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1.
Res Social Adm Pharm ; 18(10): 3744-3750, 2022 10.
Article in English | MEDLINE | ID: mdl-35581126

ABSTRACT

BACKGROUND: Workforce reform has placed a significant focus on the role of non-medical prescribers in the healthcare system. Pharmacists are trained in pharmacology and therapeutics, and therefore well placed to act as non-medical prescribers. OBJECTIVES: To assess the safety and accuracy of inpatient medication charts within a pharmacist collaborative prescribing model (intervention), compared to the usual medical model (control) in the emergency department (ED). Another objective compared venous thromboembolism (VTE) risk assessment and prescribing, between intervention and control groups. METHODS: Adult patients in ED referred for hospital admission were randomised into control or intervention by a block randomisation method, until the required sample size was reached. Medication charts were audited retrospectively by an independent auditor, using validated audit forms. RESULTS: Intervention group medication charts contained significantly fewer prescribing errors, omissions and discrepancies compared to the control group, and improved documentation of adverse drug reactions. VTE risk assessment and prescribing had higher guideline concordance in the intervention group compared to the control group. CONCLUSIONS: This collaborative prescribing trial showed excellent results in safety and accuracy of pharmacist prescribing when compared to the usual medical model of prescribing. The admitting medical practitioner and extended scope pharmacist prescriber worked as a collaborative team in emergency, which improved Australian national prescribing safety indicators.


Subject(s)
Pharmacists , Venous Thromboembolism , Adult , Australia , Emergency Service, Hospital , Humans , Retrospective Studies , Venous Thromboembolism/drug therapy
2.
Opt Express ; 29(21): 34748-34761, 2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34809257

ABSTRACT

In this paper we propose a new method to jointly design a sensor and its neural-network based processing. Using a differential ray tracing (DRT) model, we simulate the sensor point-spread function (PSF) and its partial derivative with respect to any of the sensor lens parameters. The proposed ray tracing model makes no thin lens nor paraxial approximation, and is valid for any field of view and point source position. Using the gradient backpropagation framework for neural network optimization, any of the lens parameter can then be jointly optimized along with the neural network parameters. We validate our method for image restoration applications using three proves of concept of focus setting optimization of a given sensor. We provide here interpretations of the joint optical and processing optimization results obtained with the proposed method in these simple cases. Our method paves the way to end-to-end design of a neural network and lens using the complete set of optical parameters within the full sensor field of view.

3.
Crop Sci ; 60(3): 1450-1461, 2020.
Article in English | MEDLINE | ID: mdl-32742003

ABSTRACT

Understanding the genetic relationships among farmer-preferred cassava (Manihot esculenta Crantz) varieties is indispensable to genetic improvement efforts. In this study, we present a genetic analysis of 547 samples of cassava grown by 192 smallholder farmers, which were sampled at random within four districts in Uganda. We genotyped these samples at 287,952 single nucleotide polymorphisms using genotyping-by-sequencing and co-analyzed them with 349 cassava samples from the national breeding program in Uganda. The samples collected from smallholders consisted of 86 genetically unique varieties, as assessed using a genetic distance-based approach. Of these varieties, most were cultivated in only one district (30 in Kibaale, 19 in Masindi, 14 in Arua, and three in Apac), and only three were cultivated across all districts. The genetic differentiation we observed among farming districts in Uganda (mean fixation index [F ST] = .003) is similar to divergence observed within other countries. Despite the fact that none of the breeding lines were directly observed in farmer fields, genetic divergence between the populations was low (F ST = .020). Interestingly, we detected the presence of introgressions from the wild relative M. glaziovii Müll. Arg. on chromosomes 1 and 4, which implies ancestry with cassava breeding lines. Given the apparently similar pool of alleles in the breeding germplasm, it is likely that breeders have the raw genetic material they require to match the farmer-preferred trait combinations necessary for adoption. Our study highlights the importance of understanding the genetic makeup of cassava currently grown by smallholder farmers and relative to that of plant breeding germplasm.

4.
Dent Mater J ; 39(4): 601-607, 2020 Aug 02.
Article in English | MEDLINE | ID: mdl-32213764

ABSTRACT

The aim of this study was to evaluate the physical properties of calcium-silicate based cements as retrograde filling in different pH and blood conditions using micro-CT. Eighty-four teeth were obturated and after root-end resection, 3 mm-deep root-end cavity was ultrasonically prepared. The samples were divided into four test groups (n=21). Cements were freshly prepared and analyzed with micro-CT before and after exposed. The test groups were exposed for four days to environments containing acid, alkali, or blood. An acidic pH significantly reduced the volume of all materials after four days and differed from the other environments. Biodentine has the highest percentage of loss in volume and density after treatment in an acidic environment. Porosity formation in the acidic medium was observed in Biodentine amongst all materials. The three-dimensional structures of all materials changed after exposed to an acidic pH, while fewer changes were observed in the structures of materials treated with blood and alkali.


Subject(s)
Root Canal Filling Materials , Aluminum Compounds , Calcium Compounds , Calcium Hydroxide , Drug Combinations , Hydroxyapatites , Oxides , Pemetrexed , Silicates , X-Ray Microtomography
5.
J Genet ; 982019 Nov.
Article in English | MEDLINE | ID: mdl-31767816

ABSTRACT

Seedling and adult plant (field) resistance to yellow rust in the durum wheat (Triticum turgidum ssp. durum) cross Kunduru-1149 x Cham-1 was characterized using a functionally-targeted DNA marker system, NBS-profiling. Chi-squared analysis indicated a four gene model conferring seedling yellow rust resistance against Puccinia striiformis f. sp. tritici isolate WYR85/22 (virulent on Yr2, Yr6, Yr7 and Yr9). Interval mapping located two QTL for yellow rust resistance on the long arm of chromosome 1B, while Kruskal-Wallis single marker regression identified a number of additional marker loci associated with seedling and/or adult plant, field resistance to yellow rust. These results suggested that much of the yellow rust resistance seen in the field may be due to seedling expressed resistance (R) genes. Characterization of the DNA sequence of three NBS marker loci indicated that all showed significant homology to functionally-characterized R-genes and resistance gene analogues (RGAs), with the greatest homology being NBS-LRR-type R-genes and RGAs from cereal species.


Subject(s)
Disease Resistance/genetics , Triticum/genetics , Triticum/immunology , Basidiomycota/pathogenicity , Chromosome Mapping , Genes, Plant/genetics , Genetic Markers , Genome, Plant , Immunity, Innate/genetics , Immunity, Innate/immunology , Plant Diseases/genetics , Plant Diseases/immunology , Plant Diseases/microbiology , Quantitative Trait Loci , Seedlings/genetics , Sequence Analysis , Transcriptome , Triticum/microbiology
6.
Dig Dis Sci ; 64(12): 3502-3517, 2019 12.
Article in English | MEDLINE | ID: mdl-31187328

ABSTRACT

BACKGROUND: Gastrointestinal (GI) motility dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Studies have indicated that GI motility functions are impaired before the onset of PD. AIMS: To investigate the underlying mechanism of PD-induced GI dysmotility in MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine)-induced animal model. METHODS: C57BL/6 mice were administered with or without a selective dopamine neurotoxin, MPTP, to induce parkinsonian symptoms. In addition to in vivo studies, in vitro experiments were also conducted in colon specimens using l-methyl-4-phenylpyridinium (MPP+), a metabolic product of MPTP. Gastric emptying, colon motility, nitrergic relaxation, and western blot experiments were performed as reported. RESULTS: MPTP-induced PD mice showed decreased expression of nuclear factor erythroid 2-related factor (Nrf2) and its target phase II genes in gastric and colon neuromuscular tissues. Decreased levels of tetrahydrobiopterin (BH4, a critical cofactor for nNOS dimerization) associated with uncoupling of nNOS in gastric and colon tissues exposed to MPTP. Impaired enteric nitrergic system led to delayed gastric emptying and slower colonic motility compared to the control mice. In vitro results in colon specimens confirm that activation of Nrf2 restored MPP+-induced suppression of alpha-synuclein, tyrosine hydroxylase (TH), Nrf2, and heme oxygenase-1. In vitro exposure to L-NAME [N(w)-nitro-L-arginine methyl ester], a NOS synthase inhibitor, reduced protein expression of TH in colon tissue homogenates. CONCLUSIONS: Loss of Nrf2/BH4/nNOS expression in PD impairs antioxidant gene expression, which deregulates NO synthesis, thereby contributing to the development of GI dysmotility and constipation. Nitric oxide appears to be important to maintain dopamine synthesis in the colon.


Subject(s)
Gastrointestinal Motility/physiology , MPTP Poisoning/genetics , NF-E2-Related Factor 2/genetics , Nitric Oxide Synthase Type I/genetics , Nitric Oxide/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , 1-Methyl-4-phenylpyridinium/pharmacology , Animals , Biopterins/analogs & derivatives , Biopterins/metabolism , Blotting, Western , Colon/drug effects , Colon/metabolism , Colon/physiopathology , Constipation , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Gastric Emptying/physiology , Gene Expression Regulation , Heme Oxygenase-1/drug effects , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , MPTP Poisoning/metabolism , MPTP Poisoning/physiopathology , Male , Membrane Proteins/drug effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase Type I/metabolism , Parkinson Disease/physiopathology , Parkinsonian Disorders , Tyrosine 3-Monooxygenase/drug effects , Tyrosine 3-Monooxygenase/genetics , Tyrosine 3-Monooxygenase/metabolism , alpha-Synuclein/drug effects , alpha-Synuclein/genetics , alpha-Synuclein/metabolism
7.
Niger J Clin Pract ; 22(1): 101-107, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30666027

ABSTRACT

AIM: This study evaluated the effect of different irrigation protocols on elastic modulus and biomechanics of single-rooted premolar tooth using with nano-indentation and finite element analysis (FEA). MATERIALS AND METHODS: Root canals of single-rooted human teeth were prepared, divided into eight groups, and irrigated with (1) 2.5% NaOCl + 17% EDTA; (2) 2.5% NaOCl + 17% EDTA + 2.5% NaOCl; (3) 2.5% NaOCl + SmearClear; (4) 2.5% NaOCl + 2% chlorhexidine; (5) 1.3% NaOCl + MTAD; (6) 5.25% NaOCl; (7) 17% EDTA; and (8) saline. The roots were vertically sectioned, and elastic modulus of the root dentine was measured using nano-indenter device at coronal, middle, and apical third. Data were recorded as megapascal and statistically analyzed (one-way analysis of variance, Tukey tests). Three-dimensional FEA model of a premolar tooth was created, and the inner root dentine was modified to simulate the effect of irrigation protocols on root dentine. The elastic properties of inner root dentine layer in the FEA models were modified for each group according to the data obtained with nano-indentation. A 300-N load was applied at the buccal cusp and central fossa of the models with a 45° angle. The stresses were calculated using von Mises stress criteria. RESULTS: All irrigation protocols affected the elastic modulus of root dentine. Groups 2 and 3 showed similar elastic modulus values (P > 0.05), whereas the lowest values were obtained in group 7 (P < 0.05). No statistically significant differences were found between groups 4, 5, and 8 (P > 0.05). CONCLUSION: Despite the effect of different clinically used irrigation protocols on elastic modulus of the inner dentine, this does not affect the biomechanics of the roots.


Subject(s)
Dental Pulp Cavity/drug effects , Dentin/drug effects , Disinfectants/pharmacology , Elastic Modulus , Finite Element Analysis , Root Canal Irrigants/pharmacology , Sodium Hypochlorite/pharmacology , Tooth Root/drug effects , Bicuspid , Chlorhexidine/pharmacology , Edetic Acid/pharmacology , Hardness Tests , Humans , Root Canal Preparation/methods
8.
Appl Ergon ; 60: 30-42, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28166889

ABSTRACT

A large portion of road traffic crashes occur at intersections for the reason that drivers lack necessary visual information. This research examined the effects of an audio-visual display that provides real-time sonification and visualization of the speed and direction of another car approaching the crossroads on an intersecting road. The location of red blinking lights (left vs. right on the speedometer) and the lateral input direction of beeps (left vs. right ear in headphones) corresponded to the direction from where the other car approached, and the blink and beep rates were a function of the approaching car's speed. Two driving simulators were linked so that the participant and the experimenter drove in the same virtual world. Participants (N = 25) completed four sessions (two with the audio-visual display on, two with the audio-visual display off), each session consisting of 22 intersections at which the experimenter approached from the left or right and either maintained speed or slowed down. Compared to driving with the display off, the audio-visual display resulted in enhanced traffic efficiency (i.e., greater mean speed, less coasting) while not compromising safety (i.e., the time gap between the two vehicles was equivalent). A post-experiment questionnaire showed that the beeps were regarded as more useful than the lights. It is argued that the audio-visual display is a promising means of supporting drivers until fully automated driving is technically feasible.


Subject(s)
Acoustic Stimulation , Automobile Driving , Computer Simulation , Photic Stimulation , Safety , Accidents, Traffic/prevention & control , Adult , Aged , Feedback, Sensory , Female , Humans , Male , Middle Aged , Task Performance and Analysis , Time Factors
10.
PLoS One ; 9(5): e96642, 2014.
Article in English | MEDLINE | ID: mdl-24846209

ABSTRACT

Cassava (Manihot esculenta) is a major food staple in sub-Saharan Africa, which is severely affected by cassava brown streak disease (CBSD). The aim of this study was to identify resistance for CBSD as well as to understand the mechanism of putative resistance for providing effective control for the disease. Three cassava varieties; Kaleso, Kiroba and Albert were inoculated with cassava brown streak viruses by grafting and also using the natural insect vector the whitefly, Bemisia tabaci. Kaleso expressed mild or no disease symptoms and supported low concentrations of viruses, which is a characteristic of resistant plants. In comparison, Kiroba expressed severe leaf but milder root symptoms, while Albert was susceptible with severe symptoms both on leaves and roots. Real-time PCR was used to estimate virus concentrations in cassava varieties. Virus quantities were higher in Kiroba and Albert compared to Kaleso. The Illumina RNA-sequencing was used to further understand the genetic basis of resistance. More than 700 genes were uniquely overexpressed in Kaleso in response to virus infection compared to Albert. Surprisingly, none of them were similar to known resistant gene orthologs. Some of the overexpressed genes, however, belonged to the hormone signalling pathways and secondary metabolites, both of which are linked to plant resistance. These genes should be further characterised before confirming their role in resistance to CBSD.


Subject(s)
Disease Resistance/genetics , Manihot/genetics , Manihot/virology , Plant Diseases/genetics , Plant Diseases/virology , Potyviridae/genetics , Potyviridae/metabolism
11.
J Clin Endocrinol Metab ; 99(5): 1648-55, 2014 May.
Article in English | MEDLINE | ID: mdl-24517152

ABSTRACT

CONTEXT AND OBJECTIVE: The incidence of TSH receptor (TSHR) stimulating autoantibodies (TSAbs) in pediatric Graves' disease (GD) is controversial. This large, multicenter study evaluated the clinical relevance of TSAbs in children with GD both with Graves' orbitopathy (GO) and without orbital disease. DESIGN: We conducted a cross-sectional retrospective study. SETTING: Sera were collected in seven American and European academic referral centers and evaluated in a central laboratory. PATIENTS AND SAMPLES: A total of 422 serum samples from 157 children with GD, 101 control individuals with other thyroid and nonthyroid autoimmune diseases, and 50 healthy children were studied. MAIN OUTCOME MEASURES: TSAbs were measured using a novel, chimeric TSHR bioassay and a cAMP response element-dependent luciferase. TSH binding-inhibitory Ig (TBII) and parameters of thyroid function were also determined. RESULTS: In 82 untreated children with GD, sensitivity, specificity, and positive and negative predictive values for TSAb and TBII were: 100 and 92.68% (P = .031), 100 and 100%, 100 and 100%, and 100 and 96.15%, respectively. TSAb and TBII were present in 147 (94%) and 138 (87.9%) of the 157 children with GD (P < .039), respectively; and in 247 (94%) and 233 (89%) of the 263 samples from this group (P < .0075), respectively. In children with GD and GO, TSAb and TBII were noted in 100 and 96% (P < .001), respectively. Hyperthyroid children with GD and GO showed markedly higher TSAb levels compared to those with thyroidal GD only (P < .0001). No significant differences were noted for TBII between the two groups. After a 3-year (median) medical treatment, the decrease of TSAb levels was 69% in GD vs 20% in GD and GO (P < .001). All 31 samples of euthyroid children with GO were TSAb positive; in contrast, only 24 were TBII positive (P = .016). All children with Hashimoto's thyroiditis, nonautoimmune hyperthyroidism, type 1 diabetes, and juvenile arthritis and the healthy controls were TSAb and TBII negative. CONCLUSIONS: Serum TSAb level is a sensitive, specific, and reproducible biomarker for pediatric GD and correlates well with disease severity and extrathyroidal manifestations.


Subject(s)
Graves Disease/immunology , Immunoglobulins, Thyroid-Stimulating/immunology , Adolescent , Autoimmune Diseases/blood , Autoimmune Diseases/immunology , Child , Female , Graves Disease/blood , Humans , Immunoglobulins, Thyroid-Stimulating/blood , Male , Retrospective Studies , Sensitivity and Specificity , Thyroid Hormones/blood , Young Adult
12.
J Vet Intern Med ; 28(2): 571-5, 2014.
Article in English | MEDLINE | ID: mdl-24467263

ABSTRACT

BACKGROUND: Standard practice in canine blood banking is to produce fresh frozen plasma (FFP) by separating and freezing plasma produced from blood within 8 hours of collection. Within canine blood donation programs, this can limit the number of units collected. HYPOTHESIS/OBJECTIVES: The aim was to compare the coagulation factor and hemostatic protein content (CF&HPC) of plasma produced from blood stored at ambient temperature for 8, 12, and 24 hours. Another aim was to compare the CF&HPC between Greyhound types and other breeds. ANIMALS: None. METHODS: In vitro study. A convenience sample of 58 units of canine blood from a blood donor pool was processed to prepare and freeze plasma 8, 12, or 24 hours following collection. RESULTS: Regardless of time of processing, the units contained therapeutic CF&HPC. Frozen plasma prepared after 24 hours had significantly higher factor VIII (P = .014) and factor X (P = .03) when compared with the frozen plasma prepared at 8 hours. Factor X (P < .01), fibrinogen (P < .01), and vWF (P = .04) were significantly lower in plasma collected from Greyhound types than in plasma collected from other breeds. CONCLUSIONS AND CLINICAL IMPORTANCE: Storing whole blood for up to 24 hours is a suitable method for producing FFP. Lower values for some coagulation factors and hemostatic proteins in plasma produced from Greyhound types would not preclude these dogs as FFP donors.


Subject(s)
Blood Coagulation Factors/analysis , Dogs/blood , Animals , Blood Specimen Collection/veterinary , Factor IX/analysis , Factor V/analysis , Factor VII/analysis , Factor VIII/analysis , Factor X/analysis , Female , Fibrinogen/analysis , Male , Prothrombin/analysis , Species Specificity , von Willebrand Factor/analysis
13.
Virus Res ; 186: 130-4, 2014 Jun 24.
Article in English | MEDLINE | ID: mdl-24361352

ABSTRACT

Asymptomatic field plants are the normal source of the vine cuttings used as sweetpotato planting material in Africa. Previous and new tests of such East African material, mostly using the very sensitive method of graft inoculation to the indicator plant Ipomoea setosa, showed that a majority tested virus-negative. This was despite their never having undergone any science-based therapy. To investigate how this occurs, in a replicated greenhouse experiment, plants of susceptible cultivars from the USA and Peru and three resistant Ugandan cultivars were graft-inoculated with Sweet potato feathery mottle virus (SPFMV), the commonest virus infecting sweetpotato. When the grafts were established, cuttings were taken, rooted and proved to be infected. The health status of each of these new plants was then followed over a 10-week period using a quantitative polymerase chain reaction assay. Most of the plants of the Ugandan cultivars eventually tested SPFMV-negative whereas those of the USA and Peru seldom did. Furthermore, in subsequent graft-inoculations of scions from the tip, top, middle and base of the vine of every plant to I. setosa plants, again, most of the scions of the Ugandan cultivars tested SPFMV-negative whereas those of the USA and Peru seldom did. These tests demonstrate the phenomenon of reversion in the Ugandan cultivars and can explain how most unprotected Ugandan sweetpotato field plants tested SPFMV-negative.


Subject(s)
DNA, Viral/genetics , Ipomoea batatas/immunology , Plant Diseases/immunology , Plant Immunity/genetics , Plant Leaves/immunology , Potyvirus/genetics , Breeding , Host-Pathogen Interactions , Ipomoea batatas/genetics , Ipomoea batatas/virology , Plant Diseases/genetics , Plant Diseases/virology , Plant Leaves/genetics , Plant Leaves/virology , Polymerase Chain Reaction , Potyvirus/pathogenicity , Uganda
14.
BMJ Open ; 3(7)2013.
Article in English | MEDLINE | ID: mdl-23847268

ABSTRACT

OBJECTIVES: Current evidence to support non-medical prescribing is predominantly qualitative, with little evaluation of accuracy, safety and appropriateness. Our aim was to evaluate a new model of service for the Australia healthcare system, of inpatient medication prescribing by a pharmacist in an elective surgery preadmission clinic (PAC) against usual care, using an endorsed performance framework. DESIGN: Single centre, randomised controlled, two-arm trial. SETTING: Elective surgery PAC in a Brisbane-based tertiary hospital. PARTICIPANTS: 400 adults scheduled for elective surgery were randomised to intervention or control. INTERVENTION: A pharmacist generated the inpatient medication chart to reflect the patient's regular medication, made a plan for medication perioperatively and prescribed venous thromboembolism (VTE) prophylaxis. In the control arm, the medication chart was generated by the Resident Medical Officers. OUTCOME MEASURES: Primary outcome was frequency of omissions and prescribing errors when compared against the medication history. The clinical significance of omissions was also analysed. Secondary outcome was appropriateness of VTE prophylaxis prescribing. RESULTS: There were significantly less unintended omissions of medications: 11 of 887 (1.2%) intervention orders compared with 383 of 1217 (31.5%) control (p<0.001). There were significantly less prescribing errors involving selection of drug, dose or frequency: 2 in 857 (0.2%) intervention orders compared with 51 in 807 (6.3%) control (p<0.001). Orders with at least one component of the prescription missing, incorrect or unclear occurred in 208 of 904 (23%) intervention orders and 445 of 1034 (43%) controls (p<0.001). VTE prophylaxis on admission to the ward was appropriate in 93% of intervention patients and 90% controls (p=0.29). CONCLUSIONS: Medication charts in the intervention arm contained fewer clinically significant omissions, and prescribing errors, when compared with controls. There was no difference in appropriateness of VTE prophylaxis on admission between the two groups. TRIAL REGISTRATION: Registered with ANZCTR-ACTR Number ACTRN12609000426280.

15.
Mol Ecol Resour ; 13(5): 776-80, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23647806

ABSTRACT

We developed a simple and reliable genetic method to determine sex in bats from the Vespertilionidae and Molossidae families. Polymerase chain reaction was used to amplify a portion of the introns within the zinc-finger-X (Zfx) and zinc-finger-Y (Zfy) genes. We designed primers to produce size variation between the Zfx and Zfy products that could be visualized using gel electrophoresis. Using an example from our wind-wildlife research, we show how sex data generated using this method are superior to sex data based on external morphology. Our method allows for the generation of sex data across a wide range of bats that can be used to address key questions in wildlife forensics, behavioural ecology, conservation and evolutionary biology.


Subject(s)
Chiroptera/classification , Chiroptera/genetics , Polymerase Chain Reaction/methods , Sex Determination Analysis/methods , Animals , DNA Primers/genetics , DNA-Binding Proteins/genetics , Female , Male , Molecular Sequence Data , Sequence Analysis, DNA
17.
Dig Dis Sci ; 58(6): 1507-15, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23504347

ABSTRACT

BACKGROUND: Gastroparesis affects predominantly females; however, the biological basis for this gender bias is completely unknown. Several lines of evidence suggest that nitrergic dependent stomach motility function is reduced in diabetic gastroparesis and that nNOS is estrogen-regulated. AIMS: The purpose of this study was to investigate whether reduced levels of estradiol-17ß (E2) down-regulates tetrahydrobiopterin (BH4, a cofactor for nNOS dimerization and enzyme activity) biosynthesis and therefore nNOS mediated gastric motility would be impaired in a mouse model of chronic estrogen deficiency, follicle stimulating hormone receptor knock-out female mice (FORKO). METHODS: In-bred 12-week-old female FORKO mice were obtained from our FORKO breeding colony. Gastric emptying was measured in overnight fasting mice. Nitrergic relaxation (AUC/mg tissue) was measured at 2 Hz through electric field stimulation using gastric antrum strips prepared from WT and FORKO mice. Protein expression for nNOSα, BH4 biosynthesis enzymes (GCH-1, DHFR) and estrogen receptors (α, ß) were measured in gastric antrum by western blotting. Levels of BH4 and oxidized BH2, B biopterin levels were determined by HPLC. RESULTS: In FORKO, compared to wild type (WT) stomachs we indentified (1) reduced (%) gastric emptying (64 ± 2.5 vs. 77.6 ± 0.88), (2) greater reduction in nitregic relaxation (-0.13 ± 0.012 vs. -0.28 ± 0.012), (3) increased nNOS dimerization (0.48 ± 0.02 vs. 0.34 ± 0.05), (4) decreased NO release whether measured at 24 h (0.6 ± 0.04 vs. 1.7 ± 0.22, p < 0.05) or at 48 h (3.4 ± 0.26 vs. 5.0 ± 0.15, p < 0.05) of incubation, (5) decreased GCH-1 (1.9 ± 0.06 vs. 2.3 ± 0.04), DHFR (1.8 ± 0.14 vs. 2.4 ± 0.07) and ERα (2.7 ± 0.4 vs. 3.9 ± 0.4) and (6) increased oxidized biopterin levels and decreased ratio of BH4 versus BH2 + B. CONCLUSION: We conclude that chronic estrogen deficiency negatively modifies the function of both BH4 and nNOS thereby contributing to the development of gastroparesis in a FORKO mouse model.


Subject(s)
Biopterins/analogs & derivatives , Estradiol/deficiency , Gastroparesis/etiology , Nitric Oxide Synthase Type I/metabolism , Animals , Biomarkers/metabolism , Biopterins/metabolism , Blotting, Western , Chromatography, High Pressure Liquid , Chronic Disease , Down-Regulation , Female , Gastric Emptying/physiology , Gastroparesis/enzymology , Mice , Mice, Knockout , Sex Factors
18.
Article in English | MEDLINE | ID: mdl-23410402

ABSTRACT

We introduce a way of characterizing an ensemble of interacting oscillators in terms of their mean-field variability index κ, a dimensionless parameter defined as the variance of the oscillators' mean field r divided by the mean square of r. Based on the assumption that the overall mean field is the sum of a very large number of oscillators, each giving a small contribution to the total signal, we show that κ depends on the mutual interactions between the oscillators, independently of their number or spectral properties. For purely random phasors, or a noninteracting ensemble of oscillators, κ converges on 0.215. Interactions push κ in different directions: lower where there is interoscillator phase coherence, tending to zero for complete phase synchronization, or higher for amplitude synchronization or intermittent synchronization. We calculate κ for several different cases to illustrate its utility, using both numerically simulated data and electroencephalograph signals from the brains of human subjects while awake, while anesthetized, and while undergoing an epileptic fit.


Subject(s)
Biological Clocks , Brain/physiopathology , Models, Neurological , Nerve Net/physiology , Oscillometry/methods , Seizures/physiopathology , Computer Simulation , Humans
19.
Ann R Coll Surg Engl ; 94(7): 476-80, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23031764

ABSTRACT

INTRODUCTION: The use of imaging and laparoscopy in patients with right iliac fossa pain as tools to make or exclude a diagnosis of appendicitis is at the discretion of the clinician. We sought to establish a consensus of opinion on this matter by surveying professional bodies for laparoscopic surgery in France, Italy and the US. METHODS: A survey was sent to members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), the French Society for Endoscopic Surgery (SFCE) and the Italian Society for Endoscopic Surgery (SICE). The survey asked about management of both male and female patients presenting with right iliac fossa pain and what operative strategy the respondents would pursue should they find a macroscopically normal appendix at laparoscopy. RESULTS: A total of 364 responses were returned from the three groups. The responses from SAGES showed computed tomography to be the preferred modality for investigating patients with right iliac fossa pain, irrespective of sex. Both SFCE and SICE preferred the use of diagnostic laparoscopy, especially in the female patient group. The majority of all respondents stated that they would remove a macroscopically normal appendix at laparoscopy. CONCLUSIONS: Laparoscopy remains a potent tool in the management of appendicitis. However, the dilemma of when to remove a macroscopically normal appendix remains. Our study shows that removal of the appendix in this instance would be supported by an international consensus.


Subject(s)
Appendectomy , Appendicitis/diagnosis , Appendicitis/surgery , Appendix/surgery , Abdominal Pain/etiology , Abdominal Pain/surgery , Appendix/pathology , England , Female , France , Health Care Surveys , Humans , Laparoscopy , Male , United States
20.
Mol Plant Pathol ; 13(7): 653-65, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22243838

ABSTRACT

Members of the Wheat-Induced Resistance 1 (TaWIR1) gene family are highly induced in response to a wide range of pathogens. Homologues have been identified in barley, but not in Brachypodium, whereas, in rice, only distant WIR1 candidates are known. Phylogenetic analysis placed TaWIR1a and TaWIR1b within a distinct clade of wheat transcripts, whereas TaWIR1c clustered with HvWIR1 genes. Transcripts of all three TaWIR1 genes were strongly induced by a wheat-adapted isolate of Magnaporthe oryzae. Virus-induced gene silencing of the TaWIR1 gene family had no effect on the initial penetration of epidermal cells by M. oryzae. However, following the establishment of an infection site, the fungus was able to grow more extensively within the leaf tissue, relative to control leaves, indicating a role for the TaWIR1 gene family in the cell-to-cell movement of M. oryzae. In contrast, the silencing of TaWIR1 transcripts had no effect on epidermal cell penetration by a wheat-adapted isolate of Blumeria graminis, or on the subsequent growth of hyphae. Differential transcription of TaWIR1 genes was also seen in epidermal peels, relative to the remaining leaf tissue, following inoculation with M. oryzae.


Subject(s)
Ascomycota/physiology , Disease Resistance/genetics , Genes, Plant/genetics , Magnaporthe/physiology , Plant Diseases/microbiology , Plant Proteins/genetics , Triticum/microbiology , Ascomycota/growth & development , Gene Expression Regulation, Plant , Gene Silencing , Magnaporthe/growth & development , Mosaic Viruses/physiology , Multigene Family/genetics , Oligonucleotide Array Sequence Analysis , Plant Diseases/genetics , Plant Leaves/genetics , Plant Leaves/microbiology , Plant Proteins/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Triticum/genetics , Triticum/virology
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