Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease.
Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs) and effects on PI susceptibility associated with the L76V mutation were studied in a large database. Of 20,501 sequences with ≥1 PI RAM, 3.2% contained L76V; L76V was alone in 0.04%. Common partner mutations included M46I, I54V, V82A, I84V, and L90M. L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir.


Elemental uptake by seaweed, Plocamium corallorhirza along the Kwazulu-natal coast of Indian Ocean, South Africa.
This study reports the elemental uptake by Plocamium corallorhiza, a Rhodophyta class of coralline alga grown richly along KwaZulu-Natal coastline. The uptake of seven important elements, namely Fe, Mn, As, B, Ti, Zn and Hg, selected based on their abundance in the samples, were investigated for a one-year cycle, from June 2002 to May 2003, at four chosen sites located along the KwaZulu-Natal coastline. The sites spread over 150 km from North to South Coast are Zinkwasi, Ballito, Treasure Beach and Park Rynie. P. corallorhiza possess good manganese and arsenic-accumulating ability and has potential to be an excellent indicator for most of the metals studied. A typical P. corallorhiza sample at Park Rynie (winter) recorded Mn (14 ppm), Fe (6.02 ppm), As (8.4 ppm), B (1580 ppb), Zn (234 ppb), Ti (751 ppb) and Hg (15.8 ppb). The general trend found at all sites was a large decrease in iron concentration in spring and summer and increase in winter. Mercury uptake was lowest in winter and autumn at all sites. The highest mercury levels in the seaweeds were recorded during spring or summer.


Vitamin D in systemic lupus erythematosus.
There is growing interest in the contribution of vitamin D deficiency to autoimmunity. It is therefore timely to review the immunologic actions of vitamin D and the evidence linking vitamin D deficiency to autoimmune disease in animal models and to systemic lupus erythematosus in epidemiologic studies. A number of recent studies have highlighted the association between systemic lupus erythematosus and vitamin D deficiency. Vitamin D deficiency skews the immunologic response towards loss of tolerance. Adding vitamin D in vitro reverses immunologic abnormalities characteristic of systemic lupus erythematosus. Multiple systemic lupus erythematosus cohorts have low vitamin D levels. The physiologic and clinical consequences of vitamin D deficiency in systemic lupus erythematosus are not entirely known. Prospective studies of vitamin D in systemic lupus erythematosus are limited, but most cross-sectional studies show an inverse relationship between levels of vitamin D and disease activity. This suggests that repletion of vitamin D may have benefits beyond bone health for patients with systemic lupus erythematosus.


X-ray photoelectron spectroscopy study of disordering in Gd2(Ti1-xZrx)2O7 pyrochlores.
The dramatic increases in ionic conductivity in Gd2(Ti1-xZrx)2O7 solid solution are related to disordering on the cation and anion lattices. Disordering in Gd2(Ti1-xZrx)2O7 was characterized using x-ray photoelectron spectroscopy (XPS). As Zr substitutes for Ti in Gd2Ti2O7 to form Gd2(Ti1-xZrx)2O7 (0.25 < x < or =0.75), the corresponding O 1s XPS spectrum merges into a single symmetric peak. This confirms that the cation antisite disorder occurs simultaneously with anion disorder. Furthermore, the O 1s XPS spectrum of Gd2Zr2O7 experimentally suggests the formation of a split vacancy.


The association of lumican polymorphisms and high myopia in a Southern Chinese population.
To investigate the correlation between lumican (LUM) gene and high myopia in a Southern Chinese population. The study comprised of 95 high myopia patients with a spherical equivalent ≤-6.5 diopters (D). The control group recruited 95 individuals with a spherical equivalent ranging from -0.5 D to +0.5 D. Direct sequencing was used to detect the single nucleotide polymorphisms (SNPs) of LUM gene in coding region. Genotype distributions were tested for Hardy-Weinberg disequilibrium. Genotypic and allelic frequencies were analyzed through Chi-square test or Fisher's exact test. We identified 3 SNPs of the LUM gene: LUM c.32 (rs577456426), LUM c.507 (rs17853500) and LUM c.849 (rs181915277). Among the three SNPs, the genotype and allele frequencies of rs17853500 showed a significant difference between patients and control subjects (P<0.05). However, there were no significant differences in rs181915277 and rs577456426 between the two groups (P>0.05). LUM c.507 polymorphism may be a risk factor for the pathogenesis of high myopia in the Southern Chinese population.


Long-term effects of cataract surgery with topical levofloxacin on ocular bacterial flora.
To clarify the long-term effect of topical antibiotics on the ocular bacterial flora after cataract surgery. Miyata Eye Hospital, Miyazaki, Japan. Prospective case series. Patients who had cataract surgery between November 2014 and January 2015 were included. Levofloxacin 1.5% was administered 4 times a day by topical instillation from 3 days before surgery to 1 month postoperatively. The conjunctival sacs of patients were scraped before the procedure and 0, 3, 6, 9, and 12 months after the last instillation. The samples were cultured, and minimum inhibitory concentrations (MICs) of levofloxacin for Staphylococcus epidermidis and Propionibacterium acnes were evaluated using mixed-effects models. The study evaluated 50 patients. Diverse bacterial species, predominantly S epidermidis and P acnes, were isolated before the application of topical levofloxacin. Bacterial diversity was substantially reduced after the final topical levofloxacin application and subsequently increased after 3 months. However, the geometric mean levofloxacin MICs for S epidermidis isolates were still significantly higher at 0 months and 3 months than before treatment (P < .01 and P = .03, respectively) and reached pretreatment levels 6 months and 12 months after the last application. Propionibacterium acnes did not show significant changes in the geometric mean levofloxacin MIC over time. The restoration of the bacterial flora required more than 6 months after cataract surgery and topical levofloxacin.


Characteristic attributes in cancer microarrays.
Rapid advances in genome sequencing and gene expression microarray technologies are providing unprecedented opportunities to identify specific genes involved in complex biological processes, such as development, signal transduction, and disease. The vast amount of data generated by these technologies has presented new challenges in bioinformatics. To help organize and interpret microarray data, new and efficient computational methods are needed to: (1) distinguish accurately between different biological or clinical categories (e.g., malignant vs. benign), and (2) identify specific genes that play a role in determining those categories. Here we present a novel and simple method that exhaustively scans microarray data for unambiguous gene expression patterns. Such patterns of data can be used as the basis for classification into biological or clinical categories. The method, termed the Characteristic Attribute Organization System (CAOS), is derived from fundamental precepts in systematic biology. In CAOS we define two types of characteristic attributes ('pure' and 'private') that may exist in gene expression microarray data. We also consider additional attributes ('compound') that are composed of expression states of more than one gene that are not characteristic on their own. CAOS was tested on three well-known cancer DNA microarray data sets for its ability to classify new microarray samples. We found CAOS to be a highly accurate and robust class prediction technique. In addition, CAOS identified specific genes, not emphasized in other analyses, that may be crucial to the biology of certain types of cancer. The success of CAOS in this study has significant implications for basic research and the future development of reliable methods for clinical diagnostic tools.


Metabolism As a Function of Water Potential in Air-Dry Seeds of Charlock (Sinapis arvensis L.).
A new method is described for studying the metabolism of air-dry seeds. An initial pulse of (14)CO(2) was supplied to seeds maintained in air at controlled low water potentials for 6 months. Seeds were also infiltrated with 2-(14)C-acetate and with (14)C-l-leucine at 0 C, redried rapidly at 0 C, and maintained at controlled low water potentials for 4 to 6 weeks. The metabolism of the air-dry seeds was a function of the water content of the tissues, which was in equilibrium with the water potential at the seed surface. The fixation of (14)CO(2) and the utilization of 2-(14)C-acetate increased exponentially with water content. The incorporation of (14)C-l-leucine into protein increased linearly with water content. Metabolism was not reduced to a low rate except in air-dry seeds at the lowest water potentials (-1716 to -762 bars) with 4 to 6% water.


Renal Subcapsular Hematoma after Intravenous Thrombolysis in a Patient with Acute Cerebral Infarction.
A 74-year-old female with acute cerebral infarction was treated with intravenous recombinant tissue plasminogen activator. Subsequent percutaneous transfemoral angiography and mechanical thrombectomy were performed due to a right middle cerebral artery occlusion, which was successfully recanalized. Two days after treatment, the patient complained of vague right abdominal pain and a laboratory test showed anemia. Abdominal computed tomography showed a right renal subcapsular hematoma. After conservative management, the patient was discharged without complications. We report a rare complication after intravenous thrombolysis in a patient with acute cerebral infarction.


[Apitherapy and problems in treating gastroenterology patients].
The disputable questions demanding the urgent decision on the development and specification of the recommendations and contraindications for using the honey and other beekeeping products in the therapy of various so-called gastroenterologic diseases are presented in this article. The aspects of efficiency and expediency of honey using as monotherapy and in complex combination with medicamentous preparations and (or) with other substances of national medicine are discussed.


Humidity response properties of a potentiometric sensor using LaF3 thin film as the solid electrolyte.
A thin-film type potentiometric sensor has been prepared by the implementation of electro-beam evaporation, rf magnetron sputtering methods, and micromachining processes. Sn film was deposited on n-Si/SiO(2) (400 nm) substrate. A deposited LaF(3) film was applied as solid electrolyte and sputtered Pt film was used as the sensing electrode. The patterns of the Pt and LaF(3) were realized by the micromachining processes. The LaF(3) film was characterized by scanning electron microscopy and energy dispersive x ray. Saturated aqueous solutions were used to achieve controlled humidity environments. When the sensor was exposed to humidity environments, the electromotive force (EMF) of the sensor was examined. It was found that the sensor varies with the relative humidity (RH). The stable response curve was presented and non-Nernst behavior between the average EMF values and RH may be shown.


Origin of the low critical observing temperature of the quantum anomalous Hall effect in V-doped (Bi, Sb)2Te3 film.
The experimental realization of the quantum anomalous Hall (QAH) effect in magnetically-doped (Bi, Sb)2Te3 films stands out as a landmark of modern condensed matter physics. However, ultra-low temperatures down to few tens of mK are needed to reach the quantization of Hall resistance, which is two orders of magnitude lower than the ferromagnetic phase transition temperature of the films. Here, we systematically study the band structure of V-doped (Bi, Sb)2Te3 thin films by angle-resolved photoemission spectroscopy (ARPES) and show unambiguously that the bulk valence band (BVB) maximum lies higher in energy than the surface state Dirac point. Our results demonstrate clear evidence that localization of BVB carriers plays an active role and can account for the temperature discrepancy.


[A case of measles meningoencephalitis with marked increase of plasma cells in cerebrospinal fluid].
Marked increase of plasma cells in cerebrospinal fluid (CSF) was observed in a 22-year-old female patient with measles meningoencephalitis. Typical measles exanthema was followed, 3 days later, by neurological abnormalities such as confusion, severe meningeal signs and bilateral pyramidal signs. Immunological examination showed slight elevation of IgG, normal T cell subsets and NK cell activity in peripheral blood. The antibody titer of measles was 32x in serum (4x after 2 months). CSF contained 167 cells/mm3, 66% of which was plasma cells. Total protein was 75 mg/dl, and IgG (24.5 mg/dl) showed high values. The antibody titer of measles was 4x (1x after 2 months). The antibody index was 7.15 (N = 2). The anti-myelin antibody was 8x. Oligoclonal band in CSF was negative. The appearance of large number of plasma cells in CSF in viral meningoencephalitis is extremely rare in the literature. However, B cell activation in peripheral blood in measles encephalitis has been reported. Therefore, immunologically abnormal findings in CSF of this case suggest marked B cell activation occurring in the central nervous system in measles meningoencephalitis.


Regulated upon activation normal T-cell expressed and secreted (RANTES) contributes to abortion caused by Brucella abortus infection in pregnant mice.
Brucella abortus (B. abortus) is a facultative intracellular pathogen that can survive inside macrophages and trophoblast giant cells, and the causative agent of brucellosis. In the present study, we found that production of regulated upon activation normal T-cell expressed and secreted (RANTES) due to B. abortus infection contributes to abortion in pregnant mice. B. abortus infected pregnant interferon-gamma (IFN-gamma) knockout mice died within 15 days of infection, but non-pregnant IFN-gamma knockout mice were still alive. With infection by wild type B. abortus, a large amount of RANTES production was observed in pregnant IFN-gamma knockout mice, and induction of RANTES was also observed in normal pregnant mice infected with the wild type, but not in those infected with the intracellular replication-defective mutant. Production of RANTES and IFN-gamma were inhibited in mice inoculated with the respective RANTES or IFN-gamma antibody. Neutralization of RANTES, induced by B. abortus infection, served to prevent abortion. These results indicate that the production and function of RANTES are correlated with IFN-gamma in pregnant mice infected with B. abortus.


Evidence for a pro-proliferative feedback loop in prostate cancer: the role of Epac1 and COX-2-dependent pathways.
In human prostate cancer cells, a selective Epac agonist, 8-CPT-2Me-cAMP, upregulates cell proliferation and survival via activation of Ras-MAPK and PI- 3-kinase-Akt-mTOR signaling cascades. Here we examine the role of inflammatory mediators in Epac1-induced cellular proliferation by determining the expression of the pro-inflammatory markers p-cPLA2, COX-2, and PGE2 in prostate cancer cells treated with 8-CPT-2Me-cAMP. We employed inhibitors of COX-2, mTORC1, and mTORC2 to probe cyclic AMP-dependent pathways in human prostate cancer cells. RNAi targeting Epac1, Raptor, and Rictor was also employed in these studies. 8-CPT-2Me-cAMP treatment caused a 2-2.5-fold increase of p-cPLA2(S505), COX-2, and PGE2 levels in human prostate cancer cell lines. Pretreatment of cells with the COX-2 inhibitor SC-58125 or the EP4 antagonist AH-23848, or with an inhibitor of mTORC1 and mTORC2, Torin1, significantly reduced the Epac1-dependent increase of p-cPLA2 and COX-2, p-S6-kinase(T389), and p-AKT(S473). In addition, Epac1-induced protein and DNA synthesis were greatly reduced upon pretreatment of cells with either COX-2, EP4, or mTOR inhibitors. Transfection of prostate cancer cells with Epac1 dsRNA, Raptor dsRNA, or Rictor dsRNA profoundly reduced Epac1-dependent increases in p-cPLA2 and COX-2. We show that Epac1, a downstream effector of cAMP, functions as a pro-inflammatory modulator in prostate cancer cells and promotes cell proliferation and survival by upregulating Ras-MAPK, and PI 3-kinase-Akt-mTOR signaling.


Impact of profilin on actin-bound nucleotide exchange and actin polymerization dynamics.
We have investigated the effects of profilin on nucleotide binding to actin and on steady state actin polymerization. The rate constants for the dissociation of ATP and ADP from monomeric Mg-actin at physiological conditions are 0.003 and 0.009 s-1, respectively. Profilin increases these dissociation rate constants to 0.08 s-1 for MgATP-actin and 1.4 s-1 for MgADP-actin. Thus, profilin can increase the rate of exchange of actin-bound ADP for ATP by 140-fold. The affinity of profilin for monomeric actin is found to be similar for MgATP-actin and MgADP-actin. Continuous sonication was used to allow study of solutions having sustained high filament end concentrations. During sonication at steady state, F-actin depolymerizes toward the critical concentration of ADP-actin [Pantaloni, D., et al. (1984)J. Biol. Chem. 259, 6274-6283], our analysis indicates that under these conditions a significant number of filaments contain terminal ADP-actin subunits. Addition of profilin to this system increases the polymer concentration and increases the steady state ATPase activity during sonication. These data are explained by the fast exchange of ATP for ADP on the profilin-ADP-actin complex, resulting in rapid ATP-actin regeneration. An important function of profilin may be to provide the growing ends of filaments with ATP-actin during periods when the monomer cycling rate exceeds the intrinsic nucleotide exchange rate of monomeric actin.


Causes of blindness and visual impairment in Nigeria: the Nigeria national blindness and visual impairment survey.
Determine causes of blindness and visual impairment among adults aged >or=40 years. Multistage, stratified, cluster random sampling with probability proportional to size procedures were used to identify a nationally representative sample of 15,027 persons >or=40 years of age. Distance vision was measured with a reduced logMAR tumbling E-chart. Clinical examination included a basic eye examination of all subjects and a more detailed examination of those who had presenting vision <6/12 in either eye. Cause for vision loss was assigned to all subjects with presenting vision <6/12 in any eye. Of the 15,122 persons aged >or=40 years who were enumerated, 13,599 (89.9%) were examined. In 84%, blindness was avoidable. Uncorrected refractive errors were responsible for 57.1% of moderate (<6/18-6/60) visual impairment. Cataract (43%) was the commonest cause of blindness (<3/60). Prevalence of cataract-related blindness was 1.8% (95% CI: 1.57-2.05) and glaucoma-related blindness was 0.7% (95% CI: 0.55-0.88). Increasing age was associated with increasing prevalence of all major blinding conditions. Females, illiterate persons, and residents in the North East geopolitical zone had significantly higher odds of cataract-induced blindness and severe visual impairment. The high proportion of avoidable blindness, with half being attributable to cataract alone and uncorrected refractive errors being responsible for 57% of moderate visual impairment, means that appropriate and accessible refraction and surgical services need to be provided. If priority attention is not given, the number of blind and severely visually impaired adults in Nigeria will increase by >40% over the next decade.


Yearly trend of acute venous thromboembolism in patients admitted with heart failure in the United States.
Introduction: Heart failure (HF) patients are at risk for venous thromboembolism (VTE) during the hospital stay. We aim to study the recent trend of deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE in heart failure patients from years 2000-2013. Methods: We utilized the National (Nationwide) Inpatient Sample database and selected non-pregnant patients over the age of 18 years for this purpose. We selected HF, DVT, PE, and VTE based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We used STATA for analysis. Results: We noted an increase in prevalence of DVT, PE and composite VTE among HF hospitalizations from 0.55%, 0.17% and 0.76% in 2000 to 0.96%, 0.4% and 1.46%, respectively, in 2013 and a decrease in trend of mortality among HF hospitalizations associated with DVT, PE and VTE from 8.95%, 16.36% and 10.80% in 2000 to 6.78%, 7.92% and 7.20%, respectively, in 2013. Conclusion: Increasing prevalence of VTE is concerning and suggests that we still need to work on delivering prophylaxis to all HF inpatients.


[FCGR3B gene frequencies and FCGR3 gene variants in Chinese: a study in 487 Chinese individuals from Zhejiang Province].
To investigate the FCGR3B gene frequencies and FCGR3 variants in a Chinese population from Zhejiang Province. DNA was extracted from the blood specimens of 487 healthy blood donors from Zhejiang Province. The FCGR3B gene frequencies were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP). The 19 specimens with 3 different FCGR3B genotypes underwent FCGR3 gene cloning and sequencing. The gene frequencies of FCGR3B(*1), FCGR3B(*2), and FCGR3B(*3) in these 487 individuals were 0.564, 0.429, and 0.000 respectively. The genotype frequency of FCGR3B(null) was 0.62% (3/487). Sequencing of FCGR3 revealed that in 7 out of the 19 Chinese individuals variants caused by single nucleotide exchanges at one or more of the polymorphic positions 141, 147, 227, 266 and 277 in exon 3 also existed in this Chinese population. FCGR3B(*1) gene is more frequent in a Chinese population from Zhejiang Province than the FCGR3B(*2) gene, and the FCGR3B(*3) gene seems to be absent. Gene variants caused by single nucleotide exchanges are found in addition to the well known forms, but the reason for this remains unclear.


Bone Fragility in Gastrointestinal Disorders.
Osteoporosis is a common systemic disease of the skeleton, characterized by compromised bone mass and strength, consequently leading to an increased risk of fragility fractures. In women, the disease mainly occurs due to the menopausal fall in estrogen levels, leading to an imbalance between bone resorption and bone formation and, consequently, to bone loss and bone fragility. Moreover, osteoporosis may affect men and may occur as a sequela to different diseases or even to their treatments. Despite their wide prevalence in the general population, the skeletal implications of many gastrointestinal diseases have been poorly investigated and their potential contribution to bone fragility is often underestimated in clinical practice. However, proper functioning of the gastrointestinal system appears essential for the skeleton, allowing correct absorption of calcium, vitamins, or other nutrients relevant to bone, preserving the gastrointestinal barrier function, and maintaining an optimal endocrine-metabolic balance, so that it is very likely that most chronic diseases of the gastrointestinal tract, and even gastrointestinal dysbiosis, may have profound implications for bone health. In this manuscript, we provide an updated and critical revision of the role of major gastrointestinal disorders in the pathogenesis of osteoporosis and fragility fractures.


Surface-Charge Effects on Voltammetry in Carbon Nanocavities.
Ion transport controlled by electrostatic interactions is an important phenomenon in biological and artificial membranes, channels, and nanopores. Here, we employ carbon-coated nanopipets (CNPs) for studying permselective electrochemistry in a conductive nanopore. A significant accumulation (up to 2000-fold) of cationic redox species and anion depletion inside a CNP by diffuse-layer and surface-charge effects in a solution of low ionic strength were observed as well as the shift of the voltammetric midpeak potential. Finite-element simulations of electrostatic effects on CNP voltammograms show permselective ion transport in a single conducting nanopore and semiquantitatively explain our experimental data. The reported results are potentially useful for improving sensitivity and selectivity of CNP sensors for ionic analytes.


Factors governing intrinsic chemical reactivity differences between clavulanic and penicillanic acids.
To help elucidate why penicillin-G is inactivated by certain bacterial beta-lactamase enzymes, whereas clavulanic acid (Clav, which is similar to penicillin-G except at positions 1, 2, and 6) inhibits beta-lactamase, the intrinsic chemical reactivities of these two antibiotics were assessed in this work. Ab initio and continuum dielectric methods were used to map out the gas-phase and solution-phase free-energy profiles for the alkaline hydrolyses of Clav and penicillanic acid (Peni, which is similar to penicillin-G except at position 6) as well as of a fictitious hybrid compound, Peni-db, which is similar to Clav and Peni except at positions 1 and 2, respectively. Furthermore, the ring strain energies of various lactam rings and the five-membered rings of Peni and Clav as well as their respective rate-limiting transition states were computed to assess the contribution of four- and five-membered ring strains to the antibiotic's activity. The predicted product distribution, rate-limiting step, and relative reaction rates for the alkaline hydrolysis of Peni and Clav are in accord with the experimental findings. The rate-limiting step in the alkaline hydrolysis of Peni, Clav, or Peni-db is the approach of the negatively charged hydroxide ion toward the anionic reactant to form a tetrahedral intermediate. The alkaline hydrolysis of Clav generates more stable products than that of Peni mainly because the O1 atom and the hydroxyethylidene group in Clav facilitate the opening of the five-membered ring; furthermore, the O1 atom can abstract a proton easier than the less polar S1 in Peni. Clav undergoes basic hydrolysis faster than Peni mainly because its hydroxyethylidene group leads to an increase in the positive charge on the carbonyl C7 atom, therefore enhancing favorable electrostatic interactions with the incoming hydroxide anion. To a lesser extent, the oxygen at position 1 in Clav also contributes to the rate acceleration because of the greater solvent stabilization of the oxygen-containing transition state as compared to the respective ground state. The inherent strain of the four-membered beta-lactam ring or five-membered ring does not enhance the alkaline hydrolyses of beta-lactam molecules such as Peni or Clav, consistent with the observation that the rate-limiting step does not involve a breakdown of the four-membered beta-lactam ring or five-membered thiazolidine/oxazolidine rings.


Right ventricular outflow tract function in chronic obstructive pulmonary disease.
It is clinically important to evaluate the severity of right ventricular (RV) overload in patients with chronic obstructive pulmonary disease (COPD), which is often associated with changes in the structure and the function of the right ventricle. Noninvasive and reliable assessment of RV function would be an essential determinant of RV load and a clinically useful factor for assessing cardiovascular risk in COPD patients. The aim of this study was to investigate the clinical application value of right ventricular outflow tract (RVOT) systolic function measured by transthoracic echocardiography in patients with COPD. We prospectively investigated COPD male patients and compared them with healthy controls. In addition to RV conventional echocardiographic parameters, RVOT size and fractional shortening (RVOT-FS) parameters were also assessed. Fifty-five COPD patients (all men; mean age, 62 ± 9 years) participated in the study, and were compared with a control group consisting of 21male, healthy, nonsmoking subjects with a mean age of 58 ± 11 years. The RVOT-FS was impaired in COPD patients than healthy controls (27.8 ± 15.5 vs. 57.5 ± 8.6, p < 0.001), and was correlated positively with tricuspid annular plane systolic excursion (TAPSE; r = 0.583, p < 0.001) and pulmonary acceleration time (r = 0.666, p < 0.001) and inversely with pulmonary artery systolic pressure (r = 0.605, p < 0.001) and functional capacity(r = - 0.589, p < 0.001). There was a statistically significant difference in RVOT-FS among the COPD subgroups with regard to New York Heart Association functional classification (p < 0.001). The RVOT-FS is a noninvasive easily applicable measure of RV systolic function and is well correlated with functional capacity in COPD patients. Its combination with long-axis measurements via TAPSE and transtricuspid Doppler analysis may provide a comprehensive evaluation of the RV performance in COPD patients.


Chemical Composition of Fresh Leaves Headspace Aroma and Essential Oils of Four Coriander Cultivars.
Aroma is one of the key food characteristics determining consumers' perception and acceptability of products. Coriandrum sativum L. is an aromatic herb commonly used as a food additive and taste enhancer. Besides the culinary applications, coriander is also used in traditional medicine, cosmetics, and the food industry. In this study, we aimed to determine aroma composition of fresh chopped leaves and essential oils extracted from the leaves of four coriander cultivars. The essential oils were extracted from the fresh leaves using steam distillation and volatile aroma components were collected from the headspace by solid phase micro extraction technique. Analyses were carried out by gas chromatography-mass spectrometry. Free radical scavenging activity of essential oils was determined by using 2,2-diphenyl-1-picrylhydrazyl assay. The essential oils were also investigated for their anti-microbial potential. The aroma of freshly chopped coriander leaves was characterized by thirteen compounds, including six aldehydes, four alcohols, one ester and one hydrocarbon. The essential oils were comprised of twenty-seven compounds, where (E)-2-decenal, decanal, (E)-2-dodecenal and (E)-2-tetradecenal were the main components in all cultivars. Free radical scavenging activity of the essential oil samples was in the range of 6-15%. The essential oils of Desi and Hybrid cultivars exhibited least minimum inhibitory concentration (MIC) against all tested bacterial strains. Fresh green leaves of the Desi and Peshawari cultivars were found to be the richest in six carbon chain length alcohols and acetates, which are important constituents of the aroma giving a characteristic odor referred to as the "green note." The Hybrid cultivar showed the highest free radical scavenging activity, bearing the highest amount of antioxidants. The study revealed that the fresh leaves HS aroma of Desi and Hybrid cultivars were different, however, their essential oils possessed almost similar chemistry and anti-bacterial activity.


Intraventricular corticosterone increases the rate of body weight gain in underweight adrenalectomized rats.
Circulating glucocorticoids are necessary for hyperphagia and excessive weight gain in obese rodents. It has been reported that intraventricular administration of selected glucocorticoids restores hyperphagia and weight gain in anorexic adrenalectomized gold thioglucose-treated mice. We wanted to determine whether administration of glucocorticoids directly into the central nervous system of normal (nonobese) rats will enhance the rate of weight gain. In the initial experiment rats were allowed ad libitum access to chow or were rendered underweight by a 7- to 10-day period of food restriction. Animals were then adrenalectomized or sham operated and allowed ad libitum access to chow. Both groups of adrenalectomized animals consumed less food and gained weight less rapidly than their respective sham controls. Previously food-restricted and therefore underweight adrenalectomized rats consumed significantly more food and gained weight more rapidly than previously ad libitum-fed adrenalectomized rats. These data support the conclusion that adrenalectomized rats, like intact rats, regulate their weight, albeit at a lower level than intact rats. To determine a possible role of central glucocorticoids in this phenomenon, food-restricted or ad libitum-fed rats received a single intraventricular injection of corticosterone or its vehicle on the day after adrenalectomy or sham surgery. Whereas intraventricular corticosterone had no effect on weight gain in ad libitum-fed rats, it significantly increased the rate of weight gain in food-restricted adrenalectomized rats relative to that in vehicle-treated controls. Peripheral administration of corticosterone had no effect in this paradigm. It is concluded that glucocorticoids act directly on the central nervous system of underweight lean rats to augment weight gain.


[Synthesis of small peptides containing hydroxy-amino-acid, and its effects on progesterone production].
Eleven peptides containing hydroxy-amino-acid have been synthesized manually by stepwise solid-phase method. Three of them were started on BHA-resin, the others on Merrifield-resin. TFMSA/TFA/p-cresol were used as cleaving reagent in all peptide-resin (1-11) cleavage. Furthermore, HF cleaving procedure was also used parallelly to five of those peptide-resins for contrast. No conspicuous difference in yield was found between TFMSA and HF. The purity of all products was checked by the profiles of analytical reversed phase HPLC (C-18) and the data of amino acid analysis. All synthetic peptides were tested for the effect on progesterone production by rat corpus luteum in vitro. Among them, three peptides, GlyTyr-NH2, LysTyr-NH2 and GlySer Lys-OH, showed significant effect (p less than 0.01) on inhibiting hCG-induced progesterone production.


Quantitative x-ray microanalysis of model biological samples in the SEM using remote standards and the XPP analytical model.
It is shown that accurate x-ray microanalysis of frozen-hydrated and dry organic compounds, such as model biological samples, is possible with a silicon drift detector in combination with XPP (exponential model of Pouchou and Pichoir matrix correction) software using 'remote standards'. This type of analysis is also referred to as 'standardless analysis'. Analyses from selected areas or elemental images (maps) were identical. Improvements in x-ray microanalytical hardware and software, together with developments in cryotechniques, have made the quantitative analysis of cryoplaned frozen-hydrated biological samples in the scanning electron microscope a much simpler procedure. The increased effectiveness of pulse pile-up rejection renders the analysis of Na, with ultrathin window detectors, in the presence of very high concentrations of O, from ice, more accurate. The accurate analysis of Ca (2 mmol kg-1 ) in the presence of high concentrations of K is possible. Careful sublimation of surface frost from frozen-hydrated samples resulted in a small increase in analysed elemental concentrations. A more prolonged sublimation from the same resurfaced sample and other similar samples resulted in higher element concentrations.


[Airway inflammatory cell dynamics during late asthmatic reactions induced by toluene diisocyanate in guinea pigs. I. Bronchoalveolar lavage study].
We developed a guinea pig model of late asthmatic reactions (LAR) induced by toluene diisocyanate (TDI), and investigated airway inflammatory cell dynamics during LAR by bronchoalveolar lavage (BAL) in this model. The guinea pigs were sensitized by nasal application of 10% TDI solution once daily for 7 consecutive days. Thereafter, the animals were challenged with 5% TDI solution, in the same manner, on every 7th day for 4 to 11 times. Each guinea pig was pretreated with metyrapone before challenge. BAL was performed at each time point after the final challenge. The immediate asthmatic reaction and the LAR induced in the challenges were found to be 66% and 55%, respectively. A significant BAL fluid eosinophilia was observed in the guinea pigs during and after LAR (i.e., 3, 6, 24 and 168 hours after challenge), in comparison to the animals without LAR and to the control animals only exposed to ethyl acetate, a solvent for TDI. The number of eosinophils peaked at 6 hours after challenge. However, no significant changes were observed in the numbers of macrophages, lymphocytes or neutrophils in BAL fluid during LAR. We conclude that eosinophils play an important role in LAR in this model. This model seems to be useful in investigating the pathophysiology of TDI-induced asthma.


Occupational musculoskeletal pain amongst ENT surgeons - are we looking at the tip of an iceberg?
Surgeons are exposed to a variety of occupational risks, including work-related musculoskeletal disorders. This study investigated the prevalence of these latter disorders amongst UK ENT surgeons and compared this with the existing literature. A survey containing questions on work-related musculoskeletal disorders was distributed to the entire membership of ENT-UK electronically, with the assistance of its Survey Guardian. A literature review on the subject was then performed. A total of 323 completed questionnaires were received (a 24 per cent response rate). Work-related musculoskeletal disorders had been experienced by 47.4 per cent of respondents. There were no statistical differences between the occurrence of work-related musculoskeletal disorders and: grade, length of time spent in the specialty or the subspecialty of respondents. Eighty-five per cent of affected surgeons sought treatment, with 22.9 per cent taking time off work and six surgeons retiring early. The literature review only identified five related studies. Despite the scarcity of studies, work-related musculoskeletal disorders are common amongst ENT surgeons in the UK. Such disparity highlights the need for more research and appropriate ergonomic intervention within the specialty.


Cytogenetic biomonitoring of Brazilian workers exposed to pesticides: micronucleus analysis in buccal epithelial cells of soybean growers.
Pesticides have been considered potential chemical mutagens and various agrochemical ingredients possess mutagenic properties. Biomonitoring provides a useful tool to estimate the genetic risk from exposure to a complex mixture of chemicals. In general genetic damage associated with pesticides occurs in human populations subject to high exposure levels due to intensive use, misuse or failure of control measures. Few studies have been carried out using the micronucleus (MN) analysis in buccal cells of farm workers and, from the available data, only one has found a positive relationship. Micronuclei were analyzed in 29 Brazilian workers exposed to pesticides in soybean fields and in 37 non-exposed individuals. The results obtained indicate that the mean number of cells with MN in the exposed group (3.55+/-2.13) was significantly higher than in the control group (1.78+/-1.23). The number of cells with MN was not influenced by age, smoking habit, smoking time, number of cigarettes/day, alcohol consumption and years of exposure to pesticides. The genotoxic potential of the pesticides used in soybean fields may explain the detectable increase of cells with MN in exposed workers.


Late-Stage Functionalisation of Polycyclic (N-Hetero-) Aromatic Hydrocarbons by Detoxifying CYP5035S7 Monooxygenase of the White-Rot Fungus Polyporus arcularius.
Functionalisation of polycyclic aromatic hydrocarbons (PAHs) and their N-heteroarene analogues (NPAHs) is a tedious synthetic endeavour that requires diverse bottom-up approaches. Cytochrome P450 enzymes of white-rot fungi were shown to participate in the fungal detoxification of xenobiotics and environmental hazards via hydroxylation of PAH compounds. In this paper, the recently discovered activity of the monooxygenase CYP5035S7 towards (N)PAHs was investigated in detail, and products formed from the substrates azulene, acenaphthene, fluorene, anthracene, and phenanthrene by whole-cell biocatalysis were isolated and characterised. The observed regioselectivity of CYP5035S7 could be explained by a combination of the substrate's electron density and steric factors influencing the substrate orientation giving insight into the active-site geometry of the enzyme.


Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe2+/Cu2+ Chelator in Cell and Animal Models of Parkinson's Disease.
Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson's disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ ∼ Fe2+ > Zn2+ > Fe3+. No binding capacity was detected for Hg2+, Co2+, Ca2+, Mn2+, Mg2+, Ni2+, Pb2+, or Cd2+. DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts and oxidation of C11-BODIPY581/591. DHC12 also blocked the decrease in mitochondrial membrane potential, detected by tetramethylrhodamine distribution. DHC12 inhibited MAO-A and MAO-B activity. Oral administration of DHC12 to mice (0.25 mg/kg body weight) protected substantia nigra pars compacta (SNpc) neurons against MPTP-induced death. Taken together, our results support the concept that DHC12 is a mitochondrial-targeted neuroprotective iron-copper chelator and MAO-B inhibitor with potent antioxidant and mitochondria protective activities. Oral administration of low doses of DHC12 is a promising therapeutic strategy for the treatment of diseases with a mitochondrial iron accumulation component, such as PD.


[Three-dimensional MR brain image using volume rendering method].
3-dimensional image reconstructed from the data of computer tomography has provided useful informations for the pre-operative evaluation in the field of neurosurgery and plastic surgery. However CT has failed to visualized the 3-dimensional surface image of the central nervous system. On the other hand the progress of high-speed data acquisition technique and 3-dimensional fourier transformation has enabled the practical 3-dimensional image using magnetic resonance imager. However for the visualization of a pure surface image of the brain and spinal cord a sophisticated method and special image work station has been necessary. The authors describe a technique for the pure surface image of the brain and spinal cord using a normal mini-computer system and magnetic resonance imager. This image has a good correlation to the macroscopic anatomical brain surface (sulci and gyri).


AtBGAL10 is the main xyloglucan β-galactosidase in Arabidopsis, and its absence results in unusual xyloglucan subunits and growth defects.
In growing cells, xyloglucan is thought to connect cellulose microfibrils and regulate their separation during wall extension. In Arabidopsis (Arabidopsis thaliana), a significant proportion of xyloglucan side chains contain β-galactose linked to α-xylose at O2. In this work, we identified AtBGAL10 (At5g63810) as the gene responsible for the majority of β-galactosidase activity against xyloglucan. Xyloglucan from bgal10 insertional mutants was found to contain a large proportion of unusual subunits, such as GLG and GLLG. These subunits were not detected in a bgal10 xyl1 double mutant, deficient in both β-galactosidase and α-xylosidase. Xyloglucan from bgal10 xyl1 plants was enriched instead in XXLG/XLXG and XLLG subunits. In both cases, changes in xyloglucan composition were larger in the endoglucanase-accessible fraction. These results suggest that glycosidases acting on nonreducing ends digest large amounts of xyloglucan in wild-type plants, while plants deficient in any of these activities accumulate partly digested subunits. In both bgal10 and bgal10 xyl1, siliques and sepals were shorter, a phenotype that could be explained by an excess of nonreducing ends leading to a reinforced xyloglucan network. Additionally, AtBGAL10 expression was examined with a promoter-reporter construct. Expression was high in many cell types undergoing wall extension or remodeling, such as young stems, abscission zones, or developing vasculature, showing good correlation with α-xylosidase expression.


Receipt and Perceived Helpfulness of Mental Illness Information: Findings from the Australian National Survey of Mental Health and Wellbeing.
The distribution of mental illness information is a crucial element of mental health promotion initiatives. We assessed the receipt and perceived helpfulness of such information in Australia. Data from the Australian National Survey of Mental Health and Wellbeing indicated that, during the year prior to the survey, 33.7% of Australians received mental illness information; of these, 51.2% found it helpful. Among people with a mental disorder, 46.1% received information; of these, 67.4% found it helpful. Non-English speakers and the socially disadvantaged were less likely to receive mental illness information. Older and less educated respondents were less likely to both receive mental illness information and find it helpful. Mental health service users were more likely to receive mental illness information perceived as helpful than those who had not accessed such services. Better targeted information interventions are required to ensure those most likely to benefit receive mental illness-related information.


Analysis of reactivation of latent pseudorabies virus infection in tonsils and Gasserian ganglia of pigs.
Multiplication of pseudorabies virus (PRV) strain TOP and establishment of latency were followed in the tonsils and Gasserian ganglia (GG) of 8-week-old pigs after oral infection. Already within 24 hr, the titre of PRV in tonsils reached 10(2) TCID50/g tissue, its presence in the oropharynx being detectable by swabbing. Virus multiplication in tonsils culminated on days 3-6 p.i. (10(6)-10(6.5) TCID50/g) and continued till day 11 post-infection (p.i.), when its titre was 10(1.5) TCID50/g the swabs being still positive. The presence of the virus in GG was first proved at 48 hr p.i., but no virus could be found there by titration on day 11. The virus titre in the GG had essentially followed that in tonsils, however, it was substantially lower during the whole experiment. After primoinfection no shedding of PRV was detected by oropharyngeal swabs taken at 3-5 day intervals during the period of 360 days. Nevertheless, explantation of tonsils and GG, performed between days 60-360 p.i., revealed the presence of PRV latency in 41.1 per cent of animals. The total activation rate in GG cultures was 71.5 per cent, while in the cultures of tonsils 28.5 per cent only. Cocultivation of cell suspensions obtained by trypsinization of GG and tonsillar tissue with chick embryo cells (CEC) did not result in detection of the latent virus though latency was confirmed by explantation of the same tissue samples. However, already 24 hr in culture were sufficient for activation of latency as judged by trypsinization of the explanted tonsillar and GG fragments and their inoculation onto CEC. Estimation of the number of cells carrying PRV in the GG showed that activation occurred in one out of 10(4)-10(5) ganglion cells.


Multilayered Films Produced by Layer-by-Layer Assembly of Chitosan and Alginate as a Potential Platform for the Formation of Human Adipose-Derived Stem Cell aggregates.
The construction of multilayered films with tunable properties could offer new routes to produce biomaterials as a platform for 3D cell cultivation. In this study, multilayered films produced with five bilayers of chitosan and alginate (CHT/ALG) were built using water-soluble modified mesyl and tosyl⁻CHT via layer-by-layer (LbL) self-assembly. NMR results demonstrated the presences of mesyl (2.83 ppm) and tosyl groups (2.39, 7.37 and 7.70 ppm) in the chemical structure of modified chitosans. The buildup of multilayered films was monitored by quartz-crystal-microbalance (QCM-D) and film thickness was estimated using the Voigt-based viscoelastic model. QCM-D results demonstrated that CHT/ALG films constructed using mesyl or tosyl modifications (mCHT/ALG) were significantly thinner in comparison to the CHT/ALG films constructed with unmodified chitosan (p < 0.05). Adhesion analysis demonstrated that human adipose stem cells (hASCs) did not adhere to the mCHT/ALG multilayered films and formed aggregates with sizes between ca. 100⁻200 µm. In vitro studies on cell metabolic activity and live/dead staining suggested that mCHT/ALG multilayered films are nontoxic toward hACSs. Multilayered films produced via LbL assembly of ALG and off-the-shelf, water-soluble modified chitosans could be used as a scaffold for the 3D aggregates formation of hASCs in vitro.


Role of reactive oxygen species in hyperadrenergic hypertension: biochemical, physiological, and pharmacological evidence from targeted ablation of the chromogranin a (Chga) gene.
Oxidative stress, an excessive production of reactive oxygen species (ROS) outstripping antioxidant defense mechanisms, occurs in cardiovascular pathologies, including hypertension. In the present study, we used biochemical, physiological, and pharmacological approaches to explore the role of derangements of catecholamines, ROS, and the endothelium-derived relaxing factor nitric oxide (NO(•)) in the development of a hyperadrenergic model of hereditary hypertension: targeted ablation (knockout [KO]) of chromogranin A (Chga) in the mouse. Homozygous ⁻(/)⁻ Chga gene knockout (KO) mice were compared with wild-type (WT, +/+) control mice. In the KO mouse, elevations of systolic and diastolic blood pressure were accompanied by not only elevated catecholamine (norepinephrine and epinephrine) concentrations but also increased ROS (H₂O₂) and isoprostane (an index of lipid peroxidation), as well as depletion of NO(•). Renal transcript analyses implicated changes in Nox1/2, Xo/Xdh, and Sod1,2 mRNAs in ROS elevation by the KO state. KO alterations in blood pressure, catecholamines, H₂O₂, isoprostane, and NO(•) could be abrogated or even normalized (rescued) by either sympathetic outflow inhibition (with clonidine) or NADPH oxidase inhibition (with apocynin). In cultured renal podocytes, H₂O₂ production was substantially augmented by epinephrine (probably through β₂-adrenergic receptors) and modestly diminished by norepinephrine (probably through α₁-adrenergic receptors). ROS appear to play a necessary role in the development of hyperadrenergic hypertension in this model, in a process mechanistically linking elevated blood pressure with catecholamine excess, renal transcriptional responses, ROS elevation, lipid peroxidation, and NO(•) depletion. Some of the changes appear to be dependent on transcription, whereas others are immediate. The cycle could be disrupted by inhibition of either sympathetic outflow or NADPH oxidase. Because common genetic variation at the human CHGA locus alters BP, the results have implications for antihypertensive treatment as well as prevention of target-organ consequences of the disease. The results document novel pathophysiological links between the adrenergic system and oxidative stress and suggest new strategies to probe the role and actions of ROS within this setting.


[Contraception and thrombophilia].
The risk of thromboembolic events (TE) is increased by acquired or inherited thrombophilias (IT). We know that some hormonal contraceptives also increase the risk of thrombosis, thus, the use of such contraceptives are discussed as contraindications in women with IT. TEs are infrequent events in children and adolescents and in the majority of cases are associated with secondary complications from underlying chronic illness. Although adolescents are not typically considered to be at high-risk for TE, this cohort is frequently using hormonal contraception, leading to an increased risk in cases with unknown IT. The risk of TE with pregnancy alone is higher than associated with combined hormonal contraception. Progestin-only methods have not been found to increase the risk of TE with only moderate changes of coagulation proteins compared to normal reference values. Thrombophilic women are good candidates for progestin-only contraceptive methods.


Early alterations in the function of sarcoplasmic reticulum in a naturally occurring model of congestive cardiomyopathy.
In a naturally occurring model of congestive cardiomyopathy-round heart disease of turkeys, Ca2+ transport of isolated cardiac sarcoplasmic reticulum was evaluated at 1, 10, 28, and 56 days of age. Ca2+ binding in round heart disease birds was reduced to between 55% and 75% of values measured in age-matched commercial control turkeys (P less than 0.05 to less than 0.01). Similarly, Ca2+ uptake in round heart disease birds was reduced to between 52% and 87% of values measured in age-matched commercial control turkeys (P less than 0.05 and less than 0.01). Ca2+-stimulated ATPase values were similar in 1-, 10-, and 28-day-old round heart disease and commercial control turkeys. However at 56 days of age, when all round heart disease birds showed moderate to marked left ventricular dilatation. Ca2+-stimulated ATPase was reduced to 75% of control values (P less than 0.05). Depression of Ca2+ binding and Ca2+ uptake preceded the appearance of cardiac dilatation and may contribute to the pathogenesis of round heart disease. Depression of Ca2+-stimulated ATPase, present only after cardiac dilatation developed, appears to be secondary to cardiac failure. Sarcoplasmic reticulum function in round heart disease birds immunosuppressed by cyclophosphamide treatment (40 mg . kg-1 . d-1 for the first 4 days of age) was evaluated at 10 days of age. This treatment increased Ca2+ binding by 73% (P less than 0.05), and Ca2+-uptake by 58% (P less than 0.01) over values measured in untreated round heart disease birds. Reversal of the altered Ca2+ transport in sarcoplasmic reticulum by early immunosuppression supports the hypothesis that the immune system plays an integral part in the development of the congestive cardiomyopathy of round heart disease.


Influence of Flow Disturbances behind the 90° Bend on the Indications of the Ultrasonic Flow Meter with Clamp-On Sensors on Pipelines.
The subject matter of the article concerns velocities/flow rate measurements in the area of disturbed flows-behind the 90° bend. They were conducted by means of an ultrasonic flowmeter with clamp-on sensors on pipeline, for water and two different Reynolds numbers of 70,000 and 100,000, corresponding to two velocities of approximately 1.42 m/s and 2.04 m/s. The tests were carried out at 12 distances from the disturbance. Sensors on the circumference of the pipeline were mounted 30° each. The correction factor values were calculated for the given measurement geometry. The measurements have shown that the values of this coefficient are always greater than 1, which means that the ultrasonic flow meter understates the speed values. They also showed that already at a distance of 8 nominal diameters from the disturbance, the correction factor does not exceed 1.02, so the measurement errors are within the maximum permissible error (MPE) of a typical ultrasonic flow meter. For distances less than eight nominal diameters from the disturbance, not taking the correction factor value into the account can lead to systematic errors of up to 10.8%. Studies have also proved that in each measurement plane behind the disturbance there are two mounting angles for the ultrasonic sensors, 60° and 240° respectively, for which the correction factor values are minimal. Additionally, using the laser Doppler anemometry (LDA) method, velocity solids were determined at individual distances from the disturbance, and the projections of velocity blocks on the appropriate plane represented velocity profiles and indicated the distances from the disturbance at which these profiles stabilise.


Broadband transient dichroism spectroscopy in chiral molecules.
We perform time-resolved broadband transmission ellipsometry using the ultrafast pump-probe technique in an original setup. Our setup allows us to measure, over a wide spectral range, the optical rotary dispersion of the sample or, when needed, its circular dichroism by adding a broadband quarter-wave plate. While our experiment has been designed to study the transient states in chiral molecules, it performs sufficiently well to also characterize the ground state.


Use of glucosamine and chondroitin sulfate in the management of osteoarthritis.
The goals of osteoarthritis therapy are to decrease pain and to maintain or improve joint function. The pharmacologic treatment of this condition has included the use of aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs. More recently, numerous studies have investigated the potential role of chondroprotective agents in repairing articular cartilage and decelerating the degenerative process. The reports of limited clinical experience with two of these agents, glucosamine and chondroitin sulfate, as well as the accompanying publicity in the popular media, have generated controversy. Advocates of these alternative modalities cite reports of progressive and gradual decline of joint pain and tenderness, improved mobility, sustained improvement after drug withdrawal, and a lack of significant toxicity associated with short-term use of these agents. Critics point out that in the great majority of the relevant clinical trials, sample sizes were small and follow-up was short-term.


Difficult diagnosis of atypical cystic pancreatic lesions in von Hippel-Lindau disease.
von Hippel-Lindau disease is a progressive, autosomal dominant disorder with multiorgan involvement. There are 2 types of pancreatic lesions from von Hippel-Lindau disease: cystic lesions and endocrine pancreatic tumors. Only the latter type is potentially malignant and may justify pancreatic resection. The differential diagnosis between these 2 types of lesions can be difficult. We report 3 patients with atypical cystic pancreatic lesions who underwent surgery for suspected malignant tumors. The pathological-radiological correlations and the diagnostic and management strategies are discussed.


[A case of cancer successfully treated by chemotherapy of S-1 as first-line chemotherapy].
The patient was an 83-year-old man who had undergone pancreaduodenectomy for a diagnosed lower bile duct cancer in April 2004. CT demonstrated intra-abdominal lymph node enlargement 2 years postoperatively and CA19-9 increased. S-1, an oral fluoropyrimidine anticancer drug, was started as first-line chemotherapy. A complete response was confirmed after the first two courses of S-1 monotherapy. CR persisted for 2 years and S-1 was discontinued after 25th course because of long CR. No grade 3 or more toxicities were noted.


MsVRL: Self-Supervised Multiscale Visual Representation Learning via Cross-Level Consistency for Medical Image Segmentation.
Automated medical image segmentation for organs or lesions plays an essential role in clinical diagnoses and treatment plannings. However, training an accurate and robust segmentation model is still a long-standing challenge due to the time-consuming and expertise-intensive annotations for training data, especially 3-D medical images. Recently, self-supervised learning emerges as a promising approach for unsupervised visual representation learning, showing great potential to alleviate the expertise annotations for medical images. Although global representation learning has attained remarkable results on iconic datasets, such as ImageNet, it can not be applied directly to medical image segmentation, because the segmentation task is non-iconic, and the targets always vary in physical scales. To address these problems, we propose a Multi-scale Visual Representation self-supervised Learning (MsVRL) model, to perform finer-grained representation and deal with different target scales. Specifically, a multi-scale representation conception, a canvas matching method, an embedding pre-sampling module, a center-ness branch, and a cross-level consistent loss are introduced to improve the performance. After pre-trained on unlabeled datasets (RibFrac and part of MSD), MsVRL performs downstream segmentation tasks on labeled datasets (BCV, spleen of MSD, and KiTS). Results of the experiments show that MsVRL outperforms other state-of-the-art works on these medical image segmentation tasks.


Aerobic Oxidation of Olefins and Lignin Model Compounds Using Photogenerated Phthalimide-N-oxyl Radical.
A metal-free protocol to generate phthalimide-N-oxyl (PINO) radicals from N-hydroxyphthalimide (NHPI) via a photoinduced proton-coupled electron transfer process is reported. Using donor-substituted aromatic ketones, such as 4,4'-bis(diphenylamino)benzophenone (DPA-BP), PINO radicals are efficiently produced and subsequently utilized to functionalize olefins to afford a new class of alkyl hydroperoxides. The DPA-BP/NHPI/O2 photocatalytic system exhibits high efficiency toward the aerobic oxidation of β-O-4 lignin models.


Vital gas exchange and hatchability of turkey eggs at high altitude.
Conductance of turkey eggshells was observed to be significantly (P less than .01) greater at 2000 than at 200 m elevation. It was concluded that the increased conductance may have been due to the Chapman-Enskog relation. Eggshells of nonhatching eggs from the high altitude were examined, and it was determined that despite the increased conductance rate, eggshells with significantly (P less than .05) less functional pore area hatched poorly in both oxygenated and nonoxygenated environments. When oxygen was not supplemented to the incubators at high altitudes, eggshells required significantly (P less than .01) fewer pore concentrations to allow embryos to survive to late stages of embryonic development than eggs in oxygen supplemented environments. However, greater pore concentrations on the air space were required in both environments to complete hatching. Cuticle removal from eggshells incubated in oxygen supplemented incubators at high altitudes significantly (P less than .05) reduced late embryonic mortality. It was concluded that eggshell cuticle removal may be more advantageous to hatchability at high altitude than oxygen supplementation.


BJ-HCC-20, a potential novel cancer-testis antigen.
In an effort to identify novel Cancer-Testis genes, we analyzed the sequence in the q26-28 region of human X chromosome by several on-line tools. The candidate sequences were then confirmed by experiments. We have obtained a novel Cancer-Testis gene, BJ-HCC-20. In vivo, it was found to have two isoforms. In samples of liver, colon, gastric and lung cancer tested, the expression frequency of BJ-HCC-20 is 25%, 17%, 21% and 15%, respectively. Full-length cDNAs of both BJ-HCC-20 isoforms were isolated and their gene structures and promoter regions were characterized. BJ-HCC-20 might have implications in theoretical and practical tumor biology.


Serum tonicity, extracellular volume and clinical manifestations in symptomatic dialysis-associated hyperglycemia treated only with insulin.
The absence of osmotic diuresis modifies the effects of hyperglycemia on body fluids in patients with advanced renal failure. To determine the relationship between clinical manifestations and abnormalities in tonicity and extracellular volume in such patients, we analyzed 43 episodes of severe dialysis-associated hyperglycemia (serum glucose exceeding 600 mg/dL) treated only with insulin. The main manifestations were dyspnea in 22 cases (pulmonary edema in 19), nausea and vomiting in 15, coma in 13 and seizures in 3, while 5 patients had no symptoms. Treatment with insulin resulted in a decrease in serum glucose value from 913 +/- 197 mg/dL to 170 +/- 78 mg/dL, an increase in serum sodium level from 125 +/- 5 to 136 +/- 5 mmol/L, and a fall in calculated serum tonicity value from 300 +/- 13 to 282 +/- 11 mmol/kg (all at p < 0.001). The ratio of the change in serum sodium level over change in serum glucose concentration was -1.50 +/- 0.22 mmol/L per 100 mg/dL. The percent increase in extracellular volume secondary to hyperglycemia developing from the prior euglycemic state and calculated from changes in serum sodium and chloride concentrations, was 10.9% +/- 4.6% (1.5% +/- 0.6% per 100 mg/dL increase in serum glucose level). All clinical manifestations dissipated after correction of hyperglycemia in 42 patients. One woman developed during treatment a fatal myocardial infarction. Dialysis patients with severe hyperglycemia may develop symptoms as a result of hypertonicity and extracellular expansion. Insulin alone may be sufficient treatment for these symptoms. The changes in serum tonicity and electrolytes during treatment are consistent with theoretical predictions.


Dynamic molecular structure of plant biomass-derived black carbon (biochar).
Char black carbon (BC), the solid residue of incomplete combustion, is continuously being added to soils and sediments due to natural vegetation fires, anthropogenic pollution, and new strategies for carbon sequestration ("biochar"). Here we present a molecular-level assessment of the physical organization and chemical complexity of biomass-derived chars and, specifically, that of aromatic carbon in char structures. Brunauer-Emmett-Teller (BET)-N(2) surface area (SA), X-ray diffraction (XRD), synchrotron-based near-edge X-ray absorption fine structure (NEXAFS), and Fourier transform infrared (FT-IR) spectroscopy are used to show how two plant materials (wood and grass) undergo analogous but quantitatively different physical-chemical transitions as charring temperature increases from 100 to 700 degrees C. These changes suggest the existence of four distinct categories of char consisting of a unique mixture of chemical phases and physical states: (i) in transition chars, the crystalline character of the precursor materials is preserved; (ii) in amorphous chars, the heat-altered molecules and incipient aromatic polycondensates are randomly mixed; (iii) composite chars consist of poorly ordered graphene stacks embedded in amorphous phases; and (iv) turbostratic chars are dominated by disordered graphitic crystallites. Molecular variations among the different char categories likely translate into differences in their ability to persist in the environment and function as environmental sorbents.


Virtual setup: application in orthodontic practice.
A plaster dental model is a patient's traditional three-dimensional (3D) record. If the dental crowns from a plaster model are separated and positioned in wax, this setup of the crowns can be used to simulate orthodontic treatment. The traditional way to make this dental setup requires significant time by the orthodontist and in the orthodontic lab. New developments in dentistry and orthodontics include the possibility of virtual setups. In this article, the differences between conventional setups with plaster models and virtual setups are discussed. A clinical patient is described for whom two different setups were made and compared by model superimposition with Geomagic Qualify software. According to the literature and the results from this study, virtual setups and conventional setups with plaster models are equally accurate. Virtual setups present several advantages, e.g., digital storage, digital models cannot be damaged, the same model can undergo several treatment simulations, and communication between dental and surgical professionals and between dental professionals and patients is facilitated. Despite these advantages, considerable time and training are needed for dental professionals to master and adopt the general use of digital models and virtual setups in dentistry.


miR-190a-5p Partially Represses the Abnormal Electrical Activity of SCN3B in Cardiac Arrhythmias by Downregulation of IL-2.
Cardiac arrhythmias (CAs) are generally caused by disruption of the cardiac conduction system; interleukin-2 (IL-2) is a key player in the pathological process of CAs. This study aimed to investigate the molecular mechanism underlying the regulation of IL-2 and the sodium channel current of sodium voltage-gated channel beta subunit 3 (SCN3B) by miR-190a-5p in the progression of CAs. ELISA results suggested the concentration of peripheral blood serum IL-2 in patients with atrial fibrillation (AF) to be increased compared to that in normal controls; fluorescence in situ hybridization indicated that the expression of IL-2 in the cardiac tissues of patients with AF to be upregulated and that miR-190a-5p to be downregulated. Luciferase reporter assay, quantitative real-time-PCR, and whole-cell patch-clamp experiments confirmed the downregulation of IL-2 by miR-190a-5p and influence of the latter on the sodium current of SCN3B. Overall, miR-190a-5p suppressed the increase in SCN3B sodium current caused by endogenous IL-2, whereas miR-190a-5p inhibitor significantly reversed this effect. IL-2 was demonstrated to be directly regulated by miR-190a-5p. We, therefore, concluded that the miR-190a-5p/IL-2/SCN3B pathway could be involved in the pathogenesis of CAs and miR-190a-5p might acts as a potential protective factor in pathogenesis of CAs.


Long pentraxin 3 (PTX3) in the light of its structure, mechanism of action and clinical implications.
Pentraxins are a group of evolutionarily conserved ancient proteins. Depending on their structure, pentraxins are divided into short and long pentraxin families. Pentraxin 3 (PTX3) is the prototype of the long pentraxin group. PTX3 synthesis is stimulated by a variety of molecules involved in the inflammatory process. The inflammatory mediator is typically produced at inflammatory sites; however, it can also be released at the sites remote from the original inflammatory insult. Although mainly expressed by vascular endothelium and smooth muscle cells, PTX3 is also synthesized by myeloid dendritic cells, mononuclear macrophages/phagocytes, vascular endothelial and smooth muscle cells, fibroblasts, adipocytes, cumulus oophorus cells mesangial cells, synovial cells and chondrocytes. PTX3 binds to several ligands including complement component C1q, factor H, ficolin-1 (M-ficolin), mannose-binding lectin, fibroblast growth factor 2, P-selectin, matrix protein TSG6 and Klebsiella pneumoniae; it is also known to play a role in humoral innate immunity as well as in degenerated and apoptotic cells clearance. PTX3 acts as a modulator of inflammatory processes, modifies angiogenesis and atherosclerotic lesion development, and participates in extracellular matrix formation. Due to the fact of PTX3 being primarily produced and released by vascular wall cells, it might be used as a sensitive and independent inflammatory marker.


Temporal lobe surgery for intractable epilepsy in children: What to do with the hippocampus?
Resection of the hippocampus can cause verbal memory decline, especially in the pediatric population. Thus, preservation of the hippocampus can be crucial for the quality of life of children with intractable temporal lobe epilepsy (TLE) who are candidates for epilepsy surgery. We investigated techniques that determine whether the hippocampus is part of the epileptogenic zone and the outcomes of pediatric surgery aimed to spare the hippocampus. We accessed data of children with normal hippocampus on MRI, who underwent surgery for medically refractory TLE. To identify epileptogenic areas, electrocorticography was performed in patients with space occupying lesions adjacent to the hippocampus, and long term invasive monitoring in patients with nonlesional TLE. Postoperative seizure control was classified according to Engel I-IV; Class I indicates seizure-free. Eleven females and 11 males met study inclusion criteria; the mean age at surgery was 11.3 years. Cortical and hippocampal electrocorticography was performed in 15 patients and long term invasive hippocampal monitoring in seven. The hippocampus was preserved in 16 patients (73%) while hippocampectomy was performed in 6 (27%). At the end of a mean follow-up of 3.5 years, 94% (15/16) of the patients who did not undergo hippocampectomy were classified as Engel I, compared to 50% (3/6) who underwent hippocampectomy. Sparing the hippocampus in temporal lobe epilepsy surgery is possible with excellent seizure outcome, while using the proper intraoperative technique.


Visible-to-ultraviolet-C upconverted photon for multifunction via Ca2SiO4:Pr3.
The ultraviolet C (UVC) photon plays a key role in a broad spectrum of fields. With the implementation of the Minamata Convention, searching for a new way to achieve UVC light is highly desired. Here we develop a material of Ca2SiO4:Pr3+ that can emit UVC light upon excitation of a 450-nm laser or even a very cheap 450-nm LED, a fact confirmed by using a solar blind camera to capture UVC emission from Ca2SiO4:Pr3+. In addition, smart anti-counterfeiting and inactivation of Bacillus subtilis applications using Ca2SiO4:Pr3+ are also confirmed.


Dengue and post-infection fatigue: findings from a prospective cohort-the Colombo Dengue Study.
Previous studies on post-infection fatigue in dengue are few but suggest that up to 25% of dengue patients may suffer from fatigue. This study aimed to evaluate the prevalence and associations of post-infection fatigue in dengue patients compared with non-dengue fever patients. Post-infection fatigue and its demographic and clinical associations were assessed in adult dengue and non-dengue fever patients 2 months after the acute infection in a prospective cohort study in Sri Lanka. Fatigue at 2 months (primary endpoint) was assessed with the fatigue questionnaire as a dichotomous outcome based on a pre-recommended cut-off (score ≥4) and as the total score from the questionnaire (higher score indicates more fatigue). Of 260 patients, 158 had dengue and, of these, 51 (32%) had fatigue at 2 months. Risk was higher in dengue patients (vs non-dengue; relative risk [RR] 4.93 [95% confidence interval {CI} 2.3 to 10.4]) and more so in female dengue patients (vs male dengue patients; RR 2.45 [95% CI 1.24 to 4.86]). Severe dengue patients had a higher mean fatigue score (p=0.024). Post-infection fatigue is an underappreciated burden of this widely prevalent infection. Our findings are useful to triage patients at risk of fatigue for follow-up.


Group structure and physical characteristics of Simakobu monkeys (Simias concolor) on the Mentawai Island of Siberut, Indonesia.
We present data on group structure and physical characteristics from free-ranging Simias concolor. Mean group size (n = 3) was 8.7 +/- 1.1 individuals with an average adult male:female sex ratio of 1:3. All individuals were sexed and allocated into three categories (infants, juveniles plus subadults and adults) on the basis of their physical development. Within age categories, head-body lengths ranged from 19.6 to 25, 34 to 44 and 42 to 53 cm. Corresponding body weights ranged from 0.5 to 0.9, 2.35 to 4.4 and 5.2 to 7.85 kg, respectively; on average adult males were 13% larger and 23% heavier than adult females. Results indicate that for S. concolor living in undisturbed habitat (i) group sizes are larger than previously reported and (ii) polygyny is the most likely mating system. Both results support an earlier proposal that group size and social organization in Simakobu monkey are related to the degree of habitat disturbance.


Work-related fatigue: A hazard for workers experiencing disproportionate occupational risks.
Long working hours and fatigue are significant occupational safety and health (OSH) hazards for working populations who experience disproportionate risks of injury and illness. These groups include young or new workers, aging workers, contingent and temporary workers, immigrant and nonnative workers, female workers, minority workers, workers with low levels of education and lower socioeconomic status, and small business employees. An increasing focus on newer determinants of health in the workplace, such as health equity and work-life conflict, in worker populations at greater risk for injury or illness, provides an opportunity for researchers to address the causes and consequences of work-related fatigue in high-risk populations. Articles in the OSH literature that addressed fatigue in higher-risk workers were identified by the authors or recommended by subject matter experts in workplace fatigue as part of a Working Hours, Sleep and Fatigue Forum. Additional articles were identified by searching for a combination of specific at-risk worker group titles (e.g., female workers, temporary workers) with fatigue or working hours. There remains a paucity of research specifically addressing working hours and fatigue among disproportionately at-risk worker populations. The literature reviewed in this paper suggests that several of these populations are at increased risk of fatigue due to multiple factors, such as irregular shifts, lack of access to fatigue management resources, and socioeconomic barriers. More research is needed to identify solutions to address fatigue in working populations who may be at greater risk for its consequences by virtue of adverse socioeconomic and related factors. Interventions to address work-related fatigue in specific at-risk worker groups should also consider the multiple and overlapping categories of risk within these populations.


Increase in Free and Bound Abscisic Acid during Natural and Ethylene-induced Senescence of Citrus Fruit Peel.
Free and bound abscisic acid and neutral growth inhibitors were detected in citrus fruit peel using two bioassays and gasliquid chromatography. None of the inhibitor components seems to be directly associated with chloroplasts or chromoplasts in citrus fruit peel.Green, nonsenescent fruits contain mostly neutral inhibitors and relatively low amounts of free and bound abscisic acid. Upon harvest and storage in ethylene, 50 microliters per liter, both free and bound abscisic acid accumulate rapidly, attaining within 24 hours a level of 1 microgram per gram. After 48 hours bound abscisic acid reaches a much higher level than free abscisic acid. Fruits allowed to senesce on the tree follow a similar course of abscisic acid accumulation, attaining finally a 10: 1 ratio of bound to free abscisic acid.


Evidence that polymorphism of the angiotensin I converting enzyme gene may be related to idiopathic dilated cardiomyopathy in the Chinese population.
Angiotensin I-converting enzyme (ACE) is responsible for the production of angiotension II and the breakdown of kinins, leading to increased blood pressure (BP), induction of vascular smooth muscle cell proliferation, and the stimulation of myocardial-cell hypertrophy. A 287 bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction in a cross-sectional study of 35 patients with idiopathic dilated cardiomyopathy (IDC) and 35 patients with normally functioning hearts (NT). Compared with the deletion/deletion (D/D) frequency in the control population, the frequency of the deletion allele was 0.757 in IDC patients and 0.600 in NTs; the difference between observed alleles in all subjects in each group was significant (x2 = 3.96; P < 0.05). The data thus provide evidence in favor of an association between idiopathic dilated cardiomyopathy and a polymorphism at the ACE locus (17q23), thus implicating this locus, and possibly a genetic variant of ACE, itself, in human idiopathic dilated cardiomyopathy.


Piracetam for dementia or cognitive impairment.
To determine the clinical efficacy of piracetam for the features of dementia or cognitive impairment, classified according to the major subtypes of dementia: vascular, Alzheimer's disease or mixed vascular and Alzheimer's disease, or unclassified dementia, or cognitive impairment not fulfilling the criteria for dementia. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 November 2000 using the term spiracetam, nootropic and 2-Oxo-1-pyrrolidine. In addition the pharmaceutical company responsible for marketing most of the piracetam worldwide, UCB Pharma, provided a comprehensive list of abstracts, which included many unpublished studies. As many of these unpublished, placebo-controlled studies will be reviewed as possible. All unconfounded trials specified as randomized in which treatment with piracetam was administered for more than a day and compared with placebo in patients with dementia of Alzheimer type, vascular dementia,or mixed vascular and Alzheimer's disease, or unclassified dementia, or cognitive impairment not fulfilling the criteria for dementia. Data were extracted independently by two reviewers. Each study was independently verified as fulfilling the inclusion criteria. Studies were rated for methodological quality by assessment of blinding and loss before analysis as described by Jadad et al. (1996). Studies were pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat analyses were undertaken. Sensitivity analyses were performed to determine if successive elimination of those studies performing most poorly on these quality criteria changed the effect estimate. Unfortunately, many of the studies were of cross-over design and first-phase data were unavailable, or could not be extracted. Global Impression of Change was the only outcoeme for which there was a significant volume of evidence from the pooled data. There was evidence of heterogeneity in the results from the individual studies, chi-square test = 20.8 (df=5). Using a fixed effects model the odds ratio for improvement in the piracetam group compared with the placebo group was 3.55, [95% CI][2.45, 5.16]. If a random effects model was used the odds ratio was 3.47 [1.29, 9.30]. If one single-blind study was excluded, the fixed effects model yielded an odds ratio of 3.36 [2.29, 4.99] and if a random effects model was applied then the odds ratio was 2.89 [1.01, 8.24]. The evidence of effects on cognition and other measures, was inconclusive. At this stage the evidence available from the published literature does not support the use of piracetam in the treatment of people with dementia or cognitive impairment. Although effects were found on global impression of change, no benefit was shown by any of the more specific measures. There is a need for further evaluation of piracetam by : 1) Obtaining the data from the identified studies for an individual patient database review, 2) Performing a randomized trial of piracetam in patients with diagnoses made by currently accepted diagnostic criteria. The trial should extend over for a period of at least 6 months and preferably longer. Specific cognitive instruments which are sensitive to change, Clinician Global Impression of Change, levels of dependency and caregiver quality of life scales should also be incorporated in such a study.


Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane.
An efficient and convenient method for the synthesis of structurally unique and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential utility of halothane for the synthesis of aryl gem-difluoroalkyl ethers containing the bromochloromethyl group.


Emergency medical services in China.
The objective of this article is to identify and describe Chinese emergency medical services (EMS) components. Chinese EMS system development began in the 1980s with "importing" of EMS principles from other systems. China is now attempting to unify these principles. Chinese EMS systems are absent in most rural areas. Urban ambulance dispatch or "rescue" centers provide both transport and inpatient care. Ambulances are staffed with either a physician or a driver. There is not extensive overlap between hospital emergency physicians and ambulance physicians and no out-of-hospital providers at the paramedic or emergency medical technician level exist. Access to EMS is accomplished by dialing 1-2-0. Emergency calls go directly to the rescue center and a physician is dispatched. No on-line radio communication between hospitals and ambulances typically takes place. China has assimilated both traditional and unique EMS components and is undergoing development. It remains unclear whether a systematized EMS structure will emerge.


Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity-A Review.
Content uniformity (CU) of the active pharmaceutical ingredient is a critical quality attribute of tablets as a dosage form, ensuring reproducible drug potency. Failure to meet the accepted uniformity in the final product may be caused either by suboptimal mixing and insufficient initial blend homogeneity, or may result from further particle segregation during storage, transfer or the compression process itself. This review presents the most relevant powder segregation mechanisms in tablet manufacturing and summarizes the currently available, up-to-date research on segregation and uniformity loss at the various stages of production process-the blend transfer from the bulk container to the tablet press, filling and discharge from the feeding hopper, as well as die filling. Formulation and processing factors affecting the occurrence of segregation and tablets' CU are reviewed and recommendations for minimizing the risk of content uniformity failure in tablets are considered herein, including the perspective of continuous manufacturing.


[Effect of angiotensin1-7 on alpha-smooth muscle actin protein expression in rat hepatic stellate cells].
To investigate the effect of angiotensin II and angiotensin1-7 on alpha-smooth muscle actin (alpha-SMA)-induced Ca(2+)-independent pathways mediated by Rho kinase2 in hepatic stellate cells (HSCs). HSC-T6 cells were treated with 10 micromol/L of AngII, Ang1-7, AngII +Ang1-7, and Ang1-7+A779. RT-PCR was used to detect the expression of Rho kinase2 (Rock2) in Ca(2+)-independent pathways, and alpha-SMA protein expression was detected by Western blotting. The mRNA expression of Rock2 increased significantly in the cells after AngII treatment (P<0.01), but decreased following Ang1-7 treatment. Ang1-7 treatment significantly reduced alpha-SMA level in AngII-induced cells (P<0.01). Ang1-7 can inhibit AngII-induced activation of Rock2 and reduce alpha-SMA expression in HSCs.


Clinical profile of an atypical antipsychotic: risperidone.
Stimulated by Dawkins and colleagues' (1999) and Remington and Kapur's (2000) calls to develop clinical profiles of the new atypical antipsychotic drugs and by Mattes's critiques (1997, 1998), we performed two sets of analyses for risperidone. First, we reanalyzed data from the North American risperidone trial: risperidone was superior to haloperidol to an equal degree in patients with and without the deficit syndrome, in patients with paranoid and nonparanoid schizophrenia, in treatment-resistant and treatment-responsive patients (patients hospitalized for longer and shorter periods), and in patients with or without weight gain. Moreover, risperidone was more effective than haloperidol on symptoms nonresponsive and responsive to haloperidol; its effects on negative symptoms were independent of its effects on extrapyramidal symptoms; and it was effective in treating depression in schizophrenia. Second, we performed a meta-analysis of 18 controlled risperidone trials: risperidone was consistently more effective than conventional antipsychotics in treating positive and negative symptoms.


The father(to)child affiliative bond: convergent evolution with the canid analogue.
Primate homologues, especially from the African great apes, can usually be successfully utilized to form comparisons with the human condition. However, the man(to)child pair-bond is not paralleled by any terrestrial primate nor even many mammals. Hence, knowledge of primate behavior would not be predictive of the pan-human social father. It is suggested that female choices of mating partners shifted in the direction of a canid analogue in that men's motivations to share resources with the female and to exhibit paternalistic behaviors were positively selected. Accordingly, it is argued that, for humans, convergent evolution occurred which trended toward the canid template. Consequently, it would be predicted that, compared to other terrestrial primates, the neuro-hormonal basis for the mother-child affiliative bond would be similar, but the basis for man(to)child affiliative bond would be dissimilar.


Acquired ungual fibrokeratoma: a systematic review of the literature.
Acquired ungual fibrokeratomas (AUFKs) are benign recurrent fibrokeratotic tumors of the nail unit of uncertain etiology. Little is known about the optimal modality to successfully treat these lesions. No systematic review addressing ungual fibrokeratomas has been published to date. The aim of this study is to summarize all the published data regarding diagnostic and therapeutic challenges of AUFKs. On August 9, 2019, a systematic search of Medline and Cochrane databases was conducted. All the studies describing the treatment of ungual fibrokeratomas, procedure description, pathological findings, outcome, and follow-up period were included in this review. After full-text article review, 103 articles were included, representing a total of 78 lesions. The commonly used treatments for fibrokeratomas were complete tumor resection (90.5%), shave excision (8.3%), and cryotherapy (1.2%). Complete surgical excision yielded the highest cure rate among all treatment modalities (90.8%) compared to partial surgical excision (28.6%) and cryotherapy (0%). The mean follow-up period was 12.1 months (1-144). Complete surgical removal preserving the matrix showed the highest cure rates and should be considered as first-line treatment for AUFKs. Future adequately designed randomized control trials are warranted to compare different treatment modalities.


Effect of a Methanol-Acetone Extract of Skim Milk Fermented by Streptococcus thermophilus on Color, Microbial Counts, and pH of Fresh Beef.
Fresh beef steaks were treated with two concentrations of a methanol-acetone (MA) extract ( Streptococcus thermophilus -fermented skim milk) for color stability, pH change, and microbial growth at storage temperatures of 0 and 10°C. Beef color was measured by a color difference meter (Gardner) and a sensory panel. The Gardner "a/b" values for the untreated samples (control) were significantly higher (P<0.05) than values for treated samples (500 and 1000 ppm MA) through 9 d of storage (0°C). At 15 d of storage (0°C) there were no significant differences between treatments (P>0.05). The "a/b" values at 10°C indicated a significant difference (P<0.05) after 3 d of storage between untreated and treated samples. After 6 d of storage (10°C), no significant difference (P<0.05) was found between untreated and treated meat. Sensory panel scores indicated that both untreated and treated samples were of an acceptable quality through 9 d of storage (0°C); however, the untreated samples were of inferior color quality compared to treated (P< 0.05). All samples stored at 10°C deteriorated to an unacceptable color quality between 3 and 6 d. The growth of Pseudomonas fluorescens on beef steaks was significantly higher (P<0.05) in the untreated samples (by 1 to 2 log10 cycles) than the treated (0°C, 15-d storage). The same pattern was observed at 10°C; however, spoilage was apparent after 6 d of storage while spoilage was apparent after 9 d at 0°C. The pH change, between 0 and 3 d of storage, was not significant (P>0.05) at either storage temperature (0°C and 10°C). From 3 through 15 d, the pH increased from 5.3 to 6.1, with no significant difference (P>0.05) between treatments (after 15 d of storage, 0°C). At 10°C, no significant difference (P>0.05) was observed between treatments (after 6-d storage). Results from this experiment indicate that the MA extract may have some practical use in extending the shelf life of fresh beef by reducing factors that are responsible for color deterioration, e.g., microbial activity. However, it seems likely that higher concentrations of the MA extract would be necessary to control microbial activity at higher storage temperatures.


Nursing, nursing education, and anxiety.
One hundred seventy-one graduating students in associate degree, diploma, and baccalaureate nursing programs completed a questionnaire concerning various state and trait measures of emotions (including general anxiety, apprehension about communication, and anxiety about one's future nursing career). Differences among the three groups of nursing students on the various dimensions of emotions, anxiety, and communication apprehension were assessed from the perspective of Mehrabian's theory of emotion. Predictors of anxiety about one's nursing career were investigated for the overall sample and for the three groups separately. Findings indicate that baccalaureate students are least apprehensive about communicating and feel most dominant in their setting. In addition, associate degree students were most anxious about nursing if they did not feel dominant, diploma students were most anxious if they did not feel dominant or were apprehensive about communication, and baccalaureate students were most anxious if they were generally unhappy. The results are discussed in terms of Mehrabian's emotion theory, the current crisis in and future direction of nursing education, and the use of theory in designing a strategy for nursing as a profession.


Landscape character and fish assemblage structure and function in western Lake Superior streams: general relationships and identification of thresholds.
As part of a comparative watershed project investigating land-cover/land-use disturbance gradients for streams in the western Lake Superior Basin, we examined general relationships between landscape character and fish assemblage structure and function. We also examined the shape of those relationships to identify discontinuity thresholds where small changes in landscape character were associated with marked shifts in the fish assemblages. After completing a geographic analysis of second- and third-order watersheds in the western Lake Superior drainage, we randomly selected 48 streams along mature forest and watershed storage gradients in 2 hydrogeomorphic regions as our study sites. During the summers of 1997 and 1998, we used electrofishing to sample fish assemblages from each stream. Each of the landscape factors was significantly associated with fish assemblage structure and function based on analysis of covariance. Watershed storage was related to the greatest number of fish assemblage characteristics, but hydrogeopmorphic region and mature forest cover were strongly associated as well. The hydrogeomorphic region also mediated relationships between watershed character and fish assemblages. Discontinuity thresholds for our fish assemblages averaged 11% for watershed storage and 50% for watershed mature forest cover based on piecewise regression analysis. Although many of the landscape-fish relationships might have been manifest through effects on in-stream habitat, our results highlight the importance of management and land-use planning decisions at the watershed and landscape scales.


Simultaneous sensing of cysteine/homocysteine and glutathione with a fluorescent probe based on a single atom replacement strategy.
In recent years, there have been many reports of fluorescent probes for multi-channel detection of Cys, Hcy and GSH. Particularly, reports of fluorescent probes using NBD (7-nitro-1,2,3-benzoxadiazole) or SNBD (7-nitro-1,2,3-benzothiadiazole) moieties as fluorophores are particularly common. Unfortunately, their 4-sulfhydryl derivatives exhibited negligible fluorescence, which makes them incapable of detecting GSH directly. Herein, by performing single selenium-for-oxygen atom replacement within 4-chloro-substituted NBD (NBD-Cl), we developed a small molecule fluorescent probe based on a single atom replacement strategy, which enables the probe to be used for simultaneously distinguishing Cys/Hcy and GSH, along with fluorescence imaging of Cys/Hcy and GSH in live cells from red and green emission channels, respectively.