Technical properties of biomass and solid recovered fuel (SRF) co-fired with coal: Impact on multi-dimensional resource recovery value.
The power plant sector is adopting the co-firing of biomass and solid recovered fuel (SRF) with coal in an effort to reduce its environmental impact and costs. Whereas this intervention contributes to reducing carbon emissions and those of other pollutants related with the burning of fossil fuel, it may also result in hidden impacts that are often overlooked. When co-firing, the physical and chemical properties of the mixed fuels and the subsequent technical implications on the process performance and by-products are significant. Interconnections between multiple values nested within four domains of value, i.e. environmental, economic, technical and social, mean that changes in the one domain (in the co-firing case, the technical one) can have considerable implications in the other domains as well. In this study, using a systematic and flexible approach to conceptualising multi-dimensional aspects associated with the co-firing of biomass and SRF with coal, we unveil examples of such interconnections and implications on overall value delivered through the use and recovery of waste resources. Such an analysis could underpin the selection of useful metrics (quantitative or semi-quantitative descriptors) for enabling a systemic multi-dimensional value assessment, and value's distribution amongst interconnected parts of resource recovery systems; key in enabling sound analysis and decision-making.


Diagnosis-related groups and general hospital psychiatry: the APA Study.
Psychiatric units in general hospitals are exempt from diagnosis-related groups (DRGs), a system of per case prospective payment that is used for the majority of patients covered by Medicare. The American Psychiatric Association purchased a large hospital discharge data base and studied the potential impact of DRGs on psychiatric patients and inpatient psychiatric units in general hospitals. There was substantial inaccuracy in the psychiatric DRGs' prediction of resource use, which could lead to inappropriate discharge of patients and financial risk to hospitals that treat more severe cases. The authors advocate further research because psychiatry must anticipate prospective payment in the future.


Pulmonary embolism as a complication of transfemoral arteriography--incidence, symptoms, and prevention.
In order to evaluate the pulmonary embolism as a complication of transfemoral arteriography, we performed lung perfusion scintigrams before and after arteriography in consecutive 120 patients. Of the initial 60 patients who did not receive subcutaneous low-dose heparin, 19 (32%) demonstrated new pulmonary perfusion defects. There was no significant difference in regard to the incidence of new defects with or without right heart catheterization. On the other hand, in the latter 60 patients who received prophylactic heparin, the incidence of new defects decreased to 10%, without increasing clinically important bleeding. We believe that the source of emboli is from the leg vein thrombosis due to compression of the groin and subsequent bed rest. These data suggest that pulmonary embolism is a more common complication of transfemoral arteriography than previously appreciated and low-dose heparin is useful in reducing this complication.


Economic analysis of investment priorities for measles control.
An investment strategy in measles control should strike an appropriate balance among three areas: implementation of existing vaccination programs with existing technology, operations research to improve the use of existing technology, and vaccine development. As a benchmark, the existing Schwarz vaccine costs approximately $17 per DALY (disability-adjusted life year), already making it one of the most cost-effective health interventions in developing countries. National measles vaccination campaigns, such as Brazil's, are a promising extension of this technology. Operations research is indicated to study the organization of campaigns, supplying and delivering vitamin A to hospitalized children, and other issues. The development and application of an early one-dose measles vaccine would be particularly cost-effective ($5 per DALY), as it could avoid the costs to families and health institutions of the separate visit at 9 months now required for measles vaccination. All three areas present opportunities for cost-effective investments and deserve a place in an investment strategy.


Functional analysis of paired box missense mutations in the PAX6 gene.
Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, we performed a functional analysis of two missense mutations in the paired domain: the R26G mutation, previously reported in a case of Peters' anomaly, and an unreported I87R mutation, which we identified in a patient with aniridia. While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA. We showed that the R26G mutant failed to bind a subset of paired domain binding sites but, surprisingly, bound other sites and successfully transactivated promoters containing those sites. In contrast, the I87R mutant had lost the ability to bind DNA at all tested sites and failed to transactivate promoters. Our data support the haploid-insufficiency hypothesis of aniridia, and the hypothesis that R26G is a hypomorphic allele.


Ocular manifestations of Sturge-Weber syndrome: pathogenesis, diagnosis, and management.
Sturge-Weber syndrome has been included in the group of phakomatoses that is characterized by hamartomas involving the brain, skin, and eyes. The characteristic facial port-wine stain, involving the first branch of the trigeminal nerve and the embryonic vasculature distribution in this area, leads to several ocular complications of the anterior segment and can involve the eyelids and conjunctiva. The posterior segment of the eyes is also affected with diffuse choroidal hemangiomas. However, the most frequent ocular comorbidity is glaucoma with a prevalence rate ranging from 30%-70%. Glaucoma is related to anterior chamber malformations, high episcleral venous pressure (EVP), and changes in ocular hemodynamics. Glaucoma can be diagnosed at birth, but the disease can also develop during childhood and in adults. The management of glaucoma in Sturge-Weber syndrome patients is particularly challenging because of early onset, frequently associated severe visual field impairment at the time of diagnosis, and unresponsiveness to standard treatment. Several surgical approaches have been proposed, but long-term prognosis for both intraocular pressure control and visual function remains unsatisfactory in these patients. Choroidal hemangiomas may also lead to visual impairment thorough exudative retinal detachment and macular edema. Treatment of exudative hemangioma complications is aimed at destructing the tumor or decreasing tumor leakage.


Cystinuria-specific rBAT(R365W) mutation reveals two translocation pathways in the amino acid transporter rBAT-b0,+AT.
Apical reabsorption of dibasic amino acids and cystine in kidney is mediated by the heteromeric amino acid antiporter rBAT/b(0,+)AT (system b(0,+)). Mutations in rBAT cause cystinuria type A, whereas mutations in b(0,+)AT cause cystinuria type B. b(0,+)AT is the catalytic subunit, whereas it is believed that rBAT helps the routing of the rBAT/b(0,+)AT heterodimeric complex to the plasma membrane. In the present study, we have functionally characterized the cystinuria-specific R365W (Arg(365)-->Trp) mutation of human rBAT, which in addition to a trafficking defect, alters functional properties of the b(0,+) transporter. In oocytes, where human rBAT interacts with the endogenous b(0,+)AT subunit to form an active transporter, the rBAT(R365W) mutation caused a defect of arginine efflux without altering arginine influx or apparent affinities for intracellular or extracellular arginine. Transport of lysine or leucine remained unaffected. In HeLa cells, functional expression of rBAT(R365W)/b(0,+)AT was observed only at the permissive temperature of 33 degrees C. Under these conditions, the mutated transporter showed 50% reduction of arginine influx and a similar decreased accumulation of dibasic amino acids. Efflux of arginine through the rBAT(R365W)/b(0,+)AT holotransporter was completely abolished. This supports a two-translocation-pathway model for antiporter b(0,+), in which the efflux pathway in the rBAT(R365W)/b(0,+)AT holotransporter is defective for arginine translocation or dissociation. This is the first direct evidence that mutations in rBAT may modify transport properties of system b(0,+).


Liver function tests during antithyroid therapy in hyperthyroidism.
To investigate the liver function tests during antithyroid treatment in the patients with hyperthyroidism. Four hundred sixty five patients with hyperthyroidism (285 Graves' disease and 180 toxic nodular/multinodular goiter) and fifty healthy subjects were included in the study. The patients who had abnormal liver function tests were excluded from the study. Blood levels of thyrotropin (TSH), free thyroxine (FT4), alanine transaminase (ALT) and aspartate transaminase (AST) were detected at the beginning of the treatment (basal levels), and at the third and sixth months of the treatment. The patients were treated with propylthiouracil (PTU). Average of age was 40.1 +/- 5.8 years in the patient group and was 37.3 +/- 4.5 years in the control group. TSH, FT4, ALT and AST levels measured in the patient and control group are shown in Table 1. Basal levels of TSH were lower in the study group than in the control group (p<0.001), and basal levels of FT4 were higher in the study group than in the control group (p<0.001). Basal levels of ALT and AST, and the levels of TSH, FT4, ALT and AST measured at the third and sixth months were similar in both groups. We did not find abnormal liver function tests during the antithyroid treatment in the patients with hyperthyroidism.


Borrelia burgdorferi malQ mutants utilize disaccharides and traverse the enzootic cycle.
Borrelia burgdorferi, the causative agent of Lyme disease, cycles in nature between a vertebrate host and a tick vector. We demonstrate that B. burgdorferi can utilize several sugars that may be available during persistence in the tick, including trehalose, N-acetylglucosamine (GlcNAc), and chitobiose. The spirochete grows to a higher cell density in trehalose, which is found in tick hemolymph, than in maltose; these two disaccharides differ only in the glycosidic linkage between the glucose monomers. Additionally, B. burgdorferi grows to a higher density in GlcNAc than in the GlcNAc dimer chitobiose, both of which may be available during tick molting. We have also investigated the role of malQ (bb0166), which encodes an amylomaltase, in sugar utilization during the enzootic cycle. In other bacteria, MalQ is involved in utilizing maltodextrins and trehalose, but we show that, unexpectedly, it is not needed for B. burgdorferi to grow in vitro on any of the sugars assayed. In addition, infection of mice by needle inoculation or tick bite, as well as acquisition and maintenance of the spirochete in the tick vector, does not require MalQ.


[Thoracoscopic interventions].
The technique of minimal invasive surgery has successfully been introduced into the area of thoracic surgery. Surgery of the intrathoracic organs may now be performed without compromise of respiratory mechanics, thus allowing the operative treatment of an ever widening range of pathological conditions. An analysis of our experience (287 thoracoscopic interventions in the last three years) reveals that the diverse procedures performed on the pleura (pleurectomy and pleurodesis), on the lung (wedge resection, fistula closure and ligature of parenchymatous leaks) and on other defined anatomical structures such as the sympathetic nerves or the thoracic duct, are effective in the therapy of intrathoracic disease. The most important pathological conditions which may be treated by thoracoscopy are listed. The range of complications and their causes, which developed in 8% of all procedures, are discussed. The current limitations of this method are defined in the context of the situations where thoracoscopy was discontinued (9 times), a thoracotomy performed (17 times) or a further procedure became necessary (14 times). Current developments and innovations are summarized by a short review of the literature.


Defective implantation and placentation: laying the blueprint for pregnancy complications.
Normal implantation and placentation is critical for pregnancy success. Many pregnancy-related complications that present late in gestation (such as pre-eclampsia and preterm labour) appear to have their origins early in pregnancy with abnormalities in implantation and placental development. Implantation is characterized by invasion of the maternal tissues of the uterus by fetal trophoblast, and the degree to which trophoblast invades these tissues appears to be a major determinant of pregnancy outcome. Excessive invasion can lead to abnormally firm attachment of the placenta to the myometrium (placenta accreta) with increased maternal and perinatal morbidity. Inadequate invasion, specifically restricted endovascular invasion, has been implicated in the pathophysiology of such conditions as pre-eclampsia (gestational proteinuric hypertension), preterm premature rupture of membranes, preterm labour, and intrauterine growth restriction. The molecular and cellular mechanisms responsible for implantation remain enigmatic. This review will include an overview of implantation followed by a discussion of a number of molecular mechanisms implicated in defective implantation and placentation including the role of decidual prostaglandins and haemorrhage in regulating trophoblast invasion. An improved understanding of the molecular mechanisms responsible for abnormal implantation and placentation will likely improve clinicians' abilities to treat disorders that occur along this continuum, including infertility, recurrent pregnancy loss, pre-eclampsia, and preterm birth.


Influence of skin illumination on blood glucose level of the rabbit.
The effects of skin illumination with light beam on blood glucose level are tested on the rabbit. Significant difference in glucose values was observed only between continuous and discontinuous lighted animals 90 minutes after skin illumination (P less than 0.02).


Non-Gaussian dynamics in smectic liquid crystals of parallel hard rods.
Using computer simulations, we studied the diffusion and structural relaxation in equilibrium smectic liquid-crystal bulk phases of parallel hard spherocylinders. These systems exhibit a non-Gaussian layer-to-layer diffusion due to the presence of periodic barriers and transient cages and show remarkable similarities with the behavior of out-of-equilibrium supercooled liquids. We detect a very slow interlayer relaxation dynamics over the whole density range of the stable smectic phase which spans a time interval of four time decades. The intrinsic nature of the layered structure yields a hopping-type diffusion which becomes more heterogeneous for higher packing fractions. In contrast, the in-layer dynamics is typical of a dense fluid with a relatively fast decay. Our results on the dynamic behavior agree well with that observed in systems of freely rotating hard rods but differ quantitatively as the height of the periodic barriers reduces to zero at the nematic-smectic transition for aligned rods, while it remains finite for freely rotating rods.


Visualization of medical concepts represented using word embeddings: a scoping review.
Analyzing the unstructured textual data contained in electronic health records (EHRs) has always been a challenging task. Word embedding methods have become an essential foundation for neural network-based approaches in natural language processing (NLP), to learn dense and low-dimensional word representations from large unlabeled corpora that capture the implicit semantics of words. Models like Word2Vec, GloVe or FastText have been broadly applied and reviewed in the bioinformatics and healthcare fields, most often to embed clinical notes or activity and diagnostic codes. Visualization of the learned embeddings has been used in a subset of these works, whether for exploratory or evaluation purposes. However, visualization practices tend to be heterogeneous, and lack overall guidelines. This scoping review aims to describe the methods and strategies used to visualize medical concepts represented using word embedding methods. We aim to understand the objectives of the visualizations and their limits. This scoping review summarizes different methods used to visualize word embeddings in healthcare. We followed the methodology proposed by Arksey and O'Malley (Int J Soc Res Methodol 8:19-32, 2005) and by Levac et al. (Implement Sci 5:69, 2010) to better analyze the data and provide a synthesis of the literature on the matter. We first obtained 471 unique articles from a search conducted in PubMed, MedRxiv and arXiv databases. 30 of these were effectively reviewed, based on our inclusion and exclusion criteria. 23 articles were excluded in the full review stage, resulting in the analysis of 7 papers that fully correspond to our inclusion criteria. Included papers pursued a variety of objectives and used distinct methods to evaluate their embeddings and to visualize them. Visualization also served heterogeneous purposes, being alternatively used as a way to explore the embeddings, to evaluate them or to merely illustrate properties otherwise formally assessed. Visualization helps to explore embedding results (further dimensionality reduction, synthetic representation). However, it does not exhaust the information conveyed by the embeddings nor constitute a self-sustaining evaluation method of their pertinence.


Functional domain studies uncover novel roles for the ZTL Kelch repeat domain in clock function.
The small LOV/F-box/Kelch family of E3 ubiquitin ligases plays an essential role in the regulation of plant circadian clocks and flowering time by sensing dusk. The family consists of three members, ZEITLUPE (ZTL), LOV KELCH PROTEIN 2 (LKP2), and FLAVIN-BINDING KELCH REPEAT F-BOX PROTEIN 1 (FKF1), which share a unique protein domain architecture allowing them to act as photoreceptors that transduce light signals via altering stability of target proteins. Despite intensive study of this protein family we still lack important knowledge about the biochemical and functional roles of the protein domains that comprise these unique photoreceptors. Here, we perform comparative analyses of transgenic lines constitutively expressing the photoreceptor LOV domain or the Kelch repeat protein-protein interaction domains of ZTL, FKF1, and LKP2. Expression of each domain alone is sufficient to disrupt circadian rhythms and flowering time, but each domain differs in the magnitude of effect. Immunoprecipitation followed by mass spectrometry with the ZTL Kelch repeat domain identified a suite of potential interacting partners. Furthermore, the ZTL Kelch repeat domain can interact with the ZTL homologs, LKP2 and FKF1, and the LOV domain of ZTL itself. This suggests a hypothesis that the Kelch repeat domain of ZTL may mediate inter- and intra-molecular interactions of the three LOV/F-box/Kelch proteins and provides added insight into the composition of the protein complexes and an additional role for the Kelch repeat domain.


[Central venous cannulation under ultrasonographic and fluoroscopic navigation - 2 year experience].
The aim of our study was to evaluate the influence of ultrasonographic and fluoroscopic navigation on the rate of procedural and early complications during central venous cannulation. We retrospectively evaluated procedural and early complications in patients who had undergone central venous cannulation under sonographic and fluoroscopic control within a two year period (from January 2010 to December 2011). We studied procedural and early complications (within 24 hours after the procedure). We summarized all cases of pneumothorax, haemothorax and haematoma of soft tissue larger than 5 cm in long axis, and other severe complications e.g. ardiac arrhythmias or hypotension. The set of patients indicated for central venous cannulation included mainly oncological patients who were implanted central venous port systems, and a small group of patients who were cannulated either at the intensive care unit (ICU) or at the department of anesthesiology after unsuccessful blind cannulation. There were three patients cannulated because of transjugular liver biopsy. We cannulated 165 patients under sonographic control within two years. There were 66 men, the mean age of 58.6 years (20-82) and 99 women, the mean age of 58.3 years (36- 94). We cannulated internal jugular vein 148 times and subclavian vein 17 times. The primary technical success was 100% in our study group. Totally, we had 6 complications (3.6%). Immediatelly after the procedure we observed two pneumothoraxes (1.2%) which did not require chest drainage. We punctured artery wall three times, but without haematoma developement, and after a ten-minute commpression, all procedures were successfully finished. We had serious vagal reaction during the cannulation in one patient. We had no fatal procedural complication in our group. There are significantly fewer complications using jugular approach compared to subclavian one. We conclude that the ultrasonographic central venous cannulation is a very safe method with a low risk of procedural and early complications. There were significantly fewer complications in case of jugular cannulation compared to subclavian approach in our group of patients. Ultrasonographically navigated central venous cannulation should be used more fequently in emergency medicine as well as in case of non-acute central venous cannulation performed a tan intensive care unit or by anesthesiologists.


What can the clinician trust--research? Theory? Clinical knowledge?: introduction to a serious problem and preview of some solutions.
This article addresses a serious problem faced by the field of psychotherapy in relying upon and trusting research, theory, clinical knowledge, or other sources as real, hard, and objective. The serious underlying problem is that the field lives and works in an aerie-faerie world composed of ethereal, illusory, false "psychorealities." Although grand solutions have been introduced, none has succeeded in solving the problem. The introduction concludes with a preview of some current solutions by some of the leading proponents dealing with the problem of what the clinician can trust.


A novel approach to enhancing ganoderic acid production by Ganoderma lucidum using apoptosis induction.
Ganoderma lucidum is one of most widely used herbal medicine and functional food in Asia, and ganoderic acids (GAs) are its active ingredients. Regulation of GA biosynthesis and enhancing GA production are critical to using G. lucidum as a medicine. However, regulation of GA biosynthesis by various signaling remains poorly understood. This study investigated the role of apoptosis signaling on GA biosynthesis and presented a novel approach, namely apoptosis induction, to increasing GA production. Aspirin was able to induce cell apoptosis in G. lucidum, which was identified by terminal deoxynucleotidyl transferase mediated dUPT nick end labeling assay positive staining and a condensed nuclear morphology. The maximum induction of lanosta-7,9(11), 24-trien-3α-01-26-oic acid (ganoderic acid 24, GA24) production and total GA production by aspirin were 2.7-fold and 2.8-fold, respectively, after 1 day. Significantly lower levels of GA 24 and total GAs were obtained after regular fungal culture for 1.5 months. ROS accumulation and phosphorylation of Hog-1 kinase, a putative homolog of MAPK p38 in mammals, occurred after aspirin treatment indicating that both factors may be involved in GA biosynthetic regulation. However, aspirin also reduced expression of the squalene synthase and lanosterol synthase coding genes, suggesting that these genes are not critical for GA induction. To the best of our knowledge, this is the first report showing that GA biosynthesis is linked to fungal apoptosis and provides a new approach to enhancing secondary metabolite production in fungi.


Does loss of residual renal function lead to malnutrition in peritoneal dialysis patients?
It is usually believed that loss of residual renal function is associated with anorexia and the development of malnutrition. We conducted a retrospective study in our center to evaluate the effect of declining residual renal function on patients' nutritional status. All incident uremic patients (n = 46) who began peritoneal dialysis from January 1, 2003 June 1, 2003 in our center were closely followed for 1 year with focus on maintaining strict volume control with time on dialysis. Patient's residual renal function (RRF) was assessed by the average renal urea and creatinine clearances. Those patients who had more than 50% decrease in GFR were selected for the present analysis. Serum albumin (ALB), dietary protein intake (DPI) and subjective global assessment (SGA) were closely followed. There were 16 patients (9 males and 7 females) included in the present analysis, among whom 31.3% were diabetics. Patients' GFR declined significantly (RRF were 4.32 +/- 2.69, 2.99 +/- 2.21 and 1.24 +/- 0.99 ml/min for Months 1, 6 and 12, respectively, p < 0.05), along with a significant decline in urine volume (985.62 +/- 543.29, 698.13 +/- 463.59 and 425.63 +/- 320.52 ml/d for Months 1, 6 and 12, respectively, p < 0.01). Although weekly peritoneal Kt/V did not increase significantly, peritoneal ultrafiltration increased significantly during this period (428.75 +/- 408.96, 534.38 +/- 296.39, 844.38 +/- 440.35 ml for Months 1, 6 and 12, respectively, p < 0.05). Serum ALB increased significantly (32.34 +/- 5.07, 34.74 +/- 4.89 and 36.21 +/- 3.98 g/l for Months 1, 6 and 12, respectively, p < 0.01). DPI also increased significantly. The prevalence of malnutrition (by SGA) decreased from 62.5% at the start of dialysis to 18.8% at the end of this study (p < 0.05). Our study suggests that rapid decline of residual renal function in PD patients does not necessarily lead to decreased dietary protein intake and deteriorated nutritional status. Focus on incremental peritoneal fluid removal along with the decline in residual renal function and, thus, maintaining volume control may be one of the critical reasons for the success.


A New Versatile Water-Soluble Iniferter Platform for the Preparation of Molecularly Imprinted Nanoparticles by Photopolymerisation in Aqueous Media.
The multi-step synthesis of a new water-soluble dithiocarbamate iniferter platform for the preparation of nanoparticles and -gels in aqueous solvents by photoinduced living-radical polymerisation is described herein. The water solubility of the dithiocarbamate iniferter was achieved by incorporating two unprotected glucose units into the iniferter structure by copper(I)-catalysed azide-alkyne cycloaddition ("click chemistry"). Molecularly imprinted nanoparticles (MIPs) specific for 2,4-dichlorophenoxyacetic acid and the corresponding non-imprinted particles (NIPs) were prepared in pure water by using the prepared iniferter as photoinitiator. Radioligand binding tests confirmed a high imprinting factor, and the living character of the iniferter was demonstrated by re-initiating a second photochemical polymerisation on the NIP nanoparticles in water by using ethylene glycol methacrylate phosphate. Our newly synthesised structure is a promising tool for iniferter-mediated photopolymerisations in aqueous media for the preparation of biocompatible nanomaterials with high potential for biomedical applications in a bottom-up fashion.


Flow cytometric analysis of phenotypes of canine red blood cells with FITC-labeled Clerodendron trichotomum lectin.
Canine red blood cells were divided into a positive type (C type) and a negative type (c type) by a agglutination test with Clerodendron trichotomum lectin (CTL). Blood cells changed from c to C type after suffering from mammary tumor were named cm. The c type blood cells treated with neuraminidase were named cn. These red blood cells were studied with flow cytometry using a directly fluoresceinated CTL. Positive percents of C type, cm type, and cn type were 49.3%, 43.8% and 81.0% respectively. While C showed one peak in histogram, cm showed two peaks. The positive peak in the cm blood cells suggested an appearance of a new blood cell population with a novel sugar chain structure after suffering from the tumor.


Dispersion-Corrected Spin-Component-Scaled Double-Hybrid Density Functional Theory: Implementation and Performance for Non-covalent Interactions.
The implementation of 300 combinations of generalized gradient approximation/local density approximation exchange-correlation dispersion-corrected spin-component-scaled double-hybrid (DSD) density functional theory (DFT) methods has been carried out and the performance assessed against several DFT and post-Hartree-Fock methods, enabling further advancements toward the long-standing challenge of accurate prediction of interaction energies and associated properties. The resulting framework is flexible and has been further extended to include the resolution of identity (RI) approximation for solving the critical four-center two-electron repulsion integrals in the basis of the Kohn-Sham orbitals for cost effectiveness. To evaluate the performance of this set of new cost-effective methods, denoted as RI-DSD-DFTs, seven validation data sets were designed to cover a broad range of non-covalent interactions with characteristic stabilizing contributions. Inclusion of the perturbative treatment of correlation effects is shown to significantly improve the description of weak interactions. The set of DSD-DFTs provide interaction energies with root-mean-square deviations and mean absolute errors within 0.5 kcal/mol. The cost-effective RI-DSD-DFT counterparts deviate by less than 0.18 kcal/mol on average with only 2% of the computational cost.


Surface Processes Control the Fate of Reactive Oxidants Generated by Electrochemical Activation of Hydrogen Peroxide on Stainless-Steel Electrodes.
Low-cost stainless-steel electrodes can activate hydrogen peroxide (H2O2) by converting it into a hydroxyl radical (•OH) and other reactive oxidants. At an applied potential of +0.020 V, the stainless-steel electrode produced •OH with a yield that was over an order of magnitude higher than that reported for other systems that employ iron oxides as catalysts under circumneutral pH conditions. Decreasing the applied potential at pH 8 and 9 enhanced the rate of H2O2 loss by shifting the process to a reaction mechanism that resulted in the formation of an Fe(IV) species. Significant metal leaching was only observed under acidic pH conditions (i.e., at pH <6), with the release of dissolved Fe and Cr occurring as the thickness of the passivation layer decreased. Despite the relatively high yield of •OH production under circumneutral pH conditions, most of the oxidants were scavenged by the electrode surface when contaminant concentrations comparable to those expected in drinking water sources were tested. The stainless-steel electrode efficiently removed trace organic contaminants from an authentic surface water sample without contaminating the water with Fe and Cr. With further development, stainless-steel electrodes could provide a cost-effective alternative to other H2O2 activation processes, such as those by ultraviolet light.


Aortic distensibility and extent and complexity of coronary artery disease in patients with stable hypertensive and nonhypertensive coronary artery disease.
To assess the relationship between aortic distensibility (AD) and the extent and complexity of atherosclerotic lesions assessed with SYNTAX score (SS) in patients with stable coronary artery disease. Three hundred and seventy-six consecutive patients (230 males and 146 females; mean age: 61.6 ± 9.9 years) with angiographically proven coronary artery disease were included in the study. The SS was calculated using the SS algorithm on the baseline diagnostic angiogram in the 376 patients. AD was calculated from the echocardiographically derived ascending aorta diameters and hemodynamic pressure measurements in all patients. Frequencies of risk factors, biochemical and hematological data were recorded. The patients were divided into two groups according to the median AD value as AD(low) and AD(high) groups. The SS was higher in the AD(low) group compared with the AD(high) group (18.5 ± 10.2 vs. 8.3 ± 5.9, p < 0.001). The AD was independently related to age (β = -0.104, p = 0.019), hypertension (β = -0.202, p < 0.001) and SS (β = -0.457, p < 0.001) and was more strongly associated with SS in hypertensive patients compared to nonhypertensive patients (r = -0.524 vs. r = -0.414, p < 0.001 for all). The findings showed that impaired AD might be an independent predictor for the severity of coronary atherosclerosis, particularly in patients with hypertension.


Infant Feeding Websites and Apps: A Systematic Assessment of Quality and Content.
Internet websites and smartphone apps have become a popular resource to guide parents in their children's feeding and nutrition. Given the diverse range of websites and apps on infant feeding, the quality of information in these resources should be assessed to identify whether consumers have access to credible and reliable information. This systematic analysis provides perspectives on the information available about infant feeding on websites and smartphone apps. A systematic analysis was conducted to assess the quality, comprehensibility, suitability, and readability of websites and apps on infant feeding using a developed tool. Google and Bing were used to search for websites from Australia, while the App Store for iOS and Google Play for Android were used to search for apps. Specified key words including baby feeding, breast feeding, formula feeding and introducing solids were used to assess websites and apps addressing feeding advice. Criteria for assessing the accuracy of the content were developed using the Australian Infant Feeding Guidelines. A total of 600 websites and 2884 apps were screened, and 44 websites and 46 apps met the selection criteria and were analyzed. Most of the websites (26/44) and apps (43/46) were noncommercial, some websites (10/44) and 1 app were commercial and there were 8 government websites; 2 apps had university endorsement. The majority of the websites and apps were rated poor quality. There were two websites that had 100% coverage of information compared to those rated as fair or poor that had low coverage. Two-thirds of the websites (65%) and almost half of the apps (47%) had a readability level above the 8th grade level. The findings of this unique analysis highlight the potential for website and app developers to merge user requirements with evidence-based content to ensure that information on infant feeding is of high quality. There are currently no apps available to consumers that address a variety of infant feeding topics. To keep up with the rapid turnover of the evolving technology, health professionals need to consider developing an app that will provide consumers with a credible and reliable source of information about infant feeding, using quality assessment tools and evidence-based content.


[Multifocal electroretinogram for assessing sun damage following the solar eclipse of 11 August 1999].
Following the eclipse of 11 August 1999, the ophthalmological clinic of Strasbourg cared for 4 patients who suffered from sun damage. The multifocal electroretinogram (ERG) carried out on our first patient enabled us to not only confirm the existence of a residual maculopathy as shown by the static visual field, but also, and above all to quantify the foveolar deficit. Moreover, with the other 3 patients, the multifocal ERG enabled us to detect a foveolar deficit completely overlooked by the other usual tests. In light of our clinical study, we can assert that the multifocal ERG has yet to be equaled by any other test for analysis of macular function.


When traditional model meets competencies in Singapore: beyond conflict resolution.
The implementation of competency-based internal medicine (IM) residency programme that focused on the assurance of a set of 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies in Singapore marked a dramatic departure from the traditional process-based curriculum. The transition ignited debates within the local IM community about the relative merits of the traditional versus competency-based models of medical education, as well as the feasibility of locally implementing a training structure that originated from a very different healthcare landscape. At the same time, it provided a setting for a natural experiment on how a rapid integration of 2 different training models could be achieved. Our department reconciled the conflicts by systematically examining the existing training structure and critically evaluating the 2 educational models to develop a new training curriculum aligned with institutional mission values, national healthcare priorities and ACGME-International (ACGME-I) requirements. Graduate outcomes were conceptualised as competencies that were grouped into 3 broad areas: personal attributes, interaction with practice environment, and integration. These became the blueprint to guide curricular design and achieve alignment between outcomes, learning activities and assessments. The result was a novel competency-based IM residency programme that retained the strengths of the traditional training model and integrated the competencies with institutional values and the unique local practice environment. We had learned from this unique experience that when 2 very different models of medical education clashed, the outcome may not be mere conflict resolution but also effective consolidation and transformation.


Expression and function of CD4 in a murine T-cell hybridoma.
The CD4 (T4) antigen was originally described as a phenotypic marker specific for helper T cells, and has recently been shown to be the receptor for the human immunodeficiency virus (HIV). Functional studies using monoclonal antibodies directed at CD4 and major histocompatibility complex (MHC) class II molecules led to the suggestion that CD4 binds to the MHC class II molecules expressed on stimulator cells, enhancing T-cell responsiveness by increasing the avidity of T cell-stimulator cell interaction and/or by transmitting a positive intracellular signal. But recent evidence that antibodies to CD4 inhibit T-cell responsiveness in the absence of any putative ligand for CD4 has been interpreted as suggesting that antibody-mediated inhibition may involve the transmission of a negative signal via the CD4 molecule instead. We have infected a murine T-cell hybridoma that produces interleukin 2 (IL-2) in response to human class II HLA-DR antigens with a retroviral vector containing CD4 cDNA. The resulting CD4-expressing hybridoma cell lines produce 6- to 20-fold more IL-2 in response to HLA-DR antigens than control cell lines. Furthermore, when antigen levels are suboptimal, the response of the cell lines is entirely CD4-dependent. The data presented here clearly demonstrate that CD4 can enhance T-cell responsiveness and may be crucial in the response to suboptimal levels of antigen.


The detection of foodborne bacteria on beef: the application of the electronic nose.
This study aims to investigate the application of a fast electronic nose system (Cyranose 320) for detecting foodborne bacteria. The system proved to be very efficient in detecting microbes in beef and sausage samples. In the first part of the study, the total viable counts (TVC) from fresh and frozen beef samples were determined using the standard microbiological method and by the application of the electronic nose. The second part applied the electronic nose to beef before and after contamination with different bacterial pathogens separately: E. coli O157: H7, Salmonellatyphimurium 857, Staphylococcus aureus 29213 and Pseudomonas aeruginosa 27853. The results revealed that the Cyranose 320 can detect the TVC in different beef and sausage samples and quantify the volatile organic compounds produced at concentrations from 50 ppb to > 350 ppb. The concentrations of gases collected from the samples before and after separate contamination with these pathogenic bacteria were highly significantly correlated (P < 0.005). From this study one can conclude that the electronic nose system is a rapid way for detecting volatile organic compounds produced by foodborne bacteria that contaminate beef.


Synchronous multi-color laser network with daily sub-femtosecond timing drift.
Filming atoms in motion with sub-atomic spatiotemporal resolution is one of the distinguished scientific endeavors of our time. Newly emerging X-ray laser facilities are the most likely candidates to enable such a detailed gazing of atoms due to their angstrom-level radiation wavelength. To provide the necessary temporal resolution, numerous mode-locked lasers must be synchronized with ultra-high precision across kilometer-distances. Here, we demonstrate a metronome synchronizing a network of pulsed-lasers operating at different center wavelengths and different repetition rates over 4.7-km distance. The network achieves a record-low timing drift of 0.6 fs RMS measured with 2-Hz sampling over 40 h. Short-term stability measurements show an out-of-loop timing jitter of only 1.3 fs RMS integrated from 1 Hz to 1 MHz. To validate the network performance, we present a comprehensive noise analysis based on the feedback flow between the setup elements. Our analysis identifies nine uncorrelated noise sources, out of which the slave laser's inherent jitter dominates with 1.26 fs RMS. This suggests that the timing precision of the network is not limited by the synchronization technique, and so could be much further improved by developing lasers with lower inherent noise.


Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Modulate the Function of Myelinated Fibers after Chemotherapy: A Quantitative Sensory Testing Study.
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have sufficient scientific support for their use as tissue protectors. Preliminary studies suggest that their angiotensin-II type 2 receptor (AT2R)-blocking properties have a beneficial profile in the treatment of neuropathic pain. The purpose of the current study was to quantify the extent of the somatosensory effects of ACEI and ARB in cancer patients with chemotherapy-induced peripheral neuropathy. We performed a retrospective review of cancer patients with peripheral neuropathy of the upper limbs induced by known neurotoxic anti-cancer agents. Pain Medicine department at academic tertiary care cancer center. Using our quantitative sensory testing (QST) data bank, we retrospectively compared the tactile function and the touch, sharp, and thermal thresholds of patients who were previously receiving ACEI or ARB for high blood pressure with these variables in controls who were not receiving ACEI or ARB. Of the 209 patients available for analysis, 145 met inclusion criteria. Baseline characteristics of patients included were generally similar. We identified 29 patients who were receiving AT2R inhibitors prior to starting chemotherapy. Touch thresholds were statistically lower in the thenar aspect of hand in the study group (patients who received AT2R inhibitors) than in the control group [mean (± SD), median 3.03 g (± 11.05), median 0.56 g and 6.75 g (± 18.28), 0.56 g, respectively (P = 0.0441)]. Similarly, the cold pain threshold was statistically higher at the thenar area for the study group [mean (± SD), median 13.23°C (± 8.02), 11.73°C] than for controls [9.89°C (± 6.62), 10.05°C (P = 0.0369)]. Inadequacies in the original data acquisition and documentation of the QST and the medical records could not be addressed due to the retrospective nature of the study. Similarly, a discrepancy on the size of the comparison groups could not be reconciled. In addition, based on the available information and the lack of documented concomitant pain levels, we did not find an objective parameter able to correlate the QST findings with pain levels. AT2R inhibitors might offer partial and selective neuroprotective qualities of the myelinated fibers A-beta; and A-delta in cancer patients who receive neurotoxic chemotherapy.


Recognition of nucleic acids by Toll-like receptors and development of immunomodulatory drugs.
Microbial as well as endogenous nucleic acids are recognized by a group of endosomal Toll-like receptors TLR3, TLR7, TLR8 and TLR9. Recent discoveries significantly improved our understanding of molecular mechanism of their activation and their physiological role. Those include recognition of dsRNA through two nucleic acid binding sites of TLR3 ectodomain, activation of TLR9 by phosphodiester backbone of ssDNA, independent of the nucleotide sequence and phosphorothioate modified bonds, and the role of proteolysis in activation of TLR9. In addition, proteins that chaperone nucleic acids, such as HMGB1 or LL-37, have been described to mediate TLR activation. There is growing evidence that supports involvement of endosomal TLRs in a number of autoimmune diseases, suggesting a therapeutic potential of immunomodulatory endosomal TLR ligands. So far, inhibitory nucleic acids against TLR7, TLR8 and TLR9 as well as small compounds targeting downstream signal transduction of single or several endosomal TLRs have been reported. TLR-targeting drugs have been included in clinical trials as vaccine adjuvants or as therapeutic agents for the treatment of diseases, ranging from cancer, infections, asthma and allergy to autoimmune diseases.


Silver Nanowire Reinforced Conductive and Injectable Colloidal Gel for Effective Wound Healing via Electrical Stimulation.
The remarkable biocapacity, injectability, and adaptability of colloidal gels have led to their widespread usage in tissue engineering as irregular defect implants. However, multifunctionalities including electroconductivity and antibacterial property are highly required for colloidal gels. In addition, the inherently weak mechanical property of physically crosslinked colloidal gels limits their application. Herein, we present Ag nanowires (Ag NWs)-reinforced colloidal gels composed of biocompatible gelatin nanoparticles and polydopamine-modified Ag NWs through the controlled electrostatic assembly, which are injectable and conductive. One-dimensional Ag NWs can significantly improve the mechanical and electrical properties of the colloidal gel while maintaining its inherent excellent injectability. Owing to the network of Ag NWs, the storage modulus and conductivity of the optimized Ag NW colloidal gel are 7.5 and 13 times higher, respectively, than those of the colloidal gel made up of polydopamine-modified Ag nanoparticles with equivalent Ag concentration. Furthermore, this Ag NW colloidal gel can adapt to sharp wounds on skin, which accelerates the healing of a MRSA-infected wound via electrical stimulation. This article is protected by copyright. All rights reserved.


Perceptual deficits in patients with impaired recognition of biological motion after temporal lobe lesions.
"Biological motion" may be defined by the pattern of movement of a small number of lights attached to the major joints of a human performing simple actions. Normal observers watching such displays immediately recognize a person and his or her actions. In the present study, we investigated the effects of lesions of anterior cortical regions on the perception of biological motion. We measured the performance on psychophysical static and motion tasks and on object and action recognition tests in four stroke patients who presented with a disorder of recognition of biological motion. We relate our results to the finding that neurons in the rostral part of the superior temporal gyrus (the superior temporal polysensory area) respond selectively to biological motion, and to the idea that the superior temporal polysensory area integrates the late stages of the dorsal and ventral cortical visual streams, as well as to recent functional MRI studies on biological motion.


[Evaluation of asthma and COPD awareness in primary care doctors in Turkey].
Chronic pulmonary diseases cause significant morbidity and mortality. However awareness about the risk factors, symptoms, diagnosis and traetment of these disorders is low among patients and health care providers. Our aim was to evaluate the awareness of asthma and chronic obstructive pulmonary disease among primary care doctors. This study was performed by the national Global Alliance Against Chronic Respiratory Diseases programme. Primary care doctors employed by the Ministry of Healthy were included to the study. Turkish Statistical Institute randomly selected 680 doctors. Questionnaires evaluating the awareness of asthma and COPD which were developed by the Turkish Thoracic Society COPD and asthma assemblies were completed online by these doctors. 84% of the doctors described asthma as airway obstruction. Dyspnea was reported as the most common symptom of asthma (78.8%) and inspiratory rhonci was reported as the most common physical exam finding (42.3%). Around 50% of doctors thought impairment of pulmonary function tests (PFT) was important for diagnosis and evaluation of severity of asthma while 24.2% thought physical exam was more important. When treatment options were evaluated 87.6% chose inhaled treatment for asthma. COPD was described as bronchiectasis and chronic bronchitis by 9.1%, chronic bronchitis and emphysema by 61.6%, chronic bronchitis and asthma by 22.2% and asthma and emphysema by 7.1%. 1.2% of the doctors did not consider cigarette smoking as a risk factor for COPD. PFT was recommended for diagnosis by 83%. Most correctly differentiated asthma and COPD. Bronchodilators were the first choice for COPD by 72.5%. Awareness is low for asthma and COPD among primary care doctors. Awareness should be raised among health care professionals for these diseases with high economical burden to improve outcome.


Using a machine learning approach to determine the space group of a structure from the atomic pair distribution function.
A method is presented for predicting the space group of a structure given a calculated or measured atomic pair distribution function (PDF) from that structure. The method utilizes machine learning models trained on more than 100 000 PDFs calculated from structures in the 45 most heavily represented space groups. In particular, a convolutional neural network (CNN) model is presented which yields a promising result in that it correctly identifies the space group among the top-6 estimates 91.9% of the time. The CNN model also successfully identifies space groups for 12 out of 15 experimental PDFs. Interesting aspects of the failed estimates are discussed, which indicate that the CNN is failing in similar ways as conventional indexing algorithms applied to conventional powder diffraction data. This preliminary success of the CNN model shows the possibility of model-independent assessment of PDF data on a wide class of materials.


[Comparative study of three culture media for detecting group B Streptococcus colonization in pregnant women].
To compare the efficacy of three culture media to detect vaginal and rectal colonization by group B streptococci (GBS) in pregnant women. We processed 1334 samples from 861 pregnant women: in 388 patients only vaginal swab was cultured (Group A) and in 473 vaginal and rectal swabs were cultured (Group B). Samples were inoculated on blood agar with colistin-nalidixic acid (BA-CNA), on plates with Granada medium, and on Todd-Hewitt broth (THB) with amikacin followed by subculture in BA-CNA. GBS was isolated in 181 samples (13.6%): 114 vaginal swabs (13.2%) and 67 rectal swabs (14.2%). Among the positive samples, GBS was isolated on BA-CNA in 60.5% of vaginal swabs and in 59.7% of rectal swabs, on Granada medium in 80.7% of vaginal swabs and in 91% of rectal swabs, and on THB in 97.4% of vaginal swabs and in 97% of rectal swabs.We detected 130 GBS carriers, 54 (13.9%) in Group A and 76 (16.1%) in Group B. The percent of carriers detected in groups A and B, respectively, was 59.3% and 75% with BA-CNA, 77.8% and 93.4% with Granada medium, and 96.3% and 97.4% with THB. THB was the most reliable medium for the detection of GBS. Use of Granada medium allows fast detection of about 87% of carriers. The combination of THB and an initial plate of Granada medium or BA-CNA allows detection of more than 99% of GBS carriers.


Hyperemesis gravidarum and fetal gender: a retrospective study.
This retrospective study of 9,980 women who delivered at the James Paget Hospital, Norfolk, UK, over 5 years, aimed to primarily determine whether the incidence of hyperemesis gravidarum (HG) is higher in the presence of a female fetus. The results showed that more women with HG had a female fetus compared with women without HG. Also found was that heavy ketonuria was more prevalent in women with a female fetus compared with women with a male fetus, and the mean number of admissions per woman was also higher in women with a female fetus compared with women with a male fetus. It can be concluded that women presenting with HG are more likely to have a female fetus and that women with HG and a female fetus tend to a higher level of ketonuria and an increased number of hospital admissions.


Nuclear magnetic resonance structure elucidation of peptide b2 ions.
Tandem mass spectrometry (MS/MS) is powerful for chemical identification but it is still insufficient for explicit ion structure determination. A strategy is introduced to elucidate MS fragment ion structures using NMR spectroscopy for the first time. In our experiments, precursor ions are dissociated at atmospheric pressure and the resulting fragment ions are identified by mass spectrometry but collected outside the mass spectrometer, making the subsequent NMR measurements possible. This new strategy has been applied to determine the chemical structure of the characteristic b2 fragment ion, a subject of longstanding debate in MS-based proteomics.


Socioeconomic factors and substances involved in poisoning-related emergency department visits in British Columbia, Canada.
Canada's opioid crisis has taken thousands of lives, increasing awareness of poisoning-related injuries as an important public health issue. However, in British Columbia (BC), where overdose mortality rates are the highest in Canada, studies have not yet identified which demographic populations most often visit emergency departments (ED) due to all poisonings, nor which substances are most commonly involved. The aim of this study was to explore these gaps, after developing a methodology for calculating ED visit rates in BC. Poisoning-related ED visit rates during fiscal years 2012/13 to 2016/17, inclusive, were calculated by sex, age group, poisoning substance and socioeconomic status, using a novel methodology developed in this study. ED data were sourced from the National Ambulatory Care Reporting System and population data from Statistics Canada's 2016 (or 2011) census profiles. During the study period, there were an estimated 81 463 poisoning-related ED visits (351.2 per 100 000 population). Infants, toddlers, youth and those aged 20-64 years had elevated risks of poisoning-related ED visits. Rates were highest among those in neighbourhoods with the greatest material (607.8 per 100 000 population) or social (484.2 per 100 000 population) deprivation. Over time, narcotics and psychodysleptics became increasingly common poisoning agents, while alcohol remained problematic. A methodology for estimating ED visit rates in BC was developed and applied to determine poisoning-related ED visit rates among various demographic groups within BC. British Columbians most vulnerable to poisoning have been identified, emphasizing the need for efforts to limit drug overdoses and excessive alcohol intoxication to reduce rates of these preventable injuries.


Regulation and function of autophagy during cell survival and cell death.
Autophagy is an important catabolic process that delivers cytoplasmic material to the lysosome for degradation. Autophagy promotes cell survival by elimination of damaged organelles and proteins aggregates, as well as by facilitating bioenergetic homeostasis. Although autophagy has been considered a cell survival mechanism, recent studies have shown that autophagy can promote cell death. The core mechanisms that control autophagy are conserved between yeast and humans, but animals also possess genes that regulate autophagy that are not present in yeast. These regulatory differences may be explained by the need to control autophagy in a cell context-specific manner in multicellular animals, such as during cell survival and cell death. Autophagy was thought to be a bulk cytoplasmic degradation mechanism, but recent studies have shown that specific cargo is recruited for degradation. This suggests the possibility that either cell survival or death may be regulated by selective autophagic clearance of cytoplasmic material. Here we summarize the mechanisms that regulate autophagy and how they may contribute to cell survival and death.


Matrix effect on baked milk tolerance in children with IgE cow milk allergy.
Children with IgE-mediated cow's milk allergy (IgE-CMA) often tolerate baked milk within a wheat matrix. In our study we evaluated the impact of wheat matrix and of little standardised cooking procedures on tolerance of baked milk. We also tested tolerance versus parmigiano reggiano (PR) and whey-based partially hydrolysed formula (pHF). Forty-eight children with IgE-CMA were enrolled. They underwent prick-by-prick (PbP) and open oral food challenge (OFC) with baked cow's milk (CM), both within a wheat matrix (an Italian cake named ciambellone) and without (in a liquid form), with PR and with pHF. After a passed OFC, children continued to eat the food tolerated. In particular, after passed OFC with ciambellone, children were allowed to eat any food containing CM within a wheat matrix, with the only condition that it was baked at 180°C for at least 30min. Three months after, parents were asked to answer a survey. 81% of children tolerated ciambellone, 56% liquid baked CM, 78% PR and 82% pHF. Negative predictive value of PbP performed with tested foods was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. Wheat matrix effect on tolerance of baked milk was relevant in slightly less than half of cases. If our results are confirmed by larger studies, a negative PbP will allow patients to eat processed CM without undergoing OFC. Moreover, in order to guarantee tolerance towards baked milk, strict standardised cooking procedures do not seem to be necessary.


Separation of brain-RNA by micro-electrophoresis on agarose-acrylamide gels.
A simple method is described for RNA fractionation on the microscale (10(-8) to 10(-7) g). The optimal conditions for electrophoretic separation of low molecular weight RNA (4S-16S) on such a scale have been determined running a standard mixture of 4S, 5S and 16S E. coli RNAs on agarose-polyacrylamide gels at three different concentrations of acrylamide. The separations were evaluated for resolution of the different species and for linearity in the relationship between mobility and logarithm of molecular weight. A straight linear relationship and good resolution was obtained on a 3.48 per cent polyacrylamide - 0.7 per cent agarose gel. When a sample of 10(-2) O.D.U.260 of macroextracted cerebral RNA was separated on such a gel, six unusual RNA bands were detected between 5A and 18S. To find out optimal conditions for RNA fractionation in the 16S-28S range a standard mixture of 16S, 18S, 23S and 28S RNA was run on gels of three different acrylamide concentrations. The separations were again evaluated with regard to both the resolution and the linearity of the relationship between the logarithms of the molecular weights and the mobilities of the standard RNA species. A 0.7 per cent agarose - 2.5 per cent polyacrylamide gel appeared to be quite suitable with regard to both. The fractionation of a microsample of RNA macroextracted from whole rat brain is presented. We also present the fractionation of the RNA microextracted from 1 mg of the CA3 region of rat hippocampus.


Efficacy of Spirulina platensis diet supplements on disease resistance and immune-related gene expression in Cyprinus carpio L. exposed to herbicide atrazine.
The present study evaluated the immunotoxicological effects of the herbicide atrazine (ATZ) at sub-lethal concentrations and the potential ameliorative influence of Spirulina platensis (SP) over a sub-chronic exposure period on Cyprinus carpio L., also known as common carp. Common carp was sampled after a 40-days exposure to ATZ (428 μg/L) and SP (1%), individually or in combination to assess the non-specific immune response, changes in mRNA expression of immune-related genes [lysozyme (LYZ), immunoglobulin M (IgM), and complement component 3 (C3)] in the spleen, and inflammatory cytokines (interleukins IL-1ß and IL-10) in the head kidney using real-time PCR. Additionally, disease resistance to Aeromonas sobria was evaluated. The results revealed that ATZ exposure caused a significant decline in most of the hematological variables, lymphocyte viability, and lysozyme and bactericidal activity. Moreover, ATZ increased the susceptibility to disease, reflected by a significantly lower post-challenge survival rate of the carp. ATZ may induce dysregulated expression of immune-related genes leading to downregulation of mRNA levels of IgM and LYZ in the spleen. However, expression of C3 remained unaffected. Of the cytokine-related genes examined, IL-1B was up-regulated in the head kidney. In contrast, the expression of IL-10 gene was down-regulated in the ATZ-exposed group. The SP supplementation resulted in a significant improvement in most indices; however, these values did not match with that of the controls. These results may conclude that ATZ affects both innate and adaptive immune responses through the negative transcriptional effect on genes involved in immunity and also due to the inflammation of the immune organs. In addition, dietary supplements with SP could be useful for modulation of the immunity in response to ATZ exposure, thereby presenting a promising feed additive for carps in aquaculture.


Sports participation during adolescence: a shift from environmental to genetic factors.
A twin design was used to assess the relative contribution of genetic and environmental influences on the variation in sports participation of Dutch male and female twins between the ages of 13 and 20 yr. Survey data from 2628 complete twin pairs were available (443 male and 652 female monozygotic twin pairs, 377 male and 434 female dizygotic twin pairs, and 722 opposite-sex twin pairs). Subjects were classified as participating in sports if they engaged in competitive or noncompetitive leisure-time sports activities with a minimal intensity of 4 METs for at least 60 min.wk. An overall main effect of age and sex was found on the sports participation dichotomy. Younger twins participated more in sports than older twins, and for each age group males participated more often than females. Genetic analyses of twin resemblance showed a shift in the factors contributing to sports participation from adolescence to adulthood. Between the ages of 13 and 16 yr, environmental factors shared by children from the same family largely account for individual differences in sports participation (78-84%), whereas genes are of no importance. At the age of 17-18 yr, genetic influences start to appear (36%), and the role of common environment decreases (47%). After the age of 18 yr, genes largely explain individual differences in sports participation (85%), and common environmental factors no longer contribute. Environmental factors shared by family members determine sports participation in young adolescence but cease to be of importance in adulthood when individual differences in sports participation are largely due to genetic variation.


Impaired kidney graft survival is associated with the TNF-alpha genotype.
The TNF2 allele at position -308 of the tumor necrosis factor (TNF)-alpha gene is associated with high TNF production. The purpose was to study the association of this gene polymorphism with rejection episodes and graft survival after kidney transplantation. A retrospective analysis of transplant outcomes of patients who only had been treated with one single form of immunosuppression consisting of cyclosporine, azathioprine, and prednisolon was performed. We found that 115 (73%) patients had the TNF1/TNF1 genotype, whereas 42 (27%) were TNF2 positive. There was no difference in the overall acute rejection frequency between these two groups (50% in each), but our data showed a non-significant tendency towards a higher frequency of steroid resistant rejections in the TNF2 positive group (57% vs. 40%). There was no significant difference in graft survival between the two genotype groups, although an early tendency towards worse survival was seen in TNF2 recipients. However, the TNF2 positive recipients with rejection episodes had far worse graft survival compared with the TNF1/TNF1 recipients with rejection episodes (P<0.02). No difference was seen between the two genotype groups in patients without rejection episodes. Our data propose that potentially high TNF producers with the TNF2 allele do not have an increased risk for rejection episodes, but if rejection episodes occur, they have a significantly increased risk for early graft loss. TNF production may intensify rejection, but is not a primary factor for the induction of such acute immune activation.


Developing drug strategies for the neuroprotective treatment of acute ischemic stroke.
Developing new treatment strategies for acute ischemic stroke in the last twenty years has offered some important successes, but also several failures. Most trials of neuroprotective therapies have been uniformly negative to date. Recent research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline, albumin and cerebrolysin have been tested with findings worthy of further evaluation in larger randomized clinical trials. Understanding the complexities of the ischemic cascade is essential to developing pharmacological targets for acute ischemic stroke in neuroprotective or flow restoration therapeutic strategies.


Cigarette smoking and its effects on the platelet-vessel wall interaction.
The effect of smoking and of carbon monoxide on the platelet-vessel wall interaction was investigated. After smoking two high-nicotine content cigarettes (2.6 mg nicotine/cigarette) the mean bleeding time decreased 1.6 min (P less than 0.05) in five habitual smokers whereas the platelet aggregability was only moderately inhibited. After inhibiting the platelet cyclooxygenase by ingesting acetylsalicylic acid (ASA) 2 days prior to the study, smoking caused a markedly and significantly shortened bleeding time (-3.8 min; P less than 0.05). The bleeding time was unaffected by smoking when both the platelet cyclooxygenase and the vessel wall prostaglandin was inhibited by ASA 1 h prior to the study. When smoking two cigarettes with a low content of nicotine (0.25 mg nicotine/cigarette) no changes in the haemostatic mechanism were observed. Inhalation of carbon monoxide in high amounts in five non-smokers had a significant short-lasting effect on the bleeding time (-1.2 min, P less than 0.05). No changes in the bleeding time were observed after carbon monoxide inhalation when the platelet cyclooxygenase or when both the platelet cyclooxygenase and the vessel wall prostaglandin production were blocked. Based on the results it is concluded that the effect of smoking on the haemostasis is mainly mediated through an inhibitory effect on the prostacyclin production in the vessel wall by nicotine and that carbon monoxide only plays a minor role.


An emerging problem: methamphetamine abuse among treatment seeking youth.
This study examined correlates of methamphetamine (MA) and marijuana (MJ) use and treatment response among treatment-involved youth (N = 4,430) in Los Angeles County, California treated between 2000 and 2005. Of the sample, 912 (21%) were primary MA and 3,518 (79%) were primary MJ users. Correlates of increased MA use included being female, White, Asian or Latino, older age, previous treatment involvement, legal status of probation or parole, and initiating drug use at an older age. Treatment trends showed a rise in treatment admissions for MA, with more MA users enrolling in residential treatment compared to outpatient treatment. Predictors of retention, drug use at discharge, and completion by treatment modality are discussed. Results can guide the development of effective strategies for treatment assessment and planning tailored towards minimizing drug use and maximizing treatment response among youth.


Same-day discharge vs. observation after laparoscopic pediatric appendectomy: a prospective cohort study.
Through 2015, the practice at our university based free-standing children's hospital was to admit uncomplicated appendicitis patients for overnight observation post-operatively. Given the increasing body of evidence suggesting the safety and feasibility of same-day discharge after appendectomy for uncomplicated appendicitis, we elected to perform a prospective study evaluating the complication rates of same-day discharge compared to overnight observation at our institution, given our large volume of appendicitis. Pediatric patients who underwent laparoscopic appendectomies for uncomplicated appendicitis in 2016 were analyzed. Data regarding demographics, admission, and discharge times and outcomes of complications, as well as readmissions, return to the emergency department, and nonscheduled clinic visits were collected and analyzing using chi-square and multivariate regression. Cost of stay data was obtained and analyzed using Mann-Whitney U test to compare non-parametric variables. Eight hundred and forty-nine laparoscopic appendectomies were performed for uncomplicated appendicitis during the study period, of which 382 resulted in same-day discharge and 467 in an admission for observation. Univariate analysis revealed no statistical difference between readmission rates for same day vs. observation (2 vs. 6 patients; P=0.21) or in emergency department visits within 30 days (22 vs. 27 patients; P=0.98). There was no difference in the number of surgical site infections or extra clinic visits. There was a significantly lower median cost of stay for patients discharged home the same day at 29,150 dollars (25,644, 32,276, IQR) compared to a median of 34,827 dollars (31,154, 39,457, IQR) (P<0.0001). Same-day discharge for laparoscopic uncomplicated appendectomy should be the new standard of care. This study found no differences in outcomes between the timing of discharge, with a significantly lower cost of stay for patients discharged home the same day.


Lithography-based fabrication of nanopore arrays in freestanding SiN and graphene membranes.
We report a simple and scalable technique for the fabrication of nanopore arrays on freestanding SiN and graphene membranes based on electron-beam lithography and reactive ion etching. By controlling the dose of the single-shot electron-beam exposure, circular nanopores of any size down to 16 nm in diameter can be fabricated in both materials at high accuracy and precision. We demonstrate the sensing capabilities of these nanopores by translocating dsDNA through pores fabricated using this method, and find signal-to-noise characteristics on par with transmission-electron-microscope-drilled nanopores. This versatile lithography-based approach allows for the high-throughput manufacturing of nanopores and can in principle be used on any substrate, in particular membranes made out of transferable two-dimensional materials.


Fontan procedure and surgical modification in tricuspid atresia.
Nineteen patients with tricuspid atresia and reduced lung perfusion (valvular-and/or subvalvular pulmonary stenosis, transposition of the great arteries and/or single atrium) were operated in the period 1975--1979. The surgical procedures employed varied according to the additional cardiac defects. The age of the patients was between 2 and 18 years. Eleven children received a contuit with a Hancock valve, 8 children a valveless conduit. In 9 patients it was possible to connect the conduit to the right ventricle using the pumping action of the right ventricle with an anatomically intact pulmonary valve. Six patients died (4 early deaths, 2 late deaths, early mortality rate 21%). In this study, the postoperative courses, which were complicated in several cases, are related to the hemodynamical findings. Thirteen children were examined between 1 and 38 months following the operation. Cardiac catheterization was performed in 10 patients. Of the 13, 10 had fully saturated arterial blood. A remnant atrial defect was demonstrated in one child, and 2 displayed intrapulmonary shunts attendant to Glenn anastomoses which had been in place for 10 to 12 years. Among the patients the right atrial pressure ranged from 10 to 20 mmHg with a mean value of 14.5 +/- 0.9 mmHg. An increase in size of the right ventricle was demonstrated angiographically in the case of 2 patients who had valve-bearing conduits to the right ventricle.


Posterior reversible encephalopathy syndrome postautologous peripheral stem cell transplantation for multiple myeloma.
This is a case of a 56-year-old lady with recent autologous peripheral stem cell transplantation for multiple myeloma. She was presented with a 48 h history of worsening headache, drowsiness, nausea/vomiting and some peripheral neurological symptoms. She developed status epilepticus, was intubated and transferred to intensive care unit. After full investigation with a CT head, CT cerebral angiogram, MRI brain and cerebral angiogram, she was diagnosed with posterior reversible encephalopathy syndrome (PRES) with the help of expert opinion, based on the clinical and radiological evidence. The MRI showed bilateral occipital signal changes suggestive of PRES. She was managed with nimodipine, phenytoin and clonazepam with good effect. Eventually extubated, she made good progress on the ward with no further seizure episodes. Functionally she did not appear to have any evidence of residual damage from the PRES. This case discusses PRES on a background of a haematological malignancy and its clinical features.


Treatment of overactive bladder: a model comparing extended-release formulations of tolterodine and oxybutynin.
The objective of this study was to compare 1-year total healthcare costs for patients with overactive bladder (OAB) initiating treatment with extended-release formulations of tolterodine and oxybutynin: tolterodine tartrate extended-release capsules (tolterodine ER) versus extended-release oxybutynin chloride (oxybutynin ER). A model was developed from the payer perspective using data from the PharMetrics Patient-Centric database. Monthly discontinuation rates were derived from a cohort of newly treated patients with OAB (tolterodine ER, n = 15 394 or oxybutynin ER, n = 7934). All were assumed to be receiving therapy for at least 1 month. Medical management costs were based on reimbursement for all services for a matched cohort of patients taking tolterodine ER and oxybutynin ER. Medical management costs for those discontinuing therapy were based on patients receiving OAB care without pharmacotherapy (n = 29 992). Drug costs were from AnalySource (December 2004). After the 11-month follow-up period, 21% of patients taking tolterodine ER and 15% of patients taking oxybutynin ER remained on original therapy. One-year average total costs per patient for those started on tolterodine ER were dollar 8876 and dollar 9080 for oxybutynin ER, a difference of dollar 204 per year. Sensitivity analyses indicated results were robust to changes in drug cost and probability of discontinuation. When discontinuation rates were held equal, cost differences continued to favor tolterodine ER (21%, dollar 272/yr; 15%, dollar 233/yr). Those taking tolterodine ER had lower monthly drug and medical management costs. This resulted in a total average annual cost savings of dollar 204 per patient for those started on tolterodine ER. At the end of 1 year, patients with OAB were more likely to remain on original drug treatment taking tolterodine ER versus oxybutynin ER.


Crystal structure of the LUFS domain of human single-stranded DNA binding Protein 2 (SSBP2).
The human single-stranded DNA binding Protein 2 (SSBP2) is a tumor suppressor implicated in multiple cancer forms. The SSBP2 and related SSBP3/SSBP4 proteins are predicted to be intrinsically disordered excepted for their highly conserved N-terminal LUFS (LUG/LUH, Flo8, and SSBP/SSDP) domain. LUFS domains are found in a number of proteins including some transcriptional co-repressors. Although LUFS domains contain an N-terminal Lis homology (LisH) motif that typically forms a stable dimer, no 3D structure of any LUFS domain is available. Here, we report a crystal structure of the LUFS domain of human SSBP2 at 1.52 Å resolution. We show that the SSBP2 LUFS domain forms a homo-tetramer and reveal how an alpha-helix C-terminal to the LisH motif mediates SSBP2 tetramerization (dimerization of dimers). Conservation of the tetramerization interface among LUFS domains suggests that other LUFS domains may also form tetramers in similar manners.


Comparison of Candida Albicans Adherence to Conventional Acrylic Denture Base Materials and Injection Molding Acrylic Materials.
Candida species are believed to play an important role in initiation and progression of denture stomatitis. The type of the denture material also influences the adhesion of candida and development of stomatitis. The aim of this study was comparing the adherence of candida albicans to the conventional and injection molding acrylic denture base materials. Twenty injection molding and 20 conventional pressure pack acrylic discs (10×10×2 mm) were prepared according to their manufacturer's instructions. Immediately before the study, samples were placed in sterile water for 3 days to remove residual monomers. The samples were then sterilized using an ultraviolet light unit for 10 minutes. 1×108 Cfu/ml suspension of candida albicans ATCC-10231 was prepared from 48 h cultured organism on sabouraud dextrose agar plates incubated at 37oC. 100 μL of this suspension was placed on the surface of each disk. After being incubated at 37oC for 1 hour, the samples were washed with normal saline to remove non-adherent cells. Attached cells were counted using the colony count method after shaking at 3000 rmp for 20 seconds. Finally, each group was tested for 108 times and the data were statistically analyzed by t-test. Quantitative analysis revealed that differences in colony count average of candida albicans adherence to conventional acrylic materials (8.3×103) comparing to injection molding acrylic resins (6×103) were statistically significant (p<0.001). Significant reduction of candida albicans adherence to the injection acrylic resin materials makes them valuable for patients with high risk of denture stomatitis.


CD8+ T cells are preferentially activated during primary low dose leishmania major infection but are completely dispensable during secondary anti-Leishmania immunity.
We previously showed that CD8+ T cells are required for optimal primary immunity to low dose Leishmania major infection. However, it is not known whether immunity induced by low dose infection is durable and whether CD8+ T cells contribute to secondary immunity following recovery from low dose infection. Here, we compared primary and secondary immunity to low and high dose L. major infections and assessed the influence of infectious dose on the quality and magnitude of secondary anti-Leishmania immunity. In addition, we investigated the contribution of CD8+ T cells in secondary anti-Leishmania immunity following recovery from low and high dose infections. We found that the early immune response to low and high dose infections were strikingly different: while low dose infection preferentially induced proliferation and effector cytokine production by CD8+ T cells, high dose infection predominantly induced proliferation and cytokine production by CD4+ T cells. This differential activation of CD4+ and CD8+ T cells by high and low dose infections respectively, was imprinted during in vitro and in vivo recall responses in healed mice. Both low and high dose-infected mice displayed strong infection-induced immunity and were protected against secondary L. major challenge. While depletion of CD4+ cells in mice that healed low and high dose infections abolished resistance to secondary challenge, depletion of CD8+ cells had no effect. Collectively, our results show that although CD8+ T cells are preferentially activated and may contribute to optimal primary anti-Leishmania immunity following low dose infection, they are completely dispensable during secondary immunity.


Using a Comprehensive Proximal Stress Model to Predict Alcohol Use.
Purpose: The gender minority stress model has been proposed by researchers to explain the high rates of substance use found within transgender communities, but its explanatory power has never been directly tested. Further, qualitative research has noted that premedically transitioned and nonbinary individuals are more likely to engage in avoidant coping such as drinking to cope. As such, the current study tested the relationship between proximal stress (comprised of internalized transphobia, anticipated stigma, concealment, and gender dysphoria), drinking to cope, and problematic alcohol use. Methods: Transgender and nonbinary participants over the age of 18 (N=297) completed an online survey on alcohol use. To test for differences in drinking to cope across gender identity and medical transition, analysis of variance and independent t-tests were conducted. Further, a structural equation model of proximal stress was developed to test whether drinking to cope mediated the relationship between proximal stress and alcohol use. Results: There were no significant differences across gender identity or medical transition status in severity of drinking to cope. Proximal stress was significantly related to problematic alcohol use and the relationship was explained by an indirect relationship with drinking to cope. Conclusion: Findings from this study suggest that drinking to cope is an important aspect of high rates of alcohol use found in the transgender community. Implications for clinical practice with transgender individuals are discussed.


Prognosis of chronic glomerulonephritis with special reference to hypertension and renal function.
Incidence of hypertension in chronic glomerulonephritis and its influence on the clinical course of the disease were studied using statistic technique, especially that of Markovian process. 1. Incidence of hypertension in a total of 283 cases was 15.2%, while in the patients of which renal function reduced to approximately one half of the normal was about 50%. 2. The average of blood pressure in this disease tends to elevate with the decrease in 15 minute value of PSP excretion test and with the increasing serum creatinine level, although the variations are large. 3. After a fall of renal function to approximately one-third of the normal, the rate of clinical course is markedly rapid. 4. The prognosis of the progressive type of chronic glomerulonephritis is obviously affected to be shorten by the presence of hypertension. 5. According to the results obtained by the Markovian approach, survival years of the patients with wide range of renal function can be predicted with relative accuracy.


Smartphone Photographs to Document Preoperative Dental Examination.
Dental injury is a common cause of malpractice claims involving anesthesiologists. Inadequate preoperative dental evaluations and incomplete documentation are often cited as contributing factors during reviews of closed claims. Point-of-care smartphone photographs are widely used in other medical fields such as dermatology and plastic surgery. We discuss the use of smartphone photographs for documenting preoperative dental examinations.


Signatures of an energetic charged body streaming in a plasma.
A charged body moving in a plasma can excite a variety of linear and nonlinear waves in the form of trailing wakes, fore-wake shocks, and precursor solitons. These structures can further interact with the background plasma to create secondary effects that can serve as signatures of the passage of the charged body. Using particle-in-cell simulations, we carry out a basic investigation of the dynamics of a plasma system that is being traversed by an energetic charged body. Using two different shapes of this charged source, namely, an idealized infinite length planar source and a two-dimensional thin rectangular source, we examine the differences in the nature of the excited wave structures and their consequent impact on the background plasma. Our simulations reveal interesting features such as the dependence of the precursor speeds on the total charge on the driving source, local particle trapping, and energization of the trapped particles in various regions along the traversal path leading to the formation of energetic charged beamlets. Our basic findings could find practical applications such as in analyzing the trajectories of charged objects like space debris orbiting in the ionosphere.


Association of aquaporin-4 antibody-seropositive optic neuritis with vision-related quality of life and depression.
Aquaporin-4 (AQP4) antibody-seropositive optic neuritis (AQP4-ON) is one of the most common types of optic neuritis in China. However, the association between AQP4-ON and vision-related quality of life (QoL) and depression remains poorly understood. In this cross-sectional study, 57 patients with optic neuritis were evaluated for their vision-related QoL using a Chinese version of the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) and assessed for depressive symptoms using a Chinese version of the Beck Depression Inventory-II (BDI-II). Data regarding participants' age, sex, visual acuity, and the number of recurrence events were gathered. Linear regression analysis was employed to investigate the relationships between AQP4-ON and vision-related QoL, as well as depression. Of the 57 included patients, 28 were AQP4-ON, and 29 were idiopathic optic neuritis (ION). AQP4-ON demonstrated a significant correlation with a decreased VFQ-25 composite score (Mean difference, -11.65 [95% CI, -21.61 to -1.69]; p = 0.023) and an increased BDI-II score (Mean difference, 6.48 [95% CI, 0.25 to 12.71]; p = 0.042) when compared to ION. The BDI-II score was correlated with the VFQ-25 composite score (Spearman ρ = -0.469; p < 0.001) but not with the visual acuity in the worse-seeing eye (Spearman ρ = 0.024; p = 0.860) or in the better-seeing eye (Spearman ρ = -0.039; p = 0.775), bilateral severe visual impairment (Spearman ρ = 0.039; p = 0.772) or the number of recurrence events (Spearman ρ = 0.184; p = 0.171). AQP4-positive optic neuritis is associated with a decline in vision-related quality of life as well as an increased likelihood of experiencing depression. It is crucial for clinicians to assess both vision-related QoL and depression in patients with AQP4-positive optic neuritis to provide patient-centered care.


Perinatal fluoxetine effects on social play, the HPA system, and hippocampal plasticity in pre-adolescent male and female rats: Interactions with pre-gestational maternal stress.
Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the hippocampus of pre-adolescent offspring.


Cloning of thyroid hormone receptor genes expressed in metamorphosing flounder.
Two distinct cDNAs encoding thyroid hormone receptors (THRs) were cloned from a lambda gt10 library prepared from the whole bodies of metamorphosing flounder larvae (Paralichthys olivaceus). Deduced amino acid sequences of the two isolated cDNAs shared 96% and 92% homologies in their DNA- and hormone-binding domains, respectively. These were highly conserved when compared to THRs for other vertebrates: 88-96% in the DNA-binding domain and 84-94% in the hormone-binding domain. Other receptors in the nuclear receptor family showed lower homologies than those of THRs. Both THRs for the flounder had higher homologies with the alpha-type THRs of other vertebrates than with the beta-type. Thus, the two THRs for flounder were designated as fTHR alpha A and fTHR alpha B.


Regulation of Mycobacterium bovis BCG and foreign body granulomas in mice by the Bcg gene.
Natural bactericidal resistance to Mycobacterium bovis BCG is under the control of a single gene, designated Bcg. Lung granuloma formation in susceptible (Bcgs) and resistant (Bcgr) mice was studied in two sets of Bcg-congenic systems, namely, the BALB/c (Bcgs)-C.D2 (BALB/c.Bcgr) pair and the B10.A (Bcgs)-B10.Ar (Bcgr) pair, by using BCG as well as foreign body granuloma-inducing agents (dextran beads). Large granulomas of the lung induced by the intratracheal instillation of either BCG or dextran beads developed in Bcgs mice. In contrast, minimal inflammation was produced in Bcgr mice given BCG or dextran beads. Aqueous extracts prepared from pulmonary granuloma lesions induced by Bcgs mice by either BCG or dextran beads contained high levels of interleukin-1 (IL-1) activity but not interleukin-2 (IL-2) or interleukin-4 (IL-4) activity. Very low IL-1 activity was detected in extracts from Bcgr mice injected with BCG and dextran beads. The activity of IL-1 was correlated closely with the activity and size of the granulomatous inflammation in mice. These results suggest that pleiotropic effects of the Bcg gene are involved in the development of granulomas induced by either BCG or nonspecific foreign body agents (dextran beads) and that monokines participate in granuloma formation.


Efficiency of charge transfer in changing the dissociation dynamics of OD+ transients formed after the photo-fragmentation of D2O.
We present an investigation of the relaxation dynamics of deuterated water molecules after direct photo-double ionization at 61 eV. We focus on the very rare D+ + O+ + D reaction channel in which the sequential fragmentation mechanisms were found to dominate the dynamics. Aided by theory, the state-selective formation and breakup of the transient OD+(a1Δ, b1Σ+) is traced, and the most likely dissociation path-OD+: a1Δ or b1Σ+ → A 3Π → X 3Σ- → B 3Σ--involving a combination of spin-orbit and non-adiabatic charge transfer transitions is determined. The multi-step transition probability of this complex transition sequence in the intermediate fragment ion is directly evaluated as a function of the energy of the transient OD+ above its lowest dissociation limit from the measured ratio of the D+ + O+ + D and competing D+ + D+ + O sequential fragmentation channels, which are measured simultaneously. Our coupled-channel time-dependent dynamics calculations reproduce the general trends of these multi-state relative transition rates toward the three-body fragmentation channels.


beta-Sitosterolemia with generalized eruptive xanthomatosis.
The clinical features of the first case of a patient with sitosterolemia and generalized eruptive xanthomatosis are described. A six-year-old girl with generalized eruption was referred to the lipid clinic because of the high plasma cholesterol levels determined by the enzymatic method. Neither clinical signs nor results of laboratory examinations appeared to be abnormal, except for the eruption and the increase in the plasma cholesterol concentration. A family survey revealed high plasma cholesterol concentrations in the mother and one of two other siblings. Histological examination showed the eruption to be a xanthoma. Plasma sterol analysis by high-performance liquid chromatography revealed a noticeable increase in plasma plant sterol as well as cholestanol concentrations in the proband and the hypercholesterolemic sibling. The other family members had slightly high plasma sterol concentrations. This is the first case of a sitosterolemic patient with eruptive xanthomatosis. The case indicates that the clinical features of the xanthoma in sitosterolemia are not only tuberous or tendon but also eruptive, and also suggests that sitosterolemia should be considered in the differential diagnosis of hypercholesterolemia in almost every case with tuberous or eruptive xanthoma. The diagnosis is clinically important, since the disease can be treated successfully by diet therapy and bile acid binding resins.


Regenerative Medicine Technologies to Treat Dental, Oral, and Craniofacial Defects.
Additive manufacturing (AM) is the automated production of three-dimensional (3D) structures through successive layer-by-layer deposition of materials directed by computer-aided-design (CAD) software. While current clinical procedures that aim to reconstruct hard and soft tissue defects resulting from periodontal disease, congenital or acquired pathology, and maxillofacial trauma often utilize mass-produced biomaterials created for a variety of surgical indications, AM represents a paradigm shift in manufacturing at the individual patient level. Computer-aided systems employ algorithms to design customized, image-based scaffolds with high external shape complexity and spatial patterning of internal architecture guided by topology optimization. 3D bioprinting and surface modification techniques further enhance scaffold functionalization and osteogenic potential through the incorporation of viable cells, bioactive molecules, biomimetic materials and vectors for transgene expression within the layered architecture. These computational design features enable fabrication of tissue engineering constructs with highly tailored mechanical, structural, and biochemical properties for bone. This review examines key properties of scaffold design, bioresorbable bone scaffolds produced by AM processes, and clinical applications of these regenerative technologies. AM is transforming the field of personalized dental medicine and has great potential to improve regenerative outcomes in patient care.


Exercise Therapy Downregulates the Overexpression of TLR4, TLR2, MyD88 and NF-κB after Cerebral Ischemia in Rats.
Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) are considered to mediate the inflammatory reaction of cerebral ischemia injury, and exercise can inhibit the activity of the Toll-like receptor signaling pathway in the peripheral blood of humans. Although physical exercise has been demonstrated to be neuroprotective in both clinical and laboratory settings, the underlying mechanism remains unclear. To clarify this critical issue, this study investigated the effects of treadmill training on the recovery of neurological function and the expression of TLR2 and TLR4 and their main downstream targets, nuclear factor-kappaB (NF-κB) and myeloid differentiation factor 88 (MyD88), in the ischemic rat brain after middle cerebral artery occlusion-reperfusion (MCAo/R). Rats were divided into seven groups: sham control without MCAo/R and five, nine and 16 days post-ischemic exercise or non-exercise. The neurological function and infarct volume were measured, and reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression of TLR2, TLR4, NF-κB and MyD88 in ischemic brain tissue. The results indicated that treadmill training promoted functional recovery and reduced the overexpression of TLR2, TLR4, NF-κB and MyD88 in rat brain tissue after ischemia, a finding that may have implications for understanding the mechanism of exercise therapy after brain ischemia and indicating new therapeutic strategies for the pharmacological modulation of TLR signaling.