mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update.
Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression is sufficient to induce epilepsy in experimental models, while rescuing autophagy prevents epileptogenesis, improves behavioral alterations, and provides neuroprotection in seizure-induced neuronal damage. The implication of autophagy in epileptogenesis and maturation phenomena related to seizure activity is supported by evidence indicating that autophagy is involved in the molecular mechanisms which are implicated in epilepsy. In general, mTOR-dependent autophagy regulates the proliferation and migration of inter-/neuronal cortical progenitors, synapse development, vesicular release, synaptic plasticity, and importantly, synaptic clustering of GABAA receptors and subsequent excitatory/inhibitory balance in the brain. Similar to autophagy, the ubiquitin-proteasome system is regulated downstream of mTOR, and it is implicated in epileptogenesis. Thus, mTOR-dependent cell-clearing systems are now taking center stage in the field of epilepsy. In the present review, we discuss such evidence in a variety of seizure-related disorders and models. This is expected to provide a deeper insight into the molecular mechanisms underlying seizure activity.


Reproducible, Quantitative, and Flexible Molecular Subtyping of Clinical DLBCL Samples Using the NanoString nCounter System.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with distinct molecular subtypes. The most established subtyping approach, the "Cell of Origin" (COO) algorithm, categorizes DLBCL into activated B-cell (ABC) and germinal center B-cell (GCB)-like subgroups through gene expression profiling. Recently developed immunohistochemical (IHC) techniques and other established methodologies can deliver discordant results and have various technical limitations. We evaluated the NanoString nCounter gene expression system to address issues with current platforms. We devised a scoring system using 145 genes from published datasets to categorize DLBCL samples. After cell line validation, clinical tissue segmentation was tested using commercially available diagnostic DLBCL samples. Finally, we profiled biopsies from patients with relapsed/refractory DLBCL enrolled in the fostamatinib phase IIb clinical trial using three independent RNA expression platforms: NanoString, Affymetrix, and qNPA. Diagnostic samples showed a typical spread of subtypes with consistent gene expression profiles across matched fresh, frozen, and formalin-fixed paraffin-embedded tissues. Results from biopsy samples across platforms were remarkably consistent, in contrast to published IHC data. Interestingly, COO segmentation of longitudinal fostamatinib biopsies taken at initial diagnosis and then again at primary relapse showed 88% concordance (15/17), suggesting that COO designation remains stable over the course of disease progression. DLBCL segmentation of patient tumor samples is possible using a number of expression platforms. However, we found that NanoString offers the most flexibility and fewest limitations in regards to robust clinical tissue subtype characterization. These subtype distinctions should help guide disease prognosis and treatment options within DLBCL clinical practice.


Intraoperative and perioperative complications in minimally invasive transforaminal lumbar interbody fusion: a review of 513 patients.
OBJECT Transforaminal lumbar interbody fusion (TLIF) has become one of the preferred procedures for circumferential fusion in the lumbar spine. Over the last decade, advances in surgical techniques have enabled surgeons to perform the TLIF procedure through a minimally invasive approach (MI-TLIF). There are a few studies reported in the medical literature in which perioperative complication rates of MI-TLIF were evaluated; here, the authors present the largest cohort series to date. They analyzed intraoperative and perioperative complications in 513 consecutive MI-TLIF-treated patients with lumbar degenerative disc disease. METHODS The authors performed a retrospective review of prospectively collected data on 513 consecutive patients treated over a 10-year period for lumbar degenerative disc disease using MI-TLIF. All patients undergoing either a first-time or revision 1- or 2-level MI-TLIF procedure were included in the study. Demographic, intraoperative, and perioperative data were collected and analyzed using bivariate analyses (Student t-test, analysis of variance, odds ratio, chi-square test) and multivariate analyses (logistic regression). RESULTS A total of 513 patients underwent an MI-TLIF procedure, and the perioperative complication rate was 15.6%. The incidence of durotomy was 5.1%, and the medical and surgical infection rates were 1.4% and 0.2%, respectively. A statistically significant increase in the infection rate was seen in revision MI-TLIF cases, and the same was found for the perioperative complication rate in multilevel MI-TLIF cases. Instrumentation failure occurred in 2.3% of the cases. After analysis, no statistically significant difference was seen in the rates of durotomy during revision and multilevel surgeries. There was no significant difference between the complication rates when stratified according to presenting diagnosis. CONCLUSIONS To the authors' knowledge, this is the largest study of perioperative complications in MI-TLIF in the literature. A total of 513 patients underwent MI-TLIF (perioperative complication rate 15.6%). The most common complication was a durotomy (5.1%), and there was only 1 surgical wound infection (0.2%). There were significantly more perioperative infections in revision MI-TLIF cases and more perioperative complications in multilevel MI-TLIF cases. The results of this study suggest that MI-TLIF has a similar or better perioperative complication profile than those documented in the literature for open-TLIF treatment of degenerative lumbar spine disease.


First Evidence for cos2β>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity.
We present first evidence that the cosine of the CP-violating weak phase 2β is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2β=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2β=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle β of the CKM Unitarity Triangle is β=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2β>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-β=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.


Evaluation of genotype quality parameters for SowPro90, a new genotyping array for swine1.
Understanding early predictors of sow fertility has the potential to improve genomic predictions. A custom SNP array (SowPro90 produced by Affymetrix) was developed to include genetic variants overlapping quantitative trait loci for age at puberty, one of the earliest indicators of sow fertility, as well as variants related to innate and adaptive immunity. The polymorphisms included in the custom genotyping array were identified using multiple genomic approaches including deep genomic and transcriptomic sequencing and genome-wide associations. Animals from research and commercial populations (n = 2,586) were genotyped for 103,476 SNPs included in SowPro90. To assess the quality of data generated, genotype concordance was evaluated between the SowPro90 and Porcine SNP60 BeadArray using a subset of common SNP (n = 44,708) and animals (n = 277). The mean genotype concordance rate per SNP was 98.4%. Differences in distribution of data quality were observed between the platforms indicating the need for platform specific thresholds for quality parameters. The optimal thresholds for SowPro90 (≥97% SNP and ≥93% sample call rate) were obtained by analyzing the data quality distribution and genotype concordance per SNP across platforms. At ≥97% SNP call rate, there were 42,151 SNPs (94.3%) retained with a mean genotype concordance of 98.6% across platforms. Similarly, ≥94% SNPs and ≥85% sample call rates were established as thresholds for Porcine SNP60 BeadArray. At ≥94% SNPs call rate, there were 41,043 SNPs (91.8%) retained with a mean genotype concordance of 98.6% across platforms. Final evaluation of SowPro90 array content (n = 103,476) at ≥97% SNPs and ≥93% sample call rates allowed retention of 89,040 SNPs (86%) for downstream analysis. The findings and strategy for quality control could be helpful in identifying consistent, high-quality genotypes for genomic evaluations, especially when integrating genotype data from different platforms.


Unmasking the magnitude estimation response.
The fuzzy judgement model of Ward (1979) predicts an inverse relation between the amount of stimulus information available to subjects and the magnitude of sequential dependencies on previous stimuli and responses in psychophysical scaling tasks. Ward confirmed this prediction for magnitude estimations of interdot distance for previous responses but not for previous stimuli, although the inverse relation has been repeatedly reported for both the previous stimuli and responses in absolute identification (e.g., Mori, 1989). This paper further explores this seemingly puzzling contradiction. A magnitude estimation of loudness experiment was conducted in which the amount of stimulus information available to subjects was manipulated by a modified version of informational masking (Watson, 1987). An absolute-identification-with-feedback experiment was also conducted to check the effectiveness of the informational masking in reducing the amount of stimulus information. The results of the magnitude estimation experiment show a striking similarity with those of Ward and generalize the failure of sequential dependencies on previous stimuli to vary inversely with stimulus information. An additional assumption that judgement strategies are altered under low-information conditions is necessary to explain this result.


Aflatoxicol H1: a major metabolite of aflatoxin B1 produced by human and rhesus monkey livers in vitro.
Among the major metabolites of aflatoxin B1 produced by human and monkey livers in vitro is a derivative with the ketone carbonyl on the cyclopentane ring reduced to a secondary alcohol, and a hydroxyl introduced onto the carbon beta to the alcohol group. The metabolite was formed from aflatoxin B1 at a level similar to that of aflatoxin M1.Both the microsomal hydroxylase and the cytoplasmic reductase systems are required for its formation. Bioassay using chicken embryos and a mutant of Salmonella typhimurium revealed no toxicity. This newly identified metabolite was named aflatoxicol H1.


Quantum dot loaded liposomes as fluorescent labels for immunoassay.
Liposomes loaded with water-soluble and water-insoluble quantum dots (QD) were for the first time applied as labels in different heterogeneous immunoassays for the determination of food contaminants, using mycotoxin zearalenone (ZEN) as a model. A great deal of work was devoted to the optimal choice of phospholipids for the liposomes preparation and to the factors which are important for the stability and size of obtained liposomes. Thin-film hydration and reverse-phase evaporation techniques were evaluated in terms of stability of the obtained liposomes and their efficiency for QD loading. Conjugation of liposomes with proteins and the influence of cross-linkers to the nonspecific interaction of the obtained liposomes with the surface of microtiter plates and cartridges were investigated and 3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide ester was found as the optimal cross-linker. The limits of detection (LOD) for ZEN of fluorescence-labeled immunosorbent assays were 0.6 μg kg(-1), 0.08 μg kg(-1), and 0.02 μg kg(-1), using QD, liposomes loaded with water-soluble QD, and water-insoluble QD, respectively. Similarly, the developed qualitative on-site tests using the different QD labels and taking into account the EU maximum residues level for ZEN in unprocessed cereals showed cutoff levels of 100, 50, and 20 μg kg(-1).


Engineering a nanotubular mesoporous cobalt phosphide electrocatalyst by the Kirkendall effect towards highly efficient hydrogen evolution reactions.
Tailoring the size and controlling the morphology of particular nano-architectures are considered as two promising strategies to improve the catalytic performance of metal nanocrystals towards hydrogen evolution reactions (HERs). Herein, mesoporous cobalt phosphide nanotubes (CoP-NTs) with a three-dimensional network structure have been obtained through a facile and efficient electrospinning technique combined with thermal stabilization and phosphorization treatments. The thermal stabilization process has been demonstrated to play a key role in the morphological tailoring of Co3O4 nanotubes (Co3O4-NTs). As a result, the CoP-NTs show one-dimensional hollow tubular architecture instead of forming a worm-like tubular CoP structure (W-CoP-NTs) or severely aggregated CoP powder (CoP-NPs) which originate from the Co3O4 nanotubes without thermal stabilization treatment and Co3O4 nanoparticles, respectively. Satisfyingly, under an optimized phosphorization degree, the CoP-NT electrode exhibits a low onset overpotential of 53 mV with a low Tafel slope of 50 mV dec-1 during the HER process. Furthermore, the CoP-NT electrode is capable of driving a large cathodic current density of 10 mA cm-2 at an overpotential of 152 mV, which is much lower than those of its contrast samples, i.e. CoP-NPs (211 mV) and W-CoP-NTs (230 mV). Therefore, this work provides a feasible and general strategy for constructing three-dimensionally organized mesoporous non-noble metal phosphide nanotubes as promising alternative high-performance electrocatalysts for the commercial platinum ones.


Molecular Mean-Field Theory of Ionic Solutions: A Poisson-Nernst-Planck-Bikerman Model.
We have developed a molecular mean-field theory-fourth-order Poisson-Nernst-Planck-Bikerman theory-for modeling ionic and water flows in biological ion channels by treating ions and water molecules of any volume and shape with interstitial voids, polarization of water, and ion-ion and ion-water correlations. The theory can also be used to study thermodynamic and electrokinetic properties of electrolyte solutions in batteries, fuel cells, nanopores, porous media including cement, geothermal brines, the oceanic system, etc. The theory can compute electric and steric energies from all atoms in a protein and all ions and water molecules in a channel pore while keeping electrolyte solutions in the extra- and intracellular baths as a continuum dielectric medium with complex properties that mimic experimental data. The theory has been verified with experiments and molecular dynamics data from the gramicidin A channel, L-type calcium channel, potassium channel, and sodium/calcium exchanger with real structures from the Protein Data Bank. It was also verified with the experimental or Monte Carlo data of electric double-layer differential capacitance and ion activities in aqueous electrolyte solutions. We give an in-depth review of the literature about the most novel properties of the theory, namely Fermi distributions of water and ions as classical particles with excluded volumes and dynamic correlations that depend on salt concentration, composition, temperature, pressure, far-field boundary conditions etc. in a complex and complicated way as reported in a wide range of experiments. The dynamic correlations are self-consistent output functions from a fourth-order differential operator that describes ion-ion and ion-water correlations, the dielectric response (permittivity) of ionic solutions, and the polarization of water molecules with a single correlation length parameter.


The impact of livestock grazing on plant diversity: an analysis across dryland ecosystems and scales in southern Africa.
A general understanding of grazing effects on plant diversity in drylands is still missing, despite an extensive theoretical background. Cross-biome syntheses are hindered by the fact that the outcomes of disturbance studies are strongly affected by the choice of diversity measures, and the spatial and temporal scales of measurements. The aim of this study is to overcome these weaknesses by applying a wide range of diversity measures to a data set derived from identical sampling in three distinct ecosystems. We analyzed three fence-line contrasts (heavier vs. lighter grazing intensity), representing different degrees of aridity (from arid to semiarid) and precipitation regimes (summer rain vs. winter rain) in southern Africa. We tested the impact of grazing intensity on multiple aspects of plant diversity (species and functional group level, richness and evenness components, alpha and beta diversity, and composition) at two spatial scales, and for both 5-yr means and interannual variability. Heavier grazing reduced total plant cover and substantially altered the species and functional composition at all sites. However, a significant decrease in species alpha diversity was detected at only one of the three sites. By contrast, alpha diversity of plant functional groups responded consistently across ecosystems and scales, with a significant decrease at heavier grazing intensity. The cover-based measures of functional group diversity responded more sensitively and more consistently than functional group richness. Beta diversity of species and functional types increased under heavier grazing, showing that at larger scales, the heterogeneity of the community composition and the functional structure were increased. Heavier grazing mostly increased interannual variability of alpha diversity, while effects on beta diversity and cover were inconsistent. Our results suggest that species diversity alone may not adequately reflect the shifts in vegetation structure that occur in response to increased grazing intensity in the dryland biomes of southern Africa. Compositional and structural changes of the vegetation are better reflected by trait-based diversity measures. In particular, measures of plant functional diversity that include evenness represent a promising tool to detect and quantify disturbance effects on ecosystems.


Haemodipsus leporis Blagoveshtchensky, 1966 (Phthiraptera: Anoplura: Polyplacidae) on a Hare (Lepus europaeus, L.): new record for Turkish Phthiraptera fauna.
This study was carried out to detect lice species found on hares (L. europaeus, L.) in the Konya province. Several lice individuals were collected on a hare and were kept in 70% alcohol. Then, they were cleaned in 10% KOH for 24 hours, washed in distilled water, stored in 70%, 80%, 90% and 96% alcohol for 24 hours for each step. They were mounted on the slides in Canada balsam and examined under a binocular light microscope. Two of the species were identified as Haemodipsus leporis Blagoveshtchensky, 1966, while the others were H. lyriocephalus (Burmeister, 1839). H. leporis was found on L. europaeus for the first time in Turkey, and it was also detected on this host species for the first time throughout the world. The morphological characteristics of this species are given in this paper.


SupplAzithromycin for Prevention of Graft-Versus-Host Disease: A Randomized Placebo-Controlled Trial.
Background: Allogeneic hematopoietic stem cell transplantation has been used widely to treat various types of malignant and non-malignant disorders. Graft-versus-host disease is one of the main complications of this procedure which is associated with considerable mortality and affects quality of life. Despite careful selection of HLA-matched donors and implementing immunosuppressive therapy, the incidence rate of graft-versus-host disease remains high. Macrolide antibiotics are well-known immunomodulatory agents and have been effective as prophylaxis for graft-versus-host disease in preclinical studies. Materials and Methods: Ninety-six adult patients with acute leukemia were recruited into a double-blind, randomized, placebo-controlled trial. All patients were first-time transplant candidates for a full-matched related or unrelated donor. Patients were allocated to receive azithromycin 500 mg daily (n=48) or placebo (n=48) from day -6 to +12. All patients received high-dose chemotherapy, standard immunosuppressive regimen and supportive care according to institutional protocols. Results: The incidence of acute graft-versus-host disease grade III-IV and chronic graft-versus-host disease garde I-III was not significantly different between the two study arms. Oral mucositis grade 1-3 occurred in significantly lower number of patients in the azithromycin group compared with placebo. Conclusion: Based on the results of this study, protective effect of azithromycin on graft-versus-host disease could not be demonstrated.


Some aspects of equine embryo transfer.
The number of successful embryo recoveries was 56.0% in experimental mares with no history of breeding problems but in barren mares only 34.3% of embryo recovery attempts were successful. When a recovery attempt was successful, the incidence of twin embryos was 10.7% in experimental mares and 16.7% in barren mares. Maintenance of embryos in vitro for greater than 6 h before non-surgical transfer significantly reduced pregnancy rates compared to maintenance for less than 3 h. The pregnancy rate in recipients at 100 days after ovulation was lower (P less than 0.05) than those at 24 and 30 days after ovulation.


Secular trends in hospital emergency department visits for dental care in Kansas City, Missouri, 2001-2006.
We determined the trends, risk factors, and costs of emergency department (ED) visits for dental complaints during a six-year period in Kansas City, Missouri (KCMO). We used de-identified hospital discharge data from all facilities serving KCMO during 2001-2006. Using the International Classification of Diseases, Ninth Revision codes, we determined both counts and rates of ED visits related to toothache or tooth injury and analyzed the discharge diagnosis and costs of these visits. We used multivariable regression analysis to assess risk factors for the ED visits for dental complaints. We found a significant increasing trend in dental complaint visits during the six-year period (from 13.1% to 19.0%, p < 0.01). Dental caries accounted for 20.4%, pulpitis or periapical abscess accounted for 14.8%, dental injury accounted for 8.7%, temporomandibular joint (TMJ) disorders accounted for 1.5%, and all other unspecified dental diseases accounted for 54.6% of the ED visits for dental complaints. The mean charge was approximately $360 per visit and was highest for TMJ disorders ($747) and lowest for unspecified other dental diseases ($277). Self-pay (38.3%) and Medicaid (32.3%) constituted the majority of the payment sources. Multivariable regression analysis indicated that self-payers, nonwhite people, adults, people with lower family income, and weekends were associated with increased use of ED visits for dental complaints. There was a significant increasing trend in dental complaint-related ED visits. EDs have become an important site for people with dental problems to seek urgent care, particularly for individuals who self-pay or are on Medicaid.


Ehrlich ascites tumour cells show tissue-specific adherence and modify their shape upon contact with embryonic fibroblasts and myotubes.
Adhesiveness of Ehrlich ascites tumour (EAT) cells to glass, to mouse peritoneal membrane, living and aldehyde-fixed mouse embryo fibroblasts and chick embryo fibroblasts, myoblasts and myotubes was investigated. The ascitic EAT cells (and leukaemia L1210 cells) did not adhere to glass and peritoneum but readily adhered to embryo fibroblasts, myoblasts and myotubes. The attachment was followed by cell spreading and migration. Fixation of fibroblasts or myogenic cells with aldehydes did not prevent ascitic cells from attaching but reduced the rate of spreading. Only direct interaction of ascitic cells with embryo myoblasts or fibroblasts induced changes in tumour cell adhesiveness followed by cell spreading and locomotion. These results are discussed in relation to an observation that ascitic cells growing as a cell suspension intraperitoneally grow as a solid tumour when injected subcutaneously.


Consistency of option prices under bid-ask spreads.
Given a finite set of European call option prices on a single underlying, we want to know when there is a market model that is consistent with these prices. In contrast to previous studies, we allow models where the underlying trades at a bid-ask spread. The main question then is how large (in terms of a deterministic bound) this spread must be to explain the given prices. We fully solve this problem in the case of a single maturity, and give several partial results for multiple maturities. For the latter, our main mathematical tool is a recent result on approximation by peacocks.


Indirect magnetic coupling in light-element-doped single-walled carbon nanotubes.
Single-walled carbon nanotubes substitutionally doped with the light-element phosphorus are synthesized and are investigated by electrical and nuclear magnetic resonance measurements. Decreased spin-lattice relaxation times compared to undoped tubes point toward enhanced spin-sensitive scattering. Temperature dependence of the zero-bias conductance shows step-like features, a signature of scattering from a very low density (few sites per nanotube) of localized spin moments at oxidized phosphorus sites, consistent with density functional calculations. This supports recent predictions that localized magnetic moments must be indirectly magnetically coupled through the nanotube conduction electrons.


PAX3-FOXO1 induces up-regulation of Noxa sensitizing alveolar rhabdomyosarcoma cells to apoptosis.
Alveolar rhabdomyosarcoma (ARMS) has a much poorer prognosis than the more common embryonal subtype. Most ARMS tumors characteristically possess a specific genomic translocation between the genes of PAX3/7 and FOXO1 (FKHR), which forms fusion proteins possessing the DNA binding domains of PAX3/7 and the more transcriptionally potent transactivation domain of FOXO1. We have shown that the proapoptotic BH3-only family member Noxa is upregulated by the PAX3-FOXO1 fusion transcription factor in a p53-independent manner. The increased expression of Noxa renders PAX3-FOXO1-expressing cells more susceptible to apoptosis induced by a γ-secretase inhibitor (GSI1, Z-LLNle-CHO), the proteasome inhibitor bortezomib, and BH3 mimetic ABT-737. Apoptosis in response to bortezomib can be overcome by shRNA knockdown of Noxa. In vivo treatment with bortezomib reduced the growth of tumors derived from a PAX3-FOXO1-expressing primary myoblast tumor model and RH41 xenografts. We therefore demonstrate that PAX3-FOXO1 up-regulation of Noxa represents an unanticipated aspect of ARMS tumor biology that creates a therapeutic window to allow induction of apoptosis in ARMS cells.


A new metabolomics analysis technique: steady-state metabolic network dynamics analysis.
With the recent advances in experimental technologies, such as gas chromatography and mass spectrometry, the number of metabolites that can be measured in biofluids of individuals has markedly increased. Given a set of such measurements, a very common task encountered by biologists is to identify the metabolic mechanisms that lead to changes in the concentrations of given metabolites and interpret the metabolic consequences of the observed changes in terms of physiological problems, nutritional deficiencies, or diseases. In this paper, we present the steady-state metabolic network dynamics analysis (SMDA) approach in detail, together with its application in a cystic fibrosis study. We also present a computational performance evaluation of the SMDA tool against a mammalian metabolic network database. The query output space of the SMDA tool is exponentially large in the number of reactions of the network. However, (i) larger numbers of observations exponentially reduce the output size, and (ii) exploratory search and browsing of the query output space is provided to allow users to search for what they are looking for.


Follicle-stimulating hormone is secreted more irregularly than luteinizing hormone in both humans and sheep.
Recently introduced statistical tools capable of discerning differences between the pattern of luteinizing hormone (LH) secretion and that of follicle-stimulating hormone (FSH) could be valuable in understanding ovulation and menopause, and ultimately in making diagnostic decisions and treating infertility and polycystic ovary syndrome. We assessed the validity and scope of the hypothesis that FSH is secreted more irregularly than LH in ewes and fertile women. We compared secretory irregularity of LH to that of FSH in both ovariectomized ewes (n = 7) and women of proven fertility (n = 5) during the follicular and luteal phases of their reproductive cycles. In each sheep, time series from both hypophyseal portal blood (HPB) and peripheral blood were evaluated in 72 samples obtained every 5 min; in each human, both luteal and follicular periods were studied in 192 samples obtained every 7.5 min. To quantify serial irregularity, we used approximate entropy (ApEn), a scale- and model-independent statistic. FSH secretion was consistently more irregular than that of LH in each subject. For sheep HPB, ApEn(FSH) = 1.415+/-0.097 was larger than ApEn(LH) = 0. 822+/-0.213, P < 0.0001 (mean+/-SD, paired t test). This difference persisted peripherally: ApEn(FSHper) = 1.431+/-0.101 > ApEn(LHper) = 1.252+/-0.086, P = 0.024. In women, ApEn(FSH) = 1.467+/-0.217 > ApEn(LH) = 0.923+/- 0.305, P < 0.0001. ApEn(FSH) > ApEn(LH) in 100% of women (peripheral) and sheep HPB. Secretion during the follicular phase was more irregular than during the luteal phase for both FSH and LH (P < 0.01). LH mean level secretion showed a wake/sleep difference in women, P < 0.005, with higher values awake. The consistency and statistical significance of these findings suggest that this LH/FSH difference may be broadly based within higher mammals. Ranges of normative and abnormal regularity values of LH, FSH, and their difference can be used in a number of settings, both (currently) research and (potentially ultimately) clinical milieus.


Epidemiology of breast cancer in Connecticut women.
At least 50% of breast cancer may be "explained" by known or suspected risk factors, including modifiable behaviors involving diet, overweight, exercise, and alcohol use. Interest continues to grow in "hereditary" breast (and ovarian) cancer due to germ cell mutations, but most breast cancers are due to environmentally induced (somatic) mutations. According to data from the Connecticut Tumor Registry, the incidence of invasive breast cancer has changed little since 1990. The proportion of breast cancers diagnosed at the in situ stage has increased while the proportions diagnosed at the regional and distant stages have decreased, which is consistent with an effect of increased screening. Breast cancer mortality rates, the crucial yardstick of progress in cancer control, have declined slightly in Connecticut (and nationally) since 1989, reflecting the effects of earlier detection (through screening) and improved treatment. Primary care physicians have an important role in primary and secondary prevention.


Use of Continuous Traits Can Improve Morphological Phylogenetics.
The recent surge in enthusiasm for simultaneously inferring relationships from extinct and extant species has reinvigorated interest in statistical approaches for modeling morphological evolution. Current statistical methods use the Mk model to describe substitutions between discrete character states. Although representing a significant step forward, the Mk model presents challenges in biological interpretation, and its adequacy in modeling morphological evolution has not been well explored. Another major hurdle in morphological phylogenetics concerns the process of character coding of discrete characters. The often subjective nature of discrete character coding can generate discordant results that are rooted in individual researchers' subjective interpretations. Employing continuous measurements to infer phylogenies may alleviate some of these issues. Although not widely used in the inference of topology, models describing the evolution of continuous characters have been well examined, and their statistical behavior is well understood. Also, continuous measurements avoid the substantial ambiguity often associated with the assignment of discrete characters to states. I present a set of simulations to determine whether use of continuous characters is a feasible alternative or supplement to discrete characters for inferring phylogeny. I compare relative reconstruction accuracy by inferring phylogenies from simulated continuous and discrete characters. These tests demonstrate significant promise for continuous traits by demonstrating their higher overall accuracy as compared to reconstruction from discrete characters under Mk when simulated under unbounded Brownian motion, and equal performance when simulated under an Ornstein-Uhlenbeck model. Continuous characters also perform reasonably well in the presence of covariance between sites. I argue that inferring phylogenies directly from continuous traits may be benefit efforts to maximize phylogenetic information in morphological data sets by preserving larger variation in state space compared to many discretization schemes. I also suggest that the use of continuous trait models in phylogenetic reconstruction may alleviate potential concerns of discrete character model adequacy, while identifying areas that require further study in this area. This study provides an initial controlled demonstration of the efficacy of continuous characters in phylogenetic inference.


Subcutaneous myiasis caused by Dermatobia hominis.
A case of subcutaneous myiasis caused by the larvae of the Dermatobia hominis fly is described, involving the ankle region of a 25-y-old man who had returned from Peru. After removal of 4 larvae from the affected sites, the lesions healed in 2 weeks without further treatment. Because of the increasing number of people travelling to tropical America, physicians in Slovenia will have to consider Dermatobia myiasis in the differential diagnosis of furuncular lesions in patients with a relevant travel history.


New Cu(I)-ethylene complexes based on tridentate imine ligands: synthesis and structure.
A new bulky facially coordinating N3-donor tach-based ligand (tach: cis,cis-1,3,5-triaminocyclohexane) [1: cis,cis-1,3,5-tris(2-fluoro-6-(trifluoromethyl)benzylideneamino)cyclohexane] has been obtained from the condensation of tach with 3 equiv of the appropriate benzaldehyde. Reaction of 1 with [Cu(NCMe)4][PF6] gave the complex [(1)Cu(NCMe)][PF6]. Displacement of the acetonitrile ligand is possible with CO and C2H4 (3-5 bar). Cu(I)-ethylene complexes of ligands 1 and 2 [2: cis,cis-1,3,5-(mesitylideneamino)cyclohexane] were prepared successfully by treatment of the ligands with CuBr and AgSbF6 in the presence of ethylene. These complexes display reversible complexation of the ethylene molecule under mild changes to pressure, suggesting possible application in olefin separation and extraction.


Omega-3 fatty acid supplementation in advanced kidney disease.
Long-chain polyunsaturated omega-3 fatty acids (n-3 PUFA), which are obtained primarily from dietary sources such as coldwater fish, have diverse and potent mediating effects on the immune, inflammatory, and metabolic pathways, signal transduction, and cell membrane physiology. N-3 PUFA are increasingly being studied for their clinical benefits in a variety of medical conditions, some of which are relevant to individuals with advanced chronic kidney disease (CKD). These include, among others, renoprotection in IgA nephropathy, cardioprotective effects via a variety of mechanisms including blood pressure and triglyceride reduction, maintenance of dialysis access patency, sparing of inflammation-associated muscle loss, and even mortality. However, further confirmatory work needs to be performed before establishing formal intake recommendations and dosing goals for advanced CKD patients. In the meantime, the current American Heart Association n-3 PUFA intake guidelines can be applied to CKD patients, especially given n-3 PUFA's potential benefits and negligible risk profile. Over time, it will be incumbent upon the nephrology community to more clearly define the utility and optimal dosing of n-3 PUFA in CKD patients with advanced disease via randomized clinical trials.


Organ donation workshop - a survey on nurses' knowledge and attitudes toward organ and tissue donation in Iran.
Despite increasing transplantation in Iran, organ shortage and long waiting lists remain major problems in the country. Many publications have demonstrated that the willingness of healthcare professionals to participate in the donation process can improve the donation rate. Since nurses are usually the first people among the healthcare staff to recognize a patient as a potential donor, they have an important role in the procurement of organ and tissue from cadaveric donors. Our objectives were to survey nurses' knowledge and attitudes toward organ and tissue donation and to examine the effect of having them attend a workshop on organ donation. A 39-item questionnaire was completed by 66 nurses, before and after participation in a 1-day organ donation workshop that was held at the Iranian Tissue Bank (in Tehran, Iran). The questionnaire contained demographic data, 29 questions regarding knowledge, and 8 questions on attitudes toward organ and tissue donation. 69.7% women and 30.3% men participated in this study. The mean score for knowledge was 16.89 (SD= 3.33) before and 23.76 (SD=1.66) after the workshop (p=0.000). The mean attitudes score was 4.76 (SD=1.71) before and 5.08 (SD=1.34) after the workshop (p=0.235). Although 63.63% claimed they were willing to have a donation card only 15.15% actually carried one. This study demonstrated that educational programs can enhance nurses' knowledge and commitment to the organ donation process and, ultimately, increase the donation rate. Consequently, it is of great importance for organ procurement units to focus on regular training programs for all their healthcare staff.


[Investigation of organophosphorous insecticides residue in Chinese crude drugs].
To study eleven organophosphorus insecticides residuals in four kinds of Chinese crude drugs. The organophosphorus insecticides were extracted with dichloromethane and cleaned-up with a mixture of Celite 545-activated carbon. The extracts were analyzed by gas chromatography equipped with a flame photometric detector (FPD). Analysis of fortified Chinese crude drug showed that the average recoveries ranged from 77.5% -112.3% at three different levels, the RSDs were below 10% (n = 4). Trace organophosphorous pesticide residues were found in samples of Rhizoma Atractylodis Macrocephalae and Flos Chrysanthemi. A method was established for determination multi-residues in Rhizma Atractylodis Macrocephalae, Radix Curcumae, Bulbus Fritillariae Thunbergii and Flos Chrysanthemi. It provides a method for the risk assessment of organophosphorous pesticide in Chinese crude drugs.


A reanalysis of five studies on sexual orientation and the relative length of the 2nd and 4th fingers (the 2D:4D ratio).
Five studies have examined the relationship between sexual orientation and the relative lengths of the 2nd and 4th fingers (the 2D:4D ratio). Although differences have commonly been found between heterosexuals and homosexuals, the direction of the difference has not been consistent across studies. The original data from all five studies were reanalyzed in a search for possible explanations of the discrepancies. Because ethnicity is known to affect the 2D:4D ratio, the reanalysis focused on participants who identified themselves as White or Caucasian, the ethnic group that was most numerous in all of the studies. Age differences did not account for the discrepancies. Differences in variability within different groups were minor. One interesting result to emerge from the reanalysis was that the 2D:4D ratios for the homosexual groups were relatively similar across studies. It was the 2D:4D values for the heterosexual participants that varied most, particularly between the USA and the British studies, and these were responsible for many of the discrepancies in the conclusions across studies. The constancy of the 2D:4D ratio for the White homosexuals did not appear to extend to homosexuals of three other ethnicities, and there were also subpopulation differences related to right or left hands.


[Assessment of patient-reported outcomes by questionnaires in patients with Moderate and severe chronic obstructive pulmonary disease treated with glycopyrroniUm in the reaL lifE setTing in Hungary (AMULET)].
Introduction: Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder, therefore, airflow limitation alone does not reflect the full burden of COPD. In Hungary, no national data are available yet about the results obtained with the different COPD questionnaires in daily patient care, and about difficulties of questionnaires for patients. Aim and method: The aim of the study was to evaluate patient-reported outcomes with guideline-suggested questionnaires (CCQ, CAT, mMRC, EQ-5D-5L) in patients treated with glycopyrronium-bromide (therapy naïve, add-on combination or switch from another therapy) in the real life setting during 16 weeks treatment. This study was open-label, multi-centre, non-interventional, observational. Results: 527 patients were enrolled in the study (mean age: 63.8 ± 9.64 years, mean FEV1: 59.8 ± 15.12%). In all of the groups, the CCQ mean scores, all of the CCQ subscores, CAT and mMRC scores significantly decreased from visit 1 to visit 3. The EQ-5D-5L index and VAS scores increased significantly between visits. According to investigators' opinion, the CAT test reflects the patient's condition better (84.7%) than CCQ or mMRC; also, from the patient's point of view, CAT was simpler and easier to understand (83.2%). There was a positive, statistically significant correlation between CCQ and CAT (rs = 0.711, p<0.001), between CCQ and mMRC (rs = 0.524, p<0.001) and between CAT and mMRC scores at visit 3 (rs = 0.475, p<0.001). Conclusion: Our results suggest that the CAT test may be simpler and easier to understand for patients. Also, according to investigators' opinion, CAT reflects the patient's condition better, so CAT appears to be the most promising tool in COPD evaluation. Orv Hetil. 2020; 161(8): 295-305.


Salivary alpha-amylase enzyme is a non-invasive biomarker of acute stress in Japanese macaques (Macaca fuscata).
Salivary alpha-amylase (sAA) enzyme functions as a digestive enzyme in many species that consume starch in their diet. Human studies have also revealed that sAA enzyme activity levels are positively correlated with the release of the stress hormone norepinephrine, allowing sAA to act as a biomarker for sympathetic nervous system activity. Recent non-human primate studies have incorporated sAA as a physiological stress marker. However, no published reports have investigated the time course of sAA from a stressful event to return to baseline levels in non-human primates. Furthermore, no validation of sAA as a stress biomarker has been reported for Japanese macaques (Macaca fuscata). This study had two primary aims: (1) to develop a systematic method for non-invasive saliva collection and, (2) to investigate sAA as a biomarker of acute stress in M. fuscata in order to better understand its acute stress-related characteristics. We developed a non-invasive method for cooperative saliva collection using positive reinforcement training (PRT) and tracked individual progress over 595 trials in ten individually housed Japanese macaques. We detected sAA enzyme in M. fuscata via kinetic reaction assay, then performed 22 acute stress tests. Four tests met conditions for interpreting sAA in response to an acute stressor and these results show that on average sAA activity rapidly increased post-stressor (mean ± SD = 4.2 ± 0.9 min) and returned to baseline shortly thereafter (10.4 ± 0.6 min). Our report reveals for the first time the temporal dynamics of sAA when applying acute stress to Japanese macaques and could be a useful tool for assessing animal welfare.


Environment sensing in spring-dispersed seeds of a winter annual Arabidopsis influences the regulation of dormancy to align germination potential with seasonal changes.
Seed dormancy cycling plays a crucial role in the lifecycle timing of many plants. Little is known of how the seeds respond to the soil seed bank environment following dispersal in spring into the short-term seed bank before seedling emergence in autumn. Seeds of the winter annual Arabidopsis ecotype Cvi were buried in field soils in spring and recovered monthly until autumn and their molecular eco-physiological responses were recorded. DOG1 expression is initially low and then increases as dormancy increases. MFT expression is negatively correlated with germination potential. Abscisic acid (ABA) and gibberellin (GA) signalling responds rapidly following burial and adjusts to the seasonal change in soil temperature. Collectively these changes align germination potential with the optimum climate space for seedling emergence. Seeds naturally dispersed to the soil in spring enter a shallow dormancy cycle dominated by spatial sensing that adjusts germination potential to the maximum when soil environment is most favourable for germination and seedling emergence upon soil disturbance. This behaviour differs subtly from that of seeds overwintered in the soil seed bank to spread the period of potential germination in the seed population (existing seed bank and newly dispersed). As soil temperature declines in autumn, deep dormancy is re-imposed as seeds become part of the persistent seed bank.


Exercise and nutritional needs of elderly people: effects on muscle and bone.
Advancing age is associated with a remarkable number of changes in body composition. Reductions in lean body mass have been well characterized. This decreased lean body mass occurs primarily as a result of losses in skeletal muscle mass. This age-related loss in muscle mass has been termed sarcopenia. Loss in muscle mass accounts for the age-associated decreases in basal metabolic rate, muscle strength, and activity levels, which, in turn is the cause of the decreased energy requirements of the elderly. In sedentary individuals, the main determinant of energy expenditure is fat-free mass, which declines by about 15% between the third and eighth decade of life. It also appears that declining caloric needs are not matched by an appropriate decline in caloric intake, with the ultimate result an increased body fat content with advancing age. Increased body fatness along with increased abdominal obesity are thought to be directly linked to the greatly increased incidence of Type II diabetes among the elderly. This review will discuss the extent to which regularly performed exercise can effect nutritional needs and functional capacity in the elderly. In addition, some basic guidelines for beginning an exercise program for older men and women, and establishing community-based programs are provided.


Total duplication of the small single copy region in the angiosperm plastome: Rearrangement and inverted repeat instability in Asarum.
As more plastomes are assembled, it is evident that rearrangements, losses, intergenic spacer expansion and contraction, and syntenic breaks within otherwise functioning plastids are more common than was thought previously, and such changes have developed independently in disparate lineages. However, to date, the magnoliids remain characterized by their highly conserved plastid genomes (plastomes). Illumina HiSeq and MiSeq platforms were used to sequence the plastomes of Saruma henryi and those of representative species from each of the six taxonomic sections of Asarum. Sequenced plastomes were compared in a phylogenetic context provided by maximum likelihood and parsimony inferences made using an additional 18 publicly available plastomes from early-diverging angiosperm lineages. In contrast to previously published magnoliid plastomes and the newly sequenced Saruma henryi plastome published here, Asarum plastomes have undergone extensive disruption and contain extremely lengthy AT-repeat regions. The entirety of the small single copy region (SSC) of A. canadense and A. sieboldii var. sieboldii has been incorporated into the inverted repeat regions (IR), and the SSC of A. delavayi is only 14 bp long. All sampled Asarum plastomes share an inversion of a large portion of the large single copy region (LSC) such that trnE-UUC is adjacent to the LSC-IR boundary. Plastome divergence in Asarum appears to be consistent with trends seen in highly rearranged plastomes of the monocots and eudicots. We propose that plastome instability in Asarum is due to repetitive motifs that serve as recombinatory substrates and reduce genome stability.


Sarcocystosis in neonatal bison fed Sarcocystis cruzi sporocysts derived from cattle.
A 6-day-old female (Bison bison) was inoculated with 10 million sporocysts of the B1 isolate of Sarcocystis cruzi originally obtained by feeding heart of a naturally infected cow (Bos taurus) to a laboratory-raised coyote. The bison became febrile, lethargic, and anorectic at about 25 days after inoculation of the sporocysts, and was euthanatized 3 days later. There were widespread hemorrhages, hepatitis, myocarditis, nephritis, and enteritis; intravascular meronts were found in the adrenal cortex and lamina propria of the small intestine. Another 7-day-old male bison was inoculated with 100,000 sporocysts of the same B1 isolate of S cruzi. Except for mild fever and transient diarrhea, the bison remained clinically normal. Sarcocysts were found at necropsy on day 76 after inoculation. It was concluded that S cruzi of cattle is transmissible to bison.


Supplementing goat kids with coconut medium chain fatty acids in early life influences growth and rumen papillae development until 4 months after supplementation but effects on in vitro methane emissions and the rumen microbiota are transient.
The aim of this study was to investigate the methane (CH4) reducing potential of a combination of prenatal and/or postnatal treatment with coconut oil medium chain fatty acids (CO MCFA) in goat kids. The hypothesis is that influencing rumen function during early life has more chances for success than in the adult life, related to the resilience of the mature rumen microbiota. Forty-eight pregnant does were split into two experimental groups: treated does (D+) received 40 g/d of CO MCFA in a test compound feed, while control does (D-) received a control compound feed, during the last 3 wk of gestation. Twin kids from 10 does of each group were split up into a treated (K+) and nontreated (K-) group, resulting in four experimental groups: D+K+, D+K-, D-K+, and D-K-. The K+ kids received 1.8 mL/d of CO MCFA from birth until 2-wk postweaning (11 wk). Irrespective of treatment, the experimental rearing conditions resulted in absence of rumen protozoa at all sampling times, assessed by quantitative PCR (qPCR). In vitro incubations with rumen fluid at 4 wk old showed 82% lower CH4 production of inoculum from D+K+ kids compared to D-K- kids (P = 0.01). However, this was accompanied by lower total volatile fatty acids (tVFA) production (P = 0.006) and higher hydrogen accumulation (P = 0.008). QPCR targeting the mcrA and rrs genes confirmed a lower abundance of total methanogens (P < 0.02) and total eubacteria (P = 0.02) in D+K+ kids at 4 wk old. Methanogenic activity, as assessed by mcrA expression by RT-qPCR, was also lower in these kids. However, activity did not always reflect methanogen abundance. At 11 and 28 wk old, prenatal and postnatal effects on in vitro fermentation and rumen microbiota disappeared. Nevertheless, lower milk replacer intake in the first 4 wk resulted in reduced BW in K+ kids, persisting until 28 wk of age. Additionally, differences assigned to postnatal treatment were found in papillae density, width, and length in different areas of the rumen, recorded at 28 wk old. prenatal and postnatal supplementation with CO MCFA reduced in vitro CH4 emissions until 4 wk old by depressing methanogen abundance and activity but at the expense of rumen fermentation and eubacterial abundance. Unfortunately, daily gain of K+ kids was suppressed. Some rumen papillae characteristics differed at 28 wk old due to postnatal treatment which ended at 11 wk old, indicating rumen papillary development can be affected by the early-life nutritional circumstances.


Model Testing of the Factors That Influence Performance of Function Focused Care and Function Among Assisted Living Residents.
The purpose of this study was to test a model of factors associated with participating in function focused care. Function focused care is a philosophy of care in which residents are encouraged to engage in functional and physical activities during care interactions. This was a secondary data analysis using data from the Dissemination and Implementation of Function Focused Care for Assisted Living Using the Evidence Integration Triangle (FFC-AL-EIT) study. Residents (n = 550) were recruited from 59 AL settings. The majority were female (n = 380, 69%) and White (n = 536, 97%). Model testing was done. Comorbidities, quality of interactions, environments, profit status, cognitive impairment, depression, and function were associated with function focused care and accounted for 17% of the variance. Next steps should include intervening on changeable factors (e.g., environments) and adding factors to better explain performance of function focused care such as motivation, resilience, and staff satisfaction.


Remembered parental bonding in adult twins: genetic and environmental influences.
One common assumption in psychology is the impact of parenting and parent-child relationships on the child's adjustment throughout the life span. Studies have indicated that there are genetic influences on memories of parenting, but how these influences are mediated has not typically been investigated. A sample of 150 pairs of monozygotic and 176 pairs of dizygotic Swedish twin women reported on personal characteristics and on remembered relationships with their mother and father using the Parental Bonding Instrument (PBI). Quantitative genetic analyses showed moderate genetic influences for remembered parental warmth, which also was partly explained by genetic influences for optimism, aggression, and humor. The other two PBI scales, authoritarianism and protectiveness, showed only shared and nonshared environmental influences. One interpretation of the findings is that heritable personal characteristics of children elicit parental warmth. However, other explanations such as personality characteristics influencing how experiences with parents are interpreted or circumstances in adult life that affect the recall of experiences could not be ruled out.


Specular microscopy in pars plana vitrectomy.
A prospective study of endothelial cell loss following pars plana vitrectomy and pars plana vitrectomy with lensectomy was performed in 21 eyes. Fifteen diabetic patients had either vitrectomy alone or vitrectomy with lensectomy. Six nondiabetic eyes were also included in this study. The average cell loss was between 2.3% and 3.9% in all cases. This difference was not statistically significant from the preoperative measurements of endothelial cell counts. These data suggest that pars plana vitrectomy does not result in significant endothelial cell loss, especially when eyes remain phakic or when the anterior capsule is maintained until the end of the case.


Changing trends in dental restorative treatment needs of naval recruits 1987-89--disease or diagnosis?
The restorative treatment needs of 9960 young men and women who entered the Naval Service at HMS Raleigh between January 1987 and April 1989 are summarised. A marked increase in the numbers of fillings required and a decrease in the proportion considered to be dentally fit occurred in May 1988 and has continued as a trend thereafter. Weighted non-orthogonal analysis of variances have been conducted to assess the significance of clinical and period variables upon the changes.


Polypeptides of feline leukaemia virus: identification of p15(E) and p12(E).
Antiserum to the p15(E) polypeptide of Rauscher murine leukaemia virus (R-MuLV) precipitated two proteins from purified virions of feline leukaemia virus (FeLV) with apparent mol. wt. of 18500 and 155000 on SDS-polyacrylamide gels. These proteins have been designated p15(E) and p12(E), in line with the nomenclature for MuLV proteins. Like the analogous protein of MuLV, FeLV p15(E) was found to be disulphide-linked to the virion glycoprotein, gp70. FeLV p15(E) was sensitive to digestion of intact virus particles with the proteolytic enzyme, bromelain, indicating that this protein is on the outer surface of the virion. An analysis of cat sera for precipitating activity for FeLV p12(E) showed this only in sera from cats which had recovered from FeLV infection and had virus-neutralizing activity.


Novel targets for anticoagulants lacking bleeding risk.
Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites. As a result currently used anticoagulants substantially raise the risk of bleeding and are associated with an increase in potentially life-threatening hemorrhage, partially offsetting the benefits of reduced thrombosis. Within the last decade, experimental and preclinical data have revealed the existence of coagulation mechanisms that principally differ in thrombosis and haemostasis. Some coagulation proteins including, XI and XII have a differential role in haemostasis and thrombosis. Targeting these proteins may provide an opportunity to prevent thromboembolic disease without causing bleeding. This review summarizes recent studies on selective targeting of coagulation proteins that may allow prevention and treatment of thrombosis without causing bleeding. These novel approaches present a possibility for selective interference with fibrin formation in pathologic thrombosis that may lead to a new generation of safe anticoagulant drugs.


Simultaneous Estimation of Tonic Dopamine and Serotonin with High Temporal Resolution In Vitro Using Deep Learning.
Quantitative measurement of the phasic (changes in several seconds) and tonic (changes in minutes to hours) level changes of neurotransmitters is an essential technique for understanding brain functions and brain diseases regulated by the neurotransmitters. However, monitoring phasic and tonic levels of multiple neurotransmitters is still a challenging technology. Microdialysis can measure the tonic levels of multiple neurotransmitters simultaneously but has a low temporal resolution (minute) to analyze precisely. Fast-scan cyclic voltammetry (FSCV) has high temporal resolution and high sensitivity, but it was not able to simultaneously measure the tonic level of multiple neurotransmitters. The recently proposed deep learning-based FSCV method was still only capable of phasic concentration estimation of neurotransmitters. In this study, we estimate the tonic levels of dopamine and serotonin simultaneously by training a deep-learning network with the extracted tonic information from the FSCV. The proposed deep learning model was validated in vitro to simultaneously estimate tonic concentrations of two neurotransmitters with statistically significantly higher accuracy than previously proposed background subtraction-based models (p<0.001). In particular, in the case of serotonin concentration estimation error, the proposed model showed higher prediction performance than the background subtraction-based model (48 nM and 73 nM, respectively). We expect that the proposed technique will help simultaneous measurement of the phasic and tonic levels of numerous neurotransmitters in vivo soon.Clinical Relevance- This study proposes a method to simultaneously measure tonic dopamine and tonic serotonin with high temporal resolution with a single electrode in the brain.


Expression of (pro)renin receptor in the human brain and pituitary, and co-localisation with arginine vasopressin and oxytocin in the hypothalamus.
(Pro)renin receptor [(P)RR], a specific receptor for renin and prorenin, is a 350 amino acid protein with a single transmembrane domain. In the present study, the expression of (P)RR in the human brain and pituitary, and its co-localisation with arginine vasopressin and oxytocin in the human hypothalamus were studied by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry. Human brain and pituitary tissues were obtained at autopsy from the subjects without neurological or endocrinological disorders. The antiserum against (P)RR was raised in a rabbit by injecting the peptide fragment of human (P)RR corresponding to 224-237 amino acids conjugated with bovine serum albumin. Quantitative RT-PCR showed that (P)RR mRNA was widely expressed in every region of brain examined and pituitary, with the highest expression levels found in the pituitary and frontal lobe. Immunocytochemistry showed that (P)RR was expressed in the paraventricular and supraoptic nuclei of human hypothalami, and in anterior pituitary cells. Immunostaining of serial sections showed that (P)RR was co-localised with arginine vasopressin and oxytocin in the magnocellular neurones of the paraventricular and supraoptic nuclei. The preabsorption of the antibody by the antigen peptide abolished the immunostaining of (P)RR in the human hypothalamus. The present study has shown that (P)RR mRNA is widely expressed in the human brain and pituitary, consistent with the hypothesis that (P)RR is related to the various brain functions, such as cognitive function and brain development. Co-localisation of (P)RR with vasopressin in the hypothalamus raised the possibility that (P)RR may be related to the central control of water-electrolyte metabolism and blood pressure.


Computerized bibliographic information service in a family practice clinic.
Access to current medical information is important for good-quality patient care. Computerized bibliographic information services (CBIS) have been evaluated in a family practice clinic as an aid to clinical decision making. Results suggest that CBIS is a relatively inexpensive, fast, easily accessible tool for clinicians, medical educators, and researchers.


Impact of minimally invasive surgery on the treatment of benign esophageal disorders.
Thanks to the development of minimally invasive surgery, the last 20 years have witnessed a change in the treatment algorithm of benign esophageal disorders. Today a laparoscopic operation is the treatment of choice for esophageal achalasia and for most patients with gastroesophageal reflux disease. Because the pathogenesis of achalasia is unknown, treatment is palliative and aims to improve esophageal emptying by decreasing the functional obstruction at the level of the gastro-esophageal junction. The refinement of minimally invasive techniques accompanied by large, multiple randomized control trials with long-term outcome has allowed the laparoscopic Heller myotomy and partial fundoplication to become the treatment of choice for achalasia compared to endoscopic procedures, including endoscopic botulinum toxin injection and pneumatic dilatation. Patients with suspected gastroesophageal reflux need to undergo a thorough preoperative workup. After establishing diagnosis, treatment for gastroesophageal reflux should be individualized to patient characteristics and a decision about an operation made jointly between surgeon and patient. The indications for surgery have changed in the last twenty years. In the past, surgery was often considered for patients who did not respond well to acid reducing medications. Today, the best candidate for surgery is the patient who has excellent control of symptoms with proton pump inhibitors. The minimally invasive approach to antireflux surgery has allowed surgeons to control reflux in a safe manner, with excellent long term outcomes. Like achalasia and gastroesophageal reflux, the treatment of patients with paraesophageal hernias has also seen a major evolution. The laparoscopic approach has been shown to be safe, and durable, with good relief of symptoms over the long-term. The most significant controversy with laparoscopic paraesophageal hernia repair is the optimal crural repair. This manuscript reviews the evolution of these techniques.


Prevalence of digestive tract colonization of carbapenem-resistant Acinetobacter baumannii in hospitals in Saudi Arabia.
Carbapenem-resistant Acinetobacter baumannii is a major health problem worldwide, especially in intensive care units (ICUs). This study aimed to detect the prevalence of A. baumannii colonization of the gastrointestinal tract of patients admitted to the ICU in two hospitals in Saudi Arabia. In addition, it aimed to characterize the molecular mechanisms of carbapenem resistance in these isolates. From January to June 2014, 565 rectal swab specimens were screened for Acinetobacer strains and carbapenem resistance using CHROMagar Acinetobacter and CHROMagar KPC agar plates, respectively. Organism identification and susceptibility were detected using the Vitek 2 system. A total of 47 Acinetobacter spp. were detected, and 35 were resistant to carbapenem, making the prevalence of Acinetobacter spp. 8.3% (47/565) and carbapenem resistance (6.2%, 35/565). The 47 strains showed remarkable clonal diversity as revealed by PFGE. Using PCR, OXA-51, a chromosomal marker for A. baumannii, was detected in 46 strains. OXA-23 β-lactamase was detected in all 35 carbapenem-resistant A. baumannii. No IMP, VIM, SPM, SIM, GIM, KPC or NDM β-lactamases were detected in these isolates. Thus, OXA-23 was the main mechanism of carbapenem resistance in these isolates. To the best of our knowledge, this is the first study to detect the prevalence of Acinetobacter colonization in the digestive tract of ICU patients in Saudi Arabia. This study revealed the importance of having well-established protocols for early identification of these multidrug-resistant organisms, optimizing infection-control strategies and having active surveillance studies to reduce morbidity, mortality and cost.


Men's Perspectives of a Gender-Sensitized Health Promotion Program Targeting Healthy Eating, Active Living, and Social Connectedness.
Men in high income countries have poorer dietary habits and higher rates of overweight and obesity than women. A major challenge with engaging men in health promotion is the perception that attention to one's health runs counter to masculine identities. Contemporary health promotion programs are believed to hold little "manly" appeal and often fail to engage and retain men. The HAT TRICK program was designed to engage men with their health by delivering an intervention in collaboration with a semi-professional ice hockey team. The program included 12 weekly sessions promoting healthy eating, active living, and social connectedness among men. Gender-sensitized elements were reflected in the program design, setting, content, and delivery. Semistructured telephone interviews were conducted with 23 men to explore perspectives of their participation in the gender-sensitized intervention. Participants were white (100%) with a mean age of 53 years ( SD ± 9.9), Body Mass Index (BMI) of 37 kg/m2 ( SD ± 6.8), and waist circumference of 127 centimeters ( SD ± 14.5). Inductive thematic analysis revealed three overarching themes, including: (a) Harnessing nostalgia for past masculinities: "Closet athletes from 30 years ago," (2) Offsetting resistance to change with sensible health advice: "Don't give up drinking beer, just have less," and (3) Gendered social spaces for doing health: "A night out with the guys," The findings support the value of gender-sensitized approaches to men's health promotion. Further research is needed to identify which gender-sensitized elements are critical to engaging men in healthy lifestyle changes.


School refusal in children and adolescents.
School refusal is a problem that is stressful for children, families, and school personnel. Failing to attend school has significant short- and long-term effects on children's social, emotional, and educational development. School refusal often is associated with comorbid psychiatric disorders such as anxiety and depression. It is important to identify problems early and provide appropriate interventions to prevent further difficulties. Assessment and management of school refusal require a collaborative approach that includes the family physician, school staff, parents, and a mental health professional. Because children often present with physical symptoms, evaluation by a physician is important to rule out any underlying medical problems. Treatments include educational-support therapy, cognitive behavior therapy, parent-teacher interventions, and pharmacotherapy. Family physicians may provide psychoeducational support for the child and parents, monitor medications, and help with referral to more intensive psychotherapy.


Medical decision making in the choice of a thrombolytic agent for acute myocardial infarction. Quebec Acute Coronary Care Working Group.
Little is known about how physicians make decisions when the evidence is incomplete or controversial. While thrombolysis improves survival following acute myocardial infarction (AMI), conflicting evidence exists as to any specific agent's superiority, particularly if cost-effectiveness is considered. Using a Bayesian hierarchical model, the authors examined the patient, physician, and hospital characteristics that are related to the decision-making process concerning the choice of thrombolytic agent in a prospective registry of 1,165 AMI patients receiving thrombolysis. Tissue plasminogen activator (t-PA) was administered to 432 patients (31.8%) and streptokinase (SK) to the remainder. The presence of an anterior infarction, a previous myocardial infarction, low blood pressure, a cardiologist decision maker, younger age, and receiving treatment within six hours after the start of symptoms were independent predictors of receiving t-PA. The levels of importance that physicians accorded to these patient characteristics differed according to their practicing institutions. Generally, they followed evidence-based medicine and reasonably targeted high-risk patients to receive the more expensive t-PA. However, they also preferentially treated younger patients, where only a small absolute advantage appears to exist.


Association of hypermobility and ingrown nails.
Ingrown nail (onychocryptosis) is a common condition with severe pain and various associated morbidities. Although some underlying factors are identified, its etiology remains largely unknown. Generalized joint hypermobility (GJH) is a common entity with clinical features that might prone affected individuals to ingrown nails. Herein, we investigated the incidence of GJH in patients with ingrown nails to determine possible association between hypermobility and ingrown nail formation. Patients 16-50 years of age who were undergoing treatment for ingrown nails at the dermatology clinic were consecutively enrolled into the study. Patients with known rheumatic diseases or orthopedic foot disorders were excluded. All patients were in a pain-free period at the time of examination. The control group was comprised of age- and sex-matched healthy subjects without a history of ingrown nail. Assessment of GJH was made according to Beighton criteria. Local hypermobility was evaluated by measurement of range of motion using a goniometer. Thirty-nine patients (male/female, 17/22, mean age 31.9 ± 11.3 years) and 32 healthy subjects (male/female 12/20, mean age 31.7 ± 10.4 years) were included. Patients with ingrown toe nails were more likely to have GJH compared to healthy subjects (35.9 vs. 9.4 %, p = 0.009). Toes with ingrown nails had significantly smaller maximum dorsiflexion angles (p < 0.001) compared to toes of healthy subjects. Ingrown nail formation may be associated with GJH. However, when examined locally, there is a limited range of motion in the affected toe rather than hypermobility, which could be due to the degenerative process facilitated by the hypermobility.


The early course of depression: a longitudinal investigation of prodromal symptoms and their relation to the symptomatic course of depressive episodes.
The present study explored longitudinal evidence for prodromal symptoms of depression episodes. A model based on previous findings of the relations between prodromal and residual symptoms was described and used to generate hypotheses tested in this study. Data were analyzed from 160 participants from the Cognitive Vulnerability to Depression (CVD) project (L. Alloy & L. Abramson, 1999) who experienced an episode of depression during the prospective follow-up period and 60 CVD participants who did not. Congruent with the hypothesis, individuals who subsequently developed an episode of depression experienced significantly greater numbers of depression symptoms in the period of time leading up to the acute episode compared with those who did not develop a depressive episode. Seven depression symptoms were particularly likely to appear before the onset of an acute episode. Furthermore, all 3 predictions from the model were supported: the durations of prodromal and residual phases were correlated, the prodromal and residual symptom profiles were quite similar, and the order of symptom onset was significantly and highly negatively correlated with the order of symptom remission. Additionally, residual symptom profiles were similar to subsequent prodromal symptom profiles in individuals who experienced more than 1 depressive episode. These findings are discussed in terms of the importance of understanding the earliest prodromal symptoms to appear and their relation to the symptomatic course of depression episodes. Implications for early intervention are also discussed.


[Long-term follow up of asymptomatic chagasic individuals with intraventricular conduction disturbances, correlating with non-chagasic patients].
This prospective study was designed to evaluate intraventricular conduction disturbances in asymptomatic patients with Chagas' disease, and patients with primary sclerosis of the conducting system of the heart (Lev-Lenègre's disease). Eighty-four asymptomatic individuals with right- or left-bundle branch block were submitted to electrophysiological evaluation and long-term follow-up. Fifty-five had positive serologic blood tests for Chagas' disease and 29 had Lev-Lenègre's disease. Mean-age of 45 years in chagasic and 63 in non-chagasic patients (p< 0.001). There were 54 (98.2%) with right-bundle branch block in chagasic and 14 (48.3%) among non-chagasic patients (p <0.001). Sinus nodal and atrioventricular nodal functions presented no differences in either group. However, mean HV interval was greater in the NCH than in the CH group (p< 0.01). After a mean follow-up of 121 +/- 63.75 months among chagasic and 94.97 +/- 67.55 months among non-chagasic patients, total mortality was 20 (36.6%) patients in chagasic and 9 (31%) among non-chagasic patients (NS). Cardiac death was recorded in 17 (85%) individuals among chagasic and 3 (33.3%) among non-chagasic patients(p <0.05). Sudden death occurred in 10 (50%) among chagasic and was not observed in non-chagasic patients (p <0. 01). 1. Asymptomatic chagasic individuals with intraventricular conduction disturbances showed higher cardiac mortality, sudden or non-sudden death in relation to non-chagasic individuals. 2. The evaluated electrophysiological parameters were of no prognostic value in relation to mortality, although programmed ventricular stimulation was not performed.


Differential regulation of glycosylated phosphatidylinositol subtypes by insulin.
Glycosylated phosphatidylinositol (gly-Pl) molecules have been implicated as precursors for insulin-sensitive second messengers (1-4) and lipid-anchored membrane proteins (5-9). The relationship between the diverse functions of these lipids and their predicted structural heterogeneity within gly-Pl subtypes was examined in human T lymphocytes. Four subtypes of gly-Pl molecules were identified in T lymphocytes after separation over high-performance thin-layer chromatography by sensitivity to Pl-specific phospholipase C and nitrous acid. Antibody probes of the glycan domain of gly-Pl were developed and used to assess the partial sensitivity of gly-Pl to insulin action. This analysis showed that the effects of insulin are linked to differential utilization of only two of the four gly-Pl subtypes in T lymphocytes. Polar fragments of this reaction were identified in extracellular supernatants from insulin-treated cells. The biological significance of insulin-dependent gly-Pl hydrolysis was demonstrated by insulin and inositol phosphoglycan regulation of glucose metabolism in intact lymphocytes. These results support the hypothesis that multifunctional roles of gly-Pl are served by discrete gly-Pl populations and that metabolites of gly-Pl subsets participate as signaling elements in insulin action.


[Diagnostic and treatment characteristics of ectopic atrial tachycardia].
Reported here are 162 cases of atrial ectopic tachycardia, a specific type of the supraventricular arrhythmia, which is characterized by the distinct P waves on the ECG, which follow at the rate of 400 and more per minute. Although atrial ectopic tachycardia is similar to the supraventricular paroxysmal tachycardia and atrial flutter, it differs from them by the mechanism of the development. Atrial ectopic tachycardia is caused by the failure or weakening the sinus node and the appearance of the ectopic focus in the atria. Such arrhythmia occurs in the following 4 types: with atrial to ventricular excitation ratio 1:1; with incomplete atrio-ventricular block; with complete atrioventricular block; and in combination with atrial fibrillation. Atrial ectopic tachycardia often takes lingering course and is hardly responsive to the medical treatment. The cases of arrhythmia, characterized by the broad P waves on the ECG tend to the progressive course. 17 cases of atrial ectopic tachycardia treated by electrostimulation (ES) which had 100% positive effect are presented and ES advantages over the drug therapy are underlined. The frequent transition of this arrhythmia into the atrial fibrillation is outlined.


The Effects of Propofol on Left Ventricular Global Longitudinal Strain.
To determine if hemodynamic changes secondary to propofol administration are a result of direct myocardial depression as measured by global longitudinal strain (GLS). The authors hypothesized that propofol would cause a significant worsening in GLS, indicating direct myocardial depression. Prospective, observational. Endoscopy suite at a single academic medical center. Patients undergoing outpatient, elective endoscopic procedures at an outpatient clinic of a single tertiary care academic medical center. None. Limited transthoracic echocardiograms were performed before and after patients received propofol for endoscopic procedures. Post-processing measurements included GLS, 2D (dimensional) ejection fraction (2D EF), and 3D EF. Using paired sample Student's t test, no statistically significant change in GLS, 2D EF, or 3D EF was found despite statistically significant hypotension. In fact, there was a trend toward more negative GLS (improved myocardial function) in patients after receiving propofol. We found propofol did not cause a reduction in systolic function as measured by GLS, a sensitive measure of myocardial contractility. Therefore, decreases in blood pressure after a propofol bolus in spontaneously breathing patients are likely due to decreased vascular tone and not impaired left ventricular systolic function. These results should be considered in the management of propofol-induced hypotension for spontaneously breathing patients.


Targeted physiotherapy for patellofemoral joint osteoarthritis: a protocol for a randomised, single-blind controlled trial.
The patellofemoral joint (PFJ) is one compartment of the knee that is frequently affected by osteoarthritis (OA) and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA. 90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA) will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week) compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks). Physiotherapy treatment will consist of (i) quadriceps muscle retraining; (ii) quadriceps and hip muscle strengthening; (iii) patellar taping; (iv) manual PFJ and soft tissue mobilisation; and (v) OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction. This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the potential to reduce the personal and societal burden of this increasing public health problem. Australia New Zealand Clinical Trials Registry ACTRN12608000288325.


The effects of the Pathways Obesity Prevention Program on physical activity in American Indian children.
Inadequate opportunities for physical activity at school and overall low levels of activity contribute to the high prevalence of overweight and obesity in American-Indian children. A school-based physical activity intervention was implemented which emphasized increasing the frequency and quality of physical education (PE) classes and activity breaks. Changes in physical activity were assessed using the TriTrac-R3D accelerometer in a subsample of 580 of the students (34%) randomly selected from the Pathways study cohort. Baseline measures were completed with children in second grade. Follow-up measurements were obtained in the spring of the fifth grade. Intervention schools were more active (+6.3 to +27.2%) than control schools at three of the four sites, although the overall difference between intervention and control schools (approximately 10%) was not significant (P>0.05). Boys were more active than girls by 17 to 21% (P < or =.01) at both baseline and follow-up. Despite the trend for greater physical activity at three of four study sites, and an overall difference of approximately 10% between intervention and control schools, high variability in accelerometer AVM and the opportunity to measure physical activity on only 1 day resulted in a the failure to detect the difference as significant.


Inferior vestibular neuritis in a fighter pilot: a case report.
Spatial disorientation in airplane pilots is a leading factor in many fatal flying accidents. Spatial orientation is the product of integrative inputs from the proprioceptive, vestibular, and visual systems. One condition that can lead to sudden pilot incapacitation in flight is vestibular neuritis. Vestibular neuritis is commonly diagnosed by a finding of unilateral vestibular failure, such as a loss of caloric response. However, because caloric response testing reflects the function of only the superior part of the vestibular nerve, it cannot detect cases of neuritis in only the inferior part of the nerve. We describe the case of a Chinese naval command fighter pilot who exhibited symptoms suggestive of vestibular neuritis but whose caloric response test results were normal. Further testing showed a unilateral loss of vestibular evoked myogenic potentials (VEMPs). We believe that this pilot had pure inferior nerve vestibular neuritis. VEMP testing plays a major role in the diagnosis of inferior nerve vestibular neuritis in pilots. We also discuss this issue in terms of aeromedical concerns.


Late effects of poliomyelitis. Part I: Report of five cases.
We present five case reports to illustrate the late effects of acute paralytic poliomyelitis occurring many years after recovery. We emphasize the importance of ruling out common medical causes for the symptoms and address the question of a "postpolio syndrome." The cause of progressive muscle weakness 30 to 40 years after recovery from poliomyelitis remains unknown.


Lifestyle after Colorectal Cancer Diagnosis in Relation to Survival and Recurrence: A Review of the Literature.
This review summarizes the evidence regarding diet, physical activity, smoking, and body composition after colorectal cancer (CRC) diagnosis in relation to all-cause and CRC-specific mortality and disease recurrence and gives suggestions for future research directions. Overall, this review suggests that some, albeit not all, of the well-known modifiable risk factors for cancer incidence might also be associated with CRC survival. CRC prognosis appears to be worse with increased physical inactivity, smoking, or being underweight after CRC diagnosis. Emerging evidence suggests that diets associated with a positive energy balance, e.g., high consumption of sugar-sweetened beverages, may negatively impact survival in CRC survivors. In contrast, there is currently little evidence to support the recommendation to limit red and processed meat or alcohol intake after CRC diagnosis. Whether being overweight and obese after CRC diagnosis improves or worsens CRC prognosis remains controversial and may depend on the measure used to assess body fatness. Further research on post-diagnosis lifestyle patterns is needed to understand the multifactorial influence on CRC prognosis. Disease recurrence and the development of comorbidities should be included as key outcomes in future studies and lifestyle should preferably be repeatedly measured.


The impact of regionalization on a surgery program in the Canadian health care system.
To examine the impact of the regionalization of health care on the provision of surgical services in the Capital Health Region (Edmonton) of the province of Alberta. A 4-year retrospective descriptive analysis using data from the Canadian Institute for Health Information and from the Capital Health Region data banks. To control health care costs, the provincially funded health care system in Alberta reformed its governance structure and service provision model. We studied community hospitals and an academic health sciences center. All patients undergoing surgical care in the region. Regionalization of the organizational structure with the elimination of hospital boards, consolidation of services on specific sites within the regional system, and a major reduction in funding. Inpatient and day surgery procedure volumes, average length of hospital stay, relative value units, bed use, and mortality. The Capital Health Region has a population of 723,000 people, with 5 acute care institutions. Eighteen clinical programs now provide care through 2 referral hospitals and 3 community health centers. The reduction in operating dollars for this region was $167.1 million from fiscal years 1992-1993 to 1996-1997. Redistribution of surgical services occurred on July 1, 1995, resulting in an 18% inpatient bed reduction. Regionally, the number of acute care beds has declined from 2.25 to 1.47 per 1000 population (P < .001). Bed use has fallen from 637 to 442 inpatient days per 1000 population (P < .001). The surgery volume (1995-1996) was 44770 procedures (-3.1%). Redistribution of surgical services into high- and low-acuity settings has resulted in most surgeons working on 2 sites. Overall average length of hospital stay has decreased significantly (P < .001); however, it has increased, together with the average relative value units, in the institutions caring for patients with high-acuity surgical illnesses. Mortality remains unchanged. Regionalization and funding reductions within the surgical program in the Capital Health Region have resulted in a small reduction in surgical volumes. There have been major changes in service provision and the way surgeons practice.


Ideal amino acid profile and dietary lysine specification for broiler chickens of 20 to 40 days of age.
1. The aim of the study was to determine the ideal ratio of the essential amino acids lysine (Lys), methionine (Met), threonine (Thr), tryptophan (Trp), arginine (Arg), valine (Val) and isoleucine (Ile) and to assess the required dietary lysine concentration for optimum performance in broiler chickens of 2 commercial strains from 20 to 40 d of age. 2. An identical basal diet was used throughout all experiments. It consisted mainly of maize and soyabean meal and contained 172 g crude protein and 13.2 MJ AME(N) per kg. For each experiment, the basal diet was adequately supplemented with all essential amino acids except the one to be tested, which was supplemented in 6 graded concentrations in exchange for maize starch. One (Met, Trp, Arg, Val, Ile) or 2 (Lys, Thr) growth trials were conducted per amino acid tested and the response in weight gain, food: gain ratio, breast meat yield and abdominal fat were examined. 3. The ideal amino acid ratio relative to Lys (expressed as a percentage) was calculated to be 75% Met+Cys, 63% Thr, 19% Trp, 112% Arg, 71% Ile and 81% Val on a true faecal digestible basis when the data were subjected to broken-line regression analysis. From both lysine studies the concentration for optimum food: gain ratio was calculated, by exponential regression analysis, to be 11.5 g true faecal digestible lys per kg diet.


Duodenal GI stromal tumors: Is radical resection necessary?
Duodenal gastrointestinal stromal tumors (GISTs) are rare tumors that pose a surgical challenge, and long-term outcomes after resection have not been detailed outside of small case series. This study uses the National Cancer Database (NCDB) to examine the determinants of radical resection for duodenal GISTs as well as the impact of local vs radical resection on overall survival (OS). The NCDB was queried for nonmetastatic duodenal GISTs from 2004 to 2014. Predictors of radical resection were determined using multivariate logistic regression stratified by extent of tumor involvement. Factors associated with OS were identified with Cox proportional regression analysis. Treatment at an academic center, size >5 cm, and extra-duodenal extension were associated with radical resection. On multivariate analysis, radical resection was associated with decreased OS (HR, 1.93; P < .03). Systemic therapy, extra-duodenal extension, grade, stage, mitoses, and receipt of systemic therapy did not impact OS. Local resection of duodenal GISTs is associated with improved OS compared to radical resection after controlling for tumor factors and systemic treatment. Traditional indicators of tumor aggressiveness were associated with radical resection, but not OS. When feasible, local resection should be considered for resection of duodenal GISTs.


Brain imaging and the effects of caffeine and nicotine.
Caffeine and nicotine are the most common psychostimulant drugs used worldwide. Structural neuroimaging findings associated with caffeine and nicotine consumption are limited and primarily reflect the putative relationship between smoking and white matter hyperintensities (WMH), a finding that warrants further appraisal of its clinical implications. The application of newer brain imaging modalities that measure subtle haemodynamic changes or tissue-based chemistry in order to better elucidate brain functional processes, including mechanisms underlying addiction to nicotine and caffeine and the brain functional consequences, provide intriguing findings. Potential influences of caffeine and nicotine on the functional contrast, or metabolic response, to neural activation also necessitates the careful appraisal of the effects that these commonly used drugs may have on the results of functional imaging.


Common Entrapment Neuropathies.
This article addresses relevant peripheral neuroanatomy, clinical presentations, and diagnostic findings in common entrapment neuropathies involving the median, ulnar, radial, and fibular (peroneal) nerves. Entrapment neuropathies are a common issue in general neurology practice. Early diagnosis and effective management of entrapment mononeuropathies are essential in preserving limb function and maintaining patient quality of life. Median neuropathy at the wrist (carpal tunnel syndrome), ulnar neuropathy at the elbow, radial neuropathy at the spiral groove, and fibular neuropathy at the fibular head are among the most frequently encountered entrapment mononeuropathies. Electrodiagnostic studies and peripheral nerve ultrasound are employed to help confirm the clinical diagnosis of nerve compression or entrapment and to provide precise localization for nerve injury. Peripheral nerve ultrasound demonstrates nerve enlargement at or near sites of compression. Entrapment neuropathies are commonly encountered in clinical practice. Accurate diagnosis and effective management require knowledge of peripheral neuroanatomy and recognition of key clinical symptoms and findings. Clinical diagnoses may be confirmed by diagnostic testing with electrodiagnostic studies and peripheral nerve ultrasound.


Mechanisms controlling feed intake in ruminants: a review.
The purpose of this paper is to review our understanding of the involvement of central and peripheral factors in the control of feed intake in ruminants. The regulation of body weight under various states of energy need depends on an animal's ability to control feed intake to meet these needs. In the central nervous system (CNS), the ventromedial and lateral hypothalamus appear to be the areas involved in satiety and hunger, respectively; other important areas are the paraventricular nucleus and rostral brain areas. Intracerebroventricular injection of neurotransmitters, alpha- and beta-adrenergic agonists, 5-hydroxytryptamine and gamma aminobutyric acid (GABA) agonists, has stimulated feeding in ruminants; intravenous administration of benzodiazepines stimulated feed intake in sheep and cattle, possibly by increasing GABA levels in the brain. Neuropeptides of the opioid and cholecystokinin families have reciprocal hunger-stimulating and satiety-eliciting effects when administered centrally in sheep. Further, concentrations of these neuropeptides in specific areas of the hypothalamus have been shown to change with the state of hunger-satiety of sheep. In the periphery, none of the hormones associated with the pituitary, adrenal gland, pancreas or gastrointestinal tract has been shown to have significant effects on the control of feed intake. In addition, the physical properties of the ingested feed in the gastrointestinal tract, while possibly influencing the rate or pattern of feeding, do not appear to be primary factors in the control of feed intake under many feeding conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Nucleotide sequence of EV1, a British isolate of maedi-visna virus.
We have isolated a maedi-visna-like virus from the peripheral blood mononuclear cells of a British sheep displaying symptoms of arthritis and pneumonia. After brief passage in fibroblasts this virus (designated EV1) was used to infect choroid plexus cells. cDNA clones of the virus were prepared from these cells and sequenced. Gaps between non-overlapping clones were filled using gene amplification by the polymerase chain reaction. The genome structure is similar to that described for visna virus strain 1514, and differs from that described for visna virus strain SA-OMVV in not having a W reading frame. Overall the genome differs by about 20% between each of these strains, but there is fivefold variation in the amount of divergence of derived amino acid sequences of different open reading frames. Two sequenced EV1 clones each contain only one copy of the 43 bp repeat, with paired AP-1 sites, which is a feature of other ruminant lentiviral long terminal repeats (LTRs). However, analysis of viral DNA in infected cells by gene amplification shows that LTRs with two repeats do occur, albeit at a relatively low frequency.