Decreased Systemic and Airway Sirtuin 1 Expression in Adults With Bronchiectasis.
Aim: Whether accelerated aging, reflected by sirtuin 1 (SIRT1) expression, is implicated in bronchiectasis remains largely unknown. We sought to determine the patterns of SIRT1 and other aging markers in systemic circulation and airways and their expression levels associated with bronchiectasis severity and exacerbation. Methods: We enrolled 132 patients with bronchiectasis and 50 healthy subjects in a prospective cohort study to profile aging markers in systemic circulation and recruited 36 patients with bronchiectasis and 32 disease controls (idiopathic pulmonary fibrosis or tumors) in a cross-sectional study to profile aging markers in bronchial epithelium of both large-to-medium and small airways. We profiled aging marker expression from peripheral blood mononuclear cells and enumerated the positively stained cells for detection of aging marker expression in bronchial epithelium. Results: Compared with healthy controls, the relative telomere length (median: 0.88 vs. 0.99, p = 0.009), SIRT1 (median: 0.89 vs. 0.99, p = 0.002), and Ku80 (median: 0.87 vs. 0.96, p < 0.001) expression levels were consistently lower in the peripheral blood mononuclear cells among patients with bronchiectasis and modestly discriminated patients with bronchiectasis from healthy controls. No remarkable changes in SIRT1, telomere length, or Ku70 were identified at onset of exacerbation. Within the bronchial epithelium, the percentage of positively stained cells was lower for SIRT1 (median: 25.1 vs. 57.2%, p < 0.05) and numerically lower for p16 (median: 40.0 vs. 45.1%) and p21 (median: 28.9 vs. 35.9%) in patients with bronchiectasis than in disease controls (p > 0.05). Conclusion: SIRT1 was downregulated in systemic circulation and bronchiectatic airways, which was independent of disease severity and lung function impairment.


Complete Genome Sequence of Citrobacter Phage CVT22 Isolated from the Gut of the Formosan Subterranean Termite, Coptotermes formosanus Shiraki.
The complete genome of bacteriophage CVT22 infecting Citrobacter sp. strain TM1552 is reported here. Both the bacteriophage and Citrobacter sp. TM1552 were isolated from the gut of the Formosan subterranean termite, Coptotermes formosanus. This is the first report of a genome sequence of a bacteriophage isolated from the termite gut.


[Treating a hypertensive emergency].
A hypertensive crisis is characterized by a massive blood pressure increase of sudden onset, with systolic pressures in excess of 220 mmHg or diastolic pressures of more than 120 mmHg usually being found in patients with underlying hypertensive disease. Of decisive importance for the severity of the patient's presenting state, however, is not the absolute level of the blood pressure, but rather the extent of the acute blood pressure increase. Of decisive importance for the therapeutic approach to the acute case is whether the hypertensive crisis is accompanied by organic manifestations (hypertensive emergency) or is unaccompanied by this life-threatening clinical presentation (hypertensive urgency). The former patients must always be hospitalized, and the preferential treatment is parenteral medication, which is associated with a more rapid and calculable onset of action than can be achieved via the oral or sublingual route.


Reduced trabecular meshwork height in juvenile primary open-angle glaucoma.
To compare trabecular meshwork height in a series of patients with juvenile primary open-angle glaucoma (JPOAG) with that in normal control patients. Ultrasound biomicroscopy and A-scan biometry were performed on 16 eyes with JPOAG and 24 normal eyes. A radial, perpendicular image in the horizontal temporal meridian detailing the line of Schwalbe, scleral spur, and angle anatomy was obtained for each eye by a single examiner. Trabecular meshwork height was defined as the distance from the scleral spur to the Schwalbe line. Mean patient age (P = .85, t test), refractive error (P = .68), sex distribution (P = .26, Fisher exact test) and axial length (P = .39) were similar between the groups. Mean +/- SE trabecular meshwork heights were 0.36 +/- 0.03 mm (range, 0.19-0.53 mm) for JPOAG and 0.58 +/- 0.02 mm (range, 0.40-0.80 mm) for controls (P < .001). Eyes with greater axial length tended to have larger trabecular meshworks in both groups (P = .012, multivariate regression). A trabecular meshwork height-axial length ratio of 0.021 or less was associated with a significantly increased risk for JPOAG being present (odds ratio, 57; 95% confidence interval, 6.0-541). The trabecular meshwork is smaller in eyes with JPOAG compared with that in normal eyes. This finding suggests a structural abnormality that may underlie the reduced outflow.


Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells.
Hierridin B was isolated from a marine cyanobacterium Cyanobium sp. strain and induced cytotoxicity selectively in HT-29 adenocarcinoma cells. The underlying molecular mechanism was not yet elucidated. HT-29 cells were exposed to the IC50 concentration of hierridin B (100.2 μM) for 48 h. Non-targeted proteomics was performed using 2D gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The mRNA expression of apoptotic and cell cycle genes were analyzed by real-time PCR. Automated quantification of 160 cytoplasm and mitochondrial parameter was done by fluorescence microscopy using CellProfiler software. Proteomics identified 21 significant different proteins, which belonged to protein folding/synthesis and cell structure amongst others. Increase of VDAC1 protein responsible for formation of mitochondrial channels was confirmed by mRNA expression. A 10-fold decrease of cytoskeleton proteins (STMN1, TBCA) provided a link to alterations of the cell cycle. CCNB1 and CCNE mRNA were decreased two-fold, and P21CIP increased 10-fold, indicative of cell cycle arrest. Morphological analysis of mitochondrial parameter confirmed a reduced mitochondrial activity. Hierridin B is a potential anticancer compound that targets mitochondrial activity and function.


Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?
A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.


Smaug/SAMD4A restores translational activity of CUGBP1 and suppresses CUG-induced myopathy.
We report the identification and characterization of a previously unknown suppressor of myopathy caused by expansion of CUG repeats, the mutation that triggers Myotonic Dystrophy Type 1 (DM1). We screened a collection of genes encoding RNA-binding proteins as candidates to modify DM1 pathogenesis using a well established Drosophila model of the disease. The screen revealed smaug as a powerful modulator of CUG-induced toxicity. Increasing smaug levels prevents muscle wasting and restores muscle function, while reducing its function exacerbates CUG-induced phenotypes. Using human myoblasts, we show physical interactions between human Smaug (SMAUG1/SMAD4A) and CUGBP1. Increased levels of SMAUG1 correct the abnormally high nuclear accumulation of CUGBP1 in myoblasts from DM1 patients. In addition, augmenting SMAUG1 levels leads to a reduction of inactive CUGBP1-eIF2α translational complexes and to a correction of translation of MRG15, a downstream target of CUGBP1. Therefore, Smaug suppresses CUG-mediated muscle wasting at least in part via restoration of translational activity of CUGBP1.


Magnetically Controllable Flowerlike, Polyhedral Ag-Cu-Co3O4 for Surface-Enhanced Raman Scattering.
Syntheses of Cu-, Ag-, and Ag-Cu-Co3O4 nanomaterials are of interest for a wide range of applications including electrochemistry, thermal catalysis, energy storage, and electronics. However, Co3O4-based nanomaterials have not been explored for surface-enhanced Raman scattering (SERS). Here, we present Cu-, Ag-, and Ag-Cu-Co3O4 nanomaterials of a hierarchical flower shape comprising two separate phases: a pure Cu or Ag core and multiple Co3O4 branches, in which the optical properties of the core and the magnetic properties of the branches are integrated. In addition, a series of nonmagnetic Cu-dominant Cu-Co-O polyhedra without Co3O4 branches were derived from Cu-Co3O4. The polyhedron morphology can be controlled and transformed among cubes, cuboctahedra, and truncated octahedra by tuning the amounts of ligands and additives to vary the potential energy and growth rate of specific crystal facets. The flowerlike Cu-, Ag-, and Ag-Cu-Co3O4 were characterized for SERS enhancement, showing that Ag-Cu-Co3O4 does not enhance SERS from 4-mercaptobenzoic acid (4-MBA) but dramatically and selectively does so for adsorbed rhodamine 6G. Obviously, the synergy of Ag and Cu within the Co3O4 flower constraint promotes the SERS activity. This type of spinel with not only excellent SERS activity but also ferromagnetism could be of great potential in tandem SERS detection/magnetic separation and related applications.


The efficacy of melatonin against radiotoxicity of iodine-131 and its response to treatment in hyperthyroid patients: a randomized controlled trial.
Since melatonin is a non-toxic compound with proven radioprotective effects, we aimed to investigate its efficacy in an in-vivo setting in hyperthyroid patients who are treated with iodine-131. This double-blind placebo-controlled study was conducted on hyperthyroid patients referred to nuclear medicine centers in Babol, Iran. We excluded patients suffering from hypertension treated with warfarin, autoimmune diseases, genetic diseases, cancers, smokers, chemical wounded, radiology and radiotherapy workers, and those who were treated with chemotherapy agents. Patients were randomly assigned to receive a capsule containing 300 mg of melatonin powder or a placebo. Just before receiving iodine-131, blood samples were taken from individuals. All 52 female patients received 10 to 20 mCi iodine-131 for treating hyperthyroidism. A second blood sample was taken one hour after the administration of iodine-131. To determine the chromosomal damages before and after receiving radioiodine, we performed the cytokinesis- block micronucleus assay. Also, at phase 2, 6 months follow-up was performed, in which patients' positive responses to treatment were compared. The findings of this study indicate that the difference in micronucleus formation between the placebo and melatonin groups is not significant. However, a significant difference in the 6 months follow-up revealed that 61.5% and 85.7% of patients had a positive response to treatment in the placebo and melatonin groups, respectively. As one of the first studies dealing with the human in-vivo assessment on the radioprotective effects of melatonin, it was concluded that melatonin has a non-significant positive impact on reducing the rate of chromosomal damages in hyperthyroid patients treated with iodine-131. Nevertheless, the outcome of treatment was significantly higher by melatonin compared to the placebo group.


Eruption anomalies of the maxillary permanent cuspids in children with cleft lip and/or palate.
Eruption anomalies of the maxillary permanent cuspid on the cleft side was analyzed in a sample of 77 children with mono- and bi-lateral cleft lip/palate. The main findings were: 1) The permanent cuspid showed an initial mesial position in relation to the root of its primary predecessor in a relatively high number of cases. Nearly all those cuspids that showed an anomalous position (mesial or distal) in relation to the corresponding primary teeth at the time of the first observation erupted in malposition (palatally in the cleft area, mesially or distally to the primary cuspids). 2) In most cases presenting a mesially positioned permanent cuspid at the time of first observation, the permanent later incisor was congenitally missing, microdontic or in a mesial position in relation to the cleft. 3) Distally positioned permanent cuspids were always associated with a supernumerary lateral incisor. 4) A congenitally missing lateral incisor could represent a predisposing factor to a mesial position of the permanent cuspid. An early radiographic evaluation of the position of the permanent cuspid was suggested especially in those children presenting a congenitally missing lateral incisor.


The effect of omega-3 unsaturated fatty acids on non-alcoholic fatty liver disease: A systematic review and meta-analysis of RCTs.
During the treatment of diseases such as angiocardiopathy, blood lipid abnormalities and metabolic syndrome, omega-3 unsaturated fatty acids (PUFA) can reduce plasma lipids and improve cardiovascular status, thus ameliorating disease severity. We aimed to explore the effects of PUFA supplementation in patients with non-alcoholic fatty liver disease (NAFLD). A systematic literature search was performed during March 2016 for randomized controlled trials using PUFA or fish oil supplementation in patients with NAFLD or non-alcoholic steatohepatitis (NASH). All Randomized controlled trials were retrieved from MEDLINE and EMBASE database up to date (March 2016). A meta-analysis of key outcomes (serum level of liver enzymes and lipids) were identified in these studies. The mean difference (MD) and the corresponding 95% confidence intervals (CIs) were used as measures of effect size. Thirteen studies were included, consisting of 266 patients in the PUFA group and 402 cases in the control group. Serum level of alanine aminotransferase (ALT) was lower in the PUFA group than that in in the controls [MD=-9.18, 95% CI (-12.41, -5.96), P <0.00001]. However, PUFA treatment did not affect aspartate aminotransferase (AST) [MD=-5.07, 95% CI (-12.65, 2.51), P= 0.19], gamma-glutamyl transferase (GGT) [MD=-1.91, 95% CI (-4.15, 0.33), P <0.009]. PUFA supplementation may affects serum level of ALT and improve liver function in patients with NAFLD.


Arabidopsis Col/Ler and Ws/Ler hybrids and Hybrid Mimics produce seed yield heterosis through increased height, inflorescence branch and silique number.
The seed yield increase of the hybrids and their derived Mimics compared to parents is associated with increased plant height and inflorescence branch number which are correlated with decreased expression of FT, SOC1 and FUL. In Arabidopsis, plant size has been extensively investigated, but few studies have been carried out on seed yield heterosis. In hybrids between Columbia (Col) and Landsberg erecta (Ler), and Wassilewskija (Ws) and Ler, there was significant seed yield heterosis. F6/F7 Hybrid Mimics derived from hybrids of each of the two systems had seed yield increases similar to that of the F1 hybrid (approximately 50-70% greater than the average of the parents). Increased seed yield of the Hybrid Mimics was accompanied by changes of plant architecture with increased plant height and increased inflorescence branch number relative to the parents. Three of the Hybrid Mimic lines derived from the Ws/Ler system had 20% increase in seed yield relative to the F1 hybrid. Genes which repress flowering were up-regulated and the expression levels of flowering -promoting genes including FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) and FRUITFULL (FUL) were negatively correlated with the increase in seed yield in both hybrids and F7 Mimics of both systems.


Azole-resistant Aspergillus fumigatus in Denmark: a laboratory-based study on resistance mechanisms and genotypes.
Azole-resistant Aspergillus fumigatus originating from the environment as well as induced during therapy are continuously emerging in Danish clinical settings. We performed a laboratory-based retrospective study (2010-2014) of azole resistance and genetic relationship of A. fumigatus at the national mycology reference laboratory of Denmark. A total of 1162 clinical and 133 environmental A. fumigatus isolates were identified by morphology, thermotolerance and/or β-tubulin sequencing. Screening for azole resistance was carried out using azole agar, and resistant isolates were susceptibility tested by the EUCAST (European Committee on Antimicrobial Susceptibility Testing) E.Def 9.2 reference method and CYP51A sequenced. Genotyping was performed for outbreak investigation and, when appropriate, short tandem repeat Aspergillus fumigatus microsatellite assay. All 133 environmental A. fumigatus isolates were azole susceptible. However, from 2010 to 2014, there was an increasing prevalence of azole resistance (from 1.4 to 6% isolates (p <0.001) and 1.8 to 4% patients (p <0.05)) among the clinical isolates, with the well-known environmental CYP51A variant TR34/L98H responsible for >50% of the azole resistance mechanisms. Among 184 Danish A. fumigatus isolates, 120 unique genotypes were identified and compared to a collection of 1822 international genotypes. Seven (5.8%) Danish genotypes were shared between isolates within Denmark but with different origin, 19 (15.8%) were shared with foreign genotypes, and two (11.8%) of 17 genotypes of isolates carrying the TR34/L98H resistance mechanisms were identical to two Dutch TR34/L98H isolates. Our findings underlines the demand for correct identification and susceptibility testing of clinical mould isolates. Furthermore, although complex, genotyping supported the hypotheses regarding clonal expansion and the potential of a single origin for the TR34/L98H clone.


Finasteride in the treatment of Taiwanese men with androgenetic alopecia: a 12-month open-label study.
Finasteride 1 mg/day is effective in the treatment of androgenetic alopecia (AGA). Our open-label study assessed the efficacy and safety of finasteride for the treatment of Taiwanese men with AGA. We enrolled 34 Taiwanese men (aged 18-40 yr) with AGA of modified Norwood/Hamilton scale (MNHS) grade II-V. In investigator assessments at 12 months, five of 21 subjects (23.8%) had two-grade improvement in MNHS grade and 12 of 21 subjects (57.1%) had one-grade improvement; the others remained at the same grade. In global photographic evaluation, five of 31 subjects (15.1%) had observable hair growth at 6 months and 11 of 21 subjects (52.4%) had observable hair growth at 12 months. Patient self-assessment of hair growth was favorable across all questions in the treatment course, more significantly at 12 months than at 6 months; nine of 21 subjects (42.9%) were satisfied with their overall appearance at 12 months. Serum prostate specific antigen levels had decreased by 23.4% at 12 months. Adverse effects, including abnormal liver function (5/34), were minimal, and the causal relationship with finasteride could not be established. Thus, in Taiwanese men with AGA, finasteride 1 mg/day for 1 year slowed the progression of hair loss and increased hair growth.


Novel mesoporous solid superacidic catalysts: activity and selectivity in the synthesis of thymol by isopropylation of m-cresol with 2-propanol over UDCaT-4, -5, and -6.
The alkylation of m-cresol with isopropyl alcohol in the presence of novel superacidic catalysts named as UDCaT-4, UDCaT-5, and UDCaT-6 was investigated. The catalysts are modified versions of zirconia showing high catalytic activity, stability, and reusability in the presence of water as compared to conventional sulfated zirconia. The objective of the present investigation was to explore the potential of these catalysts in this alkylation of m-cresol with isopropyl alcohol to thymol, which has widescale applications. The reactions were conducted in liquid phase in the temperature range of 433-473 K. Both, O- and C-alkylated products were obtained at lower temperatures, while at higher temperatures, thymol was the main product of the reaction. The catalytic activity increases in the order UDCaT-5 > UDCaT-6 >UDCaT-4 > sulfated zirconia. Thymol could be efficiently obtained with selectivity reaching up to 79% at an isopropyl alcohol conversion of 92% with UDCaT-5. This process can be a replacement for the existing process based on zeolites where high temperature and pressure are required. Synergistic effects of very high sulfur content present (9% S) and preservation of the tetragonal phase in UDCaT-5, in comparison with sulfated zirconia (4% S), were responsible for higher catalytic activity. A systematic investigation of the effects of various operating parameters was accomplished, and a mathematical model is developed to describe the reaction pathway and validated with experimental results. The reaction was carried out without using solvent, and the process subscribes to the principles of green chemistry.


Apparatus for the measurement of small absorption change kinetics at 820 nm in the nanosecond range after a ruby laser flash.
An apparatus for the measurement of kinetics of small absorption changes (DeltaA approximately 10(-3)-10(-4)) at 820 nm in a biological sample in the nanosecond range after a short high-intensity ruby laser flash (200 mJ, 8 ns) is described. The laser-induced fluorescence artefact is greatly reduced by the use of a solid-state laser diode as source of measuring light, in combination with a microscope lens and a diaphragm. The signal-to-noise ratio is enhanced by the use of an avalanche photodetector connected to a laboratory-made low-noise and interference-free amplifier. The signals are processed by a transient digitizer in combination with a signal averager. The response time of the apparatus is about 20 ns. With some modifications the apparatus can be used to measure absorption changes in a broad spectral range.


[The value of bispectral index in the unconscious patients with acute brain injury due to different pathogenic factors].
To observe the differences in bispectral index (BIS) in unconscious patients with acute brain injury due to different pathogenic factors, and approach its clinical significance. A retrospective study was conducted. One hundred and twenty-two unconscious patients with acute brain injured admitted to the intensive care unit (ICU) from March 2009 to August 2012 were involved. According to the pathogenic factors, all patients were divided into direct injury group (n=66) and indirect injury group (n=56). Based on BIS value, all patients were divided into the BIS<60 group (n=80) and the BIS≥60 group (n=42). The BIS was continuously measured for 12 hours during the first 3 days, or 24 hours after stoppage of sedative after admission to ICU. The mean value of BIS (BISmean) was evaluated. The acute physiology and chronic health evaluationII (APACHEII) score, probability of survival (PS) and Glasgow coma score (GCS) were recorded. On the same day, the serum protein S100 and neuron-specific enolase (NSE) were determined. The mortality and the rate of the poor neurological outcome were analyzed. (1) There were no significant differences in the age, sex, APACHEII score, PS and days of stay in ICU between the direct and indirect injury groups. (2) BISmean and GCS in direct injury group were significantly lower than those of the indirect injury group [BISmean: 39.0 (2.5, 58.0) vs. 59.0 (42.0, 71.0), GCS score: 3 (3, 5) vs. 4 (3, 6), both P<0.01], while serum S100 levels was significantly higher [2.30 (0.75, 6.66) mg/L vs. 0.84 (0.40, 3.62) mg/L, P<0.01]. There was no significant difference in the NSE level between the direct and indirect injury groups. (3) The mortality rate and poor neurological outcome rate in BIS<60 group were significantly higher than the BIS≥60 group (mortality rate: 67.50% vs. 40.48%, poor neurological outcome rate: 86.25% vs. 66.67%, P<0.01 and P<0.05). In the BIS<60 group, there were no significant differences in the mortality and poor neurological outcome rate between direct and indirect injury group. There are differences in pathogenic factors, the injury mechanism, and the degree of the brain injury between the direct and indirect injury groups. BIS monitoring could help judge the degree of different kinds of brain injury. BIS<60 indicates poor prognosis and neurological outcome in spite of the inducing factor of brain injury.


Transbilayer motion of spin-labelled phospholipids in the plasma membrane of epididymal and ejaculated ram spermatozoa.
The transbilayer movement and distribution of spin-labelled phospholipid analogues were studied in the plasma membrane of ram sperm cells isolated from functionally different regions of the epididymis (caput, cauda) and from the ejaculate. As already shown for ejaculated cells, (i) a rapid movement of aminophospholipid analogues phosphatidylserine and phosphatidylethanolamine from the exoplasmic to the cytoplasmic leaflet, and (ii) a slow transbilayer movement of phosphatidylcholine were observed in the plasma membrane of maturating ram sperm cells. This suggests an asymmetric steady state transbilayer distribution of phospholipids, with a preferential enrichment of aminophospholipids on the cytoplasmic leaflet of those cells. The fast inward redistribution of the aminophospholipid analogues is consistent with the presence of an aminophospholipid translocase activity in all three sperm cell preparations. The translocase activity was enhanced slightly during the epididymal transit of spermatozoa. However, compared with epididymal sperm cells, a marked increase in the aminophospholipid translocase activity and a more pronounced phospholipid asymmetry for phosphatidylethanolamine was established for ejaculated spermatozoa. The physiological relevance of the rapid removal of aminophospholipids from the exoplasmic leaflet of the plasma membrane of ram sperm cells is discussed. The quality of sperm cell fractions was characterized by the cell morphology, membrane integrity and the cellular ATP concentration.


The Loss of Nuclear PTEN Increases Tumorigenesis in a Preclinical Mouse Model for Hepatocellular Carcinoma.
The PTEN gene is highly mutated in many cancers, including hepatocellular carcinoma. The PTEN protein is located at different subcellular regions-PTEN at the plasma membrane suppresses PI3-kinase signaling in cell growth, whereas PTEN in the nucleus maintains genome integrity. Here, using nuclear PTEN-deficient mice, we analyzed the role of PTEN in the nucleus in hepatocellular carcinoma that is induced by carcinogen and oxidative stress-producing hepatotoxin. Upon oxidative stress, PTEN was accumulated in the nucleus of the liver, and this accumulation promoted repair of DNA damage in wild-type mice. In contrast, nuclear PTEN-deficient mice had increased DNA damage and accelerated hepatocellular carcinoma formation. Both basal and oxidative stress-induced localization of PTEN in the nucleus require ubiquitination of lysine 13 in PTEN. Taken together, these data suggest the critical role of nuclear PTEN in the protection from DNA damage and tumorigenesis in vivo.


[Endoscopic therapy of biliary obstruction].
Obstructive jaundice is consequence of several diseases of biliary ducts which cause biliary stasis. Constant finding is jaundice on skin and visible mucosal areas, acholic stool and dark urine. Obstruction could be permanent or intermittent. It could have rapid course with severe symptoms: biliary colics, signs of acute biliary ducts inflammation, acute pancreatitis or with atypical upper abdominal disorders. Asymptomatic biliary obstruction implies malignant disease. After initial clinical evaluation (history of disease, physical examination, biochemical analyses, ultrasound orientation) treatment of choice in diagnostic and management of biliary obstruction is endoscopic retrograde cholangiopancreatography (ERCP) proceeded with endoscopic sphincterotomy of sphincter Oddi. Further procedures depend on cause of obstruction.


Chronic plantar heel pain: treatment with a short leg walking cast.
The efficacy of a short leg walking cast in the treatment of chronic plantar heel pain was assessed for 32 patients with 37 involved extremities treated over a 2-year period. All patients had failed numerous other treatment modalities and had been symptomatic for an average of 1 year. Long-term follow-up for 24 patients with 28 involved extremities revealed complete resolution of pain for 7 extremities (25%), improvement for 17 (61%), and no improvement for 4 (14%). Ten (42%) patients were completely satisfied with cast treatment, 3 (12%) were satisfied with reservations, and 11 (46%) were dissatisfied. Casting appears to be a reasonable option for patients with recalcitrant heel pain and should be offered before surgical intervention.


Hemoperfusion study with carbamazepine in vitro.
Sorption efficacy of active charcoal, Amberlite XAD-2 and Amberlite XAD-4 in hemoperfusion with carbamazepine was investigated in vitro. Authors carried out 15 hemoperfusions with carbamazepine in a closed system using the above mentioned sorbents; The perfusion solution used was 3,000 ml of 0.9% NaCl. The carbamazepine concentration in the solution was 52.5+/-3.0 mg/L. In addition, two in vitro hemoperfusions with carbamazepine using Amberlite XAD-2 sorbent and 1.500 ml of human plasma as a perfusion solution, were also performed. The concentration of carbamazepine in plasma was 50.4+/-1.2 mg/L. Individual hemoperfusions lasted 5 hours. Zero values of carbamazepine were achieved after 120 min of Amberlite XAD-2 or Amberlite XAD-4 hemoperfusion in 0.9% NaCl and after 240 min of hemoperfusion in human plasma. The results gathered suggest that the most effective in vitro hemoperfusion with carbamazepine was obtained with Amberlite XAD-2 or Amberlite XAD-4 and the least effective was with active charcoal. The authors recommend the use of hemoperfusion with Amberlite XAD-2 or Amberlite XAD-4 for acute intoxications with carbamazepine in humans. In addition, authors successfully performed 5-hour hemoperfusion using Amberlite XAD-4 in vivo, in an 18-year-old girl, who suffered from acute carbamazepine intoxication after a suicidal attempt. This treatment led to the rapid survival.


An innovative online VFA monitoring system for the anerobic process, based on headspace gas chromatography.
A new method for online measurement of volatile fatty acids (VFA) in anerobic digesters has been developed based on headspace gas chromatography (HSGC). The method applies ex situ VFA stripping with variable headspace volume and gas analysis by gas chromatography-flame ionization detection (GC-FID). In each extraction, digester sample was acidified with H(3)PO(4) and NaHSO(4), then heated to strip the VFA into the gas phase. The gas was sampled in a low friction glass syringe before injected into the GC for measurement. The system has been tested for online monitoring of a lab-scale CSTR reactor treating manure for more than 6 months and has shown good agreement with off-line analysis. The system is capable of measuring individual VFA components. This is of advantage since specific VFA components such as propionic and butyric acid can give extra information about the process status. Another important advantage of this sensor is that there is no filtration, which makes possible application in high solids environments. The system can thus be easily applied in a full-scale biogas reactor by connecting the system to the liquid circulation loop to obtain fresh sample from the reactor. Local calibration is needed but automatic calibration is also possible using standard addition method. Sampling duration is 25-40 min, depending on the washing duration, and sensor response is 10 min. This is appropriate for full-scale reactors, since dynamics within most biogas reactors are of the order of several hours.


Beta-amyloid therapies in Alzheimer's disease.
Neurones in the brain produce beta-amyloid fragments from a larger precursor molecule termed the amyloid precursor protein (APP). When released from the cell, these protein fragments may accumulate in extracellular amyloid plaques and consequently hasten the onset and progression of Alzheimer's disease (AD). A beta fragments are generated through the action of specific proteases within the cell. Two of these enzymes, beta- and gamma-secretase, are particularly important in the formation of A beta as they cleave within the APP protein to give rise to the N-terminal and C-terminal ends of the A beta fragment, respectively. Consequently, many researchers are investigating therapeutic approaches that inhibit either beta- or gamma-secretase activity, with the ultimate goal of limiting A beta; production. An alternative AD therapeutic approach that is being investigated is to employ anti-A beta antibodies to dissolve plaques that have already formed. Both of these approaches focus on the possibility that accrual of A beta leads to neuronal degeneration and cognitive impairment characterised by AD and test the hypothesis that limiting A beta deposition in neuritic plaques may be an effective treatment for AD.


Cervico-endometrial cytology and physiological aspects of the post-partum mare.
After parturition, Thoroughbred mares were mated at the first post-partum oestrus (N = 24) or at a subsequent oestrus (N = 12). All mares were examined daily for: oestrous detection, palpation per rectum of the genital tract, vaginoscopic examination and cervico-endometrial cytology. Pregnancy diagnosis was carried out at Days 18, 35 and 45 after mating. An identical first service conception rate of 50% was found in both groups. The number of neutrophils followed a descending profile to only scattered cells at the first post-partum oestrus and in Group II mares remained at this very low level during the period of study. The percentage of histiocytes and eosinophils increased on Days 10 and 17, and 5 and 6 post partum, respectively. The percentage of lymphocytes remained low and constant during the period of study. Bacterial flora decreased from Days 2 to 9 and increased from Days 13 to 17 post partum. Cellular necrosis and erythrocytes decreased and ciliocytopholia increased as mares approached the first post-partum oestrus. A positive correlation was found between amount, colour, viscosity and turbidity of secretions and all cellular types, ciliocytopholia, cellular necrosis and bacterial flora. The number of neutrophils was positively correlated with the percentage of eosinophils, bacterial flora and cellular necrosis but had a negative association with the presence of ciliocytopholia. Two mares that did not re-establish cyclic ovarian activity after parturition had delayed uterine involution. Mares not conceiving at the first post-partum oestrus exhibited a more prolonged presence of cellular necrosis and erythrocytes and an increased presence of bacterial flora and lymphocytes as compared to mares conceiving at this period.


Finding the missing link: disulfide-containing proteins via a high-throughput proteomics approach.
Top-down proteomics have recently started to gain attention as a novel method to provide insight into the structure of proteins in their native state, specifically the number and location of disulfide bridges. However, previous techniques still relied on complex and time-consuming protein purification and reduction reactions to yield useful information. In this issue of Proteomics, Zhao et al. (high-throughput screening of disulfide-containing proteins in a complex mixture, Proteomics 2013, 13, 3256-3260) devise a clever and rapid method for high-throughput determination of disulfides in proteins via reduction by tris(2-carboxyethyl)phosphine. Their work provides the foundation necessary to undertake more complex experiments in biological samples.


2021 KSCCM clinical practice guidelines for pain, agitation, delirium, immobility, and sleep disturbance in the intensive care unit.
We revised and expanded the "2010 Guideline for the Use of Sedatives and Analgesics in the Adult Intensive Care Unit (ICU)." We revised the 2010 Guideline based mainly on the 2018 "Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) in Adult Patients in the ICU," which was an updated 2013 pain, agitation, and delirium guideline with the inclusion of two additional topics (rehabilitation/mobility and sleep). Since it was not possible to hold face-to-face meetings of panels due to the coronavirus disease 2019 (COVID-19) pandemic, all discussions took place via virtual conference platforms and e-mail with the participation of all panelists. All authors drafted the recommendations, and all panelists discussed and revised the recommendations several times. The quality of evidence for each recommendation was classified as high (level A), moderate (level B), or low/very low (level C), and all panelists voted on the quality level of each recommendation. The participating panelists had no conflicts of interest on related topics. The development of this guideline was independent of any industry funding. The Pain, Agitation/Sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep Disturbance panels issued 42 recommendations (level A, 6; level B, 18; and level C, 18). The 2021 clinical practice guideline provides up-to-date information on how to prevent and manage pain, agitation/sedation, delirium, immobility, and sleep disturbance in adult ICU patients. We believe that these guidelines can provide an integrated method for clinicians to manage PADIS in adult ICU patients.


Xefiltin, a Xenopus laevis neuronal intermediate filament protein, is expressed in actively growing optic axons during development and regeneration.
Neurofilaments are an important structural component of the axonal cytoskeleton and are made of neuronal intermediate filament (nIF) proteins. During axonal development, neurofilaments undergo progressive changes in molecular composition. In mammals, for example, highly phosphorylated forms of the middle- and high-molecular-weight neurofilament proteins (NF-M and NF-H, respectively) are characteristic of mature axons, whereas nIF proteins such as alpha-internexin are typical of young axons. Such changes have been proposed to help growing axons accommodate varying demands for plasticity and stability by modulating the structure of the axonal cytoskeleton. Xefiltin is a recently discovered nIF protein of the frog Xenopus laevis, whose nervous system has a large capacity for regeneration and plasticity. By amino acid identity, xefiltin is closely related to two other nIF proteins, alpha-internexin and gefiltin. alpha-Internexin is found principally in embryonic axons of the mammalian brain, and gefiltin is expressed primarily in goldfish retinal ganglion cells and has been associated with the ability of the goldfish optic nerve to regenerate. Like gefiltin in goldfish, xefiltin in Xenopus is the most abundantly expressed nIF protein of mature retinal ganglion cells. In the present study, we used immunocytochemistry to study the distribution of xefiltin during optic nerve development and regeneration. During development, xefiltin was found in optic axons at stage 35/36, before they reach the tectum at stage 37/38. Similarly, after an orbital crush injury, xefiltin first reemerged in optic axons after the front of regeneration reached the optic chiasm, but before it reached the tectum. Thus, during both development and regeneration, xefiltin was present within actively growing optic axons. In addition, aberrantly projecting retinoretinal axons expressed less xefiltin than those entering the optic tract, suggesting that xefiltin expression is influenced by interactions between regenerating axons and cells encountered along the visual pathway. These results support the idea that changes in xefiltin expression, along with those of other nIF proteins, modulate the structure and stability of actively growing optic axons and that this stability is under the control of the pathway which growing axons follow.


Transitioning Multidisciplinary Craniofacial Care to Telehealth during the COVID-19 Pandemic: A Single Center Experience.
Craniofacial clinics are composed of multidisciplinary teams of providers to deliver coordinated and comprehensive patient care. The coronavirus disease of 2019 (COVID-19) pandemic has disrupted this model, as social distancing guidelines have precluded in-person patient appointments and forced clinics to reconsider their method of care delivery. The University of California, San Francisco, Craniofacial Center has continued to serve patients during this acute period, adopting a hybrid model in which the vast majority of patients are seen through telehealth and a limited number of patients are evaluated in-person. Surveyed patients and families reported high rates of satisfaction, with time savings cited as a particular benefit. Furthermore, most felt comfortable using the video technology required for their appointment. This experience has demonstrated to us that multidisciplinary craniofacial evaluations can be effectively delivered in a telehealth format and has informed our conception of idealized clinic structure. Moving forward, we intend to utilize telehealth visits for selected components of craniofacial evaluations in an effort to maximize efficiency and minimize burden, including addressing barriers to accessing care. Benefits of a hybrid model will include decongestion of clinics and waiting areas, allowing social distancing, addressing clinic space limits, and increased efficiency by eliminating the need for patient and family movement. Demonstration of the safety and efficacy of telehealth visits, combined with regulatory reform that improves reimbursement and allows for appointments across state lines, will be critical for this model to persist beyond the pandemic.


Evaluation on the Performance of Hydraulic Bitumen Binders under High and Low Temperatures for Pumped Storage Power Station Projects.
The high and low-temperature performance of five hydraulic bitumen binders was evaluated using the dynamic shear rheometer (DSR) test, infrared spectrum test and direct tensile (DT) test. These hydraulic bitumen binders were respectively applied for several pumped storage power stations (PSPS) projects that were constructed or under construction. In order to relate the bitumen performance to the mixture performance, the slope flow test, three-point bending test and thermal stress restrained specimen test were carried out on hydraulic asphalt mixtures. The test results indicated the DSR rheological master curves can well distinguish the difference of each bitumen binder as well as the effect of polymer modification. Phase angle master curves, black diagrams and infrared spectra all indicated that several penetration-grade hydraulic bitumen binders were not virgin bitumen binders but were modified with relatively lower SBS polymer content when compared with traditional SBS-modified bitumen. When selecting the commonly used Karamay SG70 hydraulic bitumen as a reference, the normal SBS-modified bitumen was superior to other bitumen in terms of low- and high-temperature performance. Several slightly SBS-modified bitumen binders did not always show consistent results, which indicated that slightly modified bitumen may not really have the desired performance as expected. Therefore, SBS-modified bitumen will be more promising when dealing with extremely low or high temperatures. Bitumen performance was well compared with the mixture performance by using the bitumen creep, relaxation and tensile failure strain corresponding to the asphalt concrete slope flow, the maximum bending strain and the failure temperature, respectively. Compared with the traditional penetration, softening point and ductility test, it indicated that the DSR rheological test, creep test, direct tensile test and stress relaxation test can be used as more powerful tools for the characterization and optimization of hydraulic bitumen binders.


Ophthalmic applications of preserved human amniotic membrane: a review of current indications.
Preserved human amniotic membrane (AM) is currently being used for a wide spectrum of ocular surface disorders. The AM has a basement membrane, which promotes epithelial cell migration and adhesion. The presence of a unique avascular stromal matrix reduces inflammation, neovascularization and fibrosis. The basic tenets of amniotic membrane transplantation (AMT) are to promote re-epithelialization, to reconstruct the ocular surface and to provide symptomatic relief from surface aberrations. AMT is a useful technique for reconstruction of surface defects resulting from removal of surface tumors and symblephara. AMT has effectively restored a stable corneal epithelium in eyes with, persistent epithelial defects and corneal ulcers. In the setting of acute ocular burns and SJS, AMT has satisfactorily reduced scarring and inflammation. AMT alone may be an effective alternative for partial limbal stem cell deficiency. However remarkable improvements in surface stability have resulted from concurrent AMT and limbal stem cell transplantation, wherein the limbal grafts are obtained from the normal fellow eye, living relative or cadaveric eye. In severe or bilateral cases, well being of the donor eye is a major concern. Currently, the most unique application of preserved human AM in ophthalmology is its use as a substrate for ex-vivo expansion of corneal and conjunctival epithelium. In this novel technique of tissue engineering, epithelial stem cells can be safely harvested and expanded on denuded AM. The resultant composite cultured tissue has been successfully transplanted to restore vision, as well as the structure and function of damaged ocular surfaces.


Burkitt's lymphoma in Brazil: strong association with Epstein-Barr virus.
The incidence of Burkitt's lymphoma (BL) in Brazil is intermediate between the endemic form of equatorial Africa and the sporadic form in the United States. To characterize these lymphomas, we evaluated the clinical, morphologic, and immunohistochemical features of 24 Brazilian cases of BL. We also analyzed the cases for the presence of Epstein-Barr virus (EBV)-RNA using a highly sensitive and specific method of in situ hybridization. Most cases presented with involvement of intraabdominal organs, similar to the sporadic form of BL. EBV-RNA was detected in 17 of 24 cases (71%) in all or virtually all the tumor cells. This prevalence of EBV-positivity in our cases is intermediate between the endemic form of BL in equatorial Africa (100%) and the sporadic form in the United States (30%). These findings suggest that EBV plays an important role in the pathogenesis of BL in Brazil. This intermediate incidence of EBV infection may explain in part the differences of incidence of BL in different geographic regions.


Occurrence of potential plastic microfibers in mussels and anchovies sold for human consumption: Preliminary results.
There is a global concern over the impact of microplastics on marine species and trophic webs. Microfibers commonly represent the greater portion of microplastics in the aquatic environment, but little is known about fiber uptake and accumulation by marine biota. The aim of the study was to investigate the potential plastic microfiber contamination in mussels (Mytilus galloprovincialis) and anchovies (Engraulis encrasicolus) from the Tyrrhenian Sea sold for human consumption. Anthropogenic debris was extracted from the digestive tracts of fish and the whole shellfish using a 10% KOH solution and quantified under a light microscope. The preliminary results showed the occurrence of potential plastic and natural microfibers in 73% of the samples. On average mussels contained 1.33 microfibers/g w.w. and 7.66 items/individual, while anchovies contained 9.06 microfibers/individual. Considering that mussels are consumed as a whole, and small pelagic fish, as anchovy, may be eaten without removing the gastrointestinal tract, microfiber contamination may lead to human exposure. More research is required to adequately assess the risk that microplastics, including microfibers, may pose for food safety and human health.


Nitric oxide activation of guanylyl cyclase in cells revisited.
Nitric oxide (NO) elicits physiological effects in cells largely by activating guanylyl cyclase (GC)-coupled receptors, leading to cGMP accumulation. Like other receptor-coupled effector mechanisms, NO stimulation of GC activity was previously considered to be a graded, concentration-dependent response, with deactivation following swiftly once the agonist disappeared. Recently, a new and unconventional mechanism has been proposed from experiments on purified protein [Cary, S. P. L., Winger, J. A. & Marletta, M. A. (2005) Proc. Natl. Acad. Sci. USA 102, 13064-13069]. It was concluded that GC in vivo will display a dual regulation by NO: a long-lasting tonic activity (10-20% of maximum) due to persistent occupation by NO of the heme binding site and phasic activity due to engagement of another unidentified, lower affinity site. The hypothesis was first tested by monitoring GC activity in rat platelets maintained in vitro and exposed to calibrated NO transients. The kinetics was as expected for a single binding site for NO (EC(50) = 10 nM), with activation and deactivation of enzyme activity conforming to the predictions of a simple receptor model. No tonic GC activity attributable to long-term NO binding was detected after exposure to the full range of active NO concentrations (peaking at 2-500 nM). Comparable results were obtained by using neural cells isolated from the cerebellum. After exposure to high NO concentrations, persistent GC activity could be recorded, but this activity was caused artifactually by secondary NO sources being formed in the medium. The new scheme for regulation of GC activity by NO is of doubtful relevance to cells.


Hot and sour: parasite adaptations to honeybee body temperature and pH.
Host temperature and gut chemistry can shape resistance to parasite infection. Heat and acidity can limit trypanosomatid infection in warm-blooded hosts and could shape infection resistance in insects as well. The colony-level endothermy and acidic guts of social bees provide unique opportunities to study how temperature and acidity shape insect-parasite associations. We compared temperature and pH tolerance between three trypanosomatid parasites from social bees and a related trypanosomatid from poikilothermic mosquitoes, which have alkaline guts. Relative to the mosquito parasites, all three bee parasites had higher heat tolerance that reflected body temperatures of hosts. Heat tolerance of the honeybee parasite Crithidia mellificae was exceptional for its genus, implicating honeybee endothermy as a plausible filter of parasite establishment. The lesser heat tolerance of the emerging Lotmaria passim suggests possible spillover from a less endothermic host. Whereas both honeybee parasites tolerated the acidic pH found in bee intestines, mosquito parasites tolerated the alkaline conditions found in mosquito midguts, suggesting that both gut pH and temperature could structure host-parasite specificity. Elucidating how host temperature and gut pH affect infection-and corresponding parasite adaptations to these factors-could help explain trypanosomatids' distribution among insects and invasion of mammals.


Step heights from interferograms.
For the precise determination of a step height, the surface contour in the vicinity of the step must be determined. Methods that have proven satisfactory even in the presence of aberrations caused by poor flatness of object or comparison mirrors, by auxiliary optics, or by subsequent processing are described.


The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase.
Targeted gene disruption studies have established that the c-Jun NH(2)-terminal kinase (JNK) signaling pathway is required for stress-induced release of mitochondrial cytochrome c and apoptosis. Here we demonstrate that activated JNK is sufficient to induce rapid cytochrome c release and apoptosis. However, activated JNK fails to cause death in cells deficient of members of the Bax subfamily of proapoptotic Bcl2-related proteins. Furthermore, exposure to stress fails to activate Bax, cause cytochrome c release, and induce death in JNK-deficient cells. These data demonstrate that proapoptotic members of the Bax protein subfamily are essential for JNK-dependent apoptosis.


The FDA just says yes.
Will a new and, some say, improved FDA improve the conditions, financial and otherwise, of patient care? Many argue that the acceleration of the FDA approval process comes at a high price. As new drugs hit the market faster--and with less proof of their long-term benefits--health care costs are going up, up, up, and society is facing painful rationing decisions.


Expression cloning and characterization of ROAT1. The basolateral organic anion transporter in rat kidney.
Expression cloning in Xenopus laevis oocytes was used to isolate an organic anion transport protein from rat kidney. A cDNA library was constructed from size-fractionated poly(A)+ RNA and screened for probenecid-sensitive transport of p-aminohippurate (PAH). A 2, 227-base pair cDNA clone containing a 1,656-base pair open reading frame coding for a peptide 551 amino acids long was isolated and named ROAT1. ROAT1-mediated transport of 50 mu M [3H]PAH was independent of imposed changes in membrane potential. Transport was significantly inhibited at 4 degrees C, or upon incubation with other organic anions, but not by the organic cation tetraethylammonium, by the multidrug resistance ATPase inhibitor cyclosporin A, or by urate. External glutarate and alpha-ketoglutarate (1 mM), both counterions for basolateral PAH exchange, also inhibited transport, suggesting that ROAT1 is functionally similar to the basolateral PAH carrier. Consistent with this conclusion, PAH uptake was trans-stimulated in oocytes preloaded with glutarate, whereas the dicarboxylate methylsuccinate, which is not accepted by the basolateral exchanger, did not trans-stimulate. Finally, ROAT1-mediated PAH transport was saturable, with an estimated Km of 70 mu M. Each of these properties is identical to those previously described for the basolateral alpha-ketoglutarate/PAH exchanger in isolated membrane vesicles or intact renal tubules.


Zollinger-Ellison syndrome: technique, results, and complications of portal venous sampling.
All 95 portal venous sampling (PVS) procedures performed in patients with Zollinger-Ellison syndrome in the past 10 years at the authors' institution were reviewed. It was possible to catheterize at least one branch of the pancreaticoduodenal venous arcade in all but two procedures (98%). The highest concentration of gastrin was found in a selective sample from the pancreaticoduodenal venous arcade or the transverse pancreatic vein in 56 of 91 procedures (62%). Selective sampling of pancreatic head veins yielded a gastrin gradient sufficient for localization in 60 patients (63%). Among 55 solitary sporadic gastrinomas identified at surgery, PVS allowed correct localization of the tumor in 32 (58%); if selective samples had not been obtained, only eight (15%) would have been localized (P less than .0005). Sensitivity was the same for tumors in the gastrinoma triangle (64%) and the body or tail of the pancreas (60%). There were no false-positive results. The overall complication rate was 20%, but most complications were abdominal pain lasting 3 days or less. Six patients (6%) had serious complications.


Copper and calcium binding motifs in the extracellular domains of fibroblast growth factor receptors.
High affinity fibroblast growth factor (FGF) receptors contain a cluster of acidic amino acids in their extracellular domains that is reminiscent of the calcium binding domains of some cell adhesion molecules. Based on this observation, we used a calcium blotting technique to show that FGFR-1 binds calcium and that calcium binding is not observed in a mutagenized form of the receptor that lacks the acidic box region. The acidic box also binds other divalent cations, including copper. This latter interaction appears unique since the binding of copper to FGFR-1 mediates the binding of the receptor to immobilized heparin. While this observation may help explain the angiogenic properties of copper, divalent cation binding to FGF receptors may also mediate the interaction between FGF receptors, cell adhesion molecules and other proteoglycan components of the extracellular matrix.


Immigrants, Germans and national identity in the new Germany: some policy issues.
"This paper considers how the role and status of Germany's diverse immigrant population has been affected by its new geopolitical situation, in particular unification, since 1989.... The paper shows how the integration prospects for Germany's older immigrant populations have been dented by the combination of economic restructuring and a huge upsurge in new types of immigration. Prominent among the latter are ethnic German resettlers (or Aussiedler), and the paper examines how these immigrants find themselves in a weak position.... The paper concludes that, although there would appear to be no major labour shortages within the economy, Germany has to develop a more extensive range of migration policies to cater for the huge demand for economically motivated migration. The alternative will inevitably be a further growth in illegal migration, which would not be helpful to the position of established immigrant populations."


Inferential Communication: Bridging the Gap Between Intentional and Ostensive Communication in Non-human Primates.
Communication, when defined as an act intended to affect the psychological state of another individual, demands the use of inference. Either the signaler, the recipient, or both must make leaps of understanding which surpass the semantic information available and draw from pragmatic clues to fully imbue and interpret meaning. While research into human communication and the evolution of language has long been comfortable with mentalistic interpretations of communicative exchanges, including rich attributions of mental state, research into animal communication has balked at theoretical models which describe mentalized cognitive mechanisms. We submit a new theoretical perspective on animal communication: the model of inferential communication. For use when existing proximate models of animal communication are not sufficient to fully explain the complex, flexible, and intentional communication documented in certain species, specifically non-human primates, we present our model as a bridge between shallower, less cognitive descriptions of communicative behavior and the perhaps otherwise inaccessible mentalistic interpretations of communication found in theoretical considerations of human language. Inferential communication is a framework that builds on existing evidence of referentiality, intentionality, and social inference in primates. It allows that they might be capable of applying social inferences to a communicative setting, which could explain some of the cognitive processes that enable the complexity and flexibility of primate communication systems. While historical models of animal communication focus on the means-ends process of behavior and apparent cognitive outcomes, inferential communication invites consideration of the mentalistic processes that must underlie those outcomes. We propose a mentalized approach to questions, investigations, and interpretations of non-human primate communication. We include an overview of both ultimate and proximate models of animal communication, which contextualize the role and utility of our inferential communication model, and provide a detailed breakdown of the possible levels of cognitive complexity which could be investigated using this framework. Finally, we present some possible applications of inferential communication in the field of non-human primate communication and highlight the role it could play in advancing progress toward an increasingly precise understanding of the cognitive capabilities of our closest living relatives.


In Silico Structural Prediction and Production of a Chimeric Recombinant Dickkopf-1 (DKK-1) Antigen.
Dickkopf (DKK) family of proteins are known as antagonists for the Wnt-β-catenin signaling pathway. It is suggested that the Dickkopf-1 (DKK-1) has a role in several diseases such as hepatocellular carcinomas, hepatoblastomas, Wilms' tumors, lung cancer and Myeloma bone disease. The aim of the present study was to produce a chimeric-recombinant DKK-1 protein in order to induce immune response against the antigen. The recombinant Dickkopf-1 (rDKK-1) protein was designed using bioinformatics analysis. The standard methods were used for cloning, expression and purification. The structure of recombinant protein was analyzed by spectroscopy methods. Enzyme-linked immunosorbent assay (ELISA) and Western blotting were performed to confirm the recombinant protein using a commercial anti-DKK-1 (whole protein) polyclonal antibody. The immunogenicity of the recombinant DKK-1 was assessed by immunizing, intraperitoneally, BALB/C mice four times with the 31-kDa and 45-kDa purified rDKK-1 cloned in pET28a and pET32a vectors respectively. The antibody titer was measured in due course of time. Stronger immunogenic parts of the protein were selected based on in-silico predictions and recombinant protein was successfully designed. The chimeric gene was sub-cloned, expressed, purified and refolded. The purified protein was confirmed by Western blotting and ELISA. The three dimensional structural was confirmed by CD spectrum and predicted structures by bioinformatics tools, revealed the stability of helix structures. rDKK-1 protein was capable of inducing immune response with high titer antibody and excessive humoral immune response. No significant difference was observed between immunization by 31-kDa and 45-kDa antigen.


[Treatment of inguinal hernia under local anesthesia at the Central University Hospital of Lome].
In our search study, we were allowed to do 74 opérations of inguinal hernia (71 indirect and 3 femoral hernia). All these patients were operated under local anaesthesia with zylocaine 2%. The dose was between 4 to 40 ml. After surgery, the patients were hospitalised for différent times beginning from 3 hours up to 28 days. The post operative care was done in the out clinics. 53 of our patients left in the same day of the operation (71.62%); 3 the second day of the operation (4.05%); 7 after 72 hours (9.45%). Eleven patients were afraid and refused to leave there beds using some medical causes (14.86%). The for home of some patients was also the cause of passing long time in the hospital. No surgied complications were detected. The single death registered in our serie was not due to this method of anaesthesia. It was a hypertensive patient with severe cardiac insufficiency refused by general anaesthesia. Not single anomaly was noticed by the monitor during operation, also the electrocardiogram didn't change during injection. The death was on the 3rd day post-operative and was bind to the previous cardiac condition of the patient (autopsy was not practical). We must put in mind this line of treatment which minimises complications for the resolution of insufficient materials and instruments.


Analysis of toxic norditerpenoid alkaloids in Delphinium species by electrospray, atmospheric pressure chemical ionization, and sequential tandem mass spectrometry.
A rapid electrospray mass spectrometry method was developed for screening larkspur (Delphinium spp.) plant material for toxic norditerpenoid alkaloids. The method was calibrated using two standard alkaloids, methyllycaconitine (1) and deltaline (2), with a recovery of 92% from spiked samples and relative standard deviations of 6.0% and 8.1% for the two alkaloids, respectively. Thirty-three samples of plains larkspur, Delphinium geyeri, were analyzed. Methyllycaconitine (1) concentration was 0.27% +/- 0.08% during a 1-month period in 1997 establishing the relative risk of poisoning from the plant to be low. The method was also applied to the trace analysis (<1 ppm) of 1 in serum samples from sheep dosed different levels of the alkaloid. Electrospray ionization combined with sequential tandem mass spectrometry and HPLC coupled to atmospheric pressure chemical ionization (APCI) mass spectrometry were used to detect and tentatively identify three new norditerpenoid alkaloids from Delphinium nuttallianum [bearline (6), 14-acetylbearline (7), 16-deacetylgeyerline (8)]. The tentative structure of the new alkaloids was predicted from the tandem mass spectra fragmentation patterns and assigning the substitution pattern for methoxy and acetyl groups at the C-14 and C-16 carbons.


Effects of encephalo-duro-arterio-synangiosis on childhood moyamoya patients--swift disappearance of ischemic attacks and maintenance of mental capacity.
The effect of encephalo-duro-arterio-synangiosis (EDAS) upon chronic cerebrovascular ischemia in 65 pediatric moyamoya patients was evaluated by the postoperative interval before complete disappearance of ischemic attacks and changes in pre- and postoperative intelligence (IQ) or development quotients (DQ). The ischemic attacks disappeared after a mean period of 239 days, in three-fourths of patients within a year and in about one-fourth within the second year. This was very fast compared with the natural course of the disease. There was no significant difference in DQ/IQ before and after the operation. The mentally normal (IQ/DQ greater than or equal to 86) population in the postoperative patients was greater than in the natural course of the disease, although fewer in the preoperative group. This shows that EDAS delayed or prevented the deterioration in mental capacity usually present but often overlooked in the natural course of pediatric moyamoya disease.


Management of invasive carcinoma of the uterine cervix associated with pregnancy: outcome of intentional delay in treatment.
To investigate patients with invasive cervical carcinoma associated with pregnancy, with special reference to the maternal and neonatal outcomes after planned treatment delay to improve fetal maturity. The medical records of 28 patients with invasive cervical carcinoma diagnosed during pregnancy or within 1 month after pregnancy were retrospectively reviewed. Twenty-two patients (79%) had Stage I disease and 6 (21%) had Stage II or III disease. Tumor histology revealed squamous cell carcinoma in 27 cases and adenocarcinoma in 1. Twenty cases were diagnosed before 22 weeks gestation, 4 between 22 and 36 weeks, 1 after 36 weeks gestation, and 3 were diagnosed postpartum. In the immediate treatment group (n = 16), the diseases were Stage IA in 3 cases, IB in 7, and II or III in 6. In 11 patients, hysterectomy was performed after therapeutic abortion or with fetus in situ. In 2 patients, cesarean section was followed by hysterectomy or radiotherapy. Three patients diagnosed postpartum were treated with either hysterectomy or radiotherapy. Fifteen patients were free of disease during the follow-up of 27 to 114 months. In the delayed treatment group (n = 12), the diseases were Stage IA1 in 8 cases, IA2 in 1, IB1 in 2, and IB2 in 1 case. In 8 patients with Stage IA1 tumor, the treatment was deferred until term with a delay of 6 to 25 weeks, and hysterectomy or therapeutic conization was performed after delivery. In 4 patients with Stage IA2, IB1 or IB2 tumor, the treatment was postponed until after 30 weeks gestation with a delay of 6 to 15 weeks. No disease progression was documented. Cesarean delivery was followed by hysterectomy in these patients. All patients were free from disease during the follow-up of 70 to 156 months and their babies were well with no sequelae. Delay in treatment to allow for fetal maturity is safe in patients with early Stage I cervical carcinoma associated with pregnancy.


Patient-Reported Outcome Measures and Dosimetric Correlates for Early Detection of Acute Radiation Therapy-Related Esophagitis.
We investigate the time to and clinical factors associated with patient-reported difficulty swallowing in lung cancer patients treated with radiation therapy (RT). Between October 2016 and October 2019, lung cancer patients treated with conventionally fractionated RT at a tertiary cancer center were identified. Weekly, patients reported difficulty swallowing (patient-reported outcome version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE] v.1: 0-none, 1-mild, 2-moderate, 3-severe, 4-very severe). Physicians graded dysphagia (CTCAE v.4: 0-none, 1-symptoms without altered intake, 2-symptomatic; altered eating/swallowing, 3-severely altered eating/swallowing, 4-life-threatening consequences, 5-death). Tumor-related difficulty swallowing was not recorded at baseline; thus, patients reporting ≥moderate symptoms ≤7 days of RT start were excluded. We evaluated the time to new patient reports of ≥moderate difficulty swallowing and CTCAE grade 2+ dysphagia and development over time using the cumulative incidence method. Multivariable logistic regression evaluated associations between clinical factors, esophageal V60, and development of esophageal symptoms. Of the 200 patients identified: median age was 69 years, 52% were male, and 89% had stage III+ disease. Patients received a median of 63 Gy with chemotherapy (91.5%). At least moderate difficulty swallowing during RT was reported by 76 of 200 patients (38%); clinicians rated dysphagia as altering oral intake or worse for 26 of 200 (13%). Median time to first report of symptoms was 21 days (interquartile ratio [IQR], 18-34.5) for the 76 patients who reported ≥moderate symptoms and 33 days (IQR, 24-42) in the 26 patients whose provider reported grade 2+ dysphagia. The 30-day incidence of patient-reported ≥moderate swallowing difficulty and provider grade 2+ dysphagia was 26% (95% CI: 20%-32%) and 6% (95% CI: 3%-9%), respectively. Esophageal V60 >7 % was the clinical factor most associated with patient-reported ≥moderate esophageal symptoms (odds ratio 6.1, 95% CI: 3.0-12.3). Patients report at least moderate difficulty swallowing more often and earlier than providers report grade 2+ dysphagia. Esophageal V60 ≥7% was most associated with development of moderate severity or worse patient-reported swallowing difficulty.


Persistence of a mock bio-agent in cross-contaminated mail and mailboxes.
Among the 22 confirmed or suspected cases of anthrax during the bioterrorism incidents in 2001, all but two seemed traceable to spores from threat letters. Although no anthrax spores were found in the environments frequented by two females who died of the disease, a suspicion persists that the deaths were somehow related to the mail. This study assesses the spread and persistence of a mock biological agent from a source-letter to other mail and to a receiving mailbox. Successive placement and removal of letters were found to reduce the number of residual bio-agent particles in a mailbox. This suggests that a sweeping action is taking place that can affect the quantity of bio-agent remaining. The exercise supports the possibility that the two females were exposed to spores on mail that had been in their mailboxes although no trace of spores could later be found in their boxes.


GTPase regulator associated with the focal adhesion kinase (GRAF) transcript was down-regulated in patients with myeloid malignancies.
GTPase regulator associated with the focal adhesion kinase (GRAF), a putative tumor suppressor gene, is found inactivated in hematopoietic malignancies by either genetic or epigenetic abnormalities. However, the expression level of GRAF gene has not yet been studied in leukemia. The aim of this study was to investigate the expression level of GRAF gene in those patients with myeloid malignancies including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML). The expression levels of GRAF transcript were determined in 94 patients using real-time quantitative PCR (RQ-PCR). Clinical and laboratory data of these patients were collected and analyzed. The significantly decreased level of GRAF transcript was observed in three myeloid malignancies compared to controls. Within AML, there was no difference in the level of GRAF transcript among different FAB subtypes (P > 0.05). Difference was not observed in the amount of GRAF mRNA between CML at chronic phase and controls. As CML progressed, GRAF transcript significantly decreased. In MDS, three cases with 5q deletion had lower GRAF transcript than four without 5q deletion (median 0.76 vs 2.99) (P > 0.05). our results demonstrate that the GRAF transcript is decreased in myeloid malignancies.


Exploring Factors Associated with Recent HIV Testing among Heterosexuals at High Risk for HIV Infection Recruited with Venue-based Sampling.
Annual HIV testing is recommended for high-risk populations in the United States, to identify HIV infections early and provide timely linkage to treatment. However, heterosexuals at high risk for HIV, due to their residence in urban areas of high poverty and elevated HIV prevalence, test for HIV less frequently than other risk groups, and late diagnosis of HIV is common. Yet the factors impeding HIV testing in this group, which is predominantly African American/Black and Latino/Hispanic, are poorly understood. The present study addresses this gap. Using a systematic community-based sampling method, venue-based sampling (VBS), we estimate rates of lifetime and recent (past year) HIV testing among high-risk heterosexuals (HRH), and explore a set of putative multi-level barriers to and facilitators of recent testing, by gender. Participants were 338 HRH African American/Black and Latino/Hispanic adults recruited using VBS, who completed a computerized structured assessment battery guided by the Theory of Triadic Influence, comprised of reliable/valid measures on socio-demographic characteristics, HIV testing history, and multi-level barriers to HIV testing. Logistic regression analysis was used to identify factors associated with HIV testing within the past year. Most HRH had tested at least once (94%), and more than half had tested within the past year (58%), but only 37% tested annually. In both men and women, the odds of recent testing were similar and associated with structural factors (better access to testing) and sexually transmitted infection (STI) testing and diagnosis. Thus VBS identified serious gaps in rates of annual HIV testing among HRH. Improvements in access to high-quality HIV testing and leveraging of STI testing are needed to increase the proportion of HRH testing annually for HIV. Such improvements could increase early detection of HIV, improve the long-term health of individuals, and reduce HIV transmission by increasing rates of viral suppression.


Biochemical differences between trail mucus and adhesive mucus from marsh periwinkle snails.
The composition of the adhesive form of marsh periwinkle mucus was compared to the trail mucus used during locomotion. The trail mucus consists primarily of large, carbohydrate-rich molecules with some relatively small proteins. In contrast, the adhesive mucus has 2.7 times as much protein with no significant difference in carbohydrate concentration. The resulting gel has roughly equal amounts of protein and carbohydrate. This substantial increase in protein content is due to the additional presence of two proteins with molecular weights of 41 and 36 kD. These two proteins are absent from the trail mucus. Both proteins are glycosylated, have similar amino acid compositions, and have isoelectric points of 4.75. This change in composition corresponds to an order of magnitude increase in tenacity with little clear change in overall concentration. The difference between adhesive and non-adhesive mucus suggests that relatively small proteins are important for controlling the mechanics of periwinkle mucus.


Running is the neurogenic and neurotrophic stimulus in environmental enrichment.
Environmental enrichment (EE) increases dentate gyrus (DG) neurogenesis and brain-derived neurotrophic factor (BDNF) levels. However, running is considered an element of EE. To dissociate effects of physical activity and enrichment on hippocampal neurogenesis and BDNF levels, young female C57Bl/6 mice were housed under control, running, enrichment, or enrichment plus running conditions, and injected with bromodeoxyuridine. Cell genesis was assessed after 12 d and differentiation was analyzed 1 mo later. In addition, locomotor activity in the open field and hippocampal mature BDNF peptide levels were measured. Open-field adaptation was improved in all groups, compared to controls, but more so with running. New cell proliferation, survival, neuron number, and neurotrophin levels were enhanced only when running was accessible. We conclude that exercise is the critical factor mediating increased BDNF levels and adult hippocampal neurogenesis.


The Impact of Resveratrol Supplementation on Inflammation Induced by Acute Exercise in Rats: Il6 Responses to Exercise.
Severe physical activity leads to a sharp increase in free radicals, an oxidative stress, inflammation, and tissue damage. Resveratrol as one of the antioxidants can be effective in preventing the effects of oxidative stress. Therefore, the present study was aimed to evaluate the effect of trans-resveratrol supplementation and training exercise on inflammation-related factors. Sixty-four male Wistar rats were divided into six groups, each group consisting of 16 animals: 1) excursive + trans-resveratrol, 2) exercise group, 3) trans-resveratrol group, and 4) control group. Following the familiarization sessions, a more consistent protocol with an intensity of 65% vo2 max was performed for 12 weeks. Afterward, half of the mice in each group received acute exercise training with an intensity of 70-75% of vo2 max at the age of 20 weeks, until reaching the disability level. Finally, the levels of inflammatory markers were measured using special kits. Our findings depicted that inflammatory factors such as CPR, TNF-α, IL-6, and IL-7 were not affected by endurance protocol (P > 0.05), whereas, they were significantly increased by acute exercise training (P > 0.05). Additionally, we found that RES supplements led to a decrease in CPR and IL-6 levels, while not affecting TNF-α and IL-17 levels. According to available evidence, RES appears to have anti-inflammatory and protective effects during exercise by reducing inflammatory factors. Further studies are required to clarify the role of trans-resveratrol supplementation after exercise training.


Antioxidant and Hypoglycemic Activities of Exopolysaccharide by Submerged Culture of Inocutus Hispidus.
This work was to investigate the hypoglycemic and antioxidant activities of the exopolysaccharides produced in a stirred-tank bioreactor by Inocutus hispidus. The exopolysaccharides showed significant antioxidant activities, up to 70.7±2.5% inhibition of hydroxyl radicals, 50% inhibition of 2,2-diphenyl-1-picrylhydrazyl radicals, and a Trolox equivalent antioxidant capacity of 3.3 mM. The exopolysaccharide also showed notable hypoglycemic effects in streptozotocin-induced diabetic mice, reducing the plasma glucose, total cholesterol and triacylglycerol concentrations by 18.2±1.5, 20.9±0.8 and 14.4±0.4, respectively. The results demonstrated the potential of this EPS for human health protection against oxidative damage and hyperglycemia.


Matter of Baby M., 3 February 1988.
The plaintiffs, husband and wife, sought to enforce a surrogate parenting agreement under which the defendant had been impregnated with semen of the husband and had agreed to surrender any resulting child to the plaintiffs in return for money. They also requested that the natural mother be restrained from interference with their custody of the child and that her parental rights be terminated so that the child could be adopted by the wife. The Supreme Court of New Jersey held that surrogate parenting contracts conflicted with laws prohibiting the use of money in connection with adoptions, laws requiring proof of parental unfitness or abandonment before parental rights are terminated or adoption ordered, and laws making surrender of custody and consent to adoption revocable in private placement adoptions. It also ruled that such contracts conflicted with state public policy. It awarded custody of the child to the father on the grounds that it was in the child's best interest but did not sever the mother's parental rights and gave her the right to visit the child. On 6 April 1988, the Superior Court of New Jersey ruled that the mother of the child should have liberal, unsupervised visitation rights and enjoined and restrained the parties from publicly discussing their relationship with the child or her activities and from selling movie rights without the court's approval. On 21 January 1988, the Michigan Circuit Court for Gratiot County refused to enforce a surrogacy contract. It declared it to be void as contrary to public policy. See Yates vs. Keane in Family Law Reporter, Vol. 14, 9 February 1988, pp. 1160-61.


Echocardiographic measurement of ventricular function.
We review new findings concerning ventricular function in patients in intensive care units with shock or unexplained respiratory distress syndrome analyzed using echocardiography. Bedside echocardiography is not only an imaging technique but should be considered as a hemodynamic method. Left-ventricular systolic function can be assessed in daily clinical practice by measuring shortening fraction, fraction area change and ejection fraction. But these indices are dependent on load conditions. Index of myocardial performance can be also used. Rate of left-ventricular pressure increase may be measured from mitral regurgitation. Other indices such a maximal elastance and preload-adjusted maximal power were developed to evaluate myocardial systolic function but are not still used in clinical practice in patients in intensive care. Cardiac output measurement can be calculated easily from aortic annulus diameter and the velocity time integral of aortic blood flow. To complete the assessment of ventricular function, left-ventricular diastolic function and pressure as well as right ventricular size, septal movement and right pressures should be analyzed. Using echocardiography the intensivist can examine both the mechanism and the cause of shock or pulmonary edema. It is time to increase the use of this technique in intensive care units.


Clinical characteristics of transient ischemic attacks in black patients.
We analyzed the clinical, CT, and angiographic findings in 50 black patients with carotid transient ischemic attacks (TIAs). Thirty-two percent had TIAs lasting less than 1 hour, 26% had TIAs lasting 1 to 6 hours, and 42% had TIAs lasting 6 to 24 hours. Fifty-two percent of TIA patients had CT evidence of cerebral infarction despite complete clinical recovery. CT was abnormal in two of 16 (13%) patients with TIAs lasting less than 1 hour; however, CT was abnormal in 24 of 34 (70%) patients with TIAs lasting longer than 1 hour. Angiographic findings of extracranial carotid disease appropriate to TIA symptoms were present in 12 (24%) patients. Two patients in whom the TIA episode lasted less than 1 hour later had clinical cerebral infarction, whereas 20 patients with longer-duration TIAs developed ischemic stroke within 4 months. Of these black TIA patients, 22 (44%) developed clinical cerebral infarction.


Molecular characterization of a chromosome translocation breakpoint t(11;14)(p13;q11) from the cell line KOPT-K1.
Recurrent chromosome translocations involving 11p13 and 14q11 are found in 5-10% of cases of T-ALL. The gene involved in the translocation on chromosome 14 is the T cell antigen receptor alpha or delta. The putative oncogene on chromosome 11 is rhombotin 2 (RBTN2)/translocated in T cell gene 2 (ttg-2), a member of the LIM family of proteins. In this paper we characterize a cell line KOPT-K1 that has a t(11;14)(p13;q11). The breakpoint on chromosome 11 involves an Alu-rich region with the break occurring between two Alu sequences on chromosome 11. In addition, approximately 70 bases from the break on chromosome 11 is a tetranucleotide repeat. Whether either of these structures played a role in the translocation is not known. No heptamer or nonamer sequences, implicated in other rearrangements were found near the breakpoint. The breakpoint on chromosome 11 maps more centromeric than previous translocations of this region. Despite this the RBTN2 gene is highly expressed in KOPT-K1. This cell line will be useful for investigating the role of RBTN2 in leukemogenesis and the mechanism by which the translocation alters the expression of RBTN2.


Contact lens management of keratectasia after laser in situ keratomileusis for myopia.
To present a case in which rigid gas-permeable contact lenses were fit for a patient in whom keratectasia developed after laser in situ keratomileusis (LASIK). Case report. A 21-year-old man underwent bilateral LASIK for myopia and astigmatism. The left eye was only partially corrected because of high myopia and corneal thickness restrictions. Eight months after LASIK, visual acuity was reduced in the right eye; the central cornea had steepened; and pachymetry showed central corneal thinning. Keratectasia was diagnosed, and rigid contact lenses were fitted. Four years later, the patient achieved satisfactory visual acuity and all-day lens wear with minimal complications. The options for management of iatrogenic keratectasia include contact lenses, intracorneal ring segments, and penetrating keratoplasty. This case report shows that rigid contact lenses offer a safe, reversible option for improving visual acuity in such patients by delaying or avoiding the need for further surgical intervention.


Bioavailability of hexabromocyclododecane to the polychaete Hediste diversicolor: exposure through sediment and food from a contaminated fjord.
Knowledge of the bioavailability of brominated flame retardants for sediment-dwelling organisms is limited. The present study investigated bioaccumulation of hexabromocyclododecane (HBCD) in the ragworm Hediste diversicolor exposed to field-contaminated sediments and food. Sediments and blue mussels (Mytilus edulis) were sampled from a fjord on the Norwegian west coast known to be highly contaminated with the brominated flame retardant HBCD. During a four-week experiment, ragworms were either exposed to sediment containing moderate or high concentrations of HBCD, or they were fed contaminated soft tissue from mussel. Although mean sediment concentrations were as high as 40 microg/g dry weight in the contaminated sediments, no HBCD were detected in the exposed ragworms (detection limit up to 2.0 ng/g wet wt). In contrast, the exposure to contaminated food (mussel) resulted in elevated body concentrations of 9.1 ng HBCD/g wet weight. The partitioning of HBCD in the test-sediments appeared to be influenced by the quantity and quality of the sediment organic matter (up to 15% total organic carbon). The presence of small plastic beads (<2 mm), which were shown to contain a mean of 50 microg/g dry weight of HBCD, could explain the low bioavailability of the flame retardant in the sediment. Hexabromocyclododecane in food appeared to be readily assimilated in the ragworm, however, and the diastereomer pattern indicated a relative increase of alpha-HBCD from mussel to ragworm. Hence, in the sampled areas of the fjord, trophic transfer appeared to be a more important mechanism for the entry of HBCD into the local benthic food web than sediment-to-biota accumulation.


Size-dependent phase diagram of nanoscale alloy drops used in vapor--liquid--solid growth of semiconductor nanowires.
We use in situ observations during high-temperature transmission electron microscopy to quantify the exchange of semiconductor material between Au-Ge vapor--liquid--solid seed drops and Ge nanowires (NWs). By performing simultaneous measurements under identical conditions on arrays with systematic variations in NW diameter, we establish the nanoscale size dependence of the temperature-dependent equilibrium composition of the Au-Ge binary alloy. We find a significantly enhanced Ge solubility for drops on thin NWs compared to thicker ones. The controlled modification of the surface of the NW by an ordered carbon shell leads to drastic changes in the solubility.


Cancer-associated fibroblasts suppress SOX2-induced dysplasia in a lung squamous cancer coculture.
Tumorigenesis depends on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. While oncogenic drivers in lung squamous carcinoma (LUSC) have been described, the role of stroma in modulating tissue architecture, particularly cell polarity, remains unclear. Here, we report the establishment of a 3D coculture system of LUSC epithelial cells with cancer-associated fibroblasts (CAFs) and extracellular matrix that together capture key components of the tumor microenvironment (TME). Single LUSC epithelial cells develop into acinar-like structures with 0.02% efficiency, and addition of CAFs provides proper tumor-stromal interactions within an appropriate 3D architectural context. Using this model, we recapitulate key pathological changes during tumorigenesis, from hyperplasia to dysplasia and eventually invasion, in malignant LUSC spheroids that undergo phenotypic switching in response to cell intrinsic and extrinsic changes. Overexpression of SOX2 is sufficient to mediate the transition from hyperplasia to dysplasia in LUSC spheroids, while the presence of CAFs makes them invasive. Unexpectedly, CAFs suppress the activity of high SOX2 levels, restore hyperplasia, and enhance the formation of acinar-like structures. Taken together, these observations suggest that stromal factors can override cell intrinsic oncogenic changes in determining the disease phenotype, thus providing fundamental evidence for the existence of dynamic reciprocity between the nucleus and the TME of LUSC.


[Advances in study on bark of Albizzia julibrissin].
Cortex Albizziae, the stem bark of the leguminous plant Albizzia julibrissin, is specified in Chinese pharmacopoeia as a traditional Chinese medicine used to relieve melancholia and uneasiness of body and mind, invigorate the circulation of blood and subside a swelling. This article reviews the recent advances in chemical constituents and pharmacological activities of Cortex Albizziae.


Hand-assisted laparoscopic Hassab's procedure for esophagogastric varices with portal hypertension.
Laparoscopic surgery for patients with portal hypertension is considered to be contraindicated because of the high risk of massive intraoperative hemorrhaging. However, recent reports have shown hand-assisted laparoscopic surgery for devascularization and splenectomy to be a safe and effective method of treating esophagogastric varices with portal hypertension. The aim of this study is to evaluate the efficacy of hand-assisted laparoscopic devascularization and splenectomy (HALS Hassab's procedure) for the treatment of esophagogastric varices with portal hypertension. From 2009 to 2016, seven patients with esophagogastric varices with portal hypertension were treated with hand-assisted laparoscopic devascularization and splenectomy in our institute. Four men and three women with a median age of 61 years (range 35-71) were enrolled in this series. We retrospectively reviewed the medical records for the perioperative variables, postoperative mortality and morbidity, and postoperative outcomes of esophagogastric varices. The median operative time was 455 (range 310-671) min. The median intraoperative blood loss was 695 (range 15-2395) ml. The median weight of removed spleen was 507 (range 242-1835) g. The conversion rate to open surgery was 0%. The median postoperative hospital stay was 21 (range 13-81) days. During a median 21 (range 3-43) months of follow-up, the mortality rate was 0%. Four postoperative complications (massive ascites, enteritis, intra-abdominal abscess, and intestinal ulcer) were observed in two patients. Those complications were treated successfully without re-operation. Esophagogastric varices in all patients disappeared or improved. Bleeding from esophagogastric varices was not observed during the follow-up period. Although our data are preliminary, hand-assisted laparoscopic devascularization and splenectomy proved an effective procedure for treating esophagogastric varices in patients with portal hypertension.


Classroom Enjoyment: Relations With EFL Students' Disengagement and Burnout.
As learner burnout and disengagement affect the functioning and performance of college learners and can also influence future career-related well-being, they can be an issue for higher education organizations. Conversely, the discipline of language education has experienced an emotional turn, primarily triggered by Positive Psychology, and the scholars and students have been affected by various emotions. One of the seldom mentioned constructive emotions concerning learners' disengagement and burnout is enjoyment in learning a foreign language, as has been demonstrated by literature reviews. It is important to note that this review helps scholastic institutions and policymakers in the scholastic community to take into consideration the role of constructive emotions, specifically enjoyment, and their constructive influence on language education in diminishing learners' challenges in the learning process.


Hydrodynamic properties and quaternary structure of the 90 kDa heat-shock protein: effects of divalent cations.
The 90 kDa heat-shock protein (Hsp90) is one of the major stress proteins whose overall structure remains unknown. In this study, we investigated the influence of divalent cations Mg(2+) and Ca(2+) on the hydrodynamic properties and quaternary structure of Hsp90. Using analytical ultracentrifugation, size-exclusion chromatography, and polyacrylamide gel electrophoresis, we showed that native Hsp90 was mostly dimeric. The Hsp90 dimer had a sedimentation coefficient, s(w,20) degrees, of 6.10 +/- 0.03 S, which slightly deviated from the hydrodynamics of a globular protein. Using chemical cross-linking and analytical ultracentrifugation, we showed that Mg(2+) and Ca(2+) induced a tertiary conformational change of Hsp90, leading to a self-association process. In the presence of divalent cations, Hsp90 existed as a mixture of monomers, dimers, and tetramers at equilibrium. Finally, to identify Hsp90 domains involved in this divalent cation-dependent self-association, we studied the oligomerization state of the N-terminal (positions 1-221) of Hsp90, the influence of an N-terminal specific ligand, geldanamycin (GA), and the effect of C-terminal truncation on the ability of Hsp90 to oligomerize in the presence of divalent cations. We previously showed that GA inhibits Hsp90 heat-induced oligomerization [Garnier, C., Protasevich, I., Gilli, R., Tsvetkov, P., Lobachov, V., Peyrot, V., Briand, C., and Makarov, A. (1998) Biochem. Biophys. Res. Commun. 249, 197-201], but now we observed that GA does not influence divalent cation-dependent oligomerization of Hsp90, suggesting another mechanism. This mechanism involved the C-terminal part of the protein since C-terminally truncated Hsp90 did not oligomerize in the presence of divalent cations.


Precisely Regulated Luminescent Gold Nanoparticles for Identification of Cancer Metastases.
The nanoprobes for identification of cancer metastases in the mononuclear phagocyte system (MPS) organs are of significant importance but are limited due to the long-standing challenge of low tumor-targeting specificity with inadequate targeting efficiency and high nonspecific accumulation. Here, we report a surface regulation strategy that integrates the tumor-acidity-activated charge-reversal behavior and precise control in both hydrodynamic diameter (HD) and surface charge on ultrasmall luminescent gold nanoparticles (AuNPs) to achieve significantly high tumor-targeting specificity. The precise regulation of AuNPs to a rational HD and surface charge could rapidly and selectively recognize small metastatic tumors (∼1 mm) in liver and lung with high signal-to-noise ratios of 4.6 and 4.5, respectively. These results help further understand the in vivo transport of nanoprobes and provide guidance for design of translatable nanosized nanomedicines in cancer metastasis theranostics.


[Changes of synaptic transmission efficiency in the MF-CA3 and PP-CA3 pathways of rat hippocampus during discrimination learning].
Electrophysiological and behavioral studies were performed in rat to investigate the changes of synaptic efficacy of the two inputs of hippocampal CA3 area [Mossy Fiber (MF) -CA3 and Perforant Path (PP) -CA3] during discrimination learning. The results showed that: (1) Amplitude of the population spike (PS) of both from MF-CA3 and PP-CA3 increased simultaneously with the establishment of conditioned response (CR) and both reached their maxima before CR reached the criterion of acquisition. (2) During natural extinction of CR, the amplitude of PS of both inputs decreased also simultaneously to their per-training level. These results indicated that the learning-dependent long-term potentiation (LTP) in both MF-CA3 and PP-CA3 inputs developed and extinguished synchronously, suggesting that the changes of synaptic efficacy of different inputs of hippocampal CA3 area coordinated during discrimination learning.