Positive and negative emotional verbal stimuli elicit activity in the left amygdala.
The human amygdala's involvement in negative emotion is well established, but relatively little is known regarding its role in positive emotion. Here we examined the neural response to emotionally positive, negative, and neutral words using fMRI. Relative to neutral words, positive and negative emotional words elicited greater activity in the left amygdala. Positive but not negative words elicited activity in dorsal and ventral striatal regions which have been linked in previous neuroimaging studies to reward and positive affect, including caudate, putamen, globus pallidus, and accumbens. These findings provide the first direct evidence that the amygdala is involved in emotional reactions elicited by both positive and negative emotional words, and further indicate that positive words additionally activate brain regions related to reward.


A large-scale test of the link between intergroup contact and support for social change.
Guided by the early findings of social scientists, practitioners have long advocated for greater contact between groups to reduce prejudice and increase social cohesion. Recent work, however, suggests that intergroup contact can undermine support for social change towards greater equality, especially among disadvantaged group members. Using a large and heterogeneous dataset (12,997 individuals from 69 countries), we demonstrate that intergroup contact and support for social change towards greater equality are positively associated among members of advantaged groups (ethnic majorities and cis-heterosexuals) but negatively associated among disadvantaged groups (ethnic minorities and sexual and gender minorities). Specification-curve analysis revealed important variation in the size-and at times, direction-of correlations, depending on how contact and support for social change were measured. This allowed us to identify one type of support for change-willingness to work in solidarity- that is positively associated with intergroup contact among both advantaged and disadvantaged group members.


Characterizing the admixed African ancestry of African Americans.
Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin. From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans. These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.


Liquid like nucleation in free-standing nanoscale films.
The concept of a critical nucleus size (r*) is of pivotal importance in phase transformations involving nucleation and growth. The current investigation pertains to crystallization in nanoscale thin films and study of the same using high resolution lattice fringe imaging (HRLFI) and finite element simulations. Using the CuZrAl bulk metallic glass system as a model system for this study, we demonstrate a liquid like nucleation behaviour in nanoscale free-standing films upon heating. The r* for the formation of the Cu10Zr7 phase in thin films (of decreasing thickness) approaches that of the r* for the formation of the crystal from a liquid (i.e.). Working in the nucleation dominant regime, we introduce the concept of 'depth sensitive lattice fringe imaging'. The thickness of the film is determined by electron energy loss spectroscopy and the strain energy of the system is computed using finite element computations.


Phylogenetic position of the Pentastomida and (pan)crustacean relationships.
Pentastomids are a small group of vermiform animals with unique morphology and parasitic lifestyle. They are generally recognized as being related to the Arthropoda; however, the nature of this relationship is controversial. We have determined the complete sequence of the mitochondrial DNA (mtDNA) of the pentastomid Armillifer armillatus and complete or nearly complete mtDNA sequences from representatives of four previously unsampled groups of Crustacea: Remipedia (Speleonectes tulumensis), Cephalocarida (Hutchinsoniella macracantha), Cirripedia (Pollicipes polymerus) and Branchiura (Argulus americanus). Analyses of the mtDNA gene arrangements and sequences determined in this study indicate unambiguously that pentastomids are a group of modified crustaceans probably related to branchiurans. In addition, gene arrangement comparisons strongly support an unforeseen assemblage of pentastomids with maxillopod and cephalocarid crustaceans, to the exclusion of remipedes, branchiopods, malacostracans and hexapods.


Effects of macronutrient intake in obesity: a meta-analysis of low-carbohydrate and low-fat diets on markers of the metabolic syndrome.
The metabolic syndrome (MetS) comprises cardiometabolic risk factors frequently found in individuals with obesity. Guidelines to prevent or reverse MetS suggest limiting fat intake, however, lowering carbohydrate intake has gained attention too. The aim for this review was to determine to what extent either weight loss, reduction in caloric intake, or changes in macronutrient intake contribute to improvement in markers of MetS in persons with obesity without cardiometabolic disease. A meta-analysis was performed across a spectrum of studies applying low-carbohydrate (LC) and low-fat (LF) diets. PubMed searches yielded 17 articles describing 12 separate intervention studies assessing changes in MetS markers of persons with obesity assigned to LC (<40% energy from carbohydrates) or LF (<30% energy from fat) diets. Both diets could lead to weight loss and improve markers of MetS. Meta-regression revealed that weight loss most efficaciously reduced fasting glucose levels independent of macronutrient intake at the end of the study. Actual carbohydrate intake and actual fat intake at the end of the study, but not the percent changes in intake of these macronutrients, improved diastolic blood pressure and circulating triglyceride levels, without an effect of weight loss. The homeostatic model assessment of insulin resistance improved with both diets, whereas high-density lipoprotein cholesterol only improved in the LC diet, both irrespective of aforementioned factors. Remarkably, changes in caloric intake did not play a primary role in altering MetS markers. Taken together, these data suggest that, beyond the general effects of the LC and LF diet categories to improve MetS markers, there are also specific roles for weight loss, LC and HF intake, but not reduced caloric intake, that improve markers of MetS irrespective of diet categorization. On the basis of the results from this meta-analysis, guidelines to prevent MetS may need to be re-evaluated.


Protection of Enterococcus faecalis in mixed cultures with carbapenemase-producing Escherichia coli and Bacteroide fragilis: effect of the bacterial load.
This study explores effects of pH and inoculum size on imipenem versus tigecycline activity against E. coli, B. fragilis and E. faecalis, both in individual and mixed cultures. MIC/MBCs (mg/L) of tigecycline and imipenem were 0.12/≥ 16 and 4/4 for E. coli, 0.12/0.5 and ≥ 16/≥ 16 for B. fragilis, and 0.12/≥ 16 and 2/≥ 16 for E. faecalis, respectively. Killing curves in supplemented Brucella broth were performed at pH 7 or 5.8, with two final inocula (≈ 105 or ≈ 107 cfu/ml) of each isolate (individual cultures) and with 1:1:1 mixed inocula. Tubes were 48 h incubated at 37 ºC in anaerobiosis. Final concentrations (estimated concentrations in colon) were 1.50 mg/L for tigecycline and 26.40 mg/L for imipenem, with antibiotic-free curves as controls. Experiments were performed in triplicate. Imipenem showed inoculum effect against E.coli and B. fragilis, with reductions in initial inocula in experiments with standard inocula contrasting with increases in experiments with high inocula (both individual and mixed cultures). Against E. faecalis no inoculum effect for imipenem was observed in individual cultures, with marked reductions in initial inocula regardless inoculum size. However in mixed experiments the indirect protection of E. faecalis by the two gramnegatives resulted in bacterial regrowth. This protection was inoculum-dependant since it occurred with high but not with standard inocula. Tigecycline reduced initial inocula of the three isolates regardless culture type (individual/mixed) or experimental conditions (pH/inocula size), with lower reductions for the tolerant E. faecalis. Carbapenemase activity was inoculum-dependant for self-protection and indirect protection of E. faecalis.


Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers.
Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid biomarker studies have clinically important multi-purpose utility in advanced cancer patients and further studies to pursue their incorporation into the standard of care are warranted.


Child neurology practice and neurological disorders in East Africa.
Neurological disorders, including neurodevelopmental disorders, have been identified by the World Health Organization (WHO) as one of the greatest threats to global public health. It is generally believed that these conditions are more prevalent in the developing than the developed world because of multiple known risk factors such as infections, malnutrition, and limited resources for obstetric and neonatal management. In East Africa, few investigations have been conducted to obtain data on the magnitude and description of neurological disorders among children, and the practice of child neurology is faced with challenges cutting across areas of health personnel, patient diagnosis, management, and rehabilitation. This article reviews the burden, types, and causes of neurological disorders in the East African region. The challenges and successes in the practice of child neurology and recommendations for the future are discussed.


Tolerance of macaque middle STS body patch neurons to shape-preserving stimulus transformations.
Functional imaging studies in human and nonhuman primates have demonstrated regions in the brain that show category selectivity for faces or (headless) bodies. Recent fMRI-guided single unit studies of the macaque face category-selective regions have increased our understanding of the response properties of single neurons in these face patches. However, much less is known about the response properties of neurons in the fMRI-defined body category-selective regions ("body patches"). Recently, we reported that the majority of single neurons in one fMRI-defined body patch, the mid-STS body patch, responded more strongly to bodies compared with other objects. Here we assessed the tolerance of these neurons' responses and stimulus preference for shape-preserving image transformations. After mapping the receptive field of the single neurons, we found that their stimulus preference showed a high degree of tolerance for changes in the position and size of the stimulus. However, their response strongly depended on the in-plane orientation of a body. The selectivity of most neurons was, to a large degree, preserved when silhouettes were presented instead of the original textured and shaded images, suggesting that mainly shape-based features are driving these neurons. In a human psychophysical study, we showed that the information present in silhouettes is largely sufficient for body versus nonbody categorization. These data suggest that mid-STS body patch neurons respond predominantly to oriented shape features that are prevalent in images of bodies. Their responses can inform position- and retinal size-invariant body categorization and discrimination based on shape.


Deconditioning in patients with orthostatic intolerance.
To study the frequency and degree of deconditioning, clinical features, and relationship between deconditioning and autonomic parameters in patients with orthostatic intolerance. We retrospectively studied all patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent both standardized autonomic and exercise testing. A total of 184 patients (84 with postural orthostatic tachycardia syndrome [POTS] and 100 without orthostatic tachycardia) fulfilled the inclusion criteria. Of these, 89% were women, and median age was 27.5 years (interquartile range [IQR] 22-37 years). Symptom duration was 4 years (IQR 2-7.8). Of the patients, 90% had deconditioning (reduced maximum oxygen uptake [VO(2max)%] <85%) during exercise. This finding was unrelated to age, gender, or duration of illness. The prevalence of deconditioning was similar between those with POTS (95%) and those with orthostatic intolerance (91%). VO(2max)% had a weak correlation with a few autonomic and laboratory parameters but adequate predictors of VO(2max)% could not be identified. Reduced VO(2max)% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning.


Pulmonary Fissure Detection in CT Images Using a Derivative of Stick Filter.
Pulmonary fissures are important landmarks for recognition of lung anatomy. In CT images, automatic detection of fissures is complicated by factors like intensity variability, pathological deformation and imaging noise. To circumvent this problem, we propose a derivative of stick (DoS) filter for fissure enhancement and a post-processing pipeline for subsequent segmentation. Considering a typical thin curvilinear shape of fissure profiles inside 2D cross-sections, the DoS filter is presented by first defining nonlinear derivatives along a triple stick kernel in varying directions. Then, to accommodate pathological abnormality and orientational deviation, a [Formula: see text] cascading and multiple plane integration scheme is adopted to form a shape-tuned likelihood for 3D surface patches discrimination. During the post-processing stage, our main contribution is to isolate the fissure patches from adhering clutters by introducing a branch-point removal algorithm, and a multi-threshold merging framework is employed to compensate for local intensity inhomogeneity. The performance of our method was validated in experiments with two clinical CT data sets including 55 publicly available LOLA11 scans as well as separate left and right lung images from 23 GLUCOLD scans of COPD patients. Compared with manually delineating interlobar boundary references, our method obtained a high segmentation accuracy with median F1-scores of 0.833, 0.885, and 0.856 for the LOLA11, left and right lung images respectively, whereas the corresponding indices for a conventional Wiemker filtering method were 0.687, 0.853, and 0.841. The good performance of our proposed method was also verified by visual inspection and demonstration on abnormal and pathological cases, where typical deformations were robustly detected together with normal fissures.


2018 Update of the EULAR recommendations for the management of large vessel vasculitis.
Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.


Savoring Sweet: Sugars in Infant and Toddler Feeding.
During the first years of life, the sweetness of sugars has a capacity to hinder or to help in laying a strong nutritional foundation for food preferences that often extend over a lifetime. Aside from supplying 4 g/kcal of energy, sugars are non-nutritive. However, sugars have a powerful attribute, sweetness, which strongly influences human food preference. A child's first relationship with sweet taste begins even before birth and continues to evolve throughout complementary feeding. The sweetness of breastmilk encourages consumption and soothes the neonate. Conversely, inappropriate introduction of non-milk solids and beverages that are sweet at 0-4 months of age raises the newborn's risk for later obesity and may discourage the acceptance of other bitter or sour foods. Although cereals, fruits, 100% fruit juices, and some grains have naturally occurring sugars that impart sweet flavor notes, there is no clear role for added sugars between 6 and 12 months of age. Yet, 60% of infants are introduced to foods and beverages containing added sugars, threatening diet quality. Pairing foods with naturally occurring sugars, such as fruits, with foods that tend to be resisted initially, such as vegetables, can mask bitterness and promote acceptance. Utilizing the infants' extraordinary capacity for sensory-motor exploration is another strategy to expose them repeatedly to challenging tastes and flavors. The transitional year, as breast milk and infant formula are withdrawn, is a time when nutritional needs are high and diet quality often precarious. Rapid growth, along with brain and cognitive development, demand high-quality nutrition. Snacks are necessary both for energy and valuable nutrients. However, the selection of snack foods often exposes toddlers to items that offer concentrated energy with low nutrient value. Recent trends suggest a rapid fall in added sugars among infants and toddlers. Parenting practices that use small amounts of sugars to promote nutrient-rich foods from all 5 food groups can enhance rather than hinder their child's emerging dietary pattern.


Multi-stability and multi-instability phenomena in a mathematical model of tumor-immune-virus interactions.
Recent advances in virology, gene therapy, and molecular and cell biology have provided insight into the mechanisms through which viruses can boost the anti-tumor immune response, or can infect and directly kill tumor cells. A recent experimental report (Bridle et al. in Molec. Ther. 18(8):1430-1439, 2010) showed that a sequential treatment approach that involves two viruses that carry the same tumor antigen leads to an improved anti-tumor response compared to the effect of each virus alone. In this article, we derive a mathematical model to investigate the anti-tumor effect of two viruses, and their interactions with the immune cells. We discuss the conditions necessary for permanent tumor elimination and, in this context, we stress the importance of investigating the long-term effect of non-linear interactions. In particular, we discuss multi-stability and multi-instability, two complex phenomena that can cause abrupt transitions between different states in biological and physical systems. In the context of cancer immunotherapies, the transitions between a tumor-free and a tumor-present state have so far been associated with the multi-stability phenomenon. Here, we show that multi-instability can also cause the system to switch from one state to the other. In addition, we show that the multi-stability is driven by the immune response, while the multi-instability is driven by the presence of the virus.


Differential expression of hENT1 and hENT2 in colon cancer cell lines.
Human equilibrative nucleoside transporters (hENT) 1 and 2, encoded by SLC29A1 and SLC29A2, permit the bidirectional passage of nucleoside analogues into cells and may correlate with clinical responses to chemotherapy in patients with colorectal cancer (CRC). The purpose of this study was to evaluate the expression profiles of SLC29A1 and SLC29A2 in human cancer cell lines. Using quantitative real-time polymerase chain reaction, we comprehensively profiled the transcription levels of SLC29A1 and SLC29A2 in 16 colon cancer cell lines. We validated the ubiquitous and heterogeneous distribution of SLC29A1 and SLC29A2 in human colon cancer cell lines and demonstrated that SLC29A1 was highly expressed in 25% of metastatic cell lines (Colo201 and Colo205) and 62.5% of primary cell lines (Caco2, Colo320, HCT116, RKO, and SW48). For the first time, we showed that both SLC29A1 and SLC29A2 were expressed at lower levels in colon cancer cell lines originating from metastatic sites than from primary sites. These findings indicate that most patients with metastatic CRC (mCRC) may have low hENT1 expression, and treatment with nucleoside analogues may be inefficient. However, some patients still show high hENT1 expression and have a high probability of benefiting from these drugs. Therefore, evaluating transporter expression profiles and different drug responses between primary and metastatic tumors in patients with mCRC is important. Further assessment of the association between hENTs and drug-based treatment of mCRC is required to elucidate the mechanisms of chemotherapy resistance.


Dysphagia risk assessment in acute left-hemispheric middle cerebral artery stroke.
Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (<72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control.


Enteric bacteria counteract lipopolysaccharide induction of antimicrobial peptide genes.
The humoral immunity of Drosophila involves the production of antimicrobial peptides, which are induced by evolutionary conserved microbial molecules, like LPS. By using Drosophila mbn-2 cells, we found that live bacteria, including E. coli, Salmonella typhimurium, Erwinia carotovora, and Pseudomonas aeruginosa, prevented LPS from inducing antimicrobial peptide genes, while Micrococcus luteus and Streptococcus equi did not. The inhibitory effect was seen at bacterial levels from 20 per mbn-2 cell, while antimicrobial peptides were induced at lower bacterial concentrations (< or =2 bacteria per cell) also in the absence of added LPS. Gel shift experiment suggests that the inhibitory effect is upstream or at the level of the activation of the transcription factor Relish, a member of the NF-kappaB/Rel family. The bacteria have to be in physical contact with the cells, but not phagocytosed, to prevent LPS induction. Interestingly, the inhibiting mechanism is, at least for E. coli, independent of the type III secretion system, indicating that the inhibitory mechanism is unrelated to the one earlier described for YopJ from Yersinia.


Biomolecule patterning on analytical devices: a microfabrication-compatible approach.
The present work describes a methodology for patterning biomolecules on silicon-based analytical devices that reconciles 3-D biological functionalization with standard resist lift-off techniques. Unlike classic sol-gel approaches in which the biomolecule of interest is introduced within the sol mixture, a two-stage scenario has been developed. It consists first of patterning micrometer/submicrometer polycondensate scaffold structures, using classic microfabrication tools, that are then loaded with native biomolecules via a second simple incubation step under biologically friendly environmental conditions. The common compatibility issue between the biological and microfabrication worlds has been circumvented because native recognition biomolecules can be introduced into the host scaffold downstream from all compatibility issues. The scaffold can be generated on any silicon substrate via the polycondensation of aminosilane, namely, aminopropyltriethoxy silane (APTES), under conditions that are fully compatible with resist mask lithography. The scaffold porosity and high primary amine content allow proteins and nucleic acid sequences to penetrate the polycondensate and to interact strongly, thus giving rise to micrometer/submicrometer 3-D structures exhibiting high biological activity. The integration of such a biopatterning approach in the microfabrication process of silicon analytical devices has been demonstrated via the successful completion of immunoassays and nucleic acid assays.


Diagnostic accuracy of clinical tests for the diagnosis of hip femoroacetabular impingement/labral tear: a systematic review with meta-analysis.
Surgery for hip femoroacetabular impingement/acetabular labral tear (FAI/ALT) is exponentially increasing despite lacking investigation of the accuracy of various diagnostic measures. Useful clinical utility of these measures is necessary to support diagnostic imaging and subsequent surgical decision-making. Summarise/evaluate the current diagnostic accuracy of various clinical tests germane to hip FAI/ALT pathology. A computer-assisted literature search of MEDLINE, CINAHL and EMBASE databases using keywords related to diagnostic accuracy of the hip joint, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the search and reporting phases of the study. Quality assessment of bias and applicability was conducted using the Quality of Diagnostic Accuracy Studies-2 (QUADAS-2). Random effects models were used to summarise sensitivities (SN), specificities (SP), diagnostic odds ratio (DOR) and respective confidence intervals (CI). The employed search strategy revealed 21 potential articles, with one demonstrating high quality. Nine articles qualified for meta-analysis. The meta-analysis demonstrated that flexion-adduction-internal rotation (pooled SN ranging from 0.94 (95% CI 0.90 to 0.97) to 0.99 (95% CI 0.98 to 1.00); DOR 5.71 (95% CI 0.84 to 38.86) to 7.82 (95% CI 1.06 to 57.84)) and flexion-internal rotation (pooled SN 0.96 (95% CI 0.81 to 0.99); DOR 8.36 (95% CI 0.41 to 171.3) tests possess only screening accuracy. Few hip physical examination tests for diagnosing FAI/ALT have been investigated in enough studies of substantial quality to direct clinical decision-making. Further high-quality studies across a wider spectrum of hip pathology patients are recommended to discern the confirmed clinical utility of these tests. PROSPERO Registration # CRD42014010144.


Preventive resin restorations: indications, technique, and success.
Although preventive resin restorations have been reported since 1977, there is little uniformity concerning the indications for this procedure, nor is there a standard technique. This article proposes diagnostic criteria for pit and fissure occlusal caries and diagnosis-related considerations for treatment planning for preventive resin restorations. A step-by-step "laminate" technique, which includes, successively, a glass-ionomer cement liner, a posterior composite resin, and a sealant, is described. The success rates reported for several clinical studies of preventive resin restorations are presented, although the criteria for this restoration, treatment methodology, and the determinates of success vary from study to study.


The Ferritin-like superfamily: Evolution of the biological iron storeman from a rubrerythrin-like ancestor.
The Ferritins are part of the extensive 'Ferritin-like superfamily' which have diverse functions but are linked by the presence of a common four-helical bundle domain. The role performed by Ferritins as the cellular repository of excess iron is unique. In many ways Ferritins act as tiny organelles in their ability to secrete iron away from the delicate machinery of the cell, and then to release it again in a controlled fashion avoiding toxicity. The Ferritins are ancient proteins, being common in all three domains of life. This ubiquity reflects the key contribution that Ferritins provide in achieving iron homeostasis. This review compares the features of the different Ferritins and considers how they, and other members of the Ferritin-like superfamily, have evolved. It also considers relevant features of the eleven other known families within the Ferritin-like superfamily, particularly the highly diverse rubrerythrins. The Ferritins have travelled a considerable evolutionary journey, being derived from far more simplistic rubrerythrin-like molecules which play roles in defence against toxic oxygen species. The forces of evolution have moulded such molecules into three distinct types of iron storing (or detoxifying) protein: the classical and universal 24-meric ferritins; the haem-containing 24-meric bacterioferritins of prokaryotes; and the prokaryotic 12-meric Dps proteins. These three Ferritin types are similar, but also possess unique properties that distinguish them and enable then to achieve their specific physiological purposes. A wide range of biological functions have evolved from a relatively simple structural unit.


The default mode network and EEG regional spectral power: a simultaneous fMRI-EEG study.
Electroencephalography (EEG) frequencies have been linked to specific functions as an "electrophysiological signature" of a function. A combination of oscillatory rhythms has also been described for specific functions, with or without predominance of one specific frequency-band. In a simultaneous fMRI-EEG study at 3 T we studied the relationship between the default mode network (DMN) and the power of EEG frequency bands. As a methodological approach, we applied Multivariate Exploratory Linear Optimized Decomposition into Independent Components (MELODIC) and dual regression analysis for fMRI resting state data. EEG power for the alpha, beta, delta and theta-bands were extracted from the structures forming the DMN in a region-of-interest approach by applying Low Resolution Electromagnetic Tomography (LORETA). A strong link between the spontaneous BOLD response of the left parahippocampal gyrus and the delta-band extracted from the anterior cingulate cortex was found. A positive correlation between the beta-1 frequency power extracted from the posterior cingulate cortex (PCC) and the spontaneous BOLD response of the right supplementary motor cortex was also established. The beta-2 frequency power extracted from the PCC and the precuneus showed a positive correlation with the BOLD response of the right frontal cortex. Our results support the notion of beta-band activity governing the "status quo" in cognitive and motor setup. The highly significant correlation found between the delta power within the DMN and the parahippocampal gyrus is in line with the association of delta frequencies with memory processes. We assumed "ongoing activity" during "resting state" in bringing events from the past to the mind, in which the parahippocampal gyrus is a relevant structure. Our data demonstrate that spontaneous BOLD fluctuations within the DMN are associated with different EEG-bands and strengthen the conclusion that this network is characterized by a specific electrophysiological signature created by combination of different brain rhythms subserving different putative functions.


Specific inhibition of autoimmune T cell transmigration contributes to beta cell functionality and insulin synthesis in non-obese diabetic (NOD) mice.
Human diabetes mellitus (IDDM; type I diabetes) is a T cell-mediated disease that is closely modeled in non-obese diabetic (NOD) mice. The pathogenesis of IDDM involves the transmigration of autoimmune T cells into the pancreatic islets and the subsequent destruction of insulin-producing beta cells. Therapeutic interventions leading to beta cell regeneration and the reversal of established IDDM are exceedingly limited. We report here that specific inhibition of T cell intra-islet transmigration by using a small molecule proteinase inhibitor restores beta cell functionality, increases insulin-producing beta cell mass, and alleviates the severity of IDDM in acutely diabetic NOD mice. As a result, acutely diabetic NOD mice do not require insulin injections for survival for a significant time period, thus providing a promising clue to effect IDDM reversal in humans. The extensive morphometric analyses and the measurements of both the C-peptide blood levels and the proinsulin mRNA levels in the islets support our conclusions. Diabetes transfer experiments suggest that the inhibitor specifically represses the T cell transmigration and homing processes as opposed to causing immunosuppression. Overall, our data provide a rationale for the pharmacological control of the T cell transmigration step in human IDDM.


Assessing knowledge, motivation and perceptions about falls prevention among care staff in a residential aged care setting.
Falls are a serious problem in residential aged care settings. The aims of the study were to determine the feasibility of surveying care staff regarding falls prevention, and describe care staff levels of knowledge and awareness of residents' risk of falls, knowledge about falls prevention, motivation and confidence to implement falls prevention strategies. A custom designed questionnaire was administered to care staff at one site of a large residential aged care organization in Australia. The survey response was 58.8%. Feedback from staff was used to inform the administration of the survey to the wider organization. Seven (29.2%) care staff reported they were unsure or thought residents were at low risk of falls. Only five (20.8%) care staff were able to suggest more than three preventive strategies. These preliminary findings suggest that education to change care staff behavior regarding falls prevention should target improving care staff knowledge and awareness of falls.


Nephroprotective Role of Beta vulgaris L. Root Extract against Chlorpyrifos-Induced Renal Injury in Rats.
Organophosphorus pesticides (OPs) are widely used for agricultural and housekeeping purposes. Exposure to OPs is associated with the progression of several health issues. Antioxidant agents may be powerful candidates to minimise adverse reactions caused by OPs. The aim of the present study was to evaluate the nephroprotective effects of red beetroot extract (RBR) against chlorpyrifos- (CPF-) induced renal impairments. CPF induced kidney dysfunction, as demonstrated by changes in serum creatinine and urea levels. Moreover, CPF exposure induced oxidative stress in the kidneys as determined by increased malondialdehyde and nitric oxide levels, decreased glutathione content, decreased catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, and decreased nuclear factor (erythroid-derived 2)-like-2 factor expression. In addition, CPF induced inflammation in renal tissue as evidenced by increased release of tumor necrosis factor-alpha and interleukin-1β and upregulation of inducible nitric oxide synthase. Furthermore, CPF promoted cell death as demonstrated by decreased Bcl-2 and increased Bax and caspase-3 levels. Treatment with RBR one hour prior to CPF treatment blocked the effects observed in response to CPF alone. Our results suggest that RBR could be used to alleviate CPF-induced nephrotoxicity through antioxidant, anti-inflammatory, and antiapoptotic activities.


Community integration of adults with psychiatric disabilities and histories of homelessness.
This study tests components of Wong and Solomon's (2002, Mental Health Services Research, 4(2), 13-28) model of community integration, identifying both the dimensions and predictors of integration. It evaluates community integration among adults with psychiatric disabilities assigned randomly to receive either independent scatter-site apartments with the Housing First approach (experimental) or services as usual (control). Factor analysis supported a definition of community integration that includes psychological, physical, and social domains, but also suggested the existence of another factor, independence/self-actualization. Regression analysis suggested that choice and independent scatter-site housing were predictors of psychological and social integration respectively. Psychiatric hospitalization, symptomatology and participation in substance use treatment were also found to influence aspects of integration. We discuss several issues that future studies should explore including the possibility that the same factor can differentially influence discrete aspects of integration, the role of person-environment fit, integration that is not based in the neighborhood, and, finally, conceptions of community integration from the perspective of consumers themselves.


Tranexamic acid for preventing postpartum haemorrhage.
Postpartum haemorrhage (PPH) is a common and occasionally life-threatening complication of labour. Several options for preventing PPH are available, but further advances in this field are important, especially the identification of safe, easy to use, and cost-effective regimes. Tranexamic acid, which is an antifibrinolytic that is used widely to prevent and treat haemorrhage, merits evaluation to assess whether it meets these criteria. To determine, from the best available evidence, whether tranexamic acid is effective for preventing PPH. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 September 2009). All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating the use of tranexamic acid alone or in addition to uterotonics in the third stage of labour or during caesarean section to prevent PPH. Two review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We entered the data into Review Manager software and checked for accuracy. We included two RCTs. One RCT of unclear quality of 273 women compared tranexamic acid in two doses (0.5 g intravenously and 1 g intravenously) with aminomethylbenzoic acid (0.5 g intravenously) and with no treatment in women who had vaginal birth. We excluded the aminomethylbenzoic acid arm of this trial (92 patients).Another RCT of 180 women who underwent caesarean section compared tranexamic acid (1 g intravenously given 10 minutes before incision) with placebo.Blood loss greater than 400 ml was less common in women who received tranexamic acid after vaginal birth or caesarean section in the dosage of 1 g or 0.5 g intravenously (two studies, 453 women, risk ratio (RR) 0.51, 95% confidence interval (CI) 0.36 to 0.72). Mean blood loss was lower in the group of women who received intravenous tranexamic acid postpartum (two studies, 361 women, mean difference (MD) -75.17 ml, 95% CI -108.23 ml to -42.12 ml).No serious side effects were reported in women who received tranexamic acid in these trials. Tranexamic acid decreases postpartum blood loss after vaginal birth and after caesarean section based on two RCTs of unclear quality which reported on only a few outcomes. Further investigations are needed on efficacy and safety of this regimen for preventing PPH.


Accounting for delusional misidentifications.
Accounts of the major DMSs are given using theoretical models of the functional components underlying recognition of familiar people. Thus, Capgras' syndrome is suggested to involve impairment of processes that can support 'covert' recognition of familiar faces in prosopagnosia. It therefore forms a potential 'mirror image' of the impairments underlying prosopagnosia, and earlier attempts to link the two conditions directly are questioned. Frégoli syndrome and intermetamorphosis are explained as defects at different stages of an information-processing chain. Not only are these accounts consistent with the association of different DMSs with different brain injuries, but they also offer both suggestions for new inquiries and predictions about possible preserved and impaired abilities.


Diffusion tensor imaging and fiber tractography of the median nerve at 1.5T: optimization of b value.
The objective of this study was to systematically assess the optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5 T. This is a prospective study which was carried out with institutional review board approval and written informed consent from the study subjects. Fifteen healthy volunteers (seven men, eight women; mean age, 31.2 years) underwent diffusion tensor imaging of the wrist. A single-shot spin-echo-based echo-planar imaging sequence (TR/TE, 7000/103 ms) was performed in each subject at eight different b values ranging from 325 to 1,550 s/mm(2). Number and length of reconstructed fiber tracts, fiber density index (FDi), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were calculated for the median nerve. Signal-to-noise ratio (SNR) was also calculated for each acquisition. The overall image quality was assessed by two readers in consensus by ranking representative fiber tract images for each subject using a scale range from 1 to 8 (1 = best to 8 = worst image quality). Longest fibers were observed for b values between 675 and 1,025 s/mm(2). Maximum FDi was found at b values of 1,025 s/mm(2). FA was between 0.5 and 0.6 for all b values. ADC gradually decreased from 1.44 x 10(-3) to 0.92 x 10(-3) mm(2)/s with increasing b values. Maximum SNR +/- standard deviation (175.4 +/- 72.6) was observed at the lowest b value and decreased with increasing b values. SNR at b values of 1,025 s/mm(2) was 48.5% of the maximum SNR. Optimal fiber tract image quality was found for b values of 1,025 s/mm(2). The optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5 T was 1,025 s/mm(2).


Functional Cftr in crypt epithelium of organotypic enteroid cultures from murine small intestine.
Physiological studies of intact crypt epithelium have been limited by problems of accessibility in vivo and dedifferentiation in standard primary culture. Investigations of murine intestinal stem cells have recently yielded a primary intestinal culture in three-dimensional gel suspension that recapitulates crypt structure and epithelial differentiation (Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, Van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Nature 459: 262-265, 2009). We investigated the utility of murine intestinal crypt cultures (termed "enteroids") for physiological studies of crypt epithelium by focusing on the transport activity of the cystic fibrosis transmembrane conductance regulator Cftr. Enteroids had multiple crypts with well-differentiated goblet and Paneth cells that degranulated on exposure to the muscarinic agonist carbachol. Modified growth medium provided a crypt proliferation rate, as measured by 5-ethynyl-2'-deoxyuridine labeling, which was similar to proliferation in vivo. Immunoblots demonstrated equivalent Cftr expression in comparisons of freshly isolated crypts with primary and passage 1 enteroids. Apparent enteroid differences in mRNA expression of other transporters were primarily associated with villous epithelial contamination of freshly isolated crypts. Microelectrode analysis revealed cAMP-stimulated membrane depolarization in enteroid epithelium from wild-type (WT) but not Cftr knockout (KO) mice. Morphological and microfluorimetric studies, respectively, demonstrated Cftr-dependent cell shrinkage and lower intracellular pH in WT enteroid epithelium in contrast to Cftr KO epithelium or WT epithelium treated with Cftr inhibitor 172. We conclude that crypt epithelium of murine enteroids exhibit Cftr expression and activity that recapitulates crypt epithelium in vivo. Enteroids provide a primary culture model that is suitable for physiological studies of regenerating crypt epithelium.


Follower Jealousy at Work: A Test of Vecchio's Model of Antecedents and Consequences of Jealousy.
The present study tests the validity of Robert P. Vecchio's seminal work on antecedents and consequences of jealousy. Specifically, we examine whether antecedents such as in-group status, supervisory considerateness, and supervisory differentiation of subordinates are associated with jealousy. In addition, we examine whether jealousy is associated with the outcome variable of social loafing. Leaders (n = 73) and their followers (n = 303) working in business organizations in Norway contributed data. Multilevel analyses showed that a high-quality working relationship with one's supervisor was inversely related to reports of jealousy. In addition, supervisors who displayed high levels of considerateness, for example, by providing followers with positive emotional support, were better able to reduce subordinate jealousy. This is a novel observation since previous research failed to demonstrate such a relationship. Finally, jealousy was positively associated with social loafing, suggesting that jealous followers engaged in an active counterproductive resistance response. The present study contributes to the extant literature by identifying unexamined antecedents of jealousy and a dysfunctional behavioral response to jealousy in the form of social loafing in the workplace.


Safety and efficacy of montmorillonite-illite (FIMIX 1g557) for all animal species.
Following a request from European Commission, the Panel on Additives and Products or Substances used in animal Feed (FEEDAP) was asked to deliver a scientific opinion on the modification of the terms of authorisation of montmorillonite-illite (FIMIX 1g557) for all animal species. The FEEDAP Panel adopted in 2014 an opinion on the safety and in 2015 on the efficacy of this additive. The additive montmorillonite-illite (FIMIX 1g557) is currently authorised for use in feedingstuffs for all animal species as an anticaking agent with a minimum and a maximum content of 20,000 mg/kg. The applicant proposed to use the additive in premixtures and complementary feeds for all animal species and categories at a minimum concentration of 20,000 mg/kg premixture and 10,000 mg/kg complementary feeds. The FEEDAP Panel considers that the proposed modification (reduction of the inclusion level in feed) would not affect the conclusions reached in the previous assessment as related to the safety for the target species, consumers, users and the environment. Montmorillonite-illite is efficacious as an anticaking agent in premixtures for all animal species at inclusions levels starting at 20,000 mg/kg premixture and in complementary feeds at inclusions levels starting at 10,000 mg/kg. When the premixtures or complementary feeds are incorporated into complete feed, the concentration of montmorillonite-illite would range from 50 to 100 mg/kg complete feed for poultry and all other animal species, respectively. There is no evidence that the anticaking effect of the additive will persist at these concentrations in complete feed. In the absence of specific data, the FEEDAP Panel is not in the position to comment on the efficacy of the additive at these concentrations when used in complete feed.


Hypoxia leads to abnormal epidermal differentiation via HIF-independent pathways.
Atmospheric oxygen is important for the epidermis, as the skin epidermis is not greatly affected by blood circulation. Therefore, it is necessary to understand the effect of hypoxic signals on the epidermis as some environmental stimuli can induce skin hypoxia. Here, we investigated how hypoxia (1% O2) affected skin equivalents (SEs) and normal human epidermal keratinocytes. We found that hypoxia specifically decreased the protein levels of keratin 1 (K1)/keratin 10 (K10), a representative marker of the epidermal spinous layer in the epidermis. However, hypoxia-inducible factors, the major regulators of hypoxia, did not affect hypoxia-induced down-regulation of K1/K10. We also found that N-acetyl-l-cysteine (NAC), a reactive oxygen species scavenger, antagonized the hypoxia-induced reduction of K1/K10 in keratinocytes and SEs. In contrast to the findings for NAC, inhibitors that blocked reactive oxygen species generation did not cause recovery of K1/K10 protein levels under hypoxic conditions. Taken together, these results indicate that hypoxia leads to abnormal keratinocyte differentiation by down-regulating K1/K10 and that this phenomenon can be ameliorated by NAC.


Region-based reconstruction method for fluorescent molecular tomography.
A common difficulty for the traditional methods of fluorescent molecular tomographic (FMT) reconstruction is that only a small amount of measurements can be used to recover the image comprised of a large number of pixels. This difficulty not only leads to expensive computational cost but also likely results in an unstable solution prone to be affected by the noise in the measurement data. In this paper, we propose a region-based method for reducing the unknowns, where the target areas are determined by searching for the nearest neighbor nodes. In this method, the Hessian matrix of the second-order derivatives is incorporated to speed up the optimization process. An iteration strategy of multi-wavelength measurement is introduced to further improve the accuracy of inverse solutions. Simulation results demonstrate that the proposed approach can significantly speed up the reconstruction process and improve the image quality of FMT.


Primary bone tumors of the spine revisited: A 10-year single-center experience of the management and outcome in a neurosurgical department.
To report a large clinical series of primary bone tumors of the spine (PBTS) and review the current concepts of management. We retrospectively analyzed a clinical series of PBTS treated over the last decade (2004-2014) in the spine unit of a large European tertiary care center. Every PBTS was identified from an electronic medical-record system. Analysis comprised medical records and clinical imaging. Overall survival and outcome was measured using the Glasgow Outcome Scale (GOS) at six weeks, six months and one year postoperatively. Surgical management and adjuvant/neoadjuvant strategies were analyzed. A thorough review of the current literature was performed. A total of 79 patients were included. Of these, 44 (55.7%) were male. The age ranged from 9 to 90 years (mean 55), and most patients were adults (93.6%). Local pain was the most common symptom and was present in 91.1% of the patients. The majority of the tumors occurred in the thoracic spine (52 patients, 65.8%). Overall 86% (68 patients) of PBTS were classified as malignant and at the time of diagnosis, 7 patients (8.9%) presented with non-spinal metastasis. The most common histologic types were hematopoietic tumors (72.2%), followed by chondrogenic ones (12.7%). Within hematopoietic tumors, plasmacytoma was the most frequent type (49 patients, 62%). In 12 patients (15.2%) recurrences were seen during the follow-up period. Overall mean survival of benign PBTS was 100%, malignant non-hematopoietic PBTS 50% and, malignant hematopoietic PBTS 84% at one year, respectively. At six weeks and one year after the initial surgery, 79% and 54% of the patients presented a GOS >3, respectively. PBTS were almost exclusively seen in adults. Malignant tumors were markedly more frequent than benign tumors, with hematopoietic tumors being the most common type. For PBTS, early surgery is important in order to restore spinal stability and decompress the spinal cord. This allows pain reduction and prevention of neurological deficits.


Bibliotherapy as a treatment for depression in primary care.
This study was designed to determine whether a physician-delivered bibliotherapy prescription would compare favorably with the prevailing usual care treatment for depression in primary care (that often involves medication) and potentially offer an alternative. Six family physicians were trained to write and deliver prescriptions for cognitive-behavioral bibliotherapy. Thirty-eight patients were randomly assigned to receive either usual care or a behavioral prescription to read the self-help book, Feeling Good (Burns, D. D. (1999). Feeling good: The new mood therapy. New York: HarperCollins). The treatment groups did not differ in terms of overall outcome variables. Patients in both treatment groups reported statistically significant decreases in depression symptoms, decreases in dysfunctional attitudes, and increases in quality of life. Although not statistically significant, the mean net medical expenses in the behavioral prescription group were substantially less. This study provided empirical evidence that a behavioral prescription for Feeling Good may be as effective as standard care, which commonly involves an antidepressant prescription.


Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2.
The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.


Physiologic responses to a thermogenic nutritional supplement at rest, during low-intensity exercise, and during recovery from exercise in college-aged women.
This study examined acute physiologic responses to a thermogenic nutritional supplement at rest, during exercise, and during recovery from exercise in women. Twelve women (mean ± SD age, 22.9 ± 3.1 years) were recruited for this randomized, double-blinded, placebo-controlled, crossover study. Each testing session consisted of 4 phases: 30 min of presupplementation resting, followed by the ingestion of the placebo or thermogenic nutritional supplement; 50 min of postsupplementation resting; 60 min of walking (at 3.2-4.8 km·h(-1)); and 50 min of postexercise resting. Energy expenditure (EE), oxygen consumption, respiratory exchange ratio (RER), oxygen (O2) pulse, and heart rate (HR) values were recorded during all 4 phases. Systolic (SBP) and diastolic (DBP) blood pressure were recorded during the rest, postsupplementation, and postexercise recovery phases; ratings of perceived exertion (RPE) were recorded only during exercise. There were no significant differences for EE, oxygen consumption, O2 pulse, HR, SBP, or DBP between the supplement and placebo during the presupplementation resting or postsupplementation phases. The RER, however, was higher with the supplement at 30 min postsupplementation. During exercise, EE and O2 pulse were 3%-6% greater with the supplement than placebo; there were no significant differences in RPE. Postexercise, EE, oxygen consumption, and DBP were 3%-7% greater with the supplement than placebo. These findings suggest that a thermogenic nutritional supplement, when combined with exercise, increases metabolic rate but has no effect on the perception of effort and results in only minimal changes in cardiovascular function.


Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.
Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. We bridge the species divide via integration with proteomic and transcriptomic data from the human brain to identify evolutionarily conserved, disease-relevant networks. We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration. Using a database of drug-mediated gene expression changes, we identify small molecules that can normalize the disease-associated modules and validate this experimentally. Our results highlight the utility of an integrative, cross-species network approach to drug discovery.


Dietary Factors Promoting Brown and Beige Fat Development and Thermogenesis.
Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes. Despite advances in knowledge regarding the developmental lineage and transcriptional regulators of brown and beige adipocytes, our current understanding of environmental modifiers of BAT thermogenesis, such as diet, is limited. In this review, we consolidated the latest research on dietary molecules that may serve to promote BAT thermogenesis. Here, we summarized the thermogenic function of selected phytochemicals (e.g., capsaicin, resveratrol, curcumin, green tea, and berberine), dietary fatty acids (e.g., fish oil and conjugated linoleic acids), and all-trans retinoic acid, a vitamin A metabolite. We also delineated the proposed mechanisms whereby these dietary molecules promote BAT activity and/or browning of white adipose tissue. Characterizing thermogenic dietary factors may offer novel insight into revising nutritional intervention strategies aimed at obesity and diabetes prevention and management.


Manifestations of food protein induced gastrointestinal allergies presenting to a single tertiary paediatric gastroenterology unit.
Food protein induced gastrointestinal allergies are difficult to characterise due to the delayed nature of this allergy and absence of simple diagnostic tests. Diagnosis is based on an allergy focused history which can be challenging and often yields ambiguous results. We therefore set out to describe a group of children with this delayed type allergy, to provide an overview on typical profile, symptoms and management strategies. This retrospective analysis was performed at Great Ormond Street Children's Hospital. Medical notes were included from 2002 - 2009 where a documented medical diagnosis of food protein induced gastrointestinal allergies was confirmed by an elimination diet with resolution of symptoms, followed by reintroduction with reoccurrence of symptoms. Age of onset of symptoms, diagnosis, current elimination diets and food elimination at time of diagnosis and co-morbidities were collected and parents were phoned again at the time of data collection to ascertain current allergy status. Data from 437 children were analysis. The majority (67.7%) of children had an atopic family history and 41.5% had atopic dermatitis at an early age. The most common diagnosis included, non-IgE mediated gastrointestinal food allergy (n = 189) and allergic enterocolitis (n = 154) with symptoms of: vomiting (57.8%), back-arching and screaming (50%), constipation (44.6%), diarrhoea (81%), abdominal pain (89.9%), abdominal bloating (73.9%) and rectal bleeding (38.5%). The majority of patients were initially managed with a milk, soy, egg and wheat free diet (41.7%). At a median age of 8 years, 24.7% of children still required to eliminate some of the food allergens. This large retrospective study on children with food induced gastrointestinal allergies highlights the variety of symptoms and treatment modalities used in these children. However, further prospective studies are required in this area of food allergy.


Anorectal Herpesvirus hominis infection in men.
Thirteen cases of anorectal Herpesivirus hominis infection in male homosexuals are described. Symptoms included pruitus ani in 11 cases, while 7 noticed intense and pain. Change of bowel habits and anal discharge were not presenting symptoms in the majority. None had generalized complications. Inguinal lymphadenopathy, a vesicular eruption, and superficial ulceration around the anal margin were commonly found. Some developed vesicular spread to the natal cleft. Treatment with cotrimoxazole to prevent masking of possible coexistent syphilis, though satisfactory in preventing secondary infection seemed to have little effect on early resolution of the lesions. Relapse occurred in over one third of the patients. Infection with Herpesvirus hominis seems an uncommon but increasingly recognized hazard for the passive homosexual and should be included in the differential diagnosis of lesions presenting at the anus.


Skin cancer screening among U.S. adults from 1992, 1998, and 2000 National Health Interview Surveys.
Relatively little is known about the prevalence of skin cancer screening in the context of inconsistent skin cancer screening recommendations. To determine the prevalence and predictors of skin cancer screening rates in the U.S. adult population, we used self-reported data from the 1992, 1998, and 2000 National Health Interview Surveys, a nationally representative survey of civilian noninstitutionalized adults. The percentage of the U.S. adult population who had ever had a skin examination conducted by a doctor was 20.6% in 1992, 20.9% in 1998, and 14.5% in 2000. The percentage with a recent skin examination was 10.3% in 1992, 11.0% in 1998, and 8.0% in 2000. White non-Hispanics reported being screened more frequently than persons in other racial or ethnic groups. Recent skin cancer screening exams were more common among white persons who had a family history of melanoma, had higher education, had usual place of care, and were older (> or =50 years). Frequent use of sunscreen and hats was associated with a recent skin cancer exam. In the past decade, skin cancer screening rates have been consistently low. Continued monitoring of skin cancer examination is important given conflicting current research results and potentially evolving science.


Conceptualizing child health disparities: a role for developmental neurogenomics.
Biological, psychological, and social processes interact over a lifetime to influence health and vulnerability to disease. Those interested in studying and understanding how and why racial/ethnic and social disparities emerge need to focus on the intersection of these processes. Recent work exploring molecular epigenetic mechanisms of gene expression (in humans as well and other mammalian systems) has provided evidence demonstrating that the genome is subject to regulation by surrounding contexts (eg, cytoplasmic, cellular, organismic, social). The developing stress axis is exquisitely sensitive to regulation by social forces represented at the level of the epigenome. Old assumptions about an inert genome are simply incorrect. Epigenetic processes may provide the missing link that will allow us to understand how social and political conditions, along with individual subjective experiences, can directly alter gene expression and thereby contribute to observed social inequalities in health. Developmental neurogenomics may provide the direct link between the biological and social/psychological worlds. These biological mechanisms of plasticity (at the level of gene expression and regulation) may play a profound role in how we conceptualize health inequalities by informing our concepts regarding the somatization or embodiment of social inequalities.


Correlation of HIV-specific immunity, viral control, and diversification following planned multiple exposures to autologous HIV in a pediatric population.
Repeated controlled exposure to autologous virus was previously shown to result in increased CD8 T lymphocyte response to HIV antigens and accompanying reduction in viremia. We attempted to see if this immunity contributed to virologic control by correlating the immune response with quasispecies envelope diversification, an indicator of immune selection. The greatest diversification was seen in those with the greatest reduction in viremia but was unrelated to the frequency of Env-specific gamma interferon-producing cells. There was a trend toward correlation between the response to multiple HIV antigens and diversification.


Current imaging of cerebrospinal fluid leaks.
A CSF leak results from a defect in the dura and skull base. Due to the risk of potentially devastating central nervous system infection, it is an important entity. Timely diagnosis of CSF leaks is crucial. Laboratory testing of nasal or aural fluid drainage for the presence of the protein Beta (beta)-2 transferrin plays a key role in establishing the presence of a CSF leak. Such assays are not always available, making imaging pivotal in the diagnosis of this entity. The development of minimally invasive endoscopic repair further underscores the importance of imaging as precise anatomic localization is important for repair In this article, we review the literature and make suggestions for the appropriate radiological investigation of patients with suspected CSF leaks.


Imaging of Streptomyces coelicolor A3(2) with reduced autofluorescence reveals a novel stage of FtsZ localization.
Imaging of low abundance proteins in time and space by fluorescence microscopy is typically hampered by host-cell autofluorescence. Streptomycetes are an important model system for the study of bacterial development, and undergo multiple synchronous cell division during the sporulation stage. To analyse this phenomenon in detail, fluorescence microscopy, and in particular also the recently published novel live imaging techniques, require optimal signal to noise ratios. Here we describe the development of a novel derivative of Streptomyces coelicolor A3(2) with strongly reduced autofluorescence, allowing the imaging of fluorescently labelled proteins at significantly higher resolution. The enhanced image detail provided novel localization information for the cell division protein FtsZ, demonstrating a new developmental stage where multiple FtsZ foci accumulate at the septal plane. This suggests that multiple foci are sequentially produced, ultimately connecting to form the complete Z ring. The enhanced imaging properties are an important step forward for the confocal and live imaging of less abundant proteins and for the use of lower intensity fluorophores in streptomycetes.


Improved power for characterizing longitudinal amyloid-β PET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region.
In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments. Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ+ and Aβ- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines. As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines. A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβ increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials.


Tracking and forecasting ecosystem interactions in real time.
Evidence shows that species interactions are not constant but change as the ecosystem shifts to new states. Although controlled experiments and model investigations demonstrate how nonlinear interactions can arise in principle, empirical tools to track and predict them in nature are lacking. Here we present a practical method, using available time-series data, to measure and forecast changing interactions in real systems, and identify the underlying mechanisms. The method is illustrated with model data from a marine mesocosm experiment and limnologic field data from Sparkling Lake, WI, USA. From simple to complex, these examples demonstrate the feasibility of quantifying, predicting and understanding state-dependent, nonlinear interactions as they occur in situ and in real time--a requirement for managing resources in a nonlinear, non-equilibrium world.


Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium.
We studied the effects of quinidine and lidocaine on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)max, and on the recovery kinetics of (dV/dt)max in guinea pig papillary muscles. The steady-state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)max in progressively earlier premature action potentials. Lidocaine caused a dose-dependent decrease in (dV/dt)max, shifted the curve defining the steady-state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)max. Quinidine caused a dose-dependent decrease in (dV/dt)max but did not alter the shape of the curves defining either the steady-state relationship or the recovery kinetics of (dV/dt)max. Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)max are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs.


Mechanical growth and morphogenesis of seashells.
Seashells grow through the local deposition of mass along the aperture. Many mathematical descriptions of the shapes of shells have been provided over the years, and the basic logarithmic coiling seen in mollusks can be simulated with few parameters. However, the developmental mechanisms underlying shell coiling are largely not understood and the ubiquitous presence of ornamentation such as ribs, tubercles, or spines presents yet another level of difficulty. Here we develop a general model for shell growth based entirely on the local geometry and mechanics of the aperture and mantle. This local description enables us to efficiently describe both arbitrary growth velocities and the evolution of the shell aperture itself. We demonstrate how most shells can be simulated within this framework. We then turn to the mechanics underlying the shell morphogenesis, and develop models for the evolution of the aperture. We demonstrate that the elastic response of the mantle during shell deposition provides a natural mechanism for the formation of three-dimensional ornamentation in shells.


Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies.
Osteosarcoma (OS) is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.


Differential Responses of Colletotrichum gloeosporioides and C. truncatum Isolates from Different Hosts to Multiple Fungicides Based on Two Assays.
Anthracnose is one of the most important postharvest diseases of many economically important crops worldwide. This study was conducted with the objective of investigating the sensitivity of Colletotrichum gloeosporioides and C. truncatum isolates to multiple fungicides with different modes of action. The study analyzed quantitative sensitivity data derived from conventional amended agar (AA) assays and qualitative spore responses obtained from a novel microtiter bioassay that is based on reduction of a viability dye, Alamar blue (AB). Generally, for AA assays, the percent growth inhibition (%RGI) increased with increasing concentration for all isolates and all fungicides, except for copper hydroxide. C. truncatum isolates reacted differently to increasing concentrations of the various fungicides depending on whether the isolates originated from pepper or papaya. C. truncatum from pepper had generally less %RGI than C. truncatum isolates from papaya. C. gloeosporioides isolates from papaya had generally higher %RGI than C. truncatum isolates for all concentrations tested for pyraclostrobin, chlorothalonil, and fosetyl-aluminum. C. gloeosporioides isolates from pepper had generally higher %RGI than C. truncatum isolates for all concentrations tested for most fungicides. In all cases, Colletotrichum sp. and fungicide had significant (P ≤ 0.001) effects on the log concentration of fungicide for which relative growth was inhibited by 50 and 90% (log EC50 and log EC90, respectively) calculated for all isolates, regardless of whether values were compared for only C. gloeosporioides isolates or only C. truncatum isolates. Correlation analyses of log EC50 and log EC90 values of all the isolates revealed a nonsignificant association for pyraclostrobin. In AB assays, all fungicides had an equivalent effect at inhibiting spore germination at the lower concentrations. According to binary logistic regression analyses, species, isolate, and fungicide concentration had significant predictive value in determining whether an AB test would be positive. Sequence alignments between C. gloeosporioides isolates and C. gloeosporioides f. sp. aeschynomene revealed no base substitutions at codons 198, 199, 200, and 240; however, sequence comparisons between C. truncatum isolates and C. gloeosporioides f. sp. aeschynomene revealed two codon changes located outside of the identified codon 198 or 200 associated with the benzimidazole-resistant phenotype of C. gloeosporioides isolates.


Postpartum depression: the reliability of telephone screening.
This study evaluated the reliability of screening women for symptoms of postpartum depression by a telephone assessment after hospital discharge. Correlational design with a convenience sample of women from a Midwestern community hospital. One hundred and twenty-six women agreed to participate prior to hospital discharge and 106 women were in the final sample (response rate 84%). Telephone contact was made 8 weeks after discharge, when the Postpartum Depression Screening Scale was administered. Twenty-seven percent of the women screened had scores indicating moderate-to-severe depression (score range 60-128). Reliability coefficients were calculated on the data for the short and long forms of the PDSS, as well as for all seven subscales (alpha coefficients were .72 and .94, respectively, for the short- and long-form totals). Subscale scores for the 35-item form were as follows: sleeping/eating disturbances .80, anxiety/insecurity .77, emotional lability .82, mental confusion .80, loss of self .87, guilt/shame .82, and contemplating harming oneself.90. The correlation between the short-form total and the long-form total was r = .91 (p = < 01.) Studies using the PDSS as an in-person instrument were compared with scores for telephone screening, and the overall mean scores were similar. Telephone screening is a reliable method to screen for postpartum symptomatology that may occur later than the 6-week office visit. Women who are at risk, especially those who have a history of treatment for depression, current treatment for depression or increased anxiety, should be screened for postpartum depression symptomatology.


Dicer-like (DCL) proteins in plants.
Dicer and Dicer-like (DCL) proteins are key components in small RNA biogenesis. DCLs form a small protein family in plants whose diversification time dates to the emergence of mosses (Physcomitrella patens). DCLs are ubiquitously but not evenly expressed in tissues, at different developmental stages, and in response to environmental stresses. In Arabidopsis, AtDCL1, AtDCL2, and AtDCL4 exhibit similar expression pattern during the leaf or stem development, which is distinguished from AtDCL3. However, distinct expression profiles for all DCLs are found during the development of reproductive organs flower and seed. The grape VvDCL1 and VvDCL3 may act sequentially to face the fungi challenge. Overall, the responses of DCLs to drought, cold, and salt are quite different, indicating that plants might have specialized regulatory mechanism in response to different abiotic stresses. Further analysis of the promoter regions reveals a few of cis-elements that are hormone- and stress-responsive and developmental-related. However, gain and loss of cis-elements are frequent during evolution, and not only paralogous but also orthologous DCLs have dissimilar cis-element organization. In addition to cis-elements, AtDCL1 is probably regulated by both ath-miR162 and ath-miR414. Posterior analysis has identified some critical amino acid sites that are responsible for functional divergence between DCL family members. These findings provide new insights into understanding DCL protein functions.


Selective and invariant neural responses to spoken and written narratives.
Linguistic content can be conveyed both in speech and in writing. But how similar is the neural processing when the same real-life information is presented in spoken and written form? Using functional magnetic resonance imaging, we recorded neural responses from human subjects who either listened to a 7 min spoken narrative or read a time-locked presentation of its transcript. Next, within each brain area, we directly compared the response time courses elicited by the written and spoken narrative. Early visual areas responded selectively to the written version, and early auditory areas to the spoken version of the narrative. In addition, many higher-order parietal and frontal areas demonstrated strong selectivity, responding far more reliably to either the spoken or written form of the narrative. By contrast, the response time courses along the superior temporal gyrus and inferior frontal gyrus were remarkably similar for spoken and written narratives, indicating strong modality-invariance of linguistic processing in these circuits. These results suggest that our ability to extract the same information from spoken and written forms arises from a mixture of selective neural processes in early (perceptual) and high-order (control) areas, and modality-invariant responses in linguistic and extra-linguistic areas.


A new animal model for studying Lyme disease spirochetes in a mammalian host-adapted state.
There is now substantial evidence that Borrelia burgdorferi, the Lyme disease spirochete, undergoes major alterations in antigenic composition as it cycles between its arthropod and mammalian hosts. In this report, we cultivated B. burgdorferi 297 within dialysis membrane chambers implanted into the peritoneal cavities of rats to induce antigenic changes similar to those which occur during mammalian infection. Chamber-grown spirochetes, which remained fully virulent, did not express either outer surface protein A or Lp6.6, lipoproteins known to be downregulated after mammalian infection. However, they did, express p21, a well characterized outer surface protein E homologue, which is selectively expressed during infection. SDS-PAGE, two-dimensional gel electrophoresis, and immunoblot analysis revealed that chamber-grown borreliae also expressed uncharacterized proteins not expressed by in vitro-cultivated spirochetes; reactivity with sera from mice chronically infected with B. burgdorferi 297 confirmed that many of these novel proteins are selectively expressed during experimental murine infection. Finally, we used differential display RT-PCR to identify transcripts of other differentially expressed B. burgdorferi genes. One gene (2.9-7lpB) identified with this technique belongs to a family of genes located on homologous 32- and 18-kb circular plasmids. The lipoprotein encoded by 2.9-7lpB was shown to be selectively expressed by chamber-grown spirochetes and by spirochetes during experimental infection. Cultivation of B. burgdorferi in rat peritoneal implants represents a novel system for studying Lyme disease spirochetes in a mammalian host-adapted state.


Antioxidant Activity of the Essential Oils of Different Parts of Juniperus excelsa M. Bieb. subsp. excelsa and J. excelsa M. Bieb. subsp. polycarpos (K. Koch) Takhtajan (Cupressaceae).
The essential oils of branchlets and fruits of Juniperus excelsa subsp. excelsa and Juniperus excelsa subsp. polycarpos were examined for their antioxidant activity. The compositions of the essential oils were studied by GC and GC-MS. To evaluation the antioxidants activity of the volatile oils, pure components and positive controls at different concentrations, thin-layer chromatography (TLC) screening methods, diphenylpicrylhydrazyl (DPPH) assay, deoxyribose degradation test and modified deoxyribose degradation test were employed. The results of the present study demonstrate some antioxidant activity for the tested essential oils obtained from various parts of both plants. It indicates that the use of these essential oils, in very low concentrations, may be useful as a natural preservative. However before any final conclusion, it is suggested that the antioxidant activity of these oils should also be evaluated by using lipid solvent system methods.


Do Hypertensive Individuals Who Are Aware of Their Disease Follow Lifestyle Recommendations Better than Those Who Are Not Aware?
Lifestyle modification is the first step in hypertension management. Our objective was to assess adherence to lifestyle recommendations by individuals who were aware of their hypertension and to identify characteristics associated with non-adherence. Using data from the Korea National Health and Nutrition Examination Survey conducted in 2010-2012, we compared the adherence to six lifestyle recommendations of hypertensive subjects aware of the status of their condition with that of those who were not aware, based on survey regression analysis. The characteristics associated with non-adherence were assessed by multiple logistic regression analysis. Of all hypertensive subjects, <20% adhered to a healthy diet and reduced salt intake and about 80% moderated alcohol consumption and did not smoke. Half of all subjects maintained normal body weight and engaged in physical activity. Most lifestyle features of aware hypertensive Koreans did not differ greatly from those of hypertensive individuals who were not aware. Reduction in salt intake was slightly more prevalent among those aware of their hypertensive status. Obesity was more prevalent among the aware hypertensive subjects, and the prevalence of obesity increased with the duration of hypertension. Male gender, younger age, residence in a rural area, low income, and the use of antihypertensive medication were associated with non-adherence to lifestyle recommendations by hypertensive individuals. Many hypertensive Koreans do not comply with lifestyle recommendations for the management of hypertension. The association between the use of antihypertensive medications and non-adherence suggested an over-reliance on medication rather than a commitment to a healthy lifestyle. Our study highlights that efforts encouraging healthy lifestyles, as the first step in hypertension management, need to be increased.


Pain assessment practices in Swedish and Norwegian neonatal care units.
The use of measurement scales to assess pain in neonates is considered a prerequisite for effective management of pain, but these scales are still underutilised in clinical practice. The aim of this study was to describe and compare pain assessment practices including the use of pain measurement scales in Norwegian and Swedish neonatal care units. A unit survey investigating practices regarding pain assessment and the use of pain measurement scales was sent to all neonatal units in Sweden and Norway (n = 55). All Norwegian and 92% of Swedish units responded. A majority of the participating units (86.5%) assessed pain. Swedish units assessed and documented pain and used pain measurement scales more frequently than Norwegian units. The most frequently used scales were different versions of Astrid Lindgren's Pain Scale (ALPS) in Sweden and Echelle Douleur Inconfort Noveau-Ne (EDIN), ALPS and Premature Infant Pain Profile (PIPP) in Norway. Norwegian head nurses had more confidence in their pain assessment method and found the use of pain measurement scales more important than their Swedish colleagues. The persisting difference between Swedish and Norwegian units in pain assessment and the use of pain measurement scales are not easily explained. However, the reported increased availability and reported use of pain measurement scales in neonatal care units in both countries may be seen as a contribution towards better awareness and recognition of pain, better pain management and potentially less suffering for vulnerable neonates.


Molecular insights into Down syndrome-associated leukemia.
Four years ago it was discovered that nearly all cases of transient myeloproliferative disorder and acute megakaryocytic leukemia in children with Down syndrome acquire mutations in the hematopoietic transcription factor gene GATA1. Studies within the past year, described within this review, have provided tremendous insights into the role of GATA1 mutations in these malignancies. In the past year, our understanding of the molecular and cellular consequences of GATA1 mutations has been greatly enhanced. Most importantly, we have learned that these mutations, which result in the exclusive production of the short GATA1 isoform named GATA1s, have a distinct effect on fetal liver progenitors. In addition, multiple studies have shown that GATA1s can substitute for GATA1 in many aspects of megakaryocytic maturation. Finally, an important clinical study has revealed that GATA1 mutations alone are insufficient for leukemia. Leukemia in children with Down syndrome requires at least three cooperating events--trisomy 21, a GATA1 mutation, and a third, as yet undefined, genetic alteration. Recent studies have provided tremendous insights into the GATA1 side of the story. Future experiments with human patient samples and mouse models will likely increase our awareness of the role of trisomy 21 in transient myeloproliferative disorder and acute megakaryocytic leukemia.


Peripheral 4-1BB signaling negatively regulates NK cell development through IFN-gamma.
Stimulation of 4-1BB (CD137) was shown to produce strong anticancer effects in vivo. In contrast, 4-1BB-deficient (4-1BB(-/-)) B6 mice are remarkably resistant to tumor growth. We set out to determine the mechanisms involved in these seemingly contradictory observations. We found that the therapeutic effects of 4-1BB triggering were mainly dependent on CD8(+) T cells and partially on NK cells, whereas CD8(+) T and NK cells were equally needed to suppress tumor growth in 4-1BB(-/-) mice. Cellular analysis showed that the frequency and number of NK cells in the spleen and bone marrow were decreased by 4-1BB triggering but were increased in the absence of 4-1BB signaling in tumor-challenged mice. The 4-1BB-mediated downregulation of NK cell development was primarily dependent on IFN-gamma, which was produced by peripheral CD8(+) T and NK cells. The suppression of NK cell development by 4-1BB-mediated IFN-gamma production occurred in the bone marrow. As 4-1BB signaling increased in the periphery, more CD8(+) T cells but fewer NK cells contributed to the antitumor immunity. As 4-1BB signaling decreased, more NK cells participated in the antitumor immunity. We conclude that 4-1BB signaling results in a shift of the dominant type of immune cell in antitumor immunity from the innate NK cell to the adaptive CD8(+) T cell and that the level of IFN-gamma is critical for this 4-1BB-mediated shift.


Motion-induced blindness for dynamic targets: Further explorations of the perceptual scotoma hypothesis.
Motion-induced blindness (MIB) is a striking phenomenon wherein fully visible and attended objects may repeatedly fluctuate into and out of conscious awareness when superimposed onto certain global moving patterns. Perhaps the most remarkable feature of MIB is that objects can disappear even when they are moving. Here we report several novel demonstrations of MIB for dynamic objects, including the observations that (a) MIB can occur for dynamic targets defined by various types of complex visual distortions (akin to those that may occur with various types of metamorphopsias), and (b) MIB is more robust for downward-drifting compared to upward-drifting objects (perhaps because of the related motions of floaters in the eye's vitreous humor). To interpret these results, we focus on the idea that MIB may arise not from a limitation or failure of visual processing, but instead from a perceptual scotoma: MIB may reflect a functional inference in visual processing, eliminating some novel stimuli from awareness in much the same way that the visual system chronically eliminates percepts that would otherwise arise from visual impairments (such as scotomas) or features that are not in the external world in the first place (such as shadows from retinal blood vessels).