A Cost-Benefit Analysis of Government Compensation of Kidney Donors.
From 5000 to 10 000 kidney patients die prematurely in the United States each year, and about 100 000 more suffer the debilitating effects of dialysis, because of a shortage of transplant kidneys. To reduce this shortage, many advocate having the government compensate kidney donors. This paper presents a comprehensive cost-benefit analysis of such a change. It considers not only the substantial savings to society because kidney recipients would no longer need expensive dialysis treatments--$1.45 million per kidney recipient--but also estimates the monetary value of the longer and healthier lives that kidney recipients enjoy--about $1.3 million per recipient. These numbers dwarf the proposed $45 000-per-kidney compensation that might be needed to end the kidney shortage and eliminate the kidney transplant waiting list. From the viewpoint of society, the net benefit from saving thousands of lives each year and reducing the suffering of 100 000 more receiving dialysis would be about $46 billion per year, with the benefits exceeding the costs by a factor of 3. In addition, it would save taxpayers about $12 billion each year.


An update on biostatistics requirements in U.S. medical schools.
To update the results of previous surveys of medical schools in the United States concerning their courses in introductory biostatistics and to acquire additional information about these courses. In 1993, the authors sent a questionnaire to each of the 125 U.S. medical schools listed in the 1992-93 AAMC Directory of American Education. The questionnaire sought information about biostatistics courses and the subjects covered therein. One hundred of the 125 medical schools (80%) responded to the survey. Of those, 74 required a course in biostatistics as part of their undergraduate medical curriculum. The courses had large enrollments (median, 134) and a median of only 20 hours of instructional time. Most courses included a large amount of material, with 25 possible topics covered by at least 75% of the schools with required courses. While efforts have been made to incorporate innovative instructional techniques into these courses, most still follow the traditional lecture format and make minimal use of computers. Nevertheless, medical students appeared to have a favorable attitude toward these courses at over half of the schools surveyed.


Melatonin-induced downregulation of uterine prolactin receptors in mink (Mustela vison).
A study was conducted to investigate the effects of exogenous melatonin on serum concentrations of estradiol-17 beta (E2) and progesterone (P4) and uterine prolactin (PRL) receptor concentrations in mated mink. In Experiment 1, two groups of adult, standard dark, female mink were mated to fertile males on March 8 or 9. On March 16, mink in group 1 (N = 8) received an empty Silastic implant inserted sc in the interscapular region and served as controls. Mink in group 2 (N = 8) received an implant containing 10 mg crystalline melatonin. On April 2, all animals were lightly anesthetized and blood samples collected via cardiac puncture were analyzed for serum concentrations of E2 and P4. Animals were subsequently sacrificed and uterine samples collected for analysis of PRL receptor concentrations. In Experiment 2, adult female mink were assigned randomly to three treatment groups and mated to fertile males between March 6 and 9. On March 16, mink in group 1 (N = 6) received empty Silastic implants and served as controls. Mink in group 2 (N = 6) received a Silastic implant containing 10 mg melatonin. Animals in group 3 (N = 6) received an implant containing 10 mg melatonin and in addition each mink was given daily sc injections of P4 (1 mg) from March 21 to April 5. At this time the mink were sacrificed, the number of implantation sites recorded, and uteri collected for quantification of PRL receptors. In Experiment 1, exogenous melatonin reduced serum P4 concentrations to almost nondetectable levels (controls, 8.08 +/- 0.73 vs treated, 0.82 +/- 0. 12 ng/ml; P < 0.001) and resulted in increased concentrations of E2 (controls, 13.3 +/- 1.9 vs treated, 22.0 +/- 1.9 pg/ml; P < 0.01). Uterine PRL receptor concentrations decreased (P < 0.05) from 37.74 +/- 9.37 fmol/mg protein (controls) to 23.74 +/- 9.03 fmol/mg protein in response to melatonin treatment. In those mink treated with melatonin plus P4 (Experiment 2), uterine PRL receptor concentrations were increased to levels not significantly different than those of controls. None of the mink treated with melatonin alone or in combination with P4 exhibited implantation. Uteri of mink treated with melatonin or melatonin plus P4 did not differ in weight but tended to weigh less than uteri of control mink. These data suggest that a high systemic ratio of P4 to E2 is essential for production of the uterine PRL receptor in mink and supports the findings of others that implantation in mink cannot be initiated with P4 alone.


Api m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts.
Generalized systemic reactions to stinging hymenoptera venom constitute a potentially fatal condition in venom-allergic individuals. Hence, the identification and characterization of all allergens is imperative for improvement of diagnosis and design of effective immunotherapeutic approaches. Our aim was the immunochemical characterization of the carbohydrate-rich protein Api m 10, an Apis mellifera venom component and putative allergen, with focus on the relevance of glycosylation. Furthermore, the presence of Api m 10 in honeybee venom (HBV) and licensed venom immunotherapy preparations was addressed. Api m 10 was produced as soluble, aglycosylated protein in Escherichia coli and as differentially glycosylated protein providing a varying degree of fucosylation in insect cells. IgE reactivity and basophil activation of allergic patients were analyzed. For detection of Api m 10 in different venom preparations, a monoclonal human IgE antibody was generated. Both, the aglycosylated and the glycosylated variant of Api m 10 devoid of cross-reactive carbohydrate determinants (CCD), exhibited IgE reactivity with approximately 50% of HBV-sensitized patients. A corresponding reactivity could be documented for the activation of basophils. Although the detection of the native protein in crude HBV suggested content comparable to other relevant allergens, three therapeutical HBV extracts lacked detectable amounts of this component. Api m 10 is a genuine allergen of A. mellifera venom with IgE sensitizing potential in a significant fraction of allergic patients independent of CCD reactivity. Thus, Api m 10 could become a key element for component-resolved diagnostic tests and improved immunotherapeutic approaches in hymenoptera venom allergy.


Effects of Pseudomonas fluorescens F113 on Ecological Functions in the Pea Rhizosphere Are Dependent on pH.
> Abstract The aim of this microcosm study was to determine influence of the antibiotic 2,4-diacetylphloroglucinol (DAPG) on the effect of wild-type and functionally modified Pseudomonas fluorescens F113 strains in a sandy loam soil of pH 5.4 planted with pea (Pisum sativum var Montana). The functional modification of strain F113 was a repressed production of DAPG, useful in plant disease control, creating the DAPG negative strain F113 G22; both were marked with a lacZY gene cassette. Lowering the soil pH to 4.4 significantly reduced the plant shoot and root weights and the root length, whereas the bacterial inocula had no significant effect. Both inocula significantly reduced the shoot/root ratio at pH 5.4, but this effect was not evident at the lowered or elevated (6.4) pH levels. The decrease in pH significantly increased the fungal and yeast colony-forming units from the rhizosphere (root extract), but did not affect the total bacterial c.f.u.'s. Inoculatioin with strain F113 in the pH 4.4 soil resulted in a significantly greater total bacterial population. The fungal and yeast c.f.u.'s were not significantly affected by the inocula at any pH studied. Increasing the pH significantly increased the indigenous Pseudomonas population in comparison to the reduced pH treatment and significantly increased both the introduced and total Pseudomonas populations. The antibiotic producing strain significantly reduced the total bacterial population and the NAGase activity (related to fungal activity) at pH 6.4 where the inocula population was the greatest. Alkaline phosphatase, phosphodiesterase, aryl sulfatase, beta-glucosidase, alkaline beta-galactosidase, and NAGase activities significantly increased with increasing in pH. The F113 inocula reduced the acid phosphatase activity at pH 5.4 and increased the acid beta-galactosidase activity over all the pH treatments. The results presented illustrate the variation in impact with soil pH, with implications for variability in efficacy of Pseudomonas fluorescens biocontrol agents with soil pH.http://link.springer-ny.com/link/service/journals/00248/bibs/37n4p248.html


Y-chromosome genotyping and genetic structure of Zhuang populations.
Zhuang, the largest ethnic minority population in China, is one of the descendant groups of the ancient Bai-Yue. Linguistically, Zhuang languages are grouped into northern and southern dialects. To characterize its genetic structure, 13 East Asian-specific Y-chromosome biallelic markers and 7 Y-chromosome short tandem repeat (STR) markers were used to infer the haplogroups of Zhuang populations. Our results showed that O*, O2a, and O1 are the predominant haplogroups in Zhuang. Frequency distribution and principal component analysis showed that Zhuang was closely related to groups of Bai-Yue origin and therefore was likely to be the descendant of Bai-Yue. The results of principal component analysis and hierarchical clustering analysis contradicted the linguistically derived north-south division. Interestingly, a west-east clinal trend of haplotype frequency changes was observed, which was supported by AMOVA analysis that showed that between-population variance of east-west division was larger than that of north-south division. O* network suggested that the Hongshuihe branch was the center of Zhuang. Our study suggests that there are three major components in Zhuang. The O* and O2a constituted the original component; later, O1 was brought into Zhuang, especially eastern Zhuang; and finally, northern Han population brought O3 into the Zhuang populations.


Racial/Ethnic disparities in socioeconomic status, diagnosis, treatment and survival among medicare-insured men and women with head and neck cancer.
To determine whether racial disparities persist in Medicare-insured elderly patients with head and neck cancer, we studied 7,480 patients diagnosed with head and neck cancer at age 65 or older in 1991-2002, identified from tumor registries maintained by the 16 areas participating in the Surveillance, Epidemiology and End Results program. Patients receiving cancer-directed surgery had significantly lower risks of both all-cause and disease-specific mortality than others; those with lower socioeconomic status were more likely to die of all causes than patients with higher socioeconomic status. African Americans had a marginally higher risk of all-cause mortality (hazard ratio = 1.19, 95% CI: 1.07-1.33), but had no significantly different risk of disease-specific mortality compared with Whites (1.09, 0.91-1.30). In conclusion, the risk of mortality was not significantly different among African Americans and Hispanics compared with Whites in specific tumor sites of head and neck cancer except a marginally elevated risk of all-cause mortality in African Americans with oral cavity tumor.


Color vision defects in ocular hypertension and glaucoma. Quantification with a computer-driven color television system.
In order to detect early defects of color vision caused by increased intraocular pressure, a computer graphics device and color monitor system were used to measure color contrast sensitivity. The system determines the threshold chrominance of a colored grating in which there is no change in luminance. The study included 13 control subjects aged 10 to 57 years and 19 patients with ocular hypertension or glaucoma aged 20 to 58 years. In the 13 eyes with visual field loss, color contrast sensitivity was profoundly reduced when the grating colors fell on a tritan color confusion line. In the eyes without visual field loss, tritan color contrast sensitivity was reduced to an average level considerably below the extreme limits of the control group. These results were compared with those of other color vision tests and diagnostic criteria for glaucoma. The findings suggest that among the tests used, color contrast sensitivity testing was able to discriminate most effectively between patients who had retinal damage and the normal population.


Selective NMR observation of inhibitor and sugar binding to the galactose-H(+) symport protein GalP, of Escherichia coli.
The binding of the transport inhibitor forskolin, synthetically labelled with (13)C, to the galactose-H(+) symport protein GalP, overexpressed in its native inner membranes from Escherichia coli, was studied using cross-polarization magic angle spinning (13)C NMR. (13)C-Labelled D-galactose and D-glucose were displaced from GalP with the singly labelled [7-OCO(13)CH(3)]forskolin and were not bound to any alternative site within the protein, demonstrating that any multiple sugar binding sites are not simultaneously accessible to these sugars and the inhibitor within GalP. The observation of singly (13)C-labelled forskolin was hampered by interference from natural abundance (13)C in the membranes and so the effectiveness of double-quantum filtration was assessed for the exclusive detection of (13)C spin pairs in sugar (D-[1,2-(13)C(2)]glucose) and inhibitor ([7-O(13)CO(13)CH(3)]forskolin) bound to the GalP protein. The solid state NMR methodology was not effective in creating double-quantum selection of ligand bound with membranes in the 'fluid' state (approx. 2 degrees C) but could be applied in a straightforward way to systems that were kept frozen. At -35 degrees C, double-quantum filtration detected unbound sugar that was incorporated into ice structure within the sample, and was not distinguished from protein-bound sugar. However, the method detected doubly labelled forskolin that is selectively bound only to the transport system under these conditions and provided very effective suppression of interference from natural abundance (13)C background. These results indicate that solid state NMR methods can be used to resolve selectively the interactions of more hydrophobic ligands in the binding sites of target proteins.


Outcomes of cranioplasty following decompressive craniectomy in the pediatric population.
Cranioplasty is routinely performed following decompressive craniectomy in both adult and pediatric populations. In adults, this procedure is associated with higher rates of complications than is elective cranial surgery. This study is a review of the literature describing risk factors for complications after cranioplasty surgery in pediatric patients. A systematic search of PubMed, Cochrane, and SCOPUS databases was undertaken. Articles were selected based on their titles and abstracts. Only studies that focused on a pediatric population were included; case reports were excluded. Studies in which the authors assessed bone flap storage method, timing of cranioplasty, material used (synthetic vs autogenous), skull defect size, and/or complication rates (bone resorption and surgical site infection) were selected for further analysis. Eleven studies that included a total of 441 cranioplasties performed in the pediatric population are included in this review. The findings are as follows: 1) Based on analysis of pooled data, using cryopreserved bone flaps during cranioplasty may lead to a higher rate of bone resorption and lower rate of infection than using bone flaps stored at room temperature. 2) In 3 of 4 articles describing the effect of time between craniectomy and cranioplasty on complication rate, the authors found no significant effect, while in 1 the authors found that the incidence of bone resorption was significantly lower in children who had undergone early cranioplasty. Pooling of data was not possible for this analysis. 3) There are insufficient data to assess the effect of cranioplasty material on complication rate when considering only cranioplasties performed to repair decompressive craniectomy defects. However, when considering cranioplasties performed for any indication, those in which freshly harvested autograft is used may have a lower rate of resorption than those in which stored autograft is used. 4) There is no appreciable effect of craniectomy defect size or patient age on complication rate. There is a paucity of articles describing outcomes and complications following cranioplasty in children and adolescents. However, based on the studies examined in this systematic review, there are reasons to suspect that method of flap preservation, timing of surgery, and material used may be significant. Larger prospective and retrospective studies are needed to shed more light on this important issue.


[The diagnostic value of short-term video-EEG monitoring childhood epilepsy].
To investigate the value of short-term video-EEG monitoring in a pediatric population with distinct clinical complaints in order to verify the benefits and limitations of this procedure. A prospective protocol, developed in the University of São Paulo, analyzed 38 consecutive patients (age ranging from 4 months to 17 years; mean 6.9 years). All patients were referred in order to establish the diagnosis. The patients were divided in the following groups according to the main clinical complaint: doubts about seizure/syndromic classification (Group I, n = 22); differential diagnosis with non-epileptic events (Group II, n = 8) and differential diagnosis between cognitive decline and status epilepticus (Group III, n = 8). Clinical episodes were observed in 36 patients (94.7%). In group I, seizures were reclassified in 11/22 (50%) patients and confirmed in eight (36.4%). One patient presented a sleep disorder and two did not present clinical events during monitoring. Syndromic classification was modified in nine (40.9%). In group II, four patients (50%) presented epileptic seizures; two had movement disorders and two, non-epileptic events. The cognitive deterioration was correlated with non-convulsive status epilepticus in five children (62.5%) of group III. Alterations of therapeutic and/or diagnostic approaches, as a consequence of monitoring, were performed in 21/38 (55.3%) patients. In our series, short-term video-EEG monitoring established a reliable diagnosis in most patients due to correlation between clinical and EEG data. This procedure was well tolerated by children, including infants and those with psychiatric disorders.


Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2.
Previous studies have shown that lactogenic hormones stimulate beta-cell proliferation and insulin production in pancreatic islets. However, all such studies have been conducted in cells incubated in medium containing glucose. Since glucose independently stimulates beta-cell replication and insulin production, it is unclear whether the effects of prolactin (PRL) on insulin gene expression are exerted directly or through the uptake and/or metabolism of glucose. We examined the interactions between glucose and PRL in the regulation of insulin gene transcription and the expression of glucose transporter-2 (glut-2) and glucokinase mRNAs in rat insulinoma (INS-1) cells. In the presence of 5.5 mM glucose, the levels of preproinsulin and glut-2 mRNAs in PRL-treated cells exceeded the levels in control cells (1.7-fold, P<0.05 and 2-fold, P<0.05 respectively). The maximal effects of PRL were noted at 24-48 h of incubation. PRL had no effect on the levels of glucokinase mRNA. The higher levels of glut-2 mRNA were accompanied by an increase in the number of cellular glucose transporters, as demonstrated by a 1. 4- to 2.4-fold increase in the uptake of 2-deoxy-d-[(3)H]glucose in PRL-treated INS-1 cells (P<0.001). These findings suggested that the insulinotropic effect of PRL is mediated, in part, by induction of glucose transport and/or glucose metabolism. Nevertheless, even in the absence of glucose, PRL stimulated increases in the levels of preproinsulin mRNA (3.4-fold higher than controls, P<0.0001) and glut-2 mRNA (2-fold higher than controls, P<0.01). These observations suggested that PRL exerts glucose-independent as well as glucose-dependent effects on insulin gene expression. Support for this hypothesis was provided by studies of insulin gene transcription using INS-1 cells transfected with a plasmid containing the rat insulin 1 promoter linked to a luciferase reporter gene. Glucose and PRL, alone and in combination, stimulated increases in cellular luciferase activity. The relative potencies of glucose (5.5 mM) alone, PRL alone, and glucose plus PRL in combination were 2.2 (P<0.001), 3.4 (P<0.01), and 7.9 (P<0.0001) respectively. Our findings suggest that glucose and PRL act synergistically to induce insulin gene transcription.


Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors.
The biosynthetic pathway of the CoQ polyisoprenoid side chain, starting from acetyl-CoA and proceeding through mevalonate and isopentenylpyrophosphate, is the same as that of cholesterol. We performed this study to evaluate whether vastatins (hypocholesterolemic drugs that inhibit HMG-CoA reductase) modify blood levels of ubiquinone. Thirty-four unrelated outpatients with hypercholesterolemia (IIa phenotype) were treated with 20 mg of simvastatin for a 6-month period (group S) or with 20 mg of simvastatin plus 100 mg CoQ10 (group US). The following parameters were evaluated at time 0, 45, 90, 135 and 180 days: total plasma cholesterol (TC), HDL-cholesterol, LDL-cholesterol (LDL-C), triglycerides (TG), apo A1, apo B and CoQ10 in plasma and platelets. In the S group, there was a marked decrease in TC and LDL-C (from 290.3 mg/dl to 228.7 mg/dl for TC and from 228.7 mg/dl to 167.6 mg/dl for LDL-C) and in plasma CoQ10 levels from 1.08 mg/dl to 0.80 mg/dl. In contrast, in the US group we observed a significant increase of CoQ10 in plasma (from 1.20 to 1.48 mg/dl) while the hypocholesterolemic effect was similar to that observed in the S group. Platelet CoQ10 also decreased in the S group (from 104 to 90 ng/mg) and increased in the US group (from 95 to 145 ng/mg). This study demonstrates that simvastatin lowers both LDL-C and apo B plasma levels together with the plasma and platelet levels of CoQ10, and that CoQ10 therapy prevents both plasma and platelet CoQ10 decrease, without affecting the cholesterol lowering effect of simvastatin.


Huntingtin-associated protein 1: Eutherian adaptation from a TRAK-like protein, conserved gene promoter elements, and localization in the human intestine.
Huntingtin-associated Protein 1 (HAP1) is expressed in neurons and endocrine cells, and is critical for postnatal survival in mice. HAP1 shares a conserved "HAP1_N" domain with TRAfficking Kinesin proteins TRAK1 and TRAK2 (vertebrate), Milton (Drosophila) and T27A3.1 (C. elegans). HAP1, TRAK1 and TRAK2 have a degree of common function, particularly regarding intracellular receptor trafficking. However, TRAK1, TRAK2 and Milton (which have a "Milt/TRAK" domain that is absent in human and rodent HAP1) differ in function to HAP1 in that they are mitochondrial transport proteins, while HAP1 has emerging roles in starvation response. We have investigated HAP1 function by examining its evolution, and upstream gene promoter sequences. We performed phylogenetic analyses of the HAP1_N domain family of proteins, incorporating HAP1 orthologues (identified by genomic synteny) from 5 vertebrate classes, and also searched the Dictyostelium proteome for a common ancestor. Computational analyses of mammalian HAP1 gene promoters were performed to identify phylogenetically conserved regulatory motifs. We found that as recently as marsupials, HAP1 contained a Milt/TRAK domain and was more similar to TRAK1 and TRAK2 than to eutherian HAP1. The Milt/TRAK domain likely arose post multicellularity, as it was absent in the Dictyostelium proteome. It was lost from HAP1 in the eutherian lineage, and also from T27A3.1 in C. elegans. The HAP1 promoter from human, mouse, rat, rabbit, horse, dog, Tasmanian devil and opossum contained common sites for transcription factors involved in cell cycle, growth, differentiation, and stress response. A conserved arrangement of regulatory elements was identified, including sites for caudal-related homeobox transcription factors (CDX1 and CDX2), and myc-associated factor X (MAX) in the region of the TATA box. CDX1 and CDX2 are intestine-enriched factors, prompting investigation of HAP1 protein expression in the human duodenum. HAP1 was localized to singly dispersed mucosal cells, including a subset of serotonin-positive enterochromaffin cells. We have identified eutherian HAP1 as an evolutionarily recent adaptation of a vertebrate TRAK protein-like ancestor, and found conserved CDX1/CDX2 and MAX transcription factor binding sites near the TATA box in mammalian HAP1 gene promoters. We also demonstrated that HAP1 is expressed in endocrine cells of the human gut.


WITHDRAWN. Interventions for treating plantar heel pain.
Ten percent of people may experience pain under the heel (plantar heel pain) at some time. Injections, insoles, heel pads, strapping and surgery have been common forms of treatment offered. The absolute and relative effectiveness of these interventions are poorly understood. The objective of this review was to identify and evaluate the evidence for effectiveness of treatments for plantar heel pain. We searched the Cochrane Bone, Joint and Muscle Trauma Group specialised register (September 2002), the Cochrane Central Register of Controlled Trials Register (The Cochrane Library issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1988 to September 2002) and reference lists of articles and dissertations. Four podiatry journals were handsearched to 1998. We contacted all UK schools of podiatry to identify dissertations on the management of heel pain, and investigators in the field to identify unpublished data or research in progress. No language restrictions were applied. Randomised and quasi-randomised trials of interventions for plantar heel pain in adults. Two reviewers independently evaluated randomised controlled trials for inclusion, extracted data and assessed trial quality. Additional information was obtained by direct contact with investigators. No poolable data were identified. Where measures of variance were available we have calculated the weighted mean differences based on visual analogue scale (VAS) scores. Nineteen randomised trials involving 1626 participants were included. Trial quality was generally poor, and pooling of data was not conducted. All trials measured heel pain as the primary outcome. Seven trials evaluated interventions against placebo/dummy or no treatment. There was limited evidence for the effectiveness of topical corticosteroid administered by iontophoresis, i.e. using an electric current, in reducing pain. There was some evidence for the effectiveness of injected corticosteroid providing temporary relief of pain. There was conflicting evidence for the effectiveness of low energy extracorporeal shock wave therapy in reducing night pain, resting pain and pressure pain in the short term (6 and 12 weeks) and therefore its effectiveness remains equivocal. In individuals with chronic pain (longer than six months), there was limited evidence for the effectiveness of dorsiflexion night splints in reducing pain. There was no evidence to support the effectiveness of therapeutic ultrasound, low-intensity laser therapy, exposure to an electron generating device or insoles with magnetic foil. No randomised trials evaluating surgery, or radiotherapy against a randomly allocated control population were identified. There was limited evidence for the superiority of corticosteroid injections over orthotic devices. Although there is limited evidence for the effectiveness of local corticosteroid therapy, the effectiveness of other frequently employed treatments in altering the clinical course of plantar heel pain has not been established in randomised controlled trials.At the moment there is limited evidence upon which to base clinical practice. Treatments that are used to reduce heel pain seem to bring only marginal gains over no treatment and control therapies such as stretching exercises. Steroid injections are a popular method of treating the condition but only seem to be useful in the short term and only to a small degree. Orthoses should be cautiously prescribed for those patients who stand for long periods; there is limited evidence that stretching exercises and heel pads are associated with better outcomes than custom made orthoses in people who stand for more than eight hours per day.Well designed and conducted randomised trials are required.


Mandibular mobility and occlusal relationships after orthognathic surgery.
Mandibular mobility and the occurrence of occlusal interferences were assessed in a group of 42 subjects, all of whom underwent orthognathic surgery without maxillomandibular fixation. A minimum period of 3 months (mean of 12.9 months) had elapsed since surgery. Mandibular advancement (n = 8) and bimaxillary advancement procedures (n = 8) resulted in significantly greater end-of-treatment overjet than did Le Fort I (n = 12), mandibular setback (n = 3), or maxillary advancement with mandibular setback (n = 11). Mean maximum protrusion (5.9 mm) and mean maximum excursions to right and left (6.8 and 6.1 mm, respectively) were significantly higher after Le Fort I osteotomy. The frequency of right lateral, but not left lateral, non-working-side contacts was significantly greater in the mandibular setback group and the maxillary advancement with mandibular setback group. The mandibular setback group exhibited the only severe interference between retruded contact position and intercuspal position.


How to make a large nutrient removal plant energy self-sufficient. Latest upgrade of the Vienna Main Wastewater Treatment Plant (VMWWTP).
The goal of making nutrient removal wastewater treatment energy self-sufficient or even energy producing has become a worldwide accepted goal of technology development. The latest upgrade of the Vienna Main Wastewater Treatment Plant (VMWWTP) with a design capacity of 4 million (M) population equivalent (PE) will produce about 20% more energy on a yearly basis than needed for operation due to a special process scheme. It consists of primary sedimentation, a special 2-stage activated sludge (AS) process configuration where excess sludge is only withdrawn from the first stage AS plant. Raw sludge is subject to mechanical thickening to ∼8% digested sludge (DS) for digestion at high solids concentration. The reject water after nitritation is used for denitritation in the first stage AS plant. This results in markedly reducing the energy requirement for aeration. The design of this last upgrade for energy optimization of sludge treatment is based on the long-term full-scale data from the existing plant, results of mid-term pilot investigations, sound theoretical mass balance calculations and an adapted dynamic model development. All this is presented in this paper. The full-scale upgrade is under construction and will start operating in 2020.


Orientational order and dynamics of hydration water in a single crystal of bovine pancreatic trypsin inhibitor.
The orientational order and dynamics of the water molecules in form II crystals of bovine pancreatic trypsin inhibitor (BPTI) are studied by (2)H NMR in the temperature range 6-50 degrees C. From the orientation dependence of the single crystal quadrupole splitting and linewidth, the principal components of the motionally averaged quadrupole interaction tensor and the irreducible linewidth components for the orthorhombic crystal are determined. With the aid of water orientations derived from neutron and x-ray diffraction, it is shown that the NMR data can be accounted for by a small number of highly ordered crystal waters, some of which have residence times in the microsecond range. Most of these specific hydration sites must be located at intermolecular contacts. The surface hydration layer that is also present in dilute solution is likely to be only weakly ordered and would then not contribute significantly to the splitting and linewidth from the protein crystal. To probe water dynamics on shorter time scales, the (2)H longitudinal relaxation dispersion is measured for a polycrystalline BPTI sample. The observed dispersion is dominated by rapidly exchanging deuterons in protein side chains, undergoing restricted rotational motions on a time scale of 10 ns.


Sexual selection and speciation in mammals, butterflies and spiders.
Recently refined evolutionary theories propose that sexual selection and reproductive conflict could be drivers of speciation. Male and female reproductive optima invariably differ because the potential reproductive rate of males almost always exceeds that of females: females are selected to maximize mate 'quality', while males can increase fitness through mate 'quantity'. A dynamic, sexually selected conflict therefore exists in which 'competitive' males are selected to override the preference tactics evolved by 'choosy' females. The wide variation across taxa in mating systems therefore generates variance in the outcome of intrasexual conflict and the strength of sexual selection: monandry constrains reproductive heterozygosity and allows female choice to select and maintain particular (preferred) genes; polyandry promotes reproductive heterozygosity and will more likely override female choice. Two different theories predict how sexual selection might influence speciation. Traditional ideas indicate that increased sexual selection (and hence conflict) generates a greater diversity of male reproductive strategies to be counteracted by female mate preferences, thus providing elevated potentials for speciation as more evolutionary avenues of male-female interaction are created. A less intuitively obvious theory proposes that increased sexual selection and conflict constrains speciation by reducing the opportunities for female mate choice under polyandry. We use a comparative approach to test these theories by investigating whether two general measures of sexual selection and the potential for sexual conflict have influenced speciation. Sexual size dimorphism (across 480 mammalian genera, 105 butterfly genera and 148 spider genera) and degree of polyandry (measured as relative testes size in mammals (72 genera) and mating frequency in female butterflies (54 genera)) showed no associations with the variance in speciosity. Our results therefore show that speciation occurs independently of sexual selection.


Bisphenols, Benzophenones, and Bisphenol A Diglycidyl Ethers in Textiles and Infant Clothing.
Little is known with regard to the occurrence of potentially toxic chemicals in textiles and clothes. In this study, 77 textiles and infant clothing pieces were analyzed for the determination of bisphenols including bisphenol A (BPA) and bisphenol S (BPS), benzophenones, bisphenol A diglycidyl ethers (BADGEs), and novolac glycidyl ethers (NOGEs). BPA and BPS occurred in 82% and 53% of the textile samples, respectively, and at mean concentrations of 366 and 15 ng/g, respectively. Benzophenone-3 (BP3) occurred in 70% of the samples at a mean concentration of 11.3 ng/g. Among 11 BADGEs and NOGEs analyzed, BFDGE was the predominant compound, with a mean concentration of 13.6 ng/g. Concentrations of target chemicals were assessed by fabric type, color, and uses. Socks contained the highest concentrations of BPA (mean: 1810 ng/g) with concentrations as high as 13 300 ng/g in a 97% polyester fabric marketed for infants. Calculated dermal exposure dose to BPA by infants via textiles was as high as 7280 pg/kg BW/d. This is the first study to report the occurrence of, and exposure to, BPA, BPS, BADGEs, and NOGEs in textiles and clothing.


In vitro and in vivo characterization of four fibroblast tropomyosins produced in bacteria: TM-2, TM-3, TM-5a, and TM-5b are co-localized in interphase fibroblasts.
Most cell types express several tropomyosin isoforms, the individual functions of which are poorly understood. In rat fibroblasts there are at least six isoforms; TM-1, TM-2, TM-3, TM-4, TM-5a, and TM-5b. TM-1 is the product of the beta gene. TM-4 is produced from the TM-4 gene, and TMs 2, 3, 5a, and 5b are the products of the alpha gene. To begin to study the localization and function of the isoforms in fibroblasts, cDNAs for TM isoforms 2, 3, 5a, and 5b were placed into bacterial expression vectors and used to produce TM isoforms. The bacterially produced TMs were determined to be full length by sequencing the amino- and carboxy termini. These TMs were found to bind to F-actin in vitro, with properties similar to that of skeletal muscle TM. In addition, competition experiments demonstrated that TM-5b was better than TM-5a in displacing other TM isoforms from F-actin in vitro. To investigate the intracellular localization of these fibroblast isoforms, each was derivatized with a fluorescent chromophore and microinjected into rat fibroblasts. TM-2, TM-3, TM-5a, and TM-5b were each found to associate along actin filaments. There was no preferred cellular location or subset of actin filaments for these isoforms. Furthermore, co-injection of two isoforms labeled with different fluorochromes showed identical staining. At the level of the light microscope, these isoforms from the alpha gene do not appear to achieve different functions by binding to particular subsets of actin filaments or locations in cells. Some alternative possibilities are discussed. The results show that bacterially produced TMs can be used to study in vitro and in vivo properties of the isoforms.


Effect of yoga on self-rated visual discomfort in computer users.
'Dry eye' appears to be the main contributor to the symptoms of computer vision syndrome. Regular breaks and the use of artificial tears or certain eye drops are some of the options to reduce visual discomfort. A combination of yoga practices have been shown to reduce visual strain in persons with progressive myopia. The present randomized controlled trial was planned to evaluate the effect of a combination of yoga practices on self-rated symptoms of visual discomfort in professional computer users in Bangalore. Two hundred and ninety one professional computer users were randomly assigned to two groups, yoga (YG, n = 146) and wait list control (WL, n = 145). Both groups were assessed at baseline and after sixty days for self-rated visual discomfort using a standard questionnaire. During these 60 days the YG group practiced an hour of yoga daily for five days in a week and the WL group did their usual recreational activities also for an hour daily for the same duration. At 60 days there were 62 in the YG group and 55 in the WL group. While the scores for visual discomfort of both groups were comparable at baseline, after 60 days there was a significantly decreased score in the YG group, whereas the WL group showed significantly increased scores. The results suggest that the yoga practice appeared to reduce visual discomfort, while the group who had no yoga intervention (WL) showed an increase in discomfort at the end of sixty days.


Angiotensin II regulates microRNA-132/-212 in hypertensive rats and humans.
MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are emerging as key regulators in cardiovascular development and disease. MiRNAs are involved in cardiac hypertrophy, heart failure and remodeling following cardiac infarction; however, miRNAs involved in hypertension have not been thoroughly investigated. We have recently reported that specific miRNAs play an integral role in Angiotensin II receptor (AT1R) signaling, especially after activation of the Gαq signaling pathway. Since AT1R blockers are widely used to treat hypertension, we undertook a detailed analysis of potential miRNAs involved in Angiotensin II (AngII) mediated hypertension in rats and hypertensive patients, using miRNA microarray and qPCR analysis. The miR-132 and miR-212 are highly increased in the heart, aortic wall and kidney of rats with hypertension (159 ± 12 mm Hg) and cardiac hypertrophy following chronic AngII infusion. In addition, activation of the endothelin receptor, another Gαq coupled receptor, also increased miR-132 and miR-212. We sought to extend these observations using human samples by reasoning that AT1R blockers may decrease miR-132 and miR-212. We analyzed tissue samples of mammary artery obtained from surplus arterial tissue after coronary bypass operations. Indeed, we found a decrease in expression levels of miR-132 and miR-212 in human arteries from bypass-operated patients treated with AT1R blockers, whereas treatment with β-blockers had no effect. Taken together, these data suggest that miR-132 and miR-212 are involved in AngII induced hypertension, providing a new perspective in hypertensive disease mechanisms.


Simple, Direct Routes to Polymer Brush Traps and Nanostructures for Studies of Diffusional Transport in Supported Lipid Bilayers.
Patterned poly(oligo ethylene glycol) methyl ether methacrylate (POEGMEMA) brush structures may be formed by using a combination of atom-transfer radical polymerization (ATRP) and UV photopatterning. UV photolysis is used to selectively dechlorinate films of 4-(chloromethyl)phenyltrichlorosilane (CMPTS) adsorbed on silica surfaces, by exposure either through a mask or using a two-beam interferometer. Exposure through a mask yields patterns of carboxylic acid-terminated adsorbates. POEGMEMA may be grown from intact Cl initiators that were masked during exposure. Corrals, traps, and other structures formed in this way enable the patterning of proteins, vesicles, and, following vesicle rupture, supported lipid bilayers (SLBs). Bilayers adsorbed on the carboxylic acid-terminated surfaces formed by C-Cl bond photolysis in CMPTS exhibit high mobility. SLBs do not form on POEGMEMA. Using traps consisting of carboxylic acid-functionalized regions enclosed by POEGMEMA structures, electrophoresis may be observed in lipid bilayers containing a small amount of a fluorescent dye. Segregation of dye at one end of the traps was measured by fluorescence microscopy. The increase in the fluorescence intensity was found to be proportional to the trap length, while the time taken to reach the maximum value was inversely proportional to the trap length, indicating uniform, rapid diffusion in all of the traps. Nanostructured materials were formed using interferometric lithography. Channels were defined by exposure of CMPTS films to maxima in the interferogram, and POEGMEMA walls were formed by ATRP. As for the micrometer-scale patterns, bilayers did not form on the POEGMEMA structures, and high lipid mobilities were measured in the polymer-free regions of the channels.


The pallial basal ganglia pathway modulates the behaviorally driven gene expression of the motor pathway.
The discrete neural network for songbird vocal communication provides an effective system to study neural mechanisms of learned motor behaviors in vertebrates. This system consists of two pathways--a vocal motor pathway used to produce learned vocalizations and a vocal pallial basal ganglia loop used to learn and modify the vocalizations. However, it is not clear how the loop exerts control over the motor pathway. To study the mechanism, we used expression of the neural activity-induced gene ZENK (or egr-1), which shows singing-regulated expression in a social context-dependent manner: high levels in both pathways when singing undirected and low levels in the lateral part of the loop and in the robust nucleus of the arcopallium (RA) of the motor pathway when singing directed to another animal. Here, we show that there are two parallel interactive parts within the pallial basal ganglia loop, lateral and medial, which modulate singing-driven ZENK expression of the motor pathway nuclei RA and HVC, respectively. Within the loop, the striatal and pallial nuclei appear to have opposing roles; the striatal vocal nucleus lateral AreaX is required for high ZENK expression in its downstream nuclei, particularly during undirected singing, while the pallial vocal lateral magnocellular nucleus of the anterior nidopallium is required for lower expression, particularly during directed singing. These results suggest a dynamic molecular interaction between the basal ganglia pathway and the motor pathway during production of a learned motor behavior.


Effect of keratinocyte seeding of collagen-glycosaminoglycan membranes on the regeneration of skin in a porcine model.
A collagen-glycosaminoglycan matrix, impregnated with autologous keratinocytes, was applied as island grafts onto full-thickness porcine wounds to determine whether complete epidermal coverage could be achieved in a single grafting procedure. Twenty-four grafts with seeding densities ranging from 0 to 3,000,000 cells/cm2 were used to determine the kinetics of epidermal coverage. The time sequence of epidermal formation was then studied between days 14 and 28 using four additional grafts, each seeded with a density of 500,000 cells/cm2. Autologous keratinocytes proliferated as the collagen-glycosaminoglycan matrix was vascularized to form a confluent epidermis by 2 weeks in matrices seeded with at least 100,000 cells/cm2. The epidermal thickness and the number of keratinocyte cysts observed in the neodermis at 2 weeks increased linearly with the logarithm of the seeding density. Sequential analysis of neoepidermis showed the nascent epidermis to be hyperplastic, parakeratotic, and focally lacking in granular layer differentiation at 2 weeks. After 2 weeks, it underwent normal maturation and differentiation. Irrespective of seeding density at 2 weeks the collagen-glycosaminoglycan matrix was well vascularized, contained a dense cellular infiltrate, and was almost completely degraded. These studies demonstrate that seeded keratinocytes proliferate and differentiate to form a confluent epidermis by 2 weeks in matrices seeded with at least 100,000 cells/cm2.


Differential expression and regulation of the cAMP-selective phosphodiesterase type 4A splice variants in rat brain by chronic antidepressant administration.
Chronic antidepressant treatment up-regulates the cAMP cascade in limbic brain regions, suggesting that activation of this pathway contributes to the therapeutic efficacy of antidepressants. A role for cAMP signaling is supported by the finding that rolipram, a selective inhibitor of cAMP-specific phosphodiesterases type 4 (PDE4), has antidepressant efficacy in behavioral models of depression and in clinical trials. To elucidate further the role of PDE4 isozymes, we characterized the expression and regulation of PDE4A splice variants (i.e. PDE4A1, PDE4A5, PDE4A8 and PDE4A10) in rat brain by chronic antidepressant treatment. Initial in situ hybridization studies (ISH) revealed high levels of PDE4A1 mRNA in medial septum, diagonal band, olfactory system, hippocampus and cerebellum. PDE4A5 mRNA expression was restricted to the olfactory nuclei, deep cortical layers, dentate and CA1 pyramidal layers. PDE4A10 mRNA was localized in the dentate gyrus and CA1 pyramidal layers. PDE4A8 mRNA was absent in rat brain. We determined the influence of chronic fluoxetine or electroconvulsive seizure (ECS) treatments on PDE4A splice variants expression in various brain regions. ISH analysis indicated that chronic fluoxetine or ECS treatments significantly increased PDE4A1, but not PDE4A5 or PDE4A10, mRNA levels in frontal and parietal cortices. ECS increased PDE4A5 levels in the anterior cingulate and frontoparietal cortices, CA1 and dentate gyrus, whereas chronic fluoxetine or ECS treatment increased PDE4A10 levels in the hippocampus. The differential up-regulation of PDE4A splice variants suggests compensatory region-specific responses to the antidepressant-induced increase in cAMP signaling and suggests that these splice variants may be relevant as targets for antidepressant intervention.


Real-Life Observational Studies Provide Actionable Data for Family Medicine.
This issue includes several excellent observational studies prompted by physicians' clinical questions. Many people use lots of menthol cough drops-does the menthol overall lengthen the cough duration? When should we intensify treatment of older individuals with diabetes? Do occipital nerve blocks work for acute migraine headaches? Did you know that the plantar fascia can rupture? What happens to those patients with chest pain but low pretest probability for serious cardiac disease who are admitted to the hospital? Acupuncture can work well-for the patients-but how can we incorporate it into the usual pace of the family medicine office? Is it a win-lose situation when medical assistant roles are expanded? How many practice sites do physicians have and does that make a difference in the number or type of health personnel shortage areas? What would you guess on the presence of humor in the medical office-more or less than half of the visits; introduced by doctors or patients; primary care or specialty doctors?


WNK4 kinase is a negative regulator of K+-Cl- cotransporters.
WNK kinases [with no lysine (K) kinase] are emerging as regulators of several membrane transport proteins in which WNKs act as molecular switches that coordinate the activity of several players. Members of the cation-coupled chloride cotransporters family (solute carrier family number 12) are one of the main targets. WNK3 activates the Na(+)-driven cotransporters NCC, NKCC1, and NKCC2 and inhibits the K(+)-driven cotransporters KCC1 to KCC4. WNK4 inhibits the activity of NCC and NKCC1, while in the presence of the STE20-related proline-alanine-rich kinase SPAK activates NKCC1. Nothing is known, however, regarding the effect of WNK4 on the K(+)-Cl(-) cotransporters. Using the heterologous expression system of Xenopus laevis oocytes, here we show that WNK4 inhibits the activity of the K(+)-Cl(-) cotransporters KCC1, KCC3, and KCC4 under cell swelling, a condition in which these cotransporters are maximally active. The effect of WNK4 requires its catalytic activity because it was lost by the substitution of aspartate 318 for alanine (WNK4-D318A) that renders WNK4 catalytically inactive. In contrast, three different WNK4 missense mutations that cause pseudohypoaldosteronism type II do not affect the WNK4-induced inhibition of KCC4. Finally, we observed that catalytically inactive WNK4-D318A is able to bypass the tonicity requirements for KCC2 and KCC3 activation in isotonic conditions. This effect is enhanced by the presence of catalytically inactive SPAK, was prevented by the presence of protein phosphatase inhibitors, and was not present in KCC1 and KCC4. Our results reveal that WNK4 regulates the activity of the K(+)-Cl(-) cotransporters expressed in the kidney.


Autolysis of Blakeslea trispora during carotene production from cheese whey in an airlift reactor.
The phenomenon of autolysis in Blakeslea trispora during carotene production from deproteinized hydrolyzed whey in an airlift reactor was investigated. The process of cellular autolysis was studied by measuring the changes in carotene concentration, dry biomass, residual sugars, pH, intracellular protein, specific activity of the hydrolytic enzymes (proteases, chitinase), and micromorphology of the fungus using a computerized image analysis system. All these parameters were useful indicators of autolysis, but image analysis was found to be the most useful indicator of the onset and progress of autolysis in the culture. Autolysis of B. trispora began early in the growth phase, continued during the stationary phase, and increased significantly in the decline phase. The morphological differentiation of the fungus was a result of the degradation of the cell membrane by hydrolytic enzymes. The biosynthesis of carotenes was carried out in the exponential phase, where the phenomenon of autolysis was not intense.


Network representations of immune system complexity.
The mammalian immune system is a dynamic multiscale system composed of a hierarchically organized set of molecular, cellular, and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single-cell responses to increasingly complex networks of in vivo cellular interaction, positioning, and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather nonlinear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multiscale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels, while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating 'omics' and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular- and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks.


A pseudo-three-dimensional model for quantification of oxygen diffusion from preglomerular arteries to renal tissue and renal venous blood.
To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the 11 branching levels (known as "Strahler" orders) of the preglomerular renal vasculature in the rat, with an analysis of an extensive data set obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Furthermore, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, peritubular capillaries, and veins to tissue. While a number of lines of evidence suggest AV shunting is significant, most importantly, our AV oxygen shunting model predicts AV shunting is small under normal physiological conditions (~0.9% of total renal oxygen delivery; range 0.4-1.4%), but increases during renal ischemia, glomerular hyperfiltration (~2.1% of total renal oxygen delivery; range 0.84-3.36%), and some cardiovascular disease states (~3.0% of total renal oxygen delivery; range 1.2-4.8%). Under normal physiological conditions, blood Po2 is predicted to fall by ~16 mmHg from the root of the renal artery to glomerular entry, with AV oxygen shunting contributing ~40% and oxygen diffusion from arteries to tissue contributing ~60% of this decline. Arterial Po2 is predicted to fall most rapidly from Strahler order 4, under normal physiological conditions. We conclude that AV oxygen shunting normally has only a small impact on renal oxygenation, but may exacerbate renal hypoxia during renal ischemia, hyperfiltration, and some cardiovascular disease states.


How to read a paper. Statistics for the non-statistician. II: "Significant" relations and their pitfalls.
It is possible to be seriously misled by taking the statistical competence (and/or the intellectual honesty) of authors for granted. Some common errors committed (deliberately or inadvertently) by the authors of papers are given in the final box.


Prognostic transcriptional association networks: a new supervised approach based on regression trees.
The application of information encoded in molecular networks for prognostic purposes is a crucial objective of systems biomedicine. This approach has not been widely investigated in the cardiovascular research area. Within this area, the prediction of clinical outcomes after suffering a heart attack would represent a significant step forward. We developed a new quantitative prediction-based method for this prognostic problem based on the discovery of clinically relevant transcriptional association networks. This method integrates regression trees and clinical class-specific networks, and can be applied to other clinical domains. Before analyzing our cardiovascular disease dataset, we tested the usefulness of our approach on a benchmark dataset with control and disease patients. We also compared it to several algorithms to infer transcriptional association networks and classification models. Comparative results provided evidence of the prediction power of our approach. Next, we discovered new models for predicting good and bad outcomes after myocardial infarction. Using blood-derived gene expression data, our models reported areas under the receiver operating characteristic curve above 0.70. Our model could also outperform different techniques based on co-expressed gene modules. We also predicted processes that may represent novel therapeutic targets for heart disease, such as the synthesis of leucine and isoleucine. The SATuRNo software is freely available at http://www.lsi.us.es/isanepo/toolsSaturno/.


Isoform-specific regulation of the inositol 1,4,5-trisphosphate receptor by O-linked glycosylation.
The inositol 1,4,5-trisphosphate receptor (InsP(3)R), an intracellular calcium channel, has three isoforms with >65% sequence homology, yet the isoforms differ in their function and regulation by post-translational modifications. We showed previously that InsP(3)R-1 is functionally modified by O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) (Rengifo, J., Gibson, C. J., Winkler, E., Collin, T., and Ehrlich, B. E. (2007) J. Neurosci. 27, 13813-13821). We now report the effect of O-GlcNAcylation on InsP(3)R-2 and InsP(3)R-3. Analysis of AR4-2J cells, a rat pancreatoma cell line expressing predominantly InsP(3)R-2, showed no detectable O-GlcNAcylation of InsP(3)R-2 and no significant functional changes despite the presence of the enzymes for addition (O-β-N-acetylglucosaminyltransferase) and removal (O-β-N-acetylglucosaminidase) of the monosaccharide. In contrast, InsP(3)R-3 in Mz-ChA-1 cells, a human cholangiocarcinoma cell line expressing predominantly InsP(3)R-3, was functionally modified by O-GlcNAcylation. Interestingly, the functional impact of O-GlcNAcylation on the InsP(3)R-3 channel was opposite the effect measured with InsP(3)R-1. Addition of O-GlcNAc by O-β-N-acetylglucosaminyltransferase increased InsP(3)R-3 single channel open probability. Incubation of Mz-ChA-1 cells in hyperglycemic medium caused an increase in the InsP(3)-dependent calcium release from the endoplasmic reticulum. The dynamic and inducible nature of O-GlcNAcylation and the InsP(3)R isoform specificity suggest that this form of modification of InsP(3)R and subsequent changes in intracellular calcium transients are important in physiological and pathophysiological processes.


Chemerin, a novel adipokine in the regulation of angiogenesis.
Chemerin is a new adipokine associated with obesity and the metabolic syndrome. Gene expression levels of chemerin were elevated in the adipose depots of obese compared with lean animals and was markedly elevated during differentiation of fibroblasts into mature adipocytes. The objective of the study was to identify factors that affect the regulation and potential function of chemerin using a genetics approach. Plasma chemerin levels were measured in subjects from the San Antonio Family Heart Study, a large family-based genetic epidemiological study including 1354 Mexican-American individuals. Individuals were randomly sampled without regard to phenotype or disease status. A genome-wide association analysis using 542,944 single-nucleotide polymorphisms in a subset of 523 of the same subjects was undertaken. The effect of chemerin on angiogenesis was measured using human endothelial cells and interstitial cells in coculture in a specially formulated medium. Serum chemerin levels were found to be highly heritable (h(2) = 0.25; P = 1.4 x 10(-9)). The single-nucleotide polymorphism showing strongest evidence of association (rs347344; P = 1.4 x 10(-6)) was located within the gene encoding epithelial growth factor-like repeats and discoidin I-like domains 3, which has a known role in angiogenesis. Functional angiogenesis assays in human endothelial cells confirmed that chemerin significantly mediated the formation of blood vessels to a similar extent as vascular endothelial growth factor. Here we demonstrate for the first time that plasma chemerin levels are significantly heritable and identified a novel role for chemerin as a stimulator of angiogenesis.


IPM for fresh-market lettuce production in the desert southwest: the produce paradox.
In the 'Integrated Control Concept', Stern et al. emphasized that, although insecticides are necessary for agricultural production, they should only be used as a last resort and as a complement to biological control. They argued that selective insecticide use should only be attempted after it has been determined that insect control with naturally occurring biotic agents is not capable of preventing economic damage. However, they concluded their seminal paper by emphasizing that integrated control will not work where natural enemies are inadequate or where economic thresholds are too low to rely on biological control. Thus, it is no surprise that insect control in high-value, fresh-market lettuce crops grown in the desert southwest have relied almost exclusively on insecticides to control a complex of mobile, polyphagous pests. Because lettuce and leafy greens are short-season annual crops with little or no tolerance for insect damage or contamination, biological control is generally considered unacceptable. High expectations from consumers for aesthetically appealing produce free of pesticide residues further forces vegetable growers to use chemical control tactics that are not only effective but safe. Consequently, scientists have been developing integrated pest management (IPM) programs for lettuce that are aimed at reducing the economic, occupational and dietary risks associated with chemical controls of the past. Most of these programs have drawn upon the integrated control concept and promote the importance of understanding the agroecosystem, and the need to sample for pest status and use action thresholds for cost-effective insect control. More recently, pest management programs have implemented newly developed, reduced-risk chemistries that are selectively efficacious against key pests. This paper discusses the influence that the integrated control concept, relative to zero-tolerance market standards and other constraints, has had on the adoption of pest management in desert lettuce crops.


Polarization and effective Mueller matrix for multiple scattering of light by nonspherical ice crystals.
We investigated the errors associated with the scalar approximation (i.e., an approach that neglects polarization effects) for simulating the intensity of the radiation reflected by an ice cloud. In a case for an optical thickness of tau=1, the relative errors of the scalar approximation are typically between -0.5% and 0.1%. We also investigated the effect of the order of scattering on the degree of linear polarization. It is shown that substantial errors can be introduced by the first-order scattering approximation, and thus, the multiple-scattering effect is essential to an accurate simulation of the polarization configuration of a radiation field. Furthermore, we investigate the effective Mueller matrix pertaining to multiple scattering of light by ice clouds. The effective Mueller matrix is a 4x4 matrix that relates the incident and scattered Stokes parameters. This matrix implicitly contains the effects of all orders of scattering and absorbing events in the entire radiation transfer process. The sensitivity of the (2,1) and (3,1) elements of the effective Mueller matrix to ice crystal shape and size indicates that polarimetric information may be useful for inferring the microphysical properties of ice crystals within ice clouds.


Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome.
To study the association between coxsackie B virus infection and the postviral fatigue syndrome and to assess the immunological abnormalities associated with the syndrome. Case-control study of patients with the postviral fatigue syndrome referred by local general practitioners over one year. General practitioner referrals in Dunbartonshire, Scotland. 254 Patients referred with the postviral fatigue syndrome (exhaustion, myalgia, and other symptoms referable to postviral fatigue syndrome of fairly recent onset--that is, several months) and age and sex matched controls obtained from same general practitioner; 11 patients were rejected because of wrong diagnoses, resolution of symptoms, and refusal to participate, leaving 243 patients and matched controls. Detailed questionnaire (patients and controls) and clinical examination (patients) and blind analysis of blood sample at entry and after six months for determination of coxsackie B virus IgM and IgG antibodies and other variables (including lymphocyte protein synthesis, lymphocyte subsets, and immune complexes). Percentage positive rates for coxsackie B virus IgM at entry were 24.4% for patients and 22.6% for controls and for coxsackie B virus IgG 56.2% and 55.3% respectively; there were no significant differences between different categories of patients according to clinical likelihood of the syndrome nor any predictive value in a fourfold rise or fall in the coxsackie B virus IgG titre in patients between entry and review at six months. The rates of positive antibody test results in patients and controls showed a strong seasonal variation. Of the numerous immunological tests performed, only a few detected significant abnormalities; in particular the mean value for immune complex concentration was much higher in 35 patients and 35 controls compared with the normal range and mean value for total IgM was also raised in 227 patients and 35 controls compared with the normal range. Serological tests available for detecting coxsackie B virus antibodies do not help diagnose the postviral fatigue syndrome. Percentage positive rates of the antibodies in patients simply reflect the background in the population as probably do the raised concentrations of total IgM and immune complexes.


Effect of Red Bull energy drink on muscle performance: an electromyographic overview.
The present study was aimed at investigating the effect of Red Bull Energy drink (RB) on muscle endurance and fatigue. Twenty students of second year MBBS (males N.=10, females N.=10) were involved in a cross over design separated by 7 days, where they received either RB (caffeine at 2 mg/kg body weight) or isoenergetic, isovolumetric, noncaffeinated control drink (CD). After one hour of intake of the drink, maximum isometric force (MVC) and electromyogram (EMG) (flexor carpi radialis) were recorded from the dominant hand using Biopac Systems. After MVC, all subjects performed a sustained isometric contraction at 75% of MVC to fatigue. The Root mean square amplitude (RMS) and mean frequency (MNF) were calculated from the EMG data. Statistical analysis was done using r within and across groups. Following consumption of RB, the fatigue task showed a decreased tendency to fatigue based on the MNF value for both the drinks. However the EMG index with reference to RMS was inconclusive to interpret any delaying effect on fatigue. There was no significant difference between the two drinks in the parameters assessed during MVC and endurance time. The Red Bull energy drink (caffeine at 2 mg/kg body weight) was no better than CD at significant delaying effect on fatigue during isometric contraction.


Dopamine Modulation of Intertemporal Decision-making: Evidence from Parkinson Disease.
Choosing between smaller prompt rewards and larger later rewards is a common choice problem, and studies widely agree that frontostriatal circuits heavily innervated by dopamine are centrally involved. Understanding how dopamine modulates intertemporal choice has important implications for neurobiological models and for understanding the mechanisms underlying maladaptive decision-making. However, the specific role of dopamine in intertemporal decisions is not well understood. Dopamine may play a role in multiple aspects of intertemporal choices--the valuation of choice outcomes and sensitivity to reward delays. To assess the role of dopamine in intertemporal decisions, we tested Parkinson disease patients who suffer from dopamine depletion in the striatum, in either high (on medication, PDON) or low (off medication, PDOFF) dopaminergic states. Compared with both PDOFF and healthy controls, PDON made more farsighted choices and reduced their valuations less as a function of increasing time to reward. Furthermore, reduced discounting in the high dopaminergic state was robust across multiple measures, providing new evidence for dopamine's role in making decisions about the future.


New approaches to structural evolution of limb bones in primates.
Structural analysis of primate limb bones using engineering beam theory can reduce complex biological forms to a few readily interpretable and functionally relevant parameters. Several methods of obtaining and analyzing these structural parameters are described, including computed tomography, multiple plane radiography, photon absorptiometry, and automated digital analysis. Examples of applications of these data to problems in primate adaptation and evolution include improved estimation of body mass in fossil species, investigation of relative fore- and hindlimb mechanical loadings ('dominance'), and study of more subtle within and between species differences in behavior as reflected in variations in limb bone shape. In addition, it is shown that combined analyses of diaphyseal and articular structure can provide information on aspects of structural evolution of primate limb bones not evident from independent analysis of either type of characteristic alone.


Direct observation of polymer surface mobility via nanoparticle vibrations.
Measuring polymer surface dynamics remains a formidable challenge of critical importance to applications ranging from pressure-sensitive adhesives to nanopatterning, where interfacial mobility is key to performance. Here, we introduce a methodology of Brillouin light spectroscopy to reveal polymer surface mobility via nanoparticle vibrations. By measuring the temperature-dependent vibrational modes of polystyrene nanoparticles, we identify the glass-transition temperature and calculate the elastic modulus of individual nanoparticles as a function of particle size and chemistry. Evidence of surface mobility is inferred from the first observation of a softening temperature, where the temperature dependence of the fundamental vibrational frequency of the nanoparticles reverses slope below the glass-transition temperature. Beyond the fundamental vibrational modes given by the shape and elasticity of the nanoparticles, another mode, termed the interaction-induced mode, was found to be related to the active particle-particle adhesion and dependent on the thermal behavior of nanoparticles.


Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats.
The lipid lowering and antioxidant potential of ethanolic extract of Zingiber officinale Roscoe (family, Zingiberaceae) was evaluated in streptozotocin (STZ)-induced diabetes in rats. Ethanolic extract of Zingiber officinale (200 mg/kg) fed orally for 20 days produced, significant antihyperglycaemic effect (P < 0.01) in diabetic rats. Further, the extract treatment also lowered serum total cholesterol, triglycerides and increased the HDL-cholesterol levels when compared with pathogenic diabetic rats (P < 0.01). STZ-treatment also induced a statistically significant increase in liver and pancreas lipid peroxide levels (P < 0.01) as compared to normal healthy control rats. Zingiber officinale extract treatment lowered the liver and pancreas thiobarbituric acid reactive substances (TBARS) values (P < 0.01) as compared to pathogenic diabetic rats. The results of test drug were comparable to gliclazide (25 mg/kg, orally), a standard antihyperglycaemic agent. The results indicate that ethanolic extract of Zingiber officinale Roscoe can protect the tissues from lipid peroxidation. The extract also exhibit significant lipid lowering activity in diabetic rats. The present study is the first pilot study to assess the potential of Zingiber officinale in diabetic dyslipidaemia.


Phthalocyanine with a giant dielectric constant.
Compound 1 has been prepared by the reaction of 4-nitrophthalonitrile and trans-2-methoxy-4-(2-nitrovinil)phenol by the common method of nucleophilic substitution of an activated nitro group in an aromatic ring. The metallophthalocyanines 2, 3 were prepared by the reaction of a dinitrile derivative with Co(OAc)(2) or Zn(OAc)(2) in DMSO. The lutetium bis-(phthalocyaninato) complex 4 was obtained by treating the dinitrile derivative with lutetium acetate and DBU in 1-hexanol. The new compounds were characterized by elemental analyses, FT-IR, (1)H-NMR, MALDI-TOF MS and UV/Vis spectral data. The spectroscopic data of the new compounds were in accordance with the structures. The temperature and frequency dependence of dielectric and conduction properties of the spin coated film of compounds (2-4) have been studied by fabricating metal-Pc-metal structures. The results show that compound 2 has giant dielectric constant. At a low range of frequency and room temperature, ε' is found to be equal to 2.33 × 10(6), 1.53 × 10(4) and 1.03 × 10(4) for 2, 3 and 4, respectively. The giant dielectric behavior of 2 is mainly attributed to Maxwell-Wagner polarization. The obtained results also indicated that the frequency dependence of the dielectric permittivity, ε'(ω), exhibits non-Debye type relaxation for all temperatures investigated. The ac conductivity results gave a temperature dependent frequency exponent s. The results were compared with the prediction of the Quantum Mechanical Tunneling and Correlated Barrier Hopping models.


Chronic intestinal pseudo-obstruction and neurological manifestations in early adulthood: considering MNGIE syndrome in differential diagnosis.
The mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE) is a rare and life-threatening, autosomal recessive, multisystem disorder, caused by the mutations in the thymidine phosphorylase gene. Herein, we report a case of a 21 year-old male with a long history of intestinal pseudo-obstruction who was diagnosed with MNGIE syndrome after an extensive examination. In this case, our objective was to bring the gastroenterologist's attention to this difficult to diagnose syndrome in the coexistence of intestinal pseudo-obstruction and neurologic manifestations. The patient was a member of a consanguineous family of six children, in whom two sisters had died due to this disorder and one sister was affected and is still alive. The patient presented with cachexia, abdominal pain, diarrhea and muscle weakness, and was previously considered to have gluten sensitive enteropathy and treated with dietary solutions.


The treatment of uncertainties in reactive pollution dispersion models at urban scales.
The ability to predict NO2 concentrations ([NO2]) within urban street networks is important for the evaluation of strategies to reduce exposure to NO2. However, models aiming to make such predictions involve the coupling of several complex processes: traffic emissions under different levels of congestion; dispersion via turbulent mixing; chemical processes of relevance at the street-scale. Parameterisations of these processes are challenging to quantify with precision. Predictions are therefore subject to uncertainties which should be taken into account when using models within decision making. This paper presents an analysis of mean [NO2] predictions from such a complex modelling system applied to a street canyon within the city of York, UK including the treatment of model uncertainties and their causes. The model system consists of a micro-scale traffic simulation and emissions model, and a Reynolds averaged turbulent flow model coupled to a reactive Lagrangian particle dispersion model. The analysis focuses on the sensitivity of predicted in-street increments of [NO2] at different locations in the street to uncertainties in the model inputs. These include physical characteristics such as background wind direction, temperature and background ozone concentrations; traffic parameters such as overall demand and primary NO2 fraction; as well as model parameterisations such as roughness lengths, turbulent time- and length-scales and chemical reaction rate coefficients. Predicted [NO2] is shown to be relatively robust with respect to model parameterisations, although there are significant sensitivities to the activation energy for the reaction NO + O3 as well as the canyon wall roughness length. Under off-peak traffic conditions, demand is the key traffic parameter. Under peak conditions where the network saturates, road-side [NO2] is relatively insensitive to changes in demand and more sensitive to the primary NO2 fraction. The most important physical parameter was found to be the background wind direction. The study highlights the key parameters required for reliable [NO2] estimations suggesting that accurate reference measurements for wind direction should be a critical part of air quality assessments for in-street locations. It also highlights the importance of street scale chemical processes in forming road-side [NO2], particularly for regions of high NOx emissions such as close to traffic queues.


Selenium-enriched yeast inhibited β-amyloid production and modulated autophagy in a triple transgenic mouse model of Alzheimer's disease.
As the most common cause of progressive intellectual failure in elderly humans, Alzheimer's disease (AD) is pathologically featured by amyloid plaques, synaptic loss, and neurofibrillary tangles. The amyloid plaques are mainly aggregates of amyloid β-peptide (Aβ), a primary factor contributing to the pathogenesis of AD. Elimination or reduction of the level of Aβ is considered an important strategy in AD treatment. The pharmacotherapeutic efficacy of selenium (Se), an essential biological trace element for mammalian species, has been confirmed in a number of experimental models of neurodegenerative diseases. Selenium-enriched yeast (Se-yeast) is commonly used as a nutritional supplement for Se. In this study, we investigated the effects and underlying mechanisms of Se-yeast on Aβ pathology in a 4-month-old triple transgenic mouse model of AD (3×Tg-AD mice). The administration of Se-yeast attenuated the deposition of Aβ in the brains of AD mice, which was concomitant with decreased levels of LC3II. The Se-yeast treatment decreased the level of amyloid-protein precursor (APP), downregulated the activity of AMP-activated protein kinase (AMPK) and upregulated the activity of AKT/mTOR/p70S6K. Furthermore, the levels of p62 also significantly decreased, and the cathepsin D levels increased, accompanied by increased turnover of Aβ and APP in Se-yeast-treated AD mice. In addition to decreasing the generation of Aβ, Se-yeast also inhibited the initiation of autophagy by modulating the AMPK/AKT/mTOR/p70S6K signaling pathway and enhanced autophagic clearance, thus reducing the burden of Aβ accumulation in the brains of AD mice. Our results further highlight the potential therapeutic effects of Se-yeast on AD.


Phosphorylation by cyclic adenosine 3':5'-monophosphate-dependent protein kinase regulates myosin light chain kinase.
Smooth muscle myosin light chain kinase, purified to homogeneity, has a molecular weight of 130,000 +/- 5,000 in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified enzyme has a specific activity under maximal conditions of 30 mumol Pi transferred to myosin light chain/mg kinase/min at 24 C and is totally dependent on calmodulin and calcium for activity. Incubation of myosin kinase with the catalytic subunit of cyclic adenosine 3':5'-monophosphate-dependent protein kinase results in the covalent incorporation of up to one mol of phosphate per mol of myosin kinase in the absence of bound calmodulin. Limited tryptic digestion of the radioactively labeled kinase indicates that all of the label has been incorporated into a single tryptic peptide (mol wt approximately 22,000), suggesting that a single site is being phosphorylated. Phosphorylation of myosin kinase lowers the rate at which the kinase phosphorylates myosin light chain. The lower rate of light chain phosphorylation is due to a weaker binding of calmodulin to the phosphorylated kinase than to the unphosphorylated kinase. Cyclic adenosine 3':5'-monophosphate-dependent phosphorylation of the kinase actin-myosin interaction represents a possible link between hormonal binding to smooth muscle receptors and muscle relaxation. A scheme for this sequence of events is presented.


Recurrent abdominal liposarcoma: analysis of 19 cases and prognostic factors.
To evaluate the clinical outcome of re-operation for recurrent abdominal liposarcoma following multidisciplinary team cooperation. Nineteen consecutive patients who had recurrent abdominal liposarcoma underwent re-operation by the retroperitoneal sarcoma team at our institution from May 2009 to January 2012. Patient demographic and clinical data were reviewed retrospectively. Multidisciplinary team discussions were held prior to treatment, and re-operation was deemed the best treatment. The categories of the extent of resection were as follows: gross total resection (GTR), palliative resection and partial resection. Surgical techniques were divided into discrete lesion resection and combined contiguous multivisceral resection (CMR). Tumor size was determined as the largest diameter of the specimen. Patients were followed up at approximately 3-monthly intervals. For survival analysis, a univariate analysis was performed using the Kaplan-Meier method, and a multivariate analysis was performed using the Cox proportional hazards model. Nineteen patients with recurrent abdominal liposarcoma (RAL) underwent 32 re-operations at our institute. A total of 51 operations were reviewed with a total follow-up time ranging from 4 to 120 (47.4 ± 34.2) mo. The GTR rate in the CMR group was higher than that in the non-CMR group (P = 0.034). CMR was positively correlated with intra-operative bleeding (correlation coefficient = 0.514, P = 0.010). Six cases with severe postoperative complications were recorded. Patients with tumor sizes greater than 20 cm carried a significant risk of profuse intra-operative bleeding (P = 0.009). The ratio of a highly malignant subtype (dedifferentiated or pleomorphic) in recurrent cases was higher compared to primary cases (P = 0.027). Both single-factor survival using the Kaplan-Meier model and multivariate analysis using the Cox proportional hazards model showed that overall survival was correlated with resection extent and pathological subtype (P < 0.001 and P = 0.02), however, relapse-free interval (RFI) was only correlated with resection extent (P = 0.002). Close follow-up should be conducted in patients with RAL. Early re-operation for relapse is preferred and gross resection most likely prolongs the RFI.


Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes.
Loss-of-function mutations in the methyl-DNA binding protein MeCP2 are associated with neurological dysfunction and impaired neural plasticity. However, the transcriptional changes that underlie these deficits remain poorly understood. Here, we show that mice bearing a C-terminal truncating mutation in Mecp2 (Mecp2 ( 308) ) are hypersensitive to the locomotor stimulating effects of cocaine. Furthermore, these mice have gene-specific alterations in striatal immediate-early gene (IEG) induction following cocaine administration. MeCP2 mutant mice show normal levels of baseline and cocaine-induced striatal Fos expression compared with their wild-type littermates. However, the mutant mice have enhanced cocaine-induced transcription of Junb and Arc. At the chromatin level, we find increased histone H3 acetylation at gene promoters in the Mecp2 mutant mice compared with their wild-type littermates, whereas two sites of repressive histone methylation are unchanged. Interestingly, we find that MeCP2 mutant mice show increased steady-state association of elongation-competent RNA Polymerase II (RNAP II) with the Junb and Arc promoters, whereas levels of RNAP II association at the Fos promoter are unchanged. These data reveal a gene-specific effect of MeCP2 on the recruitment of RNAP II to gene promoters that may modulate the inducibility of IEGs. In addition, our findings raise the possibility that aberrant regulation of IEGs including Junb and Arc may contribute to altered cocaine-induced neuronal and behavioral plasticity in Mecp2 mutant mice.


Nutrient and sediment concentrations and corresponding loads during the historic June 2008 flooding in eastern Iowa.
A combination of above-normal precipitation during the winter and spring of 2007-2008 and extensive rainfall during June 2008 led to severe flooding in many parts of the midwestern United States. This resulted in transport of substantial amounts of nutrients and sediment from Iowa basins into the Mississippi River. Water samples were collected from 31 sites on six large Iowa tributaries to the Mississippi River to characterize water quality and to quantify nutrient and sediment loads during this extreme discharge event. Each sample was analyzed for total nitrogen, dissolved nitrate plus nitrite nitrogen, dissolved ammonia as nitrogen, total phosphorus, orthophosphate, and suspended sediment. Concentrations measured near peak flow in June 2008 were compared with the corresponding mean concentrations from June 1979 to 2007 using a paired t test. While there was no consistent pattern in concentrations between historical samples and those from the 2008 flood, increased flow during the flood resulted in near-peak June 2008 flood daily loads that were statistically greater (p < 0.05) than the median June 1979 to 2007 daily loads for all constituents. Estimates of loads for the 16-d period during the flood were calculated for four major tributaries and totaled 4.95 x 10(7) kg of nitrogen (N) and 2.9 x 10(6) kg of phosphorus (P) leaving Iowa, which accounted for about 22 and 46% of the total average annual nutrient yield, respectively. This study demonstrates the importance of large flood events to the total annual nutrient load in both small streams and large rivers.


Three-dimensional texture analysis of optical coherence tomography images of ovarian tissue.
Ovarian cancer has the lowest survival rate among all gynecologic cancers due to predominantly late diagnosis. Optical coherence tomography (OCT) has been applied successfully to experimentally image the ovaries in vivo; however, a robust method for analysis is still required to provide quantitative diagnostic information. Recently, texture analysis has proved to be a useful tool for tissue characterization; unfortunately, existing work in the scope of OCT ovarian imaging is limited to only analyzing 2D sub-regions of the image data, discarding information encoded in the full image area, as well as in the depth dimension. Here we address these challenges by testing three implementations of texture analysis for the ability to classify tissue type. First, we test the traditional case of extracted 2D regions of interest; then we extend this to include the entire image area by segmenting the organ from the background. Finally, we conduct a full volumetric analysis of the image volume using 3D segmented data. For each case, we compute features based on the Grey-Level Co-occurence Matrix and also by introducing a new approach that evaluates the frequency distribution in the image by computing the energy density. We test these methods on a mouse model of ovarian cancer to differentiate between age, genotype, and treatment. The results show that the 3D application of texture analysis is most effective for differentiating tissue types, yielding an average classification accuracy of 78.6%. This is followed by the analysis in 2D with the segmented image volume, yielding an average accuracy of 71.5%. Both of these improve on the traditional approach of extracting square regions of interest, which yield an average classification accuracy of 67.7%. Thus, applying texture analysis in 3D with a fully segmented image volume is the most robust approach to quantitatively characterizing ovarian tissue.


Early Experience With a Novel Hybrid Vascular Graft for Hemodialysis Access Creation in Patients With Disadvantaged Anatomy.
To describe the use of the Hybrid vascular graft in disadvantaged anatomy for hemodialysis access creation and compare outcomes to standard-wall polytetrafluoroethylene (PTFE) grafts. In a retrospective analysis, 25 patients (mean age 65±14 years; 13 men) who received the Hybrid graft were compared with 35 contemporaneous patients (mean age 63±12 years; 20 men) who received a standard PTFE graft for hemodialysis access over a 2-year period. Criteria for Hybrid graft placement were (1) exhausted or inadequate peripheral veins for arteriovenous fistula (AVF) creation and concomitant small target veins that precluded conventional PTFE graft placement, (2) previous graft anastomosis or a stent in the venous target at the level of the axilla, or (3) failed brachial-basilic or brachial-brachial upper arm transposition AVF with a small target vein at the axilla. Efficacy, anatomic and clinical considerations, and technique were reviewed; patency rates, complications, and reinterventions were examined. Technical success was achieved in all cases, and all grafts were usable for hemodialysis. Seven of 25 Hybrid patients required stent-graft extensions and 3 patients required angioplasty to improve venous outflow at the time of Hybrid graft insertion. Three of 35 standard PTFE graft patients required angioplasty to improve venous outflow at the time of graft insertion. There was no perioperative mortality or procedure-related morbidity in either group. Median follow-up was 21 months. The patient survival estimate was 66% at 2 years. Estimated primary patency (24% vs 18%, p>0.05), assisted primary patency (34% vs 28%; p>0.05), and secondary patency rates (40% vs 38%, p≥0.05) at 24 months were equivalent for Hybrid vs PTFE grafts, respectively. Venous hypertension was not a complication following Hybrid graft implantation but was seen in 2 patients with the standard PTFE graft. The Hybrid graft offers a safe, technically effective alternative for patients with disadvantaged anatomy requiring hemodialysis access and has comparable outcomes to standard PTFE grafts. Further clinical experience and long-term data are required for determining the proper utility of this device in chronic dialysis-dependent patients.


The pharmacokinetics of L-tryptophan following its intravenous and oral administration.
The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The data obtained following the oral administration of L-tryptophan suggest that the total body clearance and apparent volume of distribution are saturable. The pharmacokinetics of tryptophan after intravenous administration of 5 g and 7.5 g were similar to those after the oral administration of 25 and 50 mg kg-1 (i.e. 1.75 g and 3.5 g). Similar pharmacokinetic values were obtained following intravenous tryptophan when the same subjects were retested after a period of 2-4 weeks.


An optimized protocol for multislice computed tomography of the canine brain.
Computed tomography (CT) is commonly used in veterinary practice to evaluate dogs with suspected brain disease, however contrast resolution limitations and artifacts may reduce visualization of clinically important anatomic features. The purpose of this study was to develop an optimized CT protocol for evaluating the canine brain. The head of a 5-year-old Springer Spaniel with no neurological signs was imaged immediately following euthanasia using a 4-slice CT scanner and 282 protocols. Each protocol used a fixed tube voltage of 120 kVp and 10 cm display field of view. Other acquisition and reconstruction parameters were varied. For each protocol, four selected images of the brain were reconstructed, anonymized and saved in DICOM format. Three board-certified veterinary radiologists independently reviewed each of the four images for each protocol and recorded a numerical quality score for each image. The protocol yielding the lowest total numerical score was defined as the optimal protocol. There was overall agreement that the optimal protocol was the one with the following parameters: sequential mode, 300 mAs, 1 mm slice thickness, 1 s tube rotation time, medium image reconstruction algorithm and applied beam hardening correction. Sequential imaging provided optimal image resolution. The thin-sliced images provided a small blur due to partial volume artifacts. A high tube current resulted in a relatively low noise level. Use of a medium frequency image reconstruction algorithm provided optimal contrast resolution for brain tissue. Use of a proprietary beam hardening correction filter (Posterior Fossa Optimization) markedly reduced beam-hardening artifact.


EasyGene--a prokaryotic gene finder that ranks ORFs by statistical significance.
Contrary to other areas of sequence analysis, a measure of statistical significance of a putative gene has not been devised to help in discriminating real genes from the masses of random Open Reading Frames (ORFs) in prokaryotic genomes. Therefore, many genomes have too many short ORFs annotated as genes. In this paper, we present a new automated gene-finding method, EasyGene, which estimates the statistical significance of a predicted gene. The gene finder is based on a hidden Markov model (HMM) that is automatically estimated for a new genome. Using extensions of similarities in Swiss-Prot, a high quality training set of genes is automatically extracted from the genome and used to estimate the HMM. Putative genes are then scored with the HMM, and based on score and length of an ORF, the statistical significance is calculated. The measure of statistical significance for an ORF is the expected number of ORFs in one megabase of random sequence at the same significance level or better, where the random sequence has the same statistics as the genome in the sense of a third order Markov chain. The result is a flexible gene finder whose overall performance matches or exceeds other methods. The entire pipeline of computer processing from the raw input of a genome or set of contigs to a list of putative genes with significance is automated, making it easy to apply EasyGene to newly sequenced organisms. EasyGene with pre-trained models can be accessed at http://www.cbs.dtu.dk/services/EasyGene.


Previous injuries and some training characteristics predict running-related injuries in recreational runners: a prospective cohort study.
What is the incidence of running-related injuries (RRIs) in recreational runners? Which personal and training characteristics predict RRIs in recreational runners? Prospective cohort study. A total of 200 recreational runners answered a fortnightly online survey containing questions about their running routine, races, and presence of RRI. These runners were followed-up for a period of 12 weeks. The primary outcome of this study was running-related injury. The incidence of injuries was calculated taking into account the exposure to running and was expressed by RRI/1000 hours. The association between potential predictive factors and RRIs was estimated using generalised estimating equation models. A total of 84 RRIs were registered in 60 (31%) of the 191 recreational runners who completed all follow-up surveys. Of the injured runners 30% (n=18/60) developed two or more RRIs, with 5/18 (28%) being recurrences. The incidence of RRI was 10 RRI/1000 hours of running exposure. The main type of RRI observed was muscle injuries (30%, n=25/84). The knee was the most commonly affected anatomical region (19%, n=16/84). The variables associated with RRI were: previous RRI (OR 1.88, 95% CI 1.01 to 3.51), duration of training although the effect was very small (OR 1.01, 95% CI 1.00 to 1.02), speed training (OR 1.46, 95% CI 1.02 to 2.10), and interval training (OR 0.61, 95% CI 0.43 to 0.88). Physiotherapists should be aware and advise runners that past RRI and speed training are associated with increased risk of further RRI, while interval training is associated with lower risk, although these associations may not be causative.


Progress and data gaps in quantitative microbial risk assessment.
Quantitative microbial risk assessment (QMRA) has emerged as a useful tool to develop criteria for human exposures to pathogens. There is opportunity to extend the usefulness of this tool in water and other applications if new fundamental information can be obtained to complement existing data. Such information includes effects of strain and host differences, population level disease dynamics, and ability of animal data to serve as a predictor of human potency. This paper reviews the development of QMRA and outlines the nature of additional data that would be useful for its development.