Hypothyroidism in restless legs syndrome.
The diurnal nature of restless legs syndrome (RLS) and its response to dopamine hint that hormones are central in RLS pathophysiology. Hypothyroidism has been linked to RLS, but studies are limited. This study's objective is to determine whether RLS is more prevalent in persons with hypothyroidism and whether hypothyroidism is more prevalent in RLS sufferers. Persons with hypothyroidism and controls were recruited through an on-line registry of potential research participants. RLS was assessed using the Cambridge-Hopkins questionnaire. RLS persons and controls were recruited through RLS Foundation and on-line registry advertisements and assessed for hypothyroidism by self-report. The International RLS Study Group Severity Scale assessed RLS severity; 266 hypothyroid subjects and 321 controls were comparable in age (52.3 ± 13.4 versus 53.9 ± 11.7 years; p = .14) and gender (91.7% versus 91.3% women; p = .85), as were 354 RLS and 313 controls (59.1 ± 13.2 versus 58.2 ± 13.6 years; p = .41; 80.8% versus 78.3% women; p = .42). Hypothyroid participants versus controls had a significantly higher prevalence of RLS (14.3% versus 8.1%; p = .02). RLS participants versus controls had a significantly higher prevalence of hypothyroidism (22.3% versus. 13.8%; p = .005). RLS severity was similar in persons with and without hypothyroidism. Among 73 persons with RLS and hypothyroidism, 14 previously were hyperthyroid versus 0 of 37 persons with hypothyroidism alone (p = .004). RLS prevalence is increased in individuals with hypothyroidism; hypothyroidism prevalence is increased in individuals with RLS. Persons with hypothyroidism and RLS are significantly more likely than those with hypothyroidism alone to have had hyperthyroidism prior to hypothyroidism. Associations between RLS and thyroid disease may shed light on complex biological mechanisms underlying RLS.


[Role of cortisol hypersecretion in the pathogenesis of osteoporosis].
The negative effect on bone due to the glucocorticoid excess is mediated by the direct action of cortisol in reducing bone apposition and increasing bone resorption, and by indirect mechanisms such as the calcium malabsorption, hypercalciuria and hypogonadism. The condition of overt hypercortisolism, also called Cushing's syndrome, leads to osteoporosis and fractures in up to the 70% of cases, even in the presence of normal gonadal status and in males. The recovery from Cushing's syndrome leads to a normalization of bone mineral density only after several years, even if some data show that the risk of fractures normalizes after one year from the cure. Alendronate has been demonstrated to be useful to accelerate the restoration of normal bone mass after the cure of Cushing's syndrome Several studies, even not all, have been demonstrated that also the condition of asymptomatic or "subclinical" hypercortisolism (often associated to adrenal adenoma) is associated to a reduction of bone mineral density and increased prevalence of fracture even in the presence of eugonadal status and in males. Unfortunately, data regarding the effect of the normalization of cortisol secretion on bone mass and risk of fractures are lacking. On the other hand, it is known that osteoporotic fractures may be the clinical presentation of an otherwise asymptomatic hypercortisolism. In a recent study we have demonstrated that in a population of outpatients with established osteoporosis and without known or clinically evident secondary causes, the prevalence of subclinical hypercortisolism is about 10%. This finding suggests that the presence of subclinical hypercortisolism has to be taken in to account when evaluating patients with unexplainable established osteoporosis.


Knowledge, attitude, and practice of reproductive behavior in Iranian minor thalassemia couples.
To investigate the knowledge, attitude, and practice of reproductive behavior in Iranian minor thalassemia couples in Ghaemshahr City, Mazandaran, Iran. This is a cross-sectional descriptive survey conducted in 2006. Birth rates from 1997-2005 and the number of newly registered patients from at risk couples was recorded. Tools for data collection were a valid questionnaire containing epidemiologic characteristics of couples, knowledge (20 questions), attitude 20 statements, and practice by studying the family file in health centers. Questionnaires were completed by husband and wife separately. Actual versus expected numbers of patients born in that period were compared. The data were analyzed using the Statistical Package for Social Science version 13.00, and p<0.05 was interpreted as significant. Of the 240 at risk couples, 100 were studied. Of them, 82% had good knowledge of thalassemia, and 68.5% had a positive attitude toward thalassemia prevention program. Correlations of knowledge with attitude were significant (p<0.001), and 50% of the couples had unfavorable practice including unplanned pregnancy, fetal abortion without prenatal diagnosis (PND), delivery without PND, and having a child affected by thalassemia major (TM). Without PND, 4 TM patients were born. Ninety-eight episodes of unfavorable practice were reported. Meanwhile, the contraceptive method used by 12% of couples was unsafe. Suspected TM patients with no prevention program were 25; thus, the birth of 2 TM was prevented (92% reduction). We achieved great success during the last 9 years in the region, and TM prevention program improved knowledge, attitude, and practice in high-risk couples and carrier families.


Primary polycystic ovary syndrome in a premenarchal girl. A case report.
A 12-year-old, premenarchal girl with hirsutism and virilization of nine months' duration was found to have highly elevated serum testosterone and a radiologic evaluation suggestive of bilaterally enlarged ovaries with a solid left ovarian mass. Serum gonadotropins were normal, with an LH:FSH ratio of 2:1. Exploratory laparotomy showed bilaterally enlarged polycystic ovaries, confirmed by wedge biopsies. No ovarian tumor was found. Oral contraceptives decreased the total serum testosterone to the normal female levels within three months. This was one of the youngest reported patients with primary polycystic ovary syndrome.


Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice.
To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice. PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT-cisplatin for tumor growth inhibition was studied in mice. PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT-cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice. PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.


Cyanide, protein and iodine interaction in the performance and metabolism of rats.
Performance and metabolic traits were measured in sixty-four growing rats fed on varying levels of dietary cyanide, protein and iodine. The presence of cyanide in the diets caused a non-significant reduction in both feed consumption and growth rate. Moreover, on protein deficient diets, the lowest body weight gain was obtained in the animals with 750 ppm cyanide. Iodine deficiency did not have any marked influence on performance. Dietary cyanide significantly increased serum and urinary thiocyanate concentration while iodine deficiency caused significant reductions in serum protein bound iodine (PBI). Interactions of protein deficiency and dietary cyanide also significantly reduced serum thiocyanate concentrations, while interactions of the three dietary variables significantly reduced kidney protein content.


Outcomes and prognostic contributors in patients with KRAS mutated non-small cell pulmonary adenocarcinomas: a single institution experience.
KRAS is the most frequently encountered driver mutation in advanced non-small cell lung cancer (NSCLC). With targeted therapy for the most common KRAS mutation p.G12C on the horizon, the aim of this study is to retrospectively report outcomes in patients with KRAS mutated NSCLC. This was a retrospective chart review of 7 hospitals in Texas with reflex biomarker testing in all lung adenocarcinomas. Patients were included if they had pathologically diagnosed adenocarcinoma of any stage originating in the lung with molecularly confirmed KRAS driver mutation of any genotypic subtype. Twelve-month survival was assessed and compared between KRAS p.G12C and all other detected KRAS mutations. Other outcomes including impact of age, sex, smoking status, and pack years smoked were assessed to determine if they had prognostic significance on mortality in KRAS mutated patients. There were 58 patients diagnosed with KRAS mutated NSCLC, 63.8% were at an advanced stage at diagnosis, 55.8% of patients were female, and 82.8% were white. The median age was 72 [52-88] years, and 93.1% were either current or prior smokers. KRAS p.G12C was the most common KRAS mutation (44.8%). At diagnosis, patients with KRAS p.G12C had poorer performance statuses compared to other KRAS mutations. A total of 32 (55.2%) patients died, 26 with advanced disease. In this study, current smoking status (P=0.1652), pack years smoked (P=0.6597), age (P=0.5092), sex (P=0.4309), and underlying KRAS codon mutation controlling for stage (P=0.2287) did not impact survival. However, KRAS p.G12C had a numerically lower 12 months overall survival (OS) compared to all other KRAS mutations in both early stage (56.3% vs. 90.9%) and advanced stage (25.0% vs. 47.6%) disease. Of note, 16 (27.6%) patients had prior, concurrent, or second malignancies, but these did not significantly impact OS (P=0.7696). This study did not find a prognostic difference with sex, smoking history, age, or p.G12C mutation. The patients in this cohort with KRAS p.G12C had a numerically lower 12-month overall survival in both early and advanced stage disease compared to other mutations, and over one-quarter had a notable history of previous and second primary malignancies.


A phenomenological investigation of women with Tourette or other chronic tic disorders.
There are little data concerning clinical characteristics of women with Tourette disorder and chronic tic disorders in the extant literature and what is available mostly focuses on treatment-seeking individuals. The present research was conducted to provide a phenomenological characterization of tic disorders among 185 adult women with tic disorders. In addition to providing a descriptive overview of specific tic symptoms, tic severity, self-reported history of other psychiatric conditions, and impairment/lifestyle impact due to tics, this study compares 185 women and 275 men between 18 and 79 years old with tic disorders (who completed an identical battery of measures) based on demographic, social/economic status indicators, psychiatric variables (comorbidity, family psychiatric history, symptom presentation), adaptive functioning/quality of life, and impairment variables among a nonclinical adult sample. Finally, this research examines the relationship between tic severity and impairment indicators among women with tics. Sixty-eight percent of women in our sample reported severe motor tics and 40% reported severe phonic tics. Our exploratory data suggest that a sizeable number of adult women with persistent tics are suffering from psychiatric comorbidity and psychosocial consequences such as underachievement and social distress. Tic severity in women may be associated with lifestyle interference as well as with symptoms of depression and anxiety, and such symptoms may be more common among women with tics than in men with tics.


Proteomic analysis of PAXgene-fixed tissues.
Formalin fixation and paraffin embedding is the standard technique for preserving biological material for both storage and histological analysis. Although recent progress has been made in the molecular analysis of formalin-fixed, paraffin-embedded (FFPE) tissues, proteomic applications are a special challenge due to the cross-linking property of formalin. Here we present the results of a new formalin-free tissue fixative, PAXgene, and demonstrate successful extraction of nondegraded and immunoreactive protein for subsequent standard protein assays, such as Western blot analysis and reverse-phase protein arrays. High amounts of protein can be obtained from PAXgene-fixed, paraffin-embedded (PFPE) mouse liver and human spleen, breast, duodenum, and stomach tissues, similar to frozen material. By Western blot analysis, we found that the detection of membrane, cytoplasmic, nuclear, and phosphorylated protein from PAXgene-fixed human tissue samples was comparable to cryopreserved samples. Furthermore, the distribution of protein in PAXgene-fixed human tissue specimens is adequate for matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry for in situ proteomic analysis. Taken together, we demonstrate here that PAXgene has great potential to serve as a novel multimodal fixative for modern pathology, enabling extensive protein biomarker studies on clinical tissue samples.


The role of nuclear factor-kappa B in pulmonary diseases.
Nuclear factor-kappa B (NF-kappaB) is a family of DNA-binding protein factors that are required for transcription of most proinflammatory molecules, including adhesion molecules, enzymes, cytokines, and chemokines. NF-kappaB activation seems to be a key early event in a variety of cell and animal model systems developed to elucidate the pathobiology of lung diseases. The purpose of this short review is to describe what is known about the molecular biology of NF-kappaB and to review information that implicates NF-kappaB in the pathogenesis of lung disease, including ARDS, systemic inflammatory response syndrome, asthma, respiratory viral infections, occupational and environmental lung disease, and cystic fibrosis.


In vitro production of viable eggs from isolated mouse primary follicles by successive culture.
To produce viable eggs from single primary follicles in vitro, primary follicles containing oocytes (average 39.0 ± 0.2 µm in diameter) were isolated from the ovaries of 1-week-old mice, and cultured in combination with culture membranes for the first 8 days up to the secondary follicle stage, followed by the next 12 days to the later stages. After culture with a combination of first and second culture membranes using high and low adhesion characteristics, the average oocyte diameters of the surviving follicles increased by almost two-fold in all four groups. Further, the oocyte maturation rate was the highest (74.1%) in the culture group with low adhesion with collagenase and high adhesion. In this culture group, when the O2 concentration was changed from 20% in the first culture to 5% in the second culture, the cleavage rate increased to 47.5%, which was comparable to the level of the in vivo control (34.6%). Finally, 39 embryos at the 2- to 8-cell stages were transferred into the oviducts of three pseudopregnant females, and eight live pups (20.5%) were obtained. Of the eight pups, six survived for at least six months and were fertile. The present study shows successive in vitro cultures of single isolated primary follicles for the production of viable eggs. We believe that this culture system, with a combination of culture membranes under controlled O2 conditions, is applicable to other mammalian species, including humans.


Recent advances in diagnostic technology: applications in autoimmune and infectious diseases.
Biomarkers are used ubiquitously as indicators of biological health. The development of genomic and proteomic multiplex technologies have enormously amplified biomarker discovery and application to diagnostic and therapeutic decisions in clinical practice. New technologies are now available that simultaneously identify a wide spectrum of biomarkers and save time and costs. Multiplexed assays can be coupled to other disease specific indicators (i.e., cytokines, single nucleotide polymorphisms) in order to get more powerful information. However, there is an urgent need for validation/standardization of the new assays before they are adopted into clinical diagnostics. It is worthy to note a new assay, T cell interferon gamma release (TIGRAs), which has recently been introduced in the diagnosis of latent tuberculosis infection. It seems to perform better than tuberculin skin test in patients with inflammatory rheumatic diseases. In this review, we focus on advantages and limits of novel approaches to the detection of autoantibody profiles in autoimmune diseases or pathogen signatures in microbiology.


Turbid scene enhancement using multi-directional illumination fusion.
Ambient light is strongly attenuated in turbid media. Moreover, natural light is often more highly attenuated in some spectral bands, relative to others. Hence, imaging in turbid media often relies heavily on artificial sources for illumination. Scenes irradiated by an off-axis single point source have enhanced local object shadow edges, which may increase object visibility. However, the images may suffer from severe nonuniformity, regions of low signal (being distant from the source), and regions of strong backscatter. On the other hand, simultaneously illuminating the scene from multiple directions increases the backscatter and fills-in shadows, both of which degrade local contrast. Some previous methods tackle backscatter by scanning the scene, either temporally or spatially, requiring a large number of frames. We suggest using a few frames, in each of which wide field scene irradiance originates from a different direction. This way, shadow contrast can be maintained and backscatter can be minimized in each frame, while the sequence at large has a wider, more spatially uniform illumination. The frames are then fused by post processing to a single, clearer image. We demonstrate significant visibility enhancement underwater using as little as two frames.


Hedgehog, Chamomile, and Multipetal Polymeric Structures on the Nanoparticle Surface: Computer Modelling.
A single spherical nanoparticle coated with a densely grafted layer of an amphiphilic homopolymer with identical A-graft-B monomer units was studied by means of coarse-grained molecular dynamics. In solvent, selectively poor for mainchain and good for pendant groups; the grafted macromolecules self-assemble into different structures to form a complex pattern on the nanoparticle surface. We distinguish hedgehog, multipetalar, chamomile, and densely structured shells and outline the area of their stability using visual analysis and calculate aggregation numbers and specially introduced order parameters, including the branching coefficient and relative orientation of monomer units. For the first time, the branching effect of splitting aggregates along with the distance to the grafting surface and preferred orientation of the monomer units with rearrangements of the dense compacted shell was described. The results explain the experimental data, are consistent with the analytical theory, and are the basis for the design of stimulus-sensitive matrix-free composite materials.


Association of a History of Incarceration and Solitary Confinement with Suicide-Related Outcomes in a General Population Sample from Two U.S. Cities.
To evaluate whether a history of incarceration was associated with increased odds of suicidal ideation and suicide attempts, and to determine if this association was further strengthened when combined with a history of solitary confinement. We collected cross-sectional data from a general population sample in New York City and Baltimore in March 2017. Participants were categorized based on their history of incarceration and solitary confinement: (1) no incarceration, (2) incarceration-only, and (3) incarceration plus solitary confinement. We compared these three groups, utilizing hierarchical adjustments for sociodemographic factors and adverse childhood experiences. Missing data were accounted for utilizing multiple imputation via chained equation. A total of 1221 individuals were analyzed. Those who experienced both incarceration and solitary confinement consistently had higher odds of suicidal ideation (OR, 2.80; 95% CI, 1.43 to 5.48) and suicide attempts (OR, 6.98; 95% CI, 2.77 to 17.61) than never incarcerated individuals. Those who experienced incarceration without solitary confinement had higher odds of suicide attempts (OR, 3.77; 95% CI, 1.35 to 10.56) than never incarcerated individuals, whereas this association was not evident for suicidal ideation. Solitary confinement increased the odds of suicidal ideation even compared to incarceration without solitary confinement (OR, 2.71; 95% CI, 1.09 to 6.74). Our findings support the need to address the higher likelihood of suicide-related outcomes among those in contact with the criminal justice system, and to consider alternatives to solitary confinement.


[Coronary angioplasty and stenting in patients with ischemic cardiomyopathy].
Multiple coronary artery atherosclerotic lesions are a major cause of ischemic cardiomyopathy. Myocardial revascularization in patients with ischemic cardiomyopathy in the presence of the viable myocardium and/or ischemic areas leads to improved central hemodynamic parameters and as a consequence to better quality of life and prognosis as a whole. The paper describes a clinical case of successful coronary artery angioplasty and stenting in a patient with ischemic cardiomyopathy. Following 8 months, there was a considerable improvement in the patient's general condition, an increase in left ventricular ejection fraction, and a reduction in cardiac cavity sizes.


[Heart failure: the pathogenetic continuum and biomarkers].
Molecular aspects of pathogenesis of cardiac failure touching on transmission of pathological signals through the transduction system, involvement of mechanisms of transcriptional reprogramming and metabolic changes in the myocardium, as well as processes of aging and inflammation in the pathogenetic continuum are considered in this paper. Data on markers of early diagnosis, prognosis and progression of heart failure and perspectives of discovery of its pathogenesis within framework of developing system biology integrating analysis of multiple different in their nature biomarkers are also presented.


Food safety--then and now. A Bicentennial study.
Although this is our Bicentennial year, effective measures to insure food safety date back less than a century. The first efforts toward reform were begun by Accum in England early in the nineteenth century, but they did not bear fruit there--in even a beginning form--until 1875, when Parliament passed the Sales of Food and Drug Act. Legislation came even later in the U.S.--not until the first Pure Food and Drugs Act became law in 1906, largely due to the unswerving efforts for almost twenty years of Harvey W. Wiley. Today, the scientific approach is applied in developing criteria for judging the safety of food and for regulations to insure that healthful, safe food reaches the consumer. Amendments to this law in 1938 and 1958 have further strengthened the protection the public is provided in its food supply. Today, the substances on the "GRAS" list are being examined individually to determine their safety when used in foods. However, the legalistic invoking of absolutes, as in the Delaney Clause of the 1958 amendments, goes beyond the limits of common sense. The challenge is to insure the benefits of science and technology without the loss of basic individual freedom.


From translation to version management: a history and review of methods for the cultural adaptation of the EuroQol five-dimensional questionnaire.
The EuroQol five-dimensional (EQ-5D) questionnaire is used worldwide as a patient-reported outcome (PRO) instrument for the measurement and valuation of health. Several variants of the instrument now exist, including versions with three and five levels of severity and one for respondents aged 8 to 14 years. From the outset, a demand for new language versions of the EQ-5D questionnaire meant that there was a need to implement standardized procedures, which ensured that such versions were produced following international recommendations for the cultural adaptation of patient-reported outcomes. The availability of new variants and formats of the instrument, such as telephone-administered or electronic formats, complicated the task of providing and controlling the quality of cultural adaptations. Although cultural adaptations of the instrument are widely used, the procedures currently used to produce them have not been widely disseminated. The present article therefore describes the evolution of the production of other language versions of the instrument from the earliest days of simultaneous production and translation of the EQ-5D questionnaire to the more recent, broader-based strategy of version management. We describe current adaptation procedures and innovations within those procedures. We also describe how version management is organized within the EuroQol Group, review aspects related to quality control, and provide an overview of the number of currently available language versions for each variant of the EQ-5D questionnaire: three-level, five-level, and youth versions. We conclude by discussing some of the relevant issues related to cultural adaptation for frequently used instruments such as the EQ-5D questionnaire.


Unsuitable habitat patches lead to severe underestimation of dynamics and gene flow in a zooplankton metapopulation.
Migration and re-colonization enable organisms to persist in metapopulations. Re-colonization success may be limited by the number of arriving migrants or by patch quality. In a well-studied rock pool Daphnia metapopulation, it is frequently assumed that re-colonization is limited by the number of arriving migrants, and that all patches are equally suitable for colonization. This assumption strongly influences how observations about dynamics, epidemiology and population genetics for the entire metapopulation are interpreted. Here we test this assumption. In 627 rock pools, we found that high pH, high Ca(++) and high water conductivity were positively correlated with the presence of D. magna. The experimental release of D. magna into randomly chosen natural pools revealed the highest colonization success in pools with high pH. Next, we elevated pH and Ca(++) concentrations in natural pools by adding a system-specific natural source of calcium carbonate (either from crushed oyster shells or from eider duck droppings, which contain blue mussel shells). These treatments led to a rapid increase in pH and Ca(++) and strongly raised the likelihood that introduced D. magna would establish persistent populations. Therefore, we conclude that low pH and Ca(++) result in unsuitable colonization conditions in two-thirds of the untreated pools. A further experiment revealed that natural colonization rates were about five times higher in calcium-treated pools than in untreated pools. Finally, we observed that eider droppings are more frequently found in the catchment area of occupied pools, than they are in those of unoccupied pools, suggesting that the blue mussel shells contained in the eider droppings play an important role in making pools suitable for colonization and in enabling D. magna to persist. Thus, eider ducks are ecosystem engineers in this system. We recalculate typical metapopulation parameters to account for the unsuitable pools, resulting in a much more dynamic picture of this metapopulation than previously believed, with colonization rates and gene flow three to five times higher. These results have strong implications for metapopulation persistence, local and global genetic diversity, genetic rescue, gene flow and local adaptation. Our results emphasize that without verifying patch suitability, estimated rates of metapopulation dynamics can severely underestimate the true rates.


Advancing Early Identification of Axial Spondyloarthritis: An Interobserver Comparison of Extended Role Practitioners and Rheumatologists.
To compare clinical impression and confidence of extended role practitioners (ERP) with those of rheumatologists experienced in axial spondyloarthritis (axSpA) according to (1) evaluation of patients with chronic back pain assessed for axSpA; and (2) magnetic resonance imaging (MRI) recommendation for further investigation of these patients. Patients with ≥ 3 months of back pain and age of onset < 45 years were referred for axSpA evaluation. An ERP assessed consecutive patients and recorded standardized clinical information in written form. Three rheumatologists subsequently evaluated each patient based on the recorded information. Patients were classified as having axSpA or mechanical back pain based on clinical and investigative findings. Level of confidence was noted for classification and MRI indication. Agreement between assessors was evaluated using percentage agreement and κ coefficient. Fifty-seven patients were assessed. Interobserver agreement of clinical impression for all raters was moderate (κ = 0.52). Agreement of clinical impression between ERP and rheumatologists ranged between 71.2% (κ = 0.41) and 79.7% (κ = 0.57). Agreement of clinical impression among rheumatologists ranged from 74.1% (κ = 0.49) to 79.7% (κ = 0.58). All rater agreement for MRI indication was fair (κ = 0.37). ERP agreement with rheumatologist for MRI recommendation ranged from 64.2% (κ = 0.32) to 75% (κ = 0.48). Agreement for MRI indication among rheumatologists ranged from 62.9% (κ = 0.27) to 74% (κ = 0.47). Confidence in clinical impression was similar among all practitioners. ERP with specialty training in inflammatory arthritis demonstrate clinical impressions comparable with those of rheumatologists in the assessment of axSpA. Incorporation of such roles into existing models of care may assist in early detection of axSpA.


Circulating biomarkers of pulmonary and extrapulmonary tuberculosis in children.
Tuberculosis (TB) in children is not only more likely to cause more severe disease than that seen in adults, it is also more likely to be extrapulmonary. Moreover, pediatric TB is very difficult to diagnose and suffers from a lack of understanding of host biomarkers for monitoring the progression of disease. Hence, we sought to identify the expression patterns of a variety of biomarkers in the plasma of children with pulmonary TB (PTB) and extrapulmonary TB (ETB), as well as in healthy control (HC) children. Thus, we examined a variety of circulating markers reflecting tissue inflammation, oxidative stress, innate immune activation, fibrosis, and the cytokine response. Children with active TB, compared to HC children, showed markedly elevated plasma levels of matrix metalloproteinases and their endogenous inhibitors. In addition, children with active TB had significantly elevated levels of C-reactive protein, α-2 macroglobulin, and haptoglobin, as well as hemoxygenase 1. Markers of innate immune activation (lipopolysaccharide [LPS] and lipopolysaccharide-binding protein [LBP]) were significantly lower in ETB than in PTB children. Although there were no significant differences between the two groups in their levels of cytokines (type 1 [gamma interferon (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 2 (IL-2), and IL-12], type 2 [IL-4, IL-5, IL-13, and IL-33], and most type 17 [IL-17A, IL-22, IL-1β, and IL-6] and type 1 interferons [IFN-α and IFN-β]) or most of the cytokines associated with immune modulation (IL-10 and IL-20), pediatric TB was associated with elevated plasma transforming growth factor β (TGF-β), IL-21, and IL-23 levels. Thus, pediatric TB is characterized by elevated levels of a variety of biomarkers at homeostasis, suggesting that these responses may play a crucial role in disease pathogenesis.


Placental Ischemia and Resultant Phenotype in Animal Models of Preeclampsia.
Preeclampsia is new onset (or worsening of preexisting) hypertension that occurs during pregnancy. It is accompanied by chronic inflammation, intrauterine growth restriction, elevated anti-angiogenic factors, and can occur with or without proteinuria. Although the exact etiology is unknown, it is thought that preeclampsia begins early in gestation with reduced uterine spiral artery remodeling leading to decreased vasculogenesis of the placenta as the pregnancy progresses. Soluble factors, stimulated by the ischemic placenta, shower the maternal vascular endothelium and are thought to cause endothelial dysfunction and to contribute to the development of hypertension during pregnancy. Due to the difficulty in studying such soluble factors in pregnant women, various animal models have been designed. Studies from these models have contributed to a better understanding of how factors released in response to placental ischemia may lead to increased blood pressure and reduced fetal weight during pregnancy. This review will highlight various animal models and the major findings indicating the importance of placental ischemia to lead to the pathophysiology observed in preeclamptic patients.


Clinical and neuroradiological approach to fucosidosis in a child with atypical presentation.
Fucosidosis is a rare lysosomal storage disease with clinical presentation of developmental retardation, coarse facial features, hepatosplenomegaly, dysostosis multiplex, and angiokeratomas. Here, a 7-year-old female patient with progressive dystonic movement disorder and loss of acquired motor skills is presented. Coarse facial feature and abnormal globuspallidus signaling in brain magnetic resonance imaging (MRI) led the patient to be investigated in terms of fucosidosis despite absence of hepatosplenomegaly, dysostosis multiplex, and angiokeratomas. Markedly decreased enzyme activity of alpha-fucosidosis led to the correct diagnosis. Various neurological findings have recently been reported in fucosidosis. However, neuroimaging findings have not been studied in detail except a few studies. It is critically important to discuss the wide neuroradiological spectrum of the disease and to highlight fucosidosis in differential diagnosis of bilateral pallidalhypointensity on T2-weighted images in brain MRI. In addition, description of atypical clinical findings of fucosidosis should avoid clinicians from diagnostic delay.


Low-loss light transport at the subwavelength scale in silicon nano-slot based symmetric hybrid plasmonic waveguiding schemes.
A hybrid plasmonic structure comprising a silicon slot waveguide separated from an inverse metal ridge by a thin low-index insulator gap is proposed and investigated. Owing to its symmetric hybrid configuration containing closely spaced silicon rails near the metal ridge, the fundamental symmetric hybrid slot mode supported by the structure is demonstrated to be capable of simultaneously achieving low propagation loss and subwavelength field confinement within a wide range of physical dimensions at the telecom wavelength. Comprehensive numerical investigations regarding the effects of key geometric parameters on the guided modes' properties, including the slot sizes, the shape and dimension of the silicon rails, the width of the gap region as well as the height of metallic nanoridge, have been conducted. It is revealed that the propagation distance of the symmetric mode can be more than several millimeters (even up to the centimeter range), while simultaneously achieving a subwavelength mode size and tight field confinement inside the gap region. In addition to the studies on the modal characteristics, excitation strategies of the guided hybrid modes and the conversion between dielectric slot and hybrid slot modes are also numerically demonstrated. The studied platform potentially combines the advantages of silicon slot and plasmonic structures, which might lay important groundwork for future hybrid integrated photonic components and circuits.


An investigation into the use of 3G mobile communications to provide telehealth services in rural KwaZulu-Natal.
We investigated the use of third-generation (3G) mobile communications to provide telehealth services in remote health clinics in rural KwaZulu-Natal, South Africa. We specified a minimal set of services as our use case that would be representative of typical activity and to provide a baseline for analysis of network performance. Services included database access to manage chronic disease, local support and management of patients (to reduce unnecessary travel to the hospital), emergency care (up to 8 h for an ambulance to arrive), e-mail, access to up-to-date information (Web), and teleclinics. We made site measurements at a representative set of health clinics to determine the type of coverage (general packet radio service [GPRS]/3G), its capabilities to support videoconferencing (H323 and Skype™ [Microsoft, Redmond, WA]) and audio (Skype), and throughput for transmission control protocol (TCP) to gain a measure of application performance. We found that none of the remote health clinics had 3G service. The GPRS service provided typical upload speed of 44 kilobits per second (Kbps) and download speed of 64 Kbps. This was not sufficient to support any form of videoconferencing. We also observed that GPRS had significant round trip time (RTT), in some cases in excess of 750 ms, and this led to slow start-up for TCP applications. We found audio was always so broken as to be unusable and further observed that many applications such as Web access would fail under conditions of very high RTT. We found some health clinics were so remote that they had no mobile service. 3G, where available, had measured upload speed of 331 Kbps and download speed of 446 Kbps and supported videoconferencing and audio at all sites, but we frequently experienced 3G changing to GPRS. We conclude that mobile communications currently provide insufficient coverage and capability to provide reliable clinical services and would advocate dedicated wireless services where reliable communication is essential and use of store and forward for mobile applications.


[Analysis of liquor flavor spectra and pattern recognition computation].
Chinese liquor is a complex mixture and contains a large amount of microconstituents, which affects the quality and flavor of liquor. In order to discriminate liquor flavors rapidly, the spectra of liquors were obtained by FTIR and employed as the input patterns of pattern classification algorithms, then liquor flavor discrimination models were built. This paper introduces liquor flavor pattern recognition algorithms comprehensively and systematically for the first time, and the algorithms contain statistical classifications (linear discriminant function, quadratic discriminant function, regularized discriminant analysis, and K nearest neighbor), prototype learning algorithm (learning vector quantization), support vector machine and adaboost algorithm. Experimental results show that the liquor flavor classification algorithms demonstrate good performance and achieve high accuracy, recognition rate and rejection rate.


Association between urinary N-acetyl-beta-glucosaminidase and its isoenzyme patterns and microangiopathy in type 1 diabetes mellitus.
Urinary N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes (NAG A and NAG B) in samples from 87 type 1 diabetic patients and 40 apparently healthy reference subjects were studied with enzyme immunoassays. The diabetic patients had higher concentrations of urinary NAG than did the control subjects (P less than 0.01), but the isoenzyme pattern did not differ. There was a positive correlation between metabolic control (Hb A1c concentrations) and total NAG (P less than 0.01), NAG A (P less than 0.01), and NAG B (P less than 0.001). The diabetic patients were divided into three groups, depending on the degree of retinopathy. Subjects with severe forms of retinopathy did not have increased concentrations of urinary NAG unless they had concomitant nephropathy. The isoenzyme pattern was similar irrespective of degree of retinopathy or nephropathy. The results indicate that concentrations of urinary NAG are positively correlated to the degree of nephropathy, whereas there is no such correlation to the degree of retinopathy.


An in vitro digestion test that reflects rat intestinal conditions to probe the importance of formulation digestion vs first pass metabolism in Danazol bioavailability from lipid based formulations.
The impact of gastrointestinal (GI) processing and first pass metabolism on danazol oral bioavailability (BA) was evaluated after administration of self-emulsifying drug delivery systems (SEDDS) in the rat. Danazol absolute BA was determined following oral and intraduodenal (ID) administration of LFCS class IIIA medium chain (MC) formulations at high (SEDDSH-III) and low (SEDDSL-III) drug loading and a lipid free LFCS class IV formulation (SEDDS-IV). Experiments were conducted in the presence and absence of ABT (1-aminobenzotriazole) to evaluate the effect of first pass metabolism. A series of modified in vitro lipolysis tests were developed to better understand the in vivo processing of SEDDS in the rat. Danazol BA was low (<13%) following oral and ID administration of either SEDDS. Increasing drug loading, ID rather than oral administration, and administration of SEDDS-IV rather than SEDDS-III led to higher oral BA. After pretreatment with ABT, however, danazol oral BA significantly increased (e.g., 60% compared to 2% after administration of SEDDSL-III), no effect was observed on increasing drug loading, and differences between SEDDS-III and -IV were minimal. In vitro digestion models based on the lower enzyme activity and lower dilution conditions expected in the rat resulted in significantly reduced danazol precipitation from SEDDS-III or SEDDS-IV on initiation of digestion. At the doses administered here (4-8 mg/kg), the primary limitation to danazol oral BA in the rat was first pass metabolism, and the fraction absorbed was >45% after oral administration of SEDDS-III or SEDDS-IV. In contrast, previous studies in dogs suggest that danazol BA is less dependent on first pass metabolism and more sensitive to changes in formulation processing. In vitro digestion models based on likely rat GI conditions suggest less drug precipitation on formulation digestion when compared to equivalent dog models, consistent with the increases in in vivo exposure (fraction absorbed) seen here in ABT-pretreated rats.


[Evaluation of the use of the socioeconomic deprivation index at area level in ecological studies on environment and health].
in SENTIERI surveillance system, the health risk assessment in the contaminated sites (CSs) was carried out considering the socioeconomic deprivation index (ID-SENTIERI) at the municipal level as a confounder. Pasetto et al. discussed the use of IDs in ecological studies and proposed to examine the role of ID-SENTIERI as a confounder. to evaluate the initial conditions necessary for the role of confounding, i.e., the verification of an association of the ID-SENTIERI with the risk of some of the diseases for which evidence of a relationship with the socioeconomic state (SES) is documented in the literature. the methodological approach is to exploit ecological correlations in order to assess the relationship between ID and the occurrence of mortality or congenital malformations (CMs). mortality and CM data from municipalities in the regions of Emilia-Romagna (Northern Italy), Tuscany (Central Italy), and Campania (Southern Italy) were used. Mortality for all causes, all tumours, and lung cancers were analysed for the period 1995-2008. For the CMs, data from the regional registries of Emilia-Romagna, Tuscany, and Campania in the periods 1995-2011, 1992-2011, 2004-2010, respectively, were used. Analyses of the relationship between mortality/CMs and ID-SENTIERI were carried out according to cause, region, gender, and demographic amplitude classes using a GAM-Poisson regression model. the mortality analyses show that, for the male population of the three regions under study, the relationship between ID and mortality is increasing for each outcome for municipalities with less than 50,000 inhabitants; while results for female population differ from region to region. The results of the CMs show growing associations, considering only municipalities under 10,000 inhabitants. the results of the study suggest that scientific evidence of an association between SES and health should be evaluated taking into account the gender, the study area, and the demographic size of the municipalities. For ID to be used as a confounding variable, it must be associated with the outcomes for which the influence of socioeconomic factors in the reference areas has been ascertained. If there is no such association, the ID cannot be used as a confounder, as it could lead to distortions of estimates and such distortions are difficult to predict. In these cases, ad hoc IDs should be produced.


Epidemiological surveillance of rabies in Lithuania from 1986 to 1996.
Rabies has been endemic in Lithuania for centuries. The objective of this study was to evaluate rabies incidence and seasonal trends in domestic and wild animals in Lithuania from 1986 to 1996. Annual rabies reports and data on cattle numbers were collected. Descriptive epidemiology and time series data analyses were performed to detect seasonal trends. A total of 1,475 specimens were submitted for rabies testing. Of these, 1,248 (84.6%) were confirmed as rabies cases by immunofluorescence antibody testing. Domestic animals accounted for 73.8% (921/1,248) of all rabies cases, with cattle accounting for 61.1% (563/921) of domestic animal cases. Wildlife cases were reported principally in red foxes (56%; 183/327) and raccoon dogs (31.2%; 102/327). Time series analysis indicated a strong association between the occurrence of rabies in cattle and the season of the year (P = 0.0032), with the highest incidence of rabies occurring in autumn. The incidence declined from 3.4 to 4.8 cases per 100,000 cattle in the mid-1980s to < 1.5 cases per 100,000 cattle in 1994, but increased to 4.2 cases per 100,000 cattle in 1996. However, as the cattle population dramatically decreased (by 54%) over the eleven-year period of the study, the reduction in the total number of rabies cases in cattle was not reflected in the annual incidence rate of cattle rabies.


The effect of sleep restriction, with or without high-intensity interval exercise, on myofibrillar protein synthesis in healthy young men.
Sleep restriction has previously been associated with the loss of muscle mass in both human and animal models. The rate of myofibrillar protein synthesis (MyoPS) is a key variable in regulating skeletal muscle mass and can be increased by performing high-intensity interval exercise (HIIE), although the effect of sleep restriction on MyoPS is unknown. In the present study, we demonstrate that participants undergoing a sleep restriction protocol (five nights, with 4 h in bed each night) had lower rates of skeletal muscle MyoPS; however, rates of MyoPS were maintained at control levels by performing HIIE during this period. Our data suggest that the lower rates of MyoPS in the sleep restriction group may contribute to the detrimental effects of sleep loss on muscle mass and that HIIE may be used as an intervention to counteract these effects. The present study aimed to investigate the effect of sleep restriction, with or without high-intensity interval exercise (HIIE), on the potential mechanisms underpinning previously-reported sleep-loss-induced reductions to muscle mass. Twenty-four healthy, young men underwent a protocol consisting of two nights of controlled baseline sleep and a five-night intervention period. Participants were allocated into one of three parallel groups, matched for age, V̇O2peak , body mass index and habitual sleep duration; a normal sleep (NS) group [8 h time in bed (TIB) each night], a sleep restriction (SR) group (4 h TIB each night), and a sleep restriction and exercise group (SR+EX, 4 h TIB each night, with three sessions of HIIE). Deuterium oxide was ingested prior to commencing the study and muscle biopsies obtained pre- and post-intervention were used to assess myofibrillar protein synthesis (MyoPS) and molecular markers of protein synthesis and degradation signalling pathways. MyoPS was lower in the SR group [fractional synthetic rate (% day-1 ), mean ± SD, 1.24 ± 0.21] compared to both the NS (1.53 ± 0.09) and SR+EX groups (1.61 ± 0.14) (P < 0.05). However, there were no changes in the purported regulators of protein synthesis (i.e. p-AKTser473 and p-mTORser2448 ) and degradation (i.e. Foxo1/3 mRNA and LC3 protein) in any group. These data suggest that MyoPS is acutely reduced by sleep restriction, although MyoPS can be maintained by performing HIIE. These findings may explain the sleep-loss-induced reductions in muscle mass previously reported and also highlight the potential therapeutic benefit of HIIE to maintain myofibrillar remodelling in this context.


[2 interconvertible forms of L type pyruvate kinase from the rabbit adrenal cortex].
Pyruvate kinase (PK-II) isoenzyme from rabbit adrenal cortex was isolated by chromatography on DEAE-cellulose during long-term incubation in the cold. The enzyme is resistant to fructose-1,6-diphosphate (FDP) and L-alanine. Dithiotreitol and preincubation for 10 min. at 30 degrees C did not change the resistance of the enzyme to these factors. Preincubation for 30 min. at 30 degrees C in the presence of EDTA (3.3 mM) converted the enzyme into the FDP-sensitive form, the dependency curve of the initial reaction rate on the concentration of phosphoenolpyruvate being S-form. Sucrose and dithiotreitol contributed the isolation of PK-II from rabbit adrenal cortex in the form having a higher degree of the interaction of active sites.


Curation Principles Derived from the Analysis of the SBOL iGEM Data Set.
As an engineering endeavor, synthetic biology requires effective sharing of genetic design information that can be reused in the construction of new designs. While there are a number of large community repositories of design information, curation of this information has been limited. This in turn limits the ways in which design information can be put to use. The aim of this work was to improve this situation by creating a curated library of parts from the International Genetically Engineered Machines (iGEM) registry data set. To this end, an analysis of the Synthetic Biology Open Language (SBOL) version of the iGEM registry was carried out using four different approaches-simple statistics, SnapGene autoannotation, SYNBICT autoannotation, and expert analysis-the results of which are presented herein. Key challenges encountered include the use of free text, insufficient part provenance, part duplication, lack of part removal, and insufficient continuous curation. On the basis of these analyses, the focus has shifted from the creation of a curated iGEM part library to instead the extraction of a set of lessons, which are presented here. These lessons can be exploited to facilitate the creation and curation of other part libraries using a simpler and less labor intensive process.


Methylation Density Pattern of KEAP1 Gene in Lung Cancer Cell Lines Detected by Quantitative Methylation Specific PCR and Pyrosequencing.
The KEAP1/NRF2 pathway is the key regulator of antioxidants and cellular stress responses, and is implicated in neoplastic progression and resistance of tumors to treatment. KEAP1 silencing by promoter methylation is widely reported in solid tumors as part of the complex regulation of the KEAP1/NRF2 axis, but its prognostic role remains to be addressed in lung cancer. We performed a detailed methylation density map of 13 CpGs located into the KEAP1 promoter region by analyzing a set of 25 cell lines from different histologies of lung cancer. The methylation status was assessed using quantitative methylation specific PCR (QMSP) and pyrosequencing, and the performance of the two assays was compared. Hypermethylation at the promoter region of the KEAP1 was detected in one third of cell lines and its effect on the modulation KEAP1 mRNA levels was also confirmed by in vitro 5-Azacytidine treatment on lung carcinoid, small lung cancer and adenocarcinoma cell lines. QMSP and pyrosequencing showed a high rate of concordant results, even if pyrosequencing revealed two different promoter CpGs sub-islands (P1a and P1b) with a different methylation density pattern. Our results confirm the effect of methylation on KEAP1 transcription control across multiple histologies of lung cancer and suggest pyrosequencing as the best approach to investigate the pattern of CpGs methylation in the promoter region of KEAP1. The validation of this approach on lung cancer patient cohorts is mandatory to clarify the prognostic value of the epigenetic deregulation of KEAP1 in lung tumors.


Electrical surrogate for detection of severe left ventricular systolic dysfunction.
Early diagnosis and therapy improves outcomes in heart failure with severely reduced left ventricular ejection fraction (LVEF ≤35%), but some patients may remain undiagnosed. We hypothesized that a combination of electrocardiogram (ECG) markers may identify individuals with severely reduced LVEF. From a community-based study in the Northwest US (the Oregon Sudden Unexpected Death Study), we evaluated the prevalence of conventional ECG markers by LVEF. We then evaluated the association of nine additional ECG markers and LVEF. We validated the correlation of these ECG markers and LVEF in a separate, large health system in Los Angeles, California. In the discovery population (n = 1,047), patients with LVEF ≤35% were twice as likely as those with LVEF >35% to have ≥1 conventional ECG abnormality. In the subset without conventional ECG abnormalities, ≥4 abnormal ECG markers from the expanded panel were found in 12% vs. 1% of patients with LVEF ≤35% and >35%, respectively. In the validation population (n = 9,742), 44% with LVEF ≤35% and 17% with LVEF >35% had ≥1 conventional ECG abnormality. In patients without conventional ECG abnormalities (n = 7,601), 40% with LVEF ≤35% and 5% with LVEF >35% had ≥4 abnormal ECG markers from the expanded panel. Each additional abnormal ECG marker from the expanded panel (range 0 to ≥4) more than doubled the odds of LVEF ≤35%. An expanded panel of easily obtained ECG markers correlated strongly with severely reduced LVEF in two separate populations. This electrical surrogate score could facilitate diagnosis of severely reduced LVEF, and warrants prospective evaluation.


Trajectories of pain severity in juvenile idiopathic arthritis: results from the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort.
We studied children enrolled within 90 days of juvenile idiopathic arthritis diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) prospective inception cohort to identify longitudinal trajectories of pain severity and features that may predict pain trajectory at diagnosis. A total of 1062 participants were followed a median of 24.3 months (interquartile range = 16.0-37.1 months). Latent trajectory analysis of pain severity, measured in a 100-mm visual analogue scale, identified 5 distinct trajectories: (1) mild-decreasing pain (56.2% of the cohort); (2) moderate-decreasing pain (28.6%); (3) chronically moderate pain (7.4%); (4) minimal pain (4.0%); and (5) mild-increasing pain (3.7%). Mean disability and quality of life scores roughly paralleled the pain severity trajectories. At baseline, children with chronically moderate pain, compared to those with moderate-decreasing pain, were older (mean 10.0 vs 8.5 years, P = 0.01) and had higher active joint counts (mean 10.0 vs 7.2 joints, P = 0.06). Children with mild-increasing pain had lower joint counts than children with mild-decreasing pain (2.3 vs 5.2 joints, P < 0.001). Although most children with juvenile idiopathic arthritis in this cohort had mild or moderate initial levels of pain that decreased quickly, about 1 in 10 children had concerning pain trajectories (chronically moderate pain and mild-increasing pain). Systematic periodic assessment of pain severity in the months after diagnosis may help identify these concerning pain trajectories early and lay out appropriate pain management plans. Focused research into the factors leading to these concerning trajectories may help prevent them.


Procurement of the human pancreas for pancreatic islet transplantation.
The full potential of pancreatic islet transplantation (PIT) has not been realized because of the difficulties associated with islet isolation, particularly when associated with a remote islet isolation center. Herein, we describe the principles of pancreatic procurement for PIT, which have allowed us to achieve a successful pancreatic islet isolation rate 67% of the time when using a remote islet isolation center. Between January 16, 2002 and June 30, 2003, 39 pancreata were procured and processed for PIT at a distant islet isolation center. All pancreata were procured by a single surgeon, and special attention was given to careful dissection of the pancreas, maintenance of arterial inflow and the pressure differential between arterial and venous systems during perfusion, rapid organ cooling, and rapid removal of the pancreas from the body. Twenty-six of 39 (67%) procured pancreata yielded more tha 5,000 islet equivalents (IEQ)/kg recipient weight and were transplanted. Median IEQs per isolation was 413,867, whereas median purity and viability were 65% and 100%, respectively. The median time for pancreatic excision was 34 minutes, whereas cold ischemia time was 6 hours and 40 minutes. The principles we have adopted for pancreatic procurement for PIT have resulted in a 67% islet isolation success rate despite the maintenance of more than 5,000 IEQ/kg and the use of a remote islet isolation center.


Carbon-Based Nanomaterials Electrodes of Ionic Soft Actuators: From Initial 1D Structure to 3D Composite Structure for Flexible Intelligent Devices.
With the rapid development of autonomous and intelligent devices driven by soft actuators, ion soft actuators in flexible intelligent devices have several advantages over other actuators, including their light weight, low voltage drive, large strain, good flexibility, fast response, etc. Traditional ionic polymer metal composites have received a lot of attention over the past decades, but they suffer from poor driving performance and short service lives since the precious metal electrodes are not only expensive, heavy, and labor-intensive, but also prone to cracking with repeated actuation. As excellent candidates for the electrode materials of ionic soft actuators, carbon-based nanomaterials have received a lot of interest because of their plentiful reserves, low cost, and excellent mechanical, electrical, and electrochemical properties. This research reviewed carbon-based nanomaterial electrodes of ion soft actuators for flexible smart devices from a fresh perspective from 1D to 3D combinations. The design of the electrode structure is introduced after the driving mechanism of ionic soft actuators. The details of ionic soft actuator electrodes made of carbon-based nanomaterials are then provided. Additionally, a summary of applications for flexible intelligent devices is provided. Finally, suggestions for challenges and prospects are made to offer direction and inspiration for further development.


Genomic-polygenic evaluation of Angus-Brahman multibreed cattle for feed efficiency and postweaning growth using the Illumina 3K chip.
The objectives of this study were to determine the fraction of additive genetic variance explained by the SNP from the Illumina Bovine3K chip; to compare the ranking of animals evaluated with genomic-polygenic, genomic, and polygenic models; and to assess trends in predicted values from these 3 models for residual feed intake (RFI), daily feed intake (DFI), feed conversion ratio (FCR), and postweaning BW gain (PWG) in a multibreed Angus-Brahman cattle population under subtropical conditions. Data consisted of phenotypes and genotypes from 620 bulls, steers, and heifers ranging from 100% Angus to 100% Brahman. Phenotypes were collected in a GrowSafe automated feeding facility (GrowSafe Systems, Ltd., Airdrie, Alberta, Canada) from 2006 to 2010. Variance components were estimated using single-trait genomic-polygenic mixed models with option VCE (Markov chain Monte Carlo) of the program GS3. Fixed effects were contemporary group (year-pen), age of dam, sex of calf, age of calf, Brahman fraction of calf, and heterozygosity of calf. Random effects were additive SNP, animal polygenic, and residual effects. Genomic predictions were computed using a model without polygenic effects and polygenic predictions with a model that excluded additive SNP effects. Heritabilities were 0.20 for RFI, 0.31 for DFI, 0.21 for FCR, and 0.36 for PWG. The fraction of the additive genetic variance explained by SNP in the Illumina 3K chip was 15% for RFI, 11% for DFI, 25% for FCR, and 15% for PWG. These fractions will likely differ in other multibreed populations. Rank correlations between genomic-polygenic and polygenic predictions were high (0.95 to 0.99; P < 0.0001), whereas those between genomic-polygenic and genomic predictions were low (0.65 to 0.74; P < 0.0001). Genomic-polygenic, genomic, and polygenic predictions for all traits tended to decrease as Brahman fraction increased, indicating that calves with greater Brahman fraction were more efficient but grew more slowly than calves with greater Angus fraction. Predicted SNP values were small for all traits, and those above and below 0.2 SNP SD were in multiple chromosomes, supporting the contention that quantitative traits are determined by large numbers of alleles with small effects located throughout the genome.


Quantitative amyloid imaging using image-derived arterial input function.
Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer's disease (AD). Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (VT) was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVRkinetic) without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVRREF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80). The estimated cerebellum VT was in line with literature reported values and the variability of cerebellum VT in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference normalization may not be accurate.


Postnatal Development of the Murine Notochord Remnants Quantified by High-resolution Contrast-enhanced MicroCT.
The notochord gives rise to spinal segments during development, and it becomes embedded within the nucleus pulposus of the intervertebral disc (IVD) during maturation. The disruption of the notochord band has been observed with IVD degeneration. Since the mechanical competence of the IVD relies on its structural constituents, defining the structure of the notochord during aging is critical for investigations relating to IVD function and homeostasis. The assessment and imaging of the notochord has classically relied on histological techniques, which introduces sectioning artifacts during preparation and spatial biases. Magnetic resonance imaging (MRI) does not offer sufficient resolution to discriminate the notochord from the surrounding the nucleus pulposus, especially in murine models. Current X-ray based computed tomography systems provide imaging resolutions down to the single- and sub- micron scales, and when coupled with contrast-enhancing agents, enable the high-resolution three-dimensional imaging of relatively small features. Utilizing phosphomolybdic acid to preferentially bind to collagen cationic domains, we describe the structure of the notochord remnants with aging in the lumbar IVDs of BALB/c mice. These results provide a highly quantitative and sensitive approach to monitoring the IVD during postnatal development.


Recurrent syncope and chronic ear pain.
An elderly gentleman presented to hospital with recurrent blackout episodes consistent with syncope and a 3-month history of right ear pain. Significant postural hypotension was recorded. White cell count and C reactive protein were elevated. MRI of the head and neck revealed a soft tissue abnormality in the right nasopharynx and base of skull. Tissue biopsies were obtained and microbiology specimens revealed a mixed growth of pseudomonas and diphtheroids. There was no histological evidence of malignancy. A diagnosis of skull base infection was made. Infective involvement of the carotid sinus was considered to be the cause of the recurrent syncope and postural hypotension. The patient responded well to a 12-week course of intravenous meropenem. Inflammatory markers returned to normal and a repeat MRI after 3 months of treatment showed significant resolution of infection. The syncopal episodes and orthostatic hypotension resolved in parallel with treatment of infection.


Identification and regulation of the IGFBP-4 protease and its physiological inhibitor in human trophoblasts and endometrial stroma: evidence for paracrine regulation of IGF-II bioavailability in the placental bed during human implantation.
The IGF family plays an important role in implantation and placental physiology. IGF-II is abundantly expressed by placental trophoblasts, and IGF binding protein (IGFBP)-4, a potent inhibitor of IGF actions, is the second most abundant IGFBP in the placental bed, expressed exclusively by the maternal decidua. Proteolysis of IGFBP-4 results in decreased affinity for IGF peptides, thereby enhancing IGF actions. In the current study, we have identified the IGFBP-4 protease and its inhibitor in human trophoblast and decidualized endometrial stromal cell cultures, and we have investigated their regulation in an effort to understand control of IGF-II bioavailability at the placental-decidual interface in human implantation. IGFBP-4 protease activity was detected in conditioned media (CM) from human trophoblasts and decidualized endometrial stromal cells using (125)I-IGFBP-4 substrate. Identification of the IGFBP-4 protease as pregnancy-associated plasma protein-A (PAPP-A) was confirmed by specific immunoinhibition and immunodepletion of the IGFBP-4 protease activity with specific PAPP-A antibodies. The IGFBP-4 protease activity was IGF-II-dependent in trophoblast CM. In decidualized stromal CM, PAPP-A/IGFBP-4 protease activity was also IGF-II-dependent, but was evident only when IGF-II was added in molar excess of the predominant IGFBP in decidualized stromal cell CM, IGFBP-1, supporting bioavailable IGF-II as a key cofactor of IGFBP-4 proteolysis by PAPP-A. Cultured first and second trimester human trophoblasts (n = 5) secreted PAPP-A into CM with mean +/- SEM levels of 172.4 +/- 32.8 mIU/liter.10(5) cells, determined by specific ELISA. PAPP-A in trophoblast CM (n = 3) and did not change in the presence of IGF-II (1-100 ng/ml). Cultured human endometrial stromal cells (n = 4) secreted low levels of PAPP-A (6.25 +/- 3.6 mIU/liter.10(5) cells). A physiological inhibitor of PAPP-A, the proform of eosinophil major basic protein (proMBP), was detected in trophoblast CM at levels of 1853 +/- 308 mIU/liter.10(5) cells, determined by specific ELISA, and was nearly undetectable in CM of human endometrial stromal cells. Upon in vitro decidualization of endometrial stromal cells with progesterone, PAPP-A levels in CM increased nearly 9-fold without a concomitant change in proMBP. In contrast to the experiments with trophoblasts, IGF-II and the IGF analogues, Leu(27) IGF-II, and Des (1-6) IGF-II, resulted in a dose-dependent decrease of PAPP-A levels in decidualized endometrial stromal CM by 70-90%, and a dose-dependent increase in proMBP of 14- to 41-fold. The data demonstrate conclusively that the IGF-II-dependent IGFBP-4 protease of human trophoblast and decidual origin is PAPP-A. Furthermore, the differential regulation of decidual PAPP-A and proMBP by insulin-like peptides supports a role for trophoblast-derived IGF-II as a paracrine regulator of these maternal decidual products that have the potential to regulate IGF-II bioavailability at the trophoblast-decidual interface. Overall, the data underscore potential roles for a complex family of enzyme (PAPP-A), substrate (IGFBP-4), inhibitor (proMBP), and cofactor (IGF-II) in the placental bed during human implantation.


SLAMF4 Is a Negative Regulator of Expansion of Cytotoxic Intraepithelial CD8+ T Cells That Maintains Homeostasis in the Small Intestine.
Intraepithelial T lymphocyte cells (IEL) are the first immune cells to respond to pathogens; they help maintain the integrity of the epithelial barrier. We studied the function of the mouse glycoprotein Signaling Lymphocyte Activation Molecule Family receptor (SLAMF) 4 (encoded by Slamf4) on the surface of CD8αβ αβ T-cell receptor (TCR)(+) IELs, and the roles of these cells in homeostasis of the small intestine in mice. SLAMF4(-) CD8(+) αβTCR(+) cells isolated from spleens of OT-I Rag1(-/-) mice were induced to express gut-homing receptors and transferred to C57BL/6J mice; levels of SLAMF4(+) cells were measured in small intestine tissues. After administration of anti-CD3 or antigen, with or without anti-SLAM4, to C57BL/6J and Slamf4(-/-) mice, CD8αβ αβTCR(+) IELs were collected; cytokine production and cytotoxicity were measured. Depletion of CX3CR1(+) phagocytes was assessed in mice by live-cell confocal imaging or by cytofluorometry; small intestine tissues were analyzed by histology and inflammation was quantified. Splenic CD8(+) αβTCR(+) cells began to express SLAMF4 only after migrating to the small intestine. Injection of C57BL/6J mice with anti-SLAMF4 and anti-CD3 increased levels of interleukin 10 and interferon gamma secretion by IEL, compared with injection of anti-CD3 only. Similarly, the number of granzyme B(+) cytotoxic CD8(+) αβTCR(+) IELs increased in Slamf4(-/-) mice after injection of anti-CD3 and anti-SLAMF4, administration of antigen, or injection of anti-CD3. Surprisingly, in vivo activation of CD8αβ(+) IELs with anti-CD3 or antigen caused transient depletion of CX3CR1(+) phagocytes, which was prolonged by co-injection with anti-SLAMF4 or in Slamf4(-/-) mice. Anti-CD3 aggravated inflammation in the small intestines of Slamf4(-/-) mice and Eat2a(-/-)Eat2b(-/-) mice, indicated by flattened villi and crypt hyperplasia. In mice, the intestinal environment induces SLAMF4 expression and localization to the surface of CD8(+) αβTCR(+) IELs. Signaling via SLAMF4 controls expansion of cytotoxic CD8αβ(+) IELs, which regulate the reversible depletion of lamina propria phagocytes and inflammation in the small intestine.


Evaluating How Post-Bronchodilator Vital Capacities Affect the Diagnosis of Obstruction in Pulmonary Function Tests.
Although the ratio of FEV1 to the vital capacity (VC) is universally accepted as the cornerstone of pulmonary function test (PFT) interpretation, FVC remains in common use. We sought to determine what the differences in PFT interpretation were when the largest measured vital capacity (VCmax) was used instead of the FVC. We included 12,238 consecutive PFTs obtained for routine clinical care. We interpreted all PFTs first using FVC in the interpretation algorithm and then again using the VCmax, obtained either before or after administration of inhaled bronchodilator. Six percent of PFTs had an interpretive change when VCmax was used instead of FVC. The most common changes were: new diagnosis of obstruction and exclusion of restriction (previously suggested by low FVC without total lung capacity measured by body plethysmography). A nonspecific pattern occurred in 3% of all PFT interpretations with FVC. One fifth of these 3% produced a new diagnosis of obstruction with VCmax. The largest factors predicting a change in PFT interpretation with VCmax were a positive bronchodilator response and the administration of a bronchodilator. Larger FVCs decreased the odds of PFT interpretation change. Surprisingly, the increased numbers of PFT tests did not increase odds of PFT interpretation change. Six percent of PFTs have a different interpretation when VCmax is used instead of FVC. Evaluating borderline or ambiguous PFTs using the VCmax may be informative in diagnosing obstruction and excluding restriction.


Self and proxy-reported health status and health-related quality of life in survivors of childhood cancer in Uruguay.
The incidence of cancer in children in Uruguay is similar to that in industrialized societies but the survival rate is half as great. This study assesses another important measure of treatment effectiveness: the health-related quality of life (HRQL) of survivors. All new patients diagnosed in a 3-year period were eligible if free of disease for at least 2 years after therapy and at least 7 years of age at the time of study. A sample of convenient subjects for comparison was obtained from schools and clinics for well children. During a 7-month period, Spanish language interviewer-administered questionnaires were used to collect Health Utilities Index data from survivors and the comparison group (self-reports), and from proxies (parents, physicians, and teachers). Of 113 eligible survivors, 95 (84%) participated together with 96 "control" subjects. Control subjects have a higher mean HRQL utility score than survivors (P < 0.001). The mean score for survivors of acute lymphoblastic leukemia (ALL): 0.72 (n = 49) is higher than the score for survivors of brain tumors: 0.60 (n = 20), as expected. Inter-rater agreement is highest between survivors and parents, and lowest between controls and physicians or teachers. The burden of morbidity in survivors of childhood cancer in Uruguay is considerable and greater than that in a comparative group of healthy children. Survivors of ALL have better HRQL than survivors of brain tumors, mirroring experience elsewhere. The level of inter-rater agreement is related to the degree of familiarity of the pair-members of respondents with each other.


Association between kinetic semiology of psychogenic nonepileptic spells and seizure type in dual disorder.
Epilepsy is diagnosed in 20% of patients with psychogenic nonepileptic spells (PNES). The semiology of PNES and epileptic seizures (ES) overlaps in some patients. It is unclear whether the motor phenotype of PNES predicts the type of ES. Video segments of EEGs in patients with PNES and ES treated in the Epilepsy Monitoring Unit at the University of Nebraska Medical Center were reviewed. Videos were categorized according to the validated motor-based classification of PNES. Ratings of kinetic PNES events were analyzed to determine if there was an association with focal or generalized ES. If available, the video segments of ES were categorized as hypokinetic or hyperkinetic based on the constellation of focal or generalized movements and other semiological features. Among 43 patients with documented PNES-ES (median age 34, interquartile range (IQR) 26-45), 27.9% were male. The largest proportion of patients (39.5%) had focal temporal epilepsy (TE). Other diagnostic groups included focal frontal (FE, 25.6%), generalized (GE, 25.6%), or other (9.3%) epilepsies. Thirty-three PNES patients (82.5%) were rated as having a hypokinetic phenotype. On average, hypokinetic PNES patients were receiving a median of 3 (IQR 2-4) anticonvulsants, compared to a median of 2 (IQR 2-3) in hyperkinetic PNES patients (p = 0.06). While the group with coexisting FE had a higher prevalence of hyperkinetic semiology (45.4%) than either the TE (11.7%) or GE (18.1%) patients, there was no significant association between the ES type and kinetic status of PNES. Among 20 patients who had video recordings of both PNES and ES, 40% displayed the concordant hypokinetic phenotypes for PNES and seizures while 15% had hyperkinetic presentation of both event types. Among additional 16 patients with scalp EEG-negative suspected nonepileptic events and documented ES, 6 had the recordings of seizures and 3 have presented with concordant hypokinetic PNES and ES. In patients with PNES and ES, the hypokinetic semiology of PNES prevails over hyperkinetic semiology in TE and GE syndromes. The motor status of PNES does not predict the phenotype of coexisting ES. The concordant kinetic semiology is present in more than half of the patients with dual diagnosis and available video data.


Correlation of clinical features with neuroimaging in children with mild head injury.
Mild head injury is defined as a pediatric Glasgow Coma Scale (GCS) score of 13-15 at admission following head trauma. There are no clear indications for neuroimaging in such children. The aim of our study was to analyze the correlation of symptoms commonly encountered following mild head injury with any abnormality on the computed tomography (CT) scan. This is a retrospective and observational study done in a tertiary care hospital. Records of all the children fulfilling the inclusion criteria were retrieved. Demographic details such as age, gender, and type of injury (hit by a blunt object, fall from height, and road traffic accident), symptoms such as presence and number of episodes of vomiting, presence and duration of loss of consciousness (LOC), presence of drowsiness, headache, giddiness, seizures, focal deficits and the GCS score, and CT scan findings were noted in a predesigned proforma. A CT scan with any of the following abnormalities such as skull fracture, cerebral edema, intracranial bleed (epidural hematoma, subdural hematoma, intracerebral hematoma, and subarachnoid hemorrhage), and cerebral contusion was considered as abnormal. Any neurosurgical intervention done was also noted. A total of 134 children in the age group of 1 month to 18 years with mild head injury were included in this study. The median (interquartile range) age of the children was 5 (2, 8) years, with majority being males. Road traffic accidents (34.3%) were the most common cause of injury, followed by fall from lesser than 3 feet height (31.3%). The most common symptoms were vomiting (43.6%), scalp/facial abrasions (37.2%), and LOC (31.9%). CT scan was abnormal in 53.7% of the cases, with skull fracture (35.1%) being the most common finding, followed by cerebral edema (13.4%). Among all the symptoms, ear/nosebleed or cerebrospinal fluid (CSF) otorrhea/rhinorrhea had a statistically significant association with a positive CT scan with P = 0.05 and an odds ratio of 1.4 (95% confidence interval, 1-1.9). Children with mild head injury presenting with clinical features such as bleeding from the ear or nose and CSF otorrhea/rhinorrhea are more likely to have an abnormal CT scan. Hence, such children require close neurological observation and prompt intervention if necessary. However, abnormality on CT scan cannot be reliably ruled out based on the symptoms alone.


Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator.
The pattern of somites is traced out by a mechanism involving oscillating gene expression at the tail end of the embryo. In zebrafish, two linked oscillating genes, her1 and her7, coding for inhibitory gene regulatory proteins, are especially implicated in genesis of the oscillations, while Notch signaling appears necessary for synchronization of adjacent cells. I show by mathematical simulation that direct autorepression of her1 and her7 by their own protein products provides a mechanism for the intracellular oscillator. This mechanism operates robustly even when one allows for the fact that gene regulation is an essentially noisy (stochastic) process. The predicted period is close to the observed period (30 min) and is dictated primarily by the transcriptional delay, the time taken to make an mRNA molecule. Through its coupling to her1/her7 expression, Notch signaling can keep the rapid oscillations in adjacent cells synchronized. When the coupling parameters are varied, however, the model system can switch to oscillations of a much longer period, resembling that of the mouse or chick somitogenesis oscillator and governed by the delays in the Notch pathway. Such Notch-mediated synchronous oscillations are predicted even in the absence of direct her1/her7 autoregulation, through operation of the standard Notch signaling pathway that is usually assumed simply to give lateral inhibition. Direct autorepression of a gene by its own product can generate oscillations, with a period determined by the transcriptional and translational delays. Simple as they are, such systems show surprising behaviors. To understand them, unaided intuition is not enough: we need mathematics.


Three-dimensional elastic matching of volumes.
Registering volumes that have been deformed with respect to each other involves recovery of the deformation. A 3-D elastic matching algorithm has been developed to use surface information for registering volumes. Surface extraction is performed in two steps: extraction of contours in 2-D image planes using active contours, and forming triangular patch surface models from the stack of 2-D contours. One volume is modeled as being deformed with respect to another goal volume. Correspondences between surfaces in the two image volumes are used to warp the deformed volume towards its goal. This process of contour extraction, surface formation and matching, and warping is repeated a number of times, with decreasing image volume stiffness. As the iterations continue the stretched volume is refined towards its goal volume. Registration examples of deformed volumes are presented.


Hospital at Home as a Treatment Strategy for Worsening Heart Failure.
Hospital at home (HaH) is an innovative care model that may be particularly suited for heart failure (HF). Outpatient visits and inpatient care have been the 2 traditional settings for HF care, yet may not match the social and medical needs of patients at all times. Alternative models such as HaH may represent an effective and patient-centered option for select patients with worsening HF. To date, limited research in HF and other disease states has supported HaH as being safe and lower cost than traditional inpatient admission. Supporting HaH are new payment structures, such as Medicare's Acute Hospital Care at Home waiver program. In combination with outpatient visits, outpatient intravenous diuretic clinics, inpatient care, and cardiac intensive care, HaH could be a core component of a comprehensive care model with the potential to match resource utilization with the needs of patients across the spectrum of HF severity, and improve patient outcomes.


Mid-term clinical and sonographic outcome of arthroscopic repair of the rotator cuff.
We have conducted a prospective study to assess the mid-term clinical results following arthroscopic repair of the rotator cuff. Patients were evaluated using the Constant score, subjective satisfaction levels and post-operative ultrasound scans. Of 115 consecutive patients who underwent arthroscopic repair of the rotator cuff at our institution, 102 were available for follow-up. The mean period of follow-up was for 35.8 months (24 to 73). The mean age of the patients was 57.3 years (23 to 78). There were 18 small (< or = 1 cm in diameter), 44 medium (1 cm to 3 cm in diameter), 34 large (3 cm to 5 cm in diameter) and six massive (> 5 cm in diameter) tears. There was a statistically significant increase in the size of the tear with increasing age (p = 0.0048). The mean pre-operative Constant score was 41.4 points (95% confidence interval, 37.9 to 44.9), which improved to 84.5 (95% confidence interval, 82.2 to 86.9). A significant inverse association (p = 0.0074), was observed between the size of the tear and the post-operative Constant score, with patients having smaller tears attaining higher Constant scores after repair. Post-operatively, 80 patients (78.4%) were able to resume their occupations and 84 (82.4%) returned to their pre-injury leisure activities. Only eight (7.8%) of 102 patients were not satisfied with the outcome. Recurrent tears were detected by ultrasound in 19 (18.6%) patients, and were generally smaller than the original ones. Patients with recurrent tears experienced a mean improvement of 31.6 points (95% confidence interval, 23.6 to 39.6) in their post-operative Constant scores. Those with intact repairs had significantly improved (p < 0.0001) Constant scores (mean improvement 46.3 points, 95% confidence interval, 41.9 to 50.6). Patient satisfaction was high in 94 cases (92%), irrespective of the outcome of the Constant score. Recurrent tears appear to be linked to age-related degeneration. Arthroscopic repair of the rotator cuff leads to high rates of satisfaction (92%) and good functional results, albeit with a recurrence rate of 18.6% (19 of 102).


Integrating experimental and theoretical studies in the development of a novel alginate-based bio-composite for copper anticorrosion in 3.5 % NaCl environments.
The development of new coatings based on a biopolymer, epichlorohydrin-modified alginate, and alginate-epichlorohydrin-SrTiO3 nanocomposites incorporating SrTiO3 (STO) nanoparticles in the alginate (Alg) matrix (Alg-Ep-STO), has been addressed in this study. Various characterization techniques were employed to analyze the prepared compounds, including X-ray diffraction spectroscopy (XRD), Fourier-transform infrared spectroscopy (FTIR), as well as surface analysis methods such as Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX). Furthermore, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarisation (PDP) methods were used to evaluate corrosion inhibition and protection durability. The results demonstrate that the incorporation of STO nanoparticles into the alginate matrix with epichlorohydrin significantly improved the metal's resistance to corrosion. The experimental findings received reinforcement from various computational methods, including density functional theory (DFT), Molecular Dynamics (MD) and Monte Carlo (MC) simulations, which were employed to investigate the interactions between the Alg-Ep-STO nanocomposite and the copper surface. The computational outcomes revealed that the Alg-Ep-STO nanocomposite exhibits robust adhesion to the copper surface, maintaining a flat orientation, with its alignment being notably influenced by the presence of STO nanoparticles.


Learning to deal constructively with troubled conscience related to care providers' perceptions of deficient teamwork in residential care of older people--a participatory action research study.
Conscience can be perceived as an asset that helps care providers to provide good care, but it can also be a burden that generates stress of conscience (stress related to a troubled conscience). Participatory action research (PAR) has been shown to be successful in supporting care providers in residential care of older people to learn to deal with their troubled conscience in challenging and demanding care situations. The aim of the study was to describe an intervention process to assist care providers in residential care of older people to constructively deal with their troubled conscience related to perceptions of deficient teamwork. The study design was grounded in PAR. Nine enrolled nurses (ENs), two nursing aids (NAs), one Registered Nurse (RN) and their manager participated in 12 PAR sessions. All sessions were tape-recorded, and a domain analysis of the transcriptions was performed. Findings show that a PAR-based intervention can support care providers to understand, handle and take measures against deficient teamwork. Using troubled conscience as a driving force can increase the opportunities to improve quality of care in residential care for older people. During the PAR process, participants raised their awareness of the need to view the team in a wider sense and that the manager and the Registered Nurse should also be members of the team to improve team outcome. To improve clinical practice, we suggest that teams in residential care of older people should be enabled to share and reflect on challenging situations that generate troubled conscience. However, as shown in this study, care providers might need support in order to facilitate and promote sharing and reflecting on what their conscience tells them.


Education and simulation techniques for improving reliability of care.
Multiple factors influence the dependability of intensive care provision. The management of a group of unstable, critically ill patients requires focused attention from the clinical team. Medical simulation is an important tool to improve safety and team work within the ICU. The critical care healthcare team needs to work both individually and together in such a way as to optimise patient care and prevent error. This involves nontechnical skills including decision making, task allocation, team working and situation awareness, all of which are underpinned by communication, cooperation and coordination. The use of integrated simulators to create realistic patient scenarios with structured debriefing is an excellent method for teaching in these domains. There has been a huge increase in the delivery of training and education using an expanding variety of clinical simulators. This review summarises the evidence and opinion about how simulation tools can be optimally used. In addition, we propose an educational strategy to optimise the impact on clinical practice by embedding simulation training in a multidisciplinary teaching programme based upon a specifically developed curriculum focusing on the teaching of crisis resource management and patient safety.


Time-dependent deacclimation after cold acclimation in Arabidopsis thaliana accessions.
During low temperature exposure, Arabidopsis thaliana and many other plants from temperate climates increase in freezing tolerance in a process termed cold acclimation. However, the correct timing and rate of deacclimation, resulting in loss of freezing tolerance and initiation of growth is equally important for plant fitness and survival. While the molecular basis of cold acclimation has been investigated in detail, much less information is available about deacclimation. We have characterized the responses of 10 natural accessions of Arabidopsis thaliana that vary widely in their freezing tolerance, to deacclimation conditions. Sugar, proline and transcript levels declined sharply over three days in all accessions after transfer of cold acclimated plants to ambient temperatures, while freezing tolerance only declined in tolerant accessions. Correlations between freezing tolerance and the expression levels of COR genes and the content of glucose, fructose and sucrose, as well as many correlations among transcript and solute levels, that were highly significant in cold acclimated plants, were lost during deacclimation. Other correlations persisted, indicating that after three days of deacclimation, plant metabolism had not completely reverted back to the non-acclimated state. These data provide the basis for further molecular and genetic studies to unravel the regulation of deacclimation.


The Potential Effects of Oxidative Stress-Related Plasma Abnormal Protein Aggregate Levels on Brain Volume and Its Neuropsychiatric Consequences in Parkinson's Disease.
Oxidative stress has been implicated in the pathogenesis of many diseases, including Parkinson's disease. Large protein aggregates may be produced after the breakdown of the proteostasis network due to overt oxidative stress. Meanwhile, brain volume loss and neuropsychiatric deficits are common comorbidities in Parkinson's disease patients. In this study, we applied a mediation model to determine the potential influences of oxidative stress-related plasma abnormal protein aggregate levels on brain volume and neuropsychiatric consequences in Parkinson's disease. 31 patients with PD and 24 healthy controls participated in this study. The PD patients were further grouped according to the presentation of cognitive decline or not. All participants received complete examinations to determine plasma abnormal protein aggregates levels, brain volume, and neuropsychiatric performance. The results were collected and analyzed in a single-level three-variable mediation model. Patients with PD cognitive decline exhibited higher plasma NfL levels, decreased regional brain volume, and poor neuropsychiatric subtest results compared with PD patients with normal cognition, with several correlations among these clinical presentations. The mediation model showed that the superior temporal gyrus completely mediated the effects of elevated plasma NfL levels due to the poor psychiatric performance of picture completion and digit span. This study provides insight into the effects of oxidative stress-related plasma abnormal protein aggregate levels on regional brain volume and neuropsychiatric consequences in Parkinson's disease patients.


Neuromyelitis optica: a challenging diagnosis at secondary hospital.
Known since the 19th century, neuromyelitis optica (NMO), or Devic's disease, is an idiopathic immune-mediated inflammatory demyelinating disease of the central nervous system selectively affecting the optic nerve and spinal cord. Commonly diagnosed in demyelinating diseases reference centers, we report an 18-year-old female patient who sought medical attention with a 3-month history of weight loss, headache, and vomiting, followed by diplopia, a burning sensation over the lower limbs, and difficulty walking. A few days prior to hospital admission, the muscle strength in her lower limbs became worse and ascended to the upper limbs associated with sensory changes in the trunk and voiding dysfunction. At admission, the neurological examination was consistent with a spinal cord syndrome. After few days of hospitalization, she was tetraplegic with severe signs of brainstem involvement requiring mechanical ventilatory support. Intravenous methylprednisolone and cyclophosphamide were promptly started after ruling out the diagnosis of infectious disease and cord compression. Due to no substantial early improvement, intravenous immunoglobulin was also used. From then on, the neurological status gradually improved. Magnetic resonance imaging showed extensive demyelinating features in the spinal cord, and the serum IgG autoantibody was negative. The patient was referred to a tertiary neurological reference center where she remains under treatment.