[Non small cell lung cancer and thoracic surgery: the role of the primary care physician].
Lung cancer is a frequent cause of death in Western countries. The prognosis is dismal because the vast majority of cases presents to the physician at a stage that is not operable. Surgical resection of non small cell lung carcinoma when feasible offers the best chance for survival in carefully chosen patients. A preoperative physiologic assessment can help to identify those patients who are at increased risk for cancer resection. Using the algorithm proposed in this article, the primary care physician should be able to better select patients addressed for lung cancer surgery.


CXC Chemokine Receptor Type 4 Antagonism Ameliorated Allograft Fibrosis in Rat Kidney Transplant Model.
In this study, we evaluated the effects of CXC chemokine receptor type 4 and stromal cell-derived factor 1 signaling in the progression of chronic allograft nephropathy in a rat model. Experimental rats were divided into 3 groups: Lewis-to-Lewis isograft transplant (group A), Fisher 344 rat-to-Lewis allograft transplant with immunosuppressant cyclosporine (group B), and Fisher 344 rat-to-Lewis allograft transplant treated with cyclosporine and the CXC chemokine receptor type 4 antagonist AMD3100 (1 mg/kg/d) (group C). On day 90 after the operation, renal graft function, proteinuria, and histologic Banff score were measured. The expression levels of transforming growth factor β1 and collagen IV were determined by quantitative real-time polymerase chain reaction. Renal function and urinary protein were increased in allografts of groups B and C compared with isografts of group A. The Banff score was significantly decreased in the AMD3100-treated animals (group C), with renal fibrosis being reduced. In addition, overexpressed levels of transforming growth factor β1 and collagen IV in group B allografts were significantly reduced versus that shown with treatment with the CXC chemokine receptor type 4 antagonist in group C. Together, these data strongly implicate that CXC chemokine receptor type 4 antagonism alleviated renal interstitial fibrosis in long-term surviving allografts by down-regulating expression of transforming growth factor β1.


[Peritoneovenous shunt in the treatment of therapy resistant ascites. Results of 7 years' experience].
In recent years, implantation of a peritoneo-venous shunt has proven effective in the treatment of therapy-resistant ascites. From 1976 till 1983, a total of 63 shunt systems (Le Veen-, Agishi -, Denver system) were implanted in 55 patients with a mean age of 52.3 years. The most common cause for ascites was hepatic cirrhosis. The average functional period amounted to 21.7 months and the longest implantation time to nearly 7 years. The postoperative complication rate is considerable: 19 patients died in the postoperative course. The most dreaded complication is shunt infection and intravascular thrombopathy . In spite of the high complication rate, the establishment of a peritoneo-venous shunt is recommendable for combatting therapy-resistant ascites.


Early-Life Home Environment and Obesity in a Mexican American Birth Cohort: The CHAMACOS Study.
Little is known about the impact of the home environment on biomarkers of obesity, such as adipokines, in children. In this study, we examined the relationship of maternal depressive symptoms and potentially protective social factors, including maternal support and the home learning environment, with body mass index and adipokines. Data were obtained from 326 Mexican American participants from the Center for the Health Assessment of Mothers and Children of Salinas cohort. Plasma adipokine levels were assessed in 326 children by enzyme-linked immunoassay at birth or ages 5, 9, or 14 years. Maternal depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale when children were 1, 3.5, 7, and 9 years old; social support was assessed by the Duke-University of North Carolina Questionnaire at ages 1 and 5 years; and home learning environment by the Home Observation for the Measurement of the Environment (HOME) at ages of 6 months and 1, 2, 3.5, 7, 9, and 10.5 years. Age was significantly associated with adiponectin (B = -5.0, SE = 0.2) and leptin (B = 0.01, SE = 0.003) levels. Individual time point analyses identified significant positive associations of HOME scores in childhood with adiponectin at ages 9 years (HOME score; age 3.5 years: B = 0.9, p = .04) and 14 years (HOME score; age 7 years: B = 0.6, p = .02, age 9 years: B = 0.6, p = .05, age 10.5 years: B = 0.5, p = .04). We observed significant relationships of maternal depressive symptoms at age 9 years with adiponectin and body mass index z-score at age 14 years (B = -0.2, p = .003 and B = 0.02, p = .002, resp.), which were confirmed in longitudinal models. This study adds new evidence that adverse and protective aspects of the home environment could lead to altered obesity status in children.


[Medicine in the "Nisuke-banashi"].
In the Edo period, the "Nisuke-banashi" was written in Yabe district in Higo, Kumamoto Prefecture. This book described the lives of the farmers who were very poor and lived under very difficult conditions. In the book a doctor had an important role in explaining the truth. He also advised on some medical affairs. The author of this book was presumed to be a doctor named Watanabe Tadasu who lived in Hama-machi, Yabe. I studied the medical explanations in this book and found that these stories were based on old Chinese medical texts such as Somon, Shokanron and Kinkiyoryaku.


[Acute myeloblastic leukemia in adults: evaluation of the AML 06/96 protocol].
The treatment of acute myeloid leukemia (AML) permits in a population of 25 to 60 years, a complete remission (CR) about 60 to 85% with relapse free survival at 5 years from 45 to 60%. We report our therapeutic results during two years, from june 1996 to december 1998. 104 patients with the novo AML treated according to AML 06/96 protocol, the mean age was 32.5 years old, from 16 to 55 years old. The hyperleucocytar form (GB > 50,000 elts/mm3) represented the third of the cases, only 98 patients received the induction. 6 patients died before treatment. The whole rate of CR was 55%. The rate of failure was 16%, the deaths was about 15.5%, the relapse represented 30.6% with mean delay about 14.1 months, from 4 to 35 months. The CR has been maintained in 9 patients with mean recession of 53 months, from 36 months to 62 months. The overall survival at 5 years was 9%. Our results are still unsufficient in comparison with the literature and could be improved by recess of ARA-C and donorubicin doses in induction and consolidation, as well as a good knowledge about the cytogenetical aspect of the treated population.


Art-of-Living Training: Developing an Intervention for Students to Increase Art-of-Living.
Art-of-living describes a mindful and self-determined way of dealing with one's self and way of life. It is related to measures of well-being. Art-of-living is based on strategies and attitudes which can be learned and therefore can be changed. Two types of training for students to increase art-of-living were developed and tested in two studies to determine the effects on art-of-living measures. Study 1 dealt with the initial examination of whether it is possible to enhance the art-of-living by training selected art-of-living strategies. Therefore, training with three conditions was developed and conducted with secondary school students (ages 16-19). In Study 2, a second art-of-living training was developed and conducted with children from primary school (ages 8-11). In Study 1, the art-of-living measures increased significantly for the training conditions compared to a control group. In addition, Study 2 showed that higher levels of the art-of-living lead to a better quality of life. In summary, the training successfully enhanced art-of-living. Limitations on and benefits of utilising the art-of-living training are discussed.


Two Arabidopsis genes (IPMS1 and IPMS2) encode isopropylmalate synthase, the branchpoint step in the biosynthesis of leucine.
Heterologous expression of the Arabidopsis (Arabidopsis thaliana) IPMS1 (At1g18500) and IPMS2 (At1g74040) cDNAs in Escherichia coli yields isopropylmalate synthases (IPMSs; EC 184.108.40.206). These enzymes catalyze the first dedicated step in leucine (Leu) biosynthesis, an aldol-type condensation of acetyl-coenzyme A (CoA) and 2-oxoisovalerate yielding isopropylmalate. Most biochemical properties of IPMS1 and IPMS2 are similar: broad pH optimum around pH 8.5, Mg2+ as cofactor, feedback inhibition by Leu, Km for 2-oxoisovalerate of approximately 300 microM, and a Vmax of approximately 2 x 10(3) micromol min(-1) g(-1). However, IPMS1 and IPMS2 differ in their Km for acetyl-CoA (45 microM and 16 microM, respectively) and apparent quaternary structure (dimer and tetramer, respectively). A knockout insertion mutant for IPMS1 showed an increase in valine content but no changes in Leu content; two insertion mutants for IPMS2 did not show any changes in soluble amino acid content. Apparently, in planta each gene can adequately compensate for the absence of the other, consistent with available microarray and reverse transcription-polymerase chain reaction data that show that both genes are expressed in all organs at all developmental stages. Both encoded proteins accept 2-oxo acid substrates in vitro ranging in length from glyoxylate to 2-oxohexanoate, and catalyze at a low rate the condensation of acetyl-CoA and 4-methylthio-2-oxobutyrate, i.e. a reaction involved in glucosinolate chain elongation normally catalyzed by methylthioalkylmalate synthases. The evolutionary relationship between IPMS and methylthioalkylmalate synthase enzymes is discussed in view of their amino acid sequence identity (60%) and overlap in substrate specificity.


A Comprehensive Workflow for Applying Single-Cell Clustering and Pseudotime Analysis to Flow Cytometry Data.
The introduction of single-cell platforms inspired the development of high-dimensional single-cell analysis tools to comprehensively characterize the underlying cellular heterogeneity. Flow cytometry data are traditionally analyzed by (subjective) gating of subpopulations on two-dimensional plots. However, the increasing number of parameters measured by conventional and spectral flow cytometry reinforces the need to apply many of the recently developed tools for single-cell analysis on flow cytometry data, as well. However, the myriads of analysis options offered by the continuously released novel packages can be overwhelming to the immunologist with limited computational background. In this article, we explain the main concepts of such analyses and provide a detailed workflow to illustrate their implications and additional prerequisites when applied on flow cytometry data. Moreover, we provide readily applicable R code covering transformation, normalization, dimensionality reduction, clustering, and pseudotime analysis that can serve as a template for future analyses. We demonstrate the merit of our workflow by reanalyzing a public human dataset. Compared with standard gating, the results of our workflow provide new insights in cellular subsets, alternative classifications, and hypothetical trajectories. Taken together, we present a well-documented workflow, which utilizes existing high-dimensional single-cell analysis tools to reveal cellular heterogeneity and intercellular relationships in flow cytometry data.


Down-regulation of the miRNA-200 family at the invasive front of colorectal cancers with degraded basement membrane indicates EMT is involved in cancer progression.
Cancer progression is a complex series of events thought to incorporate the reversible developmental process of epithelial-to-mesenchymal transition (EMT). In vitro, the microRNA-200 family maintains the epithelial phenotype by posttranscriptionally inhibiting the E-cadherin repressors, ZEB1 and ZEB2. Here, we used in situ hybridization and immunohistochemistry to assess expression of miR-200 and EMT biomarkers in formalin-fixed paraffin-embedded human colorectal adenocarcinomas. In addition, laser capture microdissection and quantitative real-time polymerase chain reaction were employed to quantify levels of miR-200 in the normal epithelium, tumor core, invasive front, and stroma. We find that miR-200 is downregulated at the invasive front of colorectal adenocarcinomas that have destroyed and invaded beyond the basement membrane. However, regional lymph node metastases and vascular carcinoma deposits show strong expression of miR-200, suggesting this family of miRNAs is involved in the recapitulation of the primary tumor phenotype at metastatic sites. In contrast, adenomas and adenocarcinomas with intact basement membranes showed uniform miR-200 expression from the tumor core to the tumor-host interface. Taken together, these data support the involvement of EMT and mesenchymal-to-epithelial transition (MET) in the metastasis cascade and show that miR-200 is downregulated in the initial stages of stromal invasion but is restored at metastatic sites.


Simulating the effect of surfactant structure on bending moduli of monolayers.
We have used dissipative particle dynamics to simulate amphiphilic monolayers on the interface between oil and water. An ultralow interfacial tension is imposed by means of Monte Carlo to resemble the amphiphilic films that separate oil and water regions in microemulsions. We calculate the bending modulus by analyzing the undulation spectrum. By varying the surfactant chain length and topology we investigate the effect of surfactant structure and composition of the monolayer on the bending moduli. We find that increasing the thickness has a larger effect than increasing the density of the layer. This follows from the observations that at a given interfacial tension, the bending modulus increases with chain length and is larger for linear than branched surfactants. The increase with chain length is approximately linear, which is slower than the theoretical predictions at a fixed area. We also investigated a binary mixture of short and long surfactants compared to pure layers of the same average chain length. We find a roughly linear decrease in bending modulus with mole fraction of short surfactants. Furthermore, the mixed film has a lower bending modulus than the corresponding pure film for all mole fractions. Linking the bending moduli to the structure of the surfactants is an important step in predicting the stability of microemulsions.


Optimal Anticoagulant Therapy in ST Elevation Myocardial Infarction Interventions.
Bivalirudin is a direct thrombin inhibitor. It is a new recommendation for the treatment of patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention. Bivalirudin combined with aspirin and P2Y12 inhibitors has proved to be an effective and safe choice for the management of thrombus in coronary artery disease. The use of bivalirudin compared with the combination of heparin plus glycoprotein IIb/IIIa inhibitors as anticoagulant therapy is associated with reduced severe bleeding and inpatient mortality, as well as diminished costs. There is only a slight increase of late stent thrombosis, which may be controlled with the use of thienopyridines.


Frequency analysis of the molecular vibrations of HCP.
Relevant aspects of the phase space structure corresponding to the vibrational dynamics of a two-dimensional model of the HCP molecule are studied in detail using a frequency analysis method. By performing this analysis locally for reduced periods of time, the underlying chaotic structure and the main resonances have been determined.


A system dynamics modelling approach to assess the impact of launching a new nicotine product on population health outcomes.
In 2012 the US FDA suggested the use of mathematical models to assess the impact of releasing new nicotine or tobacco products on population health outcomes. A model based on system dynamics methodology was developed to project the potential effects of a new nicotine product at a population level. A model representing traditional smoking populations (never, current and former smokers) and calibrated using historical data was extended to a two-product model by including electronic cigarettes use statuses. Smoking mechanisms, such as product initiation, switching, transition to dual use, and cessation, were represented as flows between smoking statuses (stocks) and the potential effect of smoking renormalisation through a feedback system. Mortality over a 50-year period (2000-2050) was the health outcome of interest, and was compared between two scenarios, with and without e-cigarettes being introduced. The results suggest that by 2050, smoking prevalence in adults was 12.4% in the core model and 9.7% (including dual users) in the counterfactual. Smoking-related mortality was 8.4% and 8.1%, respectively. The results suggested an overall beneficial effect from launching e-cigarettes and that system dynamics could be a useful approach to assess the potential population health effects of nicotine products when epidemiological data are not available.


Pellet Production from Pruning and Alternative Forest Biomass: A Review of the Most Recent Research Findings.
Typically, coniferous sawdust from debarked stems is used to make pellets. Given the high lignin content, which ensures strong binding and high calorific values, this feedstock provides the best quality available. However, finding alternative feedstocks for pellet production is crucial if small-scale pellet production is to be developed and used to support the economy and energy independence of rural communities. These communities have to be able to create pellets devoid of additives and without biomass pre-processing so that the feedstock price remains low. The features of pellets made from other sources of forest biomass, such as different types of waste, broadleaf species, and pruning biomass, have attracted some attention in this context. This review sought to provide an overview of the most recent (2019-2023) knowledge on the subject and to bring into consideration potential feedstocks for the growth of small-scale pellet production. Findings from the literature show that poor bulk density and mechanical durability are the most frequent issues when making pellets from different feedstocks. All of the tested alternative biomass typologies have these shortcomings, which are also a result of the use of low-performance pelletizers in small-scale production, preventing the achievement of adequate mechanical qualities. Pellets made from pruning biomass, coniferous residues, and wood from short-rotation coppice plants all have significant flaws in terms of ash content and, in some cases, nitrogen, sulfur, and chlorine content as well. All things considered, research suggests that broadleaf wood from beech and oak trees, collected through routine forest management activities, makes the best feasible feedstock for small-scale pellet production. Despite having poor mechanical qualities, these feedstocks can provide pellets with a low ash level. High ash content is a significant disadvantage when considering pellet manufacture and use on a small scale since it can significantly raise maintenance costs, compromising the supply chain's ability to operate cost-effectively. Pellets with low bulk density and low mechanical durability can be successfully used in a small-scale supply chain with the advantages of reducing travel distance from the production site and storage time.


Incorporation of [14C]glucose into lipids of bovine oligodendroglia.
Oligodendrocytes were isolated from the white matter of ox brains. Light microscopy revealed that the cells were greater than or equal to 90% phase-bright with a mean diameter of 7.6 micron. Transmission electron microscopy was employed to identify the classic morphology associated with mature oligodendrocytes. Homogenates of the isolated cells showed negligible activity of neuronal and astrocytic cell markers. Using a suspension culture method cells were incubated with [14C]glucose. This simple precursor labelled the five complex lipids choline glycerophospholipid, ethanolamine glycerophospholipid, inositol glycerophospholipid + serine glycerophospholipid, and the two cerebroside species. The incorporation of label was shown to be dependent on glucose concentration, protein concentration, and the length of incubation. In addition the glucose uptake blocker phloretin (1 mM) reduced the degree of labelling by up to 97%, and the metabolic poisons KCN (1 mM) and iodoacetate (0.5 mM) had varying deleterious effects on the amounts of labelling of the five lipids measured.


Retargeting CD19 Chimeric Antigen Receptor T Cells via Engineered CD19-Fusion Proteins.
CD19-targeted chimeric antigen receptor (CAR) T-cells (CAR19s) show remarkable efficacy in the treatment of relapsed/refractory acute lymphocytic leukemia and Non-Hodgkin's lymphoma. However, the use of CAR T-cell therapy against CD19-negative hematological cancers and solid tumors has been challenging. We propose CD19-fusion proteins (CD19-FPs) to leverage the benefits of CAR19s while retargeting this validated cellular therapy to alternative tumor antigens. We demonstrate the ability of a fusion of CD19 extracellular domain (ECD) and a human epidermal growth factor receptor 2 (HER2) single-chain antibody fragment to retarget CAR19s to kill HER2+ CD19- tumor cells. To enhance the modularity of this technology, we engineered a more robust CD19 ECD via deep mutational scanning with yeast display and flow cytometric selections for improved protease resistance and anti-CD19 antibody binding. These enhanced CD19 ECDs significantly increase, and in some cases recover, fusion protein expression while maintaining target antigen affinity. Importantly, CD19-FPs retarget CAR19s to kill tumor cells expressing multiple distinct antigens, including HER2, CD20, EGFR, BCMA, and Clec12A as N- or C-terminal fusions and linked to both antibody fragments and fibronectin ligands. This study provides fundamental insights into CD19 sequence-function relationships and defines a flexible and modular platform to retarget CAR19s to any tumor antigen.


Dynamic charge fluctuation of endohedral fullerene with coencapsulated Be atom and H2.
As one of the typical examples of characteristic reaction field generated in inclusion (enclosure) compounds, the dynamics of an endohedral metallofullerene, (Be+nH2)@C60(n=1,2), is studied with Be atom serving as a test probe. A very large dynamical and thermal fluctuation of electronic state of Be has been found, which is surprising since the highest occupied molecular orbital-lowest unoccupied molecular orbital gap of Be is so wide that such a large fluctuation in a low temperature is never expected. This finding demonstrates one of the special features of endohedral reaction field offered by the fullerene. The physical origin of this phenomenon is analyzed.


Continuous-wave and passively Q-switched laser performance with a disordered Nd:CLNGG crystal.
We demonstrated efficient high-power continuous-wave (cw) and passively Q-switched disordered Nd:CLNGG laser performance. In cw operations, the output power was obtained to be 3.81 W with a slope efficiency of 30.3%. To our knowledge, they are the highest cw power and efficiency with Nd:CLNGG as the gain medium and a laser-diode (LD) as the pump source. Recorded with a spectrum analyzer, no splitting was found in the Nd:CLNGG laser, which is different with that of its isomorph Nd:CNGG. The LD pumped passively Q-switched Nd:CLNGG laser was obtained for the first time to our knowledge. The shortest pulse width, largest pulse energy and highest peak power were achieved to be 12.3 ns, 199.1 microJ and 16 kW, respectively, with Cr(4+):YAG crystals as the saturable absorbers.


Calibration of a Thomson scattering diagnostic for fluctuation measurements.
Detailed calibrations of the Madison Symmetric Torus polychromator Thomson scattering system have been made suitable for electron temperature fluctuation measurements. All calibrations have taken place focusing on accuracy, ease of use and repeatability, and in situ measurements wherever possible. Novel calibration processes have been made possible with an insertable integrating sphere (ISIS), using an avalanche photodiode (APD) as a reference detector and optical parametric oscillator (OPO). Discussed are a novel in situ spatial calibration with the use of the ISIS, the use of an APD as a reference detector to streamline the APD calibration process, a standard dc spectral calibration, and in situ pulsed spectral calibration made possible with a combination of an OPO as a light source, the ISIS, and an APD used as a reference detector. In addition a relative quantum efficiency curve for the APDs is obtained to aid in uncertainty analysis.


The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells.
Three members of the Src family of protein tyrosine kinases Src, Fyn, and Yes associate with the activated platelet-derived growth factor (PDGF) receptor in vivo. This interaction requires the Src homology 2 (SH2) domain of the Src family member and causes activation of the intrinsic activity of the Src family kinases. We microinjected cells with DNA encoding catalytically inactive forms of the Src and Fyn proteins and examined their effects on PDGF-mediated signaling in vivo. Kinase-inactive Src and Fyn inhibited PDGF-stimulated entry of cells into S phase, whereas kinase-active forms of the proteins had no inhibitory effects. An intact SH2 domain was required for inhibition. Furthermore, when kinase-inactive Fyn was comicroinjected with a plasmid expressing activated Ras, the cells could enter S phase, indicating that the expression of kinase-inactive Fyn did not damage cell viability. Injection of an antibody specific for Src, Fyn, and Yes also reduced signal transduction through the PDGF receptor but only when injected within 8 hr of PDGF stimulation. Together these results indicate that the ubiquitously expressed Src family members are required for PDGF-induced mitogenic signaling.


Nature of Cations Critically Affects Water at the Negatively Charged Silica Interface.
Understanding the collective behavior of ions at charged surfaces is of paramount importance for geological and electrochemical processes. Ions screen the surface charge, and interfacial fields break the centro-symmetry near the surface, which can be probed using second-order nonlinear spectroscopies. The effect of electrolyte concentration on the nonlinear optical response has been semi-quantitatively explained by mean-field models based on the Poisson-Boltzmann equation. Yet, to explain previously reported ion-specific effects on the spectroscopic response, drastic ion-specific changes in the interfacial properties, including surface acidities and dielectric permittivities, or strong ion adsorption/desorption had to be invoked. Here, we use sum-frequency generation (SFG) spectroscopy to probe the symmetry-breaking of water molecules at a charged silica surface in contact with alkaline metal chloride solutions (LiCl, NaCl, KCl, and CsCl) at various concentrations. We find that the water response varies with the cation: the SFG response is markedly enhanced for LiCl compared to CsCl. We show that within mean-field models, neither specific ion-surface interactions nor a reduced dielectric constant of water near the interface can account for the variation of spectral intensities with cation nature. Molecular dynamics simulations confirm that the decay of the electrochemical potential only weakly depends on the salt type. Instead, the effect of different salts on the optical response is indirect, through the reorganization of the interfacial water: the salt-type-dependent alignment of water directly at the interface can explain the observations.


Analysis of styrene oxide-globin adducts based upon reaction with Raney nickel.
A new method has been developed for determination of styrene oxide-globin adducts. The technique takes advantage of the reaction between alkylated globin and Raney nickel, which cleaves the carbon-sulfur bond in the styrene oxide-cysteine adduct to form 1-phenylethanol (1-PE) and 2-phenylethanol (2-PE). These alcohols are then reacted with pentafluorobenzoyl chloride and analyzed by GC-ECD. The method appears useful for biological monitoring of individuals exposed to styrene and, potentially, to other chemicals or their electrophilic metabolites which can react with cysteine residues in available proteins. The detection limit of the method, which is 0.04 nmol adducts/sample, indicates that it should be possible to detect adducts in the blood of people who are occupationally exposed to at least 18 mg/m3 of styrene. Analysis of globin from human whole blood which had been modified with [14C]styrene oxide indicated that 6% of the total globin adducts were detected. The method was applied to human and rat blood which had been treated with styrene oxide in vitro and to blood from rats given a single i.p. dose of styrene in vivo. Results from these experiments indicate that 77 times more adducts were detected at a given dose from rat globin than from human globin and that only 0.015% of the styrene dose was bioavailable as styrene oxide in the blood of rats. The reaction with Raney nickel is conducted at 5 degrees C to minimize unfavorable side reactions, such as degradation of 1- and 2-PE and conversion of styrene glycol to 1- and 2-PE. The optimal amount of Raney nickel was found to be 5-6 g/g globin. Since the recovery of 1-PE was not reproducible, only 2-PE is used for quantitation.


The effect of accelerated lactation on fetal maintenance in the rat.
Rats mated post partum were permitted to nurse 2 pups until day 9, at which time laparotomy was performed and the number of implantation sites counted. Control animals were left to nurse 2 pups or none, while lactation was then accelerated in 4 other groups by the addition of more pups to totals of 3, 5, 7 or 9. On day 19 the mothers were killed and the fetuses counted, weighed and checked for normality. With increased lactational demand the proportion of fetuses maintained decreased. Total fetal weight was decreased significantly only when 7 or more pups were being nursed. Individual fetal weights and normalcy were not affected by accelerated lactation.


Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutant.
We have characterized a nondifferentiating mouse muscle cell line, NFB, that represses the activity of the helix-loop-helix (HLH) family of myogenic regulators, yet expresses sarcomeric actins. The NFB MyoD gene is silent, but can be activated upon transfection of a long terminal region-controlled chicken MyoD cDNA, resulting in myogenesis. When NFB cells are fused with H9c2 rat muscle cells in heterokaryons, the level of rat MyoD transcripts declines. Thus, the stoichiometry of MyoD and the putative repressor controls myogenesis. Although NFB cells express myogenin and Myf-5 transcripts, the activity of these regulators is also repressed:myogenesis is not induced in 10T1/2 fibroblasts and is repressed in L6 muscle cells upon fusion with NFB cells. We conclude that the myogenic HLH regulators are not required for sarcomeric actin gene activation and that myogenesis is subject to dominant-negative control.


Plasma channels produced by a laser-triggered high-voltage discharge.
A plasma waveguide scheme for high-intensity laser guiding with densities and lengths suitable for laser-plasma particle accelerators is presented. This scheme uses a laser-triggered high-voltage discharge, presents negligible jitter, allows full access to the plasma, and can be scaled to large distances. Experimental results showing the feasibility of this scheme are presented.


The nature of extinction.
The phenomenon of species extinction raises more and more concern among ecologists facing the actual crisis of biodiversity. Scientific investigations of the causes and effects of extinction must be completed by a philosophical analysis of the concept of extinction that aims to clarify the meanings of the term 'extinction' and to analyse modalities, criteria and degrees of extinction. We will focus our attention on the apparent paradox of the possible 'resurrection' of species in the near future with the help of genetic biotechnology and cloning techniques. The ontological background of the extinction concept is analysed in relation to the idea of species as classes. We will also show that there is no simple analogy between death and species extinction, and develop a conceptualist and dualistic system of supra-individual entities (species vs. population), supported by an instrumentalist approach to genetic manipulations which transform species into interactive kinds, which can go extinct and be recreated.


A prematurely terminated phase III trial of intraoperative intrapleural hypotonic cisplatin treatment in patients with resected non-small cell lung cancer with positive pleural lavage cytology: the incidence of carcinomatous pleuritis after surgical intervention.
The prognosis of patients with resected non-small cell lung cancer without carcinomatous pleuritis whose intrapleural cancer cells were detected by means of a cytologic examination of pleural lavage fluid obtained immediately after a thoracotomy has been reported to be poor. The Japan Clinical Oncology Group conducted a phase III trial for a 3-year period starting from October 1994 to determine whether intraoperative intrapleural hypotonic cisplatin treatment could effectively control pleural disease and thereby prolong the survival of these patients. The patients were randomized to receive either intraoperative intrapleural hypotonic cisplatin treatment or no treatment before closure of the open thorax. The intraoperative intrapleural hypotonic cisplatin treatment consisted of exposing the entire thorax to cisplatin (50 microg/mL) in distilled water for 15 minutes. Because of the slow registration pace, the study was prematurely terminated in January 1998. During the 41-month period from the start of the registration, 49 patients were entered into the study, and all were eligible. Twenty-five and 24 patients were randomly assigned to the treatment and control groups, respectively. No statistically significant difference in the overall survival and disease-free survival between the 2 groups was observed. However, the appearance of carcinomatous pleuritis was suppressed by the hypotonic cisplatin treatment (42% of the control group vs 8% of the treatment group, P =.008). Although the randomized trial was prematurely terminated, the intraoperative intrapleural hypotonic cisplatin treatment was found to effectively suppress the appearance of carcinomatous pleuritis in resected patients who demonstrated a positive pleural lavage cytology finding.


Subcutaneous phaeohyphomycotic abscess caused by Phialophora parasitica in a renal allograft recipient.
A 61-year-old renal transplant recipient developed a subcutaneous leg abscess caused by Phialophora parasitica. Treatment with fluconazole resulted in no improvement after 18 weeks. The abscess required excision for cure. This phaeohyphomycotic infection due to P. parasitica represents the fourth case in a renal transplant recipient described in the literature.


All optical operation of a superconducting photonic interface.
Quantum photonic processing via electro-optic components typically requires electronic links across different operation environments, especially when interfacing cryogenic components such as superconducting single photon detectors with room-temperature control and readout electronics. However, readout and driving electronics can introduce detrimental parasitic effects. Here we show an all-optical control and readout of a superconducting nanowire single photon detector (SNSPD), completely electrically decoupled from room temperature electronics. We provide the operation power for the superconducting detector via a cryogenic photodiode, and readout single photon detection signals via a cryogenic electro-optic modulator in the same cryostat. This method opens the possibility for control and readout of superconducting circuits, and feedforward for photonic quantum computing.


Daily Informal Multidisciplinary Intensive Care Unit Operational Debriefing Provides Effective Support for Intensive Care Unit Nurses.
Although most organizations have comprehensive formal stress management programs, an approach that is most likely to be helpful is the one that is curtailed specifically to the needs of a particular nursing unit. With that aim in mind, a process of daily intensive care unit (ICU) multidisciplinary operational debriefings was developed. These operational debriefings use the same concepts as traditional debriefing, yet are offered on a daily basis, rather than being reserved only for major stressful events. Furthermore, they are informal, brief (15 minutes), and multidisciplinary (intensivists, ICU nurses, chaplain, ICU social worker, ICU nutritionist, and ICU pharmacist). The purpose of this descriptive study was to determine the perceptions of attendees in relation to the implementation of daily operational debriefings. Six months into the process, the attendees were requested to fill out an anonymous voluntary survey. Questions were simple, straightforward, and close ended. Of 47 potential respondents (42 nurses, 2 nurse managers, 1 social worker, 1 pharmacist, and 1 nutritionist), 42 completed the survey. Results revealed that an overwhelming majority felt that daily operational debriefings provide an effective unit-based support system, a sense of connectedness, and a commitment to the well-being of others. Nearly 50% of the respondents felt that the overall stress level in the ICU decreased, and 98% indicated operational daily debriefings should continue. Daily Informal multidisciplinary ICU operational debriefing provides an effective support system for ICU nurses. A modified model could be replicated for non-ICU units as well.


Primary Health Care quality in Rocinha - Rio de Janeiro, Brazil, from the perspective of children caregivers and adult users.
This paper aims to evaluate the extent of PHC attributes, from the experience of users, both adults and children caregivers, comparing the area served by the health facilities of the district of Rocinha with other areas of health district 2.1 in the municipality of Rio de Janeiro. The measuring tool used to evaluate the quality of services provided was the Primary Care Assessment Tools. A cross-sectional study was conducted, with independent random samples and 802 interviewees. Results indicate a better performance for children care when compared to adult care. Attributes "access" and "comprehensiveness - available services" were the worst performers, probably due to the great external and internal migration existing within Rocinha itself. To improve these attributes, we recommend the adoption of a single list of residents by Family Health Team (ESF), with a maximum number of people, including territorial delimitation and people internal mobility. We also highlight the importance of strengthening the Family and Community Medicine Residency Program, which, since 2012, has been training specialists with the support of preceptors and enables increased portfolio of PHC services.


Platelets and bronchospasm.
The intrathoracic accumulation of radiolabelled platelets and concomitant changes in airway resistance have been recorded continuously in anaesthetised guinea pigs. Platelet-activating factor (PAF-acether) and antigen (in sensitised animals) elicited dose-related intrathoracic accumulation of platelets that could be associated with an increase in airway resistance. Maximal increases in airway resistance preceded maximal increases in platelet accumulation. Low doses of antigen could elicit substantial platelet accumulation, without detectable changes in lung function. It is concluded that physical obstruction of the pulmonary vasculature is not the sole determinant of platelet-dependent bronchoconstriction.


The role of cross-racial/ethnic friendships in social adjustment.
The purpose of this study was to examine the frequency and correlates of cross-racial/ethnic friendships. The sample consisted of 509 (188 African American, 135 European American, 106 Asian American, and 80 Latino) children in 4th grade from 39 classrooms in several public elementary schools. The authors hypothesized that (a) the frequency of cross-racial/ethnic friendships would be different across races/ethnicities and (b) these friendships would be uniquely associated with social adjustment (relational inclusion, leadership). Results showed that European American children displayed a higher frequency of cross-racial/ethnic friendships than African American children. Compared with the sample average, Latino children exhibited a lower frequency of these friendships. Further, findings revealed that children who formed cross-racial/ethnic friendships were more likely to be viewed as relationally inclusive and possessing leadership skills by teachers. Overall, the results showed that cross-racial/ethnic friendships were associated with positive developmental outcomes and that future studies that examine how these friendships are formed and maintained, and how these pathways are related to social adjustment, are warranted.


Amino acid catabolism and antibiotic synthesis: valine is a source of precursors for macrolide biosynthesis in Streptomyces ambofaciens and Streptomyces fradiae.
Targeted inactivation of the valine (branched-chain amino acid) dehydrogenase gene (vdh) was used to study the role of valine catabolism in the production of tylosin in Streptomyces fradiae and spiramycin in Streptomyces ambofaciens. The deduced products of the vdh genes, cloned and sequenced from S. fradiae C373.1 and S. ambofaciens ATCC 15154, are approximately 80% identical over all 363 amino acids and 96% identical over a span of the first N-terminal 107 amino acids, respectively, to the deduced product of the Streptomyces coelicolor vdh gene. The organization of the regions flanking the vdh genes is the same in all three species. Inactivation of the genomic copy of the vdh gene in S. fradiae and S. ambofaciens by insertion of a hygromycin resistance (hyg) gene caused loss of the valine dehydrogenase (Vdh) activity, and thus only one enzyme is responsible for the Vdh activity in these organisms. Analysis of the culture broth by bioassay revealed that the vdh::hyg mutants produce an approximately sixfold-lower level of tylosin and an approximately fourfold-lower level of spiramycin than the wild-type S. fradiae and S. ambofaciens strains, while maintaining essentially identical growth in a defined minimal medium with either 25 mM ammonium ion or 0.05% asparagine as the nitrogen source. The addition of the valine catabolite, propionate or isobutyrate, and introduction of the wild-type vdh gene back to each vdh::hyg mutant reversed the negative effect of the vdh::hyg mutation on spiramycin and tylosin production. These data show that the catabolism of valine is a major source of fatty acid precursors for macrolide biosynthesis under defined growth conditions and imply that amino acid catabolism is a vital source of certain antibiotic precursors in actinomycetes.


Cannabis use in the last year in a US national sample of twin and sibling pairs.
Three prior population-based twin studies, none of which was nationally representative, suggested that both genetic and familial-environmental factors contribute to family resemblance for lifetime cannabis use. We seek to replicate these results in a US national probability sample of twin and sibling pairs examining only last year cannabis use. Cannabis use in the last year was assessed by self-report questionnaire. Biometrical twin analyses were performed. Twin and sibling resemblance for last-year cannabis use was substantial, and much higher in monozygotic pairs than in dizygotic and sibling pairs, where levels of resemblance were similar. Modeling suggested that sibling resemblance was due to genetic factors--with a heritability of at least 60% and probably family environmental factors. No evidence was found that cannabis use was influenced by a special twin environment. Consistent with prior studies, use of cannabis is substantially influenced by genetic factors but family-environment is also possibly of importance.


Restriction fragment fingerprint and genome sizes of Staphylococcus species using pulsed-field gel electrophoresis and infrequent cleaving enzymes.
Large restriction fragments of genomic DNA from Staphylococcus species were separated by pulsed-field gel electrophoresis (PFGE). Five different strains of S. aureus (ISP8, SAU3A, PS96, ATCC 6538, ATCC 15564) and three representative strains of S. haemolyticus SM102, S. warneri MCS4, S. cohnii LK478 from human hosts, and one strain of S. aureus (ATCC 8432) from an avian host were used in this study. Since Staphylococcus is A + T rich (approximately 67%), restriction fragments were obtained by digesting chromosomal DNA with endonucleases that recognize GC-rich sequences. Five enzymes Csp I, Sma I, Ecl XI, Ksp I, or Sac II were used for generation of few (7 to 16) distinctly separated fragments, with average sizes in the range of 200-300 kb. The size distribution of restriction fragments for each enzyme for each strain produced a strain-identifying fingerprint, and the genome size of each strain was determined from such restriction fragments separated by PFGE.


New experimental platform to study high density laser-compressed matter.
We have developed a new experimental platform at the Linac Coherent Light Source (LCLS) which combines simultaneous angularly and spectrally resolved x-ray scattering measurements. This technique offers a new insights on the structural and thermodynamic properties of warm dense matter. The < 50 fs temporal duration of the x-ray pulse provides near instantaneous snapshots of the dynamics of the compression. We present a proof of principle experiment for this platform to characterize a shock-compressed plastic foil. We observe the disappearance of the plastic semi-crystal structure and the formation of a compressed liquid ion-ion correlation peak. The plasma parameters of shock-compressed plastic can be measured as well, but requires an averaging over a few tens of shots.


Individualization of post-mastectomy radiotherapy and regional nodal irradiation based on treatment response after neoadjuvant chemotherapy for breast cancer : A systematic review.
To review the evidence regarding post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NACT) for breast cancer, with a special focus on individualization of adjuvant radiotherapy based on treatment response. A systematic literature search using the PubMed/Medline database was performed. We included prospective and retrospective reports with a minimum of 10 patients that had been published since 1st January 2000, and provided clinical outcome data analyzed by treatment response and radiotherapy. Out of 763 articles identified via PubMed/Medline and hand search, 68 full text-articles were assessed for eligibility after screening of title and abstract. 13 studies were included in the systematic review, 9 for PMRT and 5 for RNI. All included studies were retrospective reports. There is a considerable lack of evidence regarding the role of adjuvant radiotherapy and its individualization based on treatment response after NACT. Results of prospective randomized trials such as NSABP B‑51/RTOG 1304 and Alliance A11202 are eagerly awaited.


Polymorphic microsatellite markers for the rare and endangered cactus Uebelmannia pectinifera (Cactaceae) and its congeneric species.
The cactus genus Uebelmannia includes 3 narrow endemic species associated with rocky savanna habitats in eastern South America. Because of their rarity and illegal over-collection, all of these species are endangered. Taxonomic uncertainties resulting from dramatic local variation in morphology within Uebelmannia species preclude effective conservation efforts, such as the reintroduction or translocation of plants, to restore declining populations. In this study, we developed and characterized 18 perfect, dinucleotide simple-sequence repeat markers for U. pectinifera, the most widely distributed species in the genus, and tested the cross-amplification of these markers in the remaining congeneric species and subspecies. All markers were polymorphic in a sample from 2 U. pectinifera populations. The effective number of alleles ranged from 1.6 to 8.7, with an average per population of 3.3 (SE ± 0.30) and 4.5 (SE ± 0.50). Expected heterozygosity ranged from 0.375 to 0.847 and 8-10 loci showed departures from Hardy- Weinberg equilibrium in the analyzed populations. Based on the observed polymorphism level of each marker, as well as the analysis of null allele presence and evidence of amplification of duplicate loci, a subset of 12 loci can be used as reliable markers to investigate the genetic structure, diversity, and species limits of the Uebelmannia genus.


Osteoporosis prevention in college women: application of the expanded health belief model.
To examine personal characteristics and expanded health belief model (EHBM) constructs associated with the practice of osteoporosis-protective behaviors among a random sample of nontraditional college women. A valid and reliable written mail questionnaire assessing osteoporosis knowledge, EHBM constructs, weight-bearing exercise (EX), and dietary calcium intake (CA) was completed by 273 women. A high proportion of women did not meet current guidelines for EX (50.7%) or CA (67.8%). Exercise self-efficacy and barriers to exercise were the best predictors of overall EX and CA behaviors. The EHBM was useful in predicting EX and CA.


Community perspectives on food insecurity and obesity: Focus groups with caregivers of metis and Off-reserve first nations children.
Aboriginal children in Canada are at a higher risk for overweight and obesity than other Canadian children. In Northern and remote areas, this has been linked to a lack of affordable nutritious food. However, the majority of Aboriginal children live in urban areas where food choices are more plentiful. This study aimed to explore the experiences of food insecurity among Métis and First Nations parents living in urban areas, including the predictors and perceived connections between food insecurity and obesity among Aboriginal children. Factors influencing children's diets, families' experiences with food insecurity, and coping strategies were explored using focus group discussions with 32 parents and caregivers of Métis and off-reserve First Nations children from Midland-Penetanguishene and London, Ontario. Four focus groups were conducted and transcribed verbatim between July 2011 and March 2013. A thematic analysis was conducted using NVivo software, and second coders ensured reliability of the results. Caregivers identified low income as an underlying cause of food insecurity within their communities and as contributing to poor nutrition among their children. Families reported a reliance on energy-dense, nutrient-poor foods, as these tended to be more affordable and lasted longer than more nutritious, fresh food options. A lack of transportation also compromised families' ability to purchase healthful food. Aboriginal caregivers also mentioned a lack of access to traditional foods. Coping strategies such as food banks and community programming were not always seen as effective. In fact, some were reported as potentially exacerbating the problem of overweight and obesity among First Nations and Métis children. Food insecurity manifested itself in different ways, and coping strategies were often insufficient for addressing the lack of fruit and vegetable consumption in Aboriginal children's diets. Results suggest that obesity prevention strategies should take a family-targeted approach that considers the unique barriers facing urban Aboriginal populations. This study also reinforces the importance of low income as an important risk factor for obesity among Aboriginal peoples.


Protective effect of Lawsonia alba Lam., against CCl4 induced hepatic damage in albino rats.
The oral administration in varying doses of aqueous suspension of extract of L. alba, bark extract to rats for 10 days afforded good hepatoprotection against CCl4 induced elevation in serum marker enzymes, serum bilirubin, liver lipid peroxidation and reduction in total serum protein, liver glutathione, glutathione peroxidase, glutathione-s-transferase, glycogen, superoxide dismutase and catalase activity. The results suggest hepatoprotective and antioxidant activity of extract of L. alba bark.


Leukemia cells accumulate zinc for oncofusion protein stabilization.
Acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) are both hematological malignancies characterized by genetic alterations leading to the formation of oncofusion proteins. The classical chromosomal aberrations in APL and CML result in the PML-RARα and BCR-ABL1 oncofusion proteins, respectively. Interestingly, our flow cytometric analyses revealed elevated free intracellular zinc levels in various leukemia cells, which may play a role in stabilizing oncofusion proteins in leukemia and thus support cell proliferation and malignancy. Long-term zinc deficiency resulted in the degradation of PML-RARα in NB4 cells (APL cell line) and of BCR-ABL1 in K562 cells (CML cell line). This degradation may be explained by increased caspase 3 activity observed in zinc deficient cells, whereas zinc reconstitution normalized the caspase 3 activity and abolished zinc deficiency-induced oncofusion protein degradation. In NB4 cells, fluorescence microscopic images further indicated enlarged and enriched lysosomes during zinc deficiency, suggesting increased rates of autophagy. Moreover, NB4 cells exhibited increased expression of the zinc transporters ZIP2, ZIP10 and ZnT3 during zinc deficiency and revealed excessive accumulation of zinc in contrast to healthy peripheral blood mononuclear cells (PBMCs), when zinc was abundantly available extracellularly. Our results highlight the importance of altered zinc homeostasis for some characteristics in leukemia cells, uncover potential pathways underlying the effects of zinc deficiency in leukemia cells, and provide potential alternative strategies by which oncofusion proteins can be degraded.


Reactivity of Hydrogen-Related Electron Centers in Powders, Layers, and Electrodes Consisting of Anatase TiO2 Nanocrystal Aggregates.
Anatase TiO2 nanoparticle aggregates were used as model systems for studying at different water activities the reactivity of electron centers at semiconductor surfaces. The investigated surface conditions evolve from a solid/vacuum interface to a solid/bulk electrolyte interface. Hydrogen-related electron centers were generated either chemically-upon sample exposure to atomic hydrogen at the semiconductor/gas interface-or electrochemically-upon bias-induced charge accumulation at the semiconductor/electrolyte interface. Based on their corresponding spectroscopic and electrochemical fingerprints, we investigated the reactivity of hydrogen-related electron centers as a function of the interfacial condition and at different levels of complexity, that is, (i) for dehydrated and (partially) dehydroxylated oxide surfaces, (ii) for oxide surfaces covered by a thin film of interfacial water, and (iii) for oxide surfaces in contact with a 0.1 M HClO4 aqueous solution. Visible (Vis) and infrared (IR) spectroscopy evidence a chemical equilibrium between hydrogen atoms in the gas phase and-following their dissociation-electron/proton centers in the oxide. The excess electrons are either localized forming (Vis-active) Ti3+ centers or delocalized as (IR-active) free conduction band electrons. The addition of molecular oxygen to chemically reduced anatase TiO2 nanoparticle aggregates leads to a quantitative quenching of Ti3+ centers, while a fraction of ∼10% of hydrogen-derived conduction band electrons remains in the oxide pointing to a persistent hydrogen doping of the semiconductor. Neither trapped electrons (i.e., Ti3+ centers) nor conduction band electrons react with water or its adsorption products at the oxide surface. However, the presence of an interfacial water layer does not impede the electron transfer to molecular oxygen. At the semiconductor/electrolyte interface, inactivity of trapped electrons with regard to water reduction and electron transfer to oxygen were evidenced by cyclic voltammetry.


Serum vitamin D₃ does not correlate with liver fibrosis in chronic hepatitis C.
To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive Chinese patients with chronic hepatitis C (CHC). From July 2010 to June 2011, we enrolled 122 CHC patients and 11 healthy controls from Dingxi city, Gansu Province, China. The patients were infected with Hepatitis C virus (HCV) during blood cell re-transfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholinesterase, prothrombin activity, albumin, γ-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HCV RNA levels were measured by real-time PCR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry. Serum levels of 25(OH)D3 but not 24,25(OH)2D3 were significantly lower in CHC patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HCV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation grades. We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive Chinese patient with CHC.


Obesity, hormone therapy, estrogen metabolism and risk of postmenopausal breast cancer.
Hormone therapy (HT) and body mass index (BMI) have been associated with postmenopausal breast cancer. Because estrogen metabolism may affect breast cancer risk and can be altered by weight and HT, it might play a role in the HT-BMI-breast cancer associations. We undertook a nested case-control study within the Observational Study of the Women's Health Initiative. Baseline levels of 2- and 16alpha-hydroxy estrone (2-OHE1 and 16alpha-OHE1) were measured in 200 women who developed breast cancer during follow-up and 200 healthy controls matched to cases by ethnicity, enrollment date, clinic site, type of HT and years since menopause. Wilcoxon nonparametric tests were used to compare estrogen metabolite levels between cases and controls. Conditional logistic regression was used to assess the relationship between BMI, estrogen metabolites and breast cancer risk. 16alpha-OHE1 levels were modestly but significantly higher in HT users among cases (median 356 pg/ml vs. 315 pg/ml) and controls (354 pg/ml vs. 298 pg/ml). 2-OHE1 levels were substantially and significantly higher in HT users among cases (369 pg/ml vs. 125 pg/ml) and controls (347 pg/ml vs. 134 pg/ml). For non-HT users only, greater BMI and higher 16alpha-OHE1 levels were individually and jointly associated with increased breast cancer risk (OR for women with high BMI and high 16alpha-OHE1 compared to those with low BMI and low 16alpha-OHE1 = 3.51, 95% CI = 1.34-9.16). No associations between BMI, estrogen metabolism and breast cancer risk were found for HT users. Estrogen metabolism differs according to both BMI and HT use, potentially explaining the interaction between BMI and HT in relation to breast cancer risk.


Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial.
Current treatment for medulloblastoma, which includes postoperative radiotherapy and 1 year of chemotherapy, does not cure many children with high-risk disease. We aimed to investigate the effectiveness of risk-adapted radiotherapy followed by a shortened period of dose-intense chemotherapy in children with medulloblastoma. After resection, patients were classified as having average-risk medulloblastoma (< or = 1.5 cm2 residual tumour and no metastatic disease) or high-risk medulloblastoma (> 1.5 cm2 residual disease or metastatic disease localised to neuraxis) medulloblastoma. All patients received risk-adapted craniospinal radiotherapy (23.4 Gy for average-risk disease and 36.0-39.6 Gy for high-risk disease) followed by four cycles of cyclophosphamide-based, dose-intensive chemotherapy. Patients were assessed regularly for disease status and treatment side-effects. The primary endpoint was 5-year event-free survival; we also measured overall survival. This study is registered with ClinicalTrials.gov, number NCT00003211. Of 134 children with medulloblastoma who underwent treatment (86 average-risk, 48 high-risk), 119 (89%) completed the planned protocol. No treatment-related deaths occurred. 5-year overall survival was 85% (95% CI 75-94) in patients in the average-risk group and 70% (54-84) in those in the high-risk group (p=0.04); 5-year event-free survival was 83% (73-93) and 70% (55-85), respectively (p=0.046). For the 116 patients whose histology was reviewed centrally, histological subtype correlated with 5-year event-free survival (p=0.04): 84% (74-95) for classic histology, 77% (49-100) for desmoplastic tumours, and 57% (33-80) for large-cell anaplastic tumours. Risk-adapted radiotherapy followed by a shortened schedule of dose-intensive chemotherapy can be used to improve the outcome of patients with high-risk medulloblastoma.


SEOM-SOGUG clinical guideline for localized muscle invasive and advanced bladder cancer (2021).
Most muscle-invasive bladder cancer (BC) are urothelial carcinomas (UC) of transitional origin, although histological variants of UC have been recognized. Smoking is the most important risk factor in developed countries, and the basis for prevention. UC harbors high number of genomic aberrations that make possible targeted therapies. Based on molecular features, a consensus classification identified six different MIBC subtypes. Hematuria and irritative bladder symptoms, CT scan, cystoscopy and transurethral resection are the basis for diagnosis. Radical cystectomy with pelvic lymphadenectomy is the standard approach for muscle-invasive BC, although bladder preservation is an option for selected patients who wish to avoid or cannot tolerate surgery. Perioperative cisplatin-based neoadjuvant chemotherapy is recommended for cT2-4aN0M0 tumors, or as adjuvant in patients with pT3/4 and or pN + after radical cystectomy. Follow-up is particularly important after the availability of new salvage therapies. It should be individualized and adapted to the risk of recurrence. Cisplatin-gemcitabine is considered the standard first line for metastatic tumors. Carboplatin should replace cisplatin in cisplatin-ineligible patients. According to the EMA label, pembrolizumab or atezolizumab could be an option in cisplatin-ineligible patients with high PD-L1 expression. For patients whose disease respond or did not progress after first-line platinum chemotherapy, maintenance with avelumab prolongs survival with respect to the best supportive care. Pembrolizumab also increases survival versus vinflunine or taxanes in patients with progression after chemotherapy who have not received avelumab, as well as enfortumab vedotin in those progressing to first-line chemotherapy followed by an antiPDL1/PD1. Erdafitinib may be considered in this setting in patients with FGFR alterations. An early onset of supportive and palliative care is always strongly recommended.


Complex dynamics in the Oregonator model with linear delayed feedback.
The Belousov-Zhabotinsky (BZ) reaction can display a rich dynamics when a delayed feedback is applied. We used the Oregonator model of the oscillating BZ reaction to explore the dynamics brought about by a linear delayed feedback. The time-delayed feedback can generate a succession of complex dynamics: period-doubling bifurcation route to chaos; amplitude death; fat, wrinkled, fractal, and broken tori; and mixed-mode oscillations. We observed that this dynamics arises due to a delay-driven transition, or toggling of the system between large and small amplitude oscillations, through a canard bifurcation. We used a combination of numerical bifurcation continuation techniques and other numerical methods to explore the dynamics in the strength of feedback-delay space. We observed that the period-doubling and quasiperiodic route to chaos span a low-dimensional subspace, perhaps due to the trapping of the trajectories in the small amplitude regime near the canard; and the trapped chaotic trajectories get ejected from the small amplitude regime due to a crowding effect to generate chaotic-excitable spikes. We also qualitatively explained the observed dynamics by projecting a three-dimensional phase portrait of the delayed dynamics on the two-dimensional nullclines. This is the first instance in which it is shown that the interaction of delay and canard can bring about complex dynamics.


α-Glucosidase inhibitor miglitol attenuates glucose fluctuation, heart rate variability and sympathetic activity in patients with type 2 diabetes and acute coronary syndrome: a multicenter randomized controlled (MACS) study.
Little is known about clinical associations between glucose fluctuations including hypoglycemia, heart rate variability (HRV), and the activity of the sympathetic nervous system (SNS) in patients with acute phase of acute coronary syndrome (ACS). This pilot study aimed to evaluate the short-term effects of glucose fluctuations on HRV and SNS activity in type 2 diabetes mellitus (T2DM) patients with recent ACS. We also examined the effect of suppressing glucose fluctuations with miglitol on these variables. This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group comparative study included 39 T2DM patients with recent ACS, who were randomly assigned to either a miglitol group (n = 19) or a control group (n = 20). After initial 24-h Holter electrocardiogram (ECG) (Day 1), miglitol was commenced and another 24-h Holter ECG (Day 2) was recorded. In addition, continuous glucose monitoring (CGM) was performed throughout the Holter ECG. Although frequent episodes of subclinical hypoglycemia (≤4.44 mmo/L) during CGM were observed on Day 1 in the both groups (35% of patients in the control group and 31% in the miglitol group), glucose fluctuations were decreased and the minimum glucose level was increased with substantial reduction in the episodes of subclinical hypoglycemia to 7.7% in the miglitol group on Day 2. Holter ECG showed that the mean and maximum heart rate and mean LF/HF were increased on Day 2 in the control group, and these increases were attenuated by miglitol. When divided 24-h time periods into day-time (0700-1800 h), night-time (1800-0000 h), and bed-time (0000-0700 h), we found increased SNS activity during day-time, increased maximum heart rate during night-time, and glucose fluctuations during bed-time, which were attenuated by miglitol treatment. In T2DM patients with recent ACS, glucose fluctuations with subclinical hypoglycemia were associated with alterations of HRV and SNS activity, which were mitigated by miglitol, suggesting that these pathological relationships may be a residual therapeutic target in such patients. Trial registration Unique Trial Number, UMIN000005874 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006929 ).


Juvenile Dermatomyositis: A Case of Calcinosis Cutis of the Elbow and Review of the Literature.
Juvenile dermatomyositis is a rare, chronic autoimmune disorder commonly associated with calcinosis cutis. Although great advances have been made in the treatment of juvenile dermatomyositis, little progress has been made in the treatment of calcinosis cutis. It remains resistant to medical treatment and surgical intervention has long been avoided due to early reports of poor wound healing and sinus track formation associated with the surgical excision of calcinosis cutis. The literature on management of calcinosis cutis is sparse and the aim of this paper is to review the literature regarding treatment options for calcinosis cutis and present a case with a large mass involving the elbow that was successfully treated with surgical excision and local fasciocutaneous flap.


The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear.
In teleosts, proper balance and hearing depend on mechanical sensors in the inner ear. These sensors include actin-based microvilli and microtubule-based cilia that extend from the surface of sensory hair cells and attach to biomineralized 'ear stones' (or otoliths). Otolith number, size and placement are under strict developmental control, but the mechanisms that ensure otolith assembly atop specific cells of the sensory epithelium are unclear. Here we demonstrate that cilia motility is required for normal otolith assembly and localization. Using in vivo video microscopy, we show that motile tether cilia at opposite poles of the otic vesicle create fluid vortices that attract otolith precursor particles, thereby biasing an otherwise random distribution to direct localized otolith seeding on tether cilia. Independent knockdown of subunits for the dynein regulatory complex and outer-arm dynein disrupt cilia motility, leading to defective otolith biogenesis. These results demonstrate a requirement for the dynein regulatory complex in vertebrates and show that cilia-driven flow is a key epigenetic factor in controlling otolith biomineralization.


[Selenium and cardiovascular disease: selected issues].
The paper presents current knowledge of the role of selenium in the development of cardiovascular system disease (CSD). Already known mechanisms of selenium action in the cardiovascular system are described, whilst underlining the fact that they do not explain all relevant observations and need to be clarified by more studies. Clinical, epidemiological, and experimental studies devoted to the relationship between the progression of CSD and selenium status indices are then reviewed. It could be expected that any explanation of the pathophysiological mechanisms of the influence of tobacco smoking (as one of the classical risk factors for CSD) on selenium status might help to bring about a better understanding of the progression of cardiovascular disorders. Based on studies conducted on animal models, the role of selenium in the antioxidant defense of cardiac muscle is described. Particular attention is paid to a dilated cardiomyopathy known as Keshan disease, for which it has been shown that selenium deficiency is an environmental factor predisposing to the onset of this disease. Similar symptoms of cardiomyopathy are also observed in patients on total parenteral nutrition and patients with AIDS.


The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis.
Ever since its presence was reported in the brain, the nature and role of hydrogen sulfide (H2S) in the Central Nervous System (CNS) have changed. Consequently, H2S has been elected as the third gas transmitter, along with carbon monoxide and nitric oxide, and a number of studies have focused on its neuromodulatory and protectant functions in physiological conditions. The research on H2S has highlighted its many facets in the periphery and in the CNS, and its role as a double-faced compound, switching from protective to toxic depending on its concentration. In this review, we will focus on the bell-shaped nature of H2S as an angiogenic factor and as a molecule released by glial cells (mainly astrocytes) and non-neuronal cells acting on the surrounding environment (paracrine) or on the releasing cells themselves (autocrine). Finally, we will discuss its role in Amyotrophic Lateral Sclerosis, a paradigm of a neurodegenerative disease.


A prospective study of postmenopausal hormone use and ovarian cancer risk.
The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82,905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of > or =5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.


Efficiency of case-control studies with multiple controls per case: continuous or dichotomous data.
The statistical efficiency of a study design which matches each case with k controls is compared with that of the standard matched-pairs setup. For the situation in which the distribution of measurements on the factor under investigation is continuous, the comparison criterion used is the reciprocal of the variance ratio of the corresponding case-control difference estimators; for dichotomous observations, the Pitman efficiency of Miettinen's test [1969] or of Pike and Morrow's test [1970] relative to McNemar's test is used. When the variances for continuously distributed case and control measurements are equal to the same result, 2k/(k + 1), is obtained for both situations and, more generally, the efficiency of k1 controls relative to k2 controls is given by k1(k2 + 1)/k2(k1 + 1). The Pitman efficiency is compared with the "practical efficiency" for large-sample dichotomous situations.


Lead toxicity and metabolism from lead sulfate fed to Holstein calves.
Sixteen Holstein intact male calves averaging 85 kg and 74 days of age were assigned randomly to four dietary lead treatments according to body weight. They were fed for ad libitum consumption a control diet containing no added lead or the control diet supplemented with 500, 1500, or 4500 ppm lead as lead sulfate. One calf fed 1500 ppm lead and all four calves fed 4500 ppm lead died within 6 to 10 days after initiation of treatments. Death was sudden with few or no clinical signs prior to death. Those clinical signs that did appear included muscular tremors, gnashing of teeth, bellowing, and convulsions. Four control, four 500 ppm lead, and two 1500 ppm lead-fed calves survived the 7-wk experimental period. Feed consumption, body weight changes, glutamic oxaloacetic transminase and alkaline phosphatase activity in blood plasma, and hemoglobin were not affected significantly by lead treatments. Packed cell volume in calves fed 500 and 1500 ppm added lead was reduced. Lead concentrations in blood, kidney, liver, bone, brain, and muscle were elevated in lead supplemented calves above those of controls. The highest concentrations of lead were in kidney and liver.


Utility of single-incision totally extraperitoneal inguinal hernia repair with intraperitoneal inspection.
To study the utility of single-incision totally extraperitoneal inguinal hernia repair with intraperitoneal inspection. A 2 cm transverse skin incision was made in the umbilicus, extending to the intraperitoneal cavity. Carbon dioxide was insufflated followed by insertion of laparoscope to observe the intraperitoneal cavity. The type of hernia was diagnosed and whether there was the presence of intestinal incarceration was confirmed. When an intestinal incarceration in the hernia sac was found, the forceps were inserted through the incision site and the intestine was returned to the intraperitoneal cavity without increasing the number of trocars. Once the peritoneum was closed, totally extraperitoneal inguinal hernia repair was performed, and finally, intraperitoneal observation was performed to reconfirm the repair. Of the 75 hernias treated, 58 were on one side, 17 were on both sides, and 10 were recurrences. The respective median operation times for these 3 groups of patients were 100 min (range, 66 to 168), 136 min (range, 114 to 165), and 125 min (range, 108 to 156), with median bleeding amounts of 5 g (range, 1 to 26), 3 g (range, 1 to 52), and 5 g (range, 1 to 26), respectively. Intraperitoneal observation showed hernia on the opposite side in 2 cases, intestinal incarceration in 3 cases, omental adhesion into the hernia sac in 2 cases, severe postoperative intraperitoneal adhesions in 2 cases, and bladder protrusion in 1 case. There was only 1 case of recurrence. Single-incision totally extraperitoneal inguinal hernia repair with intraperitoneal inspection makes hernia repairs safer and reducing postoperative complications. The technique also has excellent cosmetic outcomes.


Efficacy of Prophylactic Dexmedetomidine in Preventing Postoperative Junctional Ectopic Tachycardia After Pediatric Cardiac Surgery.
Postoperative junctional ectopic tachycardia is one of the most serious arrhythmias that occur after pediatric cardiac surgery, difficult to treat and better to be prevented. Our aim was to assess the efficacy of prophylactic dexmedetomidine in preventing junctional ectopic tachycardia after pediatric cardiac surgery. A prospective controlled study was carried out on 90 children who underwent elective cardiac surgery for congenital heart diseases. Patients were randomized into 2 groups. Group I (dexmedetomidine group): 60 patients received dexmedetomidine; Group II (Placebo group): 30 patients received the same amount of normal saline intravenously. The primary outcome was the incidence of postoperative junctional ectopic tachycardia. Secondary outcomes included bradycardia, hypotension, vasoactive inotropic score, ventilation time, pediatric cardiac care unit stay, length of hospital stay, and perioperative mortality. The incidence of junctional ectopic tachycardia was significantly reduced in the dexmedetomidine group (3.3%) compared with the placebo group (16.7%) with P<0.005. Heart rate while coming off cardiopulmonary bypass was significantly lower in the dexmedetomidine group (130.6±9) than the placebo group (144±7.1) with P<0.001. Mean ventilation time, and mean duration of intensive care unit and hospital stay (days) were significantly shorter in the dexmedetomidine group than the placebo group (P<0.001). However, there was no significant difference between the 2 groups as regards mortality, bradycardia, or hypotension (P>0.005). Prophylactic use of dexmedetomidine is associated with significantly decreased incidence of postoperative junctional ectopic tachycardia in children after congenital heart surgery without significant side effects.


Use of amifostine in the therapy of osteosarcoma in children and adolescents.
Amifostine protects normal tissue from the cytotoxic damage induced by radiation and chemotherapy. In this study, 39 consecutive newly diagnosed children with osteosarcoma were assessed; 20 received amifostine and 19 did not. The chemotherapy regimen included an induction phase of three cycles of cisplatin (100 mg/m2), carboplatin (500 mg/m2), and doxorubicin (60 mg/m2), followed by surgery. Alternating cycles of cisplatin/ifosfamide (9 mg/m2), ifosfamide/doxorubicin, carboplatin/doxorubicin, and ifosfamide/carboplatin were administered every 3 weeks to complete 26 weeks of treatment. Amifostine was administered 15 minutes before the infusions of cisplatin and carboplatin in a total of 193 infusions. Side effects during infusions and renal, hearing, and bone marrow toxicities were evaluated and compared between the two groups. Hypotension was observed in 28 (14.5%) infusions. No patient required discontinuation of therapy. Fewer than two episodes of vomiting occurred in 130 (71%) infusions and two to five episodes occurred in 51 (28%) infusions, and no patient had grade 4 toxicity. There was no difference between the two groups regarding renal toxicity (creatinine clearance). Neutropenia and leukopenia were significantly less frequent in the amifostine group. No difference was observed in platelet and hearing toxicities. Amifostine was well tolerated in doses of 740 mg/m2 in children and adolescents, and myelotoxicity was less severe in the amifostine group. This was a pilot study for further evaluation in a larger randomized trial.


Preclinical bridging studies: understanding dried blood spot and plasma exposure profiles.
Understanding the distribution of the analyte between the cellular and noncellular (plasma) components of the blood is important, especially in situations where dried blood spot (DBS) data need to be compared with plasma data, or vice versa. Pearson's coefficient, Lin's coefficient and the Bland-Altman analysis are appropriate to evaluate the concordance between DBS and plasma data from bridging studies. Percent recovery plots generated using the ex vivo blood:plasma ratio and the regression equations demonstrate the best approach for predicting plasma concentrations from DBS. Statistical analysis of bridging study data is needed to characterize the relationship or concordance between blood (DBS) and plasma. The outcomes also provide guidance on selecting the most appropriate approach to transform DBS data to plasma, or vice versa. However, the biological and statistical evidence must be weighed together when deciding if DBS is suitable for preclinical and/or clinical development.


Factors Associated with Intrapartum Cesarean Section in Women Submitted to Labor Induction.
To evaluate the results of induced labor and to determine the main factors associated with intrapartum cesarean section after patients being submitted to this procedure at the Hospital Universitário of the Universidade Federal de Santa Catarina (HU/UFSC, in the Portuguese acronym), Florianópolis, state of Santa Catarina, Brazil. A retrospective cross-sectional study that included all the pregnancies that resulted in single-fetus births, whose gestational-age was > 22 weeks and that had been submitted to labor induction at the HU/UFSC in the period from 2013 to 2016. During the proposed period, 1,491 pregnant women were submitted to the labor induction protocol. In 1,264 cases (84.8%), induction resulted in labor, with 830 (65.7%) progressing to vaginal delivery. Gestational age ≥ 41 + 0 weeks was the most common indication for induced labor (55.2%), and vaginal administration of misoprostol was the most commonly used method (72.0%). Among these pregnant women, the cesarean section rate was of 34.3%. Considering the cases of induction failure, the cesarean section rate rose to 44.3%. The factors associated with cesarean section were: previous history of cesarean delivery (PR [prevalence ratio] = 1.48; 95%CI [confidence interval]: 1.51-1.88), fetuses with intrauterine growth restriction (IUGR) (PR = 1.82; 95%CI: 1.32-2.19), Bishop score ≤ 6 (PR = 1.33; 95%CI: 1.01-1.82), and induction time either < 12 hours (PR = 1.44; 95%CI: 1.17-1.66) or > 36 hours (PR = 1.51; 95%CI 1.22-1.92) between the beginning of the induction and the birth. Labor induction was successful in most patients. In the cases in which the final outcome was a cesarean section, the most strongly associated factors were: previous history of cesarean delivery, presence of fetuses with IUGR, and either excessively short or excessively long periods of induction.


Multicenter randomised controlled trial comparing the high definition white light endoscopy and the bright narrow band imaging for colon polyps.
To compare high definition white light endoscopy and bright narrow band imaging for colon polyps' detection rates. Patients were randomised to high definition white light endoscopy (HD-WLE) or the bright narrow band imaging (bNBI) during withdrawal of the colonoscope. Polyps identified in either mode were characterised using bNBI with dual focus (bNBI-DF) according to the Sano's classification. The primary outcome was to compare adenoma detection rates (ADRs) between the two arms. The secondary outcome was to assess the negative predictive value (NPV) in differentiating adenomas from hyperplastic polyps for diminutive rectosigmoid lesions. A total of 1006 patients were randomised to HD-WLE (n = 511) or bNBI (n = 495). The mean of adenoma per patient was 1.62 and 1.84, respectively. The ADRs in bNBI and HD-WLE group were 37.4% and 39.3%, respectively. When adjusted for withdrawal time (OR = 1.19, 95%CI: 1.15-1.24, P < 0.001), the use of bNBI was associated with a reduced ADR (OR = 0.69, 95%CI: 0.52-0.92). Nine hundred and thirty three polyps (86%) in both arms were predicted with high confidence. The sensitivity (Sn), specificity (Sp), positive predictive value and NPV in differentiating adenomatous from non-adenomatous polyps of all sizes were 95.9%, 87.2%, 94.0% and 91.1% respectively. The NPV in differentiating an adenoma from hyperplastic polyp using bNBI-DF for diminutive rectal polyps was 91.0%. ADRs did not differ between bNBI and HD-WLE, however HD-WLE had higher ADR after adjustment of withdrawal time. bNBI surpassed the PIVI threshold for diminutive polyps.


Hypoglycemia in the hospital: systems-based approach to recognition, treatment, and prevention.
Hypoglycemia causes immediate adverse reactions and is associated with unfavorable clinical outcomes and increased health care costs. It is also one of the barriers to optimization of inpatient glycemic control. Prioritizing quality improvement efforts to address hypoglycemia in hospitalized patients with diabetes is of critical importance. Acute illness, hospital routine, and gaps in quality care predispose patients to hypoglycemia. Many of these factors can be minimized when approached from a systems-based perspective. This requires creation of a multidisciplinary team to develop strategies to prevent hypoglycemic events by targeting many factors, such as systemic analysis of blood glucometrics, policies and protocols, coordination of nutrition and insulin administration, transitions of care, staff and patient education, and communication. This article reviews recommendations of the American Diabetes Association, the Endocrine Society, and the Society of Hospital Medicine, and highlights our institution's approach in each of these areas. Despite a multitude of challenges, we believe that it is feasible to improve the safety and quality of inpatient diabetes care and avoid hypoglycemia without requiring significant additional hospital resources. Physician leaders play a major role in guiding this process and encouraging participation of interdisciplinary members of the hospital team.


[Assessment for efficiency of isolation of toxic substances from blood].
The authors gave assessment for efficiency of existing methods of isolation of toxic substances from blood with model substance. Some validation characteristics of the method of direct extraction from blood with organic solvent were determined.


A quaternion-based indirect Gaussian particle filter for nonlinear attitude estimation.
A recursively indirect quaternion estimator based on the Gaussian particle filter (GPF) is proposed for nonlinear attitude estimation. The key idea is to estimate an on-tangent-plane Gaussian distribution in the GPF scheme for interpreting the uncertainty of the unit quaternion manifold. The unit quaternion is provided with a global nonsingular attitude description in the prediction step, and the three-dimensional attitude error is estimated in the update step. Based on the framework of the GPF, the proposed filter does not need resampling and regularization compared with the PF. The performance of the proposed filter is verified theoretically and evaluated by experiments. The results show that the proposed filter has a faster convergence speed, lower complexity, and lower computational cost than the existing quaternion PF under a comparable accuracy.


Cardiovascular risk scores in the prediction of subclinical atherosclerosis in young adults: evidence from the cardiovascular risk in a young Finns study.
To study the utility of risk scores in the prediction of subclinical atherosclerosis in young adults. Participants were 2204 healthy Finnish adults aged 24-39 years in 2001 from a population-based follow-up study Cardiovascular Risk in Young Finns. We examined the performance of the Framingham, Reynolds, Systematic Coronary Risk Evaluation (SCORE), PROCAM, and Finrisk cardiovascular risk scores to predict subclinical atherosclerosis, that is carotid artery intima-media thickness (IMT) and plaque, carotid artery distensibility (CDist), and brachial artery flow-mediated dilatation (FMD) 6 years later. In a 6-year prediction of high IMT (highest decile or plaque), areas under the receiver operating characteristic curves (AUC) for baseline Finrisk (0.733), SCORE (0.726), PROCAM (0.712), and Reynolds (0.729) risk scores were similar as for Framingham risk score (0.728, P always ≥0.15). All risk scores had a similar discrimination in predicting low CDist (lowest decile) (0.652, 0.642, 0.639, 0.658, 0.652 respectively, P always ≥0.41). In the prediction of low FMD (lowest decile), Finrisk, PROCAM, Reynolds, and Framingham scores had similar AUCs (0.578, 0.594, 0.582, 0.568, P always ≥0.08) and SCORE discriminated slightly better (AUC=0.596, P<0.05). The prediction of subclinical outcomes was consistent when estimated from other statistical measures of discrimination, reclassification, and calibration. Cardiovascular disease risk scores had equal value in predicting subclinical atherosclerosis measured by IMT and CDist in young adults. SCORE was more accurate in predicting low FMD than Framingham risk score.


Monitoring by Parents and Hypothesized Male-Female Differences in Evidence from a Nationally Representative Cohort Re-sampled from Age 12 to 17 Years: An Exploratory Study Using a "Mutoscope" Approach.
The link between adept parental monitoring (PM) and later positive behavioral and health outcomes already has motivated intervention trials, but questions remain about which specific facets and mechanisms of PM make a difference. Our current research questions concern fundamental male-female differences in PM facets as manifest in a US cohort, re-sampled each year at age 12 through 17 years during an interval from 2004 to 2009. We hypothesized emergence, by mid-adolescence, of a specific male-female difference in a "limit time with friends" (LTF) facet of adept PM, with overall PM levels held constant. The data, arranged using a "mutoscope" approach, are from six successive nationally representative independent cross-sectional sample surveys of the cohort, with each adolescent measured only once, via a multi-item PM module nested within the larger survey. Estimates and tests of male-female differences are from a "multiple indicators, multiple causes" latent structure model appropriate for complex survey data. In evidence consistent with the advance hypothesis and with PM level held constant via the model, the LTF facet generally was more relaxed for boys as compared to girls, in a difference that emerged by mid-adolescence, possibly due to greater LTF constraints for girls at mid-adolescence. This research adds to the knowledge base about male-female similarities and differences in facets of PM. As a specific PM facet, LTF might function as a mechanism suitable for deliberate intervention and as a possible specific target in "micro-trials" of new prevention research. We acknowledge limitations such as omitted variables, including social media effects, not measured in this investigation's national surveys, but of potential importance in future research on peer influence as might have more distal parenting determinants.


Increased endothelin ET(A) receptor expression in rat carotid arteries after balloon injury.
Endothelins are vasoactive peptides and are believed to act as vascular smooth muscle mitogens. Vascular injury results in medial smooth muscle migration and proliferation with the formation of a neointima. Using quantitative autoradiography, we examined the expression of endothelin receptor subtypes ET(A) and ET(B) in the rat carotid artery 2, 8, and 16 days after balloon-catheter injury. At two and eight days after balloon catheterization, ET(A) receptor expression was significantly increased in the media of the injured vessel when compared to that in the media of the intact vessel. The enhanced expression of receptors returned to normal levels by 16 days after the injury. Neointimal cells also expressed ET(A) receptors at a lower level than that expressed by the injured media 8 days after injury, and continued to express ET(A) receptors 16 days after the injury. ET(B) receptors were not detectable in the media or the neointima at any time after the injury. Our results suggest the ET(A) receptors may have a significant role in injury induced vascular smooth muscle proliferation and neointima formation.


Developing a policy manual.
Do you really need to have a policy and procedure in the office? Frequently they are seen sitting on the shelf, collecting dust. The answer is yes for a number of very important reasons. A policy and procedure manual is a tool to set guidelines and expectations on the basis of the mission and vision of the office. A well-written manual is a powerful training tool for new staff so they can get a feel for the office culture. Furthermore, it is a provincial or state legislative requirement that can reduce management's concern about potential legal issues or problems. If an office does not have a manual to set guidelines, the employees may be forced to make their own decisions to solve problems, which can often result in confusion, inconsistencies, and mistakes.


[Analysis on funds application of community based organizations involved in HIV/AIDS response and government financial investment in China, 2014].
Objective: To understand the government financial investments to community based organizations (CBO) involved in HIV/AIDS Control and Prevention of China and its influencing factors. Methods: Questionnaire of the situation of CBO involved in HIV/AIDS control and prevention were designed, and filled by the staff of Provincial Health Administrative Departments of 31 provinces (autonomous regions and municipalities). The research focused on the fields of CBO involved in HIV/AIDS response in 31 provinces (autonomous regions and municipalities), including intervention on HIV/AIDS high risk population (female sex worker (FSW), man who sex with man (MSM), drug user (DU) and case management and care for people living with HIV/AIDS (PLWH)). 29 valid questionnaires were collecting, with Shanxi Province and Inner Mongolia Autonomous Regions not filled. Questionnaire included financial supports from local governments, transfer payment from central government for CBO involved in HIV/AIDS response in 2014, and unit cost for CBO involved in HIV/AIDS control and prevention. Multivariate analysis was conducted on the project application and financial investment of community based organizations involved in HIV/AIDS control and prevention in 2014. Results: The total amount of CBO to apply for participation in AIDS prevention and control was 64 482 828 Yuan in 2014. The actual total amount of investment was 50 616 367 Yuan, The investment came from the central government funding, the provincial level government funding, the prefecture and county level government funding investment and other sources of funding. 22 of 28 provinces (autonomous regions and municipalities) received the funds from the central government finance, and median of investment funds 500 000 Yuan. 15 provinces (autonomous regions and municipalities) gained the funds from the provincial government finance, and median of investment funds 350 000 Yuan. 12 provinces (autonomous regions and municipalities) got the funds from the prefecture and county level government finance, and median of investment funds 408 750 Yuan. 12 provinces (autonomous regions and municipalities) acquired the funds from other sources, and median of investment funds 228 400 Yuan. The median (P(25), P(75)) unit costs of intervention for FSW from 16 provinces (autonomous regions and municipalities) was 70 (23, 280) Yuan per year; DU from 14 provinces (autonomous regions and municipalities) was 83 (44, 200 ) Yuan per year; MSM from 16 provinces (autonomous regions and municipalities) was 100 (35, 280) Yuan per year; the follow-up and care for PLWH from 17 provinces (autonomous regions and municipalities) was 200 (45, 500) Yuan per year. Multivariate linear regression analysis results showed that the amount of PLWH in 2014 influenced on the total number of application funds of CBO involved in HIV/AIDS response (b=178.11, 95% CI: 51.86-305.36) and the amount of PLWH (b=77.72, 95% CI: 16.28-139.16), and Gross Domestic Product (GDP) per capita of the province (b=36.20, 95% CI: 4.60-67.80) impacted financial investment to CBO involved in HIV/AIDS response, respectively. Conclusion: Funds application and financial investment of CBO involved in HIV/AIDS control and prevention were huge. Financial investment from government was main resources for CBO in 2014. The amount of financial investment funds from governments was influenced by the HIV/AIDS epidemic situation and the development level of local economic.