Effects of polydextrose on different levels of energy intake. A systematic review and meta-analysis.
Dietary fibers help to control energy intake and reduce the risk of developing obesity. Recent studies show that the consumption of polydextrose reduces energy intake at a subsequent meal. In this systematic review and meta-analysis we examine the subsequent effects of polydextrose on different levels of energy intake (EI). The review followed the PRISMA methodology. Meta-analyses were expressed as Standardized Mean Difference (SMD). A linear regression approach was used to model the relationship between the polydextrose dose and the different levels of EI expressed as a relative change (%). All the studies included in this review administered polydextrose as part of a mid-morning snack. Six studies were included in the analysis of EI at an ad libitum lunch; and three were included in the analysis of EI during the rest of the day, as well as total daily EI. The meta-analysis showed that the consumption of polydextrose is associated with a reduction in EI at lunch time (SMD = 0.35; P <0.01; I(2) = 0). The dose of polydextrose consumed correlated significantly with this reduction in EI, EILunch (%) = -0.67 Polydextrose (g/day) (R(2) = 0.80; P <0.01). The meta-analysis of EI during the rest of the day and daily EI did not show any difference. Nevertheless, the regression equation indicates that there is a dose-dependent effect on the reduction of daily EI, EIDaily (%) = -0.35 × Polydextrose (g/day) (R(2) = 0.68; P <0.05). Sex-specific results are consistent with results for the whole group. The studies included in this meta-analysis support the notion that the consumption of polydextrose reduces voluntary energy intake at a subsequent meal. Furthermore, this reduction in energy intake occurs in a dose-dependent manner.


Beating the Stoner criterion using molecular interfaces.
Only three elements are ferromagnetic at room temperature: the transition metals iron, cobalt and nickel. The Stoner criterion explains why iron is ferromagnetic but manganese, for example, is not, even though both elements have an unfilled 3d shell and are adjacent in the periodic table: according to this criterion, the product of the density of states and the exchange integral must be greater than unity for spontaneous spin ordering to emerge. Here we demonstrate that it is possible to alter the electronic states of non-ferromagnetic materials, such as diamagnetic copper and paramagnetic manganese, to overcome the Stoner criterion and make them ferromagnetic at room temperature. This effect is achieved via interfaces between metallic thin films and C60 molecular layers. The emergent ferromagnetic state exists over several layers of the metal before being quenched at large sample thicknesses by the material's bulk properties. Although the induced magnetization is easily measurable by magnetometry, low-energy muon spin spectroscopy provides insight into its distribution by studying the depolarization process of low-energy muons implanted in the sample. This technique indicates localized spin-ordered states at, and close to, the metal-molecule interface. Density functional theory simulations suggest a mechanism based on magnetic hardening of the metal atoms, owing to electron transfer. This mechanism might allow for the exploitation of molecular coupling to design magnetic metamaterials using abundant, non-toxic components such as organic semiconductors. Charge transfer at molecular interfaces may thus be used to control spin polarization or magnetization, with consequences for the design of devices for electronic, power or computing applications (see, for example, refs 6 and 7).


A pharmacological primer of biased agonism.
Biased agonism is one of the fastest growing topics in G protein-coupled receptor pharmacology; moreover, biased agonists are used in the clinic today: carvedilol (Coreg®) is a biased agonist of beta-adrenergic receptors. However, there is a general lack of understanding of biased agonism when compared to traditional pharmacological terminology. Therefore, this review is designed to provide a basic introduction to classical pharmacology as well as G protein-coupled receptor signal transduction in order to clearly explain biased agonism for the non-scientist clinician and pharmacist. Special emphasis is placed on biased agonists of the beta-adrenergic receptors, as these drugs are highly prescribed, and a hypothetical scenario based on current clinical practices and proposed mechanisms for treating disease is discussed in order to demonstrate the need for a more thorough understanding of biased agonism in clinical settings. Since biased agonism provides a novel mechanism for treating disease, greater emphasis is being placed to develop biased agonists; therefore, it is important for biased agonism to be understood in equal measure of traditional pharmacological concepts. This review, along with many others, can be used to teach the basic concepts of biased agonism, and this review also serves to introduce the subsequent reviews that examine, in more depth, the relevance of biased agonism towards the angiotensin type 1 receptor, parathyroid hormone receptor, and natural biased ligands towards chemokine receptors.


Anticipatory brain activity predicts the success or failure of subsequent emotion regulation.
Expectations about an upcoming emotional event have the power to shape one's subsequent affective response for better or worse. Here, we used mediation analyses to examine the relationship between brain activity when anticipating the need to cognitively reappraise aversive images, amygdala responses to those images and subsequent success in diminishing negative affect. We found that anticipatory activity in right rostrolateral prefrontal cortex was associated with greater subsequent left amygdala responses to aversive images and decreased regulation success. In contrast, anticipatory ventral anterior insula activity was associated with reduced amygdala responses and greater reappraisal success. In both cases, left amygdala responses mediated the relationship between anticipatory activity and reappraisal success. These results suggest that anticipation facilitates successful reappraisal via reduced anticipatory prefrontal 'cognitive' elaboration and better integration of affective information in paralimbic and subcortical systems.


Nuclear stability and transcriptional directionality separate functionally distinct RNA species.
Mammalian genomes are pervasively transcribed, yielding a complex transcriptome with high variability in composition and cellular abundance. Although recent efforts have identified thousands of new long non-coding (lnc) RNAs and demonstrated a complex transcriptional repertoire produced by protein-coding (pc) genes, limited progress has been made in distinguishing functional RNA from spurious transcription events. This is partly due to present RNA classification, which is typically based on technical rather than biochemical criteria. Here we devise a strategy to systematically categorize human RNAs by their sensitivity to the ribonucleolytic RNA exosome complex and by the nature of their transcription initiation. These measures are surprisingly effective at correctly classifying annotated transcripts, including lncRNAs of known function. The approach also identifies uncharacterized stable lncRNAs, hidden among a vast majority of unstable transcripts. The predictive power of the approach promises to streamline the functional analysis of known and novel RNAs.


Evaluation of a capacity building intervention on malaria treatment for under-fives in rural health facilities in Niger State, Nigeria.
Despite the uptake of parasitological testing into policy and practice, appropriate prescription of anti-malarials and artemisinin-based combination therapy (ACT) in accordance with test results is variable. This study describes a National Malaria Control Programme-led capacity building intervention which was implemented in 10 States of Nigeria. Using the experience of Niger State, this study assessed the effect on malaria diagnosis and prescription practices among febrile under-fives in rural health facilities. The multicomponent capacity building intervention consisted of revised case management manuals; cascade training from national to state level carried out at the local government area (LGA) level; and on the job capacity development through supportive supervision. The evaluation was conducted in 28, principally government-owned, health facilities in two rural LGAs of Niger State, one in which the intervention case management of malaria was implemented and the other acted as a comparison area with no implementation of the intervention. Three outcomes were considered in the context of rapid diagnostic testing (RDT) for malaria which were: the prevalence of RDT testing in febrile children; appropriate treatment of RDT-positive children; and appropriate treatment of RDT-negative children. Outcomes were compared post-intervention between intervention and comparison areas using multivariate logistic regression. The intervention did not improve appropriate management of under-fives in intervention facilities above that seen for under-fives in comparison facilities. Appropriate treatment with artemisinin-based combinations of RDT-positive and RDT-negative under-fives was equally high in both areas. However, appropriate treatment of RDT-negative children, when defined as receipt of no ACT or any other anti-malarials, was better in comparison areas. In both areas, a small number of RDT-positives were not given ACT, but prescribed an alternative anti-malarial, including artesunate monotherapy. Among RDT-negatives, no under-fives were prescribed artesunate as monotherapy. In a context of significant stock-outs of both ACT medicines and RDTs, under-fives were not more appropriately managed in intervention than comparison areas. The malaria case management intervention implemented through cascade training reached only approximately half of health workers managing febrile under-fives in this setting. Implementation studies on models of cascade training are needed to define what works in what context.


Is it ethical to invite compatible pairs to participate in exchange programmes?
Living kidney transplantation offers the best results for patients with end-stage renal disease (ESRD). This form of transplantation is no longer restricted to genetically or emotionally related donors, as shown by the acceptance of non-directed living anonymous donors, and the development of exchange programmes (EPs). EPs make it possible to perform living kidney transplantation among incompatible pairs, but while such programmes can help increase living organ donation, they can also create a degree of unfairness. Kidney transplant recipients in the O blood group are at a disadvantage when it comes to EPs because they can only receive organs from O donors, whereas O donors are universal donors. This poses a major challenge in terms of distributive justice and equity. A way to remedy this situation is through altruistic unbalanced paired kidney exchange (AUPKE), in which a compatible pair consisting of an O blood group donor and a non-O recipient is invited to participate in an EP. Although the AUPKE approach appears fairer for O recipients, it still raises ethical questions. How does this type of exchange affect the donor/recipient gift relationship? Should recipients in compatible pairs receive a 'better organ' than the one they would otherwise have received from their intended donor? Finally, what is the role of transplant teams in AUPKE? This article will examine the organisational and ethical challenges associated with EPs and AUPKE, and compare different EP policies in countries where such programmes exist.


Visual versus automatic ultrasound scoring of lung B-lines: reliability and consistency between systems.
To evaluate the agreement between a visual and an automatic counting system of lung B-lines by ultrasound (US) as well as to test the inter- and intra-observer reliability of both systems in patients with lung diseases. We included four patients with different lung conditions. Four ultrasonographers expert in lung US blindly, independently and consecutively performed, in two rounds, a US B-mode assessment of 8 lung intercostal spaces of each patient. Each US assessment consisted of a visual and an automatic counting of B-lines. Agreement between visual and automatic counting of B-lines was good to excellent [intraclass correlation coefficient (ICC) 0.79-0.84, p<0.001]. Intra-observer reliability was good to excellent [ICC 0.62-0.99, p<0.001] except for one investigator in whom it was close to moderate for the automatic system [ICC 0.49, p<0.05]. Inter-observer reliability was excellent for both systems in both rounds [ICC 0.86-0.90, p<0.001]. US automatic counting was consistent with US visual counting of lung B-lines, as performed by experts in the field. Both systems showed a high intra- and interobserver reliability.


The "Guidewire-Coil"-Technique to prevent retrograde stone migration of ureteric calculi during intracorporeal lithothripsy.
Stone retropulsion represents a challenge for intracorporeal lithotripsy of ureteral calculi. The consequences are an increased duration and cost of surgery as well as decreased stone-free rates. The use of additional tools to prevent proximal stone migration entails further costs and risks for ureteral injuries. We present the simple technique of using a coil of the routinely used guidewire to prevent stone retropulsion. We retrospectively evaluated all patients with mid-to-proximal ureteral stones in 2014, which were treated by ureteroscopic lithotripsy (Ho: YAG and/or pneumatic lithotripsy). The preoperative stone burden was routinely assessed using low dose CT scan (if available) and/or intravenous pyelogram. The study population consisted of 55 patients with 61 mid-to-proximal calculi. Twentyseven patients underwent semirigid ureterorenoscopy using the "Guidewire-Coil-Technique", the second group (n = 28) served as control group using the guidewire as usual. There has been a statistically significant reduction of accidental stone retropulsion (2/27 vs. 8/28, p < 0.05) as well as a decreased use of auxiliary procedures (p < 0.05) compared to the control group. No difference was observed in operative time. One ureteral injury in the control group required a prolonged ureteral stenting. The "Guidewire-Coil-Technique" is a simple and safe procedure that may help to prevent proximal calculus migration and therefore may increase stone-free rates without causing additional costs.


The epigenome as a therapeutic target in prostate cancer.
During cancer development and progression, tumor cells undergo abnormal epigenetic modifications, including DNA methylation, histone deacetylation and nucleosome remodeling. Collectively, these aberrations promote genomic instability and lead to silencing of tumor-suppressor genes and reactivation of oncogenic retroviruses. Epigenetic modifications, therefore, provide exciting new avenues for prostate cancer research. Promoter hypermethylation is widespread during neoplastic transformation of prostate cells, which suggests that restoration of a 'normal' epigenome through treatment with inhibitors of the enzymes involved could be clinically beneficial. Global patterns of histone modifications are also being defined and have been associated with clinical and pathologic predictors of prostate cancer outcome. Although treatment for localized prostate cancer can be curative, the development of successful therapies for the management of castration-resistant metastatic disease is urgently needed. Reactivation of tumor-suppressor genes by demethylating agents and histone deacetylase inhibitors could be a potential treatment option for patients with advanced disease.


Potential of Lactobacillus plantarum ZDY2013 and Bifidobacterium bifidum WBIN03 in relieving colitis by gut microbiota, immune, and anti-oxidative stress.
Ulcerative colitis (UC) is an inflammatory bowel disease that is difficult to cure, with rising incidence in recent decades. Probiotics have become a new strategy for UC treatment. In this study, we chose 2 new multisource probiotics, Lactobacillus plantarum ZDY2013 from acid beans and Bifidobacterium bifidum WBIN03 from infant feces, and a mixture of both, to investigate the anti-inflammatory and antioxidant effect on H2O2-induced oxidative damage in a HT-29 cell model and dextran sodium sulfate (DSS)-induced UC in mice. Compared with the model group, the general relative indices results showed L. plantarum ZDY2013 and B. bifidum WBIN03 have a significant effect on DSS-induced UC in mice, by downregulating the pro-inflammatory cytokines (e.g., TNF-α) and upregulating antioxidant factors (e.g., SOD1, SOD2, GPX2) at the transcriptional level. By means of high-throughput sequencing (16S V3-V4) and systematical bioinformatics analyses, we found that colitis may be associated with the changes in intestinal flora, especially Firmicutes and Bacteroides. Administration of L. plantarum ZDY2013 increased the abundance of Lactobacillus animalis, whereas B. bifidum WBIN03 increased the abundance of Lachnospiraceae bacterium COE1. Our results revealed that a supplement of L. plantarum ZDY2013 and B. bifidum WBIN03 remit UC through modification of gut microbiota to regulate oxidative stress and inflammatory mediators.


Critical roles of RNA-binding proteins in miRNA biogenesis in Arabidopsis.
MicroRNAs (miRNAs) are key regulators of gene expression and play critical roles in modulating metabolism, development and physiology in animals and plants. miRNA levels are transcriptionally and post-transcriptionally controlled for their proper function. Recent studies have shown that RNA-binding proteins play important roles in producing miRNAs by affecting the accurate and/or efficient processing of precursors of miRNAs. Many of these RNA-binding proteins also have roles in general RNA metabolism, indicating potential connections between miRNA biogenesis and other RNA metabolism. Here, we focus on the function of several RNA-binding proteins in miRNA biogenesis in Arabidopsis.


Obligatory urea production and the cost of living in the Magadi tilapia revealed by acclimation to reduced salinity and alkalinity.
Alcolapia grahami is a unique ureotelic tilapia that lives in the highly alkaline, saline Lake Magadi, Kenya (pH, approximately 10.0; alkalinity, approximately 380 mmol L(-1); Na(+), approximately 350 mmol L(-1); Cl(-), approximately 110 mmol L(-1); osmolality, approximately 580 mosm kg(-1)). The fish survived well upon gradual exposure to dilute lake water (down to 1%, essentially freshwater). Urea excretion continued, and there was no ammonia excretion despite favorable conditions, indicating that ureotelism is obligatory. Levels of most ornithine-urea cycle enzymes in the liver were unchanged relative to controls kept for the same period in 100% lake water. The fish exhibited good abilities for hypo- and hyperregulation, maintaining plasma Na(+), Cl(-), and osmolality at levels typical of marine and freshwater teleosts in 100% and 1% lake water, respectively. Plasma total CO(2) did not change with environmental dilution. Routine oxygen consumption (Mo(2)) was extremely high in 100% lake water but decreased by 40%-68% after acclimation to dilute lake water. At every fixed swimming speed, Mo(2) was significantly reduced (by 50% at high speeds), and critical swimming speed was elevated in fish in 10% lake water relative to 100% lake water. Osmotic and Cl(-) concentration gradients from water to plasma were actually increased, and osmotic and Na(+) gradients were reversed, in 10% and 1% dilutions relative to 100% lake water, whereas acid-base gradients were greatly reduced. We suggest that approximately 50% of the animal's high metabolic demand originates from the cost of acid-base regulation in the highly alkaline Lake Magadi. When this load is reduced by environmental dilution, the energy saved can be diverted to enhanced swimming performance.


Neurobiological basis of sensory perception: welfare implications of beak trimming.
The practice of beak trimming in the poultry industry occurs to prevent excessive body pecking, cannibalism, and to avoid feed wastage. To assess the welfare implications of the procedure, an emphasis of this paper has been placed on the anatomical structures that comprise the beak and mouth parts and a representation of the structures removed following beak trimming. Five animal welfare concerns regarding the procedure have been addressed, including the following: loss of normal beak function, short-term pain and temporary debilitation, tongue and nostril damage, neuromas and scar tissue, and long-term and phantom limb pain. Because all of the concerns involve the nervous system, the current knowledge of the avian somatosensory system was summarized. The critical components include touch, pain, and thermal receptors in the buccal cavity and bill, the trigeminal system, and neural projections mapped to the pallium (cortical-like tissue in the avian forebrain). At the present time, a need remains to continue the practice of beak trimming in the poultry industry to prevent head, feather, and vent pecking in some lines of birds. The procedure, however, should involve conservative trimming and be limited to young birds. Importantly, data show that removing 50% or less of the beak of chicks can prevent the formation of neuromas and allow regeneration of keratinized tissue to prevent deformed beaks and therefore positively affect the quality of life of birds during their lifetime.


Bolstering the Three Pillars of the Essential Architecture of the Massage Therapy Profession: an Interview with Glenn M. Hymel, EdD, LMT.
As part of our interview editorial series, we bring forth a discussion with Dr. Glenn M. Hymel, the Founding Executive Editor of the International Journal of Therapeutic Massage and Bodywork. Dr. Hymel embodies the qualities set forth for the American Massage Therapy Association Dianne Polseno Lifetime Achievement Award, which he received in 2017. He has provided leadership and shown outstanding professionalism, and is a dedicated volunteer and a fervent advocate for research and education in the massage therapy profession. In this interview he discusses his massage therapy research, his interests, and his hopes for the future and the profession.


Sequestration of toxic oligomers by HspB1 as a cytoprotective mechanism.
Small heat shock proteins (sHsps) are molecular chaperones that protect cells from cytotoxic effects of protein misfolding and aggregation. HspB1, an sHsp commonly associated with senile plaques in Alzheimer's disease (AD), prevents the toxic effects of Aβ aggregates in vitro. However, the mechanism of this chaperone activity is poorly understood. Here, we observed that in two distinct transgenic mouse models of AD, mouse HspB1 (Hsp25) localized to the penumbral areas of plaques. We have demonstrated that substoichiometric amounts of human HspB1 (Hsp27) abolish the toxicity of Aβ oligomers on N2a (mouse neuroblastoma) cells. Using biochemical methods, spectroscopy, light scattering, and microscopy methods, we found that HspB1 sequesters toxic Aβ oligomers and converts them into large nontoxic aggregates. HspB1 was overexpressed in N2a cells in response to treatment with Aβ oligomers. Cultured neurons from HspB1-deficient mice were more sensitive to oligomer-mediated toxicity than were those from wild-type mice. Our results suggest that sequestration of oligomers by HspB1 constitutes a novel cytoprotective mechanism of proteostasis. Whether chaperone-mediated cytoprotective sequestration of toxic aggregates may bear clues to plaque deposition and may have potential therapeutic implications must be investigated in the future.


Immunization against an IL-6 peptide induces anti-IL-6 antibodies and modulates the Delayed-Type Hypersensitivity reaction in cynomolgus monkeys.
Interleukin-6 (IL-6) overproduction has been involved in the pathogenesis of several chronic inflammatory diseases and the administration of an anti-IL-6 receptor monoclonal antibody has been proven clinically efficient to treat them. However, the drawbacks of monoclonal antibodies have led our group to develop an innovative anti-IL-6 strategy using a peptide-based active immunization. This approach has previously shown its efficacy in a mouse model of systemic sclerosis. Here the safety, immunogenicity, and efficacy of this strategy was assessed in non human primates. No unscheduled death and clinical signs of toxicity was observed during the study. Furthermore, the cynomolgus monkeys immunized against the IL-6 peptide produced high levels of anti-IL-6 antibodies as well as neutralizing antibodies compared to control groups. They also showed an important decrease of the cumulative inflammatory score following a delayed-type hypersensitivity reaction induced by the Tetanus vaccine compared to control groups (minus 57,9%, P = 0.014). These findings are highly significant because the immunizing IL-6 peptide used in this study is identical in humans and in monkeys and this novel anti-IL-6 strategy could thus represent a promising alternative to monoclonal antibodies.


Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes.
Hydrogen-rich electrolyzed warm water (HW) was prepared at 41°C and exhibited dissolved hydrogen (DH) of 1.13 ppm and an oxidation-reduction potential (ORP) of -741 mV in contrast to below 0.01 ppm and+184 mV for regular warm water (RW). Fibroblasts OUMS-36 and keratinocytes HaCaT were used to examine effects of HW against UVA-ray irradiation. Type-I collagen was synthesized 1.85- to 2.03-fold more abundantly by HW application for 3-5 days than RW in OUMS-36 fibroblasts, and localized preferentially around the nuclei as shown by immunostain. HW application significantly prevented cell death and DNA damages such as nuclear condensation and fragmentation in UVA-irradiated HaCaT keratinocytes as estimated by WST-1 and Hoechst 33342 assays. HW significantly suppressed UVA-induced generation of intracellular superoxide anion radicals in both the cell lines according to NBT assay. Wrinkle repression was clinically assessed using a HW-bathing. Six Japanese subjects were enrolled in a trial of HW-bathing (DH, 0.2-0.4 ppm) every day for 3 months. HW-bathing significantly improved wrinkle in four subjects on the back of neck on 90th day as compared to 0 day. Thus, HW may serve as daily skin care to repress UVA-induced skin damages by ROS-scavenging and promotion of type-I collagen synthesis in dermis.


The impact of electronic health records on diagnosis.
Diagnostic error may be the largest unaddressed patient safety concern in the United States, responsible for an estimated 40,000-80,000 deaths annually. With the electronic health record (EHR) now in near universal use, the goal of this narrative review is to synthesize evidence and opinion regarding the impact of the EHR and health care information technology (health IT) on the diagnostic process and its outcomes. We consider the many ways in which the EHR and health IT facilitate diagnosis and improve the diagnostic process, and conversely the major ways in which it is problematic, including the unintended consequences that contribute to diagnostic error and sometimes patient deaths. We conclude with a summary of suggestions for improving the safety and safe use of these resources for diagnosis in the future.


Identification and functional significance of troponin I isoforms in neonatal rat heart myofibrils.
We investigated the mechanism(s) responsible for differences in the effects of acidic pH on Ca2+ activation of the activity of adult and neonatal rat heart myofilaments. Studies on preparations of myofilaments reconstituted with adult troponin-tropomyosin (Tn-Tm) and either adult or neonatal thick filaments indicated that the difference in effect of acidic pH is related to differences in Tn-Tm and not other myofilament proteins. Immunoblotting analysis showed that development of the rat heart myofibrils is associated with isoform switching from slow skeletal TnI to cardiac TnI and from a slow mobility isoform of TnT (TnT1) to a faster Mr isoform (TnT2. Expression of slow skeletal TnI was associated with a relative insensitivity of myofilament Ca2+ activation to deactivation by acidic pH. Moreover, the effect of acidic pH on Ca2+ activation of ATPase activity of soleus myofibrils, which contain cardiac TnC and slow skeletal TnI, was essentially the same as the effect of acidic pH on rat cardiac myofibrils in the early neonatal period. Neonatal myofilaments also contained a relative abundance of a set of polypeptides copurifying with the thin filaments. We have identified these proteins as histones. The relative amount of histones among a variety of preparations from different species was not correlated with the pH sensitivity of myofibrillar Ca2+ activation. Shifts in TnT isoforms among these species were also not correlated with an altered response to acidic pH. Our data provide evidence in support of the hypothesis that the relative insensitivity of neonatal myofilament activity to acidic pH is due to the presence of slow skeletal TnI in the thin-filament regulatory complex.


Description of Piscicapillaria bursata sp. nov. (Capillariidae) and Redescription of Parascarophis sphyrnae Campana-Rouget, 1955 (Cystidicolidae), Two Nematode Parasites of Hammerhead Sharks (Sphyrna spp.) off Australia.
Data on helminth parasites in hammerhead sharks are scarce and, therefore, new examinations of these hosts are needed to recognize the species composition of their parasites, including nematodes. Helminthological examinations of hammerhead sharks, Sphyrna lewini (Griffith et Smith) (209 specimens) and Sphyrna mokarran (Rüppell) (57 specimens) (Sphyrnidae, Carcharhiniformes), from off the northern coast of Australia revealed one new and one insufficiently known species of intestinal nematode parasites. These were studied with the use of light and scanning electron microscopy. Both nematode species are described. Piscicapillaria bursata sp. nov. (Capillariidae) from S. mokarran (type host) and S. lewini differs from its congeners mainly in the spicule length (330 µm), body length of gravid females 12.80-21.26 mm and in possessing a subterminal female anus. The specimens of Parascarophis sphyrnae Campana-Rouget, 1955 (Cystidicolidae) (type species of Parascarophis Campana-Rouget, 1955) collected from S. lewini made it possible to redescribe the female and, for the first time, to describe the male; the same species was also found in S. mokarran. Amended diagnosis of Parascarophis is provided. Parascarophis is mainly characterized by the presence of lateral alae, a unique feature within the Cystidicolidae, and by the cephalic structures (presence of a cuticular hood and a pair of anterolateral plate-like structures in the mouth). In addition to the discovery of a new nematode species, Pi. bursata sp. nov., the finding of Pa. sphyrnae in Australian waters represents a new geographical record of this parasite outside the Atlantic Ocean. The species of Parascarophis previously described from teleosts, P. bharatii Agrawal, 1965, P. oteroi Arya, 1992 and P. mulloidi Imam, Tawfik et Abdel Hady, 1982, are designated as species inquirendae and incertae sedis. The finding of P. sphyrnae in Australian waters represents a new geographical record of this parasite outside the Atlantic Ocean. Pa. sphyrnae had not been reported previously from beyond the Atlantic Ocean.


Acceptability of sodium-reduced research diets, including the Dietary Approaches To Stop Hypertension diet, among adults with prehypertension and stage 1 hypertension.
Examine the acceptability of sodium-reduced research diets. Randomized crossover trial of three sodium levels for 30 days each among participants randomly assigned to one of two dietary patterns. Three hundred fifty-four adults with prehypertension or stage 1 hypertension who were participants in the Dietary Approaches to Stop Hypertension (DASH-Sodium) outpatient feeding trial. Participants received their assigned diet (control or DASH, rich in fruits, vegetables, and low-fat dairy products), each at three levels of sodium (higher, intermediate, and lower) corresponding to 3,500, 2,300, and 1,200 mg/day (150, 100, and 50 mmol/day) per 2,100 kcal. Nine-item questionnaire on liking and willingness to continue the assigned diet and its level of saltiness using a nine-point scale, ranging from one to nine. Generalized estimating equations to test participant ratings as a function of sodium level and diet while adjusting for site, feeding cohort, carryover effects, and ratings during run-in. Overall, participants rated the saltiness of the intermediate level sodium as most acceptable (DASH group: 5.5 for intermediate vs 4.5 and 4.4 for higher and lower sodium; control group: 5.7 for intermediate vs 4.9 and 4.7 for higher and lower sodium) and rated liking and willing to continue the DASH diet more than the control diet by about one point (ratings range from 5.6 to 6.6 for DASH diet and 5.2 to 6.1 for control diet). Small race differences were observed in sodium and diet acceptability. Both the intermediate and lower sodium levels of each diet are at least as acceptable as the higher sodium level in persons with or at risk for hypertension.


School Choice in London and Paris - A Comparison of Middle-class Strategies.
Education is one major public service in which quasi-markets and other choice-based mechanisms are now established methods of delivery. The types of school people choose, and the extent to which their choices are realized, have a fundamental impact on the outcomes of any mechanism of school choice. In this article, we provide a comparative analysis of the school choice strategies of middle-class families in London and Paris. We draw on approximately 200 in-depth interviews carried out across the two cities. This enables us to investigate the extent to which middle-class school choice strategies transcend the institutional context provided by both the local (state and private) schools market and national education policy in England and France. We discuss these findings in the context of current school choice policy and consider their implications for future policy design.


Sequence-specific 1H-n.m.r. assignments and peptide backbone conformation in rat epidermal growth factor.
The solution conformation of rat epidermal growth factor (EGF) has been investigated by proton n.m.r. techniques. Two-dimensional proton n.m.r. experiments have allowed sequential resonance assignments to be made for most protons. On the basis of these assignments, two regions of anti-parallel beta-sheet structure have been derived from the n.m.r. data. A beta-sheet segment running from about V19 to V23 (capital letters refer to amino acids in the single-letter notation) is folded onto a beta-sheet segment running from R28 to N32 and joined by a chain reversal from E24 to D27. A second region involves a beta-turn from V34 to Y37, which starts a short beta-sheet up to G39, followed by a chain reversal up to Q43, which leads to folding of the C-terminal beta-sheet segment, i.e. H44-R45, running antiparallel to the short Y37 beta-sheet segment. The N-terminal segment up to G18 exists in a multiple bend conformation and is folded on to the V29-V23/R28-N32 beta-sheet such that Y10, Y13, Y22 and Y29 are proximal to each other. Structural comparison of rat, murine and human EGFs indicates a number of highly conserved structural features common to at least these species of EGF.


Place of birth, cancer beliefs and being current with colon cancer screening among US adults.
Historically, studies suggested that immigrants acquire the risk of colorectal cancer (CRC) as US-born persons within the same generation. CRC risk of immigrants is largely unknown in this era of cancer screening and widespread immigration. We investigated the association of place of birth and cancer beliefs with uptake of CRC screening. The 2007 Health Information National Trends Survey was used and 4,299 respondents (weighted population size=81,896,392) who were 50 years and older (3,960 US-born and 339 foreign-born) were identified. We defined being current with CRC screening guidelines as the use of fecal occult blood test within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared being up-to-date with CRC screening among foreign-born versus US-born respondents. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, 2,594 (63.3%) US-born and 208 (52.8%) foreign-born respondents were current with CRC screening. Foreign-born respondents were less current in unadjusted model (OR 0.65; 95% CI: 0.50-0.85) but became non-statistically significant after adjustment (OR 0.79; 95% CI: 0.51-1.24). Respondents who believed that screening finds cancer when it is easy to treat (OR 2.85; 95% CI: 1.44-3.61), those who believed that cancer can be cured when detected early (OR 1.56; 95% CI: 1.20-2.00), and those who worry about getting cancer (OR 1.34; 95% CI: 1.10-1.61) were likely to be current with CRC screening. However, respondents with fatalistic beliefs were borderline less likely to be current (OR 0.82; 95% CI: 0.65-1.04). There is a need to improve education on CRC screening, particularly among foreign-born adults.


Ensemble modelling and structured decision-making to support Emergency Disease Management.
Epidemiological models in animal health are commonly used as decision-support tools to understand the impact of various control actions on infection spread in susceptible populations. Different models contain different assumptions and parameterizations, and policy decisions might be improved by considering outputs from multiple models. However, a transparent decision-support framework to integrate outputs from multiple models is nascent in epidemiology. Ensemble modelling and structured decision-making integrate the outputs of multiple models, compare policy actions and support policy decision-making. We briefly review the epidemiological application of ensemble modelling and structured decision-making and illustrate the potential of these methods using foot and mouth disease (FMD) models. In case study one, we apply structured decision-making to compare five possible control actions across three FMD models and show which control actions and outbreak costs are robustly supported and which are impacted by model uncertainty. In case study two, we develop a methodology for weighting the outputs of different models and show how different weighting schemes may impact the choice of control action. Using these case studies, we broadly illustrate the potential of ensemble modelling and structured decision-making in epidemiology to provide better information for decision-making and outline necessary development of these methods for their further application.


Accuracy and reproducibility of probe forces during simulated periodontal pocket depth measurements.
The aim of the present study was to measure the accuracy and reproducibility of probe forces in simulated assessments of periodontal pocket depth. The study included experienced and inexperienced examiners and used manual and pressure-sensitive probes. Sixty-one participants were divided into seven groups and asked to probe selected anterior and posterior sites with three different probes (Williams 14W, Chapple UB-CF-15, and Vivacare TPS probes). The model was positioned on a digital electronic balance to measure force, which was recorded initially and after 15 min. Probe preferences were recorded. Accuracy was measured by comparing to a standardized 25 g force, and reproducibility was calculated for all duplicate measurements. The Vivacare probe produced the most accurate and most reproducible forces, whereas the Williams probe produced the least accurate and least reproducible forces. Probe forces were lighter at anterior sites compared to posterior sites at baseline. Probe forces were reduced at both sites after 15 min compared to baseline. Vivacare TPS periodontal probes are more accurate and reproducible than Chapple and Williams probes. Many clinicians in this study preferred the Chapple probe.


Cited3 activates Mef2c to control muscle cell differentiation and survival.
Vertebrate muscle development occurs through sequential differentiation of cells residing in somitic mesoderm - a process that is largely governed by transcriptional regulators. Our recent spatiotemporal microarray study in zebrafish has identified functionally uncharacterized transcriptional regulators that are expressed at the initial stages of myogenesis. cited3 is one such novel gene encoding a transcriptional coactivator, which is expressed in the precursors of oxidative slow-twitch myofibers. Our experiments placed cited3 into a gene regulatory network, where it acts downstream of Hedgehog signaling and myoD/myf5 but upstream of mef2c. Knockdown of expression of cited3 by antisense morpholino oligonucleotides impaired muscle cell differentiation and growth, caused muscle cell death and eventually led to total immotility. Transplantation experiments demonstrated that Cited3 cell-autonomously activates the expression of mef2c in slow myofibers, while it non-cell-autonomously regulates expression of structural genes in fast myofibers. Restoring expression of cited3 or mef2c rescued all the cited3 loss-of-function phenotypes. Protein truncation experiments revealed the functional necessity of C-terminally conserved domain of Cited3, which is known to mediate interactions of Cited-family proteins with histone acetylases. Our findings demonstrate that Cited3 is a critical transcriptional coactivator functioning during muscle differentiation and its absence leads to defects in terminal differentiation and survival of muscle cells.


Visual versus semi-quantitative analysis of 18F-FDG-PET in amnestic MCI: an European Alzheimer's Disease Consortium (EADC) project.
We aimed to investigate the accuracy of FDG-PET to detect the Alzheimer's disease (AD) brain glucose hypometabolic pattern in 142 patients with amnestic mild cognitive impairment (aMCI) and 109 healthy controls. aMCI patients were followed for at least two years or until conversion to dementia. Images were evaluated by means of visual read by either moderately-skilled or expert readers, and by means of a summary metric of AD-like hypometabolism (PALZ score). Seventy-seven patients converted to AD-dementia after 28.6 ± 19.3 months of follow-up. Expert reading was the most accurate tool to detect these MCI converters from healthy controls (sensitivity 89.6%, specificity 89.0%, accuracy 89.2%) while two moderately-skilled readers were less (p < 0.05) specific (sensitivity 85.7%, specificity 79.8%, accuracy 82.3%) and PALZ score was less (p < 0.001) sensitive (sensitivity 62.3%, specificity 91.7%, accuracy 79.6%). Among the remaining 67 aMCI patients, 50 were confirmed as aMCI after an average of 42.3 months, 12 developed other dementia, and 3 reverted to normalcy. In 30/50 persistent MCI patients, the expert recognized the AD hypometabolic pattern. In 13/50 aMCI, both the expert and PALZ score were negative while in 7/50, only the PALZ score was positive due to sparse hypometabolic clusters mainly in frontal lobes. Visual FDG-PET reads by an expert is the most accurate method but an automated, validated system may be particularly helpful to moderately-skilled readers because of high specificity, and should be mandatory when even a moderately-skilled reader is unavailable.


Four persistent rural healthcare challenges.
Today, 25% of Canadians live in rural and remote parts of Canada. The evidence is that these Canadians do not enjoy the same health status as citizens living in more urban settings. This article explores four persistent healthcare challenges: population demographics, place, professionals, and public participation. By exploring solutions that some rural communities have used to address these challenges, this article aims to provide insights into lessons that have been learned that they may be considered and potentially applied to both rural and urban environments in the interest of better healthcare for all.


Urine Cytokine and Chemokine Levels Predict Urinary Tract Infection Severity Independent of Uropathogen, Urine Bacterial Burden, Host Genetics, and Host Age.
Urinary tract infections (UTIs) are among the most common infections worldwide. Diagnosing UTIs in older adults poses a significant challenge as asymptomatic colonization is common. Identification of a noninvasive profile that predicts likelihood of progressing from urine colonization to severe disease would provide a significant advantage in clinical practice. We monitored colonization susceptibility, disease severity, and immune response to two uropathogens in two mouse strains across three age groups to identify predictors of infection outcome. Proteus mirabilis caused more severe disease than Escherichia coli, regardless of mouse strain or age, and was associated with differences in interleukin-1β (IL-1β), beta interferon (IFN-β), CXCL5 (LIX), CCL5 (RANTES), and CCL2 (MCP-1). In a comparison of responses to infection across age groups, mature adult mice were better able to control colonization and prevent progression to kidney colonization and bacteremia than young or aged mice, regardless of mouse strain or bacterial species, and this was associated with differences in IL-23, CXCL1, and CCL5. A bimodal distribution was noted for urine colonization, which was strongly associated with bladder CFU counts and the magnitude of the immune response but independent of age or disease severity. To determine the value of urine cytokine and chemokine levels for predicting severe disease, all infection data sets were combined and subjected to a series of logistic regressions. A multivariate model incorporating IL-1β, CXCL1, and CCL2 had strong predictive value for identifying mice that did not develop kidney colonization or bacteremia, regardless of mouse genetic background, age, infecting bacterial species, or urine bacterial burden. In conclusion, urine cytokine profiles could potentially serve as a noninvasive decision support tool in clinical practice and contribute to antimicrobial stewardship.


Attenuation-based estimation of patient size for the purpose of size specific dose estimation in CT. Part II. Implementation on abdomen and thorax phantoms using cross sectional CT images and scanned projection radiograph images.
To estimate attenuation using cross sectional CT images and scanned projection radiograph (SPR) images in a series of thorax and abdomen phantoms. Attenuation was quantified in terms of a water cylinder with cross sectional area of A(w) from both the CT and SPR images of abdomen and thorax phantoms, where A(w) is the area of a water cylinder that would absorb the same dose as the specified phantom. SPR and axial CT images were acquired using a dual-source CT scanner operated at 120 kV in single-source mode. To use the SPR image for estimating A(w), the pixel values of a SPR image were calibrated to physical water attenuation using a series of water phantoms. A(w) and the corresponding diameter D(w) were calculated using the derived attenuation-based methods (from either CT or SPR image). A(w) was also calculated using only geometrical dimensions of the phantoms (anterior-posterior and lateral dimensions or cross sectional area). For abdomen phantoms, the geometry-based and attenuation-based methods gave similar results for D(w). Using only geometric parameters, an overestimation of D(w) ranging from 4.3% to 21.5% was found for thorax phantoms. Results for D(w) using the CT image and SPR based methods agreed with each other within 4% on average in both thorax and abdomen phantoms. Either the cross sectional CT or SPR images can be used to estimate patient attenuation in CT. Both are more accurate than use of only geometrical information for the task of quantifying patient attenuation. The SPR based method requires calibration of SPR pixel values to physical water attenuation and this calibration would be best performed by the scanner manufacturer.


Propolis extract a new reinforcement material in improving bone healing: An in vivo study.
Propolis is known for its antioxidant, immune response modulating, and wound healing effects. In the present study in order to determine the bone healing capacity of the propolis extract, a critical sized, nonunion, radial bone defect model was repaired in rat, using chitosan and demineralized bone matrix (DBM) scaffolds along with propolis extract. Seventy-two radial bone defects in 36 healthy male rats were randomly divided into 6 groups (n = 12/group). The groups included autograft, defect or untreated group, chitosan, DBM, chitosan and propolis (chitosan-propolis), and DBM and propolis (DBM-propolis). The bone repairing capability was characterized using radiography at 28th, 42nd and 56th postoperative days. Gross morphologic, histopathologic, histomorphometric and biomechanical examinations were performed following euthanasia at the 56th post-operative day. The DBM-propolis group, showed better structural and biomechanical properties compared to the untreated, DBM, chitosan and chitosan-propolis groups. The defect site in the chitosan and untreated groups were mainly restored by fibrous connective tissue while the lesions in the autograft group were mostly filled by cartilage and a lesser amount of woven bone. The woven bone, and the hyaline cartilage were the main constituents of the newly formed tissues in the DBM-propolis group, at the 56th day after injury. The results of this study showed that percutaneous injection of diluted aqueous propolis extract in the bone defect (25 mg/defect) can improve bone formation in the critical radial bone defect in rat. Since there was no significant difference between the autograft and DBM-propolis group, probably this therapeutic strategy has high potential in augmentation of autologous bone grafting.


Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.
Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens. Overall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children. www.controlled-trials.com ISRCTN13968779


Case Study on Ancestry Estimation in an Alaskan Native Family: Identity and Safeguards Against Reductionism.
Understanding the complexities of ancestry-related identity is a necessary component of ethically sound research related to the genetic ancestry of modern-day communities. This is especially true when working with indigenous populations, given the legal and social implications that genetic ancestry interpretations may have in these communities. This study employs a multicomponent approach to explore the intricacies of ancestry-related identity within one extended family with members who identify as Alaskan Native. The seven participants were interviewed about their own self-identity, perceptions regarding genetic ancestry estimation, and their knowledge of oral family history. Additionally, each participant consented to having his or her genetic ancestry estimated. The researchers also surveyed ancestry-related documents, such as census records, birth certificates, and Certificates of Indian Blood. These three different perspectives-oral family history and self-identity, genetic ancestry estimation, historical and legal documentation-illustrate the complex nature of ancestry-related identity within the context of indigenous and colonial interactions in North America. While estimates of genetic ancestry broadly reflected each individual's self-reported biogeographic ancestry and supported all described and historically reported biological relationships, the estimates did not always match federally recorded blood quantum values, nor did they provide any information on relationships at the tribe or clan level. Employing a multicomponent approach and engaging study participants may help to safeguard against genetic essentialism and provide a more nuanced understanding of ancestry-related identity within a larger political, legal, and historical context.


Efficacy of oral bisphosphonates for preventing hip fracture in disabled patients with neurological diseases: a meta-analysis of randomized controlled trials among the Japanese population.
Neurological diseases such as amyotrophic lateral sclerosis (ALS), stroke, and Parkinson's disease cause disability and immobilization that increases the risk of hip fracture. The purpose of the present study was to clarify the efficacy of oral bisphosphonates for preventing hip fracture in disabled patients with such neurological diseases. A literature search (PubMed) was done from 1995 to the present for randomized controlled trials (RCTs), and a meta-analysis was conducted. Seven RCTs met the criteria, including two of etidronate (ALS and stroke), two of alendronate (stroke and Parkinson's disease), and three of risedronate (stroke and Parkinson's disease). All of the RCTs were performed on Japanese patients. According to the results of pooled data analysis, the relative risk (95% confidence interval) of hip fracture in patients receiving etidronate, alendronate, and risedronate treatment compared with placebo or active control treatment was 0.16 (0.03-0.87), 0.29 (0.10-0.80), and 0.24 (0.10-0.58), respectively, suggesting a reduction of risk by more than 70% with oral bisphosphonates. There was no statistical evidence of heterogeneity among RCTs, and publication bias was not identified by the funnel plot and Begg's rank correlation test. No severe adverse events due to oral bisphosphonate treatment were reported. It remains uncertain whether the findings are relevant for Western patients with an increased risk of hip fracture due to neurological diseases. A meta-analysis of RCTs suggested that oral bisphosphonate treatment prevents hip fracture in disabled Japanese patients with neurological diseases, including ALS, stroke, and Parkinson's disease. Oral bisphosphonate treatment was well tolerated by such patients.


Fetal abnormality: an audit of its recognition and management. Northern Regional Survey Steering Group.
A voluntary survey set up by local clinicians has documented all lethal abnormality in a geographically defined area of northern England where there were 361,037 registered births between 1982 and 1990, and monitored the incidence of all significant physical abnormality since January 1984. The survey aims to maintain a register of all pregnancies where an abnormality is suspected before birth, and those where an abnormality is only identified after birth, together with a record of how the diagnosis was established. Information on management and outcome a year after birth is also collected. Nearly half the total decline in perinatal mortality in the region between 1982 and 1990 is accounted for by an increase in the antenatal recognition of lethal abnormality, isolated hydrocephalus, or a neural tube defect and subsequent termination of pregnancy. Although the reporting of many non-lethal conditions was incomplete during the pilot study in 1984, it has become progressively more complete since then. The number of cases confirmed postnatally varied little between units between 1985-9, but audit showed that the proportion recognised antenatally varied fivefold for reasons unconnected with unit size or the amount of antenatal ultrasound work done. For a number of serious conditions more than 10% of all antenatal diagnoses were completely wrong. Survey data are, for the first time, making it possible to monitor the accuracy of the ultrasound-based screening and diagnostic services for identifying specific fetal abnormalities. They are also providing clinicians with an invaluable confidential database of a whole region's collective experience of dealing with complex fetal abnormality.


Reviewing audit: barriers and facilitating factors for effective clinical audit.
To review the literature on the benefits and disadvantages of clinical and medical audit, and to assess the main facilitators and barriers to conducting the audit process. A comprehensive literature review was undertaken through a thorough review of Medline and CINAHL databases using the keywords of "audit", "audit of audits", and "evaluation of audits" and a handsearch of the indexes of relevant journals for key papers. Findings from 93 publications were reviewed. These ranged from single case studies of individual audit projects through retrospective reviews of departmental audit programmes to studies of interface projects between primary and secondary care. The studies reviewed incorporated the experiences of a wide variety of clinicians, from medical consultants to professionals allied to medicine and from those involved in unidisciplinary and multidisciplinary ventures. Perceived benefits of audit included improved communication among colleagues and other professional groups, improved patient care, increased professional satisfaction, and better administration. Some disadvantages of audit were perceived as diminished clinical ownership, fear of litigation, hierarchical and territorial suspicions, and professional isolation. The main barriers to clinical audit can be classified under five main headings. These are lack of resources, lack of expertise or advice in project design and analysis, problems between groups and group members, lack of an overall plan for audit, and organisational impediments. Key facilitating factors to audit were also identified: they included modern medical records systems, effective training, dedicated staff, protected time, structured programmes, and a shared dialogue between purchasers and providers. Clinical audit can be a valuable assistance to any programme which aims to improve the quality of health care and its delivery. Yet without a coherent strategy aimed at nurturing effective audits, valuable opportunities will be lost. Paying careful attention to the professional attitudes highlighted in this review may help audit to deliver on some of its promise.


Simultaneous necrotizing glomerulonephritis and Hodgkin's lymphoma: a case report and review of the literature.
Glomerulonephritis occurs in 1% of Hodgkin's lymphoma patients. In the even rarer setting of rapidly progressive glomerulonephritis, lymphoma may go unrecognized. We describe a case of necrotizing glomerulonephritis in which treatment with cyclophosphamide and steroids led to resolution of lymphadenopathy. Two years later, recrudescent lymphadenopathy was shown to be Hodgkin's lymphoma, but renal disease did not recur.


Structured Correspondence Topic Models for Mining Captioned Figures in Biological Literature.
A major source of information (often the most crucial and informative part) in scholarly articles from scientific journals, proceedings and books are the figures that directly provide images and other graphical illustrations of key experimental results and other scientific contents. In biological articles, a typical figure often comprises multiple panels, accompanied by either scoped or global captioned text. Moreover, the text in the caption contains important semantic entities such as protein names, gene ontology, tissues labels, etc., relevant to the images in the figure. Due to the avalanche of biological literature in recent years, and increasing popularity of various bio-imaging techniques, automatic retrieval and summarization of biological information from literature figures has emerged as a major unsolved challenge in computational knowledge extraction and management in the life science. We present a new structured probabilistic topic model built on a realistic figure generation scheme to model the structurally annotated biological figures, and we derive an efficient inference algorithm based on collapsed Gibbs sampling for information retrieval and visualization. The resulting program constitutes one of the key IR engines in our SLIF system that has recently entered the final round (4 out 70 competing systems) of the Elsevier Grand Challenge on Knowledge Enhancement in the Life Science. Here we present various evaluations on a number of data mining tasks to illustrate our method.


Epigallocatechin-3-gallate reduces myometrial infiltration, uterine hyperactivity, and stress levels and alleviates generalized hyperalgesia in mice induced with adenomyosis.
In an effort to search for novel therapeutics for adenomyosis, we sought to determine whether treatment with epigallocatechin-3-gallate (EGCG) would suppress the myometrial infiltration, improve pain behavior, lower stress level, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 28 female ICR mice neonatally dosed with tamoxifen, while another 12 (group C) were dosed with solvent only, which served as a blank control. Starting from 4 weeks after birth, hot plate test was administrated to all mice every 4 weeks. At the 16th week, all mice induced with adenomyosis were randomly divided into 3 groups: low-dose EGCG (5 mg/kg), high-dose EGCG (50 mg/kg), and untreated. Group C received no treatment. After 3 weeks of treatment, the hot plate test was administered again, a blood sample was taken to measure the plasma corticosterone level by enzyme-linked immunosorbent assay, and then all mice were sacrificed. The depth of myometrial infiltration and uterine contractility were also evaluated. We found that the induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and frequency of uterine contractions as well as elevated plasma corticosterone levels. The EGCG treatment dose dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility, and lowered plasma corticosterone levels. These results suggest that induced adenomyosis causes pain and elevates stress levels in mice. Uterine hyperactivity may contribute to dysmenorrhea in women with adenomyosis who might also have elevated stress level due to pain. The EGCG appears to be a promising compound for treating adenomyosis.


Stabilization of platinum oxygen-reduction electrocatalysts using gold clusters.
We demonstrated that platinum (Pt) oxygen-reduction fuel-cell electrocatalysts can be stabilized against dissolution under potential cycling regimes (a continuing problem in vehicle applications) by modifying Pt nanoparticles with gold (Au) clusters. This behavior was observed under the oxidizing conditions of the O2 reduction reaction and potential cycling between 0.6 and 1.1 volts in over 30,000 cycles. There were insignificant changes in the activity and surface area of Au-modified Pt over the course of cycling, in contrast to sizable losses observed with the pure Pt catalyst under the same conditions. In situ x-ray absorption near-edge spectroscopy and voltammetry data suggest that the Au clusters confer stability by raising the Pt oxidation potential.


Lateral gene transfer from the dead.
In phylogenetic studies, the evolution of molecular sequences is assumed to have taken place along the phylogeny traced by the ancestors of extant species. In the presence of lateral gene transfer, however, this may not be the case, because the species lineage from which a gene was transferred may have gone extinct or not have been sampled. Because it is not feasible to specify or reconstruct the complete phylogeny of all species, we must describe the evolution of genes outside the represented phylogeny by modeling the speciation dynamics that gave rise to the complete phylogeny. We demonstrate that if the number of sampled species is small compared with the total number of existing species, the overwhelming majority of gene transfers involve speciation to and evolution along extinct or unsampled lineages. We show that the evolution of genes along extinct or unsampled lineages can to good approximation be treated as those of independently evolving lineages described by a few global parameters. Using this result, we derive an algorithm to calculate the probability of a gene tree and recover the maximum-likelihood reconciliation given the phylogeny of the sampled species. Examining 473 near-universal gene families from 36 cyanobacteria, we find that nearly a third of transfer events (28%) appear to have topological signatures of evolution along extinct species, but only approximately 6% of transfers trace their ancestry to before the common ancestor of the sampled cyanobacteria.


Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns.
Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.


Time dependence of multiorder stimulated Raman scattering from single droplets.
An optical multichannel detection technique was used to measure simultaneously the time profiles of the input laser pulse and the elastic scattering, as well as the time profiles of the spectrally resolved multiorder stimulated Raman scattering (SRS), from single droplets. The time delay between the multiorder SRS and the input laser pulse is consistent with the generalized four-wave mixing process for first-order stimulated Raman growth, starting from spontaneous noise or the parametric signal. The presence of an internal plasma associated with laser-induced breakdown within a droplet quenches the SRS and increases the elastic scattering.


An overview of recent studies on the potential of pulp-mill effluents to alter reproductive parameters in fish.
In the early 1990s, many Canadian pulp and paper mills implemented process changes to comply with new regulations that came into effect in 1993. These regulations placed stricter guidelines on a number of parameters in effluent discharges, including limits on acute toxicity, on the discharges of suspended solids, and on biochemical oxygen demand. To meet these new regulations, many of the older Canadian pulp and paper mills had to install secondary treatment systems. The investment by the Canadian pulp and paper industry was in excess of $5 billion, and the implementation of the new regulations and the process changes took several years. The new regulations were an extension of regulations designed in the early 1970s and were not designed specifically to address the reproductive responses recently reported in fish collected downstream of mills in Scandinavia and North America. This report describes a series of projects conducted between 1991 and 1996 to evaluate the effectiveness of the new regulations to address the issue of reproductive responses in fish associated with exposure to pulp-mill effluents. These studies have shown that the existing short-term bioassays do not adequately predict the potential of effluents to affect reproduction in wild fish. Laboratory testing using fathead minnows exposed over a full life cycle confirmed depression in sex steroid production, delay in sexual maturity, reduced egg production, and changes in secondary sex characteristics documented at some sites. Our studies demonstrated that both steroid hormone changes and induction of liver detoxification enzymes take place quickly. While short-term exposures can predict the potential of some effluents to impact steroid hormone production, there is no readily available assay that can be widely applied. In the absence of a usable and transferable laboratory bioassay, field collections were conducted at a number of sites. Generalizations are not possible at this time, but impacts have been seen at a variety of sites, and partial recovery has been documented at five sites in North America following various process and waste treatment changes. Data gaps and critical research areas are identified.


Medial prefrontal cortex activity during memory encoding of pictures and its relation to symptomatic improvement after citalopram treatment in patients with major depression.
Brain imaging studies of major depressive disorder have shown alterations in the brain regions typically involved in episodic memory, including the prefrontal cortex and medial temporal areas. Some studies of major depressive disorder have linked episodic memory performance to treatment response. In this study, we sought to identify brain regions whose activity, measured during the encoding of pictures, predicted symptomatic improvement after 8 weeks of citalopram treatment. We included 20 unmedicated depressed patients. These patients performed an episodic recognition memory task during functional magnetic resonance imaging. During the encoding phase, 150 pictures depicting emotionally positive, negative or neutral content were presented, and the participants were required to classify each picture according to its emotional valence. The same 150 pictures were presented, along with 150 new ones, for a recognition task. We asked participants to distinguish the old pictures from the new ones. We assessed symptom severity by use of the 21-item Hamilton Rating Scale for Depression (HAM-D) at baseline and after 8 weeks of citalopram treatment. We performed subsequent memory effect analyses using SPM2 software. We explored the relation between brain activation during successful encoding of pictures and symptomatic improvement. Patients showed a mean symptomatic improvement of 54.5% on the HAM-D after 8 weeks. Symptomatic improvement was significantly and positively correlated with picture recognition memory accuracy. We also found that the activity of the ventromedial prefrontal cortex and anterior cingulate cortex during successful encoding was significantly correlated with symptomatic improvement. Finally, we found greater activation in the ventromedial prefrontal cortex during the successful encoding of positive pictures in comparison with neutral pictures. During the recognition memory task, 5 participants (among the best responders to treatment) were not included in the valence-specific analyses because they had very few errors. A more challenging task would have allowed the inclusion of most patients. Different types of functional imaging paradigms have been used to explore whether the activity of specific brain regions measured at baseline is predictive of a better response to treatment in major depressive disorder. Among these regions, the medial prefrontal cortex and anterior cingulate cortex usually show the strongest predictive value. According to our results, the medial prefrontal cortex and anterior cingulate cortex could have an effect on treatment response in major depressive disorder by contributing to the successful encoding of positively valenced information.


Strategies to prevent contrast nephropathy.
Contrast nephropathy (CN) is a common cause of iatrogenic acute renal failure. Its incidence rises with the growing use of intra-arterial contrast in older patients for diagnostic and interventional procedures. Aim of the present review is to discuss the mechanisms and risk factors of CN, to summarize the controlled studies evaluating measures for prevention, and to conclude with evidence-based strategies for prevention. Pathophysiological mechanisms of CN are intrarenal vasoconstriction, leading to medullary ischemia, direct cytotoxicity, oxidative tissue damage and apoptosis. Nephro-toxicity is related to osmolality, dose and route of the contrast agent and only occurs in synergy with patient factors, such as previous renal impairment, cardiovascular disease, oxidant stress and the use of certain drugs. CN has impact on morbidity and mortality. In patients at risk, the following measures are recommended: discontinuation of potentially nephrotoxic drugs, treatment of intravascular volume depletion, hydration with sodium-bicarbonate (which seems superior to sodium-chloride), limitation of contrast volume and the use of low-osmolal contrast. Furthermore, if starting the day before is feasible, administer oral N-acetylcysteine, or, with urgent interventions, theophylline 200 mg i.v. (once before the intervention) or high dose ascorbic acid. In patients with combined severe cardiac and renal insufficiency, periprocedural hemofiltration may be considered; this is the only intervention with proven clinical improvement. Large randomised controlled trials are necessary to show whether pharmacological interventions can improve clinical outcomes.


Absence of mutations in the Gs alpha and Gi2 alpha genes in sporadic parathyroid adenomas and insulinomas.
1. Activating mutations of the alpha-subunits of the Gs and Gi2 proteins give rise to the oncogenes gsp and gip2, respectively, which are found in a variety of endocrine tumours. 2. In this study the polymerase chain reaction and direct sequencing have been used to screen a small sample of parathyroid adenomas and insulinomas for these mutations. 3. No mutations were identified in nine insulinomas and 13 parathyroid adenomas screened for gsp, and 11 parathyroid adenomas and four insulinomas screened for gip2. In addition, two gastrinomas from patients with multiple endocrine neoplasia type 1 were found to be negative for both oncogenes. 4. This is the first report of screening for gip2 in parathyroid adenomas and gsp/gip2 in insulinomas, and it extends the range of tumours examined for these oncogenes.


Hitchhiking effect of a beneficial mutation spreading in a subdivided population.
A central problem in population genetics is to detect and analyze positive natural selection by which beneficial mutations are driven to fixation. The hitchhiking effect of a rapidly spreading beneficial mutation, which results in local removal of standing genetic variation, allows such an analysis using DNA sequence polymorphism. However, the current mathematical theory that predicts the pattern of genetic hitchhiking relies on the assumption that a beneficial mutation increases to a high frequency in a single random-mating population, which is certainly violated in reality. Individuals in natural populations are distributed over a geographic space. The spread of a beneficial allele can be delayed by limited migration of individuals over the space and its hitchhiking effect can also be affected. To study this effect of geographic structure on genetic hitchhiking, we analyze a simple model of directional selection in a subdivided population. In contrast to previous studies on hitchhiking in subdivided populations, we mainly investigate the range of sufficiently high migration rates that would homogenize genetic variation at neutral loci. We provide a heuristic mathematical analysis that describes how the genealogical structure at a neutral locus linked to the locus under selection is expected to change in a population divided into two demes. Our results indicate that the overall strength of genetic hitchhiking--the degree to which expected heterozygosity decreases--is diminished by population subdivision, mainly because opportunity for the breakdown of hitchhiking by recombination increases as the spread of the beneficial mutation across demes is delayed when migration rate is much smaller than the strength of selection. Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations. This raises a possibility of detecting a "hidden" geographic structure of population by carefully analyzing the pattern of a selective sweep.


Sudden cardiac death in cardiac transplant recipients.
Sudden cardiac death (SCD) remains a significant cause of mortality in the general population. Its role in cardiac transplant patients-including its incidence, mechanism, potential risk factors, or influence on survival in this patient population-has not been well described. We undertook a retrospective analysis of the clinical and autopsy records of 257 patient deaths. SCD was analyzed in relation to severity and frequency of rejection episodes, clinical history of arrhythmias, coronary artery disease (CAD), hypertension, diabetes, left ventricular dysfunction, and clinical history of premorbid symptoms. A total of 25 patients were identified as having died of SCD, an incidence of 9.7%: 20% died < or = 12 months after transplantation, 80% died after > 12 months, and 20% died after > or = 60 months. Patient survival ranged from 2.5 to 138 months (mean, 45.7 months). The mean number of rejection episodes per patient was 2.6, most occurring within 12 months after transplantation. Echocardiography or multigated acquisition scan revealed an ejection fraction (EF) > or = 50% in 68% of patients; however, the presence of arrhythmias, primarily atrial, was evident in 68% of patients and was equally distributed between patients with EFs > or = 50% and EFs < 50%. CAD was present in 53% of patients (10 of 19) whose angiograms were available, and the appearance of CAD after transplantation was between 29 and 85 months (mean, 51.4 months). Of the 9 patients with normal cardiac catheterization studies, 6 with available autopsy reports had documented CAD. Autopsy data in 13 of 25 patients revealed CAD in 92% and rejection in 15% (International Society for Heart and Lung Transplantation grade > 3A). Of the deaths, 64% occurred within 3 months of the last endomyocardial biopsy, 96% had normal biopsies, and the only rejection was without hemodynamic compromise. SCD occurs relatively frequently in the cardiac transplant population, and CAD is present in most of the patients. Because the frequency of arrhythmias is relatively high in this group, more aggressive antiarrhythmic therapy may be beneficial for patients with allograft CAD in the prevention of SCD.


Orbitofrontal lesions impair use of cue-outcome associations in a devaluation task.
The orbitofrontal cortex (OFC) has been implicated in the use of outcome expectancies to guide behavior. The present study used a devaluation task to examine this function. Rats first received light-food pairings followed by food-toxin pairings designed to devalue the food. After either excitotoxic or sham OFC lesions, responding to the light was reassessed. Sham-lesioned rats showed reduced responding to the light relative to behavioral controls, which had received food and toxin unpaired. In contrast, OFC-lesioned rats showed no such reductions. Combined with previous data (C. L. Pickens, M. P. Saddoris, B. Setlow, M. Gallagher, P. C. Holland, & G. Schoenbaum, 2003), these results indicate that the OFC is critical for the maintenance of information about the current incentive value of reinforcers or the use of that information to guide behavior.


Autofluorescence characterisation of isolated whole crypts and primary cultured human epithelial cells from normal, hyperplastic, and adenomatous colonic mucosa.
In vivo autofluorescence endoscopic imaging and spectroscopy have been used to detect and differentiate benign (hyperplastic) and preneoplastic (adenomatous) colonic lesions. This fluorescence is composed of contributions from the epithelium, lamina propria, and submucosa. Because epithelial autofluorescence in normal and diseased tissues is poorly understood, this was the focus of the present study. Whole colonic crypts were isolated, and short term primary cultures of epithelial cells were established from biopsies of normal, hyperplastic, and adenomatous colon. Autofluorescence (488 nm excitation) was examined by confocal fluorescence microscopy. Fluorescently labelled organelle probes and transmission electron microscopy were used to identify subcellular sources of fluorescence. Mitochondria and lysosomes were identified as the main intracellular fluorescent components in all cell types. Normal and hyperplastic epithelial cells were weakly autofluorescent and had similar numbers of mitochondria and lysosomes, whereas adenomatous (dysplastic) epithelial cells showed much higher autofluorescence, and numerous highly autofluorescent lysosomal (lipofuscin) granules. Short term primary cell cultures from endoscopic biopsies provide a novel model to understand differences in colonic tissue autofluorescence at the glandular (crypt) and cellular levels. The differences between normal, hyperplastic, and adenomatous epithelial cells are attributed in part to differences in the intrinsic numbers of mitochondria and lysosomes. This suggests that the detection of colonic epithelial fluorescence alone, if possible, may be sufficient to differentiate benign (hyperplastic) from preneoplastic and neoplastic (adenomatous) colonic intramucosal lesions during in vivo fluorescence endoscopy. Furthermore, highly orange/red autofluorescent intracellular granules found only in dysplastic epithelial cells may serve as a potential biomarker.


Long-term outcome and progression of osteoarthritis in uncomplicated cases of cranial cruciate ligament rupture treated by tibial plateau leveling osteotomy in dogs.
The object of this study is to evaluate the long-term outcome of hind limb weight-bearing function and progression of stifle osteoarthritis (OA) after tibial plateau leveling osteotomy (TPLO). Groups were classified by the degree of cranial cruciate ligament (CrCL) damage and presence or absence of medial meniscus damage as macroscopically evaluated during surgery. Weight-bearing function was assessed via the peak vertical force (PVF), and OA progression was assessed via the radiographic OA score (OAS) preoperatively and 1, 3, 6, 12, 18, 24, and 36 months postoperatively. In all stifles, PVF was significantly higher within 6 months postoperatively than preoperatively, and this high ratio was maintained for 36 months. The OAS was significantly higher 24 months postoperatively than preoperatively in stifles with a partial CrCL tear, and significantly increased at each timepoint after 3 months postoperatively in stifles with complete CrCL rupture. The OAS remained consistently lower in stifles with a partial CrCL tear and no treatment of the medial meniscus than in stifles with complete rupture. Thus, after TPLO, the weight-bearing function improved in the early postoperative period and was maintained for as long as 36 months. Although OA progressed over time after TPLO, the progression was more gradual in stifles with partial tears than in those with complete rupture. Canine patients would benefit from earlier surgical intervention through development of technology that enables early detection of ligament degeneration.


Axillary apocrine carcinoma with benign apocrine tumours: a case report involving a pathological and immunohistochemical study and review of the literature.
Apocrine carcinoma is rare and often occurs in the axilla. This is the second apocrine carcinoma arising in bilateral axillae with associated apocrine hyperplasia to be reported. Because benign apocrine tumours may be precursors of cancer, this case was investigated immunohistochemically and histologically, and a literature (English and Japanese) review undertaken of cases with coexistent malignant and benign apocrine tumours in the axilla to elucidate the relation between apocrine carcinoma and benign apocrine tumours. Only four cases of axillary apocrine carcinoma with benign apocrine tumours were identified in the literature. In each case, benign apocrine hyperplasia was situated within and surrounding the adenocarcinomatous nests. Staining for epithelial membrane antigen revealed three patterns: (1) poorly differentiated tumour cells showing strong cytoplasmic staining; (2) combined luminal surface and cytoplasmic staining of glandular cells; and (3) a strongly positive lineal staining pattern at the luminal membrane surface, comprising one or two apocrine hyperplastic secretory cells. The basal lesions of apocrine hyperplasia were strongly positive for alpha smooth muscle actin, whereas the periphery of adenomatous lesions showed weaker positive staining, even though the periphery of adenocarcinomatous lesions was negative. All five apocrine carcinomas with benign apocrine tumours occurred in elderly Japanese men who had bilateral benign apocrine tumours even if affected by unilateral axillary apocrine carcinoma. The immunohistochemical results support the notion that apocrine hyperplasia is a precursor of cancer and that apocrine carcinoma, adenoma, and hyperplasia may be successive steps in the linear progression to carcinoma.


Temporal dynamics of the cellular, humoral and cytokine responses in chickens during primary and secondary infection with Salmonella enterica serovar Typhimurium.
Salmonella enterica serovar Typhimurium (S. Typhimurium) infections cause systemic disease in the young chick, whereas in the older chicken the infection is mainly restricted to the intestine. Chickens infected orally with S. Typhimurium (F98) at 6 weeks of age and re-infected 10 weeks later were monitored for antibody production, T-cell proliferation and production of selected cytokines (interferon-gamma, interleukin-1beta and transforming growth factor-beta(4)). A strong coordinated antigen-specific humoral and cellular immune response was temporally linked to resolution of the primary infection. Enhanced levels of mRNA encoding the cytokines, interleukin-1beta, transforming growth factor-beta(4) and interferon-gamma were also evident during early phases of primary infection. Secondary infection was restricted to the intestine and of shorter duration than primary infection. Splenic immune responses were not further enhanced by secondary infection; indeed, antigen-specific proliferation was significantly reduced at 1 day after secondary infection, which may be interpreted as the trafficking of reactive T cells from the spleen to the gut.


Speckle properties of the logarithmically transformed signal in optical coherence tomography.
We discuss the statistical properties of speckle of the logarithmically transformed signal in optical coherence tomography (OCT) both theoretically and experimentally. OCT signals of Intralipid solution with different volume particle concentrations ρ (correspondingly, scattering coefficient μ(s) ranges from 1.25 to 25.11 mm(-1)) were measured and analyzed under two different focusing conditions [numerical apertures (NAs) of the objective lens of 0.13 and 0.25]. We found that the effect of the speckle noise can be suppressed by displaying OCT images in the logarithmic scale and by using the objective lens with a higher NA. We also found that the speckle properties are correlated with the scattering properties of the sample, which may be used to characterize the scattering properties of biological tissue. The simulated OCT image and the in vitro OCT image of a rat liver are used as examples to demonstrate the feasibility of the method.


How different types of conceptual relations modulate brain activation during semantic priming.
Semantic priming, a well-established technique to study conceptual representation, has thus far produced variable fMRI results, both regarding the type of priming effects and their correlation with brain activation. The aims of the current study were (a) to investigate two types of semantic relations--categorical versus associative--under controlled processing conditions and (b) to investigate whether categorical and associative relations between words are correlated with response enhancement or response suppression. We used fMRI to examine neural correlates of semantic priming as subjects performed a lexical decision task with a long SOA (800 msec). Four experimental conditions were compared: categorically related trials (couch-bed), associatively related trials (couch-pillow), unrelated trials (couch-bridge), and nonword trials (couch-sibor). We found similar behavioral priming effects for both categorically and associatively related pairs. However, the neural priming effects differed: Categorically related pairs resulted in a neural suppression effect in the right MFG, whereas associatively related pairs resulted in response enhancement in the left IFG. A direct contrast between them revealed activation for categorically related trials in the right insular lobe. We conclude that perceptual and functional similarity of categorically related words may lead to response suppression within right-lateralized frontal regions that represent more retrieval effort and the recruitment of a broader semantic field. Associatively related pairs that require a different processing of the related target compared to the prime may lead to the response enhancement within left inferior frontal regions. Nevertheless, the differences between associative and categorical relations might be parametrical rather than absolutely distinct as both relationships recruit similar regions to a different degree.


Plastic ingestion by fulmars and shearwaters at Sable Island, Nova Scotia, Canada.
Plastic pollution is widespread in the marine environment, and plastic ingestion by seabirds is now widely reported for dozens of species. Beached Northern Fulmars, Great Shearwaters, Sooty Shearwaters and Cory's Shearwaters are found on Sable Island, Nova Scotia, Canada regularly, and they can be used to assess plastic pollution. All species except Cory's Shearwaters contained plastic debris in their gastrointestinal tracts. Northern Fulmars, Sooty Shearwaters and Great Shearwaters all showed high prevalence of plastic ingestion (>72%), with Northern Fulmars having the highest number and mass of plastics among the species examined. There was no difference in plastic ingestion between sexes or age classes. In all species user plastics made up the majority of the pieces found, with industrial pellets representing only a small proportion in the samples. Sable Island could be an important monitoring site for plastic pollution in Atlantic Canada.


Chemoenzymatic synthesis of 7-deaza cyclic adenosine 5'-diphosphate ribose analogues, membrane-permeant modulators of intracellular calcium release.
An optimized synthetic route to 7-deaza-8-bromo-cyclic adenosine 5'-diphosphate ribose (7-deaza-8-bromo-cADPR 3), an established cell-permeant, hydrolysis-resistant cyclic adenosine 5'-diphosphate ribose (cADPR) antagonist, is presented. Using NMR analysis, we found that 3 adopted a C-2' endo conformation in the N9-linked ribose and a syn conformation about the N9-glycosyl linkage, which are similar to that of cADPR. The synthetic route was also employed to produce 7-deaza-2'-deoxy-cADPR 4, a potential cell-permeant cADPR analogue. 3 and 4 were more stable to chemical hydrolysis, consistent with the observation that 7-deaza-cADPR analogues are more stable than their parent adenosine derivatives. 3 was also found to be stable to enzyme-mediated hydrolysis using CD38 ectoenzyme.


Factors affecting carcass value and profitability in early-weaned Simmental steers: II. Days on feed endpoints and sorting strategies.
In a 4-yr study, early-weaned Simmental steers (n = 192) of known genetics were individually fed to determine EPD, performance, and carcass measurements explaining variation in carcass value and profitability across incremental days on feed (DOF) when sorted by HCW, calculated yield grade (YG), or at their highest profit endpoint (BEST). Steers were weaned at 88.0 +/- 1.1 d of age, pen-fed a high-concentrate diet for 84.5 +/- 0.4 d, individually fed for 249.7 +/- 0.7 d, and slaughtered at 423.3 +/- 1.4 d of age. Carcass weight, YG, and marbling score (MS) were predicted using real-time ultrasound throughout the finishing period to calculate carcass value and profitability at 90, 60, 30 d preslaughter and under three individual sorting strategies. Sorting strategies included marketing the 25 and 50% heaviest HCW, the highest YG at d 60 and 30, or the remaining 25% at 0-d endpoints. Independent variables were year, weaning weight EPD, yearling weight EPD, marbling EPD, DMI, ADG, HCW, YG, and MS. Profit was quadratic in response to increased DOF; the greatest economic return was noted on d 30 (pre-slaughter). Final weight, DMI, HCW, MS, and YG increased (linear; P < 0.001) with additional DOF, and ADG and G:F decreased (linear; P < 0.001). Total cost of gain was quadratic (P < 0.001), and incremental cost of gain rose at an increasing rate (quadratic; P < 0.001) with increased DOF. With increasing DOF, HCW importance decreased from 58 to 21%; MS was variable, ranging from 18 to 23%; and YG and DMI were minor contributors to profit variation. Among sorting strategies, final BW and HCW were greater for BEST, whereas other measurements were similar. Sorting individuals by HCW, YG, or at BEST increased profitability 3.70 dollars, 2.52 dollars, or 30.65 dollars over the optimal group DOF endpoint (d 30). Retrospective analyses illustrated that sorting does not need to pinpoint each animal's profit optimum to result in economic gains; rather, increasing HCW and decreasing weight- and YG-related penalties improved profitability. Opportunities may exist with existing and new technology to uniformly allocate cattle into feeding and marketing groups, decrease overfeeding, and increase carcass value and profitability.


Regulation of CRE-mediated transcription in mouse brain by amphetamine.
Previous work has demonstrated that acute and chronic administration of amphetamine causes phosphorylation of the transcription factor CREB, the cAMP response element (CRE) binding protein, in striatum, a brain region important for the behavioral actions of the drug. To determine whether such phosphorylation is associated with changes in CREB transcriptional activity, we mapped beta-galactosidase (beta-gal) expression in a CRE-LacZ transgenic mouse, in which the beta-gal reporter is downstream of CRE sequences, following acute or chronic amphetamine administration. We found that acute amphetamine induced beta-gal expression in a relatively small number of brain regions, including nucleus accumbens (ventral striatum), amygdala, ventral tegmental area, and locus coeruleus. Chronic amphetamine generally produced greater changes in CRE-mediated transcription in most brain regions and induced CRE-transcription in several regions unaffected by acute drug exposure. Interestingly, amphetamine regulation of CRE activity differed dramatically between males and females. In nucleus accumbens, beta-gal expression colocalized predominantly with dynorphinergic neurons after acute amphetamine administration, while chronic administration induced beta-gal expression in both dynorphinergic and enkephalinergic neurons. In ventral tegmental area, acute and chronic amphetamine induced beta-gal expression mainly in dopaminergic neurons, while induction in the locus coeruleus occurred mainly in nonnoradrenergic neurons. This study identifies several brain regions where CRE-mediated transcription may play a key role in the development of neuronal plasticity associated with amphetamine administration.