Is Computed Tomography Imaging of Deviated Nasal Septum Justified for Obstruction Confirmation?
Third-party payers request objective confirmation of the nasal septum deviation (NSD) severity by computed tomography (CT) before authorizing financial support for septoplasty. Previous studies have provided contradictory results related to the link between obstruction severity and CT-measured angle of the NSD. The aim of this study was to investigate whether the diverse CT morphology of NSDs (including previously neglected types and shapes) could predict obstruction severity. The study included 225 patients with NSD. The CT morphology of the septum was analyzed using 5 different classifications of NSD that are commonly used in the clinical practice and research. The angle of NSD was also measured. Nasal obstruction was assessed by the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire. A relationship between CT morphology and the angle of the NSD and NOSE scores was analyzed using appropriate regression models. Patients with NSDs located in the anterior part of the septum always have some degree of nasal obstruction, while those with posterior NSDs did not necessarily report obstruction symptoms no matter how complicated NSD they have. Regression analysis did not reveal any causal relationship between NOSE scores and CT morphology and the angle of NSD. The presence of spurs and whether they divide nasal passages have no statistically significant predictive effect on the obstruction severity. The CT morphology and the angle of the NSD could not predict severity of the nasal obstruction. Requesting CT examination just to objectively confirm nasal obstruction is not justified.


Electrospray ionisation tandem mass spectrometry in the characterisation of isomeric benzofurocoumarins.
A set of aminoalkoxy-substituted, differently annullated furocoumarins, differing in the position of the aminoalkoxy chain and in the unsaturation level of the fused ring, has been subjected to electron impact and electrospray ionisation (ESI) experiments. In order to achieve a distinct characterisation of isomeric compounds, which partially failed under electron impact conditions, collision-induced dissociation experiments were performed on protonated molecules. The breakdown curves obtained by varying the tickle voltage on an ion trap ESI instrument led to the desired characterisation.


Acute laryngeal trauma: a review of 77 patients.
Acute laryngeal trauma is a rare injury. In the past 18 years, 77 patients with acute laryngeal trauma have been evaluated at our institution. Each patient's care was overseen by the senior author (E.S.P.). The 61 patients who were seen within 48 hours of their accident are compared with those treated after 48 hours. All patients are classified by both injury (groups 1 through 5) and treatment (types I through III). Results are reported for voice, airway, and swallowing. Our methods of evaluation and treatment are outlined, and controversial aspects of patient management are addressed. We conclude that conservative treatment of group 1 and 2 injuries is 100% effective, expeditious repair of laryngeal injuries greatly reduces poor outcome, and the type of injury can be used to roughly predict patient outcome. Further, with use of current methods of diagnosis and management, almost all patients will be decannulated (98%) with functional speech (100%) and normal deglutition (100%).


Pulmonary Arteriovenous Malformations: What the Interventional Radiologist Should Know.
Pulmonary arteriovenous malformations (PAVMs) are abnormal connections between the pulmonary artery and pulmonary vein bypassing the normal capillary bed causing a right-to-left shunt. The majority (80-90%) of PAVMs are associated with hereditary hemorrhagic telangiectasia (HHT). PAVMs may be asymptomatic or present with symptoms of hypoxia, shortness of breath, migraines, sequelae of paradoxical embolization, or rupture. Transcatheter embolization has become the standard of care. This article will review the clinical presentation, workup, genetics, imaging findings, embolization, complications, and follow-up for patients with PAVMs.


Gall-Inducing Parasites: Convergent and Conserved Strategies of Plant Manipulation by Insects and Nematodes.
Gall-inducing insects and nematodes engage in sophisticated interactions with their host plants. These parasites can induce major morphological and physiological changes in host roots, leaves, and other tissues. Sedentary endoparasitic nematodes, root-knot and cyst nematodes in particular, as well as gall-inducing and leaf-mining insects, manipulate plant development to form unique organs that provide them with food from feeding cells. Sometimes, infected tissues may undergo a developmental switch resulting in the formation of aberrant and spectacular structures (clubs or galls). We describe here the complex interactions between these plant-reprogramming sedentary endoparasites and their infected hosts, focusing on similarities between strategies of plant manipulation. We highlight progress in our understanding of the host plant response to infection and focus on the nematode and insect molecules secreted in planta. We suggest thatlooking at similarities may identify convergent and conserved strategies and shed light on the promise they hold for the development of new management strategies in agriculture and forestry.


[Cyclooxygenase inhibitors in chemoprevention and treatment of esophageal squamous cell carcinoma].
Cyclooxygenase inhibitors (COX) are a complex group of pharmacological compounds characterized by significant efficacy in chemoprevention of epithelial origin tumors, especially colorectal ones. It was found that inducible isoform of COX - COX-2 plays an important role in cancer growth and dissemination, e.g., by increase of cellular proliferation, reduction of apoptosis, promotion of local invasiveness and angiogenesis. COX inhibitors decrease prostaglandins' synthesis, but COX-independent mechanisms of their preventive and therapeutical activity were also proven. The influence of COX inhibitors on growth of esophageal squamous cell carcinoma and its precursor lesions was not completely clear. Most studies based on human cancer cell lines revealed antiproliferative and proapoptotic ability of both nonselective (previously called non-steroidal antiinflammatory drugs--NSAIDs) and selective COX-2 inhibitors (coxibs). In in vivo studies performed on animals exposed to chemical carcinogens, the chemopreventive effect was achieved exclusively after administration of experimental selective COX-2 inhibitors, but in the only human trial, supplementation of selective COX-2 inhibitor--celecoxib turned out ineffective. However, many epidemiological data proved effect of prolonged administration of nonselective COX inhibitors, especially acetylsalicylic acid on decreased risk of esophageal squamous cell carcinoma. Few reports concerning application of selective COX-2 inhibitors in patients with invasive squamous cell carcinoma are insufficient for ultimate evaluation of this method of therapy.


A comprehensive infectious disease management system.
An efficient electronic management system is now an essential tool for the successful management and monitoring of those affected by communicable infectious diseases (Human Immunodeficiency Virus - HIV, hepatitis C - HEP C) during the course of the treatment. The current methods which depend heavily on manual collecting, compiling and disseminating treatment information are labor-intensive and time consuming. Clinics specialized in the treatment of infectious diseases use a mix of electronic systems that fail to interact with each other, result in data duplication, and do not support treatment of the patient as a whole. The purpose of the Infectious Disease Management System is to reduce the administrative overhead associated with data collection and analysis while providing correlation abilities and decision support in accordance with defined treatment guidelines. This Infectious Disease Management System was developed to: Ensure cost effectiveness by means of low software licensing costs, Introduce a centralized mechanism of collecting and monitoring all infectious disease management data, Automate electronic retrieval of laboratory findings, Introduce a decision support mechanism as per treatment guidelines, Seamlessly integrate of application modules, Provide comprehensive reporting capabilities, Maintain a high level of user friendliness.


Assessing the role of inferior olivary sensory signaling in the expression of conditioned eyeblinks using a combined glutamate/GABAA receptor antagonist protocol.
The inferior olive (IO) is a major component of the eyeblink conditioning neural network. The cerebellar learning hypothesis assumes that the IO supplies the cerebellum with a "teaching" unconditioned stimulus input required for the acquisition of the conditioned response (CR) and predicts that inactivating this input leads to the extinction of CRs. Previous tests of this prediction attempted to block the teaching input by blocking glutamatergic sensory inputs in the IO. These tests were inconclusive because blocking glutamate neurotransmission in the IO produces a nonspecific tonic malfunction of cerebellar circuits. The purpose of the present experiment was to examine whether the behavioral outcomes of blocking glutamate receptors in the IO could be counterbalanced by reducing GABA-mediated inhibition in the IO. We found that injecting the IO with the glutamate antagonist γ-d-glutamylglycine (DGG) abolished previously learned CRs, whereas injecting the GABA(A) receptor antagonist gabazine at the same site did not affect CR incidence but shortened CR latencies and produced tonic eyelid closure. To test whether the glutamate antagonist-induced behavioral deficit could be offset by elevating IO activity with GABA(A) antagonists, rabbits were first injected with DGG and then with gabazine in the same training session. While DGG abolished CRs, follow-up injections of gabazine accelerated their recovery. These findings suggest that the level of IO neuronal activity is critical for the performance of CRs, and that combined pharmacological approaches that maintain spontaneous activity at near normal levels hold tremendous potential for unveiling the role of IO-mediated signals in eyeblink conditioning.


Pharmacokinetics of cyclosporin: influence of rate of constant intravenous infusion in renal transplant patients.
1 The pharmacokinetics of cyclosporin were studied in 12 renal transplant patients. Five patients received a constant rate (7 mg kg-1 day-1) intravenous infusion over 72 h and the remainder received rates of 7, 4 and 10 mg kg-1 day-1, consecutively each for at least 24 h. 2 Plasma, separated at 37 degrees C, was analysed by h.p.l.c. 3 The data were best described by a biexponential model. 4 Following the 72 h infusion, a plateau was reached by 24 h and clearance was 0.60 l h-1 kg-1. 5 Clearance associated with the 10 mg kg-1 day-1 infusion rate (0.43 l h-1 kg-1) was estimated to be lower than that following the 4 and 7 mg kg-1 day-1 rates (0.52 and 0.54 l h-1 kg-1 respectively) but the difference is unlikely to be of clinical significance.


Inclusion Complexes of Citronella Oil with β-Cyclodextrin for Controlled Release in Biofunctional Textiles.
Biofunctional textiles with integrated drug-delivery systems can help in the fight against vector-borne diseases. The use of repellent agents derived from plants and oils is an alternative to DEET (N,N-diethyl-m-methylbenzamide), which has disadvantages that include toxic reactions and skin damage. However, some researchers report that oils can be ineffective due to reasons related to uncontrolled release. In this work, the mechanism of control of citronella oil (OC) complexed with β-cyclodextrin (βCD) on cotton (COT) and polyester (PES) textiles was investigated. The results obtained reveal that finishing cotton and polyester with β-cyclodextrin complexes allows for control of the release mechanism of the drug from the fabric. To assess the complexes formed, optical microscopy, SEM, and FTIR were carried out; the yield of complex formation was obtained by spectroscopy in the ultraviolet region; and controlled release was performed in vitro. Oil complexation with βCD had a yield of 63.79%, and it was observed that the release, which was in seconds, moved to hours when applied to fabrics. The results show that complexes seem to be a promising basis when it comes to immobilizing oils and controlling their release when modified with chemical crosslinking agents.


The "Five Risks algorithm": an easy tool for cardiovascular risk estimation.
The aim of this study is to provide an easy tool to identify patients with a high cardiovascular risk, especially those qualifying for lipid-lowering treatment. The decision to treat with lipid-lowering drugs was assessed with five new risk algorithms. The Five Risk algorithm (5R) takes into account male gender, high systolic blood pressure, high total cholesterol, smoking and high blood sugar as independent risk factors. Patients with three independent risk factors qualify for lipid-lowering treatment. Compared to the Framingham Risk Score, the 5R has a Kappa coefficient of 0.62. Compared to the SCORE, the Six Risk algorithm (6RDF) has a Kappa coefficient of 0.70. The 6RDF uses only four independent risk factors (male gender, high systolic blood pressure, high total cholesterol and smoking) but having diabetes or a family history of premature coronary heart disease are exclusion criteria for which treatment with lipid-lowering drugs is always indicated.


Haemophilus influenzae pneumonia in Melanesian adults: report of 15 cases.
In a prospective study of 170 adult patients with acute pneumonia, Haemophilus influenzae was found to be the aetiological agent in 15 cases (8.8%). The diagnosis in all cases was based on positive cultures of blood or percutaneous lung aspirate, or both. Chronic lung disease was significantly more common in patients with H influenzae pneumonia than in patients with pneumonia due to other organisms but age, sex, and smoking history did not differ significantly. Lobar consolidation was the most common radiological pattern, being present in 10 of the 15 cases. Type b was the commonest serotype isolated, but three cases were due to non-typable (non-capsulate) strains. All patients survived, responding well to treatment with penicillin, ampicillin, or chloramphenicol. Haemophilus influenzae should be considered as a possible cause of pneumonia in adults, particularly those with underlying chronic lung disease.


A national study of Helicobactor pylori infection in gastric biopsy specimens.
We investigated whether infection with Helicobacter pylori and signs of chronic active gastritis and intestinal metaplasia in gastric biopsy samples were inversely associated with Barrett's metaplasia. We studied gastric biopsy samples from 78,985 unique patients. Histologic findings were correlated with sociodemographic patient characteristics using multivariate logistic regression to calculate odds ratios and 95% confidence intervals. H pylori infection, chronic active gastritis, and intestinal metaplasia had similar epidemiologic patterns. The presence of each, based on histology analyses, was significantly associated with that of the others. They were also characterized by similar geographic distributions within the United States. All 3 disorders were more common among men and among Medicaid patients (compared with those with other insurance) and were inversely associated with Barrett's metaplasia (less frequent in patients with Barrett's metaplasia). H pylori infection and associated disorders, such as chronic active gastritis and intestinal metaplasia, are inversely associated with Barrett's metaplasia.


Performance of horizontal subsurface-flow treatment wetlands in fecal bacteria removal.
This work evaluated sub-surface flow (SSF) constructed wetlands and activated sludge plant efficiency in pathogen removal. The two were also compared. The removal of fecal bacteria (total coliforms, fecal coliforms, fecal streptococci) was evaluated. Analysis was carried out during one year by determining the amount of bacteria in the inflow and the outflow of four systems: three SSF systems (two were pilot plants and one a fully operating plant) and an activated sludge plant. MPN techniques were used to determine the quantity-value of the microorganisms. Percentages of fecal bacteria removal in wetlands systems were as good as (and sometimes better than) those recorded in the activated sludge plant. Optimal values of these bacteria were obtained in the outflow of the post-treatment pilot plant: very high bacterial removal percentages (>99%) were recorded. SFS constructed wetlands are a valid solution for the final treatment of the outflow of existing plants.


RGD modified PLGA/gelatin microspheres as microcarriers for chondrocyte delivery.
Poly(lactide-co-glycotide) (PLGA)/gelatin composite microspheres were prepared by an emulsion solvent evaporation technique. RGDS peptides were further immobilized under the catalyzation of water soluble carbodiimide (EDAC). Confocal laser scanning microscopy and transmission electron microscopy revealed that the gelatin was entrapped in the PLGA/gelatin microspheres with a manner of separated domains. The contents of the entrapped gelatin and immobilized RGDS peptides were quantified as 0.9 mg/20 mg and approximately 2.1 microg/20 mg microspheres by hydroxyproline analysis and bicinchoninic acid protein assay, respectively. Moreover, difference in morphology of PLGA, PLGA/gelatin and RGDS modified PLGA/gelatin (PLGA/gelatin-RGDS) microspheres was observed by scanning electron microscopy. The PLGA/gelatin and PLGA/gelatin-RGDS microspheres lost their weight rapidly in PBS, but slowly in DMEM/fetal bovine serum. Rabbit auricular chondrocytes were seeded onto the microspheres in vitro to assess their biological performance and applicability as cell carriers. Results show that amongst the PLGA, PLGA/gelatin and PLGA/gelatin-RGDS microspheres, the latter ones have the best performance in terms of chondrocyte attachment, proliferation, viability and sulfated glycosaminoglycans secretion.


Growth curves and the international standard: How children's growth reflects challenging conditions in rural Timor-Leste.
Population-specific growth references are important in understanding local growth variation, especially in developing countries where child growth is poor and the need for effective health interventions is high. In this article, we use mixed longitudinal data to calculate the first growth curves for rural East Timorese children to identify where, during development, deviation from the international standards occurs. Over an eight-year period, 1,245 children from two ecologically distinct rural areas of Timor-Leste were measured a total of 4,904 times. We compared growth to the World Health Organization (WHO) standards using z-scores, and modeled height and weight velocity using the SuperImposition by Translation And Rotation (SITAR) method. Using the Generalized Additive Model for Location, Scale and Shape (GAMLSS) method, we created the first growth curves for rural Timorese children for height, weight and body mass index (BMI). Relative to the WHO standards, children show early-life growth faltering, and stunting throughout childhood and adolescence. The median height and weight for this population tracks below the WHO fifth centile. Males have poorer growth than females in both z-BMI (p = .001) and z-height-for-age (p = .018) and, unlike females, continue to grow into adulthood. This is the most comprehensive investigation to date of rural Timorese children's growth, and the growth curves created may potentially be used to identify future secular trends in growth as the country develops. We show significant deviation from the international standard that becomes most pronounced at adolescence, similar to the growth of other Asian populations. Males and females show different growth responses to challenging conditions in this population.


Inhibition of influenza A virus hemagglutinin and induction of interferon by synthetic sialylated glycoconjugates.
Multivalent forms of neoglycoproteins and polyacrylamides containing sialic acid were prepared and shown to be potent inhibitors of influenza A virus (H3N2) hemagglutinin with chick red blood cells. The synthetic sialylated glycoconjugates, although they were neuraminidase substrates, did not suppress viral neuraminidase and did not reduce infectivities in chick embryos. The copolyacrylamide conjugate containing a spacer group of approximately 11 A (1 A = 0.1 nm) between the polymer backbone and the sialic acid residues was the best hemagglutinin inhibitor. Moreover, it exhibited promising interferon-inducing properties.


Mg-25 ultra-high field solid state NMR spectroscopy and first principles calculations of magnesium compounds.
Due to sensitivity problems, (25)Mg remains a largely under-explored nucleus in solid state NMR spectroscopy. In this work at an ultrahigh magnetic field of 21.1 T, we have studied at natural abundance the (25)Mg solid state (SS) NMR spectra for a number of previously unreported magnesium compounds with known crystal structures. Some previously reported compounds have been revisited to clarify the spectra that were obtained at lower fields and were either not sufficiently resolved, or misinterpreted. First principles calculations of the (25)Mg SS NMR parameters have been carried out using plane wave basis sets and periodic boundary conditions (CASTEP) and the results are compared with experimental data. The calculations produce the (25)Mg absolute shielding scale and give us insight into the relationship between the NMR and structural parameters. At 21.1 T the effects of the quadrupolar interactions are reduced significantly and the sensitivity and accuracy in determining chemicals shifts and quadrupole coupling parameters improve dramatically. Although T(1) measurements were not performed explicitly, these proved to be longer than assumed in much of the previously reported work. We demonstrate that the chemical shift range of magnesium in diamagnetic compounds may approach 200 ppm. Most commonly, however, the observed shifts are between -15 and +25 ppm. Quadrupolar effects dominate the (25)Mg spectra of magnesium cations in non-cubic environments. The chemical shift anisotropy appears to be rather small and only in a few cases could the contribution of the CSA be detected reliably. A good correspondence between the calculated shielding constants and experimental chemical shifts was obtained, demonstrating the good potential of computational methods in spectroscopic assignments of solid state (25)Mg NMR spectroscopy.


Prenatal Hypoxia Induces Cl- Cotransporters KCC2 and NKCC1 Developmental Abnormality and Disturbs the Influence of GABAA and Glycine Receptors on Fictive Breathing in a Newborn Rat.
Prenatal hypoxia is a recognised risk factor for neurodevelopmental disorders associated with both membrane proteins involved in neuron homeostasis, e.g., chloride (Cl-) cotransporters, and alterations in brain neurotransmitter systems, e.g., catecholamines, dopamine, and GABA. Our study aimed to determine whether prenatal hypoxia alters central respiratory drive by disrupting the development of Cl- cotransporters KCC2 and NKCC1. Cl- homeostasis seems critical for the strength and efficiency of inhibition mediated by GABAA and glycine receptors within the respiratory network, and we searched for alterations of GABAergic and glycinergic respiratory influences after prenatal hypoxia. We measured fictive breathing from brainstem in ex vivo preparations during pharmacological blockade of KCC2 and NKCC1 Cl- cotransporters, GABAA, and glycine receptors. We also evaluated the membrane expression of Cl- cotransporters in the brainstem by Western blot and the expression of Cl- cotransporter regulators brain-derived neurotrophic factor (BDNF) and calpain. First, pharmacological experiments showed that prenatal hypoxia altered the regulation of fictive breathing by NKCC1 and KCC2 Cl- cotransporters, GABA/GABAA, and glycin. NKCC1 inhibition decreased fictive breathing at birth in control mice while it decreased at 4 days after birth in pups exposed to prenatal hypoxia. On the other hand, inhibition of KCC2 decreased fictive breathing 4 days after birth in control mice without any change in prenatal hypoxia pups. The GABAergic system appeared to be more effective in prenatal hypoxic pups whereas the glycinergic system increased its effectiveness later. Second, we observed a decrease in the expression of the Cl- cotransporter KCC2, and a decrease with age in NKCC1, as well as an increase in the expression of BDNF and calpain after prenatal hypoxia exposure. Altogether, our data support the idea that prenatal hypoxia alters the functioning of GABAA and glycinergic systems in the respiratory network by disrupting maturation of Cl- homeostasis, thereby contributing to long-term effects by disrupting ventilation.


The neuroprotective effects of apocynin.
The recognition of health benefits of phytomedicines and herbal supplements lead to an increased interest to understand the cellular and molecular basis of their biological activities. Apocynin (4-hydroxy-3-methoxy-acetophenone) is a constituent of the Himalayan medicinal herb Picrorhiza kurroa which is regarded as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, a superoxide-producing enzyme. NADPH oxidase appears to be especially important in the modulation of redox-sensitive signaling pathways and also has been implicated in neuronal dysfunction and degeneration, and neuroinflammmation in diseases ranging from stroke, Alzheimer's and Parkinson's diseases to psychiatric disorders. In this review, we aim to give an overview of current literature on the neuroprotective effects of apocynin in the prevention and treatment of neurodegenerative disorders. Particular attention is given to in vivo studies.


[Consumers and health policies: reports and perspectives].
The French public power-base imagined that the involvement and participation of consumers in decision-making could render the debates on health policies more transparent when faced with the opposing professional and techno-administrative logics. One could also ask oneself what is the true reality of this participation. The research strategy is based on the intersection and overlap of data resulting from the analysis of minutes reported from semi-guided interviews with regional and national referential persons, consumers and from documents concerning the construction and implementation of national, regional and local health policies. This study demonstrates that, from 1996 to 2002, consumers were associated with and implicated in the development and implementation of national, regional and local health policies. Exemplary success stories exist which testify to the possibility of anchoring a democratic consultation model in health institutions irrespective of the level of decision-making, application or operationalisation. Recommendations are proposed in order to strengthen these dynamic forces and relationships.


No personalization without participation: on the active contribution of psychiatric patients to the development of a mobile application for mental health.
Despite the increasing pervasiveness of mobile computational technologies, knowledge about psychiatric patients' preferences regarding the design and utility of mobile applications is very poor. This paper reports on a pilot-study that involved 120 psychiatric patients in the development of a mobile application (app) that is being used for data entry into the Signature Project data bank at the Institut universitaire en santé mentale de Montréal (IUSMM), Canada. Participants were invited to comment on the 'look and feel' of the Signature App. Their input also extended the procedures for data collection. These suggestions may contribute to increased mental health literacy and empowerment of persons with mental illness receiving services at the IUSMM. Participants were recruited to fill out a questionnaire on a tablet computer while waiting at the Emergency Room (ER, n = 40), Psychotic Disorders outpatient clinic (n = 40) or Anxiety and Mood Disorders outpatient clinic (n = 40) of IUSMM. Nine patients from each of these sub-groups participated in a focus group to review the results and to discuss how the design and use of the Signature App could be improved to better meet the needs of patients. This study (n = 120) indicated that psychiatric patients are clearly capable of using a tablet computer to fill out questionnaires for quantitative data entry, and that they enjoyed this experience. Results from the focus groups (n = 27) highlight that the app could also be used by patients to communicate some personal and contextual qualitative information. This would support a holistic and person-centered approach, especially at the ER where people acutely need to describe their recent history and receive emotional support. This pilot-study has confirmed the necessity of involving patients not only in the testing of a new mobile application, but also as active contributors in the entire research and development process of a person-centered information and communication technology infrastructure. The input of participants was essential in designing the Signature Project computational procedure and making use of the app a positive and empowering experience. Participants also gave critical feedback remarks that went beyond the initial scope of the pilot-study, for example they suggested the addition of a client-clinician component.


Involvement of the CYP1A1 inhibition-mediated activation of aryl hydrocarbon receptor in drug-induced hepatotoxicity.
Hepatotoxicity is one of the most common toxicities observed in non-clinical safety studies of drug candidates, and it is important to understand the hepatotoxicity mechanism to assess the risk of drug-induced liver injury in humans. In this study, we investigated the mechanism of hepatotoxicity caused by 2-[2-Methyl-1-(oxan-4-yl)-1H-benzimidazol-5-yl]-1,3-benzoxazole (DSP-0640), a drug candidate that showed hepatotoxicity characterized by centrilobular hypertrophy and vacuolation of hepatocytes in a 4-week oral repeated-dose toxicity study in male rats. In the liver of rats treated with DSP-0640, the expression of aryl hydrocarbon receptor (AHR) target genes, including Cyp1a1, was upregulated. In in vitro reporter assays, however, DSP-0640 showed only minimal AHR-activating potency. Therefore, we investigated the possibility that DSP-0640 indirectly activated AHR by inhibiting the CYP1 enzyme-dependent clearance of endogenous AHR agonists. In in vitro assays, DSP-0640 showed inhibitory effects on both rat and human CYP1A1 and enhanced rat and human AHR-mediated reporter gene expression induced by 6-formylindolo[3,2-b]carbazole, a well-known endogenous AHR agonist. The possible involvement of CYP1A1 inhibition in AHR activation was also demonstrated with other hepatotoxic compounds tacrine and albendazole. These results suggest that CYP1A1 inhibition-mediated AHR activation is involved in the hepatotoxicity caused by DSP-0640 and that DSP-0640 might induce hepatotoxicity in humans as well. We propose that CYP1A1 inhibition-mediated AHR activation is a novel mechanism for drug-induced hepatotoxicity.


Arbuscular mycorrhizal fungal community response to warming and nitrogen addition in a semiarid steppe ecosystem.
Understanding the response of arbuscular mycorrhizal (AM) fungi to warming and nitrogen (N) fertilization is critical to assess the impact of anthropogenic disturbance on ecosystem functioning under global climate change scenarios. In this study, AM fungal communities were examined in a full factorial design with warming and N addition in a semiarid steppe in northern China. Warming significantly increased AM fungal spore density, regardless of N addition, whilst N addition significantly decreased AM fungal extraradical hyphal density, regardless of warming. A total of 79 operational taxonomic units (OTUs) of AM fungi were recovered by 454 pyrosequencing of SSU rDNA. Warming, but not N addition, had a significant positive effect on AM fungal OTU richness, while warming and N addition significantly increased AM fungal Shannon diversity index. N addition, but not warming, significantly altered the AM fungal community composition. Furthermore, the changes in AM fungal community composition were associated with shifts in plant community composition indirectly caused by N addition. These findings highlight the different effects of warming and N addition on AM fungal communities and contribute to understanding AM fungal community responses to global environmental change scenarios in semiarid steppe ecosystems.


Principles of voltammetry and microelectrode surface states.
In vivo voltammetry is approaching the end of its second decade as a technique to explore extracellular concentrations in the brain. The issues of selectivity and sensitivity, which caused considerable discussion and confusion in the early 1980s, are now resolved. It is clear that in vivo voltammetry and dialysis are complimentary tools to understand neurotransmitter dynamics. The two chief advantages of voltammetry compared to dialysis, improved temporal resolution and reduced tissue damage, make this technique exceptionally well suited for providing information which is complementary to that obtained by single-unit recording and is uniquely capable of providing information on the short-term regulation of extracellular levels of biogenic amines.


Assessment of Surgeon Judgment during Resection of Laryngeal Carcinoma.
Carbon dioxide (CO2) laser surgery as a conservative tool plays a peculiar role in the management of head and neck cancer. Numerous patients who were candidates for transoral laryngeal microsurgery have forced us to eliminate frozen-section evaluation of surgical margins and use a magnified view of the larynx. The present study evaluated surgeon-judged negative margins with permanent microscopic pathologic evaluation. In this cross-sectional study, we evaluated the permanent pathologic margins of the resected laryngeal specimen which were considered negative by judgment of surgeons. Patients consisted of 61 pathologic proven T1-T2 laryngeal squamous cell carcinoma (SCC) cases. In all patients, tumor resection was performed via a transoral route with CO2 laser, and no residual laryngeal tumor was observed according to judgment of the surgeon. The patients with positive margin (s) underwent another resection. Patients were followed up for 18 months for tumor recurrence. The obtained results demonstrated that pathologic margins were reported in 6 patients, with the deep margin being the most common positive margin. During the 18-month follow-up, 8 cases of recurrence were detected. Judgment of the surgeon was in agreement with permanent pathologic evaluation in transoral laryngeal laser resection at the early stages of laryngeal SCC in most cases. Nevertheless, it is suggested that further direct studies be conducted to evaluate the frozen section on oncologic outcomes in transoral laser surgery for laryngeal cancer.


Stranded dolphin stomach contents represent the free-ranging population's diet.
Diet is a fundamental aspect of animal ecology. Cetacean prey species are generally identified by examining stomach contents of stranded individuals. Critical uncertainty in these studies is whether samples from stranded animals are representative of the diet of free-ranging animals. Over two summers, we collected faecal and gastric samples from healthy free-ranging individuals of an extensively studied bottlenose dolphin population. These samples were analysed by molecular prey detection and these data compared with stomach contents data derived from stranded dolphins from the same population collected over 22 years. There was a remarkable consistency in the prey species composition and relative amounts between the two datasets. The conclusions of past stomach contents studies regarding dolphin habitat associations, prey selection and proposed foraging mechanisms are supported by molecular data from live animals and the combined dataset. This is the first explicit test of the validity of stomach contents analysis for accurate population-scale diet determination of an inshore cetacean.


Displacement of occluded plastic endoprostheses into the duodenum during percutaneous biliary drainage: description of an under-reported technique.
Percutaneous transhepatic biliary drainage (PTBD) is occasionally requested in patients with an occluded plastic stent in situ. We describe a technique for dislodging the stent into the duodenum during PTBD. Twelve patients (M:F, 9:3 mean age 70 years) with plastic stents in the common bile duct (CBD) underwent PTBD. Eleven patients had malignant obstruction and one patient had Mirizzi's syndrome and a large duodenal diverticulum. PTBD was performed using right lobe access in nine patients and a left hepatic access in three patients. The level of biliary obstruction was at the lower CBD in five patients, mid-CBD in four patients and upper CBD in three patients. After standard percutaneous biliary access was established, an 8mm by 4 cm balloon catheter was gently inflated alongside the upper end of the plastic stent and advanced over a stiff guidewire, towards the duodenum, to dislodge the plastic stent. Plastic stents were successfully dislodged in all 11 patients with malignancy and metallic stents were deployed for palliation. In nine of 11 patients with malignant lesions the PTBD dislodgement of the plastic stent and insertion of a metallic stent was carried out as a single-step procedure. In two patients with biliary sepsis, a two-step procedure was necessary. In the patient with Mirizzi's syndrome the plastic stent could not be dislodged. No complications were observed. Plastic stents, inserted at ERCP, can be dislodged in the majority of cases at PTBD using a balloon catheter inserted alongside the failed stent without complication.


[Clinical and pathological analysis of jaw ameloblastomas in 890 patients].
To investigate the clinical and pathological features of jaw ameloblastomas in 890 patients, in order to provide reference for clinical diagnosis and treatment. Eight hundred and ninty cases with jaw ameloblastomas treated in our department from January 2003 to June 2014 were retrospectively analyzed, including their gender, age, primary sites, pathological subtypes and therapies. The age of patients ranged from 6 to 101 years old, with a mean age of 40.15 years. The distribution between males and females were 61.91% (551/890) males to 38.08% (339/890) females (1.62:1). 724 (81.35%) were located in the mandible, 166 (18.65%) were located in the maxilla. The occurrence of jaw ameloblastomas in this series of 890 patients was same in both sides of the jaw. Jaw ameloblastomas occurred in any parts of the jaw. Solid (378/890) and unicystic ameloblastoma (427/890) were the most common pathological subtypes. 414 cases underwent curettage, 212 cases underwent decompression, and 264 cases underwent mandibulectomy or maxillectomy. Jaw ameloblastoma mainly happens in mandible and young people. Men are more vulnerable to suffer from than women. The most common sites are mandibular molar region and ramus. Curettage is the most commonly used treatment for ameloblastomas. Supported by Scientific Research Fund of Oromaxillofacial Head and Neck Surgery of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine.


Release and Modification of nod-Gene-Inducing Flavonoids from Alfalfa Seeds.
Traces of luteolin, an important rhizobial nod gene inducer in Rhizobium meliloti, are released by alfalfa (Medicago sativa L.) seeds, but most luteolin in the seed exudate is conjugated as luteolin-7-O-glucoside (L7G). Processes affecting the production of luteolin from L7G in seed exudate are poorly understood. Results from this study establish that (a) seed coats are the primary source of flavonoids, including L7G, in seed exudate; (b) these flavonoids exist in seeds before imbibition; and (c) both the host plant and the symbiotic R. meliloti probably can hydrolyze L7G to luteolin. Glycolytic cleavage of L7G is promoted by glucosidase activity released from sterile seeds during the first 4 hours of imbibition. Thus, L7G from imbibing alfalfa seeds may serve as a source of the nod-gene-inducing luteolin and thereby facilitate root nodulation by R. meliloti.


[Superficial esophageal carcinoma successfully treated with combined chemotherapy and radiotherapy].
A 47-year-old man was admitted to our hospital with the chief complaint of epigastralgia. Endoscopic examination revealed a 0-IIa + IIc lesion in the middle thoracic esophagus, and a biopsy specimen was diagnosed as squamous cell carcinoma. The depth of the cancerous invasion was judged to be sm by endoscopic ultrasonography, and no metastasis to other organs or lymph nodes was detected. Although we believed curative resection was possible, we performed combined chemotherapy and radiotherapy because the patient refused surgery. After 2 courses of chemoradiotherapy, the cancer had disappeared clinically. We have found no evidence of recurrence for 1 year and 8 months. For the patient with superficial esophageal carcinoma who has a high risk or refuses surgery, chemoradiotherapy may be a reasonable alternative.


Myelodysplastic syndrome without ring sideroblasts and with Janus kinase 2 gene mutation: An unusual case report.
Myelodysplastic syndrome (MDS) cases comprise a heterogeneous group of hematological disorders that are characterized by impaired hematopoiesis, with cytopenias of different grades and risk of developing acute myeloid leukemia. MDS may rarely be associated with thrombocytosis. In such cases, myelodysplasia and myeloproliferative disorders may overlap, making correct diagnosis difficult. We herein describe a case of MDS with thrombocytosis, Janus kinase 2 gene mutation-positive and Perls' staining-negative, which was initially classified as essential thrombocythemia (ET). This case highlights that MDS may be misdiagnosed as ET and inappropriate treatment may be initiated. Therefore, it is crucial to carefully combine all available data on morphology and immunophenotyping, and to perform the necessary molecular, cytogenetic and molecular cytogenetic analyses, in order to correctly diagnose this disease.


Global screening of potential Candida albicans biofilm-related transcription factors via network comparison.
Candida albicans is a commonly encountered fungal pathogen in humans. The formation of biofilm is a major virulence factor in C. albicans pathogenesis and is related to antidrug resistance of this organism. Although many factors affecting biofilm have been analyzed, molecular mechanisms that regulate biofilm formation still await to be elucidated. In this study, from the gene regulatory network perspective, we developed an efficient computational framework, which integrates different kinds of data from genome-scale analysis, for global screening of potential transcription factors (TFs) controlling C. albicans biofilm formation. S. cerevisiae information and ortholog data were used to infer the possible TF-gene regulatory associations in C. albicans. Based on TF-gene regulatory associations and gene expression profiles, a stochastic dynamic model was employed to reconstruct the gene regulatory networks of C. albicans biofilm and planktonic cells. The two networks were then compared and a score of relevance value (RV) was proposed to determine and assign the quantity of correlation of each potential TF with biofilm formation. A total of twenty-three TFs are identified to be related to the biofilm formation; ten of them are previously reported by literature evidences. The results indicate that the proposed screening method can successfully identify most known biofilm-related TFs and also identify many others that have not been previously reported. Together, this method can be employed as a pre-experiment screening approach that reveals new target genes for further characterization to understand the regulatory mechanisms in biofilm formation, which can serve as the starting point for therapeutic intervention of C. albicans infections.


The effect of pergolide on cognitive performance of young and middle-aged rats.
In this study, we investigated the effect of pergolide, a dopaminergic agonist, on cognitive ability in young and middle-aged rats using the Morris Water Maze (MWM). Pergolide 0.5/mg/day i.p. was administered to young and middle-aged rats, whereas only vehicle was given to their age-matched controls. During the acquisition period of 6 days, young rats showed normal escape latency pattern, which was not affected by pergolide. Middle-aged rats, however, showed poor escape latency pattern, and this poor pattern was also not affected by pergolide. On the 7th day, pergolide decreased retention time of young rats compared to control values. Middle-aged rats also showed reduced retention time. In contrast to the findings of young rats, retention time was not affected by pergolide in middle-aged rats. We concluded that pergolide does not alter escape latency at any age. It has a negative effect on retention time of young rats, whereas it has no effect on middle-aged ones.


Epidemiologic study of decubital ulcers in sows.
To determine prevalence and risk factors for decubital ulcers of the shoulder in sows. Descriptive cross-sectional study. All females of breeding age in a large confinement swine facility. 1,916 females were examined for lesions of the skin over the tuber of the spine of the scapula and for body condition scoring. Observational data were combined with sow data (parity, date of farrowing, litter size) contained in computerized records. Decubital ulcers were observed in 8.3% of females, predominantly lactating sows. Ulcer prevalence was strongly associated with time after farrowing. Lesions apparently healed rapidly after weaning. Ulcer prevalence was associated with low body condition scores, but was not associated with parity. Decubital ulcers are a multifactorial condition. Housing on concrete floors per se did not result in ulcers. Prolonged recumbency during parturition, reduced activity in early lactation, periparturient illness, thin body condition, moist skin, and floor type are potential risk factors.


A secure base for mindful dreaming: dispositional and contextually variable attachment security and the experiential quality of dreams.
In this study, we examined the utility of attachment theory for explaining individual differences in dream experiences. Seventy-six Israeli undergraduates completed a measure of attachment anxiety and avoidance and participated in a daily diary study for 15 consecutive days. Each evening, they rated their daily sense of attachment security. Each morning, they described in writing any dreams they recalled and rated the extent to which they (a) were aware of their sensations and mental states while dreaming and (b) reflected on their subjective experience during the dream. Two judges made similar ratings for each dream. Dispositional attachment anxiety and avoidance were associated with lower levels of within-dream awareness and reflection across the 15-day period. In addition, attachment security on a given day was associated with higher within-dream awareness and reflection that night. The findings provide new evidence concerning the contribution of attachment orientations to the experiential quality of dreams.


Effect of chorioamnionitis on early childhood asthma.
To examine the association between chorioamnionitis and childhood asthma based on gestational age at birth and race/ethnicity. A retrospective cohort study using the Kaiser Permanente Southern California (KPSC) Matched Perinatal records. Kaiser Permanente Southern California, Pasadena, California. All singleton children born in KPSC hospitals between 1991 and 2007 (N = 510 216). Clinically diagnosed chorioamnionitis. Physician-diagnosed asthma in children aged 8 years or younger. The incidence rates of asthma among preterm- and full term-born children of pregnancies complicated by chorioamnionitis were 100.7 and 39.6 per 1000 person-years, respectively (incidence rate ratio, 2.9; 95% confidence interval [CI], 2.6-3.3). Children aged 8 years or younger with asthma were more likely to be born to women who were aged 35 years or older, African American, had 13 or more years of education, had maternal asthma, used antibiotics, had chorioamnionitis during the pregnancy, and had a male child. Multivariable Cox regression analysis revealed that children born at 23 to 28, 29 to 33, and 34 to 36 weeks' gestation after pregnancies complicated by chorioamnionitis had a 1.23-fold (95% CI, 1.02-1.49), 1.51-fold (95% CI, 1.26-1.80), and 1.20-fold (95% CI, 1.03-1.47), respectively, increased risk of asthma compared with children of similar gestational age born after pregnancies not complicated by chorioamnionitis. A preterm pregnancy complicated by chorioamnionitis was associated with increased risk of asthma among white (hazard ratio [HR], 1.66; 95% CI, 1.32-2.07), African American (HR, 1.98; 95% CI, 1.60-2.44), and Hispanic (HR, 1.70; 95% CI, 1.45-2.00), but not Asian/Pacific Islander (HR, 1.15; 95% CI, 0.83-1.58) women. Findings suggest that chorioamnionitis at preterm gestation is independently associated with increased risk of childhood asthma.


Human beta cells are exceedingly resistant to streptozotocin in vivo.
Streptozotocin (STZ) causes beta cell death in rodents via the mechanism of DNA damage precipitating poly(ADP-ribose) synthetase activation followed by lethal nicotinamide adenine dinucleotide depletion. It is unclear whether humans are susceptible to this mechanism. Islets were isolated from STZ-sensitive (CD1 mice and Lewis rats) and resistant [fish (tilapia)] species and from man and then were transplanted into diabetic nude mice under the kidney capsule. Normoglycemic recipients with normal glucose tolerance tests on d 30 were injected with increasing iv doses of STZ and their plasma glucose levels followed for 5 d; glucose tolerance tests were repeated on nondiabetic mice. Mice were then killed; grafts and native pancreata were examined. Based upon three criteria (i.e. nonfasting plasma glucose levels, glucose tolerance tests, and islet histology), the following observations were made: 1) Recipients of rat islets were resistant to 25 mg/kg but were uniformly diabetic at doses of 50 or 75 mg/kg. 2) Recipients of mouse islets were resistant to 75 mg/kg but were uniformly diabetic at 150 or 200 mg/kg. 3) Recipients of the fish islets were resistant to 300, 400, and 450 mg/kg. 4) Recipients of human islets were resistant to 100, 200, 300, 400, and 450 mg/kg. The results in recipient mice bearing long-term rat, mouse, or fish islet grafts were the same as previously published dose-response data for each donor species. We extrapolate from our results based on human islet grafts in mice that human beta cells are exceedingly resistant to STZ.


Theoretical and electrochemical analysis of dissociative electron transfers proceeding through formation of loose radical anion species: reduction of symmetrical and unsymmetrical disulfides.
The dissociative reduction of a series of symmetrical (RSSR, R = H, Me, t-Bu, Ph) and unsymmetrical disulfides (RSSR', R = H, R' = Me and R = Ph, R' = Me, t-Bu) was studied theoretically, by MO ab initio calculations and, for five of them, also experimentally, by convolution voltammetry in N,N-dimethylformamide. The reduction is dissociative but proceeds by a stepwise mechanism entailing the formation of the radical anion species. The electrochemical data led to estimated large intrinsic barriers, in agreement with an unusually large structural modification undergone by the disulfide molecules upon electron transfer. The theoretical results refer to MP2/3-21G*//MP2/3-21G*, MP2/3-21*G*//MP2/3-21G*, CBS-4M, and G2(MP2), the latter approach being used only for the molecules of small molecular complexity. A loose radical-anion intermediate was localized and the dissociation pattern for the relevant bonds analyzed. For all compounds, the best fragmentation pathway in solution is cleavage of the S-S bond. In addition, S-S bond elongation is the major structural modification undergone by the disulfide molecule on its way to the radical anion and eventually to the fragmentation products. The calculated energy of activation for the initial electron transfer was estimated from the crossing of the energy profiles of the neutral molecule and its radical anion (in the form of Morse-like potentials) as a function of the S-S bond length coordinate. The inner intrinsic barrier obtained in this way is in good agreement with that determined by convolution voltammetry, once the solvent effect is taken into account.


Tissue factor: mechanisms of decryption.
It is generally believed that only a small fraction of the tissue factor (TF) found on cell surfaces is active whereas the vast majority is cryptic in coagulation. It is unclear how cryptic TF differs from the coagulant active TF or potential mechanisms involved in transformation of cryptic TF to the coagulant active form. Exposure of phosphatidylserine (PS) in response to various chemical or pathophysiological stimuli has been considered as the most potent inducer of TF decryption. In addition to PS, TF self-association and association with specialized membrane domains may also play a role in TF decryption. It has been suggested recently that protein disulfide isomerase regulates TF decryption through its oxidoreductase activity by targeting Cys186-Cys209 disulfide bond in TF extracellular domain or regulating the PS equilibrium at the plasma membrane. However, this hypothesis requires further validation to become an accepted mechanism. In this article, we critically review literature on TF encryption/decryption with specific emphasis on recently published data and provide our perspective on this subject.


Acute Myopericarditis caused by Human Metapneumovirus.
Human metapneumovirus is known to be similar to respiratory syncytial virus. Because of an incomplete protective immune response to new genotypes, re-infection occurs frequently, especially in the elderly. However, the clinical manifestations of human metapneumovirus need to be further characterized in adults. A 73-year-old woman presented to the emergency room with acute dyspnea, chest discomfort and influenza-like illness. The patient was diagnosed with human metapneumovirus infection, complicated by pneumonia and myopericarditis. With supportive care including oxygen supplementation, the patient recovered completely without any serious sequelae. Human metapneumovirus infection may contribute to the development of cardiovascular manifestations, particularly in the elderly population.


Population geography.
The author reviews recent changes in population research from a geographical perspective. "The deaths in 1990 of two of France's most distinguished demographers, Alfred Sauvy (1899-1990) and Jean Bourgeois-Pichat (1912-90)...seem an appropriate starting point from which to review progress in population research in the early 1990s....Relative to the lifespans and works of Bourgeois-Pichat and Sauvy, it is possible to discern progress in population studies as a whole and population geography in particular. Advances in technical aspects of measuring mortality, fertility and migration have been most marked, as have attempts to inter-relate these demographic processes. Progress towards explanation of population-related phenomena has been slower. Advances have not been towards building more sophisticated general theories, but towards new and more insightful forms of explanation." The author then summarizes other research literature on fertility, migration, and population subgroups. The geographical scope is worldwide.


[Simple artificial mouth model].
A simple artificial mouth model is established under our laboratory condition. Development of monobacterial plaque and mixed bacterial plaque was studied in this artificial mouth model. The samples were subjected to viable count, microhardness measurement, etc. The result showed that the controlled conditions of the model can be used to study plaque development and earlier enamel lesion production on a time-dependent basis. It is concluded that the simple artificial mouth model is suitable for a wide range of dental applications.


Purification of a 90-kDa protein (Band VII) from cardiac sarcoplasmic reticulum. Identification as calnexin and localization of casein kinase II phosphorylation sites.
Purification and sequencing of proteins from cardiac sarcoplasmic reticulum (SR) vesicles have provided a framework for the study of SR function. Included among the SR proteins so far investigated are a collection of intralumenal proteins that stain blue with the protein dye Stains-All in sodium dodecyl sulfate-polyacrylamide gels. A single prominent blue staining SR protein of apparent M(r) = 90,000 (Band VII), however, has remained uncharacterized. In the work described here, purification of Band VII from dog cardiac SR vesicles, along with amino acid sequencing and cDNA cloning, identified this protein as calnexin, a homologue of calreticulin recently described in dog pancreatic microsomes. Using ryanodine-mediated calcium oxalate loading of SR vesicles followed by density gradient centrifugation, we have shown that calnexin is a bona fide SR protein and an integral constituent of both junctional and free SR vesicles. Calnexin was found to be a substrate for casein kinase II and was phosphorylated at two distinct sites localized to the carboxyl- and amino-terminal ends of the molecule. Enrichment of calnexin in cardiac SR vesicles indicates a role for calnexin involving the specialized function of the SR membrane.


Importance of n-3 fatty acids in health and disease.
In the past 2 decades, views about dietary n-3 fatty acids have moved from speculation about their functions to solid evidence that they are not only essential nutrients but also may favorably modulate many diseases. Docosahexaenoic acid (22:6n-3), which is a vital component of the phospholipids of cellular membranes, especially in the brain and retina, is necessary for their proper functioning. n-3 Fatty acids favorably affect atherosclerosis, coronary heart disease, inflammatory disease, and perhaps even behavioral disorders. The 38 articles in this supplement document the importance of n-3 fatty acids in both health and disease.


Comparative landscape genetics of two pond-breeding amphibian species in a highly modified agricultural landscape.
Evaluating fine-scale population structure of multiple species in the same landscape increases our ability to identify common patterns as well as discern ecological differences among species' landscape genetic relationships. In the Palouse bioregion of northern Idaho, USA, 99% of the native prairie has been converted to nonirrigated agriculture and exotic grasslands. Columbia spotted frogs (Rana luteiventris) and long-toed salamanders (Ambystoma macrodactylum) in this area breed almost entirely in artificial ponds on private land. We used genetic distances (F(ST) and D(c)) derived from eight microsatellite loci in 783 samples to evaluate the relationships among sympatric breeding populations (N = 20 and 26) of these species in a 213-km(2) landscape. Both species showed a pattern of isolation by distance that was not improved when distance was measured along drainages instead of topographically corrected straight lines (P < 0.01). After testing for autocorrelation among genetic distances, we used an information theoretic approach to model landscape resistance based on slope, soil type, solar insolation, and land cover, and multi-model inference to rank the resistance of landscape surfaces to dispersal (represented by genetic distance). For both species, urban and rural developed land cover provided the highest landscape resistances. Resistance values for long-toed salamanders followed a moisture gradient where forest provided the least resistance, while agriculture and shrub/clearcut provided the least resistance for Columbia spotted frogs. Comparative landscape genetics can be a powerful tool for detecting similarities and differences between codistributed species, and resulting models can be used to predict species-specific responses to landscape change.


S-genotype identification based on allele-specific PCR in Japanese pear.
Gametophytic self-incompatibility in Japanese pear (Pyrus pyrifolia Nakai) is controlled by the single, multi-allelic S-locus. Information about the S-genotypes is important for breeding and the selection of pollen donors for fruit production. Rapid and reliable S-genotype identification system is necessary for efficient breeding of new cultivars in Japanese pear. We designed S allele-specific PCR primer pairs for ten previously reported S-RNase alleles (S (1)-S (9) and S (k)) as simple and reliable method. Specific nucleotide sequences were chosen to design the primers to amplify fragments of only the corresponding S alleles. The developed primer pairs were evaluated by using homozygous S-genotypes (S (1)/S (1)-S (9)/S (9) and S (4sm)/S (4sm)) and 14 major Japanese pear cultivars, and found that S allele-specific primer pairs can identify S-genotypes effectively. The S allele-specific primer pairs developed in this study will be useful for efficient S-genotyping and for marker-assisted selection in Japanese pear breeding programs.


Studies on the different conditions for rabies virus neutralization by monoclonal antibodies #1-46-12 and #7-1-9.
Virus-neutralizing activity of two monoclonal antibodies (mAbs), #7-1-9 and #1-46-12, against rabies virus glycoprotein (G) was compared. Although these mAbs affected the virion's ability to bind to host cells similarly, a big difference was found in the titres of virus neutralization (1:7132 and 1:32 for mAbs #1-46-12 and #7-1-9, respectively, at a concentration of 10 micro g protein/ml). Although no big difference in virion-binding affinity between the two mAbs was found, the number of antibodies required for virus neutralization was very low, </=20 molecules for mAb #1-46-12 and >/=250 molecules for mAb #7-1-9. In the latter case, the mAbs cover a major part of the virion surface and cause steric hindrance of viral receptor-binding activity. The infectivity of an epitope-preserved escape mutant virus (R-61) was not affected by the binding of high numbers of mAb #1-46-12 to the virion, which implies that mAb binding does not mask the receptor-binding site of the viral spikes. Based on these results, it is hypothesized that mAb #1-46-12 affected virus infectivity by a mechanism different from covering the virion spikes. Possible virus-neutralizing mechanisms by low numbers of mAb #1-46-12 in comparison to that of mAb #7-1-9 are discussed.


Evaluation of platelet function in dogs with cardiac disease using the PFA-100 platelet function analyzer.
Cardiac disease has the potential to alter platelet function in dogs. Evaluation of platelet function using the PFA-100 analyzer in dogs of multiple breeds and with a broad range of cardiac conditions would help clarify the effect of cardiac disease on platelets. The objective of this study was to assess differences in closure time (CT) in dogs with cardiac disease associated with murmurs, when compared with that of healthy dogs. Thirty-nine dogs with cardiac murmurs and turbulent blood flow as determined echocardiographically were included in the study. The dogs represented 23 different breeds. Dogs with murmurs were further divided into those with atrioventricular valvular insufficiency (n=23) and subaortic stenosis (n=9). Fifty-eight clinically healthy dogs were used as controls. CTs were determined in duplicate on a PFA-100 analyzer using collagen/ADP cartridges. Compared with CTs in the control group (mean+/-SD, 57.6+/-5.9 seconds; median, 56.5 seconds; reference interval, 48.0-77.0 seconds), dogs with valvular insufficiency (mean+/-SD, 81.9+/-26.3 seconds; median, 78.0 seconds; range, 52.5-187 seconds), subaortic stenosis (71.4+/-16.5 seconds; median, 66.0 seconds; range, 51.5-95.0 seconds), and all dogs with murmurs combined (79.6+/-24.1 seconds; median, 74.0 seconds; range, 48.0-187 seconds) had significantly prolonged CTs (P<.01). The PFA-100 analyzer is useful in detecting platelet function defects in dogs with cardiac murmurs, most notably those caused by mitral and/or tricuspid valvular insufficiency or subaortic stenosis. The form of turbulent blood flow does not appear to be an important factor in platelet hypofunction in these forms of cardiac disease.


[Effects of simvastatin on blood levels of lipoprotein (a)].
The efficacy of Simvastatin to reduce plasma cholesterol is well documented. Other molecule within the lipo-lipoprotein family, such as, particularly, lipoprotein (a) -Lp(a)-, have been recently found to have a predictive and/or causative role in atherosclerosis. Based on the above consideration, we studied 20 patients (7 females and 13 males), mean age 52.4 +/- 14.2 years, affected by primary hypercholesterolemia to evaluate the effect of simvastatin on Lp(a), in addition to the classic lipidic parameters. Five weeks after suspension of lipid-lowering drugs and on a normal caloric-fat diet, were given 20 mg simvastatin/day for 12 months. Clinical and laboratory parameters, cholesterol (CH), triglycerides (TG), high density and low density lipoprotein cholesterol (HDL-CH and LDH-CH) measured enzymatically, apoproteins A1, B measured radial immunodiffusion technique and Lp(a) measured as apoprotein(a) with immunoradiometric assay and were evaluated before therapy and after 12 months of therapy. Simvastatin determined a significant reduction in total cholesterol and cholesterol-LDL (CH 327.7 +/- 44.4 vs 255.5 +/- 37.3, p < 0.0001; LDL-CH 257.1 +/- 60.9 vs 183.8 +/- 46.9, p < 0.0001) and a significant increase in HDL-CH (36.7 +/- 5.9 vs 40.2 +/- 5.7, p < 0.005); no variation was observed in triglycerides (TG) levels. Simvastatin therapy further determined a significant increase in Lp(a) plasma levels (43.8 +/- 25.6 vs 50.5 +/- 28.0, p < 0.02). The our data, in agreement with those documenting the beneficial effect of Simvastatin in greatly decreasing CH and LDL-CH, but point out the need for further studies concerning the long-ter effect of simvastatin on Lp(a), in order to fully establish its role in the secondary prevention of atherosclerosis.


The prognostic value of serial measurements of serum albumin concentration in patients admitted to an intensive care unit.
The prognostic value of serial measurements of serum albumin concentration during the first 72 h after admission to a general adult intensive care unit was retrospectively reviewed in 348 consecutive critically ill patients over a one year period. The accuracy of the admission APACHE II (Acute Physiology And Chronic Health Evaluation) score in correctly predicting patient outcome was compared with the serum albumin concentration measured at different times after intensive care unit admission. Multiple logistical regression analyses were performed to evaluate whether combining APACHE II and serum albumin into a unified risk index improved prognostic accuracy. Serum albumin concentration on admission was lower in non-survivors than in survivors and decreased more rapidly in non-survivors (p < 0.001). The admission serum albumin concentration was found to be an insensitive prognostic indicator. However, serum albumin measured after 24 h was as accurate as the admission APACHE II score in correctly classifying patients according to outcome. There was a good correlation between the admission APACHE II score and serum albumin measured after 24 h but not between the admission APACHE II and the admission serum albumin. Combining the APACHE II score and serial albumin concentrations into a unified risk of death equation did not improve the accuracy of outcome prediction.


Aminophenol-modified gold nanoparticles kill bacteria with minimal ototoxicity.
We report aminophenol (A)-modified gold nanoparticles (AGNPs), which have potent antibacterial effects against multidrug-resistant bacteria with a broad antibacterial spectrum. Moreover, a series of in vitro and in vivo models indicate that AGNPs are much less ototoxic than aminoglycosides. AGNPs thus have the potential to replace aminoglycosides as novel antibacterial agents for clinical applications.


Fluid Dynamics of Microgel-Covered Drops Reveal Impact on Interfacial Conditions.
Microgels are deformable polymer-networks with conspicuous properties. Their surface- activity associated with their switchability makes their application in liquid-liquid systems, such as extraction processes, particularly promising. For their application as switchable stabilizers at the interface, a detailed understanding of their impact on process relevant phenomena, such as the sedimentation behavior, is necessary. So far, the focus of research has been on microscopic-scale properties, whereby the propagation to macroscopic effects has rarely been quantified. In this study, single microgel-covered n-butyl acetate drops rising in a quiescent continuous water phase are investigated experimentally. The dependency of the microgel properties, in terms of size and cross-linking density, on the fluid dynamics are addressed. The impact of microgels is studied in detail by sedimentation velocity, drop deformation and the resulting drag coefficient. The deformation of drops is related to shape conserving interfacial properties such as the interfacial tension. Counter to our expectations, microgel-covered drops deform less than the drops of the pure system although microgels reduce the interfacial tension. Moreover, the sedimentation velocity is of special interest, since it reveals the mobility of the interface and friction conditions at the interface. Our results demonstrate the correlation between microgel properties at the interface on a microscopic scale and the macroscopic behavior of microgel-covered drops.


HER-dimerization inhibitors: evaluating pertuzumab in women's cancers.
Pertuzumab is a human EGF receptor (HER)-dimerization inhibitor that represent a novel class of agents aimed at blocking HER2 from pairing with other receptors of the HER family. In this review, we discuss the background and scientific rationale, related to pertuzumab as it has undergone development for women's cancers. Pre-clinical and clinical trials, published or presented at national meetings from 1995 to the present, are included in this review. A Phase II trial in HER2-positive metastatic breast cancer showed promising activity of pertuzumab when it was combined with trastuzumab and a randomized Phase III trial is now underway. Pertuzumab, when evaluated in recurrent ovarian cancer showed limited activity when combined with chemotherapy in platinum-sensitive and platinum-resistant disease. However, a recent subset analysis suggests that HER3 mRNA levels may predict response to pertuzumab in ovarian cancer. HER-dimerization inhibitors represent a novel mechanism of inhibition of HER pathways. Pertuzumab may play a role in the management of HER2-positive breast cancer. The potential benefit of pertuzumab in ovarian cancer is unclear, but low HER3 levels may suggest a sub-group of patients that can benefit from pertuzumab.


Model for Predicting the Micro-Grinding Force of K9 Glass Based on Material Removal Mechanisms.
K9 optical glass has superb material properties used for various industrial applications. However, the high hardness and low fracture toughness greatly fluctuate the cutting force generated during the grinding process, which are the main factors affecting machining accuracy and surface integrity. With a view to further understand the grinding mechanism of K9 glass and improve the machining quality, a new arithmetical force model and parameter optimization for grinding the K9 glass are introduced in this study. Originally, the grinding force components and the grinding path were analyzed according to the critical depth of plowing, rubbing, and brittle tear. Thereafter, the arithmetical model of grinding force was established based on the geometrical model of a single abrasive grain, taking into account the random distribution of grinding grains, and this fact was considered when establishing the number of active grains participating in cutting Nd-Tot. It should be noted that the tool diameter changed with machining, therefore this change was taking into account when building the arithmetical force model during processing as well as the variable value of the maximum chip thickness amax accordingly. Besides, the force analysis recommends how to control the processing parameters to achieve high surface and subsurface quality. Finally, the force model was evaluated by comparing theoretical results with experimental ones. The experimental values of surface grinding forces are in good conformity with the predicted results with changes in the grinding parameters, which proves that the mathematical model is reliable.


Adult Wilms' tumour. A case report with immunohistochemical studies.
The case of a 27-year-old female patient presenting with a Wilms' tumour is reported. The tumour was dominantly of blastemal type showing minor epithelial (tubular) areas and anaplastic portions. Thorough immunohistochemical examinations were performed to solve differential diagnostic problems. Keratin positivity was found to be of differential diagnostic value in the distinction of this tumour from the so called small round cell tumours. Prognostic aspects of Wilms' tumour are also discussed.


UVS112--A gene involved in excision repair of yeast.
In this study we show that the previously described uvs112 (uvs12) mutation blocks one of the steps of the excision repair pathway. The properties of this mutation permit the assignment of the UVS112 gene to the RAD3 epistasis group. It was established that the uvs112 mutation caused a 2.5-fold reduction in the number of recombinants produced by conversion and also significantly increased the frequency of mitotic crossing-over in interplasmid recombination. Tetrad analysis placed the UVS112 gene on the left arm of chromosome IX, approximately 20 cM from HIS5. The analysis of mitotic recombination revealed that UVS112 lies between HIS6 and HIS5, and is an allele of the RAD25 gene.


Free fatty acid metabolism of the human heart at rest.
Myocardial substrate metabolism was studied in 13 subjects at the time of diagnostic cardiac catheterization by means of palmitic acid-(14)C infusion with arterial and coronary sinus sampling. Two subjects were considered free of cardiac pathology and all, with one exception, demonstrated lactate extraction across the portion of heart under study. Data for this single lactate-producing subject were treated separately.The fractional extraction of (14)C-labeled free fatty acids (FFA) (44.4+/-9.5%) was nearly twice that of unlabeled FFA (23.2+/-7.8%) and raised the possibility of release of FFA into the coronary sinus. FFA uptake, based on either the arterial minus coronary sinus concentration difference or the FFA-(14)C fractional extraction, was directly proportional to the arterial FFA concentration. Gas-liquid chromatography failed to demonstrate selective handling of any individual FFA by the heart. Fractional oxidation of FFA was 53.5+/-12.7%, accounting for 53.2+/-14.4% of the heart's oxygen consumption while nonlipid substrates accounted for an additional 30.0+/-17.3%. Determinations of both labeled and unlabeled triglycerides suggested utilization of this substrate by the fasting human heart. Direct measurement of FFA fractional oxidation as well as FFA uptake, exclusive of possible simultaneous FFA release, would appear necessary in studies concerned with human myocardial FFA metabolism.


A chilling sensitive mutant of Arabidopsis with altered steryl-ester metabolism.
A chilling-sensitive mutant of Arabidopsis thaliana was isolated and subjected to genetic, physiological, and biochemical analysis. The chilling-sensitive nature of the mutant line is due to a single recessive nuclear mutation at a locus designated chs1. In contrast to wild-type plants, which are not adversely affected by low temperatures, the chs1 mutant is killed by several days of exposure to temperatures below 18 degrees C. Following exposure to chilling temperatures, the mutant displays two common symptoms of chilling injury-leaf chlorosis and electrolyte leakage. In these respects, the physiological response of the mutant to low temperatures mimics the response observed in some naturally occurring chilling sensitive species. The biochemical basis of chilling sensitivity was explored by examining the pattern of incorporation of (14)CO(2) into soluble metabolites and lipids in wild-type and mutant plants. The only difference observed between the mutant and wild type was that following low temperature treatment, the mutant accumulated 10-fold more radioactivity in a specific class of neutral lipids which were identified by a variety of criteria to be steryl-esters. The accumulation of radioactivity in the steryl-ester fraction occurs 24 hours before there is any visible evidence of chilling injury. These results suggest one of two possible explanations: either the mutation directly affects sterol metabolism, which in turn leads to chilling sensitivity, or the mutation affects another unidentified function and the accumulation of radioactivity in steryl-esters is a secondary consequence of chilling injury.


Molecular evolution of the avian growth hormone gene and comparison with its mammalian counterpart.
The molecular evolution of all available avian growth hormone (GH) gene sequences was investigated using both maximum-likelihood and parsimony methods, and the patterns compared to those found in mammals. In contrast to the rapid bursts of evolution observed for mammalian GH, the evolutionary rate of the avian GH mature peptide appears to have been more constant. However several positively selected sites were identified at functionally important positions in the avian signal peptide by the site-specific likelihood method. This implies that sequence variation in the avian GH signal peptide may be adaptive, although more conservative parsimony methods failed to confirm this. Nevertheless, the differing patterns of avian and mammalian GH signal peptide molecular evolution are consistent with the apparently differing roles of GH in controlling growth in these taxonomic groups and support the hypothesis that signal peptide sequence variation may in fact be the basis for increased functional complexity.


Effects of hypophysectomy and human chorionic gonadotrophin on Leydig cell function in mature rats.
The biochemical activities involved in the maintenance of Leydig cell functions, and the effects of hypophysectomy and human chorionic gonadotrophin (hCG) on these functions are largely unknown. In the present study, adult hypophysectomized rats were used as a model to determine the effects of these treatments on a number of biochemical and morphological parameters. After 33 days of hypophysectomy, the morphology of the Leydig cells had been drastically altered. In addition, alpha-naphthol and beta-naphthol esterase activity as well as the steroidogenic capacity of the Leydig cells were greatly reduced at this time. In contrast, the level of sterol carrier protein 2 (SCP2), a Leydig cell-specific protein, was affected by hypophysectomy much less than the other parameters measured. Two daily injections of hCG to rats hypophysectomized for 31 days resulted in no change in the morphology of the Leydig cells, or in their proliferative activity. Non-specific esterase activities were also unaffected by 2 days of treatment with hCG. However, two injections of hCG to rats hypophysectomized for 31 days resulted in nearly complete restoration of steroidogenic capacity, and a 3.5-fold increase in the level of SCP2. These findings indicate that hypophysectomy results in significant morphological and biochemical changes in Leydig cells, and that hCG is capable of restoring some of these capacities within a short time.


Idiopathic granulomatous meningoencephalitis presenting as an intracranial tumor.
A 2-year-old girl presented with a single episode of generalized seizure. Magnetic resonance imaging examination showed an intracranial mass with a diameter of 2.5 cm in the right parieto-occipital region of the cerebrum. These clinicoradiological findings were suggestive of intracranial tumor. Histologically, fibroblastic proliferation of storiform pattern was noted, associated with epithelioid granulomas. The etiological pathogens for the granulomas could not be detected even though investigation of special histochemical staining, immunohistochemical study and DNA analysis of Mycobacterium tuberculosis by polymerase chain reaction technique was performed. On electron microscopic examination, the area appearing as a storiform pattern consisted of fibroblasts showing much dilated rough endoplasmic reticulum and slender tappering cytoplasmic processes without cellular junctional complex. No organisms were identified in the granulomatous area of the lesion. From those findings the diagnosis as idiopathic granulomatous meningoencephalitis was made.


Protocol: Benefits and harms of remdesivir for COVID-19 in adults: A systematic review with meta-analysis.
Effective drug treatments for Covid-19 are needed to decrease morbidity and mortality for the individual and to alleviate pressure on health care systems. Remdesivir showed promising results in early randomised trials but subsequently a large publicly funded trial has shown less favourable results and the evidence is interpreted differently in clinical guidelines. Systematic reviews of remdesivir have been published, but none have systematically searched for unpublished data, including regulatory documents, and assessed the risk of bias due to missing evidence. We will conduct a systematic review of randomised trials comparing remdesivir to placebo or standard of care in any setting. We will include trials regardless of the severity of disease and we will include trials examining remdesivir for indications other than Covid-19 for harms analyses. We will search websites of regulatory agencies, trial registries, bibliographic databases, preprint servers and contact trial sponsors to obtain all available data, including unpublished clinical data, for all eligible trials. Our primary outcomes will be all-cause mortality and serious adverse events. Our secondary outcomes will be length of hospital stay, time to death, severe disease, and adverse events. We will assess the risk of bias using the Cochranes Risk of Bias 2 tool and the risk of bias due to missing evidence (e.g. publication bias, selective reporting bias) using the ROB-ME tool. Where appropriate we will synthesise study results by conducting random-effects meta-analysis. We will present our findings in a Summary of Findings table and rate the certainty of the evidence using the GRADE approach. By conducting a comprehensive systematic review including unpublished data (where available), we expect to be able to provide valuable information for patients and clinicians about the benefits and harms of remdesivir for the treatment of Covid-19. This will help to ensure optimal treatment for individual patients and optimal utilisation of health care resources. CRD42021255915.


In vivo biostability of shore 55D polyether polyurethanes with and without fluoropolymer surface modifying endgroups.
Polyether polyurethanes are subject to autooxidation and environmental stress cracking (ESC) because of interactions with lysosomal oxygen-free radicals. Oxidation can also be catalyzed by and caused by direct (redox) reaction with transition metal ions (metal ion oxidation, MIO). The source of the ions is corrosion of metallic parts within an implanted device. A previous study on a Shore 80A polyether polyurethane modified with fluoropolymer surface modifying end groups demonstrated improved biostability over unmodified controls. We predicted that this could be extrapolated to the inherently more biostable Shore 55D version (E55DF). While it is difficult to demonstrate significant biodegradation in the harder polymers within a reasonable time frame, we did see excellent biologic autooxidation and ESC resistance for both E55DF and its unmodified Shore 55D (P55D) control. E55DF was slightly, but significantly more resistant to MIO than P55D. This was particularly evident in molecular weight distributions with P55D exhibiting a large decrease in number average molecular weight compared to no change for E55DF. Both were markedly superior to the softer Shore 80A control. It does appear that one can extrapolate accelerated in vivo biostability results with the softer polymers to their harder analogues.


Sweet memories: epigenetic control in flowering.
Many plants respond to winter with epigenetic factors that gradually dampen repression of flowering so that they can flower in spring. The study of this process was important for the identification of the plant Polycomb group (PcG) of proteins and their role in the epigenetic control of plant gene expression. Fittingly, these studies continue to illuminate our understanding of PcG function. We discuss recent advances, particularly the role of noncoding RNA in the recruitment of PcG to target genes, and the role of the PcG in regulating the stem cell pool in flowers.


The eccentric lumenology.
Coronary angiography has a poor predictive value for the detection of eccentric plaque morphology. Many reports have demonstrated discordance between the angiographic classification and the intravascular ultrasound (IVUS) classification. Although eccentricity is usually considered a dichotomous character, more than two-thirds of all coronary stenosis have some degree of eccentricity. The American College of Cardiology/American Heart Association (ACC/AHA) Task force included lesion eccentricity as a risk factor for moderate procedural success (60-85%) and moderate complications (type B). Although lesion eccentricity has been implicated as a risk factor for reduced short-term procedural results, current available data does not support the adverse impact of eccentricity on procedural success or restenosis. The present article reviews the incidence and the various clinical scenarios known to be associated with the eccentric lumenogram and the impact of coronary artery remodeling contributing to misinterpretation of disease eccentricity. Various therapeutic modalities with reference to eccentric lesions are also considered.


[Effect of indomethacin on the intracranial pressure].
Twenty patients subjected to craniotomy for supratentorial cerebral tumours were anaesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. A significant decrease in intracranial pressure from 6.5 to 1.5 mmHg (medians) was found after indomethacin administration. This decrease was caused by a significant decrease in cerebral blood flow associated with a significant increase in the arterio-venous oxygen difference. Indomethacin did not affect cerebral oxygen uptake, arteriovenous difference in lactate or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischaemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients, and dura was opened without the occurrence of cerebral swelling. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anaesthesia for craniotomy.


Electron transfer from cytochrome c to O2.
Transient-state kinetic results on the reaction between oxygen and cytochrome oxidase alone and in its electrostatic complex with cytochrome c are reported. Time courses at 830 nm for the enzyme alone reacting with O2 reveal complex kinetics for the oxidation of CuA. The time course begins with a lag phase, which becomes progressively shorter as the O2 concentration is increased. When cytochrome c is included the lag phase is extended. Cytochrome c oxidation proceeds to a level of 80% in 5 milleseconds, and it is possible to resolve two rates over this time range. The dependence of these rates upon O2 concentration is reported here. The second, slower phase is rate-limited at a first-order value of 500 sec-1 at or above 200 microM O2. In contrast, the initial phase is proportional to O2 up to the highest O2 concentration used here (i.e. 340 microM) and reaches a rate of 6500 sec-1. In addition the time course of cytochrome c oxidation begins immediately (i.e., without a lag). It is proposed that the fast phase of cytochrome c oxidation is the result of electron transfer to O2, either via CuA or direct to the oxygen binding site. These pathways for electron transfer are not observed in the reductive half-reaction and may be the result of a conformational change in the oxidase that lowers a kinetic barrier to electron transfer present in the oxidized enzyme.


A controlled study of 20 mg famotidine nocte vs. 150 mg ranitidine nocte for the prevention of duodenal ulcer relapse.
A 24-week, double-blind, randomized study at 13 centres compared the efficacy and safety of 20 mg famotidine nocte and 150 mg ranitidine h.s. for the prevention of duodenal ulcer recurrence. All participants had been successfully treated for an acute duodenal ulcer with 40 mg famotidine nocte. Patients were endoscoped at baseline and at 24 weeks, unless symptoms warranted earlier examination: of the 208 patients enrolled, 86 who received famotidine and 84 who received ranitidine met all protocol criteria and were considered evaluable. Intention to treat and per protocol analyses showed non-significant trends in favour of famotidine (P = 0.44 and 0.16, respectively). During the 24-week observation period, 16.3% of the famotidine group and 25% of the ranitidine group had an ulcer recurrence (95% CI of percentage difference -0.22 + 0.04). At 24 weeks, relief of day and night pain was reported by 81.2% and 91.8% of the famotidine-treated patients, respectively. The corresponding figures in the ranitidine group were 73.5% and 85.5%. No laboratory abnormalities related to the study-drugs were noted and only two drug related (possibly or probably) adverse experiences were reported, both in the famotidine group. The data from this study therefore, supports the conclusion that the efficacy of 20 mg famotidine nocte is comparable to that of ranitidine in preventing duodenal ulcer recurrence, with comparable tolerability for long-term therapy.


On the size of tokamak fusion power plants.
Figures of merit for future tokamak fusion power plants (FPPs) are presented. It is argued that extrapolation from present-day experiments to proposed FPPs must follow a consistent development path, demonstrating the largest required leaps in intermediate devices to allow safe extrapolation to an FPP. This concerns both plasma physics and technology. At constant plasma parameters, the figures of merit depend on both major radius R and magnetic field B. We propose to use the term 'size' for a combination of R and B to avoid ambiguities in scaling arguments. Two routes to FPPs are discussed: the more conventional one increasing R, based on the assumption that B is limited by present technology; and an alternative approach assuming the availability of new technology for superconducting coils, allowing higher B. It is shown that the latter will lead to more compact devices, and, assuming a criterion based on divertor impurity concentration, is in addition more favourable concerning the exhaust problem. However, in order to obtain attractive steady-state tokamak FPPs, the required plasma parameters still require considerable progress with respect to present experiments. A credible strategy to arrive at these must hence be shown for both paths. In addition, the high-field path needs a demonstration of the critical technology items early on. This article is part of a discussion meeting issue 'Fusion energy using tokamaks: can development be accelerated?'.


Bipolar Button Transurethral Enucleation of Prostate in Benign Prostate Hypertrophy Treatment: A New Surgical Technique.
To evaluate the safety and efficacy of transurethral bipolar enucleation with a button electrode (B-TUEP) for the treatment of bladder outlet obstruction due to benign prostatic hyperplasia. Between July 2011 and March 2012, a single surgeon performed 50 B-TUEP. Preoperative and postoperative assessments included prostate-specific antigen, International Prostate Symptoms Score (IPSS), International Index of Erectile Function-5 (IIEF-5), quality of life (QoL) index, uroflowmetry with postvoiding residual (PVR) urinary volume, and prostate volume measured by transrectal ultrasonography. Intraoperatively, we evaluated B-TUEP time (enucleation and resection time). Perioperatively, we evaluated hemoglobin dosage, bladder irrigation time, catheterization time, acute urinary retention events, length of stay, patient readmission, and any endoscopic retreatments. Three months after surgery, 82% of the patients presented a significant improvement in maximum urine flow (Qmax; P <.001). At 6 and 12 months, 80% and 83.3% of patients maintained the significant improvement (P <.001). The secondary end points IPSS, QoL, IIEF-5, and PVR presented a statistically significant improvement compared with baseline values. No significant change in hemoglobin values was observed before and after surgery. Bladder irrigation time was comprised between 24 and 36 hours for about 80% of patients. In one case, second-look hemostatic endoscopy was needed. Length of stay after surgery was <48 hours in 88% of cases. Readmission was required for 6% of patients for hematuria, and 6 months later, 2 other patients developed bladder neck contracture treated with transurethral incision of the prostate. B-TUEP using the Gyrus PK system is a rapid and safety technique with optimal outcomes.


Identifying the key performance improvement domains for home health agencies.
The objective of this study was to support home health agencies (HHAs) in the United States (US) in their individualized quality assessment and performance improvement (QAPI) initiatives by identifying their key performance improvement domains (KPIDs). Qualitative research was conducted by following the Framework method. Rich contextual data were obtained through focus group meetings participated by domain experts. The analysis results were further refined in an online forum and validated at a final meeting. Four focus groups involving a total of 20 participants resulted in useful discussions during which various perspectives were expressed by the expert participants. A well-defined set of 17 KPIDs emerged under four categories, namely, economical value, sociocultural sensitivity, interpersonal relationships, and clinical capabilities. The feedback we received from the focus groups indicates that performance improvement in HHAs is a lot more complicated than simply assessing whether certain clinical tasks are performed. The KPIDs identified in this study can help HHAs in their focused and individualized QAPI initiatives. Therefore, the results should be immediately relevant, interesting, and useful to the home care industry and policy makers in the US.


Rapidoxy® 100: A Solvent-Free Pre-treatment for Production of Canolol.
RapidOxy® 100 is an automated instrument originally designed for measuring the oxidative stability of both solid and liquid samples. The compact and portable design of RapidOxy® 100, and its built-in pressurized heating chamber, provides a suitable environment for studying processing conditions. The feasibility of using oxygen or an inert atmosphere provides the ideal environment to study the effect of dry heat pre-treatment on canola antioxidants. The current study used RapidOxy® 100 to examine the impact of pressurized dry heat pre-treatment, under nitrogen, on the ultrasonic extraction of phenolic compounds. The effect of different pre-treatment temperature-time combinations of 120, 140, 160, and 180°C for 2, 5, 10, 15, and 20 min on the subsequent extraction of canola phenolic compounds was examined. The major sinapates identified by HPLC were sinapine, sinapic acid, and canolol. The optimum RapidOxy® condition for the maximum recovery of canolol was 160°C for 10 min. RapidOxy® 100 proved to be a novel and versatile instrument for enhancing the extraction of phenolic compounds.


Magnetic resonance myocardial perfusion imaging at 3.0 Tesla for the identification of myocardial ischaemia: comparison with coronary catheter angiography and fractional flow reserve measurements.
To assess image quality and diagnostic performance of 3.0 Tesla (3T) cardiac magnetic resonance (CMR) myocardial perfusion imaging with a dual radiofrequency source to detect functional relevant coronary artery disease (CAD), using coronary angiography and invasive pressure-derived fractional flow reserve (FFR) as reference standard. We included 116 patients with suspected or known CAD, who underwent 3T adenosine myocardial perfusion CMR (resolution 2.97 × 2.97 mm) and coronary angiography plus FFR measurements in intermediate lesions. Image quality of myocardial perfusion CMR was graded on a 4-point scale (1 = poor to 4 = excellent). Diagnostic accuracy was assessed by ROC analyses using a 16-myocardial segment-based summed perfusion score (0 = normal to 3 = transmural perfusion defect) and by determining sensitivity, specificity, positive and negative predictive value on the coronary vessel territory and the patient level. Diagnostic image quality was achieved for all stress myocardial perfusion CMR studies with an average quality score of 2.5, 3.1, and 3.0 for LAD, LCX, and RCA territories. The ability of the myocardial perfusion CMR perfusion score to detect significant coronary artery stenosis yielded an area under the curve of 0.93 on ROC analysis. Values for sensitivity, specificity, positive and negative predictive value on a vessel territory level and the patient level were 89, 95, 87, 96% and 85, 87, 77, 92%, respectively. In patients with suspected or known significant CAD, 3T myocardial perfusion CMR with standard perfusion protocols provides consistently high image quality and an excellent diagnostic performance.