system plays an important role in cell proliferation and survival. However, more recently, a small number of studies have shown that IGFs induce apoptosis in some cells. Our initial studies showed this occurred in LIM 1215 colon cancer cells but not RD rhabdomyosarcoma cells. IGFs induced both proliferation and apoptosis in LIM 1215 cells, and the induction of apoptosis was dose-dependent. [R54, R55]IGF-II, which binds to the IGF-I receptor with normal affinity but does not bind to the IGF-II receptor, induced apoptosis to the same extent as IGF-II, whereas [L27]IGF-II, which binds to the IGF-I receptor with 1000-fold reduced affinity, had no effect on apoptosis. These results suggest that the IGF-I receptor is involved in induction of apoptosis. Western blot analyses demonstrated that Akt and Erk1/2 were constitutively activated in RD cells. In contrast, phosphorylation of Akt and Erk1/2 were transient and basal expression of Akt protein was lower in LIM 1215 cells. Analysis of apoptosis-related proteins showed that IGFs decreased pro-caspase-3 levels and increased expression of pro-apoptotic Bad in LIM 1215 cells. IGFs co-activate proliferative and apoptotic pathways in LIM 1215 cells, which may contribute to increased cell turnover. Since high turnover correlates with poor prognosis in colorectal cancer, this study provides further evidence for the role of the IGF system in its progression.


External beam management of stage I and II uterine cancer.
This review article highlights the treatment paradigms for early-stage endometrial cancer with a focus on the role of external beam radiation therapy. We aim for this review to serve as an introductory resource for gynecological oncologists, radiation oncologists, medical oncologists, and other practitioners to understand the treatments for this disease. The main treatment of endometrial cancer is surgical resection with total hysterectomy and bilateral salpingo-oophorectomy. The benefit of adjuvant radiation after surgery is primarily to prevent local recurrence. Patients with low risk of recurrence can be observed post-operatively. Vaginal cuff brachytherapy, which has been shown to be equally effective as pelvic radiation with fewer side effects, is typically recommended for high-intermediate risk patients (with characteristics such as lymphovascular space invasion, high grade, or significant myometrial invasion). In the adjuvant setting, pelvic radiation therapy is reserved for patients who have deeply invasive stage I grade 2 or 3 disease, stage II disease, and non-endometrioid histologies. In patients who are not medically operable, definitive treatment consists of brachytherapy±pelvic external beam radiation therapy. We have highlighted the main acute and long-term side effects of pelvic radiation as well as recommendations for symptom management and summarized promising evidence showing improved rates of toxicities with more conformal radiation techniques.


Commercial bumble bee Bombus impatiens (Hymenoptera: Apidae) as a pollinator in lowbush blueberry (Ericale: Ericaceae) fields.
Here, we evaluate the potential of the bumble bee Bombus impatiens Cresson, obtained from commercial colonies, as a pollen vector for lowbush blueberry, Vaccinium augustifolium Aiton. We wanted to gain insight into the relationships between pollination by introduced bumble bees, the categories of seeds produced, and the weight and the maturity of the blueberries. The effect of B. impatiens foraging in blueberry stands was measured quantitatively through fruit set and seed set analysis. We created a density gradient of B. impatiens by clustering 72 small hives at the southern extremity of blueberry fields located in Girardville (49 degrees 00' N, 72 degrees 33' W), Quebec, Canada. Observers recorded plant and insect data in 52 plots of 1 by 10 m, distributed at distances ranging from 25 to 1,500 m from the hives. From these data, we evaluated the fruit set rate, the weight and maturity of the berries, and the number of seed structures per berry, including true seeds of large, medium, and small size, pseudo-seeds, and ovules. Positive correlations were found between the density of B. impatiens and fruit set as well as the number of large seeds per berry. Large seeds influenced the weight and maturity of berries. B. impatiens acted as a "near-nest central forager" and increased fruit set and seed production up to 100 and 150 m respectively, from the hives.


Therapeutic effects of triptolide on interleukin-10 gene-deficient mice with colitis.
Triptolide, the principal active ingredient in the extract of Chinese herb Tripterygium wilfordii Hook , has both anti-inflammatory and immunomodulatory activities. However, the potential therapeutic role of triptolide in IBD was still unknown. Interleukin-10 deficient mice, a well characterized experimental model of inflammatory bowel disease, spontaneously developed a Th1 T cell-mediated colitis with many similarities to Crohn's disease. This study was designed to investigate the therapeutic effect of triptolide on the chronic colitis in IL-10-/- mice. Triptolide was intraperitoneally administrated every another day for 8 weeks to IL-10-/- mice. The gross and histological appearances of the colon, the level of inflammatory mediators and transcription factor activation in the colon were evaluated and compared with the control group. The 8-week administration of triptolide resulted in a significant decrease in the severity of colitis, together with lower production of TNF-alpha ,IFN-gamma and IL-4 in colon. The level of serum amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and IL-23 in colon were also downregulated after treatment. Furthermore, administration of triptolide markedly reduced NF-small ka, CyrillicB activation in colon mucosa of IL-10-/- mice. The efficacy of tritpolide treatment for the reduction of intestinal inflammation in IL-10-/- mice is a result of both anti-inflammatory and immunosuppressive activity. Triptolide holds significant potential for clinical applications for CD treatment.


Inhibition of DNA synthesis by an electrophilic metabolite of benzo[a]pyrene.
Mitogen-stimulated scheduled DNA synthesis and DNA excision repair in human lymphocytes, as well as DNA polymerase a activity in a cell-free system, were inhibited by an electrophilic metabolite of benzo[a]pyrene. This metabolite, (+/-)-anti-(7r,8t)-dihydroxy-(9,10t)-epoxy-7,8,9,10-tetrahyd robenzo[a]pyrene (BPDE), covalently binds to cellular macromolecules and is mutagenic, carcinogenic, and cytotoxic. Human lymphocytes treated with BPDE at concentrations greater than 500-800 ng/ml showed decreases in both mitogen-stimulated DNA synthesis and excision repair of damaged DNA but did not exhibit overt cytotoxicity (excluded trypan blue and maintained an adenylate charge of greater than 0.7). Formation of, and total concentration of, BPDE-DNA adducts was not correlated with inhibition of DNA synthesis. DNA polymerase alpha studies using a cell-free system showed that enzymatic activity was not diminished when purified polymerase was treated with BPDE prior to the addition of template DNA. When the template DNA concentration was varied, BPDE inhibition of enzyme activity was uncompetitive. BPDE inhibition of enzyme activity was found to be noncompetitive when concentrations of dATP, dCTP, or dTTP were varied and competitive when the concentration of dGTP was varied. The data indicate that BPDE competitively inhibits interaction of dGTP with the template-DNA polymerase alpha complex.


Osteoblast adhesion and proliferation on poly(3-octylthiophene) thin films.
In this study we assessed the suitability of semiconducting P3OT thin films (30 nm) to sustain attachment, spreading, and proliferation of MC3T3-E1 osteoblasts. Cell area correlated with surface wettability: area was larger on the more hydrophilic surface (TCPS) and lower on the more hydrophobic surface (P3OT). Cells were rounder, characterized by higher circularity values, on TCPS and Si compared to P3OT. P3OT proliferation rate at 24 h fell twofold after 48 h, then recovered at 72 h to a value significantly higher than that on TCPS. Presoaking experiments showed no evidence of cytotoxic effects or leachants from P3OT. Overall, we conclude that P3OT is a viable substrate for osteoblast attachment and proliferation.


Telehealth Use in a Rural State: A Mixed-Methods Study Using Maine's All-Payer Claims Database.
This study assesses trends in telehealth use in Maine-a rural state with comprehensive telehealth policies-across payers, services, and rurality, and identifies barriers and facilitators to the adoption and use of telehealth services. Using a mixed-methods approach, researchers analyzed data from Maine's All Payer Claims Database (2008-2016) and key informant interviews with health care organization leaders to examine telehealth use and explore factors impacting telehealth adoption and implementation. Despite a 14-fold increase in the use of telehealth over the 9-year study period, use remains low-0.28% of individuals used telehealth services in 2016 compared with 0.02% in 2008. Services provided via telehealth varied by rurality; speech language pathology (SLP) was the most common type of service among rural residents, while psychiatric services were most common among urban residents. Medicaid was the primary payer for over 70% of telehealth claims in both rural and urban areas of the state, driving the increase of telehealth claims over time. Issues challenging organizations seeking to deploy telehealth included provider resistance, staff turnover, provider shortages, and lack of broadband. Key informants identified inadequate and inconsistent reimbursement as barriers to comprehensive, systematic billing for telehealth services, resulting in underrepresentation of telehealth services in claims data. Claims covered by Medicaid account for much of the observed expansion of telehealth use in Maine. Telehealth appears to be improving access to behavioral health and SLP services. Provider shortages, broadband, and Medicare and commercial coverage policies limit the use of telehealth services in rural areas.


Patterned electroconvective states in a bent-core nematic liquid crystal.
We report the results of investigations on the anisotropic electrohydrodynamic states arising in a highly conducting, planarly aligned, bent-core nematic liquid crystal driven by ac fields of frequency f in the range from 10 Hz to 1 MHz. Pattern morphologywise, two f regimes are distinguished. The low-f regime, wherein the primary bifurcation is to a state of periodic longitudinal stripes (LS), extends to an unprecedentedly large f, in the range 150-550 kHz, depending on the temperature T. This is followed by the high-f regime wherein periodic normal stripes (NS) constitute the primary instability. Both instabilities involve predominant director modulations and streamlines in the layer plane. The transitional frequency between the two regimes is linear in temperature. The curve V(c)(f) shows a nonlinear increase for the LS state and decrease for the NS state. V(c)(T) is an ever increasing curve close to the nematic-isotropic point for both states. The wavenumber of LS varies directly as V, and that of NS shows nearly the same behavior. The pattern period versus f is increasing for LS but decreasing for NS. Both instability states exhibit complex, light-polarization-dependent lens action. Well above the threshold, disclination loops of regular geometry appear along the stripes. They drift in a coordinated manner along the flow lines. At very high voltages, the instability turns strongly time dependent. The current models of anisotropic convection based on static electrical parameters fail to account for the observed instabilities.


[Influence of odor cueing on the retrieval processes for autobiographical memories].
This study investigated the influence of odor cueing on the retrieval process for autobiographical memories. In Experiment 1, forty two participants were asked to retrieve autobiographical memories in response to a label cue only, or a label cue with a congruent odor cue, or label cue with an incongruent odor cue. The results showed that in the label cue only condition and the incongruent odor cue condition, the latency with a concurrent task was slower than with no concurrent task. However, this was not observed in the congruent odor cue condition. In order to verify the results of Experiment 1, in Experiment 2, twenty participants were investigated with regard to autobiographical memories cued by odors having a high or low rate of identification. The results showed that memories cued by odors with a high rate of identification were retrieved faster. These results suggest that dual processing by odor and label promotes retrieval processes for autobiographical memories.


Types and amounts of complementary foods and beverages consumed and growth, size, and body composition: a systematic review.
Systematic reviews (SRs) were conducted by the Nutrition Evidence Systematic Review (NESR) team for the USDA's and the Department of Health and Human Services' Pregnancy and Birth to 24 Months Project. The aim was to describe the SRs examining the relationship between types and amounts of complementary foods and beverages (CFBs) and growth, size, and body-composition outcomes. The NESR team collaborated with subject matter experts to conduct this SR. The literature was searched and screened using predetermined criteria. For each included study, data were extracted and risk of bias was assessed. The evidence was qualitatively synthesized to develop a conclusion statement, and the strength of evidence was graded. This SR includes 49 articles that examined type, amount, or both of CFBs consumed and growth, size, and body-composition outcomes. Moderate evidence suggests that consuming either different amounts of meat, meat instead of iron-fortified cereal, or types of CFBs with different fats or fatty acids does not favorably or unfavorably influence growth, size, or body composition. In relation to overweight/obesity, insufficient evidence is available with regard to the intake of meat or CFBs with different fats or fatty acids. Limited evidence suggests that type and amount of fortified infant cereal does not favorably or unfavorably influence growth, size, body composition, or overweight/obesity. Limited evidence suggests that sugar-sweetened beverage consumption during the complementary feeding period is associated with increased obesity risk in childhood but is not associated with other measures of growth, size, or body composition. Limited evidence showed a positive association between juice intake and infant weight-for-length and child body mass index z scores. Insufficient evidence is available on other CFBs or dietary patterns in relation to outcomes. Although several conclusions were drawn, additional research is needed that includes randomized controlled trials, examines a wider range of CFBs, considers issues of reverse causality, and adjusts for potential confounders to address gaps and limitations in the evidence.


Rationale for a national multi-centre study of magnetic resonance imaging screening in women at genetic risk of breast cancer.
In 1994, the UK National Health Service identified as a research priority that magnetic resonance imaging (MRI) should be assessed as a screening tool for young, pre-menopausal women who are at a high genetic risk of developing breast cancer. In 1997 a national multicentre study was established to compare MRI with X-ray mammography as a method for screening for breast cancer in this group of women. This paper reviews the relevant literature and describes the rationale that led to the setting up of this study.


Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage.
To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.


Updates on the genetic variations of norovirus in sporadic gastroenteritis in Chungnam Korea, 2009-2010.
Previously, we explored the epidemic pattern and molecular characterization of noroviruses (NoVs) isolated in Chungnam, Korea in 2008, and the present study extended these observations to 2009 and 2010. In Korea, NoVs showed the seasonal prevalence from late fall to spring, and widely detected in preschool children and peoples over 60 years of age. Epidemiological pattern of NoV was similar in 2008 and in 2010, but pattern in 2009 was affected by pandemic influenza A/H1N1 2009 virus. NoV-positive samples were subjected to sequence determination of the capsid gene region, which resolved the isolated NoVs into five GI (2, 6, 7, 9 and 10) and eleven GII genotypes (1, 2, 3, 4, 6, 7, 8, 12, 13, 16 and 17). The most prevalent genotype was GII.4 and occupied 130 out of 211 NoV isolates (61.6%). Comparison of NoV GII.4 of prevalent genotype in these periods with reference strains of the same genotype was conducted to genetic analysis by a phylogenetic tree. The NoV GII.4 strains were segregated into seven distinct genetic groups, which are supported by high bootstrap values and previously reported clusters. All Korean NoV GII.4 strains belonged to either VI cluster or VII cluster. The divergence of nucleotide sequences within VI and VII intra-clusters was > 3.9% and > 3.5%, respectively. The "Chungnam(06-117)/2010" strain which was isolated in June 2010 was a variant that did not belong to cluster VI or VII and showed 5.8-8.2%, 6.2-8.1% nucleotide divergence with cluster VI and VII, respectively.


MicroRNAs as Targets for Cancer Diagnosis: Interests and Limitations.
MicroRNAs are small RNAs with ability to attach to the large number of RNA that regulate gene expression on post-transcriptional level via inhibition or degradation of specific mRNAs. MiRNAs in cells are the primary regulators of functions such as cell growth, differentiation, and apoptosis and considerably influence cell function. The expression levels of microRNAs change in human diseases, including cancer. These changes highlight their essential role in cancer pathogenesis. Ubiquitous irregular expression profiles of miRNAs have been detected in various human cancers using genome-wide identification techniques, which are emerging as novel diagnostic and prognostic cancer biomarkers of high specificity and sensitivity. The measurable miRNAs with enhanced stability in blood, tissues, and other body fluids provide a comprehensive source of miRNA-dependent biomarkers for human cancers. The leading role of miRNAs as potential biomarkers in human cancers is discussed in this article. In addition, the interests and difficulties of miRNAs as biomarkers have been explored.


Bioactive proteins in human milk: mechanisms of action.
Human milk contains a multitude of bioactive proteins, with very diverse functions. Some of these proteins are involved in the synthesis and expression of milk, but the majority appears to have evolved to provide physiological activities in the breast-fed infant. These activities are exerted by a wide variety of mechanisms and have largely been unraveled by in vitro studies. To be active in the gastrointestinal tract, these proteins must be able to resist proteolytic degradation, at least for some time. We have evaluated the human milk proteins lactoferrin, haptocorrin, alpha(1)-antitrypsin, and transforming growth factor -beta in an in vitro digestion model, mimicking the conditions of the infant gastrointestinal milieu. These bioactive proteins are resistant against proteolysis and can remain intact or as larger fragments through passage of the gastrointestinal tract. In vitro digestibility assays can be helpful to assess which human milk proteins can resist proteolysis and to what extent.


Probiotics in Counteracting the Role of Neutrophils in Cancer Metastasis.
Neutrophils are known for their role geared towards pathogen clearance by different mechanisms that they initiate, primarily by the release of neutrophil extracellular traps (NETs). However, their immune-surveillance capacity accompanied with plasticity in existing as interchangeable subsets, discovered recently, has revealed their property to contribute to complex cancer pathologies including tumor initiation, growth, angiogenesis and metastasis. Although there is a growing body of evidence suggesting a critical balance between the protumoral and antitumoral neutrophil phenotypes, an in-depth signaling pathway analysis would aid in determination of anticipatory, diagnostic and therapeutic targets. This review presents a comprehensive overview of the potential pathways involved in neutrophil-triggered cancer metastasis and introduces the influence of the microbial load and avenues for probiotic intervention.


The power and possibility in listening.
In this column, the author describes the power of listening. There are three engaging listening modalities that are explored that form a foundation for exploring the power and possibility in listening: living true presence, participating in the council process; and engaging in strategic questioning. Several strategic questions are raised to explore the possibility of integrating these listening modalities into the nursing academy.


The role of ultrasonography in monitoring long-standing rheumatoid arthritis: a pilot study.
Rheumatoid arthritis (RA) is a condition that poses many diagnostic problems. As a result, it is often diagnosed too late, which makes effective treatment more difficult. The course of the disease is chronic, and it causes irreversible changes in the musculoskeletal system, as well as bone destruction, and this in turn impairs the proper monitoring of the treatment. Therefore, in order to assess the treatment's efficacy, as well as a clinical examination of the patient and laboratory tests, diagnostic imaging is being used more frequently in routine practice. The aim of this paper is to assess the usefulness of power Doppler ultrasonography in the assessment of MCP joints in patients with chronic RA (LSRA), in comparison with DAS28, X-ray, and MRI. The study involved 26 patients with LSRA, treated with biologics. It lasted for a year. At the moment of enrolment, the condition had lasted for a minimum of 5 years, and DAS28 was > 5.1. The patients had visits every three months. During every visit, a PDUS test was performed and the DAS28 was determined. In the first and last month of the study the patients underwent X-ray and MRI tests. At the end of the study, the DAS28 of 26 (100%) patients was lower or equal to 3.2. Based on PDUS and MRI tests, no synovitis was found in 21 (81%) and 18 (69%) patients, respectively. According to the MRI results, radiological changes progressed in 5 (19%) of them. All patients who showed progress of radiological changes also had visible synovitis during their PDUS test. PDUS in patients with LSRA can be helpful in selecting patients, who are likely to develop a progression of radiological changes.


Robust detection and tracking of annotations for outdoor augmented reality browsing.
A common goal of outdoor augmented reality (AR) is the presentation of annotations that are registered to anchor points in the real world. We present an enhanced approach for registering and tracking such anchor points, which is suitable for current generation mobile phones and can also successfully deal with the wide variety of viewing conditions encountered in real life outdoor use. The approach is based on on-the-fly generation of panoramic images by sweeping the camera over the scene. The panoramas are then used for stable orientation tracking, while the user is performing only rotational movements. This basic approach is improved by several new techniques for the re-detection and tracking of anchor points. For the re-detection, specifically after temporal variations, we first compute a panoramic image with extended dynamic range, which can better represent varying illumination conditions. The panorama is then searched for known anchor points, while orientation tracking continues uninterrupted. We then use information from an internal orientation sensor to prime an active search scheme for the anchor points, which improves matching results. Finally, global consistency is enhanced by statistical estimation of a global rotation that minimizes the overall position error of anchor points when transforming them from the source panorama in which they were created, to the current view represented by a new panorama. Once the anchor points are redetected, we track the user's movement using a novel 3-degree-of-freedom orientation tracking approach that combines vision tracking with the absolute orientation from inertial and magnetic sensors. We tested our system using an AR campus guide as an example application and provide detailed results for our approach using an off-the-shelf smartphone. Results show that the re-detection rate is improved by a factor of 2 compared to previous work and reaches almost 90% for a wide variety of test cases while still keeping the ability to run at interactive frame rates.


Fungal Septic Knee Arthritis Caused by Aspergillus fumigatus following Anterior Cruciate Ligament Reconstruction.
Postoperative infections after arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) represent a rare but severe complication. An extremely rare case of Aspergillus septic arthritis in a 27-year-old patient following arthroscopic ACLR is reported. The patient presented with signs of knee infection 14 days after ACLR. Two consecutive arthroscopic debridements were performed, while eventually histopathology, cultures and multiplex PCR test revealed Aspergillus identified as A. fumigatus by mass spectrometry. The patient commenced long-term treatment with voriconazole. Fungal arthritis or osteomyelitis following ACLR has a mild local and general inflammatory reaction when compared to the bacterial ones. Nevertheless, such infections may lead to aggressive osseous destruction and necrosis. A high index of suspicion is of utmost importance for early detection, while microscopic, histological examination and multiplex PCR may be more helpful for the diagnosis than cultures since cultures are more time-consuming and may vary depending on different factors.


Urogenital atrophy.
The major cause of urogenital atrophy in menopausal women is estrogen loss. The symptoms are usually progressive in nature and deteriorate with time from the menopausal transition. The most prevalent urogenital symptoms are vaginal dryness, vaginal irritation and itching. The classical changes in an atrophic vulva include loss of labial and vulvar fullness, with narrowing of the introitus and inflamed mucosal surfaces. Dyspareunia and vaginal bleeding from fragile atrophic skin are common problems. Other urogenital complaints include frequency, nocturia, urgency, incontinence and urinary tract infections. Atrophic changes of the vulva, vagina and lower urinary tract can have a large impact on the quality of life of the menopausal woman. However, hormonal and non-hormonal treatments can provide patients with the solution to regain previous level of function. Therefore, clinicians should sensitively question and examine menopausal women, in order to correctly identify the pattern of changes in urogenital atrophy and manage them appropriately.


[Cerebral salt wasting syndrome: experimental study in rats].
The cerebral salt wasting syndrome (CSWS) is characterized by hyponatraemia secondary to excessive natriuesis with osmotic duiresis. This syndrome, frequently, occurs after subarachnoid haemorrhage (SAH), but may occur after any acute cerebral aggression. The aim of the study was to assess the frequency of the CSWS in animal models with, SAH, cerebral ischemia (CI), and cranial trauma (CT), and its correlation with the secretion of brain natriuretic peptide (BNP). Four groups of rats were selected: group SAH (n=7) consisted of SAH induced by perforation of the carotid artery in its intracerebral part; group CI (n=7) consisted of CI induced by ligature of the carotid artery; group CT (n=7) consisted of induced CT; and a control group Sham (n=7). Weight, serum sodium, BNP, and urinary sodium, were measured at baseline and 24 hours after. Rats with SAH had significant natriuresis and diuresis with negative sodium balance (-95.9+/-447.4 mumol) with a significant difference (P<0.05) compared to the rats of the CI and the Sham groups. There was no difference in the 24 hours level of BNP between the four different groups. We conclude that SAH, in animal models, induced high diuresis with negative sodium balance in the first 24 hours. These findings were absents in the others groups. This was independent of the BNP secretion and may correspond to the early occurrence of a CSWS.


Characteristics of the Berkeley multicusp ion source.
The performance of a cubical permanent magnet generated line-cusp ion source has been investigated for use with neutral beam injectors. This source has been operated with discharge currents greater than 500 A and ion current densities higher than 400 mA/cm2 at the extraction grid. The uniformity of the density profile across the extraction area is found to be dependent on the gas pressure. By using a fast Langmuir probe sweeping circuit, the electron temperature and the plasma density and potential have been analyzed for different discharge powers and gas pressures. The heat load on the plasma grid when it is electrically floating or connected to the negative cathode has been compared calorimetrically. The use of lanthanum hexaboride and impregnated oxide cathodes have been investigated for the purpose of long pulse operation. The phenomenon of mode flipping is found to occur quite frequently during a discharge with these magnetic-field-free cathodes. Species composition as a function of discharge power and chamber length is measured by a mass spectrometer.


Emu oil based nano-emulgel for topical delivery of curcumin.
Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis.


Molecular shape and ATP binding activity of rat p50, a putative mammalian homologue of RuvB DNA helicase.
Based on partial amino acid sequences of p50 purified from a high-salt buffer extract of a rat liver nuclear matrix fraction, p50 cDNA was cloned and sequenced, and its amino acid sequence was predicted. The sequence contained helicase motifs, and showed homology with RuvB DNA helicase of Thermus thermophilus and an open reading frame for an unknown 50.5 k protein of Saccharomyces cerevisiae. p50 was expressed as a GST-fusion protein and antiserum against the protein was generated. p50 was localized to the nuclear matrix by cell fractionation and immunoblotting. p50 bound to ATP-Sepharose beads. Ultracentrifugation and gel filtration analyses showed that p50 in rat liver and Xenopus egg mitotic extracts exists as large complexes corresponding to 697 k and 447 k, respectively. A 50 k protein reactive with p50 antibodies was detected not only in rat liver nuclei, but also in a Xenopus egg cytoplasm fraction and a S. cerevisiae extract. This suggests that this putative DNA helicase is present in a wide variety of species ranging from yeast to mammals.


Low salt diet and treatment of hypertension: an old story.
A relatively low salt intake is nowadays considered one of the characteristics of a healthy diet in the Western world because several disorders appear to be unfavorably affected by excessive salt intake with the diet. The first notion about a relation between salt intake and blood pressure traces back to 2500 bc in an ancient Chinese medical textbook. This paper focuses on studies about salt and hypertension in the first half of the 20th century. The first papers in this field were published from the beginning of the century, but due to a modest scientific content were still not considered in the 1940s to provide sufficient evidence in favor of a salt restriction in hypertensive patients. A major practical contribution came from the Kempner rice diet, an effective antihypertensive dietary treatment which included a severe restriction of salt intake. After that, several studies in animals and humans showed that, with regard to the antihypertensive effect, the key element of the Kempner diet was the low salt content. By the first years of the 1950s, the evidence was already available that salt restriction is an effective antihypertensive treatment and that adherence to the treatment should be assessed by monitoring urinary electrolytes.


[Autologous buccal mucosal graft pre-transplantation for urethral reconstruction of complicated hypospadias].
Applicate autologous buccal mucosal graft pre-transplantation for urethral reconstruction of complicated hypospadias by staging. From 1999 to 2003, 40 patients have been treated by method of autologous buccal mucosal graft pre-placing. There were two models: graft onlay and graft-tube for urethral reconstruction, and the 2rd operation was accomplished half year later. All patients healed without urethral fistula. The method is valuable for treatment of complicated hypospadias.


New Insights Into c.815_824dup Pathogenic Variant of BRCA1 in Inherited Breast Cancer: A Founder Mutation of West African Origin.
Founder mutations have been reported in BRCA1 and BCRA2 in different ethnic groups with inherited breast cancer. Testing of targeted mutations in specific populations is important for cancer prevention in mutation carriers. In Sub-Saharan Africa, only a few studies have reported specific founder mutations in inherited breast cancer. The pathogenic variant c.815_824dup of BRCA1 has been reported as the most frequent among African American populations with inherited breast cancer and was supposed to have a West African origin. Recent report from Senegal identified this variant in women with inherited breast cancer at the highest frequency ever reported. The variant was linked to a common haplotype confirming its founder effect in West Africa. In this article, we review the mutation history of c.815_824dup and discuss how it spread out of Africa through the transatlantic slave trade.


The role of psychotherapy in the treatment of depression: review of two practice guidelines.
We review two recent practice guidelines' assessments of the role of psychotherapy in the treatment of major depression in adults. We examine the practice guideline published by the American Psychiatric Association (APA) and that published by the Depression Guideline Panel of the Agency for Health Care Policy and Research. We focus on the guidelines' evaluations of psychotherapies, their statements about the role of psychotherapy in first-line treatment of depression, and the procedures they recommend for choosing among psychotherapies. We argue that the APA guideline understates the value of cognitive, behavioral, brief psychodynamic, and group therapies. Both guidelines understate the value of psychotherapy alone in the treatment of more severely depressed outpatients. The APA guideline overvalues the role of combined psychotherapy-pharmacotherapy regimens, particularly in view of the greater cost of this strategy. The APA guideline also makes recommendations about choosing among psychotherapies that are not well supported by empirical evidence. We conclude with some guidelines for guideline development.