[Inhibitory mechanism on growth of MA-891 cells by arsenic trioxide].
To investigate the apoptosis in MA-891 cells induced by different concentrations of As2O3 and to study its influence on the activity of telomerase and telomerase mTERT-mRNA, which provide theoretical and experimental basis for breast carcinoma. The MA-891 breast carcinoma cell lines were used as the object. Different concentration of As2O3 was cultivated with MA-891 cells, and the growth inhibition of MA-891 cells was analyzed by MTT. The rate of apoptosis in MA-891 cells was detected by flow cytometry. The telomerase activity was determined by TRAP-PAGE-SILVER staining and was analyzed by specific soft ware. The expression mTERT-mRNA was examined by RT-PCR assay in untreated and As2O3-treated cells. As2O3 could inhibit the growth of MA-891 cells remarkably; the IC50 value of As2O3 for MA-891 was 9.68 micromol x L(-1) and 5.50 micromol x L(-1) respectively during 24,48 h. The percentage of the apoptosis in MA-891 cells was 30.21%, 48.26%, 57.43%, as the cells were treated with 5, 10, 20 micromol x L(-1) As2O3 for 24 hours. Treated with As2O3 for 24 hand 48 h, the telomerase activity of MA-891 cells was inhibited remarkably, which showed obvious time and concentration dependence. The mTERT-mRNA expression of MA-891 cells were significantly inhibited when treated with As2O3 for 24 h and 48h. As2O3 could remarkably inhibit the growth of MA-891 cells and could promote the apoptosis of the cells. Treated with As2O3, the activities of telomerase and telomerase mTERT-mRNA were inhibited remarkably and were obvious dosage-effect correlation.


Properties of the motor unit action potential shape in proximal and distal muscles of the upper limb in healthy and post-stroke individuals.
Spectral analysis of surface electromyograms (sEMG) is often used to estimate central and peripheral characteristics of a motor unit (MU) population, such as average conduction velocity, proportion of muscle fiber types, and pattern of MU recruitment. This estimation is based on the assumption that the sEMG adequately reflects the frequency characteristics of the underlying MU action potentials (MUAP). However, sEMG has limitations in this respect, based on physiological and non-physiological factors that influence its frequency content. We present a method to examine characteristics of a MU population more reliably by assessing the distributions of frequency content and amplitude for a collection of individual MUAPs, identified using high-density sEMG decomposition. We demonstrate the use of this approach to examine how MU characteristics differ across muscles and in the post-stroke state by presenting preliminary data from deltoid (DELT), biceps (BIC), and finger flexor (FF) MU populations from 12 post-stroke individuals and 8 able-bodied controls. The results show differences in the magnitude and range of MUAP median frequencies across muscles in both groups. The group median values were higher in the stroke group for the DELT and FF and lower in the stroke group for the BIC. The range of frequencies was larger in the stroke group for all muscles. The distribution of MUAP RMS amplitude in both stroke and control groups had a substantially larger range in FF than in DELT and BIC. The group median values for the FF were twice as large in the stroke group. In addition, there were differences in the frequency and amplitude results between MUAP and global sEMG analyses. The implications of these findings and possible applications of the approach are discussed.


Hatching in the sea urchin Lytechinus pictus is accompanied by a shift in histone H4 gene activity.
There is a distinct shift in histone mRNA synthesis at approximately 11--12 hr of sea urchin emhryogenesis, coincident with embryonic hatching. The synthesis of the blastula type (early) histone mRNAs gradually ceases at this stage and a new class of posthatching (late) histone mRNAs is produced. Briefly labeled early and late mRNAs were isolated and identified by means of RNA-DNA hybridization to different cloned histone genes. The late histone HI mRNA is approximately 40 nucleotides longer than the early HI mRNA. The H3, H2A, H2B, and H4 late mRNAs are 15--40 nucleotides shorter than their early counterparts. We present sequence evidence to show that the genes coding for the late H4 mRNA are a separate class from those that code for the early histone H4 message.


FRET Effect between Fluorescent Polydopamine Nanoparticles and MnO2 Nanosheets and Its Application for Sensitive Sensing of Alkaline Phosphatase.
As an essential and universal hydrolase, alkaline phosphatase (ALP) has been identified as a crucial indicator of various diseases. Herein, we, for the first time, expanded the application of fluorescent polydopamine (F-PDA) nanoparticles to nanoquencher-based biosensing system, as well as discovered the reversible quenching effect of manganese dioxide (MnO2) nanosheets on the fluorescence of F-PDA nanoparticles and intensively confirmed the quenching mechanism of Förster resonance energy transfer by using transmission electron microscopy, UV-vis, Fourier transform infrared spectroscopy, and fluorescence lifetime experiments. By means of the ALP-triggered generation of ascorbic acid (AA) from the substrate ascorbic acid 2-phosphate, the AA-triggered reduction of MnO2 nanosheets to Mn2+, as well as the clear quenching mechanism of F-PDA nanoparticles by MnO2 nanosheets, we have developed a label-free, low-cost, visual, and facile synthetic fluorescent biosensor for convenient assay of ALP activity. The fluorescent bioassay shows a good linear relationship from 1 to 80 mU/mL (R2 = 0.999), with a low detection limit of 0.34 mU/mL, and the excellent applicability in human serum samples demonstrates potential applications in clinical diagnosis and biomedical research.


Expression and function of connexin 43 protein in mouse and human retinal pigment epithelial cells as hemichannels and gap junction proteins.
The changes in the transport function of the outer blood-retinal barrier (BRB), formed by retinal pigment epithelial (RPE) cells, under pathological conditions need to be understood to normalize the retinal homeostasis in retinal diseases. Connexin 43 (Cx43) is known to be one of the basic units of gap junctions and hemichannels, which are opened by changes in extracellular conditions. The purpose of this study was to clarify the expression of Cx43 in RPE cells of the retina and Cx43 contribution to compound transport functions in RPE cells. Immunohistochemistry using guinea pig-derived polyclonal anti-Cx43 antibodies indicated that Cx43 is localized at the apical and intercellular membrane of mouse RPE cells. In addition, the immunoprecipitation study using the anti-Cx43 antibodies suggested that Cx43 at the intercellular membrane is associated with gap and adherent junctions in mouse RPE cells. The intercellular transfer after scrape loading of Lucifer Yellow (457 g/mol) among a human RPE cell line, ARPE-19 cells, was greater than that of fluorescein isothiocyanate-dextran (∼3000 g/mol). This Lucifer Yellow transfer was significantly inhibited by carbenoxolone, a connexin inhibitor, suggesting that connexins take part in compound transfer via gap junctions. In addition, Lucifer Yellow uptake by ARPE-19 cells in the absence of extracellular Ca2+, which is a condition of hemichannel opening, was increased compared with that under normal conditions. This uptake of Lucifer Yellow in the absence of extracellular Ca2+ was significantly reduced in the presence of hemichannel inhibitors and Cx43-gene silencing conditions. This study suggests the involvement of Cx43 in dye transfer via gap junctions among RPE cells and hemichannel-mediated compound transport between the neural retina and RPE cells.


Down-regulation of amygdala activation with real-time fMRI neurofeedback in a healthy female sample.
Psychiatric conditions of emotion dysregulation are often characterized by difficulties in regulating the activity of limbic regions such as the amygdala. Real-time functional magnetic resonance imaging (rt-fMRI) allows to feedback brain activation and opens the possibility to establish a neurofeedback (NF) training of amygdala activation, e.g., for subjects suffering from emotion dysregulation. As a first step, we investigated whether feedback of the amygdala response to aversive scenes can improve down-regulation of amygdala activation. One group of healthy female participants received amygdala feedback (N = 16) and a control group was presented with feedback from a control region located in the basal ganglia [N(sum) = 32]. Subjects completed a one-session rt-fMRI-NF training where they viewed aversive pictures and received continuous visual feedback on brain activation (REGULATE condition). In a control condition, subjects were advised to respond naturally to aversive pictures (VIEW), and a neutral condition served as the non-affective control (NEUTRAL). In an adjacent run, subjects were presented with aversive pictures without feedback to test for transfer effects of learning. In a region of interest (ROI) analysis, the VIEW and the REGULATE conditions were contrasted to estimate brain regulation success. The ROI analysis was complemented by an exploratory analysis of activations at the whole-brain level. Both groups showed down-regulation of the amygdala response during training. Feedback from the amygdala but not from the control region was associated with down-regulation of the right amygdala in the transfer test. The whole-brain analysis did not detect significant group interactions. Results of the group whole-brain analyses are discussed. We present a proof-of-concept study using rt-fMRI-NF for amygdala down-regulation in the presence of aversive scenes. Results are in line with a potential benefit of NF training for amygdala regulation.


Classification of neural differentiation-associated genes in P19 embryonal carcinoma cells by their expression patterns induced after cell aggregation and/or retinoic acid treatment.
Expression of neural differentiation-associated genes was examined by RT-PCR and macroarray analyses during neural differentiation of P19 embryonal carcinoma cells induced by cell aggregation and/or retinoic acid (RA) treatment. Results revealed that the neural genes examined could be classified into 4 groups based on their expression patterns. The 1st group included the Wnt-1, Id-1, Id-3 and cdc42 genes, expression of which was altered by cell aggregation alone, but not by RA treatment alone. The 2nd group included the alphaN-catenin, Neuro D and GDNFRbeta genes, expression of which was altered by RA treatment alone, but not by cell aggregation. The 3rd group consisted of the Brn-2, TrkA, bcl-X, N-cadherin, E-cadherin and Otx-2 genes, expression of which was altered by either treatment. The 4th group included the ACTH, D4DR, NGC and Oct-3 genes, the expression of which changed only when both treatments were applied simultaneously. Expression of the Ets-1 and Fli-1 transcription factor genes was up-regulated by either treatment alone at initial stages of neural differentiation of P19 cells, although overexpression of these genes alone could not induce cell differentiation. Our results suggest that although both treatments are required for complete neural differentiation of P19 cells, cell aggregation or RA treatment alone drive differentiation to a certain extent at the gene expression level.


Paramecium caudatum as a source of nitric oxide: Chemiluminescent detection based on Bluestar® Forensic reagent connected with microdialysis.
Nitric oxide (NO) chemistry inside the body is the most interesting part of its behavior. NO is involved in controlling blood pressure, and in transmitting nerve signals and a variety of other signaling processes. To explain the behavior of NO, it is necessary to determine its immediate concentration or observe time-dependent changes in its concentration. In Paramecium caudatum, NO is formed by calcium-dependent nNOS (NOS1)-like protein, which is distributed in the cytoplasm. NO synthesis affects the ciliary beat and consequent motility of cells and blocked NO synthesis reduces the ability of cells to move. The possibility of online coupling of microdialysis (of P. caudatum solution) with NO detection is demonstrated. Direct measurement of NO is carried out using dilute Bluestar® Forensic reagent (luminol-H2 O2 system; one of the NO detections is based upon the chemiluminescent reaction between NO and the luminol-H2 O2 system, which is specifically reactive to NO). The effect of a nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester was observed. NO production was inhibited and the movement of P. caudatum was restricted. These effects were time dependent and after a specific time were reversed.


Identification of CD101 in Glioma: A Novel Prognostic Indicator Expressed on M2 Macrophages.
Glioma represents the most common primary intracranial malignancy worldwide, with low overall survival rates and limited therapeutic options. The protein CD101, mainly expressed on several immune cells, has been demonstrated to exert potent effects on blunting T cell immune responses across infectious and autoimmunity diseases. Nevertheless, the prognostic value of CD101 expression and its role in the immune microenvironment of various malignancies currently remains elusive. Herein, by adopting bioinformatics methodology, we comprehensively illustrated the potential function and predictive value of CD101 in stratifying clinical prognosis among patients with glioma, for which a high CD101 level predicted an unfavorable clinical outcome in glioma patients. Results from enrichment analyses manifested that CD101 predominantly expressed on the tumor-associated macrophages and was significantly associated with the immune regulatory processes, as evidenced by its positive correlation with immune-related genes and the putative infiltration of immune cells. Evidence provided by in-situ multicolor immunofluorescence staining further validated our findings at the protein level. Taken together, CD101 may serve as a novel biomarker in predicting clinical prognosis and immune status for glioma patients.


Translesion DNA synthesis and mutagenesis in eukaryotes.
The structural features that enable replicative DNA polymerases to synthesize DNA rapidly and accurately also limit their ability to copy damaged DNA. Direct replication of DNA damage is termed translesion synthesis (TLS), a mechanism conserved from bacteria to mammals and executed by an array of specialized DNA polymerases. This chapter examines how these translesion polymerases replicate damaged DNA and how they are regulated to balance their ability to replicate DNA lesions with the risk of undesirable mutagenesis. It also discusses how TLS is co-opted to increase the diversity of the immunoglobulin gene hypermutation and the contribution it makes to the mutations that sculpt the genome of cancer cells.


Is the Mouse a Good Model of Human PPARγ-Related Metabolic Diseases?
With the increasing number of patients affected with metabolic diseases such as type 2 diabetes, obesity, atherosclerosis and insulin resistance, academic researchers and pharmaceutical companies are eager to better understand metabolic syndrome and develop new drugs for its treatment. Many studies have focused on the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which plays a crucial role in adipogenesis and lipid metabolism. These studies have been able to connect this transcription factor to several human metabolic diseases. Due to obvious limitations concerning experimentation in humans, animal models-mainly mouse models-have been generated to investigate the role of PPARγ in different tissues. This review focuses on the metabolic features of human and mouse PPARγ-related diseases and the utility of the mouse as a model.


Resistive wall mode instability at intermediate plasma rotation.
Experimental observation of resistive wall mode (RWM) instability in the National Spherical Torus Experiment (NSTX) at plasma rotation levels intermediate to the ion precession drift and ion bounce frequencies suggests that low critical rotation threshold models are insufficient. Kinetic modifications to the ideal stability criterion yield a more complex relationship between plasma rotation and RWM stability. Good agreement is found between an experimental RWM instability at intermediate plasma rotation and the RWM marginal point calculated with kinetic effects included, by the MISK code. By self-similarly scaling the experimental plasma rotation profile and the collisionality in the calculation, resonances of the mode with the precession drift and bounce frequencies are explored. Experimentally, RWMs go unstable when the plasma rotation is between the stabilizing precession drift and bounce resonances.


Subgenotypes and mutations in the s and polymerase genes of hepatitis B virus carriers in the West Bank, palestine.
The mutation rate and genetic variability of hepatitis B virus (HBV) are crucial factors for efficient treatment and successful vaccination against HBV. Until today, genetic properties of this virus among the Palestinian population remain unknown. Therefore, we performed genetic analysis of the overlapping S and polymerase genes of HBV, isolated from 40 Palestinian patients' sera. All patients were HBsAg positive and presented with a viral load above 105 HBV genome copies/ml. The genotyping results of the S gene demonstrated that HBV D1 was detected in 90% of the samples representing the most prominent subgenotype among Palestinians carrying HBV. Various mutations existed within the S gene; in five patients four known escape mutations including the common G145R and D144E were found. Furthermore, a ratio of 4.25 of non-synonymous to synonymous mutations in the S gene indicated a strong selection pressure on the HBs antigen loops of HBV strains circulating in those Palestinian patients. Although all patients were treatment-naïve, with the exception of one, several mutations were found in the HBV polymerase gene, but none pointed to drug resistance. The study presented here is the first report to address subgenotypes and mutation analyses of HBV S and polymerase genes in Palestine.


Mutations in the cardiac mitochondrial DNA control region associated with cardiomyopathy and aging.
An age-dependent accumulation of point mutations in the noncoding control region of human mitochondrial D-loop has been found in cultured fibroblasts and muscle cells. Damage in mitochondrial DNA (mtDNA) coding genes and decreased bioenergetic generation have also been found in human cardiac tissues with aging and in cardiac disease. We analyzed cardiac mtDNA for the incidence and distribution of point mutations in the D-loop control region involved in mtDNA replication (from nucleotides 110 to 570) in 47 patients with cardiomyopathy and 40 subjects with no history of cardiac disease. The nucleotide changes in the control region were compared with changes in a cytb fragment of roughly the same size in controls and patients. Frequency and distribution of mutations in relation to age and cardiac disease were assessed. No significant accumulation of point mutations in the D-loop control region or in cytb was found as a function of age. However, mutations in important sites within the D-loop control region were present in 8 patients (17%). We found specific mutations at critical sites in the D-loop in cardiomyopathy that may play a role in cardiac pathogenesis. Age does not appear to be a factor in mutation accumulation.


Application of ozone for reduction of mycological infection in wheat grain.
In 2004-2005 means were sought to clean grain from microbiological contamination during transportation and storage. For this purpose, grains with a moisture content of 23.2 % of the "Tauras" variety were selected and ventilated daily for 8 hours until grain wetness was reduced to 14.0 %. The effect of ventilation duration and ozone impact was evaluated according to the changes in grain contamination with micromycetes propagules (cfu x g (-1)), and alternation of micromycetes species on the grain surface. At drying grains by active ventilation with an ozone--air mixture, at O (3) concentration of 700 ppb, the drying period was reduced by about 20 %, and mycological contamination depends on initial grain moisture content (w): when w=15.2 %, contamination was reduced by up to 2.2 times, and when w=22.0 %--up to 3 times. At the same time, the composition of micromycetes species on the grain surface changed significantly: in non-ventilated grain there were detected micromycetes of 26 species, and in ventilated grain--of 11 species. Efficient ozone impact was established only when the mound of wet (w>18.0 %) grains was exposed to ozone.


Appropriateness criteria for the use of cardiovascular imaging in heart valve disease in adults: a European Association of Cardiovascular Imaging report of literature review and current practice.
Heart valve disease is common and a major indication for imaging. Echocardiography is the first-line imaging technique for diagnosis, assessment, and serial surveillance. However, other modalities, notably cardiac magnetic resonance imaging and computerized tomography, are used if echocardiographic imaging is suboptimal or to obtain complementary information, particularly to aid risk assessment in individual patients. This review is a summary of current evidence for state-of-the-art clinical practice to inform appropriateness criteria for heart valve disease. It is divided according to common clinical scenarios: detection of valve disease, assessment of the valve and other cardiac structures, risk assessment, screening, and intervention.


β-Selective Reductive Coupling of Alkenylpyridines with Aldehydes and Imines via Synergistic Lewis Acid/Photoredox Catalysis.
Umpolung (polarity reversal) strategies of aldehydes and imines have dramatically expanded the scope of carbonyl and iminyl chemistry by facilitating reactions with non-nucleophilic reagents. Herein, we report the first visible light photoredox-catalyzed β-selective reductive coupling of alkenylpyridines with carbonyl or iminyl derivatives with the aid of a Lewis acid co-catalyst. Our process tolerates complex molecular scaffolds (e.g., sugar, natural product, and peptide derivatives) and is applicable to the preparation of compounds containing a broad range of heterocyclic moieties. Mechanistic investigations indicate that the key step involves single-electron-transfer reduction of aldehydes or imines followed by the addition of resulting ketyl or α-aminoalkyl radicals to Lewis acid-activated alkenylpyridines.


A Review of the Literature Concerning HIV and Cigarette Smoking: Morbidity and Mortality, Associations with Individual- and Social-Level Characteristics, and Smoking Cessation Efforts.
Cigarette smoking is endemic among many populations, but is especially prevalent among people living with HIV, and is consequently associated with a variety of types of morbidity as well as mortality. Despite this knowledge, relatively little research has been conducted among smokers living with HIV. Extant research has focused on examining individual-level characteristics associated with smoking behaviors, to the neglect of examining social-level factors. This manuscript represents a critical literature review of the intersecting research fields of HIV and cigarette smoking. Topics considered within this review include: morbidity, mortality, as well as treatment and medication adherence outcomes; individual- and social-level characteristics associated with various smoking behaviors; evidence-based smoking cessation interventions; and findings from cessation interventions among smokers living with HIV. Additionally, gaps in the existing literature, as well as directions for future research were identified and discussed.


Post-ERCP pancreatitis: randomized, prospective study comparing a low- and high-osmolality contrast agent.
Diagnostic and therapeutic ERCPs are complicated by pancreatitis in 1% to 10% of patients, and evidence suggests that the contrast agent used for ERCP may be important in the pathogenesis of such pancreatitis. This prospective, double-blind study was undertaken to determine whether the use of a low-osmolality, nonionic contrast agent (Omnipaque 300; iohexol, 672 mOsm/kg H2O) would reduce the frequency and severity of postprocedure pancreatitis as compared to a high-osmolality, ionic contrast agent (Hypaque 50%; diatrizoate sodium, 1515 mOsm/kg H20). Six hundred ninety patients undergoing diagnostic ERCP (pancreatogram, cholangiogram, or both) either with or without sphincter of Oddi manometry and therapy were randomized to iohexol or diatrizoate sodium. Postprocedure pancreatitis was diagnosed when the serum amylase or lipase level was elevated to at least four times the upper limits of normal at 18 hours and was associated with increased abdominal pain persisting for at least 24 hours after the procedure that required administration of narcotic analgesics. The pancreatitis was graded as mild, moderate, or severe depending on the length of hospital stay and the need for intervention. The overall frequency (7.2% versus 7.5%) and severity (4.3% mild, 2% moderate, 0.9% severe for the diatrizoate sodium group versus 4.3% mild, 2.6% moderate, and 0.6% severe for the iohexol group) of postprocedure pancreatitis and the frequency and severity within each procedure category were similar for the two contrast agent groups (p > .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Adherence to an exercise prescription scheme: the role of expectations, self-efficacy, stage of change and psychological well-being.
Poor rates of adherence to exercise prescription schemes present a potential barrier to the goal of increasing physical activity in patient samples. This study investigated the role of participant expectations, self-efficacy, stage of change and psychological well-being in adherence to a 12-week course of gym based exercise. It also aimed to assess the impact of failure to adhere on self-efficacy and psychological well-being. The 119 participants, referred by their medical practitioner for a course of exercise, completed questionnaires at the start of the course and 77 went on to complete second questionnaires. Objective measures included a range of physiological measures based on gym assessments. Participants typically had high expectations of the scheme. Those who completed the course had more modest expectations of change and came closer to achieving these expected changes than those who dropped out. Initial stage of change and self-efficacy did not discriminate between the two groups. While self-efficacy improved over the scheme for completers, it tended to deteriorate for drop-outs. GHQ scores also failed to improve over time for drop-outs. Overly optimistic expectations of inexperienced exercisers may lead to disappointment and attrition. Interventions to ensure realistic expectations might increase success and prevent potential negative effects of failure.


Alcohol-related homicides committed by women.
In this paper we use data derived from interviews with female homicide offenders either incarcerated or on parole in New York to examine those cases (N=35) that the respondents believed were related to their use of alcohol at the time of the homicide. We found four basic types of these homicides based on victim-offender relationships and the circumstances of the incidents. Women who committed each type of alcohol-related homicide reported a variety of motives for committing these acts. We also found that there were similarities and differences between the types, not only in terms of the kinds of motives reported but also in terms of the extent to which planning was involved. Likewise, there were similarities and differences between the different types of homicides regarding the type and amount of alcohol and other drugs used by respondents on the day of the incident, and regarding respondents' perceptions of the alcohol-relatedness of the events. The implications of our findings are discussed.


Wafer-scale 2D PtTe2 layers for high-efficiency mechanically flexible electro-thermal smart window applications.
Two-dimensional (2D) transition metal dichalcogenide (TMD) layers have gained increasing attention for a variety of emerging electrical, thermal, and optical applications. Recently developed metallic 2D TMD layers have been projected to exhibit unique attributes unattainable in their semiconducting counterparts; e.g., much higher electrical and thermal conductivities coupled with mechanical flexibility. In this work, we explored 2D platinum ditelluride (2D PtTe2) layers - a relatively new class of metallic 2D TMDs - by studying their previously unexplored electro-thermal properties for unconventional window applications. We prepared wafer-scale 2D PtTe2 layer-coated optically transparent and mechanically flexible willow glasses via a thermally-assisted tellurization of Pt films at a low temperature of 400 °C. The 2D PtTe2 layer-coated windows exhibited a thickness-dependent optical transparency and electrical conductivity of >106 S m-1 - higher than most of the previously explored 2D TMDs. Upon the application of electrical bias, these windows displayed a significant increase in temperature driven by Joule heating as confirmed by the infrared (IR) imaging characterization. Such superior electro-thermal conversion efficiencies inherent to 2D PtTe2 layers were utilized to demonstrate various applications, including thermochromic displays and electrically-driven defogging windows accompanying mechanical flexibility. Comparisons of these performances confirm the superiority of the wafer-scale 2D PtTe2 layers over other nanomaterials explored for such applications.


Effects of sex differences on constitutive nitric oxide synthase expression and activity in response to pressure overload in rats.
Clinical studies have documented sex differences in left ventricular (LV) hypertrophy patterns, but the mechanisms are so far poorly defined. This study aimed to determine whether 1) severe pressure overload altered expression and/or activity of cardiac constitutive nitric oxide synthase (NOS1 and NOS3) and 2) these changes were modulated according to sex. Analyses were performed 0.4-20 wk after thoracic aortic constriction (TAC) in male and female Wistar rats. Male rats with TAC exhibited early signs of cardiac dysfunction, as shown by echocardiographic and LV end-diastolic pressure measurements, whereas females with TAC exhibited higher LV hypertrophy (+96% vs. males at 20 wk; P < 0.05). After TAC, cardiac NOS1 expression was rapidly induced (0.4 wk) and stable afterward in males (P < 0.05 vs. sham groups), whereas it was delayed in females. Accordingly, specific NOS1 activity was increased by 2 wk in male rats with TAC (+122%; P < 0.001 vs. sham groups) and only by 20 wk in females (+220%; P < 0.001 vs. sham groups). NOS1 activity was correlated with NOS1 level. Regarding cardiac NOS3, expression was unaffected by TAC, and the decrease in activity observed at early and late times in male and female rats with TAC, respectively, is shown to be related to NOS3 allosteric regulator caveolin-1 level. The data demonstrated a unique sex-dependent regulation of the constitutive NOSs in response to TAC in rats; such a difference might play a role in the sex-dependent adaptability of the heart in response to pressure overload.


Poly I:C Exacerbates Airway Inflammation and Remodeling in Cigarette Smoke-Exposed Mice.
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder characterized by chronic inflammation and airway remodeling. Cigarette smoke (CS) and respiratory viruses are major causes of COPD development and exacerbation, but the mechanisms of these compounding factors on inflammation and pathological changes in airway structure still need further investigation. This work aimed to investigate the effects and mechanisms of Poly I:C on pathological changes in CS-induced COPD mice, such as airway inflammation and remodeling. From 1 to 8 weeks, the mice were exposed to CS, Poly I:C, or a combination of both. To compare the pathological changes among different groups over time, the mice were sacrificed at week 4, 8, 16, and 24, then the lungs were harvested to measure pulmonary pathology, inflammatory cytokines, and airway remodeling. Our data revealed that the fundamental characteristics of COPD, such as pulmonary pathological damage, the release of inflammatory mediators, and the remodeling of airway walls, were observed at week 8 in CS-exposed mice and these pathological changes persisted to week 16. Compared with the CS group, the pathological changes, including decreased lung function, inflammatory cell infiltration, alveolar destruction, and airway wall thickening, were weaker in the Poly I:C group. These pathological changes were observed at week 8 and persisted to week 16 in Poly I:C-induced mice. Furthermore, Poly I:C exacerbated lung tissue damage in CS-induced COPD mice. The decreased lung function, airway inflammation and remodeling were observed in the combined group at week 4, and these pathological changes persisted to week 24. Our research indicated that Poly I:C enhanced the expression of p-P38, p-JNK and p-NF-κB in CS-exposed mice. Poly I:C could promote airway inflammation and remodeling in CS-induced COPD mice probably by NF-κB and MAPK signaling.


Meta-analytic approaches to determine gender differences in the age-incidence characteristics of schizophrenia and related psychoses.
A recent systematic review and meta-analysis of the incidence and prevalence of schizophrenia and other psychoses in England investigated the variation in the rates of psychotic disorders. However, some of the questions of interest, and the data collected to answer these, could not be adequately addressed using established meta-analysis techniques. We developed a novel statistical method, which makes combined use of fractional polynomials and meta-regression. This was used to quantify the evidence of gender differences and a secondary peak onset in women, where the outcome of interest is the incidence of schizophrenia. Statistically significant and epidemiologically important effects were obtained using our methods. Our analysis is based on data from four studies that provide 50 incidence rates, stratified by age and gender. We describe several variations of our method, in particular those that might be used where more data is available, and provide guidance for assessing the model fit.


A needs assessment for regionalization of trauma care in a rural state.
Systems of trauma care in urban areas have a demonstrated survival benefit. Little is known of the benefit of trauma system organization in rural areas. We hypothesized that examination of all trauma deaths during a 1-year period would provide opportunities to improve care in our rural state. We used a medical examiner database of trauma deaths occurring during a 1-year period. Five board-certified surgeons analyzed deaths as preventable (P), potentially preventable (PP), and non-preventable (NP) using modified Delphi technique. There were 223 trauma deaths during a 1-year period. Most (63%) died at the scene prior to any medical intervention. Adjudication of the deaths demonstrated 5 P (2%; 95% CI 1-5%), 36 PP (16%; 95% CI 12-27%), and 179 NP (81%; 95% CI 76-86%). Agreement among trauma surgeons was only moderate with a k of 0.46. Suicide accounted for a significant number of the overall trauma deaths at 32 per cent. Rural trauma system design should focus on discovery, as that is where the majority of deaths occur. Suicide is a significant problem in this rural state that should be aggressively targeted with prevention programs.


Development of a ligand-directed approach to study the pathogenesis of invasive aspergillosis.
Invasive aspergillosis is a leading cause of infectious death in immunosuppressed patients. Here, we adapted a phage display library-based selection to screen and identify binding peptides to the surface of Aspergillus fumigatus conidia and hyphae. We identified a peptide (sequence CGGRLGPFC) that reliably binds to the surface of Aspergillus fumigatus hyphae. Binding was not Aspergillus strain specific, as it was also observed in hyphae of other Aspergillus clinical isolates. Furthermore, CGGRLGPFC-displaying phage targets Aspergillus fumigatus hyphae on formalin-fixed paraffin-embedded histopathology sections of lung tissue recovered from mice with invasive pulmonary aspergillosis. This approach may yield reagents such as peptidomimetics for novel diagnostic and therapeutic interventions in invasive aspergillosis.


The First Case of Adult Granular Acute Lymphoblastic Leukemia with DNMT3A Mutation and Monosomy 7.
Granular acute lymphoblastic leukemia (ALL) is defined by the presence of intracytoplasmic granules in lymphoblastic blasts, mimicking acute myeloblastic leukemia. The disease is extremely rare in adults, and hence, the characteristics thereof are poorly understood. We report a case of a 70-year-old man diagnosed with granular ALL. Bone marrow examination showed blasts with azurophilic granules in the cytoplasm, but immunophenotyping showed B-ALL with aberrant expression of myeloid antigens CD13 and CD33. Karyotyping revealed monosomy 7, and targeted NGS showed DNMT3A mutation, which suggested poor prognosis. Despite conventional chemotherapy treatment, the patient did not achieve complete remission. He declined further chemotherapy treatment and was maintained on only supportive care. This is the first report of adult granular ALL with DNMT3A mutation and monosomy 7.


Laser Capture Microdissection of Feline Streptomyces spp Pyogranulomatous Dermatitis and Cellulitis.
Suspected Streptomyces spp infections were identified in 4 cats at UC Davis Veterinary Medical Teaching Hospital between 1982 and 2011. Three had ulcerated, dark red mycetomas involving the dermis, subcutis, and fascia with fistulous tracts and/or regional lymphadenopathy. One cat had pyogranulomatous mesenteric lymphadenitis. Granulomatous inflammation in all cats contained colonies of Gram-positive, non-acid-fast organisms. All 4 cats failed to respond to aggressive medical and surgical treatment and were euthanized. Laser capture microdissection (LCM) was used to selectively harvest DNA from the affected formalin-fixed, paraffin-embedded (FFPE) tissues. Cloned amplicons from LCM-derived tissue confirmed the presence of Streptomyces spp in the dermatitis cases. Amplicons from the remaining cat with peritoneal involvement aligned with the 16S ribosomal RNA gene for Actinomycetales. Usually considered a contaminant, Streptomyces spp can be associated with refractory pyogranulomatous dermatitis and cellulitis in cats with outdoor access. LCM is useful in the diagnosis of bacterial diseases where contamination may be an issue.


Stormy weather in galaxy clusters
Recent x-ray, optical, and radio observations coupled with particle and gas dynamics numerical simulations reveal an unexpectedly complex environment within clusters of galaxies, driven by ongoing accretion of matter from large-scale supercluster filaments. Mergers between clusters and continuous infall of dark matter and baryons from the cluster periphery produce long-lived "stormy weather" within the gaseous cluster atmosphere-shocks, turbulence, and winds of more than 1000 kilometers per second. This weather may be responsible for shaping a rich variety of extended radio sources, which in turn act as "barometers" and "anemometers" of cluster weather.


Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.
It is now well established that the glutamatergic system contributes to the pathophysiology of depression. Exposure to stress, a major precipitating factor for depression, enhances glutamate release that can contribute to structural abnormalities observed in the brain of depressed subjects. On the other hand, it has been demonstrated that NMDA antagonists, like ketamine, exert an antidepressant effect at preclinical and clinical levels. On these bases, the purpose of our study was to investigate whether chronic mild stress is associated with specific alterations of the NMDA receptor complex, in adult rats, and to establish whether concomitant antidepressant treatment could normalize such deficits. We found that chronic stress increases the expression of the obligatory GluN1 subunit, as well as of the accessory subunits GluN2A and GluN2B at transcriptional and translational levels, particularly in the ventral hippocampus. Concomitant treatment with the antidepressant duloxetine was able to normalize the increase of glutamatergic receptor subunit expression, and correct the changes in receptor phosphorylation produced by stress exposure. Our data suggest that prolonged stress, a condition that has etiologic relevance for depression, may enhance glutamate activity through post-synaptic mechanisms, by regulating NMDA receptors, and that antidepressants may in part normalize such changes. Our results provide support to the notion that antidepressants may exert their activity in the long-term also via modulation of the glutamatergic synapse.


[Bacterial meningitis in patients with sepsis syndrome].
The authors discuss problems connected with diagnosis, management and treatment of bacterial meningitis among patients with the sepsis syndrome. Considering secondary organ changes bacterial meningitis belongs to the severest one and as a life-threathing sequel of sepsis demands immediate use of proper casual treatment. The authors show the therapeutic difficulties in this group of patients particularly when the etiological organism is unknown. They discuss this problems and present their own schemes of tretment. They indicate the value of passive immunotherapy and surgical removal of the primary source of infection. They emphasize final result depends on secondary organ changes, age, immunity of patient and the kind of etiological agent.


Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection.
After the onset of parasite egg deposition, mice infected with the helminth Schistosoma mansoni mount strong Th2 cytokine responses in the absence of significant Th1 cytokine synthesis. To examine the basis of this immunoregulatory state, spleen or lymph node cells from schistosome-infected mice were stimulated with parasite-specific Ag and the supernatants tested for their capacity to suppress IFN-gamma synthesis by a Th1 cell line. Strong inhibition was observed that was neutralized by a mAb against IL-10, a cytokine previously shown to down-regulate Th1 cytokine synthesis. By means of ELISA measurements the production of IL-10 in schistosome infection was confirmed and shown to depend on CD4+ T cells. IL-10 synthesis stimulated by either mitogen or Ag was observed only at those stages of infection when Th2 response induction and Th1 cytokine down-regulation also occurred and was not detected in mice vaccinated with attenuated parasites. Moreover, the addition of the neutralizing anti-IL-10 mAb to Ag-stimulated spleen cell cultures from infected mice caused a dramatic augmentation in IFN-gamma synthesis. These findings suggest that IL-10 is responsible for the down-regulation of Th1 responses observed in schistosome infections, a phenomenon that may enable the parasite to escape potentially harmful cell-mediated responses.


Effects of chronic haloperidol and chlordiazepoxide treatment on lateral hypothalamic self-stimulation behavior in rats.
The effects of chronic administration of haloperidol and chlordiazepoxide for 14 days on self-stimulation behavior were investigated in rats with electrodes chronically implanted in the lateral hypothalamus. Haloperidol produced a prominent decrease in self-stimulation behavior during chronic treatment, followed by a significant increase in the lever-pressing rate during a 2 week withdrawal period, with a return to the control level about 5 weeks after drug withdrawal. Chlordiazepoxide produced a significant increase in self-stimulation behavior during chronic treatment. However, the lever-pressing rate was not significantly different from the control level during a 3 week observation period following drug withdrawal. These results indicate an increase in the sensitivity of central dopaminergic receptors following chronic haloperidol treatment, but not following chronic chlordiazepoxide treatment.


[Preoperative patient education: can we improve satisfaction and reduce anxiety?].
Patients' knowledge deficits concerning anesthesia and the anesthesiologist's role in their care may contribute to anxiety. The objective of this study was to develop anesthesia patient education materials that would help improve patient's satisfaction regarding their knowledge of the perioperative process and decrease anxiety in a community hospital with a large Spanish-speaking population. A survey (Survey A) in English and Spanish was administered to all adult anesthesiology preoperative clinic patients during a 4-week period. The data were analyzed and then a patient education handout was developed in both English and Spanish to assist with our patients' major concerns. A second survey (Survey B) was administered that was completed after the education handout had been put into use at the clinic. The survey asked for basic demographic information and included questions on satisfaction with regard to understanding of anesthesia as well as worries regarding surgery and pain. In the patients who received the handout, statistically significant improvement was found in the questions that asked about satisfaction with regard to understanding of type of anesthesia, options for pain control, what patients are supposed to do on the day of surgery, and the amount of information given with regard to anesthetic plan. There was no difference in anxiety related to surgery in patients who received the educational handout compared to those patients who did not. Patient education handouts improved patient's satisfaction regarding their knowledge of the perioperative process but did not reduce anxiety related to surgery.


Masticatory ability with depression, anxiety, and stress: Does there exist any association?
Masticatory ability as a subjective response to masticatory function indicates patients' perception of their mastication. To the best of our knowledge, there has been no study on association between masticatory ability and psychological status. This study investigated the association between self-assessed masticatory ability (SAMA) and psychological status among a large sample of Iranian adults. In this cross-sectional study, data were extracted from 4135 adults who had been completed information in 20 counties across Isfahan province regarding masticatory ability and psychological statuses (depression, anxiety, and stress). An SAMA questionnaire, the Hospital Anxiety and Depression Scale and General Health Questionnaire were used to measure masticatory ability, depression and anxiety, and stress of study population. To analyze the data, ANOVA, χ(2) test, and multinomial regression were applied at 0.05 for the significance level. Masticatory ability was significantly correlated with depression (P < 0.001), anxiety (P < 0.001), and stress (P < 0.001). The participants in high masticatory ability group reported lower scores for presence of these psychological variables. Furthermore, males reported significantly higher level for masticatory ability than females (P = 0.025). In addition, there were significant association between low and moderate masticatory ability with anxiety (1.09, 1.08), depression (1.15, 1.13), and stress (1.11, 1.09), respectively. The association was still significant after adjusting for age, sex, educational level, and marital status. Despite study limitations, the results of this study provide evidence that participants with higher score of depression, anxiety, and stress suffer lower masticatory ability.


Effects of hypothyroidism induced by 6-n-propylthiouracil and its reversal by T3 on rat heart superoxide dismutase, catalase and lipid peroxidation.
The present study critically evaluates the effects of hypothyroid and hyperthyroid states on lipid peroxidation and two enzymes of active oxygen metabolism, namely superoxide dismutase (SOD) and catalase (CAT) in the rat heart mitochondrial and post-mitochondrial fractions. Lipid peroxidation, an index of oxidative stress, was elevated in the heart tissue in hypothyroid state but reduced upon T3 supplementation. Hyperthyroidism registered increased SOD activity in post-mitochondrial fraction. Mitochondrial SOD activity was reduced in hypothyroid state, which was further reduced by T3 administration. In contrast, different thyroid states had no effect on catalase activity in the mitochondrial fraction. The hypothyroid state however, significantly augmented catalase activity in post-mitochondrial fraction. The results suggest that the antioxidant defence status of cardiac tissue is well modulated by thyroid hormone.


Laser assisted microdissection, an efficient technique to understand tissue specific gene expression patterns and functional genomics in plants.
Laser assisted microdissection (LAM) is an advanced technology used to perform tissue or cell-specific expression profiling of genes and proteins, owing to its ability to isolate the desired tissue or cell type from a heterogeneous population. Due to the specificity and high efficiency acquired during its pioneering use in medical science, the LAM technique has quickly been adopted for use in many biological researches. Today, it has become a potent tool to address a wide range of questions in diverse field of plant biology. Beginning with comparative transcriptome analysis of different tissues such as reproductive parts, meristems, lateral organs, roots etc., LAM has also been extensively used in plant-pathogen interaction studies, proteomics, and metabolomics. In combination with next generation sequencing and proteomics analysis, LAM has opened up promising opportunities in the area of large scale functional studies in plants. Ever since the advent of this technique, significant improvements have been achieved in term of its instrumentation and method, which has made LAM a more efficient tool applicable in wider research areas. Here, we discuss the advancement of LAM technique with special emphasis on its methodology and highlight its scope in modern research areas of plant biology. Although we put emphasis on use of LAM in transcriptome studies, which is mostly used, we also discuss its recent application and scope in proteome and metabolome studies.


A rapid response team is associated with reduced overall hospital mortality in a Chinese tertiary hospital: a 9-year cohort study.
Although the evidence for its effectiveness remains uncertainty, rapid response systems are implemented across many hospitals across the world. Increasingly, hospitals in China have recently started to adopt a medical emergency or rapid response team (RRT). Hence, we aimed to determine whether the implementation of an RRT in Chinese hospitals also improved outcomes. Our hospital is a Joint Commission International (JCI) accredited, tertiary teaching hospital with 1,200 beds. We conducted a retrospective cohort study comparing 60 months after the implementation of the RRT (January 1, 2013, to December 31, 2017) and 36 months before implementation (January 1, 2009, to December 31, 2011). The outcomes included the overall hospital mortality and incidence of codes. We analyzed 144,673 non-obstetric hospital admissions and 1,269,621 patient days in the control period and 348,687 non-obstetric hospital admissions and 2,361,913 patient days after the RRT implementation. The RRT was activated 834 times (2.39 calls per 1,000 patients and 0.35 call per 1,000 patient-days). There was no difference in the code rate (0.23 vs. 0.17 per 1,000 patient days, P=0.379) between the two periods. Although the hospital mortality had remained stable around 3.0 per 1,000 patients from 2009 to 2011, there was a significant 40% decrease of overall hospital mortality from 2.95 to 1.77 per 1,000 non-obstetric patients after the implementation of RRT (P=0.001), and the annual mortality showed a consistent decrease (P=0.037 for the trend). Moreover, the increase of RRT activations was significantly correlated with the decrease of hospital mortality (P=0.025). RRT implementation was associated with reduced overall hospital mortality in a Chinese tertiary hospital.


Variations in the axon reaction after different types of nerve lesion. Light and electron microscopic studies on the facial nucleus of the rat.
The retrograde nerve cell reaction was studied after evulsion, transection and crush lesion of the facial nerve in rats. Crush lesion caused barely discernible light and electron microscopic changes. The Nissl bodies became slightly smaller than normal and the arrangement of the granular endoplasmic reticulum (rER) somewhat more irregular. The crush lesions were followed by complete functional and morphologic recovery. After nerve evulsion, the cells showed severe chromatolysis, nuclear caps, nuclear eccentricity, and folding of the nuclear membrane. Ultrastructurally there was a dispersion of the rER and formation of laminated dense bodies. Lager, the rER was partly degranulated and some of the polyribosomes dissociated. These neurons ultimately disappeared. Transection of the nerve caused an intermediate axon reaction and a moderate loss of neurons. It is concluded that certain neurons may regenerate after axotomy in spite of minimal light and electron microscopic changes in the nerve cell bodies, and that the same neurons may show the typical axon reaction after more severe nerve injuries. Mechanisms which may be involved in the regulation of the retrograde nerve cell reaction after axotomy are briefly discussed.


Intestinal microbiota reduces genotoxic endpoints induced by high-energy protons.
Ionizing space radiation causes oxidative DNA damage and triggers oxidative stress responses, and compromised DNA repair mechanisms can lead to increased risk of carcinogenesis. Young adult mice with developed innate and adaptive immune systems that harbored either a conventional intestinal microbiota (CM) or an intestinal microbiota with a restricted microbial composition (RM) were irradiated with a total dose of 1 Gy delivered by high-energy protons (2.5 GeV/n, LET = 0.2-2 keV/μm) or silicon or iron ions (850 MeV/n, LET ≈ 50 keV/μm and 1 GeV/n, LET = 150 keV/μm, respectively). Six hours after whole-body irradiation, acute chromosomal DNA lesions were observed for RM mice but not CM mice. High-throughput rRNA gene sequencing of intestinal mucosal bacteria showed that Barnesiella intestinihominis and unclassified Bacterodiales were significantly more abundant in male RM mice than CM mice, and phylotype densities changed in irradiated mice. In addition, Helicobacter hepaticus and Bacteroides stercoris were higher in CM than RM mice. Elevated levels of persistently phosphorylated γ-H2AX were observed in RM mice exposed to high-energy protons compared to nonirradiated RM mice, and they also were associated with a decrease of the antioxidant glutathione in peripheral blood measured at four weeks after irradiation. After radiation exposure, CM mice showed lower levels of γ-H2AX phosphorylation than RM mice and an increase in specific RM-associated phylotypes, indicating a down-regulating force on DNA repair by differentially abundant phylotypes in RM versus a radiation-sensitive complex CM.


Minimizing the risk of reporting false positives in large-scale RNAi screens.
Large-scale RNA interference (RNAi)-based analyses, very much as other 'omic' approaches, have inherent rates of false positives and negatives. The variability in the standards of care applied to validate results from these studies, if left unchecked, could eventually begin to undermine the credibility of RNAi as a powerful functional approach. This Commentary is an invitation to an open discussion started among various users of RNAi to set forth accepted standards that would insure the quality and accuracy of information in the large datasets coming out of genome-scale screens.


[Usefulness of the antisense and triplex anti-IGF-1 techniques for postoperative cellular gene therapy of malignant gliomas expressing IGF-1].
The aim of the study was to estimate the usefulness of the antineoplastic vaccination in treatment of malignant brain tumors. According to medical knowledge there is no cure for this kind of tumors. Between 2001 and 2005, ten patients suffering from malignant glial tumors were treated. There were 5 male and 5 female individuals, aged from 17 to 76 (mean age: 40.8 years). The histopathological examination showed 4 cases of glioblastoma and 6 cases of anaplastic astrocytoma. Initially, patients were operated on with dissection of 1 cm(3) of the most representative part of tumor. The neoplasm cells were cultured, transfected with episomal pMT EP vector (expressing alternatively oligonucleotide sequence forming triple helix with IGF-I gene or antisense against IGF-1 mRNA), re-cultured, irradiated and resuspended in medium to prepare antineoplastic vaccine. The patients were vaccinated subcutaneously. We examined peripheral blood lymphocyte subsets to assess the immunological response of the patients. We observed prolongation of the survival time to 21.7 months compared to 9-11 months observed in literature. The patients were additionally treated oncologically with radiotherapy and chemotherapy (temozolomide) according to the reasonable indications. Therefore, the comprehensive assessment of the genotherapy as the supplemental monotherapy was impossible. The method of treatment used in this study prolongs the survival time of patients with high-grade gliomas of the central nervous system. This gene therapy needs further investigations as a method of oncological monotherapy of brain malignant gliomas.


Inter-individual differences in binaural detection of low-frequency or high-frequency tonal signals masked by narrow-band or broadband noise.
Detection thresholds for either 500-Hz tones or 4-kHz tones were measured for a group of 19 listeners utilizing the interaural configurations NoSo and NoS pi. Both broadband (100-8500 Hz) noises and narrow-band (50-Hz-wide) noises served as maskers. In addition, direct measures of the listeners' sensitivities to changes in interaural temporal differences (ITDs) and interaural intensitive differences (IIDs) were measured using 400-Hz-wide noises centered at 500 Hz or 4 kHz. A rather large range of inter-individual differences in threshold was observed for 4-kHz tonal signals masked by narrow-band noise in the NoS pi configuration. This result is consistent with several sets of data from our previous experiments conducted over more than a decade. A broad range of thresholds was also obtained for 500-Hz tonal signals masked by narrow-band noise in the NoS pi configuration. This outcome, coupled with the fact that the use of a broadband masker did not yield a large distribution of thresholds for the detection of a 500-Hz tone masked by a broad band of noise, suggests that it is the use of a narrow-band masker, per se, that results in a large range of thresholds. Statistical analyses revealed that thresholds in the NoS pi detection tasks were not highly correlated with thresholds measured in the ITD- and the IID-discrimination tasks. Nevertheless, the five listeners who were the most sensitive in the narrow-band NoS pi detection and the five listeners who were the least sensitive in the narrow-band NoS pi detection tasks were those who were the most and least sensitive, respectively, to changes in ITDs and to changes in IIDs.


High-resolution melting analysis allowed fast and accurate closed-tube genotyping of Fusarium oxysporum formae speciales complex.
The fungus Fusarium oxysporum is a highly complex species composed by many strains put together into groups called formae speciales. As it is difficult and laborious to discriminate Fusarium formae specials via biochemical or phenotypic methods, it is very important to develop novel, rapid, and simple to perform identification methods. Herein, real-time PCR assay [using universal internal transcribed spacer (ITS) primers] coupled with high-resolution melting (HRM) analysis was developed for identifying and distinguishing F. oxysporum formae speciales complex. The melting curve analysis of these amplicons specifically classified all isolates into seven F. oxysporum formae speciales and generated seven HRM curve profiles. The smallest DNA sequence difference recognized in this study was one nucleotide. The results presented show that HRM curve analysis of Fusarium ITS sequences is a simple, quick, and reproducible method that allows both the identification of seven F. oxysporum formae speciales and at the same time their screening for variants. Our genotyping assay uses the combined information of simultaneously acquired HRM data from an unlabeled probe and the full-length amplicon. Finally, the completion of both reaction and analysis in a closed tube saves time by eliminating the separate steps and reduces the risk of contamination.


Drying capacity of a continuous vibrated fluid bed dryer - Statistical and mechanistic model development.
The drying capacity of a continuous vibrated fluid bed dryer was studied using a DoE by varying microcrystalline cellulose content in the formulation, water amount in the twin-screw granulation, inlet air temperature, air flow rate and the acceleration of the horizontal fluid-bed. Temperature and humidity profiles were measured along the dryer using wireless sensors. For the parameter space explored in this study, acceleration was the most influential process parameter of the dryer regarding the resulting granule moisture content. An empirical model was developed that allowed for fast and accurate moisture content prediction that could be incorporated into an enhanced control strategy. In addition, a mechanistic model was formulated that allow for prediction of temperature and moisture profiles, and most importantly the moisture content of the granules inside the dryer. The mechanistic model can be integrated to other unit operation models to provide overall understanding of an integrated continuous process line. The mechanistic model also makes it possible to define the equipment design requirements (e.g., length of the dryer) to meet the specific needs in terms of drying capacity, temperature and moisture profile.


Case management and the national quality agenda: partnering to improve the quality of care.
The national quality agenda has received a great deal of public attention and hospital leaders are turning to case management departments for solutions. The purpose of this article was to review the evolution of the national initiative and to describe how case management programs-regardless of the setting-can demonstrate their value to their organization through embracing the core measures. The author discusses what barriers currently exist in systems that prohibit organizations from achieving 100% performance on core measure indicators. The Case Management Standards of Practice will provide a framework of discussion identifying why case managers should participate in the improvement process. And, finally, the author will discuss suggested strategies case managers can implement in their practice.


Learning why patients with central venous catheters resist permanent access placement.
Central venous catheters (CVCs) are a well-known risk to patients on hemodialysis due to their higher morbidity and mortality compared to fistulas or grafts. One factor in the prevalence of CVCs is patients eligible for permanent access who refuse referral and permanent access placement. Objectives of this study were to identify reasons patients resist permanent access placement and develop potential strategies for intervention. A survey was distributed to Fresenius Medical Care North America (FMCNA) outpatient dialysis facilities (approximately 1600 facilities) requesting voluntary participation in documenting reasons given by patients for resisting permanent access placement. From the patient survey results, responses were collected and ranked from most frequent response to least frequent response. A collaborative workgroup of nephrology nurses and social workers reviewed the survey results. The patient survey provided 1573 responses. The three most frequently provided reasons were 1) a previous negative surgical experience, 2) having a permanent access placed in the past that did not work, and 3) cannulation fear and/or pain concerns. The workgroup identified best practices from clinics with low CVC rates and reviewed professional literature as a guide for development of potential strategies for intervention by the nephrology nurses and interdisciplinary team. Using a patient survey as a means to learn reasons why patients resist permanent access placement can be of value to the healthcare team in the development of potential strategies for interventions to reduce CVC utilization and thereby improve patient outcomes.


Concentric bodies in two species of he loculoascomycetes.
Concentric bodies were found in vegetative and pycnidial cells of Podoxythium tricothecium and in ascostromal paraphyses of Rhytidhysterium rufulum, two representatives of the Loculoascomycetes. They averages 185 nm in diameter in P. trichothecium and 255 nm in R. rufulum and consisted of three zones.


High-intensity Exercise in Men with Type 1 Diabetes and Mode of Insulin Therapy.
The purpose of this study was to evaluate the impact of high intensity exercise on glucose levels and risk of metabolic decompensation in males with type 1 diabetes (T1D), depending on the method of insulin administration. The study comprised 29 males (aged 25.3±5.1 years; duration of diabetes 10.3±3.2 years) treated with continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI). Treadmill exercise test was performed twice in each patient until subjective exhaustion as maximum according to the Borg scale. All the patients achieved ≥85% of the maximal heart rate. Distance during the test was 4 500±1 400 m and 4 473±1 559 m in the MDI and CSII groups, respectively, which was achieved in 31±8 min. During the test and in the 6 h after, no clinically significant episodes of hypoglycemia occurred. Mean glucose levels did not exceed 10 mmol/L in most patients. The risk of the composite endpoint (hypoglycemia<3.8 mmol/L, hyperglycemia≥16.6 mmol/L, ketones≥0.6 mmol/L, and lactate>2.2 mmol/L) was higher in patients treated with MDI than CSII (OR3.75, 95%CI:1.22-11.52, p=0.02). In conclusion, planned high intensity physical effort in men with well-controlled T1D is metabolically safe. CSII shows greater metabolic advantage over MDI during and after high intensity exercise in men with T1D.


Asymmetric Formal Synthesis of Azadirachtin.
An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley's synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right-hand segment starting from the known 5-hydroxymethyl-2-cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the α-oxidation of the six-membered lactone followed by methanolysis.


Physical properties of the chromosomes and implications for development.
Remarkable progress has been made in understanding chromosome structures inside the cell nucleus. Recent advances in Hi-C technologies enable the detection of genome-wide chromatin interactions, providing insight into three-dimensional (3D) genome organization. Advancements in the spatial and temporal resolutions of imaging as well as in molecular biological techniques allow the tracking of specific chromosomal loci, improving our understanding of chromosome movements. From these data, we are beginning to understand how the intra-nuclear locations of chromatin loci and the 3D genome structure change during development and differentiation. This emerging field of genome structure and dynamics research requires an interdisciplinary approach including efficient collaborations between experimental biologists and physicists, informaticians, or engineers. Quantitative and mathematical analyses based on polymer physics are becoming increasingly important for processing and interpreting experimental data on 3D chromosome structures and dynamics. In this review, we aim to provide an overview of recent research on the physical aspects of chromosome structure and dynamics oriented for biologists. These studies have mainly focused on chromosomes at the cellular level, using unicellular organisms and cultured cells. However, physical parameters that change during development, such as nuclear size, may impact genome structure and dynamics. Here, we discuss how chromatin dynamics and genome structures in early embryos change during development, which we expect will be a hot topic in the field of chromatin dynamics in the near future. We hope this review helps developmental biologists to quantitatively investigate the physical natures of chromosomes in developmental biology research.


Psychometric properties of the Valued Living Questionnaire Adapted to Dementia Caregiving.
Caring for a relative with dementia is associated with physical and emotional health problems in caregivers. There are no studies analysing the role of personal values in the caregiver stress process. This study aims to analyse the psychometric properties of the Valued Living Questionnaire Adapted to Caregiving (VLQAC), and to explore the relationship between personal values and stressors, coping strategies and caregiver distress. A total of 253 individual interviews with caregivers of relatives with dementia were conducted, and the following variables were assessed: personal values, stressors, cognitive fusion, emotional acceptance, depression, anxiety, and satisfaction with life. An exploratory factor analysis and hierarchical regression analyses were carried out. Two factors were obtained, Commitment to Own Values and Commitment to Family Values which explain 43.42% of variance, with reliability coefficients (Cronbach's alpha) of .76 and .61, respectively. Personal values had a significant effect on emotional distress (depression and anxiety) and satisfaction with life, even when controlling for socio-demographic variables, stressors and coping strategies. Results suggest that the personal values construct of dementia caregivers is two-dimensional. The personal values of the caregivers play an important role in accounting for distress and satisfaction with life in this population.


[A newborn infant with hyperventilation].
Respiratory alkalosis is an early sign of urea cycle disorder. A high level of plasma ammonia will strengthen this suspicion. It is of great importance to transfer the infant as soon as possible to a unit capable of giving specific treatment with Na-benzoate, Na-phenylbutyrate, argininchloride and carglumic acid. The early treatment may also include haemodialysis, which is preferred over peritoneal dialysis or exchange transfusion. We here describe an infant with respiratory alkalosis within the first two days of life and a high plasma level of ammonia (> 700 micromol/L). He did not respond to conventional therapy and died 48 hours after birth in spite of specific treatment. DNA-analysis showed a gene defect in the OTC gene, c.67C >T (p.R23X), a known mutation leading to urea cycle disorder (OTC). It is important to detect carriers among older siblings and to inform the parents of the possibility of prenatal diagnostics.


Establishing a health information workforce: innovation for low- and middle-income countries.
To address the shortage of health information personnel within Botswana, an innovative human resources approach was taken. University graduates without training or experience in health information or health sciences were hired and provided with on-the-job training and mentoring to create a new cadre of health worker: the district Monitoring and Evaluation (M&E) Officer. This article describes the early outcomes, achievements, and challenges from this initiative. Data were collected from the district M&E Officers over a 2-year period and included a skills assessment at baseline and 12 months, pre- and post-training tests, interviews during stakeholder site visits, a survey of achievements, focus group discussions, and an attrition assessment. An average of 2.7 mentoring visits were conducted for M&E Officers in each district. There were five training sessions over 18 months. Knowledge scores significantly increased (p < 0.05) during the three trainings in which pre/post tests were administered. Over 1 year, there were significant improvements (p < 0.05) in self-rated skills related to computer literacy, checking data validity, implementing data quality procedures, using data to support program planning, proposing indicators, and writing M&E reports. Out of the 34 district M&E Officers interviewed during site visits, most were conducting facility visits to review data (27/34; 79%), comparing data sets over time (31/34; 91%), backing up data (32/34; 94%), and analyzing data (32/34; 94%). Common challenges included late facility reports (28/34; 82%), lack of transportation (22/34; 65%), inaccurate facility reports (10/34; 29%), and colleagues' misunderstanding of M&E (10/34; 29%). Six posts were vacated in the first year (6/51; 12%). A total of 49 Officers completed the achievements survey; of these, common accomplishments related to improvements in data management (35/49; 71%), data quality (31/49; 63%), data use (29/49; 59%), and capacity development (26/49; 53%). The development of a cadre of district M&E Officers has contributed positively to the health information system in Botswana. In the absence of tertiary training related to health information, on-the-job training and mentoring of university graduates can be an effective approach for developing a new professional cadre of M&E expertise and for strengthening capacity within a national health system.


Repurposing and reshaping of hospitals during the COVID-19 outbreak in South Korea.
During the extensive outbreak of coronavirus disease 2019 (COVID-19) in South Korea, many strategies in the hospital setting, such as stratified patient care, the assignment of hospitals/beds by a task force team, and the establishment of dedicated COVID-19 hospitals, dedicated COVID-19 emergency centers, COVID-19 community facilities, and respiratory care split hospitals, were adopted to mitigate community transmission and prevent nosocomial infection. Most of these strategies were used during the Middle East Respiratory syndrome outbreak and were applied again successfully during the COVID-19 outbreak. The reallocation of health care capacity, repurposing of hospitals, and close collaboration between the government and the health care committee might have been the key to successfully addressing the crisis of COVID-19 given the shortage of health care resources.


Human peripheral blood monocytes secrete a unique form of PDGF.
PDGF isolated from platelets and forms of PDGF produced by cells transformed with the v-sis gene (PDGF B chain) or U-20S osteosarcoma cells which express the PDGF A chain gene are known to be processed as disulfide-linked dimers of approximately 30 kd. Western blot analysis with anti human PDGF antibody of the PDGF-like factor synthesized and secreted by human blood monocytes (MDGF) on SDS gels indicates that it lacks interchain disulfide bridges and behaves as a 16-kd monomer under nonreducing conditions. Additionally, MDGF exhibits different sensitivities to either formic acid or CNBr cleavage compared to PDGF A or B chain molecules indicating it may have a different primary structure. These data suggest that MDGF represents a unique form of PDGF which lacks interchain disulfide bridges and may represent a new member of the PDGF family of growth factors.


Importance of laboratory parameters in patients with obstructive sleep apnea and their relationship with cardiovascular diseases.
Ostructive sleep apnea (OSA) is an independent risk factor for the development of cardiovascular events. Platelet activation and inflammation are the mechanisms involved in the association between OSA and cardiovascular disease (CVD). The markers of platelet activation and inflammation are the mean platelet volume (MPV), platelet-lymphocyte ratio (PLR), red cell distribution width (RDW), neutrophil- lymphocyte ratio (NLR). We aimed to define the association of NLR, PLR, RDW, and MPV with the severity of disease and the presence of CVD. This study consisted of 300 patients who were admitted to the sleep laboratory. The patients were classified according to their apnea- hypopnea index (AHI) scores as OSA negative (Group A: AHI<5), mild (Group B: AHI: 5-15), moderate (Group C: AHI=15-30), and severe OSA (Group D: AHI >30). There were no significant differences in the NLR, PLR, and MPV among the groups (P>.05); only RDW differed significantly (P=.04). RDW was significantly higher in patients with than without risk factors for CVD [15.6% (15.4-15.7) vs 15.3% (15.1-15.3), respectively; P=.02]. NLR, PLR, MPV, and RDW are widely available and easily obtained from a routinely performed hemogram. Among these laboratory parameters, only RDW can demonstrate the reverse consequences of OSA-associated comorbidities, because vascular damage due to systemic inflammation is an important underlying mechanism in these diseases. RDW might be used as a marker of the response and patient compliance with continuous positive airway pressure treatment.


Negotiating the Maze: Case based, Collaborative Distance Learning in Dentistry.
The module was developed as an elective to give motivated senior dental students an opportunity to expand their horizons in planning oral rehabilitation. It comprised one tutor and 12 students, from five universities world-wide, communicating on the World Wide Web (WWW), to develop oral rehabilitation plans for simulated patients. Trigger material came from one of two Case Profiles and consisted of diagnostic casts and details of the clinical and radiographic examination in WWW/CD-ROM form. No background material was supplied as to the "patient's" age, sex, history or main concern(s). Students worked in groups of three, each student from a different location. Individual students were given a role within the group: 'Patient', who developed a "personal background" belonging to the trigger examination material, "Academic" who identified state-of-the-art treatment options available for the dental treatment needs identified by the group and "General Practitioner" who tailored these options to the "patient's" needs and wants. Student feedback focused on their perception of their experience with the program in response to a questionnaire comprising 11 structured and four "open" questions. All students felt that the program increased their confidence in planning oral rehabilitation. Ten students felt that the "best thing about the program" was the interaction with students from other universities and the exposure to different philosophies from the different schools. Eight students mentioned their increased awareness of the importance of patient input into holistic planning. Under the heading "What was the worst thing', students cited some technical hitches and the snowball effect of two sluggish students who were not identified early enough and thus impacted negatively on the working of their groups. Student feedback showed that the module succeeded in its aims but needed modification to improve the logistics of working with an extended campus.


TSE strain variation.
Studies in mice have revealed considerable strain variation in the agents causing transmissible spongiform encephalopathies (TSEs). TSE strains interact with genetic factors in the host (in particular PrP genotype) to influence characteristics of the disease such as incubation period and neuropathology. TSE strains can retain their identity after propagation in different host species or PrP genotypes, showing that these agents carry their own strain-specific information. It is not known whether this information resides in specific self-perpetuating modifications of PrP, or whether a separate informational molecule is required. Strain typing in mice can be used to explore links between TSEs occurring naturally in different species. Such studies have demonstrated that the strain causing BSE in cattle has also infected domestic cats and exotic ungulates. Most importantly, the BSE strain has also been isolated from patients with variant CJD. In contrast, different TSE strains are associated with sporadic CJD and sheep scrapie.


Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas.
Activation of the zymogen of matrix metalloproteinase 2 (proMMP-2, progelatinase A) possibly is one of the key steps in invasion and metastasis of various human carcinomas. Three different membrane-type MMPs (MT-MMPs), MT1-, MT2-, and MT3-MMPs are thought to be activators of proMMP-2 in the tissues. MT4-MMP is structurally different from the other three enzymes, and its function as proMMP-2 activator is uncertain. In the present study of human invasive breast carcinomas, we examined a correlation between the expression of MT1-, MT2-, and MT3-MMPs, immunolocalization of MT1- and MT2-MMPs, and proMMP-2 activation. Northern blot analysis demonstrated the predominant expression of MT1-MMP mRNA in carcinoma tissues (20 of 20 cases), whereas MT2-MMP was detected in only 25% of the cases (5 of 20 cases), and no detectable expression of MT3-MMP was observed. The expression levels of MT1-MMP but not MT2-MMP correlated well with the presence of lymph node and distant metastases, clinical stages, and size of tumors. Immunohistochemically, MT1-MMP was localized predominantly in the carcinoma cells in all of the samples (32 of 32 cases). Immunostaining of MT2-MMP in the carcinoma cells was observed in only 38% of the cases (12 of 32 cases). Immunoblot analysis of tumor homogenates confirmed the presence of these MT-MMPs. Activation of proMMP-2 was significantly higher in the carcinoma samples with lymph node or distant metastasis compared to carcinoma without metastasis, normal control, or fibrocystic disease (P < 0.05). An increase in the activation ratio of proMMP-2 correlated directly with the expression of MT1-MMP but not MT2-MMP, as measured by either Northern blot analysis or immunostaining. These results suggest that MT1-MMP may play a key role in human breast carcinoma invasion and metastasis by being predominantly responsible for activation of proMMP-2.


Accidental death rates and suicide.
Two hypotheses were considered for the association between accidental death rates and suicide rates: (1) that suicidal deaths may be misclassified occasionally as accidental deaths, and (2) that accidental death rates provide an index of the availability of methods for suicide. Correlations over time produced results supporting the second hypothesis.


Precocious puberty in patients with Pompe disease.
The life expectancy of Pompe disease patients has increased due to improved neonatal screening and enzyme replacement therapy. Nevertheless, the potential effect of frequent medical device exposure on pubertal development in these patients is not well understood, so further investigation is warranted. In this cross-sectional study, we assessed the growth and puberty of nine Pompe disease patients. In addition, to determine the effects of frequent plastic medical device exposure in these patients, we measured urinary phthalate metabolites before and one day after enzyme replacement therapy. Five out of nine patients (55%) with Pompe disease on enzyme replacement therapy had precocious puberty. Patients with precocious puberty had significantly shorter predicted adult heights compared to those with normal puberty (p = 0.014). The levels of mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) increased after enzyme replacement therapy, but the average levels of phthalate metabolites did not significantly differ between patients with normal and precocious puberty. Pompe disease patients on enzyme replacement therapy tend to have precocious puberty, which may reduce their adult height. There are no significant differences in urinary phthalate metabolites between normal and precocious puberty patients. Regular follow-up of growth and puberty in Pompe disease patients is important to improve their health outcomes.


Minimally Invasive Surgery Strategies to Prevent Proximal Junctional Kyphosis.
Proximal junctional kyphosis (PJK) is a common complication following long-segment thoracolumbar fusions for patients with adult spinal deformities. PJK is described as a progressive kyphosis at the upper instrumented vertebra or 1 or 2 segments adjacent to the instrumented vertebra. This condition can lead to proximal junction failure, which results in vertebral body fractures, screw pullouts, and neurological deficits. Revision surgery is necessary to address symptomatic PJK. Research efforts have been dedicated to elucidating risk factors and prevention strategies. It has been postulated that minimally invasive surgery (MIS) techniques may help prevent PJK because these techniques aim to preserve the soft tissue integrity at the top of the construct and maintain posterior element support. In this article, the authors define PJK, describe MIS strategies to prevent PJK, and compare PJK rates after MIS with PJK rates after open approaches for long-segment thoracolumbar fusion.


Expression of tung tree diacylglycerol acyltransferase 1 in E. coli.
Diacylglycerol acyltransferases (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Database search has identified at least 59 DGAT1 sequences from 48 organisms, but the expression of any DGAT1 as a full-length protein in E. coli had not been reported because DGAT1s are integral membrane proteins and difficult to express and purify. The objective of this study was to establish a procedure for expressing full-length DGAT1 in E. coli. An expression plasmid containing the open reading frame for tung tree (Vernicia fordii) DGAT1 fused to maltose binding protein and poly-histidine affinity tags was constructed and expressed in E. coli BL21(DE3). Immunoblotting showed that the recombinant DGAT1 (rDGAT1) was expressed, but mostly targeted to the membranes and insoluble fractions. Extensive degradation also occurred. Nonetheless, the fusion protein was partially purified from the soluble fraction by Ni-NTA and amylose resin affinity chromatography. Multiple proteins co-purified with DGAT1 fusion protein. These fractions appeared yellow in color and contained fatty acids. The rDGAT1 was solubilized from the insoluble fraction by seven detergents and urea, with SDS and Triton X-100 being the most effective detergents. The solubilized rDGAT1 was partially purified by Ni-NTA affinity chromatography. PreScission protease digestion confirmed the identity of rDGAT1 and showed extensive precipitation following Ni-NTA affinity purification. This study reports the first procedure for expressing full-length DGAT1 from any species using a bacterial expression system. The results suggest that recombinant DGAT1 is degraded extensively from the carboxyl terminus and associated with other proteins, lipids, and membranes.


Pituitary adenylate cyclase-activating polypeptide acts as a paracrine regulator of melatonin-responsive cells of the ovine pars tuberalis.
The pars tuberalis (PT) region of the anterior pituitary plays a physiological role in seasonal animals. The primary signal transduction mechanism of the melatonin receptor in this tissue is an inhibition of cAMP signaling. However, nothing is known about the endocrine signals that activate cAMP synthesis in the cells of the PT, as previous studies relied on the pharmacological tool, forskolin, to stimulate cAMP synthesis. Here we show that pituitary adenylate cyclase-activating polypeptide (PACAP) activates cAMP synthesis in the cells of the PT. The pharmacology of cAMP activation by PACAP peptides suggests that cAMP activation is mediated by the type I PACAP receptor. PACAP treatment of PT cells results in cellular responses that are consistent with cAMP activation in these cells, including activation of MAPK and elevation of melatonin receptor mt1 mRNA expression. These responses can be inhibited by melatonin, demonstrating that activation of cAMP occurs within the melatonin-responsive cells. However, although PACAP activates cAMP in the cells of the PT, the effect of PACAP may not be direct, as colocalization in situ hybridization studies demonstrates that the type I PACAP receptor and the melatonin mt1 receptor do not colocalize on the cells of the PT.


Circulating levels of 7 S domain of type IV collagen and atrial natriuretic peptide in normotensive type 2 diabetic patients with or without retinopathy.
Thickening of the basement membrane and other structural alterations of the vascular walls occur frequently in patients with diabetes. The vascular response to atrial natriuretic peptide (ANP) is also altered in these patients. Abnormal vascular response in diabetes may be due to alteration of vascular physicochemical properties induced by accumulation of components of vascular basement membrane. The aim of this study was to evaluate the relationship between circulating levels of the 7 S domain of type IV collagen (7 S-collagen), and ANP in normotensive type 2 diabetic patients with or without retinopathy. Forty-one normotensive type 2 diabetic patients (n = 19 with and n = 22 without retinopathy) and 18 age-matched control subjects participated in the study. Serum 7 S-collagen and plasma ANP levels were measured by radioimmunoassays. Serum 7 S-collagen (4.4 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01) levels and plasma ANP (20.8 +/- 1.0 vs 15.5 +/- 1.0 pg/ml; p < 0.01) were significantly higher in diabetic patients than in normal subjects. Serum 7 S-collagen increased significantly in diabetic patients without retinopathy compared with normal subjects (4.1 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01). Diabetic patients with retinopathy showed significantly higher circulating concentrations of 7 S-collagen (4.6 +/- 0.1 vs 4.1 +/- 0.1 ng/ml; p < 0.01) and ANP (22.9 +/- 1.4 vs 18.9 +/- 1.3 pg/ml; p < 0.05) than those without retinopathy. There was a significant and positive correlation (r = 0.51, p < 0.01) between the circulating levels of 7 S-collagen and ANP in all patients. The results of this investigation showed that increased circulating levels of ANP correlate with the abnormal metabolism of the vascular basement membrane observed in diabetic patients with microangiopathy.


Coactivator-associated arginine methyltransferase 1 promotes cell growth and is targeted by microRNA-195-5p in human colorectal cancer.
The pathogenesis of colorectal cancer remains poorly understood. Here, we show that coactivator-associated arginine methyltransferase 1 is frequently upregulated in colorectal cancer tissues and promotes cell growth in vitro and in vivo. Using bioinformatics-based prediction and luciferase reporter system, we found that coactivator-associated arginine methyltransferase 1 is post-transcriptionally targeted by microRNA-195-5p in colorectal cancer. Ectopic expression of microRNA-195-5p led to the suppression of the coactivator-associated arginine methyltransferase 1 3'-untranslated regions activity and downregulation of the endogenous coactivator-associated arginine methyltransferase 1 protein in colorectal cancer cells. Expression analysis verified that microRNA-195-5p was markedly downregulated in human colorectal cancer tissues, which was negatively correlated with the elevated levels of coactivator-associated arginine methyltransferase 1 protein. Enhanced levels of microRNA-195-5p in colorectal cancer cells resulted in a sharp reduction of cell proliferative and colony-formative capacities in vitro. Remarkably, restoration of coactivator-associated arginine methyltransferase 1 in microRNA-195-5p-transfected colorectal cancer cells partially abrogated the inhibition of cell proliferation and colony formation mediated through microRNA-195-5p. These data confirm that microRNA-195-5p might function as an anti-tumor microRNA in colorectal cancer exerting critical control over coactivator-associated arginine methyltransferase 1 expression. The newly identified microRNA-195-5p/coactivator-associated arginine methyltransferase 1 axis may act as a novel promising therapeutic target for colorectal cancer treatment.


Evaluation of the Irradiated Volume of the Heart and Cardiac Substructures After Left Breast Radiotherapy.
Backround/Aim: Adjuvant radiotherapy in patients with cancer of the left breast may lead to impaired cardiac function. The aim of our prospective study is to evaluate (i) doses to the irradiated volume of the heart and its substructures and (ii) determine whether their correlation with changes in strain echo measurements contribute to the prediction of subclinical heart morbidity. Twenty-five patients were enrolled in our study. We retrospectively assessed the radiation doses to the whole heart, left anterior descending artery (LAD) and left ventricle (LV). The mean heart dose (MHD) was 152 cGy (SD=50.56 cGy) and the range was 74-279 cGy. The LAD was the most exposed structure, with a mean dose of 448.91 cGy (SD=490.53 cGy) and range of 120-2,057cGy. Finally, the mean LV dose was 149.12 cGy (SD=69.57) with a range of 63-317 cGy. The early results of our study showed low radiation exposure of the whole heart and left ventricle, and higher exposure of the LAD. The data that will emerge from the evaluation of strain echo parameters should show whether these associations might be useful in clinical practice for the prediction of early subclinical cardiac changes.


Upgrade of absolute extreme ultraviolet diagnostic on J-TEXT.
The absolute extreme ultraviolet (AXUV) diagnostic system is used for radiation observation on J-TEXT tokamak [J. Zhang, G. Zhuang, Z. J. Wang, Y. H. Ding, X. Q. Zhang, and Y. J. Tang, Rev. Sci. Instrum. 81, 073509 (2010)]. The upgrade of the AXUV system is aimed to improve the spatial resolution and provide a three-dimensional image on J-TEXT. The new system consists of 12 AXUV arrays (4 AXUV16ELG arrays, 8 AXUV20ELG arrays). The spatial resolution in the cross-section is 21 mm for the AXUV16ELG arrays and 17 mm for the AXUV20ELG arrays. The pre-amplifier is also upgraded for a higher signal to noise ratio. By upgrading the AXUV imaging system, a more accurate observation on the radiation information is obtained.


The association between environmental tobacco smoke exposure and childhood respiratory disease: a review.
Childhood respiratory illness is a major cause of morbidity and mortality particularly in low and middle-income countries. Environmental tobacco smoke (ETS) exposure is a recognised risk factor for both acute and chronic respiratory illness. Areas covered: The aim of this paper was to review the epidemiology of ETS exposure and impact on respiratory health in children. We conducted a search of 3 electronic databases of publications on ETS and childhood respiratory illness from 1990-2015. Key findings were that up to 70% of children are exposed to ETS globally, but under-reporting may mask the true prevalence. Maternal smoking and ETS exposure influence infant lung development and are associated with childhood upper and lower respiratory tract infection, wheezing or asthma. Further, exposure to ETS is associated with more severe respiratory disease. ETS exposure reduces lung function early in life, establishing an increased lifelong risk of poor lung health. Expert commentary: Urgent and effective strategies are needed to decrease ETS exposure in young children to improve child and long-term lung health in adults especially in low and middle income countries where ETS exposure is increasing.


Effects of enteral nutrition semi-curing feeding on nutritional diarrhoea improvement in the patients with severe stroke.
The present study aims to explore the effects of enteral nutrition (EN) semi-curing feeding on nutritional diarrhoea in the patients with stroke. The patients admitted to the neurological intensive care unit of a tertiary care hospital with stroke- and EN-related diarrhoea between May 2019 and October 2020 were included in the study. The 60 patients, who met the inclusion criteria were divided into the two groups (30 patients each), the experimental group (EN solution+probiotics+90 ml of pectin) and the control group (EN solution+probiotics), in accordance with the random number table method. The stool number, total stool amount, perineal skin score, and time required to achieve the nutritional target of each patient were recorded at admission and on days 1, 3, and 7 of pectin intervention. The lymphocyte count and the haemoglobin, serum pre-albumin (PA), and total cholesterol (TC) levels were measured in order to assess the patients' nutritional statuses. The stool number and total stool amount on days 1 and 3 of pectin intervention in the experimental group were better than in the control group; the differences were statistically significant (p <0.05). On day 7 of the intervention, the stool number, total stool amount, and perineal skin score had decreased in the experimental group; the differences were statistically significant, when compared to the control group (p <0.05). Furthermore, the PA levels increased, and TC levels decreased in the experimental group; the differences were statistically significant, when compared to the control group (p <0.05). On day 3 of the intervention, the PA levels in the experimental group were increased compared to the control group; the difference was statistically significant (p <0.05). EN semi-curing feeding could improve EN-related diarrhoea and nutritional status levels in patients with stroke (Tab. 3, Ref. 9).