Dietary intake of fats and fatty acids in the Korean population: Korea National Health and Nutrition Examination Survey, 2013.
The aim of this study was to estimate average total fat and fatty acid intakes as well as identify major food sources using data from the Korea National Health and Nutrition Examination Survey (KNHANES) VI-1 (2013). Total fat and fatty acid intakes were estimated using 24-hour dietary recall data on 7,048 participants aged ≥ 3 years from the KNHANES VI-1 (2013). Data included total fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), n-3 fatty acid (n-3 FA), and n-6 fatty acid (n-6 FA) levels. Population means and standard errors of the mean were weighted in order to produce national estimates and separated based on sex, age, income, as well as residential region. Major food sources of fat, SFA, MUFA, PUFA, n-3 FA, and n-6 FA were identified based on mean consumption amounts of fat and fatty acids in each food. The mean intake of total fat was 48.0 g while mean intakes of SFA, MUFA, PUFA, n-3 FA, and n-6 FA were 14.4 g, 15.3 g, 11.6 g, 1.6 g, and 10.1 g, respectively. Intakes of MUFA and SFA were each higher than that of PUFA in all age groups. Pork was the major source of total fat, SFA, and MUFA, and soybean oil was the major source of PUFA. Milk and pork were major sources of SFA in subjects aged 3-11 years and ≥ 12 years, respectively. Perilla seed oil and soybean oil were main sources of n-3 FA in subjects aged ≥ 50 years and aged < 50 years, respectively. Estimation of mean fatty acid intakes of this study using nationally represented samples of the Korean population could be useful for developing and evaluating national nutritional policies.


Optical monitoring of oxygen tension in cortical microvessels with confocal microscopy.
Evaluating cerebral oxygenation is of critical importance for the understanding of brain function and several neuropathologies. Although several techniques exist for measuring cerebral oxygenation in vivo, the most widely accepted techniques offer limited spatial resolution. We have developed a confocal imaging system for minimally invasive measurement of oxygen tension (pO(2)) in cerebral microvessels with high spatial and temporal resolution. The system relies on the phosphorescence quenching method using exogenous porphyrin-based dendritic oxygen probes. Here we present high-resolution phosphorescence images of cortical microvasculature and temporal pO(2) profiles from multiple locations in response to varied fraction of inspired oxygen and functional activation.


The cellular basis of compensatory muscle growth in the teleost Odontesthes bonariensis.
This study evaluates white muscle growth and in vivo cell proliferation during a fasting and refeeding trial, using pejerrey (Odontesthes bonariensis) as animal model, in order to better understand the cellular basis governing catch-up growth. Experiments consisted of two groups of fish, a control group continuously fed ad libitum, and a group fasted for 2 weeks and then fed for another 2 weeks. We examined how the formation of new muscle fibers and their increase in size were related to muscle precursor cell (MPC) proliferation under both experimental conditions. During fasting, the number of 5-ethynyl-2'-deoxyuridine-positive (EdU+) cells decreased along with myogenic regulatory factor (MRF) mRNA levels related to myoblast proliferation and differentiation, and the muscle stem cell marker Pax7 mRNA level increased. Analysis of myomere cross-sectional area, distribution of muscle fiber sizes and number of fibers per myomere showed that muscle hypertrophy but not hyperplasia was inhibited during fasting. Both higher igf2 mRNA level and the persistence of cell proliferation could be supporting new myofiber formation. In contrast, an exacerbated MPC proliferation occurred during catch-up growth, and this increase in cell number could be contributing to the growth of both pre-existing and newly formed small fibers. The findings that some MPCs proliferate during fasting and that muscle growth mechanisms, hyperplasia and hypertrophy are differentially regulated could help to explain why re-fed fish could grow at faster rates, and why they return to the lost growth trajectory.


Naming the same entities from visual or from auditory stimulation engages similar regions of left inferotemporal cortices.
We have proposed that the left inferotemporal (IT) region contains structures that mediate between conceptual knowledge retrieval and word-form retrieval, and we have hypothesized that these structures are utilized for word retrieval irrespective of the sensory modality through which an entity is apprehended, thus being "modality neutral." We tested this idea in two sensory modalities, visual and auditory, and for two categories of concrete entities, tools and animals. In a PET experiment, 10 normal participants named tools and animals either from pictures or from characteristic sounds (e.g., "scissors" from a picture of a scissors or from the sound of a scissors cutting; "rooster" from a picture of a rooster or from the sound of a rooster crowing). Visual and auditory naming of tools activated the left posterior/lateral IT; visual and auditory naming of animals activated the left anterior/ventral IT. For both tools and animals, the left IT activations were similar in location and magnitude regardless of whether participants were naming entities from pictures or from sounds. The results provide novel evidence to support the notion that left IT structures contain "modality-neutral" systems for mediating between conceptual knowledge and word retrieval.


Doctors and dying declarations: the role of the state in abortion regulation in British Columbia, 1917-37.
In Canada, the history of state regulation of abortion is underexamined, leaving the general impression that the state played a secondary role to that of the medical profession in attempting to enforce the federal anti-abortion law. Studies have focused on "regular" physicians as a regulator of abortion to such an extent that the state's involvement in this process has been largely neglected or obscured. In contrast, this study highlights the actions taken by lower-level state agencies, namely, the Coroner's Inquisition and municipal and provincial police, to enforce the federal abortion law in British Columbia. The study examines the records of the inquests held into the deaths of 34 women from illegal abortion and offers three main observations. First, state agencies consistently sought information about abortionists and the circumstances surrounding the abortions from the women in hospital, their families, lovers, and doctors. Especially important is how authorities routinely attempted to extract dying declarations from the ill women. Second, while it is clear doctors participated in the investigative process, the records suggest they were often ambivalent or reluctant to do so. Finally, this study concludes that many of the actors involved in these events resisted the authorities' attempts to enforce the law, some successfully, thereby effectively undermining state regulatory practices as a result.


Community care for the elderly 1976-84.
The aging of the elderly population is of crucial importance as people who are over 80 make far greater use of health and social services than any other age group. Government guidelines on the provision of services, which are generally related to the whole population aged 65 and over, fail to take account of this change in the age structure of the elderly population and are no longer appropriate. Recent trends in the provision of domiciliary services, day care, specialist housing for the elderly, and residential care have been related to changes in the number of potential consumers. Ironically, despite the government's stated commitment to "community care," the chief growth area has been private institutional care. The number of day care places and sheltered housing units has also increased in real terms, but the provision of domiciliary services, such as home help and health visitor visits to the elderly, has either fallen behind or barely matched the increase in the number of very old people. If community care is to be made a reality and if the present inadequate levels of service are to be maintained, let alone improved, then additional resources, greater cooperation among agencies, and a more imaginative approach to the development and delivery of services are urgently needed.


Eliminating anti-nutritional plant food proteins: the case of seed protease inhibitors in pea.
Several classes of seed proteins limit the utilisation of plant proteins in human and farm animal diets, while plant foods have much to offer to the sustainable intensification of food/feed production and to human health. Reduction or removal of these proteins could greatly enhance seed protein quality and various strategies have been used to try to achieve this with limited success. We investigated whether seed protease inhibitor mutations could be exploited to enhance seed quality, availing of induced mutant and natural Pisum germplasm collections to identify mutants, whilst acquiring an understanding of the impact of mutations on activity. A mutant (TILLING) resource developed in Pisum sativum L. (pea) and a large germplasm collection representing Pisum diversity were investigated as sources of mutations that reduce or abolish the activity of the major protease inhibitor (Bowman-Birk) class of seed protein. Of three missense mutations, predicted to affect activity of the mature trypsin / chymotrypsin inhibitor TI1 protein, a C77Y substitution in the mature mutant inhibitor abolished inhibitor activity, consistent with an absolute requirement for the disulphide bond C77-C92 for function in the native inhibitor. Two further classes of mutation (S85F, E109K) resulted in less dramatic changes to isoform or overall inhibitory activity. The alternative strategy to reduce anti-nutrients, by targeted screening of Pisum germplasm, successfully identified a single accession (Pisum elatius) as a double null mutant for the two closely linked genes encoding the TI1 and TI2 seed protease inhibitors. The P. elatius mutant has extremely low seed protease inhibitory activity and introgression of the mutation into cultivated germplasm has been achieved. The study provides new insights into structure-function relationships for protease inhibitors which impact on pea seed quality. The induced and natural germplasm variants identified provide immediate potential for either halving or abolishing the corresponding inhibitory activity, along with associated molecular markers for breeding programmes. The potential for making large changes to plant protein profiles for improved and sustainable food production through diversity is illustrated. The strategy employed here to reduce anti-nutritional proteins in seeds may be extended to allergens and other seed proteins with negative nutritional effects. Additionally, the novel variants described for pea will assist future studies of the biological role and health-related properties of so-called anti-nutrients.


Antitumor activity and mechanism of action of 6-thio-3-deazaguanine.
6-Thio-3-deazaguanine (TDG), a relatively new purine antimetabolite, exhibits significant antitumor activity against a variety of experimental animal tumor models including C3H mammary adenocarcinoma, Lewis lung carcinoma, adenocarcinoma 755, and leukemias L1210 and P388. However, the drug was ineffective against 3-deazaguanine-resistant L1210 (both in vitro and in vivo) and CEM cells (in vitro). The resistant cells appear to lack HGPRTase activity because the extracts from these cell lines failed to convert hypoxanthine to IMP. These data indicate that TDG needs to be activated by hypoxanthine guanine phosphoribosyltransferase prior to its growth inhibitory effects. Cytotoxicity of TDG was completely reversed by hypoxanthine and inosine. TDG inhibited the synthesis of DNA and RNA equally and effectively, whereas the inhibition of protein synthesis required a prolonged drug exposure and appears to be a consequence of the inhibition of DNA and RNA synthesis. Data from these studies suggest that TDG is an effective antitumor agent, and its spectrum of antitumor activity and mechanism of action appears to be different from that of 3-deazaguanine.


Buckling vs. particle desorption in a particle-covered drop subject to compressive surface stresses: a simulation study.
Predicting the behaviour of particle-covered fluid interfaces under compression has implications in several fields. The surface-tension driven adhesion of particles to drops and bubbles is exploited for example to enhance the stability of foams and emulsion and develop new generation materials. When a particle-covered fluid interface is compressed, one can observe either smooth buckling or particle desorption from the interface. The microscopic mechanisms leading to the buckling-to-desorption transition are not fully understood. In this paper we simulate a spherical drop covered by a monolayer of spherical particles. The particle-covered interface is subject to time-dependent compressive surface stresses that mimic the slow deflation of the drop. The buckling-to-desorption transition depends in a non-trivial way on three non-dimensional parameters: the ratio Πs/γ of particle-induced surface pressure and bare surface tension, the ratio a/R of particle and drop radii, and the parameter f characterising the strength of adhesion of each particle to the interface. Based on the insights from the simulations, we propose a configuration diagram describing the effect of these controlling parameters. We find that particle desorption is highly correlated with a mechanical instability that produces small-scale undulations of the monolayer of the order of the particle size that grow when the surface pressure is sufficiently large. We argue that the large local curvature associated with these small undulations can produce large normal forces, enhancing the probability of desorption.


Lack of linear correlation between dynamic and steady-state cerebral autoregulation.
For correct application and interpretation of cerebral autoregulation (CA) measurements in research and in clinical care, it is essential to understand differences and similarities between dynamic and steady-state CA. The present study found no correlation between dynamic and steady-state CA indices in healthy older adults. There was variability between individuals in all (steady-state and dynamic) autoregulatory indices, ranging from low (almost absent) to highly efficient CA in this healthy population. These findings challenge the assumption that assessment of a single CA parameter or a single set of parameters can be generalized to overall CA functioning. Therefore, depending on specific research purposes, the choice for either steady-state or dynamic measures or both should be weighed carefully. The present study aimed to investigate the relationship between dynamic (dCA) and steady-state cerebral autoregulation (sCA). In 28 healthy older adults, sCA was quantified by a linear regression slope of proportionate (%) changes in cerebrovascular resistance (CVR) in response to proportionate (%) changes in mean blood pressure (BP) induced by stepwise sodium nitroprusside (SNP) and phenylephrine (PhE) infusion. Cerebral blood flow (CBF) was measured at the internal carotid artery (ICA) and vertebral artery (VA) and CBF velocity at the middle cerebral artery (MCA). With CVR = BP/CBF, Slope-CVRICA , Slope-CVRVA and Slope-CVRiMCA were derived. dCA was assessed (i) in supine rest, analysed with transfer function analysis (gain and phase) and autoregulatory index (ARI) fit from spontaneous oscillations (ARIBaseline ), and (ii) with transient changes in BP using a bolus injection of SNP (ARISNP ) and PhE (ARIPhE ). Comparison of sCA and dCA parameters (using Pearson's r for continuous and Spearman's ρ for ordinal parameters) demonstrated a lack of linear correlations between sCA and dCA measures. However, comparisons of parameters within dCA and within sCA were correlated. For sCA slope-CVRVA with Slope-CVRiMCA (r = 0.45, P < 0.03); for dCA ARISNP with ARIPhE (ρ = 0.50, P = 0.03), ARIBaseline (ρ = 0.57, P = 0.03) and PhaseLF (ρ = 0.48, P = 0.03); and for GainVLF with GainLF (r = 0.51, P = 0.01). By contrast to the commonly held assumption based on an earlier study, there were no linear correlations between sCA and dCA. As an additional observation, there was strong inter-individual variability, both in dCA and sCA, in this healthy group of elderly, in a range from low to high CA efficiency.


Clinical Features and Molecular Genetics of Autosomal Recessive Ataxia in the Turkish Population.
Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of inherited neurodegenerative disorders. The aim of this study was to present the clinical and genetic features of patients with ataxia complaints and those genetically diagnosed with ARCAs. Thirty-one children with ARCA were retrospectively analyzed. Fourteen (45.2%) were boys and 17 (54.8%) were girls with the mean age at onset of symptoms of 46.13 ± 26.30 months (12-120 months). Of the 31 patients, 21 (67.7%) were from consanguineous marriages. Eight patients had Friedreich's ataxia, five had ataxia telangiectasia, three had L-2-hydroxyglutaric aciduria, three had Joubert syndrome, two had neuronal ceroid lipofuscinosis, two had megalencephalic leukoencephalopathy with subcortical cysts, two had ataxia with ocular motor oculomotor apraxia type 1, one had cytochrome c oxidase deficiency, one had autosomal recessive spastic ataxia of Charlevoix-Saguenay, one had Niemann-Pick type C, one had congenital disorders of glycosylation, one had adrenoleukodystrophy, and one had cobalamin transport disorder. The prevalence of hereditary ataxia can vary among countries. The consanguineous marriage is an important finding in these diseases. These genetic tests will increase the number of ARCA patients diagnosed.


Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to stimulate alveolar bone and cementum formation in periodontal defects but not a functionally oriented periodontal ligament (PDL). Subcutaneous and intramuscular implants of BMP-12 have been shown to induce tendon formation and ligament-like tissue. The objective of this study was to evaluate rhBMP-12 for periodontal regeneration, in particular PDL formation. Six young adult Hound Labrador mongrel dogs were used. Routine supraalveolar periodontal defects were created around the mandibular premolar teeth. Three animals received rhBMP-12(0.04 mg/ml) in an absorbable collagen sponge (ACS) carrier vs. rhBMP-12(0.2 mg/mL)/ACS in contralateral defects. Three animals received rhBMP-12(1.0 mg/ml)/ACS vs. rhBMP-2(0.2 mg/ml)/ACS (total implant volume/defect approximately 1 ml). The animals were euthanized 8 weeks postsurgery and block biopsies were processed for histometric analysis. Bone regeneration appeared increased in sites receiving rhBMP-2/ACS compared to sites receiving rhBMP-12/ACS. Cementum regeneration was similar comparing sites implanted with rhBMP-2/ACS to sites implanted with rhBMP-12/ACS. In contrast, sites receiving rhBMP-12/ACS exhibited a functionally oriented PDL bridging the gap between newly formed bone and cementum whereas this was a rare observation in sites receiving rhBMP-2/ACS. Ankylosis appeared increased in sites receiving rhBMP-2/ACS compared to those receiving rhBMP-12/ACS. The outcomes of this study suggest that rhBMP-12 may have significant effects on regeneration of the PDL. Additional preclinical evaluation is needed to confirm these initial observations prior to clinical application.


Comprehensive nutrition plan improves cardiovascular risk factors in essential hypertension.
Increased arterial pressure is known to be influenced by a variety of nutrients. Compliance with dietary recommendations for risk reduction is often limited by the complexity of their implementation. In addition, how improvements in total diet, rather than single nutrients, influence concomitant cardiovascular risk factors has not been thoroughly explored. We assessed the effects of a nutritionally complete prepared meal program, the Campbell's Center for Nutrition and Wellness plan (CCNW), compared with dietary therapy in which participants received a structured nutritional assessment and prescription and selected their own foods, in 101 women and men with mild-to-moderate hypertension. Outcome measures included blood pressure (BP), lipids and lipoproteins, glucose, glycosylated hemoglobin (HbA1c), insulin, homocysteine, nutrient intake, compliance, and quality of life. Both dietary interventions significantly lowered BP (P < .0001), while simultaneously improving the overall cardiovascular risk profile. Significantly greater benefits were observed with the CCNW plan as compared with the participant selected diet in cholesterol and LDL levels (both P < .0001), LDL:HDL (P < .001), HbA1c (P < .05), homocysteine (P < .001), total nutrient intake (P < .0001), compliance (P < .0001), and quality of life (P < .001). This study demonstrates that improving the total diet to include the full array of recommended dietary guidelines, rather than focusing on single nutrients, has significant benefits for the cardiovascular risk profile of hypertensive persons beyond BP control. Compared with typical dietary therapy, the comprehensive CCNW meal plan has significantly greater effects on multiple cardiovascular risk factors while yielding greater compliance and improved quality of life.


Poverty and obesity: the role of energy density and energy costs.
Many health disparities in the United States are linked to inequalities in education and income. This review focuses on the relation between obesity and diet quality, dietary energy density, and energy costs. Evidence is provided to support the following points. First, the highest rates of obesity occur among population groups with the highest poverty rates and the least education. Second, there is an inverse relation between energy density (MJ/kg) and energy cost (US dollars/MJ), such that energy-dense foods composed of refined grains, added sugars, or fats may represent the lowest-cost option to the consumer. Third, the high energy density and palatability of sweets and fats are associated with higher energy intakes, at least in clinical and laboratory studies. Fourth, poverty and food insecurity are associated with lower food expenditures, low fruit and vegetable consumption, and lower-quality diets. A reduction in diet costs in linear programming models leads to high-fat, energy-dense diets that are similar in composition to those consumed by low-income groups. Such diets are more affordable than are prudent diets based on lean meats, fish, fresh vegetables, and fruit. The association between poverty and obesity may be mediated, in part, by the low cost of energy-dense foods and may be reinforced by the high palatability of sugar and fat. This economic framework provides an explanation for the observed links between socioeconomic variables and obesity when taste, dietary energy density, and diet costs are used as intervening variables. More and more Americans are becoming overweight and obese while consuming more added sugars and fats and spending a lower percentage of their disposable income on food.


Assessing the impact of a new health sector pay system upon NHS staff in England.
Pay and pay systems are a critical element in any health sector human resource strategy. Changing a pay system can be one strategy to achieve or sustain organizational change. This paper reports on the design and implementation of a completely new pay system in the National Health Service (NHS) in England. 'Agenda for Change' constituted the largest-ever attempt to introduce a new pay system in the UK public services, covering more than one million staff. Its objectives were to improve the delivery of patient care as well as enhance staff recruitment, retention and motivation, and to facilitate new ways of working. This study was the first independent assessment of the impact of Agenda for Change at a local and national level. The methods used in the research were a literature review; review of 'grey' unpublished documentation provided by key stakeholders in the process; analysis of available data; interviews with key national informants (representing government, employers and trade unions), and case studies conducted with senior human resource managers in ten NHS hospitals in England. Most of the NHS trust managers interviewed were in favour of Agenda for Change, believing it would assist in delivering improvements in patient care and staff experience. The main benefits highlighted were: 'fairness', moving different staff groups on to harmonized conditions; equal pay claim 'protection'; and scope to introduce new roles and working practices. Agenda for Change took several years to design, and has only recently been implemented. Its very scale and central importance to NHS costs and delivery of care argues for a full assessment at an early stage so that lessons can be learned and any necessary changes made. This paper highlights weaknesses in evaluation and limitations in progress. The absence of systematically derived and applied impact indicators makes it difficult to assess impact and impact variations. Similarly, the lack of any full and systematic evaluation constrained the overall potential for Agenda for Change to deliver improvements to the NHS.


Mesenchymal stem-cell immunosuppressive capabilities: therapeutic implications in islet transplantation.
Mesenchymal stem cells (MSCs) are known to be capable of suppressing immune responses and offer therapeutic potential for achieving transplantation tolerance. This review will discuss the impacts of MSCs on transplant immunity and focus on the potential role of MSCs in protecting islet grafts from both rejection and autoimmune attack.


A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos.
Epigenetic mechanisms set apart the active and inactive regions in the genome of multicellular organisms to produce distinct cell fates during embryogenesis. Here, we report on the epigenetic and transcriptome genome-wide maps of gastrula-stage Xenopus tropicalis embryos using massive parallel sequencing of cDNA (RNA-seq) and DNA obtained by chromatin immunoprecipitation (ChIP-seq) of histone H3 K4 and K27 trimethylation and RNA Polymerase II (RNAPII). These maps identify promoters and transcribed regions. Strikingly, genomic regions featuring opposing histone modifications are mostly transcribed, reflecting spatially regulated expression rather than bivalency as determined by expression profile analyses, sequential ChIP, and ChIP-seq on dissected embryos. Spatial differences in H3K27me3 deposition are predictive of localized gene expression. Moreover, the appearance of H3K4me3 coincides with zygotic gene activation, whereas H3K27me3 is predominantly deposited upon subsequent spatial restriction or repression of transcriptional regulators. These results reveal a hierarchy in the spatial control of zygotic gene activation.


Coevolution analyses illuminate the dependencies between amino acid sites in the chaperonin system GroES-L.
GroESL is a heat-shock protein ubiquitous in bacteria and eukaryotic organelles. This evolutionarily conserved protein is involved in the folding of a wide variety of other proteins in the cytosol, being essential to the cell. The folding activity proceeds through strong conformational changes mediated by the co-chaperonin GroES and ATP. Functions alternative to folding have been previously described for GroEL in different bacterial groups, supporting enormous functional and structural plasticity for this molecule and the existence of a hidden combinatorial code in the protein sequence enabling such functions. Describing this plasticity can shed light on the functional diversity of GroEL. We hypothesize that different overlapping sets of amino acids coevolve within GroEL, GroES and between both these proteins. Shifts in these coevolutionary relationships may inevitably lead to evolution of alternative functions. We conducted the first coevolution analyses in an extensive bacterial phylogeny, revealing complex networks of evolutionary dependencies between residues in GroESL. These networks differed among bacterial groups and involved amino acid sites with functional importance and others with previously unsuspected functional potential. Coevolutionary networks formed statistically independent units among bacterial groups and map to structurally continuous regions in the protein, suggesting their functional link. Sites involved in coevolution fell within narrow structural regions, supporting dynamic combinatorial functional links involving similar protein domains. Moreover, coevolving sites within a bacterial group mapped to regions previously identified as involved in folding-unrelated functions, and thus, coevolution may mediate alternative functions. Our results highlight the evolutionary plasticity of GroEL across the entire bacterial phylogeny. Evidence on the functional importance of coevolving sites illuminates the as yet unappreciated functional diversity of proteins.


Pedi-IKDC or KOOS-child: which questionnaire should be used in children with knee disorders?
The Pedi International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) child are validated questionnaires for children with knee disorders. The aim of this study was to translate these questionnaires in Dutch and to recommend which questionnaires should - based on their psychometric properties - be used in clinical practice. The English Pedi-IKDC and KOOS-Child were translated by the forward-backward procedure. Subsequently, content validity of the Pedi-IKDC and KOOS-Child was evaluated by both patients (n = 18) and experts (n = 18). To evaluate construct validity and interpretability participants with knee disorders (n = 100) completed the Numeric Rating Scale Pain, Lysholm Knee Scoring Scale, EuroQol-5 Dimension, Pedi-IKDC and KOOS-Child at baseline. Participants completed the anchor question, Pedi-IKDC and KOOS-child two weeks (n = 54) and one year (n = 71) after baseline, for evaluating the test-retest reliability and responsiveness. Psychometric properties were interpreted following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. The Pedi-IKDC showed adequate test-retest reliability (intraclass correlation coefficient (ICC) 0.9; standard error of measurement (SEM) 8.6; smallest detectable change (SDC) 23.8), adequate content validity (> 75% relevant), adequate construct validity (75% confirmed hypotheses), low floor or ceiling effects (scores between 5 and 95) and adequate responsiveness (> 75% confirmed hypotheses). The KOOS-Child showed an adequate test-retest reliability (ICC 0.8-0.9; SEM 8.9-16.9; SDC 24.7-46.9), adequate content validity (> 75% relevant, except KOOS-Child subscale ADL), adequate construct validity (75% confirmed hypotheses), low floor and ceiling effects (scores between 5 and 95, except KOOS-Child subscale activities of daily living and Sport/play) and moderate responsiveness (40% confirmed hypotheses). The Pedi IKDC showed better psychometric properties than the KOOS-Child and should therefore be used in children with knee disorders.


"Fathers' rights" and the defense of paternal authority in Australia.
Feminism's achievements regarding violence against women are a key target for the fathers' rights movement. This article provides an overview of the impact of the fathers' rights movement on men's violence against women. It documents the ways in which fathers' rights groups in Australia have influenced changes in family law, which privilege parental contact over safety, particularly through moves toward a presumption of children's joint residence. They have attempted to discredit female victims of violence, to wind back the legal protections available to victims and the sanctions imposed on perpetrators, and to undermine services for the victims of men's violence.


Dynamics of the central bottleneck: dual-task and task uncertainty.
Why is the human brain fundamentally limited when attempting to execute two tasks at the same time or in close succession? Two classical paradigms, psychological refractory period (PRP) and task switching, have independently approached this issue, making significant advances in our understanding of the architecture of cognition. Yet, there is an apparent contradiction between the conclusions derived from these two paradigms. The PRP paradigm, on the one hand, suggests that the simultaneous execution of two tasks is limited solely by a passive structural bottleneck in which the tasks are executed on a first-come, first-served basis. The task-switching paradigm, on the other hand, argues that switching back and forth between task configurations must be actively controlled by a central executive system (the system controlling voluntary, planned, and flexible action). Here we have explicitly designed an experiment mixing the essential ingredients of both paradigms: task uncertainty and task simultaneity. In addition to a central bottleneck, we obtain evidence for active processes of task setting (planning of the appropriate sequence of actions) and task disengaging (suppression of the plan set for the first task in order to proceed with the next one). Our results clarify the chronometric relations between these central components of dual-task processing, and in particular whether they operate serially or in parallel. On this basis, we propose a hierarchical model of cognitive architecture that provides a synthesis of task-switching and PRP paradigms.


Flagella-mediated secretion of a novel Vibrio cholerae cytotoxin affecting both vertebrate and invertebrate hosts.
Using Caenorhabditis elegans as an infection host model for Vibrio cholerae predator interactions, we discovered a bacterial cytotoxin, MakA, whose function as a virulence factor relies on secretion via the flagellum channel in a proton motive force-dependent manner. The MakA protein is expressed from the polycistronic makDCBA (motility-associated killing factor) operon. Bacteria expressing makDCBA induced dramatic changes in intestinal morphology leading to a defecation defect, starvation and death in C. elegans. The Mak proteins also promoted V. cholerae colonization of the zebrafish gut causing lethal infection. A structural model of purified MakA at 1.9 Å resolution indicated similarities to members of a superfamily of bacterial toxins with unknown biological roles. Our findings reveal an unrecognized role for V. cholerae flagella in cytotoxin export that may contribute both to environmental spread of the bacteria by promoting survival and proliferation in encounters with predators, and to pathophysiological effects during infections.


A penalized structural equation modeling method accounting for secondary phenotypes for variable selection on genetically regulated expression from PrediXcan for Alzheimer's disease.
As the global burden of mental illness is estimated to become a severe issue in the near future, it demands the development of more effective treatments. Most psychiatric diseases are moderately to highly heritable and believed to involve many genes. Development of new treatment options demands more knowledge on the molecular basis of psychiatric diseases. Toward this end, we propose to develop new statistical methods with improved sensitivity and accuracy to identify disease-related genes specialized for psychiatric diseases. The qualitative psychiatric diagnoses such as case control often suffer from high rates of misdiagnosis and oversimplify the disease phenotypes. Our proposed method utilizes endophenotypes, the quantitative traits hypothesized to underlie disease syndromes, to better characterize the heterogeneous phenotypes of psychiatric diseases. We employ the structural equation modeling using the liability-index model to link multiple genetically regulated expressions from PrediXcan and the manifest variables including endophenotypes and case-control status. The proposed method can be considered as a general method for multivariate regression, which is particularly helpful for psychiatric diseases. We derive penalized retrospective likelihood estimators to deal with the typical small sample size issue. Simulation results demonstrate the advantages of the proposed method and the real data analysis of Alzheimer's disease illustrates the practical utility of the techniques. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative database.


Molecular determinants of human prorenin processing.
In humans, active renin is generated by the removal of a 43-amino acid prosegment from the zymogen prorenin. This cleavage event is highly specific, occurring at only one of the seven pairs of basic amino acids in the body of preprorenin. This cleavage site selectivity is also displayed by a number of other proteases in vitro and in mouse pituitary AtT-20 cells transfected with a human preprorenin expression vector, suggesting that specificity of cleavage is directed in part by the primary sequence, the higher order structure, or both of prorenin itself. To test this hypothesis, single amino acid mutations were introduced in the region of human preprorenin surrounding the natural cleavage site, and the resultant recombinant proteins were expressed in cultured Chinese hamster ovary and AtT-20 cells. The results suggest that amino acids in addition to the pair of basic amino acids surrounding the cleavage site affect the ability of both trypsin and the endogenous AtT-20 processing enzyme to cleave prorenin. Notably, although a proline at position -4 is essential for processing of prorenin in AtT-20 cells and is correlated with predicted formation of a beta-turn at this position, site-directed mutations suggest that this structural feature in addition to a pair of basic amino acids is not sufficient to lead to proteolytic activation of prorenin. Displacement of sequences surrounding the cleavage site to a position 10 amino acids toward the amino terminus led to partial processing of a mutated prorenin.(ABSTRACT TRUNCATED AT 250 WORDS)


The reinvigoration of the Southern Ocean carbon sink.
Several studies have suggested that the carbon sink in the Southern Ocean-the ocean's strongest region for the uptake of anthropogenic CO2 -has weakened in recent decades. We demonstrated, on the basis of multidecadal analyses of surface ocean CO2 observations, that this weakening trend stopped around 2002, and by 2012, the Southern Ocean had regained its expected strength based on the growth of atmospheric CO2. All three Southern Ocean sectors have contributed to this reinvigoration of the carbon sink, yet differences in the processes between sectors exist, related to a tendency toward a zonally more asymmetric atmospheric circulation. The large decadal variations in the Southern Ocean carbon sink suggest a rather dynamic ocean carbon cycle that varies more in time than previously recognized.


Glucose inhibition of glucagon secretion from rat alpha-cells is mediated by GABA released from neighboring beta-cells.
gamma-Aminobutyric acid (GABA) has been proposed to function as a paracrine signaling molecule in islets of Langerhans. We have shown that rat beta-cells release GABA by Ca(2+)-dependent exocytosis of synaptic-like microvesicles. Here we demonstrate that GABA thus released can diffuse over sufficient distances within the islet interstitium to activate GABA(A) receptors in neighboring cells. Confocal immunocytochemistry revealed the presence of GABA(A) receptors in glucagon-secreting alpha-cells but not in beta- and delta-cells. RT-PCR analysis detected transcripts of alpha(1) and alpha(4) as well as beta(1-3) GABA(A) receptor subunits in purified alpha-cells but not in beta-cells. In whole-cell voltage-clamp recordings, exogenous application of GABA activated Cl(-) currents in alpha-cells. The GABA(A) receptor antagonist SR95531 was used to investigate the effects of endogenous GABA (released from beta-cells) on pancreatic islet hormone secretion. The antagonist increased glucagon secretion at 1 mmol/l glucose twofold and completely abolished the inhibitory action of 20 mmol/l glucose on glucagon release. Basal and glucose-stimulated secretion of insulin and somatostatin were unaffected by SR95531. The L-type Ca(2+) channel blocker isradipine evoked a paradoxical stimulation of glucagon secretion. This effect was not observed in the presence of SR95531, and we therefore conclude that isradipine stimulates glucagon secretion by inhibition of GABA release.


Congenital lobar emphysema: Thoracotomy versus minimally invasive surgery.
Congenital lobar emphysema (CLE) is a rare developmental malformation of the lung but can be associated with high morbidity and mortality. The objective of this study is to review our experience with 45 patients with CLE highlighting clinical features, aspects of diagnosis, and management. The medical records of all patients diagnosed with CLE in our center were reviewed. Patients age at the time of diagnosis, sex, clinical presentation, associated anomalies, the lobes affected, treatment modality, and outcome were described. A comparison was made between those who had lobectomy via open thoracotomy and those treated thoracoscopically. From January 2000 to December 2018, a total of 45 infants with CLE were presented to our institution. There were 30 male and 15 female, and the mean age at presentation was 3.35 months. Twenty-five patients presented with respiratory distress. Nine patients presented immediately after birth, and two of them had surgery within the 1st week of life. Twenty patients were presented with repeated chest infections. Left upper lobe was affected in 27 patients, right middle lobe in 13, and right upper lobe in 5 patients. Forty-four patients had a lobectomy, and one was managed conservatively. One patient had a postoperative bronchopleural fistula. Nine patients had a thoracoscopic lobectomy, and two of them were converted to open thoracotomy because of persistent air leak. The operative time and hospital stay were nonsignificantly longer in thoracoscopic lobectomy (P = 0.5 and 0.4, respectively). There was no operative mortality in both groups. CLE is a rare malformation with variable presentation. Infants presenting with respiratory distress or recurrent chest infection should be evaluated for the possibility of CLE. Lobectomy is the treatment of choice, and rarely, the patients may be managed conservatively. Thoracoscopic lobectomy is a safe procedure with the possibility of air leak and conversion to open lobectomy.


Assessment of fishery resources using environmental DNA: Small yellow croaker (Larimichthys polyactis) in East China Sea.
Species distribution monitoring and biomass assessment are crucial for fishery management and resource conservation. However, traditional methods such as motor trawling are costly and less effective than the novel environmental DNA (eDNA) approach. This study employs eDNA approach to investigate horizontal and vertical distributions of small yellow croaker (Larimichthys polyactis), an economically important species, in the East China Sea. The analysis of 171 eDNA samples collected from 44 stations using the species-specific primers and Taqman probe suggests a presence of small yellow croaker at 28 sampling layers in 44 stations. Significant differences in croaker eDNA concentrations were revealed among sampling stations and layers, consistent with previous findings through motor-trawl capture offshore and nearshore ichthyoplakton surveys, indicating small yellow croaker exhibits strong regional distribution and layer preference. In addition, we found a high eDNA concentration of small yellow croaker in the surface waters beyond the motor-trawl prohibition line, which confirms spawning grounds have been expanded from nearshore to offshore areas. Such expansion of spawning grounds could be a response by small yellow croaker to stressors such as overfishing, climate change, and nearshore environment contamination. To identify environmental variables potentially associated with small yellow croaker presence and absence, we conducted a correlation analysis between eDNA concentration and environmental variables, and the results provide a guideline for further investigation of fishery resources in the future. In conclusion, this study demonstrates the power of the eDNA approach in monitoring small yellow croaker at extensive geographic scales. The developed protocols and the findings are expected to assist in long-term monitoring and protection programs and benefit sustainable fishery in small yellow croaker.


Design of the oxygen and substrate pathways. VII. Different structural limits for oxygen and substrate supply to muscle mitochondria.
This paper integrates the results of a series of studies on the supply of O2 and substrates for oxidative muscle metabolism and draws conclusions on the role of structural design in partitioning and limiting substrate supply. The studies compared dogs and goats exercising at different intensities and combined physiological, biochemical and morphometric investigations. In both species, the rate of fatty acid oxidation reached an upper limit at low exercise intensities, and only glucose consumption was increased at higher exercise intensities. The supply of both glucose and fatty acids from the capillaries reached maximal rates at low exercise intensities; this limitation is related to the design of the sarcolemma as calculations suggest that the endothelium introduces only a small resistance to substrate flux. From these findings, it appears that the capillaries are designed to satisfy O2 supply up to maximal O2 demand. The increase in substrate supply to the mitochondria at higher exercise intensities is achieved by drawing on intracellular stores of glycogen and lipids. The size of these stores is larger in dogs than in goats, providing the athletic species with twice the fuel reserves. These findings are interpreted on the basis of a network model with fluxes partitioned between direct and indirect pathways and with some structures shared by more than one function. Whereas O2 is supplied through a direct pathway, the supply of both substrates is split temporally to allow, during exercise, immediate fuel supply to the mitochondria from intracellular stores; these are replaced from the vasculature, during periods of rest, to a size commensurate with high rates of combustion. Considering this complexity, we conclude that the results are compatible with the principle of symmorphosis applied to a network structure and that the adjustment of design to functional demand involves different structures for O2 and for substrates.


Impact of the COVID-19 epidemic at a high-volume facility in gynecological oncology in Tokyo, Japan: a single-center experience.
The number of cases of novel coronavirus disease 2019 (COVID-19) in Japan have risen since the first case was reported on January 24, 2020, and 6225 infections have been reported as of June 30, 2020. On April 8, 2020, our hospital began screening patients via pre-admission reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and chest computed tomography (CT). Although no patients exhibited apparent pneumonia, treatment delay or changes in treatment plans were required for a few patients based on the results of screening tests. During an emerging infectious disease pandemic, the likelihood of being infected, as well as the disease itself, affects clinical decision making in several ways. We summarized and presented our experience. After the introduction of pre-admission screening, RT-PCR and CT were performed in 200 and 76 patients, respectively, as of June 30, 2020. The treatment of five patients, including two patients with cervical cancer, two patients with ovarian tumors, and one patient with ovarian cancer, was affected by the results. Two asymptomatic RT-PCR-positive patients did not develop COVID-19, but their treatment was delayed until the confirmation of negative results. The other three patients were RT-PCR-negative, but abnormal CT findings suggested the possibility of COVID-19, which delayed treatment. The patients receiving first-line preoperative chemotherapy for ovarian cancer had clinically evident exacerbations because of the treatment delay. During the epidemic phase of an emerging infectious disease, we found that COVID-19 has several other effects besides its incidence. The postponing treatment was the most common, therefore, treatment of ovarian tumors and ovarian cancer was considered to be the most likely to be affected among gynecological diseases. Protocols that allow for easy over-diagnosis can be disadvantageous, mainly because of treatment delays, and therefore, the protocols must be developed in light of the local infection situation.


Influence of inflammatory polyarthritis on quantitative heel ultrasound measurements.
There are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements. Men and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors. 139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = -10.0; 95% confidence interval (CI) -17.4, -2.6) though BUA was similar (difference = -1.2; 95% CI -4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS. In this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.


Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling.
Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a (13)CO2 labelling method, using a custom-built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1 The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and (13)C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/α-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions.


Impacts of Changes in Atmospheric O2 on Human Physiology. Is There a Basis for Concern?
Concern is often voiced over the ongoing loss of atmospheric O2. This loss, which is caused by fossil-fuel burning but also influenced by other processes, is likely to continue at least for the next few centuries. We argue that this loss is quite well understood, and the eventual decrease is bounded by the fossil-fuel resource base. Because the atmospheric O2 reservoir is so large, the predicted relative drop in O2 is very small even for extreme scenarios of future fossil-fuel usage which produce increases in atmospheric CO2 sufficient to cause catastrophic climate changes. At sea level, the ultimate drop in oxygen partial pressure will be less than 2.5 mm Hg out of a baseline of 159 mmHg. The drop by year 2300 is likely to be between 0.5 and 1.3 mmHg. The implications for normal human health is negligible because respiratory O2 consumption in healthy individuals is only weakly dependent on ambient partial pressure, especially at sea level. The impacts on top athlete performance, on disease, on reproduction, and on cognition, will also be very small. For people living at higher elevations, the implications of this loss will be even smaller, because of a counteracting increase in barometric pressure at higher elevations due to global warming.


Risk Factors Associated with Alcohol Use in Early Adolescence among American Inner-City Youth: A Longitudinal Study.
Background: Early alcohol use is associated with an increased risk for later alcohol dependence, as well as social and mental health problems. In this study, we investigate the risk factors (internalizing and externalizing behaviors) associated with early alcohol consumption over a period of 1 year, and examine whether the association is sex-specific. Methods: U.S. inner-city adolescents (N = 1785, Mean age = 12.11) were assessed and reassessed in the sixth and seventh grades (Mean age = 13.10). Self-reported information was obtained on the lifetime level of alcohol consumption, internalizing (depression, anxiety and posttraumatic stress [PTS]), and externalizing behaviors (sensation seeking, conduct problems and affiliation with delinquent peers). Associations between the variables were examined using structural equation modeling (SEM). Results: In an adjusted SEM analysis drinking by the sixth grade was primarily associated with externalizing behaviors, whereas PTS was linked to lower levels of alcohol consumption. In addition, alcohol consumption and greater externalizing behaviors by the sixth grade predicted higher alcohol consumption by the seventh grade, whereas anxiety and African American ethnicity were associated with less alcohol consumption. No sex differences were found in the association between internalizing and externalizing behaviors and drinking. However, in the adjusted SEM analysis female sex predicted higher lifetime consumption by the seventh grade. Conclusion: Sensation seeking behavior, conduct problems and affiliation with delinquent peers should be regarded as risk factors and taken into consideration when planning prevention efforts in order to decrease alcohol use in early adolescence.


Funding for malaria control 2006-2010: a comprehensive global assessment.
The last decade has seen a dramatic increase in international and domestic funding for malaria control, coupled with important declines in malaria incidence and mortality in some regions of the world. As the ongoing climate of financial uncertainty places strains on investment in global health, there is an increasing need to audit the origin, recipients and geographical distribution of funding for malaria control relative to populations at risk of the disease. A comprehensive review of malaria control funding from international donors, bilateral sources and national governments was undertaken to reconstruct total funding by country for each year 2006 to 2010. Regions at risk from Plasmodium falciparum and/or Plasmodium vivax transmission were identified using global risk maps for 2010 and funding was assessed relative to populations at risk. Those nations with unequal funding relative to a regional average were identified and potential explanations highlighted, such as differences in national policies, government inaction or donor neglect. US$8.9 billion was disbursed for malaria control and elimination programmes over the study period. Africa had the largest levels of funding per capita-at-risk, with most nations supported primarily by international aid. Countries of the Americas, in contrast, were supported typically through national government funding. Disbursements and government funding in Asia were far lower with a large variation in funding patterns. Nations with relatively high and low levels of funding are discussed. Global funding for malaria control is substantially less than required. Inequity in funding is pronounced in some regions particularly when considering the distinct goals of malaria control and malaria elimination. Efforts to sustain and increase international investment in malaria control should be informed by evidence-based assessment of funding equity.


A GABAergic system in airway epithelium is essential for mucus overproduction in asthma.
Gamma-aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. Here we show that an excitatory, rather than inhibitory, GABAergic system exists in airway epithelial cells. Both GABAARs and the GABA synthetic enzyme glutamic acid decarboxylase (GAD) are expressed in pulmonary epithelial cells. Activation of GABAARs depolarized these cells. The expression of GAD in the cytosol and GABAARs in the apical membranes of airway epithelial cells increased markedly when mice were sensitized and then challenged with ovalbumin, an approach for inducing allergic asthmatic reactions. Similarly, GAD and GABAARs in airway epithelial cells of humans with asthma increased after allergen inhalation challenge. Intranasal application of selective GABAAR inhibitors suppressed the hyperplasia of goblet cells and the overproduction of mucus induced by ovalbumin or interleukin-13 in mice. These findings show that a previously unknown epithelial GABAergic system has an essential role in asthma.


Poor long-term blood pressure control after intracerebral hemorrhage.
Hypertension is the most important risk factor associated with intracerebral hemorrhage. We explored racial differences in blood pressure (BP) control after intracerebral hemorrhage and assessed predictors of BP control at presentation, 30 days, and 1 year in a prospective cohort study. Subjects with spontaneous intracerebral hemorrhage were identified from the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) Project. BP was compared by race at each time point. Multivariable linear regression was used to determine predictors of presenting mean arterial pressure, and longitudinal linear regression was used to assess predictors of mean arterial pressure at follow-up. A total of 162 patients were included (mean age, 59 years; 53% male; 77% black). Mean arterial pressure at presentation was 9.6 mm Hg higher in blacks than whites despite adjustment for confounders (P=0.065). Fewer than 20% of patients had normal BP (<120/80 mm Hg) at 30 days or 1 year. Although there was no difference at 30 days (P=0.331), blacks were more likely than whites to have Stage I/II hypertension at 1 year (P=0.036). Factors associated with lower mean arterial pressure at follow-up in multivariable analysis were being married at baseline (P=0.032) and living in a facility (versus personal residence) at the time of BP measurement (P=0.023). Long-term BP control is inadequate in patients after intracerebral hemorrhage, particularly in blacks. Further studies are needed to understand the role of social support and barriers to control to identify optimal approaches to improve BP in this high-risk population.


Baroreflex sensitivity, heart rate, and blood pressure variability in hypertensive pregnancy disorders.
Hypertensive pregnancy disorders are a leading cause of perinatal and maternal morbidity and mortality. Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) are relevant predictors of cardiovascular risk in humans. The aim of the study was to evaluate whether HRV, BPV, and BRS differ between distinct hypertensive pregnancy disorders. Continuous heart rate and blood pressure recordings were performed in 80 healthy pregnant women as controls (CON), 19 with chronic hypertension (CH), 18 with pregnancy-induced hypertension (PIH), and 44 with pre-eclampsia (PE). The data were assessed by time and frequency domain analysis, nonlinear dynamics, and BRS. BPV is markedly altered in all three groups with hypertensive disorders compared to healthy pregnancies, whereby changes were most pronounced in PE patients. Interestingly, this increase in PE patients did not lead to elevated spontaneous baroreflex events, while BPV changes in both the other hypertensive groups were paralleled by alterations in baroreflex parameters. The HRV is unaltered in CH and PE but significantly impaired in PIH. We conclude that parameters of the HRV, BPV, and BRS differ between various hypertensive pregnancy disorders. Thus, distinct clinical manifestations of hypertension in pregnancy have different pathophysiological, regulatory, and compensatory mechanisms.


Too few or too many? Reactions to removing versus retaining specific personality disorders in DSM-5.
The present review examines the decision of the DSM-5 Personality and Personality Disorders Working Group to retain or to remove specific personality disorders included in DSM-IV-TR and presents the reactions elicited by the decision and published between 10 February 2010 and 30 September 2012. In the first draft of Chapter P (Personality disorders), posted on the DSM-5 Internet site on 10 February 2010, the DSM-5 Personality and Personality Disorders Working Group proposed to remove paranoid, schizoid, histrionic, dependent and narcissistic personality disorders from the classification. A revised version of the draft, posted on the Internet in June 2011, reinstated narcissistic personality disorder but not the four remaining types that had been slated for removal. Underlying the decision of the Work Group for retaining versus removing specific personality disorder types are arguments concerning the clinical utility and validity of each type. The arguments provided by the Work Group have not been accepted unanimously by other personality disorder experts. DSM-5 will retain six out of the 10 personality disorder types listed in DSM-IV-TR while removing the remaining four types. Reactions to the decision and to the arguments presented for doing so have been mixed.


Commonly consumed protein foods contribute to nutrient intake, diet quality, and nutrient adequacy.
The amount of dietary protein needed to prevent deficiency in most individuals is defined in the United States and Canada by the Recommended Dietary Allowance and is currently set at 0.8 g protein · kg-1 · d-1 for adults. To meet this protein recommendation, the intake of a variety of protein food sources is advised. The goal of this article is to show that commonly consumed food sources of protein are more than just protein but also significant sources of essential nutrients. Commonly consumed sources of dietary protein frequently contribute substantially to intakes of nutrients such as calcium, vitamin D, potassium, dietary fiber, iron, and folate, which have been identified as nutrients of "concern" (i.e., intakes are often lower than recommended). Despite this, dietary recommendations to reduce intakes of saturated fat and solid fats may result in dietary guidance to reduce intakes of commonly consumed food sources of protein, in particular animal-based protein. We propose that following such dietary guidance would make it difficult to meet recommended intakes for a number of nutrients, at least without marked changes in dietary consumption patterns. These apparently conflicting pieces of dietary guidance are hard to reconcile; however, we view it as prudent to advise the intake of high-quality dietary protein to ensure adequate intakes of a number of nutrients, particularly nutrients of concern.


Partitioning in situ total spectral absorption by use of moored spectral absorption-attenuation meters.
High-temporal-resolution spectral absorption data were acquired by use of one bottom-mounted (approximately 68-m) and three moored spectral absorption and attenuation meters (ac-9 meters at 14, 37, and 52 m) on the Middle Atlantic Bight continental shelf during the fall 1996 period of the Coastal Mixing and Optics experiment. We employed a previously published spectral absorption model with the data to partition total absorption into absorption by water, phytoplankton, detritus, and gelbstoff (dissolved matter). We validated the model by comparing its results against coincident in vivo absorption coefficients derived from discrete bottle samples. Correlations between modeled and in vivo spectra range from 0.873 to 0.998. We optimized these correlations to determine the model parameters. These parameters could not be determined solely from the moored ac-9 results. Therefore a separate set of absorption measurements (from discrete bottle samples) was necessary to permit values for the model parameters to be determined. Model results allow us to separate particulate and dissolved components of absorption and to examine the temporal variability and the vertical distributions and concentrations of each component, given the total absorption in the water column.


Mapping the occupational therapy workforce research worldwide: Study protocol for a scoping review.
Human Resources for Health (HRH) research informs the development of evidence-based, population-centered HRH policies and practices. Occupational therapists are key human resources for meeting the health, rehabilitation, and occupational needs of the population worldwide. Yet, the global status of the occupational therapy workforce research remains unchartered. This study protocol depicts the methods to map out and synthesize the occupational therapy workforce research worldwide. Six scientific-literature databases and key international institutional websites will be systematically searched, complemented by snowballing searches and recommendations from key global, regional, or national representatives of the World Federation of Occupational Therapists. Two independent reviewers will screen titles-and-abstracts and then full-texts against the eligibility criteria, e.g., 10 categories of workforce research. Educational research, non-empirical papers, and papers (or their summaries) not available in English, Spanish or Portuguese are excluded. Data extraction (e.g., methods, geographies, aims, key findings) will be conducted by one author and fully verified by another. The extracted data will be computed as well as subject to content analysis to provide quantitative map of the literature and of the contents addressed, e.g., per inclusion category. The results of this review can inform wide consultation processes and strategic, concerted local and global developments of the occupational therapy workforce.


Immune responses to soluble antigens of treponemes.
Sonicates from five cultivable treponemes were used as antigens in delayed hypersensitivity tests and macrophage inhibition assays. Immunodiffusion analysis showed that the sonicate comprised two major antigenic components which were not distinguishable in the skin tests. The sonicate antigens elicited significant cell-mediated immunity in guinea-pigs. Treponema refringens biotype Nichols proved to induce the strongest delayed response. Delayed skin hypersensitivity to the antigens of Treponema pallidum was found in eight rabbits without orchitis, but not in six rabbits with T. pallidum orchitis. In contrast, the rabbits with syphilitic orchitis gave the strongest reactions with the non-pathogenic spirochetes. In terms of the cell-mediated immunity responses, Treponema phagedenis Reiter was found to be related to T. phagedenis Kazan 4 and Treponema denticola. Treponema scoliodontum was related to T. phagedenis Kazan 5, and T. refringens biotypes Nichols and refringens. The antigens of T. pallidum had the closest relationship to T. refringens biotypes refringens and Nichols ,T. phagedenis biotype Reiter, and T. scoliodontum. It was also demonstrated that some three of 12 human syphilitic sera reacted with the antigens of T. pallidum but not with control sera.


Ventral tegmental oxytocin induces grooming.
Bilateral microinjection of oxytocin (OXY) into the ventral tegmental area (VTA) of rat brain produced a significant increase in grooming behaviors at doses from 100 pg to 400 ng. Sites in the caudal region of the VTA were sensitive to lower doses of OXY than sites in the rostral region of the VTA. The time course of action of OXY in the grooming paradigm indicated onset beginning immediately after injection, and termination at 60-75 minutes after injection. Comparison of OXY-induced grooming in male, female, and ovariectomized, estrogen-treated female rats showed no differences in potency for OXY among these groups, suggesting that the grooming effects of OXY are not regulated by sex steroids. Analysis of locomotor activity in rats microinjected with OXY 200 ng bilaterally into the caudal VTA revealed that OXY had no effect on ambulatory locomotion, suggesting that this peptide may activate neurons within the VTA which mediate grooming but not locomotion. The OXY receptor antagonist, [Pen1, pMePhe2, Thr4, Orn8]-OT, blocked OXY-induced grooming when both were simultaneously microinjected into the VTA. The dopamine D-2 receptor antagonist, haloperidol, and the D-1 receptor antagonist, SCH 23390, when microinjected into the VTA five minutes before microinjection of OXY into the VTA, did not block OXY-induced grooming, suggesting that OXY is not working through a dopamine autoreceptor on the VTA neurons. Systemic pretreatment with haloperidol and SCH 23390 effectively blocked grooming induced by OXY in the VTA, suggesting that OXY is directly stimulating OXY receptors on VTA neurons to release dopamine at postsynaptic sites regulating grooming behaviors.


Malnutrition screening and treatment in pediatric oncology: a scoping review.
Malnutrition and cachexia during pediatric cancer treatment worsen toxicity and quality-of-life. Clinical practice varies with lack of standard malnutrition definition and nutrition interventions. This scoping review highlights available malnutrition screening and intervention data in childhood cancer and the need for standardizing assessment and treatment. Ovid Medline, CINAHL, and Cochrane Library were searched for studies containing malnutrition as the primary outcome with anthropometric, radiographic, or biochemical measurements. Secondary outcomes included validated nutritional assessment or screening tools. Two authors reviewed full manuscripts for inclusion. Narrative analysis was chosen over statistical analysis due to study heterogeneity. The search yielded 234 articles and 17 articles identified from reference searching. Nine met inclusion criteria with six nutritional intervention studies (examining appetite stimulants, nutrition supplementation, and proactive feeding tubes) and three nutritional screening studies (algorithms or nutrition support teams) each with variable measures and outcomes. Both laboratory evaluations (albumin, prealbumin, total protein) and body measurement (weight loss, mid-upper arm circumference) were used. Studies demonstrated improved weight, without difference between formula or appetite stimulant used. Screening studies yielded mixed results on preventing weight loss, weight gain, and survival. Our review demonstrated a paucity of evidence for malnutrition screening and intervention in pediatric cancer treatment. While a variety of malnutrition outcomes, interventions, and screening tools exist, nutritional interventions increased weight and decreased complications. Screening tools decreased malnutrition risk and may improve weight gain. Potential age- and disease-specific nutritional benefits and toxicities also exist, further highlighting the benefit of standardizing malnutrition definitions, screening, and interventions.


Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice.
Despite well-documented evidence for lifespan extension by methionine restriction (MR), underlying mechanisms remain unknown. As methionine can alter S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the substrate and product of DNA methyltransferase-1 (DNMT1), we hypothesized that MR diet alters DNA methylation. Young (8-week-old) and adult (1-year-old) male C57BL/6J mice were fed diets with different levels of methionine (0.12%-MR, 0.84%-CD) for 12weeks. Functional indicators of DNA methylation, including global methylation (GM), gene-specific methylation (GSM) and LINE-1 methylation; and biochemical factors affecting DNA methylation, SAH, SAM, and DNMT1 were assessed in different tissues. MR altered DNA methylation depending on the age of intervention. While MR had no effect on hepatic GM in young animals, it increased GM by 27% over CD in adults (p<0.01). In comparison with young animals, hepatic GM levels were 17% lower in CD adults (p<0.05), but not different in MR adults. The MR-induced increase in hepatic GM was associated with a 38% decrease in SAH levels in adults (p<0.001), with SAH and GM levels being negatively correlated (r2=0.33, p<0.001). No changes were observed in DNMT protein levels in liver. In adipose tissue, MR caused a 6% decline in GM in adults (p<0.05), a corresponding 2-fold increase in SAH (p<0.05), and a 2-fold decrease in DNMT1 (p<0.01). MR caused both increases and decreases in GSM of liver and adipose. No changes were observed in LINE-1. Together, these findings provide evidence for protective effects of MR diet on hepatic DNA hypomethylation in adults, apparently mediated by SAH. These findings also indicate that altered DNA methylation might be playing a role in benefits conferred by MR diet.


Interprofessional working or role substitution? A discussion of the emerging roles in emergency care.
This article presents a discussion of emerging non-medical roles in emergency care against the current policy context and the issues of role substitution and interprofessional working. Non-medical roles in emergency care have grown internationally in response to an increasing demand for emergency care services and to address the growing importance of the quality healthcare agenda. The blurring of role boundaries between professional groups has become more common. Data sources. Searches were made of three electronic databases; CINAHL, Medline and EMBASE. The literature relating to interprofessional healthcare roles, and new roles in emergency care was searched from 1980 to 2010 and underpinned the discussion. A theoretical framework that has emerged from the literature is that task, role substitution and interprofessional working lie on a spectrum and evolving non-medical roles can be plotted on the spectrum, usually starting at one end of the spectrum under task substitution and then potentially moving in time towards true interprofessional working. There is still a great deal of progress to be made until non-medical roles in emergency care can truly be encompassed under the umbrella of interprofessional working and that a more robust critical mass of evidence is required to substantiate the theory that interprofessional working within teams contributes to effective, cost-effective care and better patient outcomes. It is essential to understand the underlying motivation, policy context and key drivers for the development of new nursing and non-medical roles. This allows services to be established successfully, by understanding and addressing the key predicable barriers to implementation and change.


Cumulative Risk Distribution for Interval Invasive Second Breast Cancers After Negative Surveillance Mammography.
Purpose The aim of the current study was to characterize the risk of interval invasive second breast cancers within 5 years of primary breast cancer treatment. Methods We examined 65,084 surveillance mammograms from 18,366 women with a primary breast cancer diagnosis of unilateral ductal carcinoma in situ or stage I to III invasive breast carcinoma performed from 1996 to 2012 in the Breast Cancer Surveillance Consortium. Interval invasive breast cancer was defined as ipsilateral or contralateral cancer diagnosed within 1 year after a negative surveillance mammogram. Discrete-time survival models-adjusted for all covariates-were used to estimate the probability of interval invasive cancer, given the risk factors for each surveillance round, and aggregated across rounds to estimate the 5-year cumulative probability of interval invasive cancer. Results We observed 474 surveillance-detected cancers-334 invasive and 140 ductal carcinoma in situ-and 186 interval invasive cancers which yielded a cancer detection rate of 7.3 per 1,000 examinations (95% CI, 6.6 to 8.0) and an interval invasive cancer rate of 2.9 per 1,000 examinations (95% CI, 2.5 to 3.3). Median cumulative 5-year interval cancer risk was 1.4% (interquartile range, 0.8% to 2.3%; 10th to 90th percentile range, 0.5% to 3.7%), and 15% of women had ≥ 3% 5-year interval invasive cancer risk. Cumulative 5-year interval cancer risk was highest for women with estrogen receptor- and progesterone receptor-negative primary breast cancer (2.6%; 95% CI, 1.7% to 3.5%), interval cancer presentation at primary diagnosis (2.2%; 95% CI, 1.5% to 2.9%), and breast conservation without radiation (1.8%; 95% CI, 1.1% to 2.4%). Conclusion Risk of interval invasive second breast cancer varies across women and is influenced by characteristics that can be measured at initial diagnosis, treatment, and imaging. Risk prediction models that evaluate the risk of cancers not detected by surveillance mammography should be developed to inform discussions of tailored surveillance.


Dual nickel and Lewis acid catalysis for cross-electrophile coupling: the allylation of aryl halides with allylic alcohols.
Controlling the selectivity in cross-electrophile coupling reactions is a significant challenge, particularly when one electrophile is much more reactive. We report a general and practical strategy to address this problem in the reaction between reactive and unreactive electrophiles by a combination of nickel and Lewis acid catalysis. This strategy is used for the coupling of aryl halides with allylic alcohols to form linear allylarenes selectively. The reaction tolerates a wide range of functional groups (e.g. silanes, boronates, anilines, esters, alcohols, and various heterocycles) and works with various allylic alcohols. Complementary to most current routes for the C3 allylation of an unprotected indole, this method provides access to C2 and C4-C7 allylated indoles. Preliminary mechanistic experiments reveal that the reaction might start with an aryl nickel intermediate, which then reacts with Lewis acid activated allylic alcohols in the presence of Mn.


MALT1 is an intrinsic regulator of regulatory T cells.
Regulatory T cells (Tregs) are crucial for the maintenance of immunological self-tolerance and their absence or dysfunction can lead to autoimmunity. However, the molecular pathways that govern Treg biology remain obscure. In this study, we show that the nuclear factor-κB signalling mediator mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an important novel regulator of both Tregs originating in the thymus ('natural' or nTregs) and Tregs induced to differentiate from naive thymocyte helper (Th) cells in the periphery ('induced' or iTregs). Our examination of mice deficient for MALT1 revealed that these mutants have a reduced number of total Tregs. In young Malt1-/- mice, nTregs are totally absent and iTreg are diminished in the periphery. Interestingly, total Treg numbers increase in older Malt1-/- mice as well as in Malt1-/- mice subjected to experimentally induced inflammation. iTregs isolated from WT and Malt1-/- mice were indistinguishable with respect to their ability to suppress the activities of effector T cells, but Malt1-/- iTregs expressed higher levels of Toll-like receptor (TLR) 2. Treatment of WT and Malt1-/- Th cells in vitro with the TLR2 ligand Pam3Cys strongly enhanced the induction and proliferation of Malt1-/- iTregs. Our data suggest that MALT1 supports nTreg development in the thymus but suppresses iTreg induction in the periphery during inflammation. Our data position MALT1 as a key molecule that contributes to immune tolerance at steady-state while facilitating immune reactivity under stress conditions.


Deletion of the MTO2 gene related to tRNA modification causes a failure in mitochondrial RNA metabolism in the yeast Saccharomyces cerevisiae.
We report here the characterization of the yeast mto2 null mutants carrying wild-type mitochondrial DNA or 15S rRNA C1049G allele. The amounts of mitochondrial tRNA(Lys), tRNA(Glu), tRNA(Gln), tRNA(Leu), tRNA(Gly) and tRNA(Met) were markedly decreased but those of tRNA(Arg) and tRNA(His) were not affected in mto2 strains. The mto2 strains exhibited significant reduction in the aminoacylation of tRNA(Lys), tRNA(Leu) but almost no effect in those of tRNA(His). Interestingly, the strain carrying the C1049G allele exhibited an impairment of aminoacylation of those tRNAs. Furthermore, the steady-state levels of mitochondrial mRNA CYTB, COX1, COX2, COX3, and ATP6 were markedly decreased in mto2 strains. These data strongly indicate that unmodified tRNA caused by the deletion of MTO2 caused the instability of mitochondrial tRNAs and mRNAs and impairment of aminoacylation of tRNAs.


[Trends of homicide death in Brazil in the 90s: the role of firearms].
To describe the growth of homicide death in Brazil and to investigate the contribution of firearms to homicide death growth in the 90s. An ecological descriptive time series was carried out for the period 1991 to 2000. External cause mortality data were obtained according to place of residence for the overall population and by gender from the Ministry of Health Mortality Information System. Homicides were classified as firearm, non-firearm and unknown (weapon) deaths. Proportional mortality and mortality rates (by 100,000) were calculated. Homicides accounted for 33% of all external cause deaths in the 90s. Firearms were used in more than 50% of deaths in 1991 and in almost 70% in 2000. This growth was seen for both genders and in all state capitals. Homicide mortality rate grew 27.5% in the whole country, and firearm homicide mortality rate grew 72.5%. During the same period there was a drop in deaths classified as unknown weapon homicide, which could partially explain the growth seen in firearm homicide rates. Data suggest the magnitude of firearm contribution for the growing tendency of homicide deaths in Brazil in the 90s. Data quality regarding intentionality and type of weapon used has hindered data analysis.


Pup Vibrissae Stable Isotopes Reveal Geographic Differences in Adult Female Southern Sea Lion Habitat Use during Gestation.
Individuals within populations often differ substantially in habitat use, the ecological consequences of which can be far reaching. Stable isotope analysis provides a convenient and often cost effective means of indirectly assessing the habitat use of individuals that can yield valuable insights into the spatiotemporal distribution of foraging specialisations within a population. Here we use the stable isotope ratios of southern sea lion (Otaria flavescens) pup vibrissae at the Falkland Islands, in the South Atlantic, as a proxy for adult female habitat use during gestation. A previous study found that adult females from one breeding colony (Big Shag Island) foraged in two discrete habitats, inshore (coastal) or offshore (outer Patagonian Shelf). However, as this species breeds at over 70 sites around the Falkland Islands, it is unclear if this pattern is representative of the Falkland Islands as a whole. In order to characterize habitat use, we therefore assayed carbon (δ13C) and nitrogen (δ15N) ratios from 65 southern sea lion pup vibrissae, sampled across 19 breeding colonies at the Falkland Islands. Model-based clustering of pup isotope ratios identified three distinct clusters, representing adult females that foraged inshore, offshore, and a cluster best described as intermediate. A significant difference was found in the use of inshore and offshore habitats between West and East Falkland and between the two colonies with the largest sample sizes, both of which are located in East Falkland. However, habitat use was unrelated to the proximity of breeding colonies to the Patagonian Shelf, a region associated with enhanced biological productivity. Our study thus points towards other factors, such as local oceanography and its influence on resource distribution, playing a prominent role in inshore and offshore habitat use.


High Throughput Sequencing of MicroRNA in Rainbow Trout Plasma, Mucus, and Surrounding Water Following Acute Stress.
Circulating plasma microRNAs (miRNAs) are well established as biomarkers of several diseases in humans and have recently been used as indicators of environmental exposures in fish. However, the role of plasma miRNAs in regulating acute stress responses in fish is largely unknown. Tissue and plasma miRNAs have recently been associated with excreted miRNAs; however, external miRNAs have never been measured in fish. The objective of this study was to identify the altered plasma miRNAs in response to acute stress in rainbow trout (Oncorhynchus mykiss), as well as altered miRNAs in fish epidermal mucus and the surrounding ambient water. Small RNA was extracted and sequenced from plasma, mucus, and water collected from rainbow trout pre- and 1 h-post a 3-min air stressor. Following small RNA-Seq and pathway analysis, we identified differentially expressed plasma miRNAs that targeted biosynthetic, degradation, and metabolic pathways. We successfully isolated miRNA from trout mucus and the surrounding water and detected differences in miRNA expression 1-h post air stress. The expressed miRNA profiles in mucus and water were different from the altered plasma miRNA profile, which indicated that the plasma miRNA response was not associated with or immediately reflected in external samples, which was further validated through qPCR. This research expands understanding of the role of plasma miRNA in the acute stress response of fish and is the first report of successful isolation and profiling of miRNA from fish mucus or samples of ambient water. Measurements of miRNA from plasma, mucus, or water can be further studied and have potential to be applied as non-lethal indicators of acute stress in fish.


The impact of sample type and procedural attributes on relative acceptability of different colorectal cancer screening regimens.
In Australia and other countries, participation in colorectal cancer (CRC) screening using fecal occult blood testing is low. Previous research suggests that fecal sampling induces disgust, so approaches not involving feces may increase participation. This study aimed to determine population preferences for CRC screening tests that utilize different sample collections (stool, blood, and saliva) and the extent to which specific attributes (convenience, performance, and cost) impact this preference. People aged 50-74 years completed a survey. Preference for screening for CRC through stool, blood, and saliva was judged through ranking of preference and attributes critical to preference and confirmed via a discrete choice experiment (DCE) where test attributes were described as varying by performance, cost, and sample type. Participants also completed a measure of aversion to sample type. A total of 1,282 people participated in the survey. The DCE and ranking exercise confirmed that all test attributes had a statistically significant impact on respondents' preferences (P < 0.001). Blood and saliva were equally preferred over stool; however, test performance was the most influential attribute. In multivariable analyses, those who preferred blood to stool collection exhibited higher aversion to fecal (OR = 1.17; P ≤ 0.001) and saliva (OR = 1.06; P ≤ 0.05) sampling and perceived that they had less time for home sample collection (OR = 0.72, P ≤ 0.001). Those who preferred saliva to stool had higher aversion to fecal (OR = 1.15; P ≤ 0.001) and blood (OR = 1.06, P ≤ 0.01) sampling and less time for home sample collection (OR = 0.81, P ≤ 0.5). Aversion to sample type and perceived inconvenience of sample collection are significant drivers of screening preference. While blood and saliva sampling were the most preferred methods, test performance was the most important attribute of a screening test, regardless of sample type. Efforts to increase CRC screening participation should focus on a test, or combination of tests, that combines the attributes of high performance, low aversion, and convenience of use.


Fragile X- associated Neuropsychiatric Disorders: A Case Report.
Mutations in the Fragile X Mental Retardation 1 (FMR1) gene create a spectrum of developmental disorders in children in addition to neurodegenerative problems in older populations. Two types of mutations are recognized in the FMR1 gene. The full mutation (>200 CGG repeats) in the FMR1 gene leads to Fragile X Syndrome which is the most common inherited cause of intellectual disability and autism, while the premutation (55 to 200 CGG repeats) identified among carriers leads to a range of problems linked to elevated levels of the FMR1 mRNA leading to mRNA toxicity and occasionally mildly deficient FMRP levels. Two disorders among premutation carriers have been recognized namely: the Fragile X-associated Primary Ovarian Insufficiency (FXPOI) and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). Recently, in order to recognize a group of associated disorders commonly found in premutation carriers and extensively reported in co-morbidities studies, a new distinctive name was proposed: Fragile X-associated Neuropsychiatric Disorders (FXAND). This paper will present a case report of a female premutation carrier who has encountered predominantly psychiatric problems, but also chronic pain and sleep disturbances consistent with FXAND.


Literature review of trauma-informed care: Implications for mental health nurses working in acute inpatient settings in Australia.
Trauma-informed care (TIC) is increasingly recognized as an approach to improving consumers' experience of, and outcomes from, mental health services. Deriving consensus on the definition, successful approaches, and consumer experiences of TIC is yet to be attained. In the present study, we sought to clarify the challenges experienced by mental health nurses in embedding TIC into acute inpatient settings within Australia. A systematic search of electronic databases was undertaken to identify primary research conducted on the topic of TIC. A narrative review and synthesis of the 11 manuscripts retained from the search was performed. The main findings from the review indicate that there are very few studies focussing on TIC in the Australian context of acute mental health care. The review demonstrates that TIC can support a positive organizational culture and improve consumer experiences of care. The present review highlights that there is an urgency for mental health nurses to identify their role in delivering and evaluating TIC, inclusive of undertaking training and clinical supervision, and to engage in systemic efforts to change service cultures.


Effects of propolis on warfarin efficacy.
Warfarin is commonly used to avoid thromboembolism, predominantly for cardiovascular pathologies. However, the consumption of several herbal products is not permitted during its use due to the associated interactions. Propolis is a popular phytotherapy product made by honey bees. The use of propolis has been dramatically increasing in recent times. To evaluate the possible interactions between propolis and warfarin in a mouse model with determination of the international normalized ratio (INR) values. CD-1 mice were employed in the experimental model. The mice were warfarinized, and propolis was administered simultaneously. The INR values were obtained. All animals were sacrificed at the end of the study. The baseline INR value was 0.8 ±0.1. After 72 h, the INR value increased as expected. The INR value was 7.28 ±1.08 in the control group and 5.8 ±2.88 in the propolis group. At the end of the study, the INR value was 1.3 ±0.37. Propolis interacted with warfarin and caused a decrease in the INR value. Propolis interactions, especially with warfarin, should be kept in mind and further studied. Healthcare specialists should be aware of this possible interaction between warfarin and propolis and inform patients about it.


Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality.
Data on the health benefits and risks of postmenopausal hormone therapy (HT) are derived mainly from the use of conjugated equine estrogens. Estradiol-based regimens may have a different risk-benefit profile. We evaluated the risk of death caused by coronary heart disease (CHD), stroke, or any disease among users of estradiol-based HT regimens in a nationwide study in Finland. A total of 489,105 women who used HT from 1994 to 2009 (3.3 million HT exposure years), as indicated in the nationwide reimbursement register and the national Cause of Death Register, were followed. A total of 28,734 HT users died during follow-up; among the deaths, 3,843 were caused by CHD and 2,464 were caused by stroke. Mortality risk in HT users with varying duration of exposure (≤1 y, >1 to 3 y, >3 to 5 y, >5 to 10 y, or >10 y) was compared with that in an age-matched background population. Risk of CHD death was significantly reduced by 18% to 54% in HT users and was positively related to HT exposure time. Risk of stroke death was also reduced by 18% to 39%, but this reduction was not clearly related to HT exposure time. Risk of all-cause mortality was reduced in HT users by 12% to 38%, almost in linear relationship with duration of exposure. All these risk reductions were comparable in women initiating HT before age 60 years and women initiating HT at age 60 years or older. In absolute terms, the risk reductions mean 19 fewer CHD deaths and 7 fewer stroke deaths per 1,000 women using any HT for at least 10 years.


Turning negotiation into a corporate capability.
Every company today exists in a complex web of relationships formed, one at a time, through negotiation. Purchasing and outsourcing contracts are negotiated with vendors. Marketing arrangements are negotiated with distributors. Product development agreements are negotiated with joint-venture partners. Taken together, the thousands of negotiations a typical company engages in have an enormous effect on both its strategy and its bottom line. But few companies think systematically about their negotiating activities as a whole. Instead they take a situational view, perceiving each negotiation to be a separate event with its own goals, tactics, and measures of success. Coordinating them all seems an overwhelming and impracticable job. In reality, the author argues, it is neither. A number of companies are successfully building coordinated negotiation capabilities by applying four broad changes in practice and perspective. First, they've established a company-wide negotiation infrastructure to apply the knowledge gained from forging past agreements to improve future ones. Second, they've broadened the measures they use to evaluate negotiators' performance beyond matters of cost and price. Third, they draw a clear distinction between the elements of an individual deal and the nature of the ongoing relationship between the parties. Fourth, they make their negotiators feel comfortable walking away from a deal when it's not in the company's best interests. These changes aren't radical steps. But taken together, they will let companies establish closer, more creative relationships with suppliers, customers, and other partners.