Bigger, stronger, faster, fitter: the differences in physical qualities of school and academy rugby union players.
Limited research has compared the physical qualities of adolescent rugby union (RU) players across differing playing standards. This study therefore compared the physical qualities of academy and school Under-18 RU players. One-hundred and eighty-four (professional regional academy, n = 55 school, n = 129) male RU players underwent a physical testing battery to quantify height, body mass, strength (bench press and pull-up), speed (10, 20 and 40 m), 10 m momentum (calculated; 10 m velocity * body mass) and a proxy measure of aerobic fitness (Yo-Yo Intermittent Recovery Test Level 1; IRTL1). The practical significance of differences between playing levels were assessed using magnitude-based inferences. Academy players were taller (very likely small), heavier (likely moderate) and stronger (bench press possibly large; pull-up plus body mass likely small) than school players. Academy players were faster than school players over 20 and 40 m (possibly and likely small), although differences in 10 m speed were not apparent (possibly trivial). Academy players displayed greater 10 m momentum (likely moderate) and greater IRTL1 performance (likely small) than school players. These findings suggest that body size, strength, running momentum, 40 m speed and aerobic fitness contribute to a higher playing standard in adolescent rugby union.


Taste the Pain: The Role of TRP Channels in Pain and Taste Perception.
Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste-pain sensorial experiences are not fully understood. This article provides a narrative review of literature examining the role of TRP channels on taste and pain perception. Genomic variability in the TRPV1 gene has been associated with alterations in various pain conditions. Moreover, polymorphisms of the TRPV1 gene have been associated with alterations in salty taste sensitivity and salt preference. Studies of genetic variations in TRP genes or modulation of TRP pathways may increase our understanding of the shared biological mediators of pain and taste, leading to therapeutic interventions to treat many diseases.


Singlet oxygen generated by a new nonthermal atmospheric pressure air plasma device exerts a bactericidal effect on oral pathogens.
Oral diseases generally have certain bacteria associated with them. Non-thermal atmospheric pressure plasma (NTAP), generated at atmospheric pressure and room temperature, incorporates several molecules, including reactive oxygen species, that can inactivate various bacteria including oral pathogens. For this reason, several NTAP devices have been developed to treat oral diseases. Use of noble gases can enhance the bactericidal efficacy of NTAP, but this requires additional gas supply equipment. Therefore, a new NTAP device that employs ambient air as the working gas was developed. The device generates non-thermal atmospheric pressure air plasma. Here, the singlet oxygen (1O2) levels generated, their bactericidal effects on oral pathogens (Streptococcus mutans, Porphyromonas gingivalis, and Enterococcus faecalis), and the bacterial oxidative stress they imposed were measured. 1O2 generation in phosphatebuffered saline was assessed qualitatively using electron spin resonance (ESR) spectroscopy, and bactericidal efficacy was evaluated by counting of colony-forming units/mL. Bacterial oxidative stress was determined by measurement of hydrogen peroxide (H2O2) and superoxide dismutase (SOD) activity. ESR indicated that the level of 1O2 increased significantly and time-dependently, and was inversely correlated with distance, but the bactericidal effects were correlated only with treatment time (not distance) as H2O2 increased and SOD levels decreased, suggesting that the new device has potential applicability for treatment of oral disease.


Feasibility of dynamic T2 *-based oxygen-enhanced lung MRI at 3T.
To demonstrate proof-of-concept of a T2 *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers. We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R2 * and wash-in time normalized for breathing rate (τ-nBR). Inter-scanner reproducibility and intra-scanner repeatability were evaluated using intra-class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland-Altman analysis. Simulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R2 * at TE > 0.2 ms. Density correction improved signal fluctuations. Density-corrected mean PSE values, aligned with simulations, display TE-dependence, and an anterior-to-posterior PSE reduction trend at TE1 . ∆R2 * maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior-to-posterior R2 * increase. Mean T2 * values across 32 scans were 0.68 and 0.62 ms for pre- and post-O2 inhalation, respectively. Excellent or good agreement emerged from all intra-, inter-scanner and inter-rater variability tests for PSE and ∆R2 *. However, ICC values for τ-nBR demonstrated limited agreement between repeated measures. Our results demonstrate the feasibility of a T2 *-weighted method utilizing a dual-echo RF-spoiled gradient echo approach, simultaneously capturing PSE, ∆R2 * changes, and oxygen wash-in during free-breathing. The excellent or good repeatability and reproducibility on intra- and inter-scanner PSE and ∆R2 * suggest potential utility in multi-center clinical applications.


Towards precise classification of cancers based on robust gene functional expression profiles.
Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level. Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles. This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.


Molecular definition of heterogeneous nuclear ribonucleoprotein R (hnRNP R) using autoimmune antibody: immunological relationship with hnRNP P.
Serum from a patient showing symptoms related to autoimmunity was found to contain autoantibodies to the nuclear mitotic apparatus (NuMA) protein and to several novel nuclear antigens with estimated molecular weights of 40, 43, 72, 74 and 82 kDa. Using this serum for screening a human cDNA expression library a 2.5 kb cDNA clone was isolated which encoded the complete sequence of a protein of 633 amino acids. Sequence analysis revealed a modular structure of the protein: an acidic N-terminal region of approximately 150 amino acids was followed by three adjacent consensus sequence RNA binding domains located in the central part of the protein. In the C-terminal portion a nuclear localization signal and an octapeptide (PPPRMPPP) with similarity to a major B cell epitope of the snRNP core protein B were identified. This was followed by a glycine- and arginine-rich section of approximately 120 amino acids forming another type of RNA binding motif, a RGG box. Interestingly, three copies of a tyrosine-rich decapeptide were found interspersed in the RGG box region. The major in vitro translation product of the cDNA co-migrated in SDS-PAGE with the 82 kDa polypeptide that was recognized by autoantibodies. The structural motifs as well as the immunofluorescence pattern generated by anti-82 kDa antibodies suggested that the antigen was one of the proteins of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. Subsequently the 82 kDa antigen was identified as hnRNP R protein by its presence in immunoprecipitated hnRNP complexes and co-migration of the recombinant protein with this hitherto uncharacterized hnRNP constituent in two-dimensional gel electrophoresis. The concomitant autoimmune response to a hnRNP component of the pre-mRNA processing machinery and to NuMA, a protein engaged in mitotic events and reported to be associated with mRNA splicing complexes in interphase, may indicate physical and functional association of these antigens. Support for this notion comes from observations that concomitant or coupling of autoantibody responses to proteins which are associated with each other as components of subcellular particles are often found in autoimmune diseases.


Characteristics and impact of the most-cited palliative oncology studies from 1995 to 2016.
Palliative care, as a relatively young field within medicine, has increasingly used original research to validate and standardize its practice. In particular, palliative care has been incorporated into oncology to better address end-of-life decisions and care. The goal of this study is to identify seminal studies in the field of palliative oncology while more broadly characterizing the trends across the literature. The publication databases Scopus and Web of Science were queried using predefined search terms to identify palliative oncology studies published between 1995 and 2016. The 100 most-cited articles from the time periods 1995-2005 and 2006-2016 were selected and analysed for publication data and study content. Palliative oncology studies were found to primarily examine patients with multiple rather than single cancer types and rarely were randomized controlled trials. Early research topics of pain, symptoms, and survival studies have been replaced by the issues of access to care, healthcare utilization, and religion and spirituality. By identifying and analyzing notable studies in palliative oncology, we found areas of research that are commonly investigated or overlooked and identified model studies that highlight the need for additional disease-specific randomized control trials to provide high quality clinical evidence in the field.


Pathophysiology of stem cells in restenosis.
Recent evidence has shown that vascular function depends not only on cells within the vessels, but is also significantly modulated by circulating cells derived from the bone marrow. A number of studies indicate that an early reendothelialization by circulating endothelial precursors after vascular injury prevents excessive cell proliferation and restenosis. Conversely, other studies concluded that the homing of other cell fractions, consisting mainly of smooth muscle precursors, cause pathological remodelling. Different cell types have been identified and characterized so far as circulating precursors able to participate in vascular repair by homing and differentiating towards endothelial cells or smooth muscle cells. Among these, endothelial precursor cells, smooth muscle progenitor cells, mesenchymal stem cells and others have been described. The origins, the hierarchy, the role and the markers of these different cell populations are still controversial. Nevertheless, different strategies have been developed so far in animal models to induce the mobilization and the recruitment of stem cells to the injury site, based on physical training, hormone injection and application of stem cell-capturing coated stents. It should also be mentioned that the limited data currently available derived from clinical trials provide contrasting results about the effective role of vascular cell precursors in restenosis prevention, thus indicating that conclusions derived from studies in animal models cannot always be directly applied to humans and that caution should be used in the manipulation of circulating progenitor cells for therapeutic strategies.


High-resolution longitudinal N- and O-glycoprofiling of human monocyte-to-macrophage transition.
Protein glycosylation impacts the development and function of innate immune cells. The glycophenotypes and the glycan remodelling associated with the maturation of macrophages from monocytic precursor populations remain incompletely described. Herein, label-free porous graphitised carbon-liquid chromatography-tandem mass spectrometry (PGC-LC-MS/MS) was employed to profile with high resolution the N- and O-glycome associated with human monocyte-to-macrophage transition. Primary blood-derived CD14+ monocytes were differentiated ex vivo in the absence of strong anti- and proinflammatory stimuli using a conventional 7-day granulocyte-macrophage colony-stimulating factor differentiation protocol with longitudinal sampling. Morphology and protein expression monitored by light microscopy and proteomics validated the maturation process. Glycomics demonstrated that monocytes and macrophages display similar N-glycome profiles, comprising predominantly paucimannosidic (Man1-3GlcNAc2Fuc0-1, 22.1-30.8%), oligomannosidic (Man5-9GlcNAc2, 29.8-35.7%) and α2,3/6-sialylated complex-type N-glycans with variable core fucosylation (27.6-39.1%). Glycopeptide analysis validated conjugation of these glycans to human proteins, while quantitative proteomics monitored the glycoenzyme expression levels during macrophage differentiation. Significant interperson glycome variations were observed suggesting a considerable physiology-dependent or heritable heterogeneity of CD14+ monocytes. Only few N-glycome changes correlated with the monocyte-to-macrophage transition across donors including decreased core fucosylation and reduced expression of mannose-terminating (paucimannosidic-/oligomannosidic-type) N-glycans in macrophages, while lectin flow cytometry indicated that more dramatic cell surface glycan remodelling occurs during maturation. The less heterogeneous core 1-rich O-glycome showed a minor decrease in core 2-type O-glycosylation but otherwise remained unchanged with macrophage maturation. This high-resolution glycome map underpinning normal monocyte-to-macrophage transition, the most detailed to date, aids our understanding of the molecular makeup pertaining to two vital innate immune cell types and forms an important reference for future glycoimmunological studies.


Prevention effectiveness of rollover protective structures--Part I: Strategy evolution.
This is the first of three articles that evaluate the health and economic consequences of the use of rollover protective structures (ROPS) on agricultural tractors. The effectiveness of ROPS delivered through alternative intervention strategies is the subject of the three-part study. This part of the study reviews and assesses the evolution of interventions that are known to prevent injuries incurred as a result of tractor overturns. The method used is historical analysis framed against a prevention effectiveness model used by the U.S. Centers for Disease Control and Prevention. Two intervention strategies were found to be potentially effective in preventing injuries from tractor overturns. These strategies are either to install a ROPS on tractors that lack a ROPS or to replace the tractor with one that has a ROPS already mounted. Other prevention factors include the effectiveness and use of seatbelts and the integrity of the ROPS system during an overturn.


Long-term modulation by postnatal oxytocin of the alpha 2-adrenoceptor agonist binding sites in central autonomic regions and the role of prenatal stress.
The aim of this work was to evaluate whether oxytocin administered in male rats subcutaneously early in life in the absence or presence of food restriction during pregnancy has life-long effects on the alpha(2)-agonist binding sites in the nucleus of the solitarii tract (NTS), in the hypothalamus and the amygdala, as evaluated by quantitative receptor autoradiography. Maternal food restriction alone increased the affinity of the alpha(2)-agonist [(3)H]UK14.304 binding sites exclusively in the NTS. In offspring from ad libitum fed dams, oxytocin treatment significantly increased the density of alpha(2)-agonist binding sites in the NTS and in the hypothalamus. The K(d) value of the alpha(2)-agonist binding sites in the hypothalamus of these rats, but not in the other regions studied, was also significantly increased. In offspring from food-restricted dams, oxytocin treatment produced a significant increase of the B(max) values in the hypothalamus and the amygdala and the K(d) value of the alpha(2)-agonist binding sites in the NTS of these rats also was selectively and significantly increased. These results suggest that a postnatal, oxytocin-induced increase of regional alpha(2)-adrenoceptor function can be seen in adulthood by a persistent, regionally selective increase in the density of central alpha(2)-adrenoceptor agonist binding sites, in the absence of an affinity change in the NTS. Such a regional increase of alpha(2)-adrenoceptor signalling in adulthood may contribute to the anti-stress action of postnatal oxytocin. By contrast, after prenatal stress, the potential increase in alpha(2)-adrenoceptor signalling takes place via selective increases of density with no changes of affinity of the alpha(2)-agonist binding sites in the hypothalamus and the amygdala.


Diatom evidence of 20th century ecosystem change in Lake Baikal, Siberia.
Lake Baikal has been experiencing limnological changes from recent atmospheric warming since the 1950s, with rising lake water temperatures, reduced ice cover duration and reduced lake surface-water mixing due to stronger thermal stratification. This study uses lake sediment cores to reconstruct recent changes (c. past 20 years) in Lake Baikal's pelagic diatom communities relative to previous 20th century diatom assemblage records collected in 1993 and 1994 at the same locations in the lake. Recent changes documented within the core-top diatom records agree with predictions of diatom responses to warming at Lake Baikal. Sediments in the south basin of the lake exhibit clear temporal changes, with the most rapid occurring in the 1990's with shifts towards higher abundances of the cosmopolitan Synedra acus and a decline in endemic species, mainly Cyclotella minuta and Stephanodiscus meyerii and to a lesser extent Aulacoseira baicalensis and Aulacoseira skvortzowii. The north basin, in contrast, shows no evidence of recent diatom response to lake warming despite marked declines in north basin ice cover in recent decades. This study also shows no diatom-inferred evidence of eutrophication from deep water sediments. However, due to the localised impacts seen in areas of Lake Baikal's shoreline from nutrient pollution derived from inadequate sewage treatment, urgent action is vital to prevent anthropogenic pollution extending into the open waters.


Syndrome of pleural and retrosternal "bridging" fibrosis and retroperitoneal fibrosis in patients with asbestos exposure.
Two case histories are described of pleural and anterior mediastinal fibrosis presenting as a continuous fibrotic process with thick parietal pleural plaques extending from one pleura to the contralateral pleura through the retrosternal area, and with retroperitoneal fibrosis. Follow-up over 4 years in one case demonstrated rapid progression of disease, with pleural fibrosis preceding retrosternal and retroperitoneal fibrosis. Histopathological analysis in both cases showed non-tumoral fibrosis with broad fibrous bundles surrounding fibroblasts (and lymphocytes in one case). Possible causes such as infections and exposure to ergot derivatives were excluded. Both patients had been slightly or moderately exposed to asbestos. These cases represent an unusual new presentation of pleural and retrosternal fibrosis extending beyond the anatomical structures and associated with retroperitoneal fibrosis.


Live-Chat Support for People Bereaved by Suicide.
Background: People bereaved by suicide often face isolation, complicated grief, and increased suicide risk. Aims: We aimed to explore how live-chat can support survivors in their bereavement process. Method: A thematic analysis was carried out on 30 live-chat conversations through the software ATLAS.ti8. Transcripts were retrieved from a major Italian association providing online support. The users had different ages (18-60 years), degrees of kinship with the deceased (blood-related and not), and time distance from the loss (between 48 hr and 10 years). Results: Five themes were identified: meaning-making, reactions to the loss, resources, needs, and interactions with the operator. Survivors used the live-chat as a safe space in which to disclose nonsocially desirable details and to make sense of suicide through the reconstruction of events and the deceased's motivations. Given the limited social resources and the dissatisfaction with the available formal support, users resorted to justification, rationalization, or faith and found support and reassurance in the live chats. Limitations: Some conversations were fragmented and lacked detailed information on the users. Conclusion: Because of their anonymity and accessibility, live-chats represent a valid first-line form of support, from which survivors may obtain useful information and start a meaning-making process.


Caregiver behaviors and resources influence child height-for-age in rural Chad.
The purpose of this study was to identify caregiver characteristics that influence child nutritional status in rural Chad, when controlling for socioeconomic factors. Variables were classified according to the categories of a UNICEF model of care: caregiving behaviors, household food security, food and economic resources and resources for care and health resources. Sixty-four households with 98 children from ages 12 to 71 mo were part of this study. Caregivers were interviewed to collect information on number of pregnancies, child feeding and health practices, influence on decisions regarding child health and feeding, overall satisfaction with life, social support, workload, income, use of income, and household food expenditures and consumption. Household heads were questioned about household food production and other economic resources. Caregiver and household variables were classified as two sets of variables, and separate regression models were run for each of the two sets. Significant predictors of height-for-age were then combined in the same regression model. Caregiver influence on child-feeding decisions, level of satisfaction with life, willingness to seek advice during child illnesses, and the number of individuals available to assist with domestic tasks were the caregiver factors associated with children's height-for-age. Socioeconomic factors associated with children's height-for-age were the amount of harvested cereals, the sources of household income and the household being monogamous. When the caregiver and household socioeconomic factors were combined in the same model, they explained 54% of the variance in children's height-for-age, and their regression coefficients did not change or only slightly increased, except for caregiver's propensity to seek advice during child illnesses, which was no longer significant. These results indicate that caregiver characteristics influence children's nutritional status, even while controlling for the socioeconomic status of the household.


Induction of immunogenic cell death in cancer cells by a photoactivated platinum(IV) prodrug.
The platinum(IV) prodrug trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1) is stable and non-toxic in the dark, but potently cytotoxic to cancer cells when irradiated by visible light, including cisplatin-resistant cells. On irradiation with visible light, it generates reactive Pt(II) species which can attack DNA, and produces reactive oxygen species (ROS) and reactive nitrogen species (RNS) which exert unusual effects on biochemical pathways. We now show that its novel mechanism of action includes induction of immunogenic cell death (ICD). Treatment of cancer cells with 1 followed by photoirradiation with visible light induces calreticulin (CRT) expression at the surface of dying cancer cells. This is accompanied by release of high mobility group protein-1B (HMGB1) and the secretion of ATP. Autophagy appears to play a key role in this chemotherapeutically-stimulated ICD. The observed uneven distribution of ecto-CRT promotes phagocytosis, confirmed by the observation of engulfment of photoirradiated CT26 colorectal cancer cells treated with 1 by J774.A1 macrophages. The photoactivatable prodrug 1 has a unique mechanism of action which distinguishes it from other platinum drugs due to its immunomodulating properties, which may enhance its anticancer efficacy.


Doping induced dielectric anomaly below the Curie temperature in molecular ferroelectric diisopropylammonium bromide.
A dielectric anomaly induced by doping has been observed at about 340 K in chlorine-doped diisopropylammonium bromide. The dielectric anomaly has a switchable behaviour, which indicates potential applications on switches and sensors. Temperature-dependent Raman spectrum, X-ray diffraction and differential scanning calorimetry do not show any anomaly around the dielectric anomaly temperature, which prove that the dielectric anomaly does not come from structure phase transition and has no specific heat variety. It is assumed that this dielectric anomaly can be attributed to the freezing of ferroelectric domain walls induced by the pinning of point defects.


Molecular dynamics study of the M412 intermediate of bacteriorhodopsin.
Molecular dynamics simulations have been carried out to study the M412 intermediate of bacteriorhodopsin's (bR) photocycle. The simulations start from two simulated structures for the L550 intermediate of the photocycle, one involving a 13-cis retinal with strong torsions, the other a 13,14-dicis retinal, from which the M412 intermediate is initiated through proton transfer to Asp-85. The simulations are based on a refined structure of bR568 obtained through all-atom molecular dynamics simulations and placement of 16 waters inside the protein. The structures of the L550 intermediates were obtained through simulated photoisomerization and subsequent molecular dynamics, and simulated annealing. Our simulations reveal that the M412 intermediate actually comprises a series of conformations involving 1) a motion of retinal; 2) protein conformational changes; and 3) diffusion and reconfiguration of water in the space between the retinal Schiff base nitrogen and the Asp-96 side group. (1) turns the retinal Schiff base nitrogen from an early orientation toward Asp-85 to a late orientation toward Asp-96; (2) disconnects the hydrogen bond network between retinal and Asp-85 and tilts the helix F of bR, enlarging bR's cytoplasmic channel; (3) adds two water molecules to the three water molecules existing in the cytoplasmic channel at the bR568 stage and forms a proton conduction pathway. The conformational change (2) of the protein involves a 60 degrees bent of the cytoplasmic side of helix F and is induced through a break of a hydrogen bond between Tyr-185 and a water-side group complex in the counterion region.


A low calorie morning meal prevents the decline of hepatic glycogen stores: a pilot in vivo (13)C magnetic resonance study.
Previous studies have reported a meal-induced rise in hepatic glycogen stores from baseline levels following a fast and it is generally assumed that glycogen levels rise steadily following meals throughout the day. However, measurements are normally taken in conditions that are not typical of the Western breakfast, which is relatively carbohydrate rich with a lower calorific content than most experimental test meals. As such, little is known about the normal metabolic response to a realistic, low calorie morning meal. Therefore, the aim of this pilot study was to evaluate the effects of a low dose oral glucose intake on hepatic glycogen levels following an overnight fast in healthy subjects. Glycogen levels were monitored in vivo using (13)C Magnetic Resonance Spectroscopy at baseline and hourly for 4 hours following either a 50 g glucose drink (773 kJ) or a control drink (0 kJ) given over two different visits. During the control visit hepatic glycogen levels decreased throughout the experiment with statistically significant decreases from baseline at 190 minutes (P < 0.05) and 250 minutes (P < 0.05). By contrast, the low dose glucose intake maintained glycogen concentrations with no significant decrease from baseline over 4 hours. A comparison between visits revealed that mean glycogen concentrations were significantly greater during the glucose visit (control visit, AUC = 218 ± 39 mol L(-1) min(-1); glucose visit, AUC = 305 ± 49 mol L(-1) min(-1); P < 0.05). Liver volume decreased significantly from baseline at 180 minutes (P < 0.05) post consumption in both groups, with no significant difference found between visits. Gastric content volumes were significantly higher for the glucose visit immediately following consumption (P < 0.001) and at 60 minutes (P = 0.007) indicating slower gastric emptying for the glucose compared with the control. In conclusion, following an overnight fast, a low dose oral glucose challenge prevents a reduction in hepatic glycogen content but does not increase it above fasted levels.


The motor-cognitive model of motor imagery: Evidence from timing errors in simulated reaching and grasping.
Motor imagery represents an important but theoretically underdeveloped area of research in psychology. The motor-cognitive model of motor imagery was presented, and contrasted with the currently prevalent view, the functional equivalence model. In 3 experiments, the predictions of the two models were pitted against each other through manipulations of task precision and the introduction of an interference task, while comparing their effects on overt actions and motor imagery. In Experiments 1a and 1b, the motor-cognitive model predicted an effect of precision whereby motor imagery would overestimate simulated movement times when a grasping action involved a high level of precision; this prediction was upheld. In Experiment 2, the motor-cognitive model predicted that an interference task would slow motor imagery to a much greater extent than it would overt actions; this prediction was also upheld. Experiment 3 showed that the effects observed in the previous experiments could not be due to failures to match the motor imagery and overt action tasks. None of the above results were explainable by either a strong version of the functional equivalence model, or any reasonable adaptations thereof. It was concluded that the motor-cognitive model may represent a theoretically viable advance in the understanding of motor imagery. (PsycINFO Database Record


Prevalence of non-suicidal self-harm and service contact in England, 2000-14: repeated cross-sectional surveys of the general population.
The number of people presenting to hospital emergency departments after self-harming has increased in England. However, most people who self-harm do not present to hospitals, so whether this rise reflects an increase in the prevalence of self-harm in the community is unknown. Also unknown is whether the prevalence of non-suicidal self-harm (NSSH) or suicidal self-harm, or both, has increased. We aimed to establish temporal trends in the prevalence of NSSH in England. We analysed data from participants in the 2000 (n=7243), 2007 (n=6444), and 2014 (n=6477) Adult Psychiatric Morbidity Surveys of the general population, selecting those aged 16-74 years and living in England. We used weighted data and controlled for complex survey design. We generated temporal trends in lifetime prevalence and methods of, and motivations for, NSSH, and consequent service contact. We used multiple variable logistic regression analyses to investigate factors associated with service contact. The prevalence of self-reported lifetime NSSH increased from 2·4% (95% CI 2·0-2·8) in 2000, to 6·4% (5·8-7·2) in 2014. Increases in prevalence were noted in both sexes and across age groups-most notably in women and girls aged 16-24 years, in whom prevalence increased from 6·5% (4·2-10·0) in 2000, to 19·7% (15·7-24·5) in 2014. The proportion of the population reporting NSSH to relieve unpleasant feelings of anger, tension, anxiety, or depression increased from 1·4% (95% CI 1·0-2·0) to 4·0% (3·2-5·0) in men and boys, and from 2·1% (1·6-2·7) to 6·8% (6·0-7·8) in women and girls, between 2000 and 2014. In 2014, 59·4% (95% CI 54·7-63·9) of participants who had engaged in NSSH reported no consequent medical or psychological service contact, compared with 51·2% (42·2-60·0) in 2000 and 51·8% (47·3-56·4) in 2007. Male participants and those aged 16-34 years were less likely to have contact with health services than were female participants and older people. The prevalence of NSSH has increased in England, but resultant service contact remains low. In 2014, about one in five female 16-24-year-olds reported NSSH. There are potential lifelong implications of NSSH, such as an increased frequency of suicide, especially if the behaviours are adopted as a long-term coping strategy. Self-harm needs to be discussed with young people without normalising it. Young people should be offered help by primary care, educational, and other services to find safer ways to deal with emotional stress. NHS Digital, English Department of Health and Social Care, and the National Institute for Health Research.


The Pediatric AIDS Corps: a 5-year evaluation.
The Baylor College of Medicine International Pediatric AIDS Initiative at Texas Children's Hospital created a global health corps named the Pediatric AIDS Corps (PAC) in June 2005. This report provides descriptive details and outputs for PAC over its first 5 years. Demographic data were gathered about PAC physicians employed from July 2006 to June 2011. A 21-question survey was used to query PAC physicians about their experiences in the program. Data concerning clinical experiences and educational programs also were reviewed. A total of 128 physicians were employed with PAC. The median duration served was 22.7 months. Eighty-seven percent indicated that experience affected their future career choice, with half continuing to work with children and families living in resource-limited areas after they left PAC. Patient care was identified as the most rewarding part of their work (73%), whereas deaths (27%) were the most difficult. Baylor College of Medicine International Pediatric AIDS Initiative enrollment of HIV-infected children and adolescents into care and treatment increased from 6107 to 103 731 with the addition of PAC physicians. Approximately 500 local health care professionals per quarter benefited from HIV clinical attachments that were not available before PAC arrival. PAC physicians visited outreach sites providing in-depth HIV mentoring of local health care professionals, leading to 37% of the sites becoming self-sufficient. The positive evaluation by the PAC and the scale-up of clinical and educational programs support the recent calls for the development of a national global health corps program.


Meniscus Extrusion, Radial Tears, and Root Tears.
Management of meniscal radial and root tears and extrusion is complex and has changed significantly over recent years. It is important to provide a comprehensive overview of the management of radial and root tears and meniscal extrusion and be aware of the currently available evidence on repair techniques, rehabilitation, and outcomes following radial and root repairs.


Light-enhanced free radical formation and trypanocidal action of gentian violet (crystal violet).
Transmission of Chagas' disease by transfusion of blood containing Trypanosoma cruzi has often been reported, and gentian violet, a triarylmethane dye, is widely used by blood banks in attempts to eliminate such transmission. In a study of intact trypanosomes, gentian violet was found to undergo a one-electron reduction to produce a carbon-centered free radical as demonstrated by electron spin resonance spectroscopy. Either reduced nicotinamide adenine dinucleotide or the reduced dinucleotide phosphate could serve as a source of reducing equivalents for the production of this free radical by homogenates of Trypanosoma cruzi. The formation of this free radical, and the trypanocidal action of gentian violet, were enhanced by light. The enhanced free radical formation may be the basic cause of the selective toxicity of gentian violet to Trypanosoma cruzi.


Determination of venous blood flow velocity using digital videomicroscopy (A short methodical communication).
There is a limited number of methods to measure blood flow velocity in small veins. A cheap and simple new videomicroscopic method developed in our laboratories is described in the paper. A stretch of the saphenous vein of the rat was exposed by careful micropreparation on the thigh of anesthetized animals. Bolus amount (approx. 5 μl) of saline was infused into a small side branch through a microcannula to dilute flowing blood. Videomicroscopic picture of the vein was then taken of the exposed upstream stretch of the vein. Serial pictures were digitized and analyzed using macro functions of the Image J software. Sensitive areas of serial pictures were selected and fitted. Consecutive pictures were subtracted from each other to better characterize their alteration in-between frames. Greyscale intensity values measured at different points of the inner diameter were averaged for each point of the vessel axis. Cross-correlations along the axis were then computed for consecutive frames with delays of 40, 80, 120 and 160 msec. Pixel offsets producing cross-correlation maxima were determined and used to compute mean flow velocity. Combination of digital subtraction and cross-correlation computations yielded easily identifiable maximums. Mean flow velocities could be determined with limited uncertainty. The described technique gives a cheap, simple and reproducible mean to determine mean blood flow velocities in small veins in anesthetized animals, where other current techniques (ultrasonography, laser-Doppler, fluorescently labelled red cell movement) are either expensive or can be applied with difficulty only.


Binding of double-stranded DNA by Escherichia coli RecA protein monitored by a fluorescent dye displacement assay.
We have developed a new assay to characterize the double-stranded DNA (dsDNA) binding properties of RecA protein. This assay is based on measurement of changes in the fluorescence of a 4',6-diamidino-2-phenylindole (DAPI)-dsDNA complex upon RecA protein binding. The binding of RecA protein to a complex of DAPI and dsDNA results in displacement of the bound DAPI, producing a decrease in the observed fluorescence. DAPI displacement is dependent on both RecA protein and ATP; dATP and, to a lesser extent, UTP and dCTP also support the DAPI displacement reaction, but dGTP, GTP, dITP and TTP do not. Binding stoichiometry for the RecA protein-dsDNA complex measured by DAPI displacement is 3 bp per RecA protein monomer in the presence of ATP. These results, taken together with data for mutant RecA proteins, suggest that this DAPI displacement assay monitors formation of the high affinity DNA binding state of RecA protein. Since this state of RecA protein defines the form of the nucleoprotein filament that is active in DNA strand exchange, these findings raise the possibility that the RecA protein-dsDNA filament may possess a homologous pairing capacity.


Spin Order and Phase Transitions in Chains of Polariton Condensates.
We demonstrate that multiply coupled spinor polariton condensates can be optically tuned through a sequence of spin-ordered phases by changing the coupling strength between nearest neighbors. For closed four-condensate chains these phases span from ferromagnetic (FM) to antiferromagnetic (AFM), separated by an unexpected crossover phase. This crossover phase is composed of alternating FM-AFM bonds. For larger eight-condensate chains, we show the critical role of spatial inhomogeneities and demonstrate a scheme to overcome them and prepare any desired spin state. Our observations thus demonstrate a fully controllable nonequilibrium spin lattice.


Optical properties of fluids for 248 and 193 nm immersion photolithography.
We present measured values of the refractive index, thermo-optic coefficient, and absorption coefficient of a number of common organic solvents and aqueous inorganic solutions that may have application in immersion photolithography at 248 or 193 nm wavelengths. The measurements were performed with a laser-based Hilger-Chance refractometer system whose design and operation are described. The optical properties of the sample fluids are compared with those of water, the currently favored immersion medium, and we discuss the potential for finding higher-index fluids that will be suitable for this application.


Dramatic decline of serogroup C meningococcal disease incidence in Catalonia (Spain) 24 months after a mass vaccination programme of children and young people.
The objective of this study was to evaluate the effectiveness of a mass vaccination programme carried out in Catalonia (Spain) in the last quarter of 1997 in response to an upsurge of serogroup C meningococcal disease (SCMD). Vaccination coverage in the 18 month to 19 years age group was investigated by means of a specific vaccination register. Vaccination effectiveness was calculated using the prospective cohort method. Cases of SCMD were identified on the basis of compulsory reporting and microbiological notification by hospital laboratories. Vaccination histories were investigated in all cases. Unadjusted and age adjusted vaccination effectiveness referred to the time of vaccination and the corresponding 95% confidence intervals (CI) were estimated at 6, 12, 18 and 24 months of follow up. All population aged 18 months to 19 years of Catalonia. A total of seven cases of SCMD were detected at six months of follow up (one in the vaccinated cohort), 12 cases at 12 months (one in the vaccinated cohort), 19 cases at 18 months (two in the vaccinated cohort) and 24 at 24 months (two in the vaccinated cohort). The age adjusted effectiveness was 84% (95%CI 30, 97) at six months, 92% (95%CI 63, 98) at 12 months, 92% (95% CI 71, 98) at 18 months and 94% (95%CI 78, 98) at 24 months. In the target population, cases have been reduced by more than two thirds (68%) two years after the vaccination programme. In the total population the reduction was 43%. Vaccination effectiveness has been high in Catalonia, with a dramatic reduction in disease incidence in the vaccinated cohort accompanied by a relevant reduction in the overall population. Given that vaccination coverage was only 54.6%, it may be supposed that this vaccination effectiveness is attributable, in part, to the herd immunity conferred by the vaccine.


Effects of nonanticoagulant heparin on cardiovascular and hepatocellular function after hemorrhagic shock.
Although heparinization of animals before hemorrhage improves cell and organ function, the potent anticoagulant activity of conventional heparin sodium precludes its potential clinical use. To determine whether a novel nonanticoagulant heparin, GM1892, would have any beneficial effects on cardiovascular and hapatocellular functions and would decrease susceptibility to sepsis after hemorrhage, laparotomy was performed on rats (i.e., trauma induced), after which they were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleedout volume was returned in the form of Ringer lactate solution (RL). The rats were then resuscitated with three times the volume of shed blood with RL over 45 min, followed by infusion of two times RL plus GM1892 (7 mg/kg body wt; approximately 2% the anticoagulant activity of regular heparin) of saline over 60 min. At 2 and 4 h after the completion of resuscitation, cardiac output, hepatocellular function, and microvascular blood flow were determined. The results indicated that cardiac output, hepatocellular function, and microvascular blood flow in the liver, spleen, and small intestine decreased significantly after hemorrhage and resuscitation. Administration of GM1892, however, restored these parameters. The morphological abnormality observed after hemorrhage in the liver, kidney, and small gut was also attenuated with GM1892 treatment. Moreover, GM1892 normalized the elevated plasma prostaglandin E2 levels. Sepsis was induced in additional rats by cecal ligation and puncture (CLP) 20 h after hemorrhage, and the necrotic cecum was excised 10 h thereafter. GM1892 treatment significantly decreased mortality after CLP and cecal excision. Thus GM1892 appears to be a useful adjunct to fluid resuscitation, since it restores the depressed cardiovascular responses and decreases susceptibility to sepsis after trauma and hemorrhage.


Protein-protein interaction specificity is captured by contact preferences and interface composition.
Large-scale computational docking will be increasingly used in future years to discriminate protein-protein interactions at the residue resolution. Complete cross-docking experiments make in silico reconstruction of protein-protein interaction networks a feasible goal. They ask for efficient and accurate screening of the millions structural conformations issued by the calculations. We propose CIPS (Combined Interface Propensity for decoy Scoring), a new pair potential combining interface composition with residue-residue contact preference. CIPS outperforms several other methods on screening docking solutions obtained either with all-atom or with coarse-grain rigid docking. Further testing on 28 CAPRI targets corroborates CIPS predictive power over existing methods. By combining CIPS with atomic potentials, discrimination of correct conformations in all-atom structures reaches optimal accuracy. The drastic reduction of candidate solutions produced by thousands of proteins docked against each other makes large-scale docking accessible to analysis. CIPS source code is freely available at http://www.lcqb.upmc.fr/CIPS. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Effectiveness of a Facebook-Delivered Physical Activity Intervention for Postpartum Women: A Randomized Controlled Trial.
Facebook has over 1.8 billion users and offers unique opportunities for health intervention delivery due to its popularity, flexibility, high engagement, and social connectedness. This study aimed to determine the effectiveness of the Mums Step It Up (MSIU) Facebook app, a team-based, 50-day physical activity intervention for postpartum women. A total of 120 postpartum women were recruited and randomly allocated to 1 of 3 conditions: MSIU (n = 41), pedometer only (n = 39), and control (n = 40). Assessments were completed at baseline, 6 weeks, and 6 months. Primary outcomes were accelerometer moderate to vigorous physical activity and self-reported walking. Analyses were undertaken on an intention to treat basis using random effects mixed modeling (P ≤ .05). Compliance and engagement with the MSIU app were analyzed, descriptively. There were no significant differences in changes in moderate to vigorous physical activity (P = .81, 6 wk; P = .91, 6 mo) or self-reported walking (P = .55, 6 wk; P = .90, 6 mo) across the 3 conditions. High engagement with the MSIU app was evident, with participants on average visiting the app 26 times and logging steps for 48/50 days. Although engagement with the MSIU app was promising, the nonsignificant results suggest that further work needs to be done to enhance efficacy for postpartum women.


Insulin and insulinlike growth factor receptors and responses in cultured human muscle cells.
Specific receptors for insulinlike growth factors I and II (IGF-I and IGF-II) were found on cultured human myoblasts and myotubes. In contrast, myotubes but not myoblasts specifically bound insulin and were stimulated by nanomolar concentrations of insulin to take up deoxyglucose. In addition, in myoblasts, physiological concentrations of IGF-I and -II and, to a lesser extent, insulin stimulated two- to threefold the uptake of the nonmetabolizable amino acid analogue methylaminoisobutyric acid (MAIB). In myotubes, uptake of MAIB was stimulated preferentially by IGF-I. Monoclonal antibodies that preferentially recognize either the insulin receptor or the IGF-I receptor were utilized to examine which receptors mediated the biological effects of these hormones. The effects of insulin on both myoblasts and myotubes appeared to be mediated in part by the insulin receptor and in part by the IGF-I receptor. In myotubes, the effects of IGF-I and -II both appeared to be mediated through the IGF-I receptor. In myoblasts, the effects of the two IGFs appeared to be in part mediated by the IGF-I receptor and in part mediated by either the IGF-II receptor or another type of IGF-I receptor. The present results suggest that cultured human muscle cells provide a useful model system in which to study the biological actions of insulin and the IGFs.


Simultaneous Determination of Soyasaponins and Isoflavones in Soy (Glycine max L.) Products by HPTLC-densitometry-Multiple Detection.
A new high-throughput method was developed for the simultaneous analysis of isoflavones and soyasaponnins in Soy (Glycine max L.) products by high-performance thin-layer chromatography with densitometry and multiple detection. Silica gel was used as the stationary phase and ethyl acetate:methanol:water:acetic acid (100:20:16:1, v/v/v/v) as the mobile phase. After chromatographic development, multi-wavelength scanning was carried out by: (i) UV-absorbance measurement at 265 nm for genistin, daidzin and glycitin, (ii) Vis-absorbance measurement at 650 nm for Soyasaponins I and III, after post-chromatographic derivatization with anisaldehyde/sulfuric acid reagent. Validation of the developed method was found to meet the acceptance criteria delineated by ICH guidelines with respect to linearity, accuracy, precision, specificity and robustness. Calibrations were linear with correlation coefficients of >0.994. Intra-day precisions relative standard deviation (RSD)% of all substances in matrix were determined to be between 0.7 and 0.9%, while inter-day precisions (RSD%) ranged between 1.2 and 1.8%. The validated method was successfully applied for determination of the studied analytes in soy-based infant formula and soybean products. The new method compares favorably to other reported methods in being as accurate and precise and in the same time more feasible and cost-effective.


Plk1 activation by Ste20-like kinase (Slk) phosphorylation and polo-box phosphopeptide binding assayed with the substrate translationally controlled tumor protein (TCTP).
The mitotic protein kinase Plk1 catalyzes events associated with centrosome maturation, kinetocore function, spindle formation, and cytokinesis and is a target for anticancer drug design. It is composed of a N-terminal kinase domain and a C-terminal polo-box domain (PBD). The PBD domain serves to localize the kinase on cognate phosphorylated substrates, and this binding relieves the inhibition of the kinase by the PBD. Similar to many protein kinases, Plk1 is activated by phosphorylation on a threonine residue, Thr210, in the activation segment. In this work, we describe expression in Escherichia coli cells and purification of full-length Plk1 in quantities suitable for structural studies and use this material for quantitative characterization of the activation events with the substrate translationally controlled tumour protein (TCTP). The presence of the PBD-binding phosphopeptide enhances phosphorylation by the activating Ste20-like kinase (Slk). Native Plk1 exhibits a basal catalytic efficiency k cat/ K(M) of 9.9 x 10 (-5) s (-1) microM (-1). Association with a polo-box-binding phosphopeptide increased the catalytic efficiency by 11x largely through an increase in k(cat) with no change in K(M). Phosphorylation by Slk increases catalytic efficiency by 202x with a 2.3-fold reduction in K(M) and 88-fold increase in k(cat). Phosphorylation and the presence of the PBD-binding phosphopeptide result in an increase in catalytic efficiency of 1515x with a 2.3-fold decrease in K(M) and a 705-fold increase in k(cat) over the unmodified Plk1. Knowledge of kinase regulatory mechanisms and the structures of the Plk1 individual domains has allowed for a model to be proposed for these activatory events.


Structural, electronic and magnetic properties of Cu(II) complexes of 2-substituted tropones bearing a ferrocenyl group at 5-position.
Heterotrinuclear Fe(II)-Cu(II)-Fe(II) complexes [Cu(FcTropOMe)(2)(H(2)O)(2)](OTf)(2) (FcTropOMe = 5-ferrocenyl-2-methoxytropone) (1), [Cu(FcTropNEt(2))(2)](OTf)(2) (FcTropNEt(2) = 2-(N,N-diethylamino)-5-ferrocenyltropone) (2) and [Cu(FcTropNEt)(2)] (FcTropNEt = 2-(N-ethylamino)-5-ferrocenyltroponate) (3) were synthesized. In addition, a hexafluorophosphate salt of heterotrinuclear Fe(III)-Cu(II)-Fe(III) complex [Cu(FcTropNEt)(2)](2+) (3(2+)) was successfully obtained as single crystals by electrochemical oxidation of 3. By comparing the X-ray structures and absorption spectra of dicationic complexes 1 and 2, the 2-(diethylamino)tropone ligand was found to induce a greater intramolecular charge transfer (CT) from ferrocenyl to tropone-Cu(II) moieties than the 2-methoxytropone ligand. On the other hand, 3(2+) showed a broad CT band in the near-infrared (NIR) region similar to 2, which can be assigned to a transition from troponato-Cu(II) to ferrocenium moieties. As for the magnetic properties of 3(2+)(PF(6)(-))(2), measurements of temperature dependence of magnetic susceptibility and ESR on the solid state and in solution revealed the presence of a strong ferromagnetic interaction (J(Fe-Cu) = +12.0 cm(-1)) between the low spin Fe(III) ion with S = 1/2 and Cu(II) ion with S = 1/2 despite a long distance pathway via the aminotroponato and cyclopentadienyl moieties. DFT calculations supported this intramolecular ferromagnetism, which is induced by a spin polarization mechanism through the pi-spacers.


Identification and characterization of the dif Site from Bacillus subtilis.
Bacteria with circular chromosomes have evolved systems that ensure multimeric chromosomes, formed by homologous recombination between sister chromosomes during DNA replication, are resolved to monomers prior to cell division. The chromosome dimer resolution process in Escherichia coli is mediated by two tyrosine family site-specific recombinases, XerC and XerD, and requires septal localization of the division protein FtsK. The Xer recombinases act near the terminus of chromosome replication at a site known as dif (Ecdif). In Bacillus subtilis the RipX and CodV site-specific recombinases have been implicated in an analogous reaction. We present here genetic and biochemical evidence that a 28-bp sequence of DNA (Bsdif), lying 6 degrees counterclockwise from the B. subtilis terminus of replication (172 degrees ), is the site at which RipX and CodV catalyze site-specific recombination reactions required for normal chromosome partitioning. Bsdif in vivo recombination did not require the B. subtilis FtsK homologues, SpoIIIE and YtpT. We also show that the presence or absence of the B. subtilis SPbeta-bacteriophage, and in particular its yopP gene product, appears to strongly modulate the extent of the partitioning defects seen in codV strains and, to a lesser extent, those seen in ripX and dif strains.


Postural changes of the dural sac in the lumbar spines of asymptomatic individuals using positional stand-up magnetic resonance imaging.
Positional magnetic resonance imaging (MRI) study of control subjects. To determine dimensional changes in the lumbar dural sac as a function of posture, and to establish changes between the supine, erect and seated positions. Studies using computerized tomography and MRI were done to determine the mechanical effects on the lumbar spinal canal in the different positions. There has been no consecutive study, however, in which normal individuals were investigated for positional changes of the dural sac, including true standing position. Thirty-two male asymptomatic volunteers were recruited. The examination was performed using a new MRI system. All subjects were examined with sagittal T2 and axial T1-weighted spin-echo images. The subjects were studied in the supine, standing, and sitting positions. The measurements were made using OSIRIS software (Digital Imaging Unit University Hospital of Geneva, Geneva, Switzerland). On axial images, dural sac cross-sectional area and anteroposterior (AP) dural sac diameter were measured at the level of the L3/4, L4/5, and L5/S1 discs. On midsagittal images, AP dural sac diameter and the upper-endplate angles of L1 and S1 were measured. We found a disc degeneration or disc protrusion in 41% (12/29) of the subjects, but there was no obvious compression of the dural sac. Depending on the postures, the mean dural sac cross-sectional area and AP dural sac diameter changed. At all levels, mean dural sac cross-sectional area in the supine position was significantly smaller than in other postures. The dural area decreased most at the L5/S1 level due to positional change from standing to supine. The largest dural area at the L5/S1 level was in sitting extended. AP dural sac diameter on axial and midsagittal images showed a similar tendency. A significant posture-dependent difference of the dural sac cross-sectional area at the level of intervertebral disc in asymptomatic volunteers has been demonstrated. When the posture changed from supine to standing position, lumbar dural sac volume expanded by the increased pressure of cerebrospinal fluid, and the dural sac cross-sectional area increased. The smallest values were found in the supine position.


'I had to tell my GP I had lung cancer': patient perspectives of hospital- and community-based lung cancer care.
Lung cancer care spans both hospital- and community-based healthcare settings, and suboptimal communication between healthcare providers impacts on continuity and quality of care. Patients' experiences regarding: (1) communication between healthcare providers; and (2) the role of their GP during cancer treatment was explored in interviews with 47 Western Australian lung cancer patients. Thematic analysis using a phenomenological approach was undertaken to derive key themes regarding participant experiences. Poor communication between hospital cancer specialists (HCSs) influenced participants' treatment choices and perceptions of the quality of their care. Information provided by HCSs to GPs was often delayed or incomplete, and many participants perceived themselves as a messenger between healthcare settings. Participants' opinions about the GP role during cancer treatment ranged from 'no role' to an 'active member of the treating team'. A new model of cancer care is needed where the GP is considered part of the treating team. Early involvement of GPs and two-way communication between hospital and primary care during the disease continuum is required for this to occur.


Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery.
To evaluate the relationship between cerebral oxygen saturation and neuropsychological dysfunction after cardiac surgery. Prospective and observational study. Operating room and cardiac floor of a university hospital. One hundred one patients undergoing elective cardiac surgery with cardiopulmonary bypass Bilateral noninvasive cerebral oxygen saturations were monitored over the forehead. The anesthetic and surgical techniques were performed as usual, and no interventions were attempted based on the monitor. Neuropsychological outcome was assessed by the Mini-Mental State Examination (MMSE) and the antisaccadic eye movement test (ASEM). Preoperative baseline values of cerebral oxygen saturation (rSO(2)) were 58.6% +/- 10.2%. Patients with the nadir rSO(2) <35% had significantly higher incidences of postoperative ASEM and MMSE impairments than those with rSO(2) always above 35% (44% and 33% v 12% and 9%, respectively). Patients with areas of rSO(2) <40% for more than 10 minutes . % presented with a significantly higher incidence of postoperative ASEM and MMSE impairments than those with areas of rSO(2) <40% for less than 10 minutes . % (42% and 32% v 13% and 10%, respectively). Patients with postoperative ASEM or MMSE impairment had significantly lower nadir rSO(2) and significantly larger areas of rSO(2) <40%, <45%, and <50% than those with normal postoperative neuropsychological outcome. However, multivariate logistic regression analysis showed that areas of rSO(2) <40% were the only predictor for both postoperative ASEM and MMSE impairments. Intraoperative cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery with cardiopulmonary bypass. However, it remains to be determined whether interventions to maintain adequate cerebral oxygenation may improve neuropsychological outcome.


A new tool to predict survival after radiosurgery alone for newly diagnosed cerebral metastases.
Many patients with few cerebral metastases receive radiosurgery alone. The goal of this study was to create a tool to estimate the survival of such patients. To identify characteristics associated with survival, nine variables including radiosurgery dose, age, gender, Eastern cooperative oncology group performance score (ECOG-PS), primary tumor type, number/size of cerebral metastases, location of cerebral metastases, extra-cerebral metastases and time between cancer diagnosis and radiosurgery were analyzed in 214 patients. On multivariate analysis, age (p=0.03), ECOG-PS (p=0.02) and extra-cerebral metastases (p<0.01) had significant impacts on survival. Scoring points for each patient were obtained from 12-month survival rates (in %) related to the significant variables divided by 10. Addition of the scoring points of the three variables resulted in a patient's total predictive score. Two groups were designed, A (10-14 points) and B (16-17 points). Twelve-month survival rates were 33% and 77%, respectively (p<0.001). Median survival times were 8 and 20 months, respectively. Because most patients of group A died from extra-cerebral disease and/or new cerebral lesions, early systemic treatment and additional WBI should be considered. As cause of death in group B was mostly new cerebral metastases, additional WBI appears even more important for this group.


Cloning and expression in Escherichia coli of the Alcaligenes eutrophus H16 poly-beta-hydroxybutyrate biosynthetic pathway.
The poly-beta-hydroxybutyrate (PHB) biosynthetic pathway from Alcaligenes eutrophus H16 has been cloned and expressed in Escherichia coli. Initially, an A. eutrophus H16 genomic library was constructed by using cosmid pVK102, and cosmid clones that encoded the PHB biosynthetic pathway were sought by assaying for the first enzyme of the pathway, beta-ketothiolase. Six enzyme-positive clones were identified. Three of these clones manifested acetoacetyl coenzyme A reductase activity, the second enzyme of the biosynthetic pathway, and accumulated PHB. PHB was produced in the cosmid clones at approximately 50% of the level found in A. eutrophus. One cosmid clone was subjected to subcloning experiments, and the PHB biosynthetic pathway was isolated on a 5.2-kilobase KpnI-EcoRI fragment. This fragment, when cloned into small multicopy vectors, can direct the synthesis of PHB in E. coli to levels approaching 80% of the bacterial cell dry weight.


Potentially Inappropriate Prescribing in Australian Nursing Home Residents with Advanced Dementia: A Substudy of the IDEAL Study.
Prescribing medications for nursing home residents with advanced dementia should focus on optimizing function and comfort, reducing unnecessary harms and aligning care goals with a palliative approach. The aim of the study was to estimate the proportion of Australian nursing home residents with advanced dementia receiving potentially inappropriate medications, and identify those most commonly prescribed and factors associated with their use. Data were collected through retrospective audit of medication charts. Two hundred eighteen nursing home residents with advanced dementia from 20 nursing homes participated in a cluster-randomized controlled trial of case conferencing (the IDEAL Study) from June 2013 to December 2014. Inappropriate drug use was defined as medications classified as "never appropriate" by the Palliative Excellence in Alzheimer Care Efforts (PEACE) program criteria. Generalized linear mixed models were used to identify variables predicting use of "never" appropriate medications. Over a quarter (n = 65, 30%) of residents received at least one medication classed as "never" appropriate, the most common being lipid-lowering agents (n = 38, 17.4%), antiplatelet agents (n = 18, 8.3%), and acetylcholinesterase inhibitors (n = 16, 7.3%). Residents who had been at the nursing home for ≤10 months (odds ratio [OR] 5.60, 95% confidence interval [CI] 1.74-18.06) and 11-21 months (OR 5.41, 95% CI 1.67-17.75) had significantly greater odds of receiving a never appropriate medication compared with residents who had been at the nursing home for >5 years. Use of potentially inappropriate medications in Australian nursing home residents with advanced dementia is common. A greater understanding of the rationale that underpins prescribing of medications is required.


Minimum information about animal experiments: supplier is also important.
It has now been established that functional recovery after spinal cord injury (SCI) depends on several parameters, including animal strain. Here we demonstrate that rats from the same strain (Wistar) but from two independent commercial suppliers present different motor, sensory, and autonomic outcomes after a standard model of SCI, the so-called compression model. Recovery is correlated with the extension of the lesion, and we show that the vertebral canal diameter varies between the two suppliers. To substantiate this point, we carried out another set of experiments, with the so-called contusion model, which requires bone ablation and thus whose extension is not related to vertebral canal diameter. We show that there is no difference between the two suppliers. The purpose of our communication is to alert researchers on how crucial it is to control experimental parameters as closely as possible and to establish a standard for animal experiment in order to avoid unexpected biases.


Low serum concentration of obestatin as a predictor of mortality in maintenance hemodialysis patients.
Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number of beneficial cardiotropic effects in experimental studies. We hypothesized that obestatin alteration in hemodialysis patients may link to clinical outcomes. This cross-sectional study with prospective followup for almost 4 years was performed on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6, and various nutritional markers were measured. Patients with low obestatin levels, defined as a level less than median, had a worse all-cause mortality and cardiovascular mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients continued to be significant after adjustment for various confounders for all-cause mortality. Across the four obestatin-TNF-α categories, the group with low obestatin and high TNF-α (above median level) exhibited a worse outcome in both all-cause mortality and cardiovascular mortality. Clinical characteristics of patients in low obestatin high TNF-α group did not differ from other obestatin-TNF-α categorized groups. In summary, low serum obestatin concentration is an independent predictor of mortality in prevalent hemodialysis patients. Novel interactions were observed between obestatin and TNF-α, which were associated with mortality risk, especially those due to cardiovascular causes.


Relevance of neuropeptide Y (NPY) in psychiatry.
Extensive preclinical studies suggest neuropeptide Y (NPY) to be involved in stress regulation and coping. NPY counteracts the behavioral consequences of stress and anxiety to maintain emotional homeostasis. NPY is also involved in learning, memory, and cognition, all of which are dysregulated in many psychiatric states. Dense localization of NPY and NPY receptors is found in brain areas implicated in psychopathology such as the amygdala, hippocampus, neocortex, septum, caudate-putamen, hypothalamus and locus coeruleus. Impaired central NPY signaling may therefore be involved in the pathophysiology of depression, anxiety, schizophrenia, alcoholism, and trauma-induced disorders like PTSD. Studies on the readily accessible plasma from psychiatric patients have provided some information on the relevance of NPY as a marker for sympathetic tone in certain conditions. Reports on cerebrospinal fluid (CSF) NPY in subjects with depression indicate a dysregulation of central NPY in this disorder, however, other conditions still need to be investigated.


Non-steroidal anti-inflammatory drug use in acute myopericarditis: 12-month clinical follow-up.
Clinical data on the effect of non-steroidal anti-inflammatory drugs (NSAIDs) in myopericarditis are limited. Since NSAIDs are standard therapy in pericarditis, we retrospectively investigated their safety in myopericarditis. In a retrospective case-control study, we identified 60 patients with myopericarditis from September 2010 to August 2017. Diagnosis was based on clinical criteria, elevated high-sensitivity troponin T and cardiac magnetic resonance imaging (CMR). All patients received standard heart failure therapy if indicated. Twenty-nine patients (62%) received NSAIDs (acetylsalicylic acid: n=7, average daily dose =1300 mg or ibuprofen: n=22, average daily dose =1500 mg) for an average duration of 4 weeks. To create two cohorts with similar baseline conditions, 15 patients were excluded. Three months after diagnosis, 29 patients were re-evaluated by CMR to measure late gadolinium enhancement (LGE). Baseline characteristics of those treated with or without NSAIDs were similar. Mean age was 34 (±13) years, 6 (13%) were women. Mean left ventricular ejection fraction (LVEF) was 56% (±5). 82 % of the patients (14 of 17) treated with NSAIDs experienced a decrease in LGE at 3 months, while it was only 58 % (7 of 12) of those without NSAIDs (p=0.15). At 12-month follow-up, one of the patients treated without NSAIDs experienced polymorphic ventricular tachycardia (VT) with cardiac arrest, while one of the patients with NSAIDs experienced non-sustained VT. This is the first case-control study demonstrating that NSAIDs are safe in patients with myopericarditis and preserved LVEF. Our data suggest that this drug class should be tested prospectively in a large randomised clinical trial.


Studies on residue-free decontaminants for chemical warfare agents.
Residue-free decontaminants based on hydrogen peroxide, which decomposes to water and oxygen in the environment, are examined as decontaminants for chemical warfare agents (CWA). For the apparent special case of CWA on concrete, H2O2 alone, without any additives, effectively decontaminates S-2-(diisopropylamino)ethyl O-ethyl methylphosphonothioate (VX), pinacolyl methylphosphorofluoridate (GD), and bis(2-choroethyl) sulfide (HD) in a process thought to involve H2O2 activation by surface-bound carbonates/bicarbonates (known H2O2 activators for CWA decontamination). A plethora of products are formed during the H2O2 decontamination of HD on concrete, and these are characterized by comparison to synthesized authentic compounds. As a potential residue-free decontaminant for surfaces other than concrete (or those lacking adsorbed carbonate/bicarbonate) H2O2 activation for CWA decontamination is feasible using residue-free NH3 and CO2 as demonstrated by reaction studies for VX, GD, and HD in homogeneous solution. Although H2O2/NH3/CO2 ("HPAC") decontaminants are active for CWA decontamination in solution, they require testing on actual surfaces of interest to assess their true efficacy for surface decontamination.


[Effect of medium polarity and protein microenvironment on indo-1 fluorescence].
Fluorescent properties of indo-1 in protein containing solutions have been investigated. No changes have been defined in indo-1 fluorescent parameters in solutions of such proteins as trypsin, calmodulin, papain, lysozyme. Significant changes of indo-1 fluorescent parameters have been observed in solutions of histones, bovine and human serum albumins. Results obtained suggest that indo-1 binds well with protein sites containing hydrophobic "pockets" and positively charged amino-acid residues such as arginine and lysin. The destruction of the compact structure of serum albumin in 8 M urea leads to shift of indo-1 fluorescence spectrum and it approaches to the spectrum in water. Fluorescence spectra of indo-1 in dioxane prove that the binding of indo-1 by some proteins occurs in hydrophobic microenvironment of protein globule.


Elucidating multifinal and equifinal pathways to developmental disorders by constructing real-world neurorobotic models.
Vigorous research has been conducted to accumulate biological and theoretical knowledge about neurodevelopmental disorders, including molecular, neural, computational, and behavioral characteristics; however, these findings remain fragmentary and do not elucidate integrated mechanisms. An obstacle is the heterogeneity of developmental pathways causing clinical phenotypes. Additionally, in symptom formations, the primary causes and consequences of developmental learning processes are often indistinguishable. Herein, we review developmental neurorobotic experiments tackling problems related to the dynamic and complex properties of neurodevelopmental disorders. Specifically, we focus on neurorobotic models under predictive processing lens for the study of developmental disorders. By constructing neurorobotic models with predictive processing mechanisms of learning, perception, and action, we can simulate formations of integrated causal relationships among neurodynamical, computational, and behavioral characteristics in the robot agents while considering developmental learning processes. This framework has the potential to bind neurobiological hypotheses (excitation-inhibition imbalance and functional disconnection), computational accounts (unusual encoding of uncertainty), and clinical symptoms. Developmental neurorobotic approaches may serve as a complementary research framework for integrating fragmented knowledge and overcoming the heterogeneity of neurodevelopmental disorders.


Authorship decision-making in the field of orthopedic surgery and sports medicine.
To facilitate decision-making in authorship positions, the International Committee of Medical Journal Editor (ICMJE) developed a guideline that stipulates criteria authors should meet in order to merit authorship. Authors who did not meet these criteria and still enlisted as authors, are called 'honorary' authors. In this study, the prevalence and characteristics of honorary authorship (HA) is assessed in the field of Orthopedics and Sports Medicine. A survey was distributed among corresponding authors of articles published in 2019 in six Orthopedics-dedicated journals. 479 of the 1392 approached authors responded, leading to a response rate of 34.4%. 91.6% of the respondents were aware of the ICMJE guidelines, whereas 67.8% were aware of the issue of HA. Overall, the prevalence of guideline-based HA was 41.9%, while the prevalence of self-perceived HA was 14.7%. Having a senior member automatically enlisted as author on the departments, was associated with a higher rate of guideline-based HA (OR 5.03) and self-perceived HA (OR 3.31). The prevalence of HA in the field of Orthopedics and Sports Medicine is high, but comparable to other medical fields. Transparency in authorship decision-making is crucial to maintain liability in scientific articles.


Platinum(iv) oxaliplatin-peptide conjugates targeting memHsp70+ phenotype in colorectal cancer cells.
Novel Pt(iv) tumour penetrating peptide (TPP) conjugates are reported. They are the first example of metallodrugs to target a membrane bound heat shock protein 70 positive (memHSP70+) phenotype in cancer cells. The conjugates exhibit superior cytotoxicity as compared to oxaliplatin alone in Pt resistant colorectal cancer cells with relatively high memHSP70+ expression. Substitution of TPP in Pt(iv) peptide conjugates with scrambled peptide (ScP) essentially abolishes the observed cytotoxicity.


Economic Evaluation of Obesity Prevention in Early Childhood: Methods, Limitations and Recommendations.
Despite methodological advances in the field of economic evaluations of interventions, economic evaluations of obesity prevention programmes in early childhood are seldom conducted. The aim of the present study was to explore existing methods and applications of economic evaluations, examining their limitations and making recommendations for future cost-effectiveness assessments. A systematic literature search was conducted using PubMed, Cochrane Library, the British National Health Service Economic Evaluation Databases and EconLit. Eligible studies included trial-based or simulation-based cost-effectiveness analyses of obesity prevention programmes targeting preschool children and/or their parents. The quality of included studies was assessed. Of the six studies included, five were intervention studies and one was based on a simulation approach conducted on secondary data. We identified three main conceptual and methodological limitations of their economic evaluations: Insufficient conceptual approach considering the complexity of childhood obesity, inadequate measurement of effects of interventions, and lack of valid instruments to measure child-related quality of life and costs. Despite the need for economic evaluations of obesity prevention programmes in early childhood, only a few studies of varying quality have been conducted. Moreover, due to methodological and conceptual weaknesses, they offer only limited information for policy makers and intervention providers. We elaborate reasons for the limitations of these studies and offer guidance for designing better economic evaluations of early obesity prevention.


Risk factors for adverse events associated with bile leak during EUS-guided hepaticogastrostomy.
EUS-guided hepaticogastrostomy (HGS) is performed for patients with advanced cancer because of poor prognosis and compromised status, and bile peritonitis may prove critical for such patients. This adverse event has the possibility of decreasing quality of life by prolonging the time until the start of oral intake, hospital stay, or chemotherapy. Predictors of bile peritonitis in EUS-HGS thus have considerable clinical impact. The aim of this study was to retrospectively determine risk factors of bile peritonitis as adverse events of EUS-HGS. As risk factors of bile peritonitis, baseline characteristics of patients, characteristics of procedures such as number of punctures, types of fistula dilation, mean procedure time were analyzed. Furthermore, a receiver operating characteristic (ROC) curve was plotted to assess the influence of this distance and bile peritonitis and determine the optimum cutoff score for predicting the risk of bile peritonitis. Multivariate analysis using logistic regression was performed to examine factors of bile peritonitis. A total of 68 patients were enrolled in this study. A distance of 2.50 cm offered 90.3% sensitivity and 87.5% specificity in predicting bile peritonitis according to the ROC curve. Number of punctures (>1), procedure time (>20 min), distance to the hepatic parenchyma (<2.50 cm), and presence of acute cholangitis were significantly associated with bile peritonitis in univariate analysis. However, according to this multivariate analysis, distance to the hepatic parenchyma (<2.50 cm, odds ratio 96.98, 95% confidence interval 10.12-929.12, P < 0.001) were only significantly associated with bile peritonitis. The short distance of hepatic parenchyma may be a risk factor of bile peritonitis.


A case of advanced malignant pleural mesothelioma treatment with chemotherapy and photodynamic therapy.
Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his condition worsened. Thus, we recommended photodynamic therapy (PDT) to deal with the dyspnea and MPM. After PDT, the dyspnea improved and the patient then decided to take the combination chemotherapy. Our patient received chemotherapy using pemetrexed/cisplatin. Afterwards, he received a single PDT treatment and then later took chemotherapy using gemcitabine/cisplatin. The patient showed a survival time of 27 months, which is longer than median survival time in advanced MPM patients. Further research and clinical trials are needed to demonstrate any synergistic effect between the combination chemotherapy and PDT.


Lower-extremity muscle atrophy and fat infiltration after chronic spinal cord injury.
Atrophy and fatty-infiltration of lower-extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic disease and related mortality. To determine the magnitude of atrophy and fatty-infiltration of lower-extremity muscles and related factors in a group of individuals with chronic SCI and diverse impairment. Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf of 70 participants with chronic SCI [50 male, mean age 49 (standard deviation 12) years, C2-T12, AIS A-D] and matched controls. Regression models for muscle area and density were formed using 16 potential correlates selected a priori. Participants with motor-complete SCI had ≈ 32% lower muscle area, and ≈ 43% lower muscle density values relative to controls. Participants with motor-incomplete SCI had muscle area and density values that were both ≈ 14% lower than controls. Body mass (+), tetraplegia (+), motor function (+), spasticity (+), vigorous physical activity (+), wheelchair use (-), age (-), and waist circumference (-) were associated with muscle size and/or density in best-fit regression models. There are modifiable factors related to muscle size, body composition, and activity level that may offer therapeutic targets for preserving metabolic health after chronic SCI.


Counteranion effect on micellization of cationic gemini surfactants 14-2-14: Hofmeister and other counterions.
The effect of counterions was investigated and analyzed to probe the principal ionic effects influencing the micellization behavior of dimeric cationic surfactant ethanediylbis(dimethyltetradecylammonium), referred to as gemini 14-2-14. The 30 counterions were classified to four different families depending on their nature: (1) small and inorganic counterions which are typically taken from the Hofmeister series were studied to focus on the effect of ion type; (2) n-alkyl carboxylate counterions were studied to focus on the effect of the hydrophobicity of counterions; (3) aromatic carboxylate counterions were included to focus on the effect of the position of substitutions; and (4) other counterions were included in order to shed light on other parameters. By investigating the critical micelle concentration (CMC), ionization degree of micelle (alpha), free energy of micellization (DeltaG(M)), and aggregation numbers N of the gemini surfactant with these different types of anions, we demonstrated the effect of different ion properties independently. This approach allowed us to describe the effect of counterions on the micellization behavior of the gemini surfactant in terms of complex interplay between hydrophobicity of anions and other ion properties such as counterion hydration, interfacial packing of ions, and ionic morphology. Indeed, our results clearly demonstrate that a counterion effect on micellization properties cannot be described as a result of one single parameter of ions, as is too often assumed, but rather the balancing effects cooperatively affect the propensity of counterions to form ion pairs with surfactant headgroups and the entropy gain upon micellization. These results provide new insight in understanding the effect of ions on the delicate balance of forces controlling aggregate morphology and solution properties of charged amphiphilic molecules.


Banana meal for feeding pigs: digestive utilization, growth performance and feeding behavior.
The main objective of the present work was to determine the nutritional value and the strategies of using green banana meal (BM) in growing pigs. Two trials involving a total of 96 growing pigs were designed to study the effect of the harvest stage on the nutritional and energy values of BM (trial 1) and to evaluate the consequence of feeding gradual levels of BM on growth performance and feeding behavior in growing pigs (trial 2). In trial 1, the digestive utilization of three diets including 40% BM were compared with a control (C) soybean meal-corn diet in two batches of 12 pigs. BM was obtained from fruits harvested at 750 degrees-days (DD; early harvesting stage), 900 DD (normal harvesting stage) and 1150 DD (late harvesting stage). In trial 2, 72 Large White pigs were grouped in pens of nine animals and were given ad libitum access to one of the four dietary treatments (two pens/diet) differing from the rate of inclusion of 900 DD BM (0%, 20%, 40%, 60%). The estimated energy apparent digestibility coefficients of BM increased with the harvest stage (75.5%, 80.7% and 83.2% for BM at 750, 900 and 1150 DD, respectively). Digestible energy and metabolizable energy values were higher for BM at 1150 DD (13.56 and 13.05 MJ/kg DM, respectively) than at 900 DD (13.11 and 12.75 MJ/kg DM, respectively) or at 750 DD (12.00 and 11.75 MJ/kg DM, respectively). In trial 2, average daily gain and feed conversion ratio were not affected (P>0.05) by the rate of BM inclusion (822 g/day and 2.75 kg/kg on average, respectively). Feed intake and feeding behavior parameters were not significantly influenced by the dietary treatments except for the rate of feed ingestion with a lower value for the diet with 40% of BM (27.4 v. 32.2 g/min on average; P<0.01) when compared with the other diets. Results of this study indicate that the energy value of BM increases with the harvest stage and that BM can be incorporated up to 60% in growing finishing pig diets.


Pharmacological characterization of the neurotrophic sesquiterpene jiadifenolide reveals a non-convulsant signature and potential for progression in neurodegenerative disease studies.
The 'neurotrophic sesquiterpenes' refer to a group of molecules derived from the Illicium genus of flowering plant. They display neurotrophic effects in cultured neuron preparations and have been suggested to be cognitive enhancers and potential therapeutics for neurodegenerative disorders and dementias. Recent synthetic advances generated sufficient quantities of jiadifenolide for in vivo investigation into its biological effects. Jiadifenolide did not induce convulsions in mice nor did it enhance or diminish convulsions induced by pentylenetetrazole. Other negative allosteric modulators of GABAA receptors, picrotoxin, tetramethylenedisulfotetramine (TETS), and bilobalide all induced convulsions. Either i.p. or i.c.v. dosing generated micromolar plasma and brain levels of jiadifenolide but only small effects on locomotion of mice. However, jiadifenolide decreased d-amphetamine-induced hyperlocomotion in mice, an antipsychotic-like drug effect. Jiadifenolide did not significantly alter body temperature or behavior in the forced-swim test in mice. Molecular simulation data suggested a potential site in the pore/M2 helix region that is at an overlapping, yet lower position than those observed for other 'cage convulsant' compounds such as TETS and picrotoxin. We hypothesize that a position nearer to the entrance of the pore channel may allow for easier displacement of jiadifenolide from its blocking location leading to lower potency and lower side-effect liability. Like jiadifenolide, memantine (Namenda), one of the few drugs used in the symptomatic treatment of dementias, occupies a unique site on the NMDA receptor complex that creates low binding affinity that is associated with its reduced side-effect profile. Given the potential therapeutic applications of jiadifenolide and its relatively inert effects on overt behavior, the possibility of clinical utility for jiadifenolide and related compounds becomes intriguing.


Constipation. Consensual and empirical validation.
This article describes the process of consensual and empirical validation used for one nursing diagnosis, constipation. The process is illustrated with a cluster of studies, both qualitative and quantitative. Implications for practice, education, and research are described.


Hydroponic cultivation improves the nutritional quality of soybean and its products.
Hydroponic cultivation allows the control of environmental conditions, saves irrigation water, increases productivity, and prevents plant infections. The use of this technique for large commodities such as soybean is not a relevant issue on fertile soils, but hydroponic soybean cultivation could provide proteins and oil in adverse environmental conditions. In this paper, the compositions of four cultivars of soybean seeds and their derivates, soy milk and okara, grown hydroponically were compared to that of the same cultivar obtained from soil cultivation in an open field. Besides proximal composition, the concentrations of phytic acid and isoflavones were monitored in the seeds, soy milk, and okara. Results demonstrated that, independent from the cultivar, hydroponic compared to soil cultivation promoted the accumulation of fats (from 17.37 to 21.94 g/100 g dry matter) and total dietary fiber (from 21.67 to 28.46 g/100 g dry matter) and reduced isoflavones concentration (from 17.04 to 7.66 mg/kg dry matter), whereas protein concentration was unaffected. The differences found in seed composition were confirmed in the respective okara products, but the effect of cultivation system was not significant looking at the soy milk composition. Data showed that hydroponic cultivation improved the nutritional quality of soybean seeds with regard to fats and dietary fiber. They also suggest that specific cultivars should be selected to obtain the desired nutritional features of the soybean raw material depending on its final destination.


Incidence of bacteremia in stressed and unstressed populations of the blue crab, Callinectes sapidus.
The incidence of bacteremia in the blue crab, Callinectes sapidus, is reported to be in excess of 80%. Because these results have been controversial, a field study was initiated to determine the effect of commercial capture and handling stresses on the incidence and levels of infection in blue crabs. The majority (75%) of "unstressed" crabs which were captured individually and bled immediately upon removal from the water were bacteremic, with a geometric mean level of infection of 14 CFU/ml of hemolymph. Crabs collected by crab pot, confined within these pots for as long as 24 h, and sampled immediately after removal from the water had a similar mean level of infection. Crabs subjected to the stresses of commercial capture, handling, and transport showed a higher incidence of infection (91%) and a mean infection level of 46 CFU/ml. Injuries sustained by crabs during commercial handling are thought to be associated with the higher incidence of infection. Vibrio spp. were primarily responsible for progressive infections in commercially stressed crabs and were the predominant bacterial type in heavily infected crabs. Our results indicated that uninjured healthy crabs do not have sterile hemolymph but instead harbor low-level bacterial infections.


Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: An Analysis of 5721 Cases.
The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS ( P < 0.0001) and OL ( P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P <0.02). Compared to VATS, RL had lower conversion rate ( P <0.0001), shorter hospital stay ( P <0.0001) and a lower postoperative transfusion rate ( P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.


Tricho-Hepato-Enteric Syndrome mutation update: Mutations spectrum of TTC37 and SKIV2L, clinical analysis and future prospects.
Tricho-Hepato-Enteric syndrome (THES) is a very rare autosomal recessive syndromic enteropathy caused by mutations of either TTC37 or SKIV2L genes. Very little is known of these two gene products in mammals nor of the pathophysiology of the disease. Since the identification of the genes, we have set up the molecular diagnostic of THES in routine, gathering a large cohort with clinical and molecular data. Here, we report the phenotype and genotype analysis of this cohort together with an extensive literature review of THES cases worldwide, that is, 96 individuals harboring mutations in one gene or the other. We set up locus-specific databases for both genes and reviewed the type of mutation as well as their localization in the proteins. No hot spot is evidenced for any type of mutation. The phenotypic analysis was first made on the whole cohort but is limited due to heterogeneity in clinical descriptions. We then examined the lab diagnostic cohort in detail for clinical manifestations. For the first time, we are able to suggest that patients lacking SKIV2L seem more severely affected than those lacking TTC37, in terms of liver damage and prenatal growth impairment.