Intestinal injury associated with low-voltage electrocution.
A 16-month-old girl suffered low-voltage electrocution from a hairdryer while playing in the bathtub. At exploratory laparotomy about 18 hours postinjury because of distention and persistent, unexplained acidosis, a 1.5-cm diameter necrotic lesion in the terminal ileum surrounded by multiple superficial serosal burns and a 1.5 x 1.0 cm eschar in the mid-transverse colon were found. The lesion in the small intestine was resected with wide margins and the colon lesion exteriorized. The child ultimately expired 12 hours after surgery from recurrent cardiac arrest. Abdominal visceral injury associated with major electrical injury is reviewed. Although the colon is probably the most frequently injured, the esophagus, pancreas, gallbladder, and small intestine have also been reported as directly injured by electric current. The importance of meticulous examination of the abdominal contents at laparotomy is stressed. Lesions of the small intestine should be resected with wide margins when possible and lesions of the colon resected with a colostomy of the injured segment exteriorized.


Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of chromosome conformation.
Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (kb) resolution. It also includes steps to reduce random ligation and the generation of uninformative molecules, such as unligated ends, to improve the amount of valid intra-chromosomal read pairs. This protocol allows for obtaining information on conformational structures such as compartment and topologically associating domains, as well as high-resolution conformational features such as DNA loops.


Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo/Yap signalling pathway.
Context: Emodin is a compound in Rheum undulatum Linne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects.Objective: Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism.Materials and methods: We used the hepatocyte stimulated by arachidonic acid (AA) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 ∼ 30 μM) for 1 h before AA + iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP.Results: In vitro, emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 μM (EC50 > 3 μM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 μM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway. In vivo, the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage.Conclusion: Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway.


Peroxisome proliferator-activated receptor gamma (PPAR-γ) and neurodegenerative disorders.
As the growth of the aging population continues to accelerate globally, increased prevalence of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke, has generated substantial public concern. Unfortunately, despite of discoveries of common factors underlying these diseases, few drugs are available to effectively treat these diseases. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. PPAR-γ has been shown to influence the expression or activity of a large number of genes in a variety of signaling networks, including regulation of insulin sensitivity, glucose homeostasis, fatty acid oxidation, immune responses, redox balance, cardiovascular integrity, and cell fates. Recent epidemiological, preclinical animal, and clinical studies also show that PPAR-γ agonists can lower the incidence of a number of neurological disorders, despite of multiple etiological factors involved in the development of these disorders. In this manuscript, we review current knowledge on mechanisms underlying the beneficial effect of PPAR-γ in different neurodegenerative diseases, in particular, AD, PD, and stroke, and attempt to analyze common and overlapping features among these diseases. Our investigation unveiled information suggesting the ability for PPAR-γ to inhibit NF-κB-mediated inflammatory signaling at multiple sites, and conclude that PPAR-γ agonists represent a novel class of drugs for treating neuroinflammatory diseases.


[The determination of Escherichia virulence on nutrient media].
The virulence of 250 pathogenic Escherichia strains secreted from humans and from various environmental objects has been studied on nutrient media with stains, ram erythrocytes and in hemagglutination reactions. The highest percentage of strain virulence is revealed when using crystal violet and in the blood agar (44.0 and 27.2%, respectively), evidently, due to nonspecific reactions. The medium with congo red showed a positive result in 20.3 + 3.1%, and the d-mannose-resistant hemagglutination reaction--in 16.5 + 2.3% cases. In practice it is recommended to use several methods which enable estimating correctly the risk to infect humans and to conduct timely preventive measures.


Nontargeted Screening of Contaminants of Emerging Concern in the Glen Valley Wastewater Treatment Plant, Botswana.
There is growing concern about the prevalence and impact of contaminants of emerging concern (CECs). The environmental monitoring of CECs has, however, been limited in low- and middle-income countries due to the lack of advanced analytical instrumentation locally. In the present study we employed a nontargeted and suspect screening workflow via liquid chromatography coupled with high-resolution mass spectrometry (HRMS) to identify known and unknown pollutants in the Glen Valley wastewater treatment plant, Botswana, complemented by analysis of groundwater samples. The present study represents the first HRMS analysis of CECs in water samples obtained in Botswana. Suspect screening of 5942 compounds qualitatively identified 28 compounds, including 26 pharmaceuticals and two illicit drugs (2-ethylmethcathinone and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol). Nontargeted analysis tentatively identified the presence of 34 more compounds including (5ξ)-12,13-dihydroxypodocarpa-8,11,13-trien-7-one, 12-aminododecanoic acid, atenolol acid, brilliant blue, cyclo leucylprolyl, decanophenone, DL-carnitine, N,N'-dicyclohexylurea, N4-acetylsulfamethoxazole, NP-003672, and 24 polyethylene glycol polymers. The highest number of detections were in influent wastewater (26 CECs) followed by effluent wastewater (10 CECs) and, lastly, groundwater (4 CECs). Seventeen CECs detected in the influent water were not detected in the effluent waters, suggesting reduced emissions due to wastewater treatment. Two antiretroviral compounds (abacavir and tenofovir) were detected in the influent and effluent sources. This suggests that wastewater treatment plants are a major pathway of chemical pollution to the environment in Botswana and will help inform prioritization efforts for monitoring and remediation that is protective of these key ecosystems. Environ Toxicol Chem 2023;00:1-10. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


CO2 lattice laser reverses skin aging caused by UVB.
The carbon dioxide (CO2) lattice laser has been successfully used to treat facial skin photoaging induced by UV light. In this study, we analyzed the effect of CO2 lattice laser irradiation on skin photoaging, and investigated the underlying mechanisms. Our results demonstrate that the laser promoted collagen synthesis and proliferation of primary human skin fibroblasts, inhibited cell senescence, and induced expression of superoxide dismutase (SOD) and the signaling protein SMAD3. In addition, this laser reversed cell cycle arrest and fibroblast apoptosis induced by UVB irradiation, and restored fibroblast proliferation inhibited by SMAD3 silencing. Using a rat model of photoaging, our results show that the laser increased collagen expression and dermal thickness, demonstrating that the CO2 lattice laser has a profound therapeutic effect on photoaged skin. Together, our in vitro and in vivo data show that the CO2 lattice laser can reverse the skin aging caused by UVB, and indicate that this effect is mediated through SMAD3.


Biological evaluation of carbohydrate-based aprepitant analogs for neuroblastoma treatment.
Different studies using Aprepitant, a NK1R antagonist currently used as a clinical drug for treating chemotherapy-related nausea and vomiting, have demonstrated that pharmacological inhibition of NK1R effectively reduces the growth of several tumor types such as neuroblastoma (NB). In a previous work, we demonstrated that a series of carbohydrate-based Aprepitant analogs, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity. In this new study, we explore the selective cytotoxic effects of these derivatives for the treatment of NB. Furthermore, we describe the design and stereoselective synthesis of a new generation of d-glucose derivatives as Aprepitant analogs, supported by docking studies. This approach showed that most of our carbohydrate-based analogs are significantly more selective than Aprepitant. The galactosyl derivative 2α, has demonstrated a marked in vitro selective cytotoxic activity against NB, with IC50 values in the same range as those of Aprepitant and its prodrug Fosaprepitant. Interestingly, the derivative 2α has shown similar apoptotic effect to that of Aprepitant. Moreover, we can select the glucosyl amino derivative 10α as an interesting hit exhibiting higher in vitro cytotoxic activity against NB than Aprepitant, being 1.2 times more selective.


Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.
Some observational studies have suggested that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). The aim of this review was to examine the evidence as to whether or not taking vitamin or mineral supplements prevents the development of AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (2007, Issue 3), MEDLINE (1966 to August 2007), SIGLE (1980 to 2005/03), EMBASE (1980 to August 2007), National Research Register (2007, Issue 3), AMED (1985 to January 2006) and PubMed (on 24 January 2006 covering last 60 days), reference lists of identified reports and the Science Citation Index. We contacted investigators and experts in the field for details of unpublished studies. We included all randomised trials comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control. We included only studies where supplementation had been given for at least one year. Both review authors independently extracted data and assessed trial quality. Data were pooled using a fixed-effect model. Three randomised controlled trials were included in this review (23,099 people randomised). These trials investigated alpha-tocopherol and beta-carotene supplements. There was no evidence that antioxidant vitamin supplementation prevented or delayed the onset of AMD. The pooled risk ratio for any age-related maculopathy (ARM) was 1.04 (95% CI 0.92 to 1.18), for AMD (late ARM) was 1.03 (95% CI 0.74 to 1.43). Similar results were seen when the analyses were restricted to beta-carotene and alpha-tocopherol. There is no evidence to date that the general population should take antioxidant vitamin and mineral supplements to prevent or delay the onset of AMD. There are several large ongoing trials. People with AMD should see the related Cochrane review "Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration" written by the same author.


Is it possible to prefabricate a vascularized peripheral nerve graft?
The ideal technique to repair a damaged peripheral nerve is primary repair. Unfortunately, most damaged peripheral nerves have gaps making primary repair impossible. Autologous nerve grafts that are used to repair damaged nerves can either be conventional nonvascularized nerve grafts or vascularized nerve grafts. Vascularized nerve grafts are proposed to be superior to conventional nerve grafts especially in recipient beds that are scarred, with poor vascular supply. One of the disadvantages of vascularized nerve grafts is the limited donor site. It is possible to eliminate this problem by prefabricating vascularized nerve grafts. In this study, to prefabricate a vascularized nerve, segments harvested from left sciatic nerves of 10 Wistar albino rats were implanted on right femoral vessels, and intact right sciatic nerves were used as controls to evaluate the function, electrophysiologic studies, and histopathologic examination, were performed on these grafts 4 weeks after implantation. Prefabricated sciatic nerve grafts showed vascularization, but they did not show compound action potential activity to electrical stimulation and demonstrated diffuse and severe vacuolar degeneration and myelin loss. We were unable to prefabricate a functional vascularized nerve graft by this method.


Multifunctionality is affected by interactions between green roof plant species, substrate depth, and substrate type.
Green roofs provide ecosystem services through evapotranspiration and nutrient cycling that depend, among others, on plant species, substrate type, and substrate depth. However, no study has assessed thoroughly how interactions between these factors alter ecosystem functions and multifunctionality of green roofs. We simulated some green roof conditions in a pot experiment. We planted 20 plant species from 10 genera and five families (Asteraceae, Caryophyllaceae, Crassulaceae, Fabaceae, and Poaceae) on two substrate types (natural vs. artificial) and two substrate depths (10 cm vs. 30 cm). As indicators of major ecosystem functions, we measured aboveground and belowground biomasses, foliar nitrogen and carbon content, foliar transpiration, substrate water retention, and dissolved organic carbon and nitrates in leachates. Interactions between substrate type and depth strongly affected ecosystem functions. Biomass production was increased in the artificial substrate and deeper substrates, as was water retention in most cases. In contrast, dissolved organic carbon leaching was higher in the artificial substrates. Except for the Fabaceae species, nitrate leaching was reduced in deep, natural soils. The highest transpiration rates were associated with natural soils. All functions were modulated by plant families or species. Plant effects differed according to the observed function and the type and depth of the substrate. Fabaceae species grown on natural soils had the most noticeable patterns, allowing high biomass production and high water retention but also high nitrate leaching from deep pots. No single combination of factors enhanced simultaneously all studied ecosystem functions, highlighting that soil-plant interactions induce trade-offs between ecosystem functions. Substrate type and depth interactions are major drivers for green roof multifunctionality.


Paedomorphosis and simplification in the nervous system of salamanders.
Comparative neuroanatomists since Herrick [1914] have been aware of the paradox that the brain of amphibians, especially salamanders, is less complex than one would expect based on their phylogenetic position among the Tetrapoda. Many features of the brain are less differentiated in salamanders than in tetrapod outgroups, including chondrichthyans and bony fishes, and for some brain characters, the salamander brain is even more simple than that of the agnathans. Here, we perform a cladistic analysis on 23 characters of four sensory systems (visual, auditory, lateral line and olfactory) and the brain. Our taxa include myxinoids, lampreys, chondrichthyans, actinopterygians, Latimeria, Neoceratodus and the lepidosirenid lungfishes, amniotes, frogs, caecilians, salamanders and bolitoglossine salamanders. Of the 23 characters we examined, 19 are most parsimoniously interpreted as secondarily simplified in salamanders from a more complex ancestral state, two characters are equally parsimonious under both hypotheses, one character (well developed ipsilateral retinotectal projections) is more complex in bolitoglossine salamanders than in vertebrates generally, and only one character (migration of neurons in the medial pallium) is most parsimoniously interpreted as retention of the plesiomorphically simple condition. Secondary simplification of the salamander brain appears to result from paedomorphosis, or retention of juvenile or embryonic morphology into adulthood. Paedomorphosis is correlated with an increase in genome size, which in turn is positively correlated with cell size, but negatively correlated with cell proliferation and differentiation rates. Available data suggest that, although increasing genome size and paedomorphosis tend to compromise the function of the salamander brain, compensating mechanisms have evolved that may restore or even enhance brain function.


Cognition among community-dwelling individuals with spinal cord injury.
To compare the cognitive profiles of a well-characterized sample of adults with and without spinal cord injury (SCI) using the NIH Toolbox Cognition Battery NIHTB-CB. Research Method/Design: Participants were 156 community-dwelling individuals with SCI recruited from 3 academic medical centers, and 156 individuals without SCI selected from the NIHTB-CB normative database (N = 312). The main outcome measures were the demographically adjusted NIHTB-CB subtest and composite scores. Individuals with and without SCI performed equivalently on the NIHTB-CB crystallized composite score, suggesting comparable premorbid functioning. Individuals with SCI produced lower scores on the NIHTB-CB fluid composite score by an average of 4.5 T-score points (Cohen's d = 0.50; a medium effect size). As a group, individuals with SCI had the most difficulty on tests of processing speed and executive functions, and some difficulty on a test of episodic memory, although effect sizes were small. These differences remained even after accounting for fine motor speed and dexterity. Individuals with tetraplegia produced lower scores than individuals with paraplegia on tests of processing speed and executive functioning. Community-dwelling individuals with SCI are at elevated risk of mild cognitive difficulties, particularly on tasks that rely on processing speed and executive functions. The NIHTB-CB is relatively brief, samples important cognitive domains, has good normative data, and is appropriate for some individuals with SCI (those who have functional use of one hand). The battery has standardized accommodations for individuals with minor motor limitations, but timed tests are inaccessible for individuals who are unable to perform rapid button presses. (PsycINFO Database Record


[A long-term posttetanic potentiation of hippocampal evoked potentials under conditions of enriched environment].
The influence of enriched environment on the long-term posttetanic potentiation of hippocampal evoked potentials is discussed. The attention is focused on the effects of novelty, aging and the influence of enriched environment on synaptic processes in hippocampal neurons in transgenic animals. The evidence that the exposure to the enrichment of the environments prevents the negative effects of stress and other unfavorable factors on the long-term posttetanic potentiation, learning and memory is presented. The molecular-biochemical, neurochemical, neurophysiological and morphological mechanisms underling synaptic changes responsible for the transformation of hippocampal long-term potentiation under exposure to the enriched environment are considered.


Luminescence Spectroscopy of Rhodamine Homodimer Dications in Vacuo Reveals Strong Dye-Dye Interactions.
Being alone or together makes a difference for the photophysics of dyes but for ionic dyes it is difficult to quantify the interactions due to solvent screening and nearby counter ions. Gas-phase luminescence experiments are desirable and now possible based on recent developments in mass spectrometry. Here we present results on tailor-made rhodamine homodimers where two dye cations are separated by methylene linkers, (CH2 )n . In solution the fluorescence is almost identical to that from the monomer whereas the emission from bare cation dimers redshifts with decreasing n. In the absence of screening, the electric field from the charge on one dye is strong enough to polarize the other dye, both in the ground state and in the excited state. An electrostatic model based on symmetric dye responses (equal induced-dipole moments in ground state) captures the underlying physics and demonstrates interaction even at large distances. Our results have possible implications for gas-phase Förster Resonance Energy Transfer.


Development of resistance of enterocytes to rotavirus in neonatal, agammaglobulinemic piglets.
The first part of this report describes the development of a technique for evaluating the growth of rotavirus under controlled conditions that approximate a natural infection. A standard dose of rotavirus (approximately 10(9) viral particles) was injected into ligated segments in the small intestine of newborn, agammaglobulinemic, colostrum-deprived piglets. After various periods postinoculation, the segments were retrieved and the enterocytes were evaluated for the presence of rotaviral antigens by immunofluorescence and rotaviral particles by transmission electron microscopy. Peak immunofluorescence in enterocytes was detected at 8 h postinoculation in the upper and middle jejunum and ileum. Transmission electron microscopy at this time revealed fully formed virions which were not seen in sections examined before this 8-h period. The second part of our study describes the use of ligated segments in determining the susceptibility to rotavirus of enterocytes in piglets ranging in age from newborn to 2 weeks. By the time piglets were 2 days old, enterocytes in the upper half of the small intestines appeared to be resistant to rotavirus, whereas those in the lower half seemed partially resistant. Between 4 and 8 days of age, enterocytes in the lower half also became resistant. Resistance paralleled the loss in capacity of piglets to transport macromolecules through enterocytes and was not correlated with the loss in capacity to internalize macromolecules.


Endogenous adipose-derived factors diminish coronary endothelial function via inhibition of nitric oxide synthase.
Adipocytokines may be the molecular link between obesity and vascular disease. However, the effects of these factors on coronary vascular function have not been discerned. Accordingly, the goal of this investigation was to delineate the mechanisms by which endogenous adipose-derived factors affect coronary vascular endothelial function. Both isolated canine coronary arteries and coronary blood flow in anesthetized dogs were studied with and without exposure to adipose tissue. Infusion of adipose-conditioned buffer directly into the coronary circulation did not change baseline hemodynamics; however, endothelial-dependent vasodilation to bradykinin was impaired both in vitro and in vivo. Coronary vasodilation to sodium nitroprusside was unaltered by adipose tissue. Oxygen radical formation did not cause the impairment because quantified dihydroethidium staining was decreased by adipose tissue and neither a superoxide dismutase mimetic nor catalase improved endothelial function. Inhibition of nitric oxide (NO) synthase with L-NAME diminished bradykinin-mediated relaxations and eliminated the subsequent vascular effects of adipose tissue. In vitro measurement of NO demonstrated that adipose tissue exposure quickly lowered baseline NO and abolished bradykinin-induced NO production. The results indicate that adipose tissue releases factor(s) that selectively impair endothelial-dependent dilation via inhibition of NO synthase-mediated NO production.


Incisal and occlusal tooth wear in children and adolescents in a Swedish population.
The material consisted of 527 randomly selected children and adolescents from the community of Jönköping, Sweden, who in 1983 reached the age of 3, 5, 10, 15, or 20 years. The degree of incisal or occlusal tooth wear was evaluated for each single tooth in accordance with the following criteria: score 0 = no wear or negligible wear of enamel; score 1 = obvious wear of enamel or wear through the enamel to the dentin in single spots; score 2 = wear of the dentin up to one-third of the crown height; and score 3 = wear of the dentin more than one-third of the crown height. In the age groups 3 and 5 years the primary dentition was studied, and in the age groups 10, 15, and 20 years the permanent dentition. In the 3-year-old children 63% and in the 5-year-olds 19% had no or slight incisal or occlusal wear in the primary dentition. In the permanent dentition the corresponding figures for the 10-, 15-, and 20-year-olds were 78%, 51%, and 35%, respectively. The 5-year-olds had the highest percentage of primary teeth with incisal or occlusal wear related to existing teeth in accordance with criteria 1-3 (32.2%), and the 10-year-olds had the lowest score for permanent teeth (2.5%). There were small or no differences in tooth wear between the sexes in these age groups. Eighteen children (17%) among the 5-year-olds had one or more teeth with wear scored 2 in the primary dentition, and one individual had 4 primary teeth scored 3. The corresponding figures for the 3-, 10-, 15-, and 20 year-olds were 2%, 1%, 7% and 6%, respectively. No permanent teeth with wear scored 3 were found in these age groups. The number of teeth with incisal or occlusal wear increased with age both in the primary and in the permanent dentition.


Phosphor-converted LED modeling by bidirectional photometric data.
For the phosphor-converted light-emitting diodes (pcLEDs), the interaction of the illuminating energy with the phosphor would not just behave as a simple wavelength-converting phenomenon, but also a function of various combinations of illumination and viewing geometries. This paper presents a methodology to characterize the converting and scattering mechanisms of the phosphor layer in the pcLEDs by the measured bidirectional scattering distribution functions (BSDFs). A commercially available pcLED with conformal phosphor coating was used to examine the validity of the proposed model. The close agreement with the measurement illustrates that the proposed characterization opens new perspectives for phosphor-based conversion and scattering feature for white lighting uses.


Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model.
Percutaneous transluminal angioplasty (PTA) is the first line of treatment for stenosis in the arteriovenous fistula (AVF) created to provide access for hemodialysis, but resenosis still occurs. Transplants of adipose-derived mesenchymal stem cells (AMSCs) labeled with green fluorescent protein (GFP) to the adventitia could reduce pro-inflammatory gene expression, possibly restoring patency in a murine model of PTA for venous stenosis. Partial nephrectomy of male C57BL/6J mice induced CKD. Placement of the AVF was 28 days later and, 14 days after that, PTA of the stenotic outflow vein was performed with delivery of either vehicle control or AMSCs (5×105) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha TNF-α) analyzed, and histopathologic analysis performed on day 14 and 28. GFP (+) AMSCs were tracked after transplantation for up to 28 days and Doppler ultrasound performed weekly after AVF creation. Gene and protein expression of IL-1β and TNF-α, fibrosis, proliferation, apoptosis and smooth muscle actin decreased, and the proportions of macrophage types (M2/M1) shifted in a manner consistent with less inflammation in AMSC-transplanted vessels compared to controls. After PTA, AMSC-treated vessels had significantly higher wall shear stress, average peak, and mean velocity, with increased lumen vessel area and decreased neointima/media area ratio compared to the control group. At 28 days after delivery, GFP (+) AMSC were present in the adventitia of the outflow vein. AMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.


Haloparvum sedimenti gen. nov., sp. nov., a member of the family Haloferacaceae.
Two extremely halophilic archaeal strains, DYS4T and Y2, were isolated from rock salt of the Jiangcheng Salt Mine, Yunnan province, China. Cells of the two strains were non-motile, pleomorphic rods and Gram-stain-negative. The cells produced light red-pigmented colonies. Strains DYS4T and Y2 required 2.6-3.4 M NaCl, pH 7.5- 8.0 and 42 ºC in aerobic conditions for optimal growth. Mg2+ was required for growth. The major polar lipids of both strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and sulfated mannosyl glucosyl diether. An unidentified minor glycolipid spot was present for strains DYS4T and Y2, which differentiates them from the closely related species of the genera Halorubrum and Halopenitus. The lipid core of the glycolipid was sn-2,3-diphytanylglycerol (C20C20). The sequence similarity of the 16S rRNA gene demonstrated that the closest relatives of strains DYS4T and Y2 were Halorubrum aidingense 31-hongT (94.1 % and 93.6 % 16S rRNA gene sequence similarity to DYS4T and Y2, respectively) and Halopenitus salinus SKJ47T (93.4% and 93.1%). Phylogenetic analysis of the 16S rRNA gene and the rpoB' gene revealed that strains DYS4T and Y2 formed an independent lineage closely related to the genera Halorubrum and Halopenitus. The DNA G+C contents of strains DYS4T and Y2 were 68.2 and 67.0 mol%, respectively. The DNA-DNA relatedness value between strains DYS4T and Y2 was 90.0 ± 0.5%, while that between strain DYS4T and other closest relatives was less than 26 % (19 ± 0.7 % for Halorubrum aidingense 31-hongT and 25 ± 0.3% for Halopenitus salinus SKJ47T). The phenotypic, chemotaxonomic and phylogenetic properties suggest that strains DYS4T and Y2 (=CGMCC 1.15000=JCM 30892) represent a novel species of a new genus within the family Haloferacaceae, for which the name Haloparvum sedimenti gen. nov., sp. nov. is proposed. The type strain of the type species is DYS4T (=CGMCC 1.14998T=JCM 30891T).


The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon.
Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s.c.) twice weekly for 4 weeks in a single-arm, phase 1b/2a study. Within sigmoid mucosa, global transcriptomic analyses revealed 248 modulated genes (false discovery rate<0.05) including many type I interferon (IFN)-stimulated genes. MGN1703 increased the frequencies of cells exhibiting MX1 (P=0.001) and ISG15 (P=0.014) protein expression. No changes were observed in neutrophil infiltration (myeloperoxidase; P=0.97). No systematic effect on fecal microbiota structure was observed (analysis of similarity Global R=-0.105; P=0.929). TLR9 expression at baseline was inversely proportional to the change in integrated HIV DNA during MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.


Choosing a negative pressure ventilation pump: are there any important differences?
Five negative pressure ventilator pumps were assessed to determine whether there were any differences in performance which were likely to be of clinical importance. The pumps tested were the NEV-100 (Lifecare Inc.), the Negavent Respirator DA-1 (Dima Italia), the Thompson Maxivent (Puritan Bennett), the CCP-001 and Newmarket pumps (Si-Plan Electronics Research Ltd). A patient model was employed to investigate the relationship between the pressure waveform of each pump and the tidal volume generated, the stability of performance on a continuous 8 h test, and the response to a change in leak. On the continuous tests, the stability was better than +/- 1% for the inspiratory/expiratory (I:E) ratio and rate, and better than +/- 10% for the peak negative pressure for all of the pumps. The Negavent and NEV-100 pumps generated a square wave of pressure and for the same peak negative pressure produced a tidal volume up to 30% greater than the CCP-001 and the Newmarket pumps, which produced a half sine wave. The Maxivent produced an intermediate waveform, with a plateau at peak negative pressure but a curved decay back to atmospheric pressure. It is argued that if the pressure of the pumps producing a half sine wave is made more negative to compensate and produce an equivalent tidal volume, they are more likely to induce upper airway obstruction. The leak compensation of the NEV-100 and Negavent pumps was nearly complete but took several breaths to develop, the CCP-001 and Newmarket pumps had a very rapid compensation but this was less complete, whilst the Maxivent has no mechanism for leak compensation. From these results, it seems that in patients liable to upper airway obstruction the NEV-100 and Negavent pumps would be advantageous, whilst when rapidly changing leaks impair the efficiency of negative pressure ventilation the CCP-001 and Newmarket pumps would be preferable. The Maxivent pump seems to offer no advantages.


Using Danish national registry data to understand psychopathology following potentially traumatic experiences.
Research on posttraumatic psychopathology has focused primarily on posttraumatic stress disorder (PTSD); other posttraumatic psychiatric diagnoses are less well documented. The present study aimed to (a) develop a methodology to derive a cohort of individuals who experienced potentially traumatic events (PTEs) from registry-based data and (b) examine the risk of psychopathology within 5 years of experiencing a PTE. Using data from Danish national registries, we created a cohort of individuals with no age restrictions (range: 0-108 years) who experienced at least one of eight possible PTEs between 1994 and 2016 (N = 1,406,637). We calculated the 5-year incidence of nine categories of ICD-10 psychiatric disorders among this cohort and examined standardized morbidity ratios (SMRs) comparing the incidence of psychopathology in this group to the incidence in a nontraumatic stressor cohort (i.e., nonsuicide death of a relative; n = 423,270). Stress disorders (2.5%), substance use disorders (4.1%), and depressive disorders (3.0%) were the most common diagnoses following PTEs. Overall, the SMRs for the associations between any PTE and psychopathology varied from 1.9, 95% CI [1.9, 2.0], for stress disorders to 5.2, 95% CI [5.1. 5.3], for personality disorders. All PTEs except pregnancy-related trauma were associated with all forms of psychopathology. Associations were consistent regardless of whether a stress disorder was present. Traumatic experiences have a broad impact on psychiatric health. The present findings demonstrate one approach to capturing trauma exposure in medical record registry data. Increased traumatic experience characterization across studies will help improve the field's understanding of posttraumatic psychopathology.


Brucella spp. at the Wildlife-Livestock Interface: An Evolutionary Trajectory through a Livestock-to-Wildlife "Host Jump"?
Brucella infections in wildlife have gained a lot of interest from the scientific community and different stakeholders. These interests are often different and sometimes conflicting. As a result, different management perspectives and aims have been implemented (One Health, public health, veterinary public health, maintenance of a brucellosis free status in livestock, sustainable wildlife harvesting by hunters, wildlife and environmental health). When addressing Brucella infection in wildlife, the most important features of Brucella infection should be considered and the following questions need to be answered: (1) Is Brucella infection a result of a spillover from livestock or is it a sustainable infection in one or more wildlife host species? (2) Did the epidemiological situation of Brucella infection in wildlife change over time and, if so, what are the main drivers of change and does it impact the wildlife population dynamics? (3) Does Brucella infection in wildlife represent a reservoir of Brucella strains for livestock? (4) Is Brucella infection in wildlife of zoonotic concern? These questions point to the fundamental biological question of how animal (domestic and wildlife)/Brucella spp. partnerships are established. Will we be able to decipher an evolutionary trajectory through a livestock-to-wildlife "host jump"? Whole genome sequencing and new "omics" techniques will help in deciphering the molecular basis of Brucella host preference and open new avenues in brucellosis management aimed at preventing opportunities for Brucella host jumps.


Conductivity Behaviour under Pressure of Copper Micro-Additive/Polyurethane Composites (Experiment and Modelling).
In this study, micro-size copper particles (less than 25 μm) were incorporated into polyurethane (PU) using a solution mixing method and spin-coating technique to fabricate composite films in concentrations from 0.5 to 20 vol.%. The conductivity behaviour of these composites under pressure was studied experimentally and numerically. The conductivity measurements were performed in-plane and through-thickness under pressure. It was found that changes in conductivity only occurred in the z-direction under an applied pressure from 1 to 20 kPa. The results showed that pressure could induce conductivity up to about 7.2 × 10-1 S∙m-1 for composites with a Cu concentration higher than 2.6 vol.%. It seems that applied pressure reduced the thickness of the polymer film, decreasing the distance between copper particles and promoting the formation of a conductive network, thus making the material conductive. A semi-analytical model that can accurately provide the percolation threshold (PT) concentration was used to fit the experimental conductivity. The PT concentrations for PU-Cu composite ranged from 7.1 vol.% to 1.4 vol.% and decreased with the rise in pressure. This is known as a pressure-induced percolation transition phenomenon (PIPT). Finally, the finite element method based on the representative volume element model (FE-RVE) simulation technique was used to predict the conductivity behaviour. This numerical simulation provided a good description of the experimental conductivity after the PT and correctly predicted the PT concentration. This study shows that FE-RVE could be used to effectively simulate the influence of pressure on the electrical properties of a polymer-metal composite, reducing the need for costly and time-consuming experiments.


Mechanism of leptin removal from the circulation by the kidney.
This study was performed to test the hypothesis that the kidneys play a primary role in the clearance of endogenous leptin from the circulation. Lean male Sprague-Dawley rats were anesthetized and subjected to various surgical manipulations of the kidneys. Sixty minutes after surgery arterial blood samples were taken at 1-h intervals for up to 8 h. Plasma leptin levels were determined by radioimmunoassay. Bilateral nephrectomy induced a rapid increase in plasma leptin concentrations above control values, indicating that the kidneys are important for the elimination of leptin from the circulation. Leptin was not metabolized across the renal circulation and was extracted intact by the kidney. Simultaneous measurement of renal plasma flow established renal leptin extraction at approximately 6.5 ng/min for both kidneys. Compared with the quantities extracted from the plasma, leptin was only present in the urine in small quantities, indicating extensive metabolic degradation in the renal tubules. High plasma leptin levels were not maintained after binephrectomy indicating that pathways other than the kidneys are also responsible for leptin clearance. Seven hours after bilateral ureteral ligation, a procedure which lowers glomerular filtration, plasma leptin levels were slightly elevated. The renal extraction of leptin did not change over a wide range of plasma leptin concentrations suggesting that renal leptin extraction is a high capacity, non-saturable process most probably glomerular filtration. Endogenous leptin is rapidly cleared from the circulation by glomerular filtration followed by metabolic degradation in the renal tubules.


The oncofetal protein IMP3: a novel grading tool and predictor of poor clinical outcome in human gliomas.
Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas.


Flexoelectric effect in the reversal of self-polarization and associated changes in the electronic functional properties of BiFeO(3) thin films.
Flexoelectricity can play an important role in the reversal of the self-polarization direction in epitaxial BiFeO3 thin films. The flexoelectric and interfacial effects compete with each other to determine the self-polarization state. In Region I, the self-polarization is downward because the interfacial effect is more dominant than the flexoelectric effect. In Region II, the self-polarization is upward, because the flexoelectric effect becomes more dominant than the interfacial effect.


Motor control of rhythmic dance from a dynamical systems perspective: a review.
While dancers and dance educators express great interest in motor control as it relates to rhythmic dance, the subject remains largely uninvestigated. In order to advance our understanding of motor control, a theoretical framework called the dynamical systems approach (DSA) has been used. The DSA was originally developed to describe mathematically the principle of synchronization patterns in nature and their change over time. In recent decades, researchers studying human motor control have attempted to describe the synchronization of rhythmic movement using a DSA. More recently, this approach has been applied specifically to rhythmic dance movements. A series of studies that used the DSA revealed that when people synchronize rhythmic movement of a body part 1. with a different body part, 2. with other people's movement, or 3. with an auditory beat with some phase differences, unintentional and autonomous entrainment to a specific synchronization pattern occurs. However, through practice dancers are able to overcome such entrainment and dance freely. These findings provide practical suggestions for effective ways of training in dance education. The DSA can potentially be an effective tool for furthering our understanding of the motor control utilized in rhythmic dance.


Impact of Oncology Pharmacists on the Knowledge, Attitude, and Practices of Clinicians to Enhance Patient Engagement of Self-Administered Oral Oncolytics.
Oncology clinical pharmacists are uniquely positioned to make interventions to impact the knowledge, attitudes, and practices of clinicians as well as patient activation and engagement. To accomplish this goal, pharmacists can target health system-related, provider-related, and patient-related factors to enhance patient-centered care and drive behavioral health changes. Interventions that pharmacists must tackle include educating team members and patients on the medication acquisition process, communicating urgency of treatment, optimizing workflows, facilitating guideline recommendations, preventing, and managing treatment toxicities, and promoting patient self-advocacy through education and shared decision-making. As crucial members of the healthcare team, oncology pharmacists can simplify highly complex treatment regimens to facilitate and optimize patients' ownership of their care. This narrative review will focus on the example of venetoclax treatment in acute myeloid leukemia to demonstrate the impact that pharmacists provide that leads to behavioral change of patients and clinicians.


Pancreatic ductal adenocarcinoma: prevalence and diagnostic value of dark choledochal ring sign on T2-weighted MRI.
To investigate the dark choledochal ring sign on T2-weighted imaging (T2WI) as an indicator for pancreatic ductal adenocarcinoma (PDAC) among periampullary carcinomas. Sixty patients with surgically confirmed periampullary cancers [30 PDACs, 15 distal common bile duct (CBD) cancers, 13 ampullary cancers, and two duodenal cancers] who underwent liver magnetic resonance imaging (MRI) were included in this study. Two reviewers independently evaluated unenhanced and gadoxetic acid-enhanced MRI (T1WI image set), and a combined T2WI and T1WI image set for differentiation between PDAC and other periampullary carcinomas using a rating scale, and the presence of the dark choledochal ring sign on T2WI, for all 60 tumours. In PDAC, the dark choledochal ring sign on T2WI was considered positive in 23 cases by observer 1 and 24 cases by observer 2, but only in one or two CBD cancers, as determined by each observer, respectively. This resulted in sensitivities of 76.7% and 80% and specificities of 96.7% and 93.3% for observer 1 and 2, respectively, in the diagnosis of PDAC. Adding T2WI correctly led to a change of diagnosis in three and four cases of PDAC by each observer, respectively. Thus, there were significant differences between the two image sets for both observers in distinguishing between PDAC and other periampullary carcinomas (p = 0.02). The presence of the dark choledochal ring sign on axial T2WI could be a complementary imaging feature indicative of PDAC to differentiate PDAC from other periampullary carcinomas at MRI.


Interventions to facilitate return to work in adults with adjustment disorders.
Adjustment disorders are a frequent cause of sick leave and various interventions have been developed to expedite the return to work (RTW) of individuals on sick leave due to adjustment disorders. To assess the effects of interventions facilitating RTW for workers with acute or chronic adjustment disorders. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to October 2011; the Cochrane Central Register of Controlled Trials (CENTRAL) to Issue 4, 2011; MEDLINE, EMBASE, PsycINFO and ISI Web of Science, all years to February 2011; the WHO trials portal (ICTRP) and ClinicalTrials.gov in March 2011. We also screened reference lists of included studies and relevant reviews. We selected randomised controlled trials (RCTs) evaluating the effectiveness of interventions to facilitate RTW of workers with adjustment disorders compared to no or other treatment. Eligible interventions were pharmacological interventions, psychological interventions (such as cognitive behavioural therapy (CBT) and problem solving therapy), relaxation techniques, exercise programmes, employee assistance programmes or combinations of these interventions. The primary outcomes were time to partial and time to full RTW, and secondary outcomes were severity of symptoms of adjustment disorder, work functioning, generic functional status (i.e. the overall functional capabilities of an individual, such as physical functioning, social function, general mental health) and quality of life. Two authors independently selected studies, assessed risk of bias and extracted data. We pooled studies that we deemed sufficiently clinically homogeneous in different comparison groups, and assessed the overall quality of the evidence using the GRADE approach. We included nine studies reporting on 10 psychological interventions and one combined intervention. The studies included 1546 participants. No RCTs were found of pharmacological interventions, exercise programmes or employee assistance programmes. We assessed seven studies as having low risk of bias and the studies that were pooled together were comparable. For those who received no treatment, compared with CBT, the assumed time to partial and full RTW was 88 and 252 days respectively. Based on two studies with a total of 159 participants, moderate-quality evidence showed that CBT had similar results for time (measured in days) until partial RTW compared to no treatment at one-year follow-up (mean difference (MD) -8.78, 95% confidence interval (CI) -23.26 to 5.71). We found low-quality evidence of similar results for CBT and no treatment on the reduction of days until full RTW at one-year follow-up (MD -35.73, 95% CI -113.15 to 41.69) (one study with 105 participants included in the analysis). Based on moderate-quality evidence, problem solving therapy (PST) significantly reduced time until partial RTW at one-year follow-up compared to non-guideline based care (MD -17.00, 95% CI -26.48 to -7.52) (one study with 192 participants clustered among 33 treatment providers included in the analysis), but we found moderate-quality evidence of no significant effect on reducing days until full RTW at one-year follow-up (MD -17.73, 95% CI -37.35 to 1.90) (two studies with 342 participants included in the analysis). We found moderate-quality evidence that CBT did not significantly reduce time until partial RTW and low-quality evidence that it did not significantly reduce time to full RTW compared with no treatment. Moderate-quality evidence showed that PST significantly enhanced partial RTW at one-year follow-up compared to non-guideline based care but did not significantly enhance time to full RTW at one-year follow-up. An important limitation was the small number of studies included in the meta-analyses and the small number of participants, which lowered the power of the analyses.


Genome-wide association study identifies a major gene for beech bark disease resistance in American beech (Fagus grandifolia Ehrh.).
The American Beech tree (Fagus grandifolia Ehrh.), native to eastern North America, is ecologically important and provides high quality wood products. This species is susceptible to beech bark disease (BBD) and is facing high rates of mortality in North America. The disease occurs from an interaction between the woolly beech scale insect (Cryptococcus fagisuga), one of two species of the fungus Neonectria (N. faginata or N. ditissima), and American Beech trees. In this case-control genome-wide association study (GWAS), we tested 16 K high quality SNPs using the Affymetrix Axiom 1.5 K - 50 K assay to genotype an association population of 514 individuals. We also conducted linkage analysis in a full-sib family of 115 individuals. Fisher's exact test and logistic regression tests were performed to test associations between SNPs and phenotypes. Association tests revealed four highly significant SNPs on chromosome (Chr) 5 for a single gene (Mt), which encodes a mRNA for metallothionein-like protein (metal ion binding) in Fagus sylvatica. Metallothioneins represent Cys-rich metal chelators able to coordinate metal atoms and may play an important role in the resistance mechanisms against beech scale insect. The GWAS study has identified a single locus of major effect contributing to beech bark disease resistance. Knowledge of this genetic locus contributing to resistance might be used in applied breeding, conservation and restoration programs.


Estimating the global costs of vitamin A capsule supplementation: a review of the literature.
Vitamin A supplementation reduces child mortality. It is estimated that 500 million vitamin A capsules are distributed annually. Policy recommendations have assumed that the supplementation programs offer a proven technology at a relatively low cost of around US$0.10 per capsule. To review data on costs of vitamin A supplementation to analyze the key factors that determine program costs, and to attempt to model these costs as a function of per capita income figures. Using data from detailed cost studies in seven countries, this study generated comparable cost categories for analysis, and then used the correlation between national incomes and wage rates to postulate a simple model where costs of vitamin A supplementation are regressed on per capita incomes. Costs vary substantially by country and depend principally on the cost of labor, which is highly correlated with per capita income. Two other factors driving costs are whether the program is implemented in conjunction with other health programs, such as National Immunization Days (which lowers costs), and coverage in rural areas (which increases costs). Labor accounts for 70% of total costs, both for paid staff and for volunteers, while the capsules account for less than 5%. Marketing, training, and administration account for the remaining 25%. Total costs are lowest (roughly US$0.50 per capsule) in Africa, where wages and incomes are lowest, US$1 in developing countries in Asia, and US$1.50 in Latin America. Overall, this study derives a much higher global estimate of costs of around US$1 per capsule.


Tracheal Replacement Therapy with a Stem Cell-Seeded Graft: Lessons from Compassionate Use Application of a GMP-Compliant Tissue-Engineered Medicine.
Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use of tissue-engineered tracheae in compassionate use cases suggests that such an approach is a viable option. Here, a stem cell-seeded, decellularized tissue-engineered tracheal graft was used on a compassionate basis for a girl with critical tracheal stenosis after conventional reconstructive techniques failed. The graft represents the first cell-seeded tracheal graft manufactured to full good manufacturing practice (GMP) standards. We report important preclinical and clinical data from the case, which ended in the death of the recipient. Early results were encouraging, but an acute event, hypothesized to be an intrathoracic bleed, caused sudden airway obstruction 3 weeks post-transplantation, resulting in her death. We detail the clinical events and identify areas of priority to improve future grafts. In particular, we advocate the use of stents during the first few months post-implantation. The negative outcome of this case highlights the inherent difficulties in clinical translation where preclinical in vivo models cannot replicate complex clinical scenarios that are encountered. The practical difficulties in delivering GMP grafts underscore the need to refine protocols for phase I clinical trials. Stem Cells Translational Medicine 2017;6:1458-1464.


Biology of Cerotoma arcuatus (Coleoptera: Chrysomelidae) and field validation of a laboratory model for temperature requirements.
Cerotoma arcuatus Olivier is a polyphagous pest of legumes [soybean, Glycine max (L.); dry beans, Phaseolus vulgaris (L.); and cowpeas, Vigna unguiculata (L.)], all of which are considered important protein sources for humans and domestic animals. Studies on the biology and temperature requirements of C. arcuatus were made under laboratory and field (cage) conditions. In the laboratory, insects were reared on soybean plants in incubators held at 18, 20, 22, 25, 28, 30, or 32 degrees C, 70 +/- 10% RH, and a photoperiod of 14:10 (L:D) h. A degree-days (DD) model developed based on the incubator data were validated in the field based on air and soil temperatures. The duration of the egg, larva-to-adult, and egg-to-adult period was inversely correlated with the temperature within the range of 18-32 degrees C, with the highest viability found from 20 to 30 degrees C. The temperature threshold for development and the thermal constant for the egg phase and the larva-to-adult periods were 13.6 degrees C and 106.7 DD, 8.3 degrees C and 399.4 DD, and 10.7 degrees C and 489.0 DD, respectively. The DD model for the egg-to-adult period, calculated using constant temperatures in the laboratory, was found to be valid for populations of C. arcuatus in the field, based on the fluctuating air and soil temperatures, although air temperatures provided more precise predictions. These data provide support for the rational control of this pest through population predictions based on their temperature requirements.


[Mode of epithelium-fibroblast interaction in mixed heterotypic cell cultures].
The interaction between epithelium (dog kidney epithelium MDCJ/clone 20) and fibroblasts (diploid human fibroblasts M19 and AG-1523) was studied in mixed heterotypic cell cultures. The mode of cell interaction depends on the manner of their collision. At collision of the epithelium lamella and the lateral side of fibroblast, the lamella was seen to creep under the lateral side to force back the fibroblast. At the frontal collision of epithelium and fibroblast lamellae, the mode of interaction depends on the local situation. With the presence of a free substratum around, the fibroblast formed a new lamella and moved aside from the place of collision. In the case, when the neighboring cells prevented fibroblast from moving, it migrated under the epithelium. In this work, we have first demonstrated the formation of specialized intercellular adhesions between epithelium and fibroblasts. The cultures were studied by phase contrast, interference reflection or video tape recording, using an image processing system (Hamamatsu). For studying adhesion, immuno-fluorescent methods were performed.


Reducing Risks Associated With Negative-Pressure Wound Therapy: Strategies for Clinical Practice.
Negative-pressure wound therapy represents a relatively new strategy for wound management. Significant, life-threatening complications (bleeding, infection, and retained dressing material) have been associated with negative-pressure wound therapy. As a result, the Food and Drug Administration published several warnings to negative-pressure wound therapy users and recommended that clinicians ordering, managing, and/or monitoring negative-pressure wound therapy be aware of the potential complications and be prepared to take prompt action to reduce patients' risk for harm. This article reviews and organizes published consensus, expert opinion, research, and manufacturer guidelines about patient safety during negative-pressure wound therapy relevant to nurses practicing in acute and critical care settings, including in advanced practice roles.


Biochemical and structural studies of Mycobacterium smegmatis MutT1, a sanitization enzyme with unusual modes of association.
Mycobacterium smegmatis MutT1, which is made up of a Nudix domain (domain 1) and a histidine phosphatase domain (domain 2), efficiently hydrolyses 8-oxo-GTP and 8-oxo-dGTP to the corresponding nucleoside diphosphates and phosphate in the presence of magnesium ions. Domain 1 alone hydrolyses nucleoside triphosphates less efficiently. Under high concentrations and over long periods, the full-length enzyme as well as domain 1 catalyses the hydrolysis of the nucleoside triphosphates to the respective nucleoside monophosphates and pyrophosphate. The role of domain 2 appears to be limited to speeding up the reaction. Crystal structures of the apoenzyme and those of ligand-bound enzyme prepared in the presence of 8-oxo-GTP or 8-oxo-dGTP and different concentrations of magnesium were determined. In all of the structures except one, the molecules arrange themselves in a head-to-tail fashion in which domain 1 is brought into contact with domain 2 (trans domain 2) of a neighbouring molecule. The binding site for NTP (site A) is almost exclusively made up of residues from domain 1, while those for NDP (site B) and NMP (site C) are at the interface between domain 1 and trans domain 2 in an unusual instance of intermolecular interactions leading to binding sites. Protein-ligand interactions at site A lead to a proposal for the mechanism of hydrolysis of NTP to NDP and phosphate. A small modification in site A in the crystal which does not exhibit the head-to-tail arrangement appears to facilitate the production of NMP and pyrophosphate from NTP. The two arrangements could be in dynamic equilibrium in the cellular milieu.


Enhancing human cord blood hematopoietic stem cell engraftment by targeting nuclear hormone receptors.
Allogeneic hematopoietic cell transplantation (HCT) is a life-saving therapy for hematological and nonhematological diseases. Cord blood is a source of transplantable hematopoietic stem cells (HSCs), but limited numbers of HSCs in single cord blood units, which may cause delayed neutrophil, platelet, and immune cell reconstitution, is a major problem for efficient transplantation. Ex-vivo expansion and enhanced homing of cord blood HSC may overcome this disadvantage and improve its long-term engraftment. Here, we discuss the role of nuclear hormone receptors signaling in human cord blood HSC engraftment. Antagonizing retinoid acid receptor (RAR) signaling promotes human HSC expansion and increases myeloid cell production. Cord blood CD34 cells expanded by SR1 promotes efficient myeloid recovery after transplantation compared with control groups, and leads to successful engraftment. Short-term treatment of glucocorticoids enhances homing and long-term engraftment of human HSCs and HPCs in NSG mice. Peroxisome proliferator-activated receptor-γ (PPARγ) antagonism expands human HSCs and HPCs by preventing differentiation and enhancing glucose metabolism. These findings demonstrate that nuclear hormone receptor signaling components might be promising targets for improving human cord blood HCT. Better understanding of molecular mechanisms underlying human HSC expansion and homing mediated by nuclear hormone receptor signaling pathways will facilitate enhanced HCT efficacy.


Significance of hanging total spine x-ray to estimate the indicative correction angle by brace wearing in idiopathic scoliosis patients.
Although most idiopathic scoliosis patients subject to conservative treatment in daily clinical practice, there have been no ideal methods to evaluate the spinal flexibility for the patients who are scheduled the brace treatment. The purpose of this study was to investigate the value of hanging total spine x-ray to estimate the indicative correction angle by brace wearing in idiopathic scoliosis patients. One hundred seventy-six consecutive patients with idiopathic scoliosis who were newly prescribed the Osaka Medical College (OMC) brace were studied. The study included 14 boys and 162 girls with a mean age of 13 years and 1 month. The type of curves consisted of 62 thoracic, 23 thoracolumbar, 22 lumbar, 42 double major, 14 double thoracic, and 13 triple curve pattern. We compared the Cobb angles on initial brace wearing (BA) and in hanging position (HA). Of those, 108 patients who had main thoracic curves were selected and evaluated the corrective ability of OMC brace. These subjects were divided into three groups according to the relation between BA and HA (BA < HA group, BA = HA group, and BA > HA group), and then, maturity was compared among them. The average Cobb angle in upright position (UA) of all cases was 31.0 ± 7.8°. The average BA and HA of all cases were 20.3 ± 9.5° and 21.1 ± 8.4°, respectively. The average chronological age was lowest in BA < HA group. And also, maturity in BA < HA group was the lowest among each of them. The rate of BA < HA cases were decreased as the Risser stage of the patients were progressed. The use of hanging total spine x-ray served as a useful tool to estimate the degree of correction possible curve within the OMC brace for main thoracic curve in idiopathic scoliosis. Maturity had some influence on the correlation between HA and BA. Namely, in immature patients, HA tended to be larger than BA. In contrast, in mature patients, HA had a tendency to be smaller than BA. With consideration for spinal flexibility based on maturity, in mature patients, larger BA than HA may be allowed. However, in immature patients, smaller BA than HA should be aimed.


Collection of cancer Patient Reported Outcome Measures (PROMS) to link with primary and secondary electronic care records to understand and improve long term cancer outcomes: A protocol paper.
More people are living with and beyond a cancer diagnosis. There is limited understanding of the long-term effects of cancer and cancer treatment on quality of life and personal and household finances when compared to people without cancer. In a separate protocol we have proposed to link de-identified data from electronic primary care and hospital records for a large population of cancer survivors and matched controls. In this current protocol, we propose the linkage of Patient Reported Outcomes Measures data to the above data for a subset of this population. The aim of this study is to investigate the full impact of living with and beyond a cancer diagnosis compared to age and gender matched controls. A secondary aim is to test the feasibility of the collection of Patient Reported Outcomes Measures (PROMS) data and the linkage procedures of the PROMs data to electronic health records data. This is a cross-sectional study, aiming to recruit participants treated at the Leeds Teaching Hospitals National Health Service Trust. Eligible patients will be cancer survivors at around 5 years post-diagnosis (breast, colorectal and ovarian cancer) and non-cancer patient matched controls attending dermatology out-patient clinics. They will be identified by running a query on the Leeds Teaching Hospitals Trust patient records system. Approximately 6000 patients (2000 cases and 4000 controls) will be invited to participate via post. Participants will be invited to complete PROMs assessing factors such as quality of life and finances, which can be completed on paper or online (surveys includes established instruments, and bespoke instruments (demographics, financial costs). This PROMs data will then be linked to routinely collected de-identified data from patient's electronic primary care and hospital records. This innovative work aims to create a truly 'comprehensive patient record' to provide a broad picture of what happens to cancer patients across their cancer pathway, and the long-term impact of cancer treatment. Comparisons can be made between the cases and controls, to identify the aspects of life that has had the greatest impact following a cancer diagnosis. The feasibility of linking PROMs data to electronic health records can also be assessed. This work can inform future support offered to people living with and beyond a cancer diagnosis, clinical practice, and future research methodologies.


Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy.
We describe a method of obtaining optical sectioning with a standard wide-field fluorescence microscope. The method involves acquiring two images, one with nonuniform illumination (in our case, speckle) and another with uniform illumination (in our case, randomized speckle). An evaluation of the local contrast in the speckle-illumination image provides an optically sectioned image with low resolution. This is complemented with high-resolution information obtained from the uniform-illumination image. A fusion of both images leads to a full resolution image that is optically sectioned across all spatial frequencies. This hybrid illumination method is fast, robust, and generalizable to a variety of illumination and imaging configurations.


Space-related bone mineral redistribution and lack of bone mass recovery after reambulation in young rats.
This study reports the effects of a 14-day spaceflight followed by a 14-day reambulation period on bones of 56-day-old male rats compared with synchronous (S) and vivarium (V) control animals. Femur, tibia, and humerus bone mineral densities (BMD); bone calcium and phosphorus concentrations ([Ca2+] and [P]), measured by X-ray microanalysis (XRM), on tibia, vertebra, and calvaria; and histomorphometric data on proximal primary and secondary spongiosae (I and II SP, respectively) of the tibia and humerus were measured. After the flight in flown rats (compared with S), BMD was lower in the distal femur and remained similar to S in humerus and tibia, [Ca2+] and [P] were lower in tibia II SP and higher in calvaria, tibia I SP width and II SP bone volume were lower, resorption was markedly higher in tibia II SP, and no difference in formation parameters was observed. After reambulation, BMD was lower in long bones of both flight and S groups compared with V. Bone loss appeared in humeral II SP and worsened in tibial II SP in flown rats. Tibial formation parameters were higher in flown rats compared with V and S, indicating the onset of an active recovery. Tibial XRM [Ca2+] and [P] in flown rats remained below control levels.


Oesophageal eosinophilia in children with coeliac disease.
An association between coeliac disease (CD) and eosinophilic oesophagitis (EoE)/oesophageal eosinophilia (EE) has been suggested. We sought to characterise children with CD+EE in-depth and assess the contribution of each condition to the clinical presentation and treatment response. Medical records of children with both CD+EE, or isolated EoE diagnosed between 2000 and 2014, were retrospectively reviewed and compared with patients with isolated CD or epigastric pain. Frequency of EE was calculated from endoscopy results of patients with suspected CD or epigastric pain between 2011 and 2014. Missing data were obtained via a telephone questionnaire. Single large, tertiary paediatric centre. 17 CD+EE, 46 EoE, 302 isolated CD and 247 epigastric pain. The patients with CD+EE shared characteristics of both individual conditions. While age at diagnosis, family history of autoimmunity/CD and anaemia were similar to patients with CD, other characteristics such as male gender, personal/family history of atopy, peripheral eosinophilia and oesophageal white papules were more similar to patients with EoE. Combined patients (CD+EE) tended to present with CD-associated symptoms; the majority (63%) later developed typical EoE symptoms. Only a minority (21%) of combined patients had EE that resolved after a gluten-free diet; another 21% had normalisation of EE upon proton pump inhibitor treatment. The remainder required EoE-specific treatment. Patients with CD found to have EE share characteristics with both isolated CD and EoE. It appears that these are two coexisting entities presenting in the same patient rather than eosinophilia associated with CD, and therefore, interventions separately addressing each condition may be considered.


Cauda equina syndrome and dural ectasia: rare manifestations in chronic ankylosing spondylitis.
Cauda equina syndrome (CES) is a rare manifestation in patients with long-standing ankylosing spondylitis (AS). We report a 57-year-old male patient with a 30-year history of AS who developed CES in the past 4 years. The CT and MRI examinations showed unique appearances of dural ectasia, multiple dorsal dural diverticula, erosion of the vertebral posterior elements, tethering of the conus medullaris to the dorsal aspect of the spinal canal and adhesion of the nerve roots of the cauda equina to the wall of the dural sac. A large dural defect was found at surgery. De-adhesion of the tethered conus medullaris was performed but without significant clinical improvement. The possible aetiologies of CES and dural ectasia in patients with chronic AS are discussed and the literature is reviewed.


Nuclear architecture remodelling in cardiomyocytes with lamin A deficiency.
We analysed the architecture of cardiomyocyte nuclei lacking lamin A activity in three patients with dilated cardiomyopathy. The diagnosis was established on the basis of clinical and electrophysiological examinations, chest radiography and electrocardiography. An ultrastructural study of affected cardiomyocytes showed dramatic alterations in nuclear distribution and organization affecting nuclear shape, lamina structure, chromatin and nuclear interior organization. The most specific hallmark of nuclei with lamin A deficiency was the reorganization of the nuclear interior, the appearance of a various number of mitochondria within the nuclear matrix, and focal or total lack of nuclear membrane.


What is a "Good Life": Protocol for a qualitative study to explore the viewpoint of older persons.
Over the last fifteen years, Living Labs have been on the rise in Europe to bridge the gap between service providers, and the needs of end-users, and to speed up innovation, particularly in the field of healthcare and ageing. Ageing tends to be considered by institutions as a set of risks to be managed for older persons, illustrated in particular via the concepts of "ageing well" or "successful ageing". In this context, this project aims to define the meaning and the conditions for a good life from the point of view of older persons themselves, thereby improving institutions' recognition and support of older persons' ways of living well, rather than imposing a general definition of "successful ageing" based on functional capacity. This qualitative study is designed as an action research underpinned by a Living-Lab approach to co-creation. The aims are to: define the conditions for a good life as accurately as possible with older persons (Step 1); share these findings with different healthcare and service providers to adjust existing services or create new ones (Step 2); and disseminate them more broadly within the regions under study and across the scientific community (Step 3). During Step 1, the features of a "good life" will be analysed in a socio-anthropological study based on semi-directed interviews and observations made in the homes of 70 elderly people living in a wide range of accommodation types and regions. In accordance with French legislation, and as confirmed by our formal Ethics Committee, this study does not require approval. The dissemination stage is integrated into the design of this action research, and notably will provide for the appropriation of research findings by the partners of this study, by setting up creativity sessions (Step 2) and by sharing the general findings through panel discussions bringing together regional and national stakeholders (Step 3).


Lineage diversification of fringe-toed lizards (Phrynosomatidae: Uma notata complex) in the Colorado Desert: Delimiting species in the presence of gene flow.
Multi-locus nuclear DNA data were used to delimit species of fringe-toed lizards of the Uma notata complex, which are specialized for living in wind-blown sand habitats in the deserts of southwestern North America, and to infer whether Quaternary glacial cycles or Tertiary geological events were important in shaping the historical biogeography of this group. We analyzed ten nuclear loci collected using Sanger sequencing and genome-wide sequence/single-nucleotide polymorphism (SNP) data collected using restriction-associated DNA (RAD) sequencing. A combination of species discovery methods (concatenated phylogenies, parametric and non-parametric clustering algorithms) and species validation approaches (coalescent-based species tree/isolation-with-migration models) were used to delimit species, infer phylogenetic relationships, and to estimate effective population sizes, migration rates, and speciation times. Uma notata, U. inornata, U. cowlesi, and an undescribed species from Mohawk Dunes, Arizona (U. sp.) were supported as distinct in the concatenated analyses and by clustering algorithms, and all operational taxonomic units were decisively supported as distinct species by ranking hierarchical nested speciation models with Bayes factors based on coalescent-based species tree methods. However, significant unidirectional gene flow (2NM>1) from U. cowlesi and U. notata into U. rufopunctata was detected under the isolation-with-migration model. Therefore, we conservatively delimit four species-level lineages within this complex (U. inornata, U. notata, U. cowlesi, and U. sp.), treating U. rufopunctata as a hybrid population (U. notata×cowlesi). Both concatenated and coalescent-based estimates of speciation times support the hypotheses that speciation within the complex occurred during the late Pleistocene, and that the geological evolution of the Colorado River delta during this period was an important process shaping the observed phylogeographic patterns.


Association between functional Fc receptor-like 3 (FCRL3) -169 C/T polymorphism and susceptibility to seropositive rheumatoid arthritis in Asians: a meta-analysis.
The aim of this study was to determine whether the functional Fc receptor like-3 (FCRL3) -169 C/T polymorphism confers susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the FCRL3 -169 C/T polymorphism and RA. A total of 17 comparison studies including 11,170 patients and 11,142 controls were considered in the meta-analysis. The meta-analysis showed no association between RA and the FCRL3 -169 C allele in study subjects (OR = 1.046, 95% CI = 0.997-1.098, p = 0.068). Stratification by ethnicity indicated an association between the FCRL3 -169 C allele and RA in Asians (OR = 1.101, 95% CI = 1.035-1.174, p = 0.002), but not in Europeans. Stratification of patients according to the presence of rheumatoid factor (RF) revealed a different significant association between the C allele and RA in RF-positive and RF-negative RA patients. Stratification by ethnicity indicated an association between the FCRL3 -169 C allele and RF-positive RA in Asians (OR = 1.093, 95% CI = 1.004-1.189, p = 0.040), but not in Europeans. This meta-analysis demonstrates that the FCRL3 -169 C/T polymorphism may confer susceptibility to seropositive RA in Asians.


Motion interference: perturbing perceived direction.
The minimum stimulus necessary to define motion is a change in position from one location to another in time, but past studies have provided evidence that the human motion system integrates motion over more than two positions. In this study we demonstrate strong sequential interactions affecting perceived direction in apparent-motion sequences; a perturbing dot can bias the perceived direction of motion between two test dots to which it is relatively close in space (up to 100 min arc) and time (up to 300 msec). These sequential interactions suggest a motion mechanism sensitive to the spatial characteristics of motion trajectories; the interactions are greatest for evenly spaced targets positioned along a single axis. The implications for motion-detection models and models based on attention as a mechanism to create apparent motion are discussed.


Fast iterative image reconstruction methods for fully 3D multispectral bioluminescence tomography.
We investigate fast iterative image reconstruction methods for fully 3D multispectral bioluminescence tomography for applications in small animal imaging. Our forward model uses a diffusion approximation for optically inhomogeneous tissue, which we solve using a finite element method (FEM). We examine two approaches to incorporating the forward model into the solution of the inverse problem. In a conventional direct calculation approach one computes the full forward model by repeated solution of the FEM problem, once for each potential source location. We describe an alternative on-the-fly approach where one does not explicitly solve for the full forward model. Instead, the solution to the forward problem is included implicitly in the formulation of the inverse problem, and the FEM problem is solved at each iteration for the current image estimate. We evaluate the convergence speeds of several representative iterative algorithms. We compare the computation cost of those two approaches, concluding that the on-the-fly approach can lead to substantial reductions in total cost when combined with a rapidly converging iterative algorithm.


[Melanoma behavior according to age].
In recent years the incidence of melanoma in elderly patients has increased with an unfavorable oncologic outcome due not only to immune deterioration but also to greater aggressiveness of the tumor. The aim of this study was to evaluate the behavior of cutaneous melanoma in relation to age. A consecutive series of cases with melanoma operated in a reference center in the period 2001-2013 was included. The sample was divided into two groups according to the age. Group 1 (G1): under 65 years and Group 2 (G2): over 65 years. Histopathological variables and oncologic outcomes were compared between the two groups. Three hundred and eighty eight patients were operated. They belonged to G1 241 (62%) and to G2 147 (38%). Both groups were homogeneous with respect to the histological type of melanoma. Group 2 had thicker melanomas (Breslow > 4 mm 19% vs. 7%, p < 0.005) and higher rates of ulceration (37% vs. 20%, p: 0.007) and distant metastases (stage IV 11% vs. 3%, p 0.01). There was no difference between groups regarding nodal involvement. With a mean follow up of 45 (6-98) months throughout the series, recurrence of disease was higher in group 2 (26% vs. 17%, p: 0.03), but the specific mortality showed no significant difference (9.5% vs. 5.3%, p: 0.12). In conclusion, cutaneous melanoma in patients over 65 years is more aggressive with higher rates of local recurrence and distant metastases.


Mechanism of transient dyspnea induced by pegylated-liposomal doxorubicin (Doxil).
While mucositis and hand-foot syndrome are the main limiting toxicities of pegylated-liposomal doxorubicin, a small proportion of patients develop transient dyspnea at the initiation of drug infusion. Of the first 35 patients in a phase II study of pegylated-liposomal doxorubicin, three developed dyspnea, two low back pain and two pain at the site of tumor, within 1-5 min after starting the pegylated-liposomal doxorubicin infusion. The symptoms resolved within 5-15 min of stopping the infusion. In each case, the infusion was restarted without adverse effect. The mechanism of these symptoms is unclear. Because the dyspnea was reminiscent of that seen with hemodialysis neutropenia, complete blood counts were obtained in four of these patients approximately 2 min after the onset of symptoms. In all four patients, relative neutropenia was present (ANC 35, 3, 24 and 46% of pretreatment) that resolved by the end of the pegylated-liposomal doxorubicin infusion. Pegylated-liposomal doxorubicin stimulated neutrophil adhesion to human umbilical vein endothelial cells in vitro at concentrations predicted to be present in plasma during the initiation of treatment. Thus, pegylated-liposomal doxorubicin can induce an increase in neutrophil adhesion directly. We conclude that one mechanism of pegylated-liposomal doxorubicin-induced acute dyspnea is a transient sequestration of neutrophils in the pulmonary circulation, resulting in a decrease in compliance and associated dyspnea. In the patients in this study, these symptoms were transient, mild and not life threatening. Pegylated-liposomal doxorubicin is generally well tolerated and we do not routinely use premedications in patients receiving pegylated-liposomal doxorubicin.


Recent Insights into Nanoparticulate Carrier Systems of Curcumin and its Clinical Perspective in the Management of Various Health Issues.
Curcumin is a potent bioactive compound of Curcuma longa. Curcumin comprises a broad spectrum of biological activities, including hepatoprotective, anticancer, antimicrobial, anti-inflammatory, antitumor, anti-oxidant, etc. However, its low aqueous solubility, rapid excretion, and poor bioavailability restricted its therapeutic uses. To resolve these issues, novel nano-systems have now been developed to increase the bioactivity and bioavailability of curcumin by lowering the particle size, altering the surface, and increasing the efficacy of its encapsulation with various nanocarriers. Nanotechnology-based treatments can broaden the outlook for individuals with critical conditions. This article explores curcumin-based nanoparticulate carrier systems that should be employed to overcome this natural ingredient's inherent limitations. These nanocarriers also provide physical and chemical stability by encapsulating the drug into the core or matrix of the lipids or polymers. Nanotechnologists developed curcumin-encapsulated various nanoparticulate systems, including solid lipidic nanoparticles, polymeric nanoparticles, nano-structured lipid carriers, polymer conjugates, etc., to improve curcumin bioavailability and boost the sustained release of curcumin to target cells.


Long-term effect of perindopril on coronary atherosclerosis progression (from the perindopril's prospective effect on coronary atherosclerosis by angiography and intravascular ultrasound evaluation [PERSPECTIVE] study).
The multicenter EUROPA trial of 12,218 patients showed that perindopril decreased adverse clinical events in patients with established coronary heart disease. The PERSPECTIVE study, a substudy of the EUROPA trial, evaluated the effect of perindopril on coronary plaque progression as assessed by quantitative coronary angiography and intravascular ultrasound (IVUS). In total 244 patients (mean age 57 years, 81% men) were included. Evaluable paired quantitative coronary angiograms were obtained from 96 patients randomized to perindopril and from 98 patients to placebo. Concomitant treatment at baseline consisted of aspirin (90%), lipid-lowering agents (70%), and beta blockers (60%). The primary and secondary end point was the difference of minimum and mean lumen diameters (quantitative coronary angiography) or mean plaque cross-sectional area (IVUS) measured at baseline and 3-year follow-up between the perindopril and placebo groups. After a median follow-up of 3.0 years (range 1.9 to 4.1), no differences in change in quantitative coronary angiographic or IVUS measurements were detected between the perindopril and placebo groups (minimum and mean luminal diameters -0.07 +/- 0.4 vs -0.02 +/- 0.4 mm, p = 0.34; mean luminal diameter -0.05 +/- 0.2 vs -0.05 +/- 0.3 mm, p = 0.89; mean plaque cross-sectional area -0.18 +/- 1.2 vs -0.02 +/- 1.2 mm(2), p = 0.48). In conclusion, we found no progression in coronary artery disease by quantitative coronary angiography and IVUS with long-term administration of perindopril or placebo, possibly because most patients were on concomitant treatment with a statin.


[Digital platforms to place informal helpers for home care: what benefits do providers see?]
Little is known so far about the actual benefits of digital platforms that mediate volunteer helpers with households facing care responsibilities. This article presents the initial results of a survey conducted among placement agencies as part of a multistage organized interview study. The key question is what benefits do agencies ascribe to the services in their own organization for the users and on a societal or sociospatial level. For the purpose of conducting explorative guideline-based interviews, four placement agencies were selected. Of these, two use a matching platform and two do not. The data were analyzed using content analysis methods. The providers perceive advantages in efficiency, improvements in quality but also new possibilities for harnessing new helper clientele as important beneficial aspects of using digital placement platforms for their own organization. In terms of nurturing users' trust and acceptance, hybrid matching models appear to be particularly advantageous by deploying digital technologies and also enabling personal support in developing helping relationships. The findings also suggest that public welfare-oriented, quality-assured matching platforms can unfurl additional benefits at sociospatial and societal levels. Besides beneficial aspects for organizations and users it was also possible to reconstruct potential benefits in relation to local care networks.


Galvanic vesitbular test.
Galvanic stimulation of the vestibular system provokes a nystagmus as well as a tendency to fall. The direction of these phenomena depends on the localization of the anode. In this study the value of the minimal current strength (threshold), which is able to provoke nystagmus with a constant frequency during at least 30 sec was determined. Also the effects of the lesions in the vestibular system on these threshold values were measured. The method of bipolar-biaruricular stimulation showed to be the most sensitive one. A striking difference was found in the thresholds in rabbits with a vestibular organ with a lesion on that side. In that case the threshold for a nystagmus directed to the side with the intact ear was at its lowest. The conclusion is drawn that the galvanic vestibular test is suitable for the detection of the localization of a vestibular lesion in patients, especially when this lesion is located in the peripheral vestibular organ.


The association between acute mental stress and abnormal left atrial electrophysiology.
Acute stress may trigger atrial fibrillation (AF), but the underlying mechanisms are unclear. We examined if acute mental stress results in abnormal left atrial electrophysiology as detected by more negative deflection of P-wave terminal force in lead V1 (PTFV1 ), a well-known marker of AF risk. We examined this hypothesis in 422 patients (mean age = 56 ± 10 years; 61% men; 44% white) with stable coronary heart disease who underwent mental (speech task) stress testing. PTFV1 was defined as the duration (milliseconds) times the value of the depth (μV) of the downward deflection (terminal portion) of the P-wave in lead V1 measured on digital electrocardiograms (ECG). Electrocardiographic left atrial abnormality was defined as PTFV1 ≤ -4000 μV*ms. Mean PTFV1 values during stress and recovery were compared with rest. The percentage of participants who developed left atrial abnormality during stress and recovery was compared with the percentage at rest. Compared with rest, PTFV1 became more negative during mental stress (mean change = -348, 95% CI = [-515, -182]; P < 0.001) and no change was observed at recovery (mean change = 12, 95%CI = [-148, 172]; P = 0.89). A larger percentage of participants showed left atrial abnormality on ECGs obtained at stress (n = 163, 39%) and recovery (n = 142, 34%) compared with rest (n = 127, 30%). Acute mental stress alters left atrial electrophysiology, suggesting that stressful situations promote adverse transient electrical changes to provide the necessary substrate for AF.


Assessing Mathematical School Readiness.
Early math skills matter for later formal mathematical performances, academic and professional success. Accordingly, it is important to accurately assess mathematical school readiness (MSR) at the beginning of elementary school. This would help identifying children who are at risk of encountering difficulties in math and then stimulate their acquisition of mathematical skills as soon as possible. In the present study, we present a new test that allows professionals working with children (e.g., teachers, school psychologists, speech therapists, and school doctors) to assess children's MSR when they enter formal schooling in a simple, rapid and efficient manner. 346 children were assessed at the beginning of 1st Grade (6-to-7-year-olds) with a collective test assessing early mathematical abilities (T1). In addition, children's math skills were evaluated with classical curriculum math tests at T1 and a year later, in 2nd Grade (T2, 7-to-8-year-olds). After assessing internal consistency, three tasks were retained for the final version of the MSR test. Test performance confirmed to be essentially unidimensional and systematically related to the scores children obtained in classical tests in 1st and 2nd Grade. By using the present MSR test, it is possible to identify pupils at risk of developing low math skills right from the start of formal schooling in 1st Grade. Such a tool is needed, as children's level in math at school beginning (or school readiness) is known to be foundational for their future academic and professional carrier.


Self-compassion in depression: associations with depressive symptoms, rumination, and avoidance in depressed outpatients.
Self-compassion involves being kind to oneself when challenged with personal weaknesses or hardship and has been claimed to be associated with resilience in various areas. So far, there are only a handful of studies that investigate self-compassion and its relation to clinical depression. Therefore, the principal goals of the present study were (a) to compare self-compassion in clinically depressed patients and never-depressed subjects, (b) to investigate self-compassion and its relation to cognitive-behavioral avoidance and rumination in depressed outpatients, and (c) to investigate rumination and avoidance as mediators of the relationship between self-compassion and depressive symptoms. One hundred and forty-two depressed outpatients and 120 never-depressed individuals from a community sample completed a self-report measure of self-compassion along with other measures. Results indicate that depressed patients showed lower levels of self-compassion than never-depressed individuals, even when controlled for depressive symptoms. In depressed outpatients, self-compassion was negatively related to depressive symptoms, symptom-focused rumination, as well as cognitive and behavioral avoidance. Additionally, symptom-focused rumination and cognitive and behavioral avoidance mediated the relationship between self-compassion and depressive symptoms. These findings extend previous research on self-compassion, its relation to depression, as well as processes mediating this relationship, and highlight the importance of self-compassion in clinically depressed patients. Since depressed patients seem to have difficulties adopting a self-compassionate attitude, psychotherapists are well advised to explore and address how depressed patients treat themselves.


Peripheral insensitivity to thyroid hormones in a euthyroid girl with goitre.
A 9-year-old girl was euthyroid with a small goitre, exophthalmos, scaphocephalic skull, minor sketelal abnormalities, and raised serum thyroid hormone concentrations. Other members of the family did not have goitres and their thyroid hormone levels were normal. From age 3 years the patient was treated for Graves's disease, but after 4 years treatment was stopped because of enlargement of the goitre. Despite increased serum thyroxine (T4), free T4 (FT4), and triiodothyronine (T3), basal serum TSH, and the TSH response to thyrotropin-releasing hormone (TRH) were normal. Pituitary refractoriness was present because full suppression of the TSH response to TRH was achieved only after daily administration of 500 micrograms thyroxine. Urinary excretion of hydroxyproline, and the activity of red cell glucose-6-phosphate dehydrogenase remained normal when excess T4 was administered, demonstrating the tissue resistance to thyroid hormones. Peripheral lymphocytes were found to have nuclear receptors for T3 with normal affinity, but the relatively low binding capacity indicated that the biochemical defect might be a deficiency of nuclear receptor protein. The findings in this patient differ somewhat from previously reported cases of peripheral resistance to thyroid hormones.