Photoconductivity in the chalcohalide semiconductor, SbSeI: a new candidate for hard radiation detection.
We investigated an antimony chalcohalide compound, SbSeI, as a potential semiconductor material for X-ray and γ-ray detection. SbSeI has a wide band gap of 1.70 eV with a density of 5.80 g/cm(3), and it crystallizes in the orthorhombic Pnma space group with a one-dimensional chain structure comprised of infinite zigzag chains of dimers [Sb2Se4I8]n running along the crystallographic b axis. In this study, we investigate conditions for vertical Bridgman crystal growth using combinations of the peak temperature and temperature gradients as well as translation rate set in a three-zone furnace. SbSeI samples grown at 495 °C peak temperature and 19 °C/cm temperature gradient with 2.5 mm/h translation rate produced a single phase of columnar needlelike crystals aligned along the translational direction of the growth. The ingot sample exhibited an n-type semiconductor with resistivity of ∼10(8) Ω·cm. Photoconductivity measurements on these specimens allowed us to determine mobility-lifetime (μτ) products for electron and hole carriers that were found to be of similar order of magnitude (∼10(-4) cm(2)/V). Further, the SbSeI ingot with well-aligned, one-dimensional columnar needlelike crystals shows an appreciable response of Ag Kα X-ray.


Adrenal medulla and substantia nigra co-grafts in peripheral nerve: chromaffin cells survive for long time periods and prevent degeneration of nigral neurons.
A series of degenerative cytoskeletal changes characterize grafts of embryonic substantia nigra when isolated for long time periods in the peripheral nervous system. This study was designed to determine whether the adrenal medulla could modulate the cytoskeletal changes in the substantia nigra when co-grafted within peripheral nerves. The sciatic nerves of young adult rats received single transplants of embryonic day 15 substantia nigra or co-transplants of substantia nigra plus young adult adrenal medulla in close proximity. Immunocytochemistry was used to examine the expression of tyrosine hydroxylase, phosphorylated (RT97) and non-phosphorylated (SMI-32) neurofilament proteins in the grafts. Single substantia nigra grafts, examined after 1 month, consisted of numerous neurons and fibers that expressed the epitope for tyrosine hydroxylase. Normal spatial distributions of the phosphorylated and non-phosphorylated neurofilament subunits were observed. In contrast, single 1-year-old nigral transplants were shrunken, contained significantly fewer tyrosine hydroxylase positive neurons and displayed abnormal neurofilaments staining patterns including swollen axons, a reduction in the density of labeled axons and perikaryal accumulation of the phosphorylated neurofilament subunit. When co-grafted with the adrenal medulla, the nigral transplants did not show the degenerative cytoskeletal aspects evident in the single 1-year-old grafts. The loss of neurons was prevented and the neurofilament immunolabeling was indistinguishable from the young substantia nigra preparations. In addition, all the 1-year-old adrenal medulla grafts were viable within the peripheral nerves, consisting of hundreds of cells identified by immunoreactivity to tyrosine hydroxylase and the rat beta-nerve growth factor receptor (192-IgG). The experiments illustrate a strong protective effect by the adrenal medulla on neurons of the substantia nigra in the peripheral nerve environment. It is suggested that a catecholaminergic trophic source and/or neural interactions with the adrenal medulla may be important factors in the long-term survival of neurons and maintenance of normal cytoskeletal characteristics in the grafted substantia nigra neurons under these experimental circumstances.


Postdoctoral researchers in the UK: a snapshot at factors affecting their research output.
Postdoctoral training is a typical step in the course of an academic career, but very little is known about postdoctoral researchers (PDRs) working in the UK. This study used an online survey to explore, for the first time, relevant environmental factors which may be linked to the research output of PDRs in terms of the number of peer-reviewed articles per year of PDR employment. The findings showed reliable links between the research output and research institutions, time spent as PDR, and parental education, whereas no clear links were observed between PDRs' output and research area, nationality, gender, number of siblings, or work environment. PDRs based in universities tended to publish, on average, more than the ones based in research centres. PDRs with children tended to stay longer in postdoctoral employment than PDRs without children. Moreover, research output tended to be higher in PDRs with fathers educated at secondary or higher level. The work environment did not affect output directly, but about 1/5 of PDRs were not satisfied with their job or institutional support and about 2/3 of them perceived their job prospects as "difficult". The results from this exploratory study raise important questions, which need to be addressed in large-scale studies in order to understand (and monitor) how PDRs' family and work environment interact with their research output-an essential step given the crucial role of PDRs in research and development in the country.


Adjuvant Treatment of Early Ovarian Clear Cell Carcinoma: A Population-Based Study of Whole Abdominal Versus Pelvic Nodal Radiotherapy.
Adjuvant treatment in early ovarian clear cell carcinoma (OCCC) is not yet standardized. The objective of this population-based study was to compare the outcome of patients with early OCCC treated with adjuvant chemotherapy versus chemoradiotherapy (chemoRT) and evaluate the association of adjuvant radiotherapy regimens (whole abdominal radiotherapy [WART] versus pelvic nodal radiotherapy [PRT]) with outcome. Chart review was conducted to identify patients with stage I and II OCCC with complete information on staging. Patients with stage IA, IB, or IC OCCC purely resulting from capsular rupture were excluded because the provincial protocol does not recommend adjuvant treatment. Overall, 403 patients were identified and 343 received adjuvant treatment, of whom 255 had stage IC or II OCCC and 153 were eligible for final analysis. On Cox multivariable regression, receipt of chemoRT (n=90) was associated with an improvement in failure-free survival (FFS) (hazard ratio [HR], 0.57; 95% CI, 0.34-0.94) compared with chemotherapy alone (n=63). Use of chemoRT also resulted in 54% reduction in the cumulative incidence of cancer-specific mortality (subdistribution HR, 0.46; 95% CI, 0.24-0.89). However, there was no significant difference in the HR for overall survival (OS) between the chemoRT (HR, 0.70; 95% CI, 0.43-1.13) and chemotherapy group. Relative to chemotherapy + WART (chemo-WART), chemotherapy + PRT (chemo-PRT) was not associated with any significant difference in HR for FFS (HR, 1.34; 95% CI, 0.40-4.44) or OS (HR, 1.13; 95% CI, 0.37-3.46). Adjuvant chemoRT was associated with a lower risk of failure compared with chemotherapy alone. However, there was no difference in OS between the adjuvant chemotherapy and chemoRT regimens. Additionally, no significant difference in terms of FFS or OS was found between the chemo-WART and chemo-PRT groups.


Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing.
The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells in mammals are non-proliferating, how do they age? Are telomeres involved? Also oncogene activation causes cellular senescence due to altered DNA replication and DDR activation in particular at the telomeres. Is there a common mechanism shared among apparently distinct types of cellular senescence? And what is the role of telomeric DNA damage?


Gene-set and multivariate genome-wide association analysis of oppositional defiant behavior subtypes in attention-deficit/hyperactivity disorder.
Oppositional defiant disorder (ODD) is a frequent psychiatric disorder seen in children and adolescents with attention-deficit-hyperactivity disorder (ADHD). ODD is also a common antecedent to both affective disorders and aggressive behaviors. Although the heritability of ODD has been estimated to be around 0.60, there has been little research into the molecular genetics of ODD. The present study examined the association of irritable and defiant/vindictive dimensions and categorical subtypes of ODD (based on latent class analyses) with previously described specific polymorphisms (DRD4 exon3 VNTR, 5-HTTLPR, and seven OXTR SNPs) as well as with dopamine, serotonin, and oxytocin genes and pathways in a clinical sample of children and adolescents with ADHD. In addition, we performed a multivariate genome-wide association study (GWAS) of the aforementioned ODD dimensions and subtypes. Apart from adjusting the analyses for age and sex, we controlled for "parental ability to cope with disruptive behavior." None of the hypothesis-driven analyses revealed a significant association with ODD dimensions and subtypes. Inadequate parenting behavior was significantly associated with all ODD dimensions and subtypes, most strongly with defiant/vindictive behaviors. In addition, the GWAS did not result in genome-wide significant findings but bioinformatics and literature analyses revealed that the proteins encoded by 28 of the 53 top-ranked genes functionally interact in a molecular landscape centered around Beta-catenin signaling and involved in the regulation of neurite outgrowth. Our findings provide new insights into the molecular basis of ODD and inform future genetic studies of oppositional behavior. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.


Clinical Psychology in Lithuania: Current Developments in Training and Legislation.
This paper presents an overview of the current status in training and legislation of clinical psychology in Lithuania. Clinical psychology training at the university level in Lithuania started soon after the collapse of the Soviet Union in the 1990s and was influenced by the social context and historical-political situation in the country. Currently, legislation for clinical psychology in Lithuania is in progress, and several promising regulations for psychology in health care were introduced in the last decade. However, psychologists, including clinical psychologists, are not licensed in Lithuania. The lack of legislation for psychology is the main obstacle for the recognition and establishment of clinical psychology in the country. In health care, the title 'clinical psychologist' is not common; 'medical psychologist' is the title used instead to refer to both clinical psychologists and health psychologists. We conclude that while the development of clinical psychology in Lithuania is promising, there is still a long way to go to establish clinical psychology as an important profession in Lithuania.


Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies.
To investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes. We assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings. Characteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo-glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p<0.05). Paranodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo-glial junctional molecules.


Effects of spring temperatures on the strength of selection on timing of reproduction in a long-distance migratory bird.
Climate change has differentially affected the timing of seasonal events for interacting trophic levels, and this has often led to increased selection on seasonal timing. Yet, the environmental variables driving this selection have rarely been identified, limiting our ability to predict future ecological impacts of climate change. Using a dataset spanning 31 years from a natural population of pied flycatchers (Ficedula hypoleuca), we show that directional selection on timing of reproduction intensified in the first two decades (1980-2000) but weakened during the last decade (2001-2010). Against expectation, this pattern could not be explained by the temporal variation in the phenological mismatch with food abundance. We therefore explored an alternative hypothesis that selection on timing was affected by conditions individuals experience when arriving in spring at the breeding grounds: arriving early in cold conditions may reduce survival. First, we show that in female recruits, spring arrival date in the first breeding year correlates positively with hatch date; hence, early-hatched individuals experience colder conditions at arrival than late-hatched individuals. Second, we show that when temperatures at arrival in the recruitment year were high, early-hatched young had a higher recruitment probability than when temperatures were low. We interpret this as a potential cost of arriving early in colder years, and climate warming may have reduced this cost. We thus show that higher temperatures in the arrival year of recruits were associated with stronger selection for early reproduction in the years these birds were born. As arrival temperatures in the beginning of the study increased, but recently declined again, directional selection on timing of reproduction showed a nonlinear change. We demonstrate that environmental conditions with a lag of up to two years can alter selection on phenological traits in natural populations, something that has important implications for our understanding of how climate can alter patterns of selection in natural populations.


Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room.
A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99) and a specificity 0.84 (95% CI 0.58-0.94) with an AUC of 0.93 (95% CI 0.89-1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00) and specificity of 0.95 (95% CI 0.74-0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.


[A combined sulbactam/cefoperazone and amikacin therapy for the treatment of infections complicated with hematological diseases].
Eighty-six patients with infections associated with hematological disorders were treated with sulbactam/cefoperazone (SBT/CPZ) and amikacin (AMK). Among 71 evaluable cases, 30 cases had acute non-lymphocytic leukemia, 3 acute lymphoblastic leukemia, 25 malignant lymphoma, and 7 myelodysplastic syndrome as underlying diseases. Excellent responses were obtained in 33 cases (46.5%) and good responses in 14 cases (19.7%), with an overall efficacy rate of 66.2%. The efficacy rate among cases with suspected sepsis was 72.5%. This treatment was also effective in 69.2% of cases in which neutrophil counts were less than 500/microliter through the course of administration. The eradication rate was 83.3% among 6 strains in which Gram-negative rods were detected. Side effects were minimum; skin rash in 1 case, slight elevation of APTT in 3 and slight elevation of total bilirubin in 1. Thus, this combination antibacterial chemotherapy is an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.


HDL-raising strategies in the treatment of coronary artery disease: perspectives from the Armed Forces Regression Study.
Even with the aggressive reduction of LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial. The Armed Forces Regression Study was a randomized, double-blind, placebo-controlled trial of combination drug therapy aimed at raising HDL-cholesterol in patients with angiographically evident coronary artery disease. Drug therapy ultimately resulted in regression of the angiographic lesions and a reduction in cardiovascular events. This review places the Armed Forces Regression Study within the context of other recent studies. In the past few years a number of other important papers have further defined the important role HDL-cholesterol plays in the pathobiology of atherosclerosis. These studies have focused on three general areas: HDL-cholesterol metabolism and the reverse cholesterol transport pathway; novel therapeutic interventions and their effects on coronary artery disease as assessed through non-invasive imaging modalities; and finally a re-analysis of previous outcomes trials with established HDL-cholesterol modifying agents. The results of the Armed Forces Regression Study fit nicely within the evolving paradigm of targeting HDL-cholesterol in patients at risk of cardiovascular events. The use of niacin and well-tolerated fibrates as an adjunct to statins or as primary therapy in patients intolerant of statins appears reasonable in patients with low levels of HDL-cholesterol and at high risk of cardiovascular events. The further development of novel therapeutic approaches, in addition to broadening our pharmacological armamentarium, should further advance our understanding of HDL-cholesterol.


Ramlibacter solisilvae sp. nov., isolated from forest soil, and emended description of the genus Ramlibacter.
A Gram-staining-negative, strictly aerobic, white-colony-forming bacterium, designated strain 5-10(T), was isolated from forest soil of Bac Kan Province in Vietnam. Cells were non-motile rods or coccoids, showing oxidase- and catalase-positive reactions. Growth was observed at 10-37 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum, pH 7.0) and in the presence of 0-1.0 % (w/v) NaCl (optimum, 0-0.5 %). The major cellular fatty acids were summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c), C16 : 0, C10 : 0 3-OH and summed feature 8 (comprising C18 : 1ω6c and/or C18 : 1ω7c). The G+C content of the genomic DNA was 69.9 mol% and the only respiratory quinone detected was ubiquinone 8 (Q-8). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 5-10(T) formed a tight phyletic lineage with members of the genus Ramlibacter. Strain 5-10(T) was most closely related to Ramlibacter tataouinensis TTB310(T) (97.3 %), but the DNA-DNA relatedness level between the two strains was 38.2±1.8 %. Based on phenotypic, chemotaxonomic and molecular features, strain 5-10(T) was shown to represent a novel species of the genus Ramlibacter, for which the name Ramlibacter solisilvae sp. nov. is proposed. The type strain is 5-10(T) ( = KACC 17567(T) = JCM 19319(T)). An emended description of the genus Ramlibacter is also proposed.


Imaging neuronal activity during zebrafish behavior with a genetically encoded calcium indicator.
Genetically encoded calcium indicators, such as cameleon, have offered the promise of noninvasively monitoring activity of neurons, but no one has demonstrated whether these indicators can report calcium transients in neurons of behaving vertebrates. We show that cameleon can be expressed at high levels in sensory and spinal cord neurons in zebrafish by using neural-specific promoters in both transient expression experiments and in a stable transgenic line. Using standard confocal microscopy, calcium transients in identified motoneurons and spinal interneurons could be detected during escape behaviors produced by a touch on the head of the fish. Small movements of the restrained fish during the behavior did not represent a major problem for analyzing the calcium responses because of the ratiometric nature of cameleon. We conclude that cameleon can be used to noninvasively study the activity of neurons in an intact, behaving vertebrate. The ability to introduce an indicator genetically allows for studies of the functional roles of local interneurons that cannot easily be monitored with other approaches. Transgenic lines such as the one we generated can also be crossed into mutant lines of fish to study both structural and functional consequences of the mutations.


The feasibility and acceptability of mass drug administration for malaria in Cambodia: a mixed-methods study.
Mass drug administrations (MDAs) are part of the World Health Organization's Plasmodium falciparum elimination strategy for the Greater Mekong Subregion (GMS). In Cambodia, a 2015-2017 clinical trial evaluated the effectiveness of MDA. This article explores factors that influence the feasibility and acceptability of MDA, including seasonal timing, financial incentives and the delivery model. Quantitative data were collected through structured questionnaires from the heads of 163 households. Qualitative data were collected through 25 semi-structured interviews and 5 focus group discussions with villagers and local health staff. Calendars of village activities were created and meteorological and malaria treatment records were collected. MDA delivered house-to-house or at a central point, with or without compensation, were equally acceptable and did not affect coverage. People who knew about the rationale for the MDA, asymptomatic infections and transmission were more likely to participate. In western Cambodia, MDA delivered house-to-house by volunteers at the end of the dry season may be most practicable but requires the subsequent treatment of in-migrants to prevent reintroduction of infections. For MDA targeted at individual villages or village clusters it is important to understand local preferences for community mobilisation, delivery and timing, as several models of MDA are feasible.


Near infrared spectroscopic assessment of developing engineered tissues: correlations with compositional and mechanical properties.
Articular cartilage degeneration causes pain and reduces the mobility of millions of people annually. Regeneration of cartilage is challenging, due in part to its avascular nature, and thus tissue engineering approaches for cartilage repair have been studied extensively. Current techniques to assess the composition and integrity of engineered tissues, including histology, biochemical evaluation, and mechanical testing, are destructive, which limits real-time monitoring of engineered cartilage tissue development in vitro and in vivo. Near infrared spectroscopy (NIRS) has been proposed as a non-destructive technique to characterize cartilage. In the current study, we describe a non-destructive NIRS approach for assessment of engineered cartilage during development, and demonstrate correlation of these data to gold standard mid infrared spectroscopic measurements, and to mechanical properties of constructs. Cartilage constructs were generated using bovine chondrocyte culture on polyglycolic acid (PGA) scaffolds for six weeks. BMP-4 growth factor and ultrasound mechanical stimulation were used to provide a greater dynamic range of tissue properties and outcome variables. NIR spectra were collected daily using an infrared fiber optic probe in diffuse reflectance mode. Constructs were harvested after three and six weeks of culture and evaluated by the correlative modalities of mid infrared (MIR) spectroscopy, histology, and mechanical testing (equilibrium and dynamic stiffness). We found that specific NIR spectral absorbances correlated with MIR measurements of chemical composition, including relative amount of PGA (R = 0.86, p = 0.02), collagen (R = 0.88, p = 0.03), and proteoglycan (R = 0.83, p = 0.01). In addition, NIR-derived water content correlated with MIR-derived proteoglycan content (R = 0.76, p = 0.04). Both equilibrium and dynamic mechanical properties generally improved with cartilage growth from three to six weeks. In addition, significant correlations between NIRS-derived parameters and mechanical properties were found for constructs that were not treated with ultrasound (PGA (R = 0.71, p = 0.01), water (R = 0.74, p = 0.02), collagen (R = 0.69, p = 0.04), and proteoglycan (R = 0.62, p = 0.05)). These results lay the groundwork for extension to arthroscopic engineered cartilage assessment in clinical studies.


The Aging Waistline: Impact of the Geriatric Obesity Epidemic on an Urban Emergency Department: Original Communication.
Reviews adult emergency department (ED) visits for patients age 65 and older during one calendar year; determine the prevalence of weight classifications; identifies trends between BMI and discharge/admitting diagnoses, vital signs, and severity index. The electronic medical records system and data from the ED billing service was reviewed for an urban academic institution with an annual volume of 125,000 for patients age > 65. Using a random number table, a retrospective cohort of 328 elderly patients was selected for review, representing a convenience sample of 2.6% of elderly ED visits. Body Mass Index (BMI) was calculated, using the Center for Disease Control (CDC) formula with underweight (<18.5), normal (18.5 - 24.9), overweight (25 - 29.9), and obese (≥30). The majority of the cohort in this study was African-American and Hispanic (60% and 27% respectively), and there were a higher percentage of females than males (60% and 40% respectively). Approximately 29% of the patients were classified as normal weight, 35% classified as overweight, and 36% as obese. The older the patient, the more likely that patient belonged to a lower weight classification (p < 0.01). Those presenting with neurological, pulmonary or gastrointestinal complaints were more likely to be of a higher weight classification (p < 0.05). Patients who were hypertensive on arrival to the ED were more likely to be in a higher weight classification (p < 0.01). Those patients with a higher weight classification had a strong correlation with selected abnormal vital signs and disease presentations. EDs are important sources of care for the elderly. EDs can serve as a previously untapped resource for screening and early referral exercise programs aimed at improving physical function/functional status and quality of life in the elderly patient population.


Individual and contextual correlates of physical activity among a clinical sample of United States Veterans.
Veterans, especially those using U.S. Department of Veterans Affairs (VA) healthcare, have poorer health than the general population. In addition, Veterans using VA services are more likely than non-VA users to be physically inactive. Little is known about physical activity correlates among Veterans. To identify targets for health promotion interventions, understanding barriers to and facilitators of physical activity in this population is critical. This study examined individual-, social-, and perceived neighborhood-level associations of meeting weekly physical activity recommendations (150 min/week of combined leisure and transportation activity) based on the International Physical Activity Questionnaire (IPAQ) among N = 717 patients from VA Puget Sound, Seattle Division using a mailed survey sent 2012-2013 (response rate = 40%). Independent associations were identified with direct estimation of relative risks using generalized linear models (dichotomous outcome), and linear regression (continuous outcome), including variables associated in bivariate tests (p < .05). Most participants were male, Caucasian, and unemployed, and had an annual income ≤$40,000. Over two-thirds (69.9%) reported meeting physical activity recommendations. Fewer days of limitations due to physical or mental health (Relative Risk (RR) = 0.99 per day; 95% Confidence Interval (CI) = 0.98, 0.99; p = .01), others doing physical activity with the Veteran (RR = 1.18; 95% CI = 1.04, 1.33; p = .01), receiving ideas from others regarding physical activity (RR = 1.14; 95% CI = 1.01, 1.29; p = .03) and better perceived neighborhood aesthetics (RR = 1.14; 95% CI = 1.06, 1.24; p = .001) were associated with meeting physical activity recommendations. Findings were comparable for total weekly physical activity, but lower depression symptom severity was also associated with increased physical activity. This study identified individual and contextual correlates of physical activity among VA-using Veterans. Targeting these factors will be important in promoting physical activity in order to address the disproportionate disease burden facing U.S. Veterans. Existing VA interventions targeting physical activity may need to be adapted to account for the influence of contextual factors.


Locally-Procured Fish Is Essential in School Feeding Programmes in Sub-Saharan Africa.
Fish make an important contribution to micronutrient intake, long-chained polyunsaturated omega-3 fatty acids (n-3 LC-PUFAS), and animal protein, as well as ensuring food and nutrition security and livelihoods for fishing communities. Micronutrient deficiencies are persistent in sub-Saharan Africa (SSA), contributing to public health issues not only in the first 1000 days but throughout adolescence and into adulthood. School feeding programs (SFPs) and home-grown school feeding programs (HGSF), which source foods from local producers, particularly fisherfolk, offer an entry point for encouraging healthy diets and delivering essential macro- and micronutrients to schoolchildren, which are important for the continued cognitive development of children and adolescents and can contribute to the realization of sustainable development goals (SDGs) 1, 2, 3, 5, and 14. The importance of HGSF for poverty alleviation (SDG1) and zero hunger (SDG 2) have been recognized by the United Nations Hunger Task Force and the African Union Development Agency-New Partnership for African Development (AUDA-NEPAD), which formulated a strategy for HGSF to improve nutrition for the growing youth population across Africa. A scoping review was conducted to understand the lessons learned from SFPs, which included fish and fish products from small-scale producers, identifying the challenges and best practices for the inclusion of fish, opportunities for improvements across the supply chain, and gaps in nutritional requirements for schoolchildren which could be improved through the inclusion of fish. Challenges to the inclusion fish in SFPs include food safety, supply and access to raw materials, organizational capacity, and cost, while good practices include the engagement of various stakeholders in creating and testing fish products, and repurposing fisheries by-products or using underutilized species to ensure cost-effective solutions. This study builds evidence of the inclusion of nutritious fish and fish products in SFPs, highlighting the need to replicate and scale good practices to ensure sustainable, community-centred, and demand-driven solutions for alleviating poverty, malnutrition, and contributing to greater health and wellbeing in adolescence.


A national action plan to meet health care quality information needs in the age of managed care.
Concerted national action is needed to meet the growing demand for health care quality information among all health care stakeholders. We propose a coordinated national network of independent, public-private quality measurement alliances established through strong purchaser and consumer leadership at the state, regional, or local levels. These independent alliances could assume a variety of organizational forms, but all would undertake specific quality measurement and consumer information projects to meet local health care market needs by drawing on various combinations of the emerging national standardized quality measures. Local implementation of quality measures based on national standards will facilitate cross-market benchmarking and multistate comparisons useful not only to state and local market constituencies, but to national employers, health plans, provider organizations, and the federal government as well. Successful models of such alliances already exist that demonstrate the feasibility of this national strategy, but concerted national leadership and federal matching funding will be needed to meet the scope of implementation required in markets across the country.


An in-silico approach to understand the potential role of Wnt inhibitory factor-1 (WIF-1) in the inhibition of the Wnt signalling pathway.
WIF1 (Wnt inhibitory factor 1) is a potent tumour suppressor gene which is epigenetically silenced in numerous malignancies. The associations of WIF1 protein with the Wnt pathway molecules have not been fully explored, despite their involvement in the downregulation of several malignancies. In the present study, a computational approach encompassing the expression, gene ontology analysis and pathway analysis is employed to obtain an insight into the role of the WIF1 protein. Moreover, the interaction of the WIF1 domain with the Wnt pathway molecules was carried out to ascertain the tumour-suppressive role of the domain, along with the determination of their plausible interactions. Initially, the protein-protein interaction network analysis endowed us with the Wnt ligands (such as Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt8a and Wnt9a), along with the Frizzled receptors (Fzd1 and Fzd2) and the low-density lipoprotein complex (Lrp5/6) as the foremost interactors of the protein. Further, the expression analysis of the aforementioned genes and proteins was determined using The Cancer Genome Atlas to comprehend the significance of the signalling molecules in the major cancer subtypes. Moreover, the associations of the aforementioned macromolecular entities with the WIF1 domain were explored using the molecular docking studies, whereas the dynamics and stability of the assemblage were investigated using 100 ns molecular dynamics simulations. Therefore, providing us insights into the plausible roles of WIF1 in inhibiting the Wnt pathways in various malignancies.Communicated by Ramaswamy H. Sarma.


Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies.
Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut. Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age. There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, rs = 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014). Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.


Treatment of posttraumatic cubitus varus with corrective supracondylar humeral osteotomies using the methyl methacrylate external fixator.
In upper and lower extremity fractures and osteotomy fixation, the use of methyl methacrylate (MM) as an external fixator presents an alternative method. The primary aim of this retrospective study was to evaluate the midterm outcome of pediatric patients who underwent corrective humeral supracondylar lateral closing-wedge osteotomy, with the external fixation system composed of MM and multiplane K-wires. Fourteen consecutive cases with cubitus varus, who underwent corrective osteotomy with a limited lateral approach stabilized with MM and the multiplane K-wires external fixator system between January 2006 and May 2010, were retrospectively evaluated. Time of union, preoperative and postoperative elbow range of motion, and humeroulnar angle were measured. Results were rated as excellent, good, or poor, according to Bellemore criteria. There were a total of 6 female patients and 8 male patients with a mean age of 5.7 years (range, 3 to 9 y). The mean follow-up period was 28.2 months (range, 24 to 48 mo). The mean humeroulnar angle was (-) 18.6 degrees preoperatively, and (+) 16.3 degrees at the final follow-up. Thirteen patients were evaluated as excellent and 1 patient as good, according to Bellemore criteria. Union was seen in all patients at mean 7 weeks (range, 6 to 8 wk). Pin tract infection was observed in 1 patient and treated with oral antibiotics. Loss of correction was not observed in any patient during follow-up. External fixation of corrective supracondylar humeral osteotomy with MM and multiplane K-wires is a practical, effective, reliable, and cheap alternative method that can be applied. Level IV. Retrospective study.


Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18: a geospatial modelling study.
More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000-257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Bill & Melinda Gates Foundation.


Characteristics of pattern formation and evolution in approximations of Physarum transport networks.
Most studies of pattern formation place particular emphasis on its role in the development of complex multicellular body plans. In simpler organisms, however, pattern formation is intrinsic to growth and behavior. Inspired by one such organism, the true slime mold Physarum polycephalum, we present examples of complex emergent pattern formation and evolution formed by a population of simple particle-like agents. Using simple local behaviors based on chemotaxis, the mobile agent population spontaneously forms complex and dynamic transport networks. By adjusting simple model parameters, maps of characteristic patterning are obtained. Certain areas of the parameter mapping yield particularly complex long term behaviors, including the circular contraction of network lacunae and bifurcation of network paths to maintain network connectivity. We demonstrate the formation of irregular spots and labyrinthine and reticulated patterns by chemoattraction. Other Turing-like patterning schemes were obtained by using chemorepulsion behaviors, including the self-organization of regular periodic arrays of spots, and striped patterns. We show that complex pattern types can be produced without resorting to the hierarchical coupling of reaction-diffusion mechanisms. We also present network behaviors arising from simple pre-patterning cues, giving simple examples of how the emergent pattern formation processes evolve into networks with functional and quasi-physical properties including tensionlike effects, network minimization behavior, and repair to network damage. The results are interpreted in relation to classical theories of biological pattern formation in natural systems, and we suggest mechanisms by which emergent pattern formation processes may be used as a method for spatially represented unconventional computation.


Motion robust 4D-MRI sorting based on anatomic feature matching: A digital phantom simulation study.
Motion artifacts induced by breathing variations are common in 4D-MRI images. This study aims to reduce the motion artifacts by developing a novel, robust 4D-MRI sorting method based on anatomic feature matching and applicable in both cine and sequential acquisition. The proposed method uses the diaphragm as the anatomic feature to guide the sorting of 4D-MRI images. Initially, both abdominal 2D sagittal cine MRI images and axial MRI images were acquired. The sagittal cine MRI images were divided into 10 phases as ground truth. Next, the phase of each axial MRI image is determined by matching its diaphragm position in the intersection plane to the ground truth cine MRI. Then, those matched phases axial images were sorted into 10-phase bins which were identical to the ground truth cine images. Finally, 10-phase 4D-MRI were reconstructed from these sorted axial images. The accuracy of reconstructed 4D-MRI data was evaluated by comparing with the ground truth using the 4D extended Cardiac Torso (XCAT) digital phantom. The effects of breathing signal, including both regular (cosine function) and irregular (patient data) in both axial cine and sequential scanning modes, on reconstruction accuracy were investigated by calculating total relative error (TRE) of the 4D volumes, Volume-Percent-Difference (VPD) and Center-of-Mass-Shift (COMS) of the estimated tumor volume, compared with the ground truth XCAT images. In both scanning modes, reconstructed 4D-MRI images matched well with ground truth with minimal motion artifacts. The averaged TRE of the 4D volume, VPD and COMS of the EOE phase in both scanning modes are 0.32%/1.20%/±0.05 mm for regular breathing, and 1.13%/4.26%/±0.21 mm for patient irregular breathing. The preliminary evaluation results illustrated the feasibility of the robust 4D-MRI sorting method based on anatomic feature matching. This method provides improved image quality with reduced motion artifacts for both cine and sequential scanning modes.


Energy conserving thermoregulatory patterns and lower disease severity in a bat resistant to the impacts of white-nose syndrome.
The devastating bat fungal disease, white-nose syndrome (WNS), does not appear to affect all species equally. To experimentally determine susceptibility differences between species, we exposed hibernating naïve little brown myotis (Myotis lucifugus) and big brown bats (Eptesicus fuscus) to the fungus that causes WNS, Pseudogymnoascus destructans (Pd). After hibernating under identical conditions, Pd lesions were significantly more prevalent and more severe in little brown myotis. This species difference in pathology correlates with susceptibility to WNS in the wild and suggests that survival is related to different host physiological responses. We observed another fungal infection, associated with neutrophilic inflammation, that was equally present in all bats. This suggests that both species are capable of generating a response to cold tolerant fungi and that Pd may have evolved mechanisms for evading host responses that are effective in at least some bat species. These host-pathogen interactions are likely mediated not just by host physiological responses, but also by host behavior. Pd-exposed big brown bats, the less affected species, spent more time in torpor than did control animals, while little brown myotis did not exhibit this change. This differential thermoregulatory response to Pd infection by big brown bat hosts may allow for a more effective (or less pathological) immune response to tissue invasion.


Insulin degludec overdose in an adolescent with type 1 diabetes: proactive management including monitoring using the Freestyle Libre flash glucose monitoring system.
An adolescent with type 1 diabetes and a history of self-harm, which included intentional overdoses and insulin omission, presented with an insulin degludec overdose. She had been commenced on the ultra-long-acting insulin, degludec, with the aim of reducing ketoacidosis episodes in response to intermittent refusal to take insulin. Insulin degludec was administered under supervision as an outpatient. Because it was anticipated that she would attempt a degludec overdose at some stage, the attending clinicians implemented a proactive management plan for this (and related) scenarios. This included long-term monitoring of interstitial glucose using the Abbott Freestyle Libre flash glucose monitor. The patient took a witnessed overdose of 242 units of degludec (usual daily dose, 32 units). She was hospitalised an hour later. Inpatient treatment was guided primarily by interstitial glucose results, with capillary and venous glucose tests used as secondary measures to assess the accuracy of interstitial glucose values. Four days of inpatient treatment was required. The patient was managed with high glycaemic loads of food and also intermittent intravenous dextrose. No hypoglycaemia was documented during the admission. In summary, while a degludec overdose may require several days of inpatient management, in situations where proactive management is an option and the dose administered is relatively modest, it may be possible to avoid significant hypoglycaemia. In addition, this case demonstrates that inpatient interstitial glucose monitoring may have a role in managing insulin overdose, especially in situations where the effect of the insulin overdose on glucose levels is likely to be prolonged. Degludec overdoses have a prolonged effect on blood glucose levels, but if the clinical situation allows for early detection and management, treatment may prove easier than that which is typically needed following overdoses of a similar dose of shorter acting insulins.Inpatient real-time interstitial monitoring helped guide management, which in this context included the prescription of high dietary carbohydrate intake (patient led) and intravenous 10% dextrose (nurse led).Use of inpatient interstitial glucose monitoring to guide therapy might be considered 'off label' use, thus, both staff and also patients should be aware of the limitations, as well as the benefits, of interstitial monitoring systems.The Libre flash glucose monitor provided nurses with low cost, easy-to-use interstitial glucose results, but it is nevertheless advisable to check these results against conventional glucose tests, for example, capillary 'finger-stick' or venous glucose tests.


Plasma myeloperoxidase activity and apolipoprotein A-1 expression in chronic hepatitis B patients.
Hepatitis B virus initiates a complicated cascade process leading to chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. In inflammatory situations, myeloperoxidase is released in plasma and binds to apolipoprotein A-1 in high-density lipoproteins. This study aims to evaluate the level of plasma myeloperoxidase as well as the pattern of plasma proteins in patients with chronic hepatitis B. Included in this study were 30 male subjects: 19 chronic hepatitis B patients, 6 HBV-related cirrhotic patients, and 5 healthy controls. Plasma myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proteomic analysis of plasma proteins was performed by two-dimensional gel electrophoresis (2-DE) and mass spectrometry. One way ANOVA was used for data analysis. Mean plasma myeloperoxidase levels were higher in patients with liver cirrhosis (65.5±12.5; P=0.007) and chronic hepatitis B (53.7±10.6; P=0.18) when compared with healthy subjects (45±7.6). Moreover, a positive correlation was found between plasma myeloperoxidase levels and hepatic fibrosis stage (r=0.53, P=0.002; r=0.63, P=0.000). Proteomic analysis showed an altered plasma protein pattern in progressive hepatitis B and down-regulation of the major apolipoprotein A-1 along with the appearance of a variety of spots noted to be apolipoprotein A-1isoforms with different molecular masses. In this study, progressive liver injury due to HBV infection correlated with higher plasma myeloperoxidase and an altered plasma apolipoprotein A-1pattern.


Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1.
Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. Brain endothelial cells were grown alone or in co-culture with astrocytes. Astrocytes were grown either as conventional (2D) monolayers, or in a collagen-based gel which allows them to grow in a three-dimensional (3D) construct. Astrocytes were viable in 3D conditions, and displayed a marked reduction in their expression of glial fibrillary acidic protein (GFAP), suggesting reduced activation. Stimulation of astrocytes with transforming growth factor (TGF)β1 decreased transendothelial electrical resistance (TEER) and reduced expression of claudin-5 in co-cultures, whereas treatment of endothelial cells in the absence of astrocytes was without effect. The effect of TGFβ1 on TEER was significantly more pronounced in endothelial cells cultured with 3D astrocytes compared to 2D astrocytes. These results demonstrate that astrocyte culture conditions differentially affect their ability to modulate brain endothelial barrier function, and suggest a direct relationship between reactive gliosis and BBB permeability. Moreover, these studies demonstrate the potential importance of physiologically relevant culture conditions to in vitro modeling of disease processes that affect the neurovascular unit.


Life story work in health and social care: systematic literature review.
The aim of this paper is to review the literature on life story work in health and social care practice. Life story work as an intervention has been used with a number of health and social care clients, such as children people with learning disabilities, older people on medical wards and with older people who have dementia. It may help challenge ageist attitudes and assumptions, be used as a basis for individualized care, improve assessment, assist in transitions between different care environments, and help to develop improved relationships between care staff and family carers. However, to date there has been no attempt to collate the findings from published accounts. A systematic search of the literature on life story work was conducted in February 2004, using nursing, medical and social science databases and a combination of thesaurus and free text search terms. This revealed over 1000 publications; the use of carefully constructed inclusion and exclusion criteria identified 51 relevant items. Fourteen were subsequently selected and reviewed using a set of reflective critical appraisal questions. A range of methodological approaches has been adopted to explore the use of life story work with no one specific methodology prevailing. The work has been most frequently used with older people and people with a learning disability and life story books are the most common approach. Staff perceptions of life story work have been explored, but patient and carer views are less frequently reported. The findings of the studies are discussed in broad themes, offering some tentative recommendations for using life story work in practice. Evidence on the use of life story work is immature, leading to the recommendation for more research. Although appraising literature from a range of approaches is complex, there are some potentially far-reaching benefits of life story work in health and social care practice.


Imaging modalities in synchronous oligometastatic prostate cancer.
Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. A literature search on December 15th 2017 was conducted using the Pubmed database. Functional imaging techniques like 68Ga PSMA. 68Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.


Budgeting for comprehensive sexual and reproductive health and rights under universal health coverage.
Achieving universal health coverage (UHC) for sexual and reproductive health (SRH) requires informed budgeting that is aligned with UHC objectives. We draw data from Adding It Up 2019 (AIU-2019) to provide critical new country-level and regional, intervention-specific costs for the provision of SRH services. AIU-2019 is a cost-outcomes analysis, undertaken from the health system perspective, which estimates the costs and impacts of offering SRH care in low- and middle-income countries. We present direct cost estimates for 109 SRH interventions and find that human resources comprise the largest category of direct SRH service costs and that the most expensive services in the model are largely preventable. We use scenario analysis to explore the synergistic costs and impacts of providing SRH interventions in clusters, focussing on chlamydia and gonorrhoea treatment, provision of safe abortion and post-abortion care services, and safe childbirth services. When costs are considered for the preventive and impacted services in these three clusters, there are cost savings for some of the impacted services in the packages and for the abortion-related package overall. The direct cost estimates from our analysis can be used to guide UHC budgeting and planning efforts. Having these cost estimates and understanding the potential for cost savings when providing comprehensive SRH services are critical for efforts to fulfil the rights and needs of all individuals, including the most marginalised, to access this essential care.


N-substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines are opioid receptor pure antagonists.
N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctahydroisoquinolines 6a-g can exist in conformations where the 3-hydroxyphenyl substituent is either axial or equatorial, similar to the (3-hydroxyphenyl)piperidines 4. The 3-hydroxyphenyl equatorial conformation is responsible for the antagonist activity observed in the (3-hydroxyphenyl)piperidine antagonists. Single-crystal X-ray analysis of 6a shows that the 3-hydroxyphenyl equatorial conformation is favored in the solid state. Molecular modeling studies also suggest that the equatorial conformation has lower potential energy relative to that of the axial conformation. Evaluation of 6a-g in the [(35)S]GTP-gamma-S in vitro functional assay showed that they were opioid receptor pure antagonists. N-[4a-(3-Hydroxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinoline-6-yl]-3-(piperidin-1-yl)propionamide (6d) with a K(e) of 0.27 nM at the kappa opioid receptor with 154- and 46-fold selectivity relative to those of the micro and delta receptors, respectively, possessed the best combination of kappa potency and selectivity.


Different molecular consequences of the 1;19 chromosomal translocation in childhood B-cell precursor acute lymphoblastic leukemia.
The prognostically important 1;19 chromosomal translocation can alter the E2A gene on chromosome 19p13 in childhood B-cell precursor acute lymphoblastic leukemia (ALL), leading to formation of a fusion gene (E2A-PBX1) that encodes a hybrid transcription factor with oncogenic potential. It is not known whether this molecular alteration is a uniform consequence of the t(1;19) or is restricted to translocation events within specific immunologic subtypes of the disease. Therefore, we studied leukemic cells from 25 cases of B-cell precursor ALL, with or without evidence of cytoplasmic Ig mu heavy chains (cIg); 17 cases had the t(1;19) by cytogenetic analysis. Leukemic cell DNA samples were analyzed by Southern blotting to detect alterations within the E2A genomic locus; a polymerase chain reaction assay was used to identify expression of chimeric E2A-pbx1 transcripts in leukemic cell RNA; and immunoblotting with anti-Pbx1 antibodies was used to detect hybrid E2A-Pbx1 proteins. Of 11 cases of cIg+ ALL with the t(1;19), 10 had E2A-pbx1 chimeric transcripts with identical junctions and a characteristic set of E2A-Pbx1 hybrid proteins. Each of these cases had E2A gene rearrangements, including the one in which fusion transcripts were not detected. By contrast, none of the six cases of t(1;19)-positive, cIg- ALL had evidence of rearranged E2A genomic restriction fragments, detectable E2A-pbx1 chimeric transcripts, or hybrid E2A-Pbx1 proteins. Typical chimeric E2A-pbx1 transcripts and proteins were detected in one of eight cIg+ leukemias in which the t(1;19) was not identified by cytogenetic analysis, emphasizing the increased sensitivity of molecular analysis for detection of this abnormality. We conclude that the molecular breakpoints in cases of cIg- B-cell precursor ALL with the t(1;19) differ from those in cIg+ cases with this translocation. Leukemias that express hybrid oncoproteins such as E2A-Pbx1 or Bcr-Abl have had a poor prognosis in most studies. Thus, molecular techniques to detect fusion genes and their aberrant products should allow more timely and appropriate treatment of these aggressive subtypes of the disease.


Defining the Progression of Diabetic Cardiomyopathy in a Mouse Model of Type 1 Diabetes.
The incidence of diabetes and its association with increased cardiovascular disease risk represents a major health issue worldwide. Diabetes-induced hyperglycemia is implicated as a central driver of responses in the diabetic heart such as cardiomyocyte hypertrophy, fibrosis, and oxidative stress, termed diabetic cardiomyopathy. The onset of these responses in the setting of diabetes has not been studied to date. This study aimed to determine the time course of development of diabetic cardiomyopathy in a model of type 1 diabetes (T1D) in vivo. Diabetes was induced in 6-week-old male FVB/N mice via streptozotocin (55 mg/kg i.p. for 5 days; controls received citrate vehicle). At 2, 4, 8, 12, and 16 weeks of untreated diabetes, left ventricular (LV) function was assessed by echocardiography before post-mortem quantification of markers of LV cardiomyocyte hypertrophy, collagen deposition, DNA fragmentation, and changes in components of the hexosamine biosynthesis pathway (HBP) were assessed. Blood glucose and HbA1c levels were elevated by 2 weeks of diabetes. LV and muscle (gastrocnemius) weights were reduced from 8 weeks, whereas liver and kidney weights were increased from 2 and 4 weeks of diabetes, respectively. LV diastolic function declined with diabetes progression, demonstrated by a reduction in E/A ratio from 4 weeks of diabetes, and an increase in peak A-wave amplitude, deceleration time, and isovolumic relaxation time (IVRT) from 4-8 weeks of diabetes. Systemic and local inflammation (TNFα, IL-1β, CD68) were increased with diabetes. The cardiomyocyte hypertrophic marker Nppa was increased from 8 weeks of diabetes while β-myosin heavy chain was increased earlier, from 2 weeks of diabetes. LV fibrosis (picrosirius red; Ctgf and Tgf-β gene expression) and DNA fragmentation (a marker of cardiomyocyte apoptosis) increased with diabetes progression. LV Nox2 and Cd36 expression were elevated after 16 weeks of diabetes. Markers of the LV HBP (Ogt, Oga, Gfat1/2 gene expression), and protein abundance of OGT and total O-GlcNAcylation, were increased by 16 weeks of diabetes. This is the first study to define the progression of cardiac markers contributing to the development of diabetic cardiomyopathy in a mouse model of T1D, confirming multiple pathways contribute to disease progression at various time points.


Draft genome sequence of Salimicrobium sp. strain MJ3, isolated from Myulchi-Jeot, Korean fermented seafood.
Salimicrobium sp. strain MJ3 was isolated from myulchi-jeot, traditional fermented seafood made from anchovy in South Korea. Here we announce the draft genome sequence of Salimicrobium sp. MJ3 with 2,717,782 bp, which consists of 45 contigs (>500 bp in size), and provide a description of their annotation.


Short Hospital Stay after Laparoscopic Colorectal Surgery without Fast Track.
Purpose. Short hospital stay and equal or reduced complication rates have been demonstrated after fast track open colonic surgery. However, fast track principles of perioperative care can be difficult to implement and often require increased nursing staff because of more concentrated nursing tasks during the shorter hospital stay. Specific data on nursing requirements after laparoscopic surgery are lacking. The purpose of the study was to evaluate the effect of operative technique (open versus laparoscopic operation), but without changing nurse staffing or principles for peri- or postoperative care, that is, without implementing fast track principles, on length of stay after colorectal resection for cancer. Methods. Records of all patients operated for colorectal cancer from November 2004 to December 2008 in our department were reviewed. No specific patients were selected for laparoscopic repair, which was solely dependent on the presence of two specific surgeons at the same time. Thus, the patients were not selected for laparoscopic repair based on patient-related factors, but only on the simultaneous presence of two specific surgeons on the day of the operation. Results. Of a total of 540 included patients, 213 (39%) were operated by a laparoscopic approach. The median hospital stay for patients with a primary anastomosis was significantly shorter after laparoscopic than after conventional open surgery (5 versus 8 days, P < 0.001) while there was no difference in patients receiving a stoma (10 versus 10 days, ns), with no changes in the perioperative care regimens. Furthermore there were significant lower blood loss (50 versus 200 mL, P < 0.001) and lower complication rate (21% versus 32%, P = 0.006) in the laparoscopic group. Conclusion. Implementing laparoscopic colorectal surgery in our department resulted in shorter hospital stay without using fast track principles for peri- and postoperative care in patients not receiving a stoma during the operation. Consequently, we aimed to reduce hospitalisation without increasing cost in nursing staff per hospital bed. Length of stay was not reduced in patients receiving a stoma pointing at this group for specific intervention in the future. Furthermore, the complication rate was reduced in the laparoscopic group.


A new perspective on trait differences between native and invasive exotic plants.
Functional differences between native and exotic species potentially constitute one factor responsible for plant invasion. Differences in trait values between native and exotic invasive species, however, should not be considered fixed and may depend on the context of the comparison. Furthermore, the magnitude of difference between native and exotic species necessary to trigger invasion is unknown. We propose a criterion that differences in trait values between a native and exotic invasive species must be greater than differences between co-occurring natives for this difference to be ecologically meaningful and a contributing factor to plant invasion. We used a meta-analysis to quantify the difference between native and exotic invasive species for various traits examined in previous studies and compared this value to differences among native species reported in the same studies. The effect size between native and exotic invasive species was similar to the effect size between co-occurring natives except for studies conducted in the field; in most instances, our criterion was not met although overall differences between native and exotic invasive species were slightly larger than differences between natives. Consequently, trait differences may be important in certain contexts, but other mechanisms of invasion are likely more important in most cases. We suggest that using trait values as predictors of invasion will be challenging.


Prevalence of Escherichia coli O157: H7 and serogroups O26, O103, O111 and O145 in sheep presented for slaughter in Scotland.
Sheep have been proposed as a source of human verocytotoxigenic Escherichia coli infection on a number of occasions but few prevalence studies have focused on identifying rates of carriage of these pathogens in this species. The purpose of this work was to establish the frequency of excretion of E. coli of serogroups O157, O26, O103, O111 and O145 in sheep presented for slaughter in Scotland and to examine their carriage of known virulence determinants. The study involved microbiological isolation of E. coli from 1082 sheep presented for slaughter in four Scottish abattoirs between July 2005 and June 2006. Using faecal enrichment and immunomagnetic separation, the isolation rate from these samples was 3.4 % for E. coli serogroup O157, 5.2 % for E. coli serogroup O26, 2.3 % for E. coli serogroup O103 and 0.1 % for E. coli serogroup O145. E. coli O111 was not isolated. In the last month of testing, which coincided with sorbitol-fermenting E. coli O157 (SFO157) cases in children in Scotland, all 83 recta received were screened and tested negative for SFO157 strains. The study found no verocytotoxin-positive strains amongst the E. coli serogroup O103 or O145 isolates. Verocytotoxin-positive strains were identified amongst isolates of E. coli serotypes O157 : H7 and O26 : H11. E. coli O157 : H7 was not isolated from samples collected between January and March, a statistically significant drop (P<0.001) in mean shedding relative to other months. There was evidence (P = 0.003) of higher shedding of O157 in adults and hoggs than in lambs. E. coli O26 : H11 was isolated throughout the year, with a statistically significant peak in shedding in the third quarter (P = 0.003). The results showed that sheep presented for slaughter in Scotland may carry strains of E. coli, particularly of serogroups O157 and O26, which can be presumed to have potential to cause human infection. They did not support a hypothesis that human cases of E. coli O157 : H7 are higher in any particular Scottish region as a direct consequence of a higher rate of faecal carriage in sheep in that region.


Neural Style Transfer: A Review.
The seminal work of Gatys et al. demonstrated the power of Convolutional Neural Networks (CNNs) in creating artistic imagery by separating and recombining image content and style. This process of using CNNs to render a content image in different styles is referred to as Neural Style Transfer (NST). Since then, NST has become a trending topic both in academic literature and industrial applications. It is receiving increasing attention and a variety of approaches are proposed to either improve or extend the original NST algorithm. In this paper, we aim to provide a comprehensive overview of the current progress towards NST. We first propose a taxonomy of current algorithms in the field of NST. Then, we present several evaluation methods and compare different NST algorithms both qualitatively and quantitatively. The review concludes with a discussion of various applications of NST and open problems for future research. A list of papers discussed in this review, corresponding codes, pre-trained models and more comparison results are publicly available at: https://osf.io/f8tu4/.


[Changes in 5-methylcytosine content of plant DNA in proportion to the amount of flowering].
A study has been made of the content of GC pairs and 5-methylcytosine in the total DNA of generative (inflorescences, flowers, flower buds) and vegetative (shoots, leaves, vegetative buds) organs in pea, tobacco and apple due to flowering gradient. In all the plants studied, the content of 5-methylcytosine in the DNA of generative organs in high as that in the DNA of vegetative organs. The DNA from various organs of one and the same plant hardly differs by the GC content. The differences in the amount of 5-methylcytosine are probably indictive of various levels of DNA methylation. Thus tissue (cell) DNA of both plants and animals differs in the content of 5-methylcytosine. Besides, methylation of genome in them changes upon flowering, i.e. we revealed the gradient of the degree of methylation of plant genome which correlates positively with the known flowering gradient. Methylation of plant genome regulated by phytohormone is possibly associated with cell differentiation and may be considered as being one of the mechanisms of regulation of transcription.


Unplanned, urgent and emergency care: what are the roles that EMS plays in providing for older people with dementia? An integrative review of policy, professional recommendations and evidence.
To synthesise the existing literature on the roles that emergency medical services (EMS) play in unplanned, urgent and emergency care for older people with dementia (OPWD), to define these roles, understand the strength of current research and to identify where the focus of future research should lie. An integrative review of the synthesised reports, briefings, professional recommendations and evidence. English-language articles were included if they made any reference to the role of EMS in the urgent or emergency care of OPWD. Preparatory scoping and qualitative work with frontline ambulance and primary care staff and carers of OPWD informed our review question and subsequent synthesis. Seventeen literature sources were included. Over half were from the grey literature. There was no research that directly addressed the review question. There was evidence in reports, briefings and professional recommendations of EMS addressing some of the issues they face in caring for OPWD. Three roles of EMS could be drawn out of the literature: emergency transport, assess and manage and a 'last resort' or safety net role. The use of EMS by OPWD is not well understood, although the literature reviewed demonstrated a concern for this group and awareness that services are not optimum. Research in dementia care should consider the role that EMS plays, particularly if considering crises, urgent care responses and transitions between care settings. EMS research into new ways of working, training or extended paramedical roles should consider specific needs and challenges of responding to people with dementia.


A systematic random sampling scheme optimized to detect the proportion of rare synapses in the neuropil.
Synapses can only be morphologically identified by electron microscopy and this is often a very labor-intensive and time-consuming task. When quantitative estimates are required for pathways that contribute a small proportion of synapses to the neuropil, the problems of accurate sampling are particularly severe and the total time required may become prohibitive. Here we present a sampling method devised to count the percentage of rarely occurring synapses in the neuropil using a large sample (approximately 1000 sampling sites), with the strong constraint of doing it in reasonable time. The strategy, which uses the unbiased physical disector technique, resembles that used in particle physics to detect rare events. We validated our method in the primary visual cortex of the cat, where we used biotinylated dextran amine to label thalamic afferents and measured the density of their synapses using the physical disector method. Our results show that we could obtain accurate counts of the labeled synapses, even when they represented only 0.2% of all the synapses in the neuropil.


Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses.
Robust immune responses are essential for eliminating pathogens but must be metered to avoid prolonged immune activation and potential host damage. Upon recognition of microbial DNA, the cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger cGAMP to initiate the stimulator of interferon genes (STING) pathway and subsequent interferon (IFN) production. We report that the direct interaction between cGAS and the Beclin-1 autophagy protein not only suppresses cGAMP synthesis to halt IFN production upon double-stranded DNA (dsDNA) stimulation or herpes simplex virus-1 infection, but also enhances autophagy-mediated degradation of cytosolic pathogen DNA to prevent excessive cGAS activation and persistent immune stimulation. Specifically, this interaction releases Rubicon, a negative autophagy regulator, from the Beclin-1 complex, activating phosphatidylinositol 3-kinase class III activity and thereby inducing autophagy to remove cytosolic pathogen DNA. Thus, the cGAS-Beclin-1 interaction shapes innate immune responses by regulating both cGAMP production and autophagy, resulting in well-balanced antimicrobial immune responses.


Evolutionary Origins of Rhizarian Parasites.
The SAR group (Stramenopila, Alveolata, Rhizaria) is one of the largest clades in the tree of eukaryotes and includes a great number of parasitic lineages. Rhizarian parasites are obligate and have devastating effects on commercially important plants and animals but despite this fact, our knowledge of their biology and evolution is limited. Here, we present rhizarian transcriptomes from all major parasitic lineages in order to elucidate their evolutionary relationships using a phylogenomic approach. Our results suggest that Ascetosporea, parasites of marine invertebrates, are sister to the novel clade Apofilosa. The phytomyxean plant parasites branch sister to the vampyrellid algal ectoparasites in the novel clade Phytorhiza. They also show that Ascetosporea + Apofilosa + Retaria + Filosa + Phytorhiza form a monophyletic clade, although the branching pattern within this clade is difficult to resolve and appears to be model-dependent. Our study does not support the monophyly of the rhizarian parasitic lineages (Endomyxa), suggesting independent origins for rhizarian animal and plant parasites.


Pharmacological Characterization of the Spectrum of Antiviral Activity and Genetic Barrier to Drug Resistance of M2-S31N Channel Blockers.
Adamantanes (amantadine and rimantadine) are one of the two classes of Food and Drug Administration-approved antiviral drugs used for the prevention and treatment of influenza A virus infections. They inhibit viral replication by blocking the wild-type (WT) M2 proton channel, thus preventing viral uncoating. However, their use was discontinued due to widespread drug resistance. Among a handful of drug-resistant mutants, M2-S31N is the predominant mutation and persists in more than 95% of currently circulating influenza A strains. We recently designed two classes of M2-S31N inhibitors, S31N-specific inhibitors and S31N/WT dual inhibitors, which are represented by N-[(5-cyclopropyl-1,2-oxazol-3-yl)methyl]adamantan-1-amine (WJ379) and N-[(5-bromothiophen-2-yl)methyl]adamantan-1-amine (BC035), respectively. However, their antiviral activities against currently circulating influenza A viruses and their genetic barrier to drug resistance are unknown. In this report, we evaluated the therapeutic potential of these two classes of M2-S31N inhibitors (WJ379 and BC035) by profiling their antiviral efficacy against multidrug-resistant influenza A viruses, in vitro drug resistance barrier, and synergistic effect with oseltamivir. We found that M2-S31N inhibitors were active against several influenza A viruses that are resistant to one or both classes of Food and Drug Administration-approved anti-influenza drugs. In addition, M2-S31N inhibitors display a higher in vitro genetic barrier to drug resistance than amantadine. The antiviral effect of WJ379 was also synergistic with oseltamivir carboxylate. Overall, these results reaffirm that M2-S31N inhibitors are promising antiviral drug candidates that warrant further development.


Interleukin 3 promotes the in vitro proliferation of murine pluripotent hematopoietic stem cells.
Medium conditioned by activated T lymphocytes stimulates the in vitro proliferation of pluripotent hematopoietic stem cells (spleen colony-forming units [CFU-S]) but the factors involved have not been identified. Because the lymphokine interleukin 3 (IL-3) enhances in vitro colony formation by committed hematopoietic progenitor cells, we examined the effect of IL-3 on the in vitro proliferation of CFU-S using an 11-d spleen colony assay. When mouse marrow cells were placed in liquid culture, CFU-S content declined progressively and by 96 h only 13% of the CFU-S remained. By contrast, after 96 h in the presence of 20 U/ml of IL-3, the number of CFU-S were the same as that in the initial inoculum. Although the number of CFU-S eventually declined, they could still be recovered after 264 h of culture. In the absence of IL-3, the number of CFU-S synthesizing DNA was negligible; in its presence, greater than 20% of the CFU-S were in cycle. IL-3 stimulated CFU-S proliferation at a concentration of 0.2 U/ml. The dose-response curve was similar to that observed for other biologic effects of the lymphokine, and as little as 1 h of exposure to IL-3 enhanced the survival of CFU-S in vitro. Treatment of marrow cells with anti-Thy 1.2 antibody and complement before exposure to IL-3 did not inhibit spleen colony formation, but treatment of the cells with anti-Thy 1.2 antibody and complement after exposure to IL-3 reduced CFU-S recovery after 96 h of culture by 45%. The cell composition of day 11 spleen colonies formed by IL-3-treated marrow cells was similar to that of colonies formed by untreated marrow cells. Finally, day 11 CFU-S persisting in the marrow of mice treated with 5-fluorouracil required IL-3 for proliferation in vitro. Taken together, these data indicate that IL-3 promotes the proliferation of CFU-S in vitro, increases the number of CFU-S synthesizing DNA, but does not alter their commitment program, and the target cell population includes CFU-S with self-renewal and marrow-repopulating ability.


The writer's guide to education scholarship in emergency medicine: Systematic reviews and the scholarship of integration (part 4).
Reviews help scholars consolidate evidence and guide their educational practice. However, few papers describe how to effectively publish review papers. We completed a scoping review to develop a set of quality indicators that will assist junior authors to publish reviews and integrative scholarship. MEDLINE, Embase, ERIC, and Google Scholar were searched for English language articles published between 2012 and January 2016 using the terms review, medical education, how to publish, and emergency medicine. Titles and abstracts were reviewed by two authors and included if they focused on how to publish a review or outlined reporting guidelines of reviews. The articles were reviewed in parallel for calibration, and disagreements were resolved through a consensus. A full text review of the 25 articles was conducted, and 196 recommendations were extracted from 13 articles. A hand search of the included articles' reference lists and expert recommendation found an additional eight articles. These recommendations were thematically analysed into a list of seven themes and 32 items. Additionally, seven evaluation tools and reporting guidelines were found to guide researchers in optimizing their reviews for publication. In emergency medicine education, review articles can help synthesize educational research so that educators can engage in evidence-based scholarly teaching. We hope that this work will act as an introduction to those interested in engaging in integrative scholarship by providing them with a guide to key quality markers and important checklists for improving their research.


Insulin-like growth factor II supply modifies growth of intestinal adenoma in Apc(Min/+) mice.
Insulin-like growth factor-II (IGF-II) is an embryonic growth promoter and cell survival factor. IGF-II supply is normally limited by gene expression because transcription occurs predominantly from the paternal allele in mouse and man (maternal imprinting). Excess IGF-II has detrimental systemic and local effects in vivo, promoting somatic overgrowth and an increased frequency of tumors. IGF2 mRNA is overexpressed in colorectal and many other human cancers. In this paper, we show that altered IGF-II supply modifies intestinal tumor growth. Mice genetically altered in the IGF-II system were combined in crosses with ApcMin/+, a murine model of human familial adenomatous polyposis. Depending on genetic background, ApcMin/+ acquires multiple small intestinal adenoma before becoming moribund with anemia. Mice that express excess IGF-II delivered using a bovine keratin 10 promoter (k10Igf2/+) develop a disproportionate overgrowth of colon, uterus, and skin. Combination with ApcMin/+ leads to a 10-fold increase in the number and the diameter of colon adenoma (P<0.0001) compared to ApcMin/+ littermate controls (postnatal day 80), an increased susceptibility to rectal prolapse (41%), and a histological progression to carcinoma. Mice with reduced IGF-II supply, secondary to the disruption of the paternal Igf2 allele (Igf2+m/-p), are 60% the weight of wild-type littermates. Combination with ApcMin/+ leads to a 3-fold reduction in small intestinal adenoma number (P<0.0001) compared to ApcMin/+ littermate controls (postnatal day 150), and a significant decrease in adenoma diameter (P<0.001). With in situ hybridization, we show that Igf2 was expressed in all adenoma irrespective of IGF-II supply. This suggests that there is an increased maternal allele expression of Igf2 (loss of imprinting) in adenoma which form, despite paternal Igf2 allele disruption. We conclude that IGF-II supply is a modifier of intestinal adenoma growth, and we provide genetic evidence for its functional role in colorectal cancer progression.


UniDrug-target: a computational tool to identify unique drug targets in pathogenic bacteria.
Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed. A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein's critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed. The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets. UniDrug-Target is expected to accelerate pathogen-specific drug targets identification which will increase their success and durability as drugs developed against them have less chance to develop resistances and adverse impact on environment. The server is freely available at http://18.104.22.168/UDT/main.html. The standalone application (source codes) is available at http://www.bioinformatics.org/ftp/pub/bioinfojuit/UDT.rar.


Monitoring disease trends using hospital traffic data from high resolution satellite imagery: a feasibility study.
Challenges with alternative data sources for disease surveillance include differentiating the signal from the noise, and obtaining information from data constrained settings. For the latter, events such as increases in hospital traffic could serve as early indicators of social disruption resulting from disease. In this study, we evaluate the feasibility of using hospital parking lot traffic data extracted from high-resolution satellite imagery to augment public health disease surveillance in Chile, Argentina and Mexico. We used archived satellite imagery collected from January 2010 to May 2013 and data on the incidence of respiratory virus illnesses from the Pan American Health Organization as a reference. We developed dynamical Elastic Net multivariable linear regression models to estimate the incidence of respiratory virus illnesses using hospital traffic and assessed how to minimize the effects of noise on the models. We noted that predictions based on models fitted using a sample of observations were better. The results were consistent across countries with selected models having reasonably low normalized root-mean-squared errors and high correlations for both the fits and predictions. The observations from this study suggest that if properly procured and combined with other information, this data source could be useful for monitoring disease trends.


Multiple transcatheter interventions in the same session in congenital cardiopathies.
To investigate the methods of percutaneous transcatheter interventions for combined congenital heart disease and to evaluate its efficacy in children. Thirty cases (ages 3 days-13.5 years, body weight 3-35 kg) that underwent two multiple transcatheter interventions for combined or solitary congenital heart disease were retrospectively analyzed and presented. A total of 61 transcatheter interventions were performed in 30 patients as combined procedures. In 29 patients, two different procedures were combined in the same session, in remaining one patient, combination of three interventions were performed in the same catheter session. Interventions performed in combined procedures were as follows: Coarctation balloon angioplasty in 12 cases, pulmonary balloon valvuloplasty in 10, PDA coil embolization in 10, aortic balloon valvuloplasty in 8, VSD closure in 5, ASD closure in 4, ductal stent implantation in 4, palliative pulmonary balloon valvuloplasty in 3, recanalization and angioplasty of the systemic-pulmonary shunt in 2, balloon atrial septostomy in one, aortic coarctation stent implantation in one, coil embolization of a pulmonary lobar sequestration in one and pulmonary valve perforation plus pulmonary balloon valvuloplasty in one were performed as first or second procedure. There was no mortality or major morbidity in relation to combined procedures. Multiple transcatheter interventions in the same session are feasible, safe and effective with satisfactory good results. Second intervention may be performed as complementary procedure or independently to the first intervention.


Increase in serum digoxin concentration produced by quinidine does not increase the potential for digoxin-induced ventricular arrhythmias in dogs.
Chronic treatment of dogs with digoxin alone, quinidine alone and digoxin in combination with quinidine was initiated in dogs to assess changes in arrhythmogenic potential associated with the quinidine-induced increase in serum digoxin concentration observed during combined digoxin and quinidine treatment. The arrhythmogenic potential of digoxin was evaluated through the use of the acetylstrophanthidin (AcS) tolerance test. AcS was infused at a rate of 5 micrograms/kg/min until ventricular arrhythmias occurred during a drug-free period and during chronic treatment with digoxin, quinidine and digoxin plus quinidine. The dose of AcS required to initiate ventricular arrhythmias is inversely related to the arrhythmogenic potential of digoxin present at the time of AcS infusion. Administration of quinidine alone in two different dosage regimens produced serum quinidine concentrations of 5.99 +/- 1.18 and 2.99 +/- 0.43 micrograms/ml and significantly increased AcS tolerance, whereas digoxin alone, over a wide range of serum digoxin concentrations, significantly decreased AcS tolerance. This decrease in AcS tolerance was linearly related to the serum digoxin concentration. The addition of quinidine treatment to animals receiving digoxin resulted in a significant elevation in the steady-state serum digoxin concentration. However, the AcS tolerance determined during the elevated serum digoxin concentration induced by quinidine was greater than that determined during treatment with the same dose of digoxin alone. Thus, quinidine administration to animals receiving digoxin resulted in a significant increase in the steady-state serum digoxin concentration but did not increase the arrhythmogenic potential of digoxin over that observed during treatment with the same dose of digoxin alone.(ABSTRACT TRUNCATED AT 250 WORDS)


The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.
Patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis are at the highest risk for progressing to end-stage liver disease. We constructed and validated a scoring system consisting of routinely measured and readily available clinical and laboratory data to separate NAFLD patients with and without advanced fibrosis. A total of 733 patients with NAFLD confirmed by liver biopsy were divided into 2 groups to construct (n = 480) and validate (n = 253) a scoring system. Routine demographic, clinical, and laboratory variables were analyzed by multivariate modeling to predict presence or absence of advanced fibrosis. Age, hyperglycemia, body mass index, platelet count, albumin, and AST/ALT ratio were independent indicators of advanced liver fibrosis. A scoring system with these 6 variables had an area under the receiver operating characteristic curve of 0.88 and 0.82 in the estimation and validation groups, respectively. By applying the low cutoff score (-1.455), advanced fibrosis could be excluded with high accuracy (negative predictive value of 93% and 88% in the estimation and validation groups, respectively). By applying the high cutoff score (0.676), the presence of advanced fibrosis could be diagnosed with high accuracy (positive predictive value of 90% and 82% in the estimation and validation groups, respectively). By applying this model, a liver biopsy would have been avoided in 549 (75%) of the 733 patients, with correct prediction in 496 (90%). a simple scoring system accurately separates patients with NAFLD with and without advanced fibrosis, rendering liver biopsy for identification of advanced fibrosis unnecessary in a substantial proportion of patients.


Deficiency of mannose-binding lectin greatly increases susceptibility to postburn infection with Pseudomonas aeruginosa.
Burn injury disrupts the mechanical and biological barrier that the skin presents against infection by symbionts like the Pseudomonas aeruginosa, a Gram-negative bacteria. A combination of local factors, antimicrobial peptides, and resident effector cells form the initial response to mechanical injury of the skin. This activity is followed by an inflammatory response that includes influx of phagocytes and serum factors, such as complement and mannose-binding lectin (MBL), which is a broad-spectrum pattern recognition molecule that plays a key role in innate immunity. A growing consensus from studies in humans and mice suggests that lack of MBL together with other comorbid factors predisposes the host to infection. In this study we examined whether MBL deficiency increases the risk of P. aeruginosa infection in a burned host. We found that both wild-type and MBL null mice were resistant to a 5% total body surface area burn alone or s.c. infection with P. aeruginosa alone. However, when mice were burned then inoculated s.c. with P. aeruginosa at the burn site, all MBL null mice died by 42 h from septicemia, whereas only one-third of wild-type mice succumbed (p = 0.0005). This result indicates that MBL plays a key role in containing and preventing a systemic spread of P. aeruginosa infection following burn injury and suggests that MBL deficiency in humans maybe a premorbid variable in the predisposition to infection in burn victims.