[Effect of shear stress on eicosanoid metabolism in endothelial cells by metabolomics approach].
The article aims to study the effect and mechanism of shear stress on eicosanoids produced by the metabolism of polyunsaturated fatty acids in endothelial cells. First, human umbilical vein endothelial cells were treated by control (Static), laminar shear stress (LSS) and oscillatory shear stress (OSS) for 6 h. Then the endothelial cells were incubated with fresh M199 medium for 3 h, and the cell culture medium was collected. Ultra-performance liquid chromatography-mass spectrometer was used to detect the level of eicosanoid metabolites secreted by endothelial cells. The results showed that under different shear stress, the level of eicosanoid metabolites were changed significantly. We found 10 metabolites were significantly up-regulated by OSS compared with those in LSS group, including PGD2, PGE2, PGF2α and PGJ2 produced by cyclooxygenase; 11-HETE, 15-HETE, 13-HDoHE produced by lipoxygenase or spontaneous oxidation; 12,13-EpOME, 9,10-EpOME, 9,10-DiHOME produced by cytochrome P450 oxidase and soluble epoxide hydrolase. The transcription levels of these up-regulated eicosanoids metabolic enzyme-related genes were also increased in vitro and in vivo. These results indicate that OSS may promote the increase of metabolites by up-regulating the transcription level of metabolic enzyme-related genes, which playing a key role in the development of atherosclerosis. This study reveals the effect of shear stress on eicosanoid metabolism in endothelial cells, which provides a novel supplement to the systems biology approach to study systemic hemodynamics.


Genetic polymorphisms of innate immunity-related inflammatory pathways and their association with factors related to type 2 diabetes.
Type 2 diabetes mellitus (T2DM) has been linked to a state of pre-clinical chronic inflammation resulting from abnormalities in the innate immune pathway. Serum levels of pro-inflammatory cytokines and acute-phase proteins, collectively known as 'inflammatory network', are elevated in the pre-, or early, stages of T2DM and increase with disease progression. Genetic variation can affect the innate immune response to certain environmental factors, and may, therefore, determine an individual's lifetime risk of disease. We conducted a cross-sectional study in 6,720 subjects from the Twins UK Registry to evaluate the association between 18 single nucleotide polymorphisms (SNPs) in five genes (TLR4, IL1A, IL6, TNFA, and CRP) along the innate immunity-related inflammatory pathway and biomarkers of predisposition to T2DM [fasting insulin and glucose, HDL- and LDL- cholesterols, triglycerides (TGs), amyloid-A, sensitive C-reactive protein (sCRP) and vitamin D binding protein (VDBP) and body mass index (BMI)]. Of 18 the SNPs examined for their association with nine metabolic phenotypes of interest, six were significantly associated with five metabolic phenotypes (Bonferroni correction, P ≤ 0.0027). Fasting insulin was associated with SNPs in IL6 and TNFA, serum HDL-C with variants of TNFA and CRP and serum sCRP level with SNPs in CRP. Cross-correlation analysis among the different metabolic factors related to risk of T2DM showed several significant associations. For example, BMI was directly correlated with glucose (r = 0.11), insulin (r = 0.15), sCRP (r = 0.23), LDL-C (r = 0.067) and TGs (r = 0.18) but inversely with HDL-C (r = -0.14). sCRP was also positively correlated (P < 0.0001) with insulin (r = 0.17), amyloid-A (r = 0.39), TGs (r = 0.26), and VDBP (r = 0.36) but inversely with HDL-C (r = -0.12). Genetic variants in the innate immunity pathway and its related inflammatory cascade is associated with some metabolic risk factors for T2DM; an observation that may provide a rationale for further studying their role as biomarkers for disease early risk prediction.


Association between cigarette smoking and prevalence of oral mucosal lesions among Malaysian army personnel.
The association between cigarette smoking and the prevalence of oral mucosal lesions was examined in 495 Malaysian army personnel. No associations between cigarette smoking and recurrent aphthous ulcerations, pre-leukoplakia and frictional keratosis could be obtained in this study. Positive associations were found between cigarette smoking and leukoedema as well as denture stomatitis. There was a negative association between cigarette smoking and the presence of coated tongue.


Soluble proteome investigation of cobalt effect on the carotenoidless mutant of Rhodobacter sphaeroides.
To investigate the surviving capability of Rhodobacter sphaeroides under phototrophic conditions in the presence of high cobalt concentration and its influence on the photosynthetic apparatus biosynthesis. Cells from R. sphaeroides strain R26.1 were grown anaerobically in a medium containing 5.0 mmol l(-1) cobalt ions and in a control medium. Metal toxicity was investigated comparing the soluble proteome of Co(2+)-exposed cells and cells grown in control medium by two-dimensional gel electrophoretic analysis. Significant changes in the expression level were detected for 43 proteins, the majority (35) being up-regulated. The enzyme porphobilinogen deaminase (PBGD) was found down-regulated and its activity was investigated. The up-regulated enzymes mainly belong to the general category of proteins and DNA degradation enzymes, suggesting that part of the catabolic reaction products can rescue bacterial growth in photosynthetically impaired cells. Furthermore, the down-regulation of PBGD strongly indicates that this key enzyme of the tetrapyrrole and bacteriochlorophyll synthesis is directly involved in the metabolic response. Data and experiments show that the cobalt detrimental effect on the photosynthetic growth of R. sphaeroides is associated with an impaired expression and functioning of PBGD.


Pregnancy outcomes in substance-misusing pregnant women: A 10-year retrospective study.
In this ten-year retrospective study we were able to show that Maltese substance-misusing mothers (SMMs) have significantly different socio-biological characteristics from mothers in the general population which seem to impact on neonatal outcomes. Significant differences from the general population were noted in the SMM's age, age at first pregnancy, marital status, educational background, number of cigarettes smoked, number of offspring and weight gained in pregnancy. SMMs booked their pregnancy in hospital later than the general population. On the other hand their infants had a lower mean birth weight and head circumference, had lower Apgar scores, were of lesser gestational age and premature. They were less breast-fed and stayed longer in hospital after their birth.


Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues.
A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized and structurally proven by spectroscopic studies such as IR, 1H NMR, and 13C NMR as well as mass spectrometry. All substances were investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acrylic acid compound 4b demonstrated the most potent cytotoxic effect with an IC50 value of 3.24 ± 0.13 μM, as compared to CA-4 (IC50 = 1.27 ± 09 μM). Additionally, acrylic acid molecule 4b displayed an inhibitory effect against β-tubulin polymerization with a percentage inhibition of 80.07%. Furthermore, compound 4b was found to produce considerable cell cycle arrest at the G2/M stage and cellular death, as demonstrated by FACS analysis. In addition, the in vivo antitumor screening of the sodium salt of acrylic acid 4b was carried out, and the results have shown that the tested molecule showed a significant decrease in viable EAC count and EAC volume, accompanied by a considerable increase in the life span prolongation, if compared to the positive control group. Furthermore, molecular modeling studies were performed to understand how the highly efficient chemicals 4b and 5e interact with the colchicine-binding region on tubulin. This work aims to shed light on the reasons behind their exceptional cytotoxicity and their better capacity to inhibit tubulin in comparison to CA-4.


Real-time database drawn from an electronic health record for a thoracic surgery unit: high-quality clinical data saving time and human resources.
The aim of the present study was to verify whether the implementation of an electronic health record (EHR) in our thoracic surgery unit allows creation of a high-quality clinical database saving time and costs. Before August 2011, multiple individuals compiled the on-paper documents/records and a single data manager inputted selected data into the database (traditional database, tDB). Since the adoption of an EHR in August 2011, multiple individuals have been responsible for compiling the EHR, which automatically generates a real-time database (EHR-based database, eDB), without the need for a data manager. During the initial period of implementation of the EHR, periodic meetings were held with all physicians involved in the use of the EHR in order to monitor and standardize the data registration process. Data quality of the first 100 anatomical lung resections recorded in the eDB was assessed by measuring the total number of missing values (MVs: existing non-reported value) and inaccurate values (wrong data) occurring in 95 core variables. The average MV of the eDB was compared with the one occurring in the same variables of the last 100 records registered in the tDB. A learning curve was constructed by plotting the number of MVs in the electronic database and tDB with the patients arranged by the date of registration. The tDB and eDB had similar MVs (0.74 vs 1, P = 0.13). The learning curve showed an initial phase including about 35 records, where MV in the eDB was higher than that in the tDB (1.9 vs 0.74, P = 0.03), and a subsequent phase, where the MV was similar in the two databases (0.7 vs 0.74, P = 0.6). The inaccuracy rate of these two phases in the eDB was stable (0.5 vs 0.3, P = 0.3). Using EHR saved an average of 9 min per patient, totalling 15 h saved for obtaining a dataset of 100 patients with respect to the tDB. The implementation of EHR allowed streamlining the process of clinical data recording. It saved time and human resource costs, without compromising the quality of data.


Valence Bond Theory Allows a Generalized Description of Hydrogen Bonding.
This paper describes the nature of the hydrogen bond (HB), B:---H-A, using valence bond theory (VBT). Our analysis shows that the most important HB interactions are polarization and charge transfer, and their corresponding sum displays a pattern that is identical for a variety of energy decomposition analysis (EDA) methods. Furthermore, the sum terms obtained with the different EDA methods correlate linearly with the corresponding VB quantities. The VBT analysis demonstrates that the total covalent-ionic resonance energy (RECS) of the HB portion (B---H in B:---H-A) correlates linearly with the dissociation energy of the HB, ΔEdiss. In principle, therefore, RECS(HB) can be determined by experiment. The VBT wavefunction reveals that the contributions of ionic structures to the HB increase the positive charge on the hydrogen of the corresponding external/free O-H bonds in, for example, the water dimer compared with a free water molecule. This increases the electric field of the external O-H bonds of water clusters and contributes to bringing about catalysis of reactions by water droplets and in water-hydrophobic interfaces.


Evaluation of choroidal and retinal thickness measurements using optical coherence tomography in non-diabetic haemodialysis patients.
The aim of this study is to evaluate the effects of haemodialysis with a high ultrafiltration rate on the choroidal and retinal thickness of non-diabetic end-stage chronic renal failure (CRF) patients using optical coherence tomography (OCT). Twenty-one eyes of 21 male CRF patients aged between 46 and 80 years were included in this prospective study. Retinal and choroidal thicknesses of the patients were measured using high-resolution OCT line scans with the activated enhanced depth imaging mode before and shortly after haemodialysis. Retinal and choroidal thickness measurements were taken at the fovea and at two points that were 1,500 μm nasal and temporal to the fovea. The relationships between the haemodynamic changes, intraocular pressure (IOP) and central corneal thickness (CCT) were also evaluated. The mean choroidal thicknesses before haemodialysis at the subfoveal, temporal and nasal locations were 232.81 ± 71.92, 212.43 ± 70.50 and 182.14 ± 68.88 μm, respectively. The mean choroidal thicknesses after haemodialysis at the subfoveal, temporal and nasal locations were 210.90 ± 65.53, 195.38 ± 66.48 and 165.19 ± 66.73 μm, respectively. There were significant differences between the choroidal thicknesses before and after haemodialysis (p < 0.001 for all). The mean retinal thicknesses before haemodialysis at the foveal, temporal and nasal locations were 215.86 ± 41.06, 308.86 ± 37.73 and 338.00 ± 33.32 μm, respectively. The mean retinal thicknesses after haemodialysis at the foveal, temporal and nasal locations were 216.90 ± 39.70, 313.86 ± 32.89 and 335.29 ± 36.85 μm, respectively. There was no significant difference between the retinal thicknesses before and after haemodialysis (p > 0.05 for all). The mean CCT decreased insignificantly from 550.48 ± 17.46 to 548.10 ± 21.12 μm (p = 0.411). The mean IOP decreased significantly from 14.09 ± 2.58 to 12.54 ± 2.23 mmHg (p = 0.003), which did not correlate with the CCT [r = (-)0.134, p = 0.562]. Haemodialysis with a high ultrafiltration volume did not alter the retinal thickness but caused a significant choroidal thinning and an IOP decrease in non-diabetic end-stage CRF patients.


Imported hantavirus cardiopulmonary syndrome in an Italian traveller returning from Cuba.
Hantavirus hemorrhagic fever with renal syndrome is endemic in Europe and Asia, while hantavirus cardiopulmonary syndrome (HCPS) is endemic in Northern, Central and Southern America. The first case of imported HCPS involving an Italian traveller returning from Cuba is reported.


Lytic polysaccharide monooxygenases (LPMOs) facilitate cellulose nanofibrils production.
Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that cleave polysaccharides through an oxidative mechanism. These enzymes are major contributors to the recycling of carbon in nature and are currently used in the biorefinery industry. LPMOs are commonly used in synergy with cellulases to enhance biomass deconstruction. However, there are few examples of the use of monocomponent LPMOs as a tool for cellulose fibrillation. In this work, we took advantage of the LPMO action to facilitate disruption of wood cellulose fibers as a strategy to produce nanofibrillated cellulose (NFC). The fungal LPMO from AA9 family (PaLPMO9E) was used in this study as it displays high specificity toward cellulose and its recombinant production in bioreactor is easily upscalable. The treatment of birchwood fibers with PaLPMO9E resulted in the release of a mixture of C1-oxidized oligosaccharides without any apparent modification in fiber morphology and dimensions. The subsequent mechanical shearing disintegrated the LPMO-pretreated samples yielding nanoscale cellulose elements. Their gel-like aspect and nanometric dimensions demonstrated that LPMOs disrupt the cellulose structure and facilitate the production of NFC. This study demonstrates the potential use of LPMOs as a pretreatment in the NFC production process. LPMOs weaken fiber cohesion and facilitate fiber disruption while maintaining the crystallinity of cellulose.


5' Caps in hnRNA: absence of m32,2,7G and size distribution of capped molecules.
In HeLa cells the "small nuclear" RNA has a cap II 5' structure (8)-- m32,2,7G(5') pppXmpYmp-- where X and Y are 2'0 methylated adenosine and uridine. In contrast hnRNA contains only cap I structures were the 2'0 methylated residue may be any base as was earlier reported for cytoplasmic mRNA (8,9,11). With a clear distinction between the source of these two caps an analysis of the size distribution of capped hnRNA could be performed which revealed over 65% of the capped hnRNA molecules were larger than cytoplasmic mRNA.


Phylogenetic analysis of kinetoplast DNA: kDNA of Leishmania tropica in Thi-Qar province, Iraq.
Cutaneous leishmaniasis (CL) is one of wobbling endemic disease in Iraq, that cause intracellular obligate protistan parasite returned to the genusLeishmania. This study is aimed to identify epidemiology of CL, detect the prevalence of Leishmania tropica and find the phylogenetic relationship. The current study was conducted in the main hospitals of Thi-Qar province-south of Iraq for period from November 2018 to October 2019. Nested-PCR was used to amplify kinetoplast minicircle fragments DNA. It was recorded 247 clinical cases with CL, the infections of males were higher than females, while infection rate appeared gradual reduction with age progress. Furthermore, the most CL infections were as single lesions and occurred in December. The infections of upper limbs were high when compared with other body regions. The molecular diagnosis showed L. tropica was more frequently. DNA sequences of kDNA gene of L. tropica showed confirmative genetic detection of local isolates using NCBI-Blast data and phylogenetic tree analysis after comparison with global recorded isolates. The local L. tropica isolates showed genetically closed related to NCBI-Blast L. tropica with accession number AB678350.1. Generally, the analysis of kDNA nitrogen bases sequences showed that all of samples were consistent with those recorded at the NCBI. The kDNA minicircle sequences analysis results showed mismatching of the local isolates decrease whenever approached from the Iranian border. In addition, genetic heterogeneity diagnosis is important for detection of therapy, control and epidemiological studies.


Prediction of Chameleonic Efficiency.
Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Å2 was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R2 =0.92) with an experimental measure of hydrogen bond donor potential, Δlog Poct-tol , was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.


Heat stress illness hospitalizations--environmental public health tracking program, 20 States, 2001-2010.
Heat stress illness (HSI), also known as heat-related illness, comprises mild heat edema, heat syncope, heat cramps, heat exhaustion (the most common type of HSI), and heat stroke (the most severe form). CDC's Environmental Public Health Tracking Program receives annual hospitalization discharge data from 23 states that are used to assess and monitor trends of HSI hospitalization over time. May-September, 2001-2010. The Environmental Public Health Tracking Program is a comprehensive surveillance system implemented in 25 states and one city health department. The core of the system is the Tracking Network, which collects data on environmental hazards, health effects, exposures, and population. The Tracking Network provides nationally consistent environmental and health outcome data that enable federal, state, and local public health agencies to assess trends, explore associations, and generate hypotheses using these data. For HSI surveillance, the Tracking Network uses state-based hospital discharge data. During 2001-2010, approximately 28,000 HSI hospitalizations occurred in 20 states participating in the Tracking Program. Data from three states were not included in this report because of missing data for ≥3 years. Two states joined the Tracking Program after the study period and also are not included in this report. The majority of HSI hospitalizations occurred among males and persons aged ≥65 years. The highest rates of hospitalizations were in the Midwest and the South. During this period, an overall 2%-5% increase in the rate of HSI hospitalizations occurred in all 20 states compared with the 2001 rate. The correlation between the average number of HSI hospitalizations and the average monthly maximum temperature/heat index was statistically significant (at p<0.0001) in all 20 states. Consistent with previous studies, age and sex were identified as major risk factors for HSI hospitalizations. Certain Tracking states that experienced high temperatures during summer months showed an increase in rate of HSI hospitalizations over the 10-year study period. HSIs are preventable and an important focus of public health interventions at state and local health departments. Federal, state, and local public health agencies can use data on HSI hospitalizations for surveillance purposes to estimate trends over time and to design targeted intervention to reduce heat stress morbidity among at-risk populations.


AP-Loss for Accurate One-Stage Object Detection.
One-stage object detectors are trained by optimizing classification-loss and localization-loss simultaneously, with the former suffering much from extreme foreground-background class imbalance issue due to the large number of anchors. This paper alleviates this issue by proposing a novel framework to replace the classification task in one-stage detectors with a ranking task, and adopting the average-precision loss (AP-loss) for the ranking problem. Due to its non-differentiability and non-convexity, the AP-loss cannot be optimized directly. For this purpose, we develop a novel optimization algorithm, which seamlessly combines the error-driven update scheme in perceptron learning and backpropagation algorithm in deep networks. We provide in-depth analyses on the good convergence property and computational complexity of the proposed algorithm, both theoretically and empirically. Experimental results demonstrate notable improvement in addressing the imbalance issue in object detection over existing AP-based optimization algorithms. An improved state-of-the-art performance is achieved in one-stage detectors based on AP-loss over detectors using classification-losses on various standard benchmarks. The proposed framework is also highly versatile in accommodating different network architectures. Code is available at https://github.com/cccorn/AP-loss.


The IL-6 rs1800795 and rs1800796 polymorphisms are associated with coronary artery disease risk.
Studies examining the associations between the interleukin-6 (IL-6) rs1800795 and rs1800796 gene polymorphisms and risk of coronary artery disease (CAD) remain controversial. Our aim was to evaluate the accurately determine role of these two polymorphisms in CAD risk. PubMed, Embase, VIP, Wan fang and China National Knowledge Infrastructure databases were searched. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The trial sequential analysis (TSA) was conducted, and bioinformatics tools were employed. A total of thirty-seven articles were obtained. For the IL-6 rs1800795 polymorphism, 9411 CAD patients and 3161 controls were included, 4720 patients with CAD, and 5000 controls were included for the IL-6 rs1800796 polymorphism. In the pooled analysis, significant associations were only observed for the rs1800796 polymorphism (allelic: OR [95%CI] = 1.28 [1.13, 1.44], dominant: OR [95%CI] = 1.35 [1.17, 1.57], recessive: OR [95%CI] = 1.35 [1.18, 1.55], heterozygote: OR [95%CI] = 1.26 [1.15, 1.37], homozygote: OR [95%CI] = 1.62 [1.23, 2.13]). Significant associations were detected in the Asian and Mongoloid populations and 'more than 500' subgroup for the rs1800795 polymorphism. TSA confirmed the true-positive results for the rs1800796 polymorphism. The bioinformatics analysis showed that the two polymorphisms played important roles in the gene transcription. The IL-6 rs1800796 polymorphism is associated with an increased susceptibility to CAD and is a risk factor for CAD. The IL-6 rs1800795 polymorphism is associated with an increased risk of CAD in Asians, particularly in Chinese, and a decreased risk of CAD in an African population is remarkably observed.


Predictable Substituent Control of CoIII/II Redox Potential and Spin Crossover in Bis(dipyridylpyrrolide)cobalt Complexes.
A family of five easily prepared tridentate monoanionic 2,5-dipyridyl-3-(R1)-4-(R2)-pyrrolide anions (dppR1,R2)-, varying in the nature of the R1 and R2 substituents [R1, R2 = CN, Ph; CO2Et, CO2Et; CO2Me, 4-Py; CO2Me, Me; Me, Me], has been used to generate the analogous family of neutral [CoII(dppR1,R2)2] complexes, two of which are structurally characterized at both 100 and 298 K. Both the oxidation and spin states of these complexes can be switched in response to appropriate external stimuli. All complexes, except [CoII(dppMe,Me)2], exhibit gradual spin crossover (SCO) in the solid state, and SCO activity is observed for three complexes in CDCl3 solution. The cobalt(II) centers in the low spin (LS) complexes are Jahn-Teller tetragonally compressed along the pyrrolide-Co-pyrrolide axis. The complexes in their high spin (HS) states are more distorted than in the LS states, as is also usually the case for SCO active iron(II) complexes. The reversible CoIII/II redox potentials are predictably tuned by choice of substituents R1 and R2, from -0.95 (Me,Me) to -0.45 (CN,Ph) V vs Fc+/Fc, with a linear correlation observed between E1/2(CoIII/II) and the Swain-Lupton parameters of the pyrrolide substituents.


Health-related life satisfaction and its influencing factors: A cross-sectional study in China.
With the rapid development of science and technology, the pace of life has accelerated. Health and life satisfaction issues of persons are gaining more attention. China, Japan, Malaysia, and Taiwan conducted international cooperative research on health of four regional populations. This research was a part of the study in mainland China, which aimed to explore health-related life satisfaction and its influencing factors on large samples in mainland China. A random group of 1404 persons from universities, factories, companies, and elderly centers in Changchun completed a structured questionnaire. This study centered on life satisfaction indicators, which included the current whole life, income, family relationships, peer relationships, relationships with the neighbors, living environment, personal health, family health, spare time, and housework share. Other collected data included the Body Mass Index, blood pressure, self-rated health, Breslow's seven health practices, medical treatment within the past 6 months, physical examinations, General Health Questionnaire (GHQ)-12 Scale, social activities, networking relationships with persons around the community, social support, and sociodemographic variables. Associations between life satisfaction, demographics, and health-related variables were analyzed through a multiway ANOVA. The living environment and income of Chinese persons were related to their low life satisfaction. The multiway ANOVA showed that the independent relationship of self-rated health, regular physical examinations, GHQ-12 Scale, trust in the community, communication with the neighbors, education, and age related with life satisfaction accounting for 20.3% of the variance. Education and age showed interactive effects on life satisfaction. This study identified seven factors that influenced the life satisfaction of persons in mainland China. Life satisfaction can be enhanced through interventions to improve self-rated health, regular physical examinations, mental health, trust in the community, communication with the neighbors, education, and improvement in the health service.


Theoretical and experimental studies on ionic currents in nanopore-based biosensors.
Novel generation of analytical technology based on nanopores has provided possibilities to fabricate nanofluidic devices for low-cost DNA sequencing or rapid biosensing. In this paper, a simplified model was suggested to describe DNA molecule's translocation through a nanopore, and the internal potential, ion concentration, ionic flowing speed and ionic current in nanopores with different sizes were theoretically calculated and discussed on the basis of Poisson-Boltzmann equation, Navier-Stokes equation and Nernst-Planck equation by considering several important parameters, such as the applied voltage, the thickness and the electric potential distributions in nanopores. In this way, the basic ionic currents, the modulated ionic currents and the current drops induced by translocation were obtained, and the size effects of the nanopores were carefully compared and discussed based on the calculated results and experimental data, which indicated that nanopores with a size of 10 nm or so are more advantageous to achieve high quality ionic current signals in DNA sensing.


[Capsulo-synovial lesions of the hip joint at the stage of total prosthesis implantation. Study based on 328 cases].
The authors have made a systematic study of specimens of synovium and capsule removed during total hip replacement for slowly and rapidly progressive arthritis, rheumatoid coxarthritis and necrosis. Out of 1 120 cases, there were 328 tissue samples suitable for satisfactory morphological interpretation. A number of conclusions are drawn from the detailed analysis of the different types of lesion. The vast majority of cases of common arthritis consist of hyperplastic and degenerative metamorphic lesions often associated with signs of inflammation. The dominant feature at this stage of coxarthritis is the histiocytic macrophage response to foreign bodies of bone and joint cartilage; it is frequent in rapidly progressive arthritis and necrosis. Several cases of synoviocytic and pseudo-tumour histiocytic hyperplasia are identified, as well as myxoid and amyloid degenerative disease of connective tissue and microcrystal formation.


Poisoning in goats by the monofluoracetate-containing plant Palicourea aeneofusca (Rubiaceae).
The epidemiological, clinical and pathological aspects of a spontaneous outbreak of Palicourea aeneofusca poisoning in goats are reported. The main clinical signs were motor incoordination, generalized muscle tremors, broad-based posture, tachypnea, tachycardia, vocalization and respiratory distress. Two goats died 5 and 20 min after the observation of the first clinical signs. Another that was found recumbent died 80 h later. One goat with mild clinical signs recovered. Congestion and hemorrhages were observed macroscopically and histologically in most organs. Pulmonary edema was also observed. The main microscopic findings consisted of cytoplasmic vacuolization and necrosis of the renal tubular epithelium. The average concentration of monofluoroacetate obtained in sixteen samples of P. aeneofusca was 0.29 ± 0.17%. It is concluded that P. aeneofusca is toxic to goats under natural conditions.


Activation of kidney-directed neurons in the lamina terminalis by alterations in body fluid balance.
This study was undertaken to determine if neurons in the lamina terminalis, previously identified as projecting to the kidney (35), were responsive to alterations in stimuli associated with fluid balance homeostasis. Neurons in the lamina terminalis projecting to the kidney were identified by the retrograde transynaptic transport of Bartha's strain of pseudorabies virus in anesthetized rats. Rats were also exposed to 24-h water deprivation, intravenous hypertonic saline, or intracerebroventricular ANG II. To determine if "kidney-directed" neurons were activated following each stimulus, brain sections that included the lamina terminalis were examined immunohistochemically for viral antigen and Fos protein. With the exception of ANG II in the subfornical organ, all regions of the lamina terminalis contained neurons that were significantly activated by water deprivation, hypertonic saline, and ANG II. These results provide evidence for a neural substrate, which may underpin some of the effects of hypertonic saline and ANG II on renal function thought to be mediated through the lamina terminalis.


Electroacupuncture pretreatment protects against anesthesia/surgery-induced cognitive decline by activating CREB via the ERK/MAPK pathway in the hippocampal CA1 region in aged rats.
Effective preventive measures against postoperative cognitive dysfunction in older adults are urgently needed. In this study, we investigated the effect of electroacupuncture (EA) on anesthesia and surgery-induced cognitive decline in aged rats by RNA-seq analysis, behavioral testing, Golgi-Cox staining, dendritic spine analysis, immunofluorescence assay and western blot analysis. EA ameliorated anesthesia and surgery induced-cognitive decline. RNA-seq analysis identified numerous differentially-expressed genes, including 353 upregulated genes and 563 downregulated genes, after pretreatment with EA in aged rats with postoperative cognitive dysfunction. To examine the role of CREB in EA, we injected adeno-associated virus (AAV) into the CA1 region of the hippocampus bilaterally into the aged rats to downregulate the transcription factor. EA improved synaptic plasticity, structurally and functionally, by activating the MAPK/ERK/CREB signaling pathway in aged rats. Together, our findings suggest that EA protects against anesthesia and surgery-induced cognitive decline in aged rats by activating the MAPK/ERK/CREB signaling pathway and enhancing hippocampal synaptic plasticity.


In memoriam: Continuing my journey through Project LEAD.
The author spent 20 years serving in leadership positions on a local and national level. Before attending Project LEAD, the author did not value mentorship because she believed that mentoring was limited to neophyte nurses. After her experience at Project LEAD, she realized the importance of having a mentor who knew her strengths and weaknesses, and provided consistent guidance. She also realized that a mentor could also help her avoid some of the obstacles she faced during her leadership journey. Although she had some guidance from colleagues, the Project LEAD experience was instrumental in exposing her to different leadership styles and in showing her the need for mentorship on a consistent basis. The author 's mentor from Project LEAD helped her make the transition from being the head of a department to working as a faculty member who is using her leadership skills to establish collaborations with community leaders.


Glycated human albumin alters mitochondrial respiration in preadipocyte 3T3-L1 cells.
Diabetes and obesity are strongly associated with increased levels of circulating advanced glycation end products (AGEs) and reactive oxygen species (ROS). These two molecular phenomena affect the physiology of adipose tissue, a biological driver of the metabolic syndrome, leading to an inflammatory profile and insulin resistance, which could contribute to obesity/diabetes-associated complications, such as cardiovascular diseases. Herein, we investigated the impact of AGEs on mitochondrial bioenergetics in murine preadipocyte cells (3T3-L1) and cellular redox homeostasis. We show that incubation of preadipocytes with AGEs stimulates mitochondrial activity and respiration while inducing oxidative stress. This AGE-induced intracellular ROS production was blocked by diphenylene iodonium, an NAD(P)H oxidase inhibitor. In parallel, antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were found to be activated upon AGE treatment. Our results suggest that AGE-induced oxidative stress is generated by NAD(P)H oxidase and leads to a cellular proliferation arrest associated with enhanced mitochondrial metabolism and biogenesis, and with increased levels of ROS-detoxifying enzymes, as well. These new data show how AGEs may be involved in hyperglycemia-induced oxidative damage in preadipocytes and their potential links to diabetes progression. © 2017 BioFactors, 43(4):577-592, 2017.


Changes in psychosocial and physical working conditions and psychotropic medication in ageing public sector employees: a record-linkage follow-up study.
To investigate whether changes in psychosocial and physical working conditions are associated with subsequent psychotropic medication in ageing employees. Data were from the Helsinki Health Study, a cohort study of Finnish municipal employees, aged 40-60 years at phase 1 (2000-2002). Changes in psychosocial and physical working conditions were measured between phase 1 and phase 2 (2007). Survey data were longitudinally linked to data on prescribed, reimbursed psychotropic medication purchases (Anatomical Therapeutic Chemical) obtained from the registers of the Social Insurance Institution of Finland between the phase 2 survey and December 2013 (N=3587; 80% women). Outcomes were any psychotropic medication; antidepressants (N06A); anxiolytics (N05B); and sedatives and hypnotics (N05C). Cox regression analyses were performed. During the follow-up, 28% of the participants were prescribed psychotropic medication. Repeated exposures to low job control, high job demands and high physical work load were associated with an increased risk of subsequent antidepressant and anxiolytic medication. Increased and repeated exposure to high physical work load, increased job control and repeated high job demands were associated with subsequent sedative and hypnotic medication. Age and sex-adjusted HR varied from 1.18 to 1.66. Improvement in job control was associated with a lower risk of anxiolytic, but with a higher risk of sedatives and hypnotic medication. Decreased physical work load was associated with a lower risk of antidepressant and anxiolytic medications. Improvement in working conditions could lower the risk of mental ill-health indicated by psychotropic medication.


Fasting and Postprandial Hyperglycemia: Their Predictors and Contributions to Overall Hyperglycemia in Korean Patients with Type 2 Diabetes.
This study aimed to identify factors that affect fasting hyperglycemia (FHG) and postprandial hyperglycemia (PPG) and their contributions to overall hyperglycemia in Korean patients with type 2 diabetes mellitus (T2DM). This was a retrospective study conducted on 194 Korean T2DM patients with 7-point self-monitoring blood glucose (SMBG) profiles plotted in 4 days in 3 consecutive months. We calculated the areas corresponding to FHG and PPG (area under the curve [AUC]FHG and AUCPPG) and contributions (%) in the graph of the 7-point SMBG data. The levels of glycated hemoglobin (HbA1c) were categorized by tertiles, and the contributions of FHG and PPG were compared. The relative contribution of FHG increased (44.7%±5.6%, 58.0%±4.4%, 66.5%±2.8%; PANOVA=0.002, PTREND <0.001), while that of PPG decreased (55.3%±5.5%, 42.0%±4.4%, 33.5%±2.8%; PANOVA=0.002, PTREND <0.001) with the elevated HbA1c. Multivariate analysis showed that HbA1c (β=0.615, P<0.001), waist circumference (β=0.216, P=0.042), and triglyceride (β=0.121, P=0.048) had a significant association with AUCFHG. Only HbA1c (β=0.231, P=0.002) and age (β=0.196, P=0.009) was significantly associated with AUCPPG. The data suggested that in Korean T2DM patients, FHG predominantly contributed to overall hyperglycemia at higher HbA1c levels, whereas it contributed to PPG at lower HbA1c levels. It is recommended that certain factors, namely age, degree of glycemic control, obesity, or triglyceride levels, should be considered when prescribing medications for T2DM patients.


The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis.
Currently, nivolumab and ipilimumab are the most widely used immune checkpoint inhibitors. We performed a meta-analysis to evaluate the efficacy and treatment-related adverse events (TRAEs) of nivolumab plus ipilimumab therapy in cancer treatment. We examined data from PubMed, Web of Science, EBSCO, and Cochrane Library. Eleven articles fulfilled our criteria, which we divided into 3 groups: nivolumab plus ipilimumab versus nivolumab (the dose used for monotherapy is 3 mg/kg), nivolumab plus ipilimumab versus ipilimumab (the dose used for monotherapy is 3 mg/kg), and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3) versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1). We measured the complete response (CR), partial response (PR), objective response rate (ORR), and TRAEs in any grade and grade 3 or higher. The overall effect estimate favored the combined immunotherapy group in terms of the ORR (RR: 1.40, p < 0.001) and PR (RR: 1.50, p < 0.001) than nivolumab alone. Compared with ipilimumab alone, the combined immunotherapy group had better CR (RR: 4.89, p < 0.001), PR (RR: 2.75, p < 0.001), and ORR (RR: 3.31, p < 0.001). Finally, N1I3 showed better PR (RR: 1.35, p = 0.006) and ORR (RR: 1.21, p = 0.03) than N3I1. The incidence of any TRAEs was similar between both groups (RR: 1.05, p = 0.06). However, the incidence of serious adverse events (grade 3 or higher) was lower in group N3I1 than group N1I3 (RR: 1.51, p < 0.001). This meta-analysis showed that the curative effect of nivolumab plus ipilimumab was better than that of nivolumab or ipilimumab monotherapy. In the combined immunotherapy group, N1I3 was more effective than N3I1. Although the side effects were slightly increased in N1I3 group, overall safety was acceptable.


Rapid distinction between Leptospira interrogans and Leptospira biflexa by PCR amplification of 23S ribosomal DNA.
Bacterial specific primers were used to amplify 23S rRNA genes from a representative strain from each of the 23 serogroups of the pathogenic Leptospira interrogans and 8 strains from 6 serogroups of the non-pathogenic Leptospira biflexa. Only regions of extreme variability, which had been identified on the basis of homology-based search of all the 23S rRNA sequences available in GenBank database, were sequenced from the amplified products. PCR primers that had the potential to distinguish L. interrogans from L. biflexa species were designed from the derived sequences and a sensitive PCR protocol developed. The PCR method enabled the differentiation of the 59 strains of the 23 serogroups of L. interrogans from the 8 strains of 6 serogroups of L. biflexa. Further investigation by 16S rDNA sequencing of two strains of L. interrogans, which gave unexpected PCR results, provided evidence that they had been misclassified and hence we propose to reassign them to L. biflexa.


A statewide investigation of geographic lung cancer incidence patterns and radon exposure in a low-smoking population.
Lung cancer is the leading cause of cancer-related mortality in Utah despite having the nation's lowest smoking rate. Radon exposure and differences in lung cancer incidence between nonmetropolitan and metropolitan areas may explain this phenomenon. We compared smoking-adjusted lung cancer incidence rates between nonmetropolitan and metropolitan counties by predicted indoor radon level, sex, and cancer stage. We also compared lung cancer incidence by county classification between Utah and all SEER sites. SEER*Stat provided annual age-adjusted rates per 100,000 from 1991 to 2010 for each Utah county and all other SEER sites. County classification, stage, and sex were obtained from SEER*Stat. Smoking was obtained from Environmental Public Health Tracking estimates by Ortega et al. EPA provided low (< 2 pCi/L), moderate (2-4 pCi/L), and high (> 4 pCi/L) indoor radon levels for each county. Poisson models calculated overall, cancer stage, and sex-specific rates and p-values for smoking-adjusted and unadjusted models. LOESS smoothed trend lines compared incidence rates between Utah and all SEER sites by county classification. All metropolitan counties had moderate radon levels; 12 (63%) of the 19 nonmetropolitan counties had moderate predicted radon levels and 7 (37%) had high predicted radon levels. Lung cancer incidence rates were higher in nonmetropolitan counties than metropolitan counties (34.8 vs 29.7 per 100,000, respectively). Incidence of distant stage cancers was significantly higher in nonmetropolitan counties after controlling for smoking (16.7 vs 15.4, p = 0.02*). Incidence rates in metropolitan, moderate radon and nonmetropolitan, moderate radon counties were similar. Nonmetropolitan, high radon counties had a significantly higher incidence of lung cancer compared to nonmetropolitan, moderate radon counties after adjustment for smoking (41.7 vs 29.2, p < 0.0001*). Lung cancer incidence patterns in Utah were opposite of metropolitan/nonmetropolitan trends in other SEER sites. Lung cancer incidence and distant stage incidence rates were consistently higher in nonmetropolitan Utah counties than metropolitan counties, suggesting that limited access to preventative screenings may play a role in this disparity. Smoking-adjusted incidence rates in nonmetropolitan, high radon counties were significantly higher than moderate radon counties, suggesting that radon was also major contributor to lung cancer in these regions. National studies should account for geographic and environmental factors when examining nonmetropolitan/metropolitan differences in lung cancer.


Nonequilibrium molecular dynamics calculation of the thermal conductivity based on an improved relaxation scheme.
A nonequilibrium molecular dynamics (NEMD) method using stochastic energy injection and removal as uniform heat sources and sinks is developed to calculate the thermal conductivity. The stochastic energy is generated by a Maxwell function generator and is imposed on only a few individual molecules each time step. The relaxation of the thermal perturbation is improved compared to other NEMD algorithms because there are no localized heat source and sink slab regions in the system. The heat sources are uniformly distributed in the right half of the system while the sinks are in the left half, which leads to a periodically quadratic temperature distribution that is almost sinusoidal. The thermal conductivity is then easily calculated from the mean temperatures of the right and left half systems rather than by fitting the temperature profiles. This improved relaxation NEMD scheme is used to calculate the thermal conductivities of liquid and solid argons. It shows that the present algorithm gives accurate results with fast convergence and small size effects. Other stochastic energy perturbation, e.g., thermal noise, can be used to replace the Maxwell-type perturbation used in this paper to make the improved relaxation scheme more effective.


Galectin-3 ablation does not affect infarct size or inflammatory cytokines after experimental stroke in 24-month-old female mice.
The tissue damage following a focal stroke causes an inflammatory response that is thought to aggravate the disease state. Galectin-3 is a proinflammatory molecule that has been shown to play a significant role in the inflammatory responses in brain diseases and following experimental stroke. In most animal experiments, young animals are used, although attempts are often made to model diseases that affect the elderly. Therefore, in this project, we intended to investigate the role of Galectin-3 in experimental stroke in older mice. In this project, 24-month-old (aged) female mice were subjected to an experimental stroke (permanent middle cerebral artery occlusion) 7 days before sacrifice. We wanted to investigate whether the absence of the inflammatory protein Galectin-3 could affect motor phenotype, neuroinflammation and infarct size. Number of mice without Galectin-3 (Galectin-3 KO) = 9, number of wildtype controls of the same age = 6. In our aged female mice, we could not observe any significant differences between Galectin-3 KO and wildtype regarding the inclined plane test or cylinder test. We could not observe different infarct sizes between the two genotypes. In brain homogenates, we measured levels of 10 inflammatory cytokines, but we could not see any significant differences in any of them. In summary, it can be said that the absence of the inflammatory mediator Galectin-3 does not seem to have a strong poststroke effect in aged females. Unfortunately, we could not analyze these mice with immunohistochemistry, which limited our study.


Paracellular back-diffusion of H+ across bullfrog fundic mucosa resulting from Ca2+ depletion and its effects on taurocholate-induced mucosal injury.
The effects of calcium depletion (by washout and by chelation with EDTA) on the net appearance of hydrogen ions (H+) on the secretory surface of in vitro sheets of bullfrog fundic mucosa have been studied. A CO2 distribution method was used to distinguish between true and apparent inhibition of H+ secretion. Our data indicate that Ca2+ depletion produces apparent inhibition of H+ secretion by increasing paracellular back-diffusion of H+ across the mucosa. Ca2+ washout resulted in a decrement of measurable H+ (1.42 +/- 0.07 to 0.93 +/- 0.09 muEq/cm2 hr-1, P less than 0.05) without altering delta CO2 (1.18 +/- 0.15 to 1.26 +/- 0.17 muEq/cm2 hr-1, not significant). Chelation of Ca2+ with EDTA produced a similar decrease in H+ (1.61 +/- 0.09 to 0.78 +/- 0.12 muEq/cm2 hr-1, P less than 0.05) without affecting delta CO2 (1.60 +/- 0.13 to 1.68 +/- 0.22 muEq/cm2 hr-1, not significant). The possibility that H+ back-diffusion (induced by Ca2+ depletion) via a paracellular shunt might ameliorate injury was examined in bullfrog fundic mucosa exposed to a bile salt. H+ secretion, potential difference, resistance, and ultrastructural changes were studied in isolated mucosal sheets treated with 10 mM sodium taurocholate with or without Ca2+ depletion. Measurable H+, potential difference, and resistance were significantly lower in the Ca2+ depleted tissues. Scanning electron microscopy revealed identical changes in the surface epithelial cells of both depleted and nondepleted mucosae, but there was significantly less cell loss from depleted mucosae (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Performance responses of lactating Rahmani ewes fed diet supplemented with Enterococcus faecium NRC-3 or Lactobacillus rhamnosus.
Production of new types of probiotics for animal nutrition mainly depends on the appropriate bacterial strain and efficient substrate. Therefore, this study aimed to evaluate the impact of two probiotic strains containing 1.2 × 108 (CFU/g), produced on permeate media on performance responses of Rahmani ewes. Thirty early lactating ewes (about 2-3 years old and weighting on average 43.2 ± 0.3 kg) were randomly divided into three groups of 10 animals each using a completely randomized design. The 1st group was fed the basal diet (60% concentrate feed mixture (CFM) + 30% Egyptian clover + 10% bean straw). While the ewes in 2nd and 3rd groups were fed the basal diet + 2 g of Enterococcus faecium NRC-3(EF) and Lactobacillus rhamnosus (LR), respectively for 9 weeks. Ewes' diet supplementation with EF or LR increased (p < 0.05) dry matter, organic matter, crude protein, neutral detergent fiber, acid detergent fiber, and non-structural carbohydrates digestibility compared to ewes of the control group. Glucose, total protein, and albumin concentrations significantly increased in the blood of EF ewes than those of LR and control. Probiotics increased ewes' milk yield as well as milk protein, fat, and lactose yields, but no differences were observed between treatments when milk components were expressed as percentage. Milk fatty acids profile not changed due to EF or LR supplementation. Probiotics (E. faecium and L. rhamnosus) produced on cheese industry waste (permeate) have proven their ability to improve the productive performance of the lactating Rahmani ewes.


Desmoplastic fibroma of the mandible: report of case.
Desmoplastic fibroma of the bone is a rare tumor; only 48 cases of the disease have ever been reported. The tumor has most often been observed in the metaphysis of long bones. Nine cases of the lesion have been reported in the mandible. The lesion occurred in the left mandibular body of one of our patients. We treated the entity by surgically removing the tumor and concurrently reconstructing the jaw with a bone graft taken from the iliac crest. There has been no recurrence a year and eight months postoperatively.


Disulfide-Bridged (Mo3S11) Cluster Polymer: Molecular Dynamics and Application as Electrode Material for a Rechargeable Magnesium Battery.
Exploring novel electrode materials is critical for the development of a next-generation rechargeable magnesium battery with high volumetric capacity. Here, we showed that a distinct amorphous molybdenum sulfide, being a coordination polymer of disulfide-bridged (Mo3S11) clusters, has great potential as a rechargeable magnesium battery cathode. This material provided good reversible capacity, attributed to its unique structure with high flexibility and capability of deformation upon Mg insertion. Free-terminal disulfide moiety may act as the active site for reversible insertion and extraction of magnesium.


Specific heat and Lindemann-like parameter of metallic clusters: mono- and polyvalent metals.
The Brownian-type molecular dynamics simulation is revisited and applied to study the thermal and geometric properties of four mono- and two polyvalent metallic clusters. For the thermal property, we report the specific heat at constant volume CV and study the solid-liquid-like transition by scrutinizing its characteristic. For the geometric property, we calculate the root mean square relative bond-length fluctuation delta as a function of increasing temperature. The thermal change in delta reflects the movement of atoms and hence is a relevant parameter in understanding the phase transition in clusters. The simulated results for the CV of alkali and aluminum clusters whose ground state structures exhibit icosahedral symmetry generally show one phase transition. In contrast, the tetravalent lead is quite often seen to exhibit two phase transitions, a premelting process followed by a progressive melting. In connection with the premelting scenario, it is found here that those (magic number) clusters identified to be of lesser stability (among other stable ones) according to the second energy difference are clusters showing a greater possibility of undergoing premelting process. This energy criterion applies to aluminum clusters nAl=28 and 38. To delve further into the thermal behavior of clusters, we have analyzed also the thermal variation of deltaT and attempted to correlate it with CV(T). It turns out that the premelting (if exist) and melting temperatures of the smaller size clusters (n less, similar 50) extracted from CV do not always agree quantitatively with that deduced from delta.


Soft landing of polyatomic anions onto three-dimensional semiconductive and conductive substrates.
Soft landing of well-characterized polyoxometalate anions, PW12O40 3- (WPOM) and PMo12O40 3- (MoPOM), was carried out to explore the distribution of anions in the semiconducting 10 and 6 μm-long vertically aligned TiO2 nanotubes as well as 300 μm-long conductive vertically aligned carbon nanotubes (VACNTs). The distribution of soft-landed anions on the surfaces and their penetration into the nanotubes were studied using energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM). We observe that soft landed anions generate microaggregates on the TiO2 nanotubes and only reside in the top 1.5 μm of the nanotube height. Meanwhile, soft landed anions are uniformly distributed on top of VACNTs and penetrate into the top 40 μm of the sample. We propose that both the aggregation and limited penetration of POM anions into TiO2 nanotubes is attributed to the lower conductivity of this substrate as compared to VACNTs. This study provides first insights into the controlled modification of three dimensional (3D) semiconductive and conductive interfaces using soft landing of mass-selected polyatomic ions, which is of interest to the rational design of 3D interfaces for electronics and energy applications.


Testicular torsion in infants and children: diagnosis with Doppler sonography.
The accuracy of Doppler sonography in the evaluation of testicular torsion was tested in 65 boys (aged 0-18 years) with acute scrotal pain or swelling. All patients underwent pulsed Doppler sonography of both testes, followed by scintigraphy (n = 16) and/or surgery (n = 34) and a close clinical follow-up for 4-8 months (n = 31). Color Doppler sonography was performed in 29 patients. The testicular artery was deemed patent if Doppler shifts from branches within the parenchyma could be found. Surgery revealed 19 cases of testicular torsion, 17 of which were diagnosed with Doppler sonography. There were six technical failures, in which no signals could be found on either side. In four boys, no color signals were obtained in either testis but subsequent examination with a mechanical sector scanner and pulsed Doppler sonography yielded arterial signals. Doppler sonography was successful in 59 of 65 boys (91%) and yielded a sensitivity of 89% and specificity of 100%. Pulsed Doppler sonography with mechanical sector scanners was more sensitive than color Doppler sonography. Intermittent torsion was missed both with Doppler sonography and scintigraphy.


Prevalence and Associated Factors of Poststroke Depression among Outpatient Stroke Patients Who Have a Follow-Up at the Outpatient Neurology Clinic of Zewditu Memorial Hospital in Addis Ababa, Ethiopia.
Poststroke depression is the most common and burdensome poststroke psychiatric complication. Studies showed discrepancies in reporting frequencies and risk factors for poststroke depression. Updated local data are relevant for efficient strategies of poststroke depression screening and prevention. To determine the prevalence and associated factors of poststroke depression among outpatient stroke patients from the outpatient neurology clinic of Zewditu Memorial Hospital in Addis Ababa, Ethiopia. An institution-based cross-sectional study was conducted on 249 stroke patients. Data was collected through structured questionnaire using interviews and a review of medical charts. PHQ-9 depression questionnaire was used to diagnose poststroke depression. Descriptive analysis was used to see the nature of the characteristics of interests. Bivariate analysis was used to sort out variables at p values less than 0.05 for multivariate logistic regression. Significance level was obtained using an odds ratio with 95% CI and p value < 0.05. Point prevalence for poststroke depression was 27.5 percent. Female gender, unemployment, low social support level, diabetes mellitus, and poststroke period under 2 years were statistically significant and independent predictors for poststroke depression. The point prevalence estimate of poststroke depression was comparable with other studies. Low social support levels increased the odds for poststroke depression by more than eight folds. It appeared that external factors are more important in the pathogenesis of poststroke depression in the African population. Detection and prevention programs should consider disparities of poststroke depression incidence and risk factors.


Physiologic variations in granulocytic surface antigen expression: impact of age, gender, pregnancy, race, and stress.
There is a growing interest in the use of granulocytic surface markers for the diagnosis of some inherited and acquired disorders, such as Shwachman-Diamond syndrome and myelodysplastic syndromes. Understanding the impact of physiologic factors, such as age, gender, pregnancy, race, and stress on granulocytic surface markers is essential for appropriate interpretation of results. Some surface markers show marked variations at the very early and the very late stages in life. Fetal granulocytes tend to have a lower expression of CD11b, CD11c, CD18, and CD32. Term neonatal granulocytes are frequently associated with a lower expression of CD10, CD11b, CD13, CD33, and CD62L and a higher expression of CD55 and CD64. Elderly individuals have shown a higher expression of CD64. Pregnancy is associated with temporary changes in granulocytic surface markers, such as a lower expression of CD16 and a higher CD64, partially mimicking an inflammatory response. Stress also has an impact on some surface markers, particularly adhesion molecules, such as CD62L and CD54. These factors need to be taken in consideration for the optimal interpretation of granulocytic surface marker studies.


Effect of NG-nitro-L-arginine on pressor action of arginine vasopressin in normotensive (WKY) and spontaneously hypertensive (SHR) rats.
In order to find out whether the pressor effect of arginine vasopressin (AVP) is limited by release of nitric oxide (NO) and whether it is altered in hypertension, blood pressure (MAP) and heart rate (HR) responses to i.v. administration of AVP were compared in conscious normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats under control conditions and during blockade of NO synthesis induced by i.v. administration of NG-nitro-L-arginine (L-NOARG). In control experiments AVP elicited significant elevations of MAP in WKY and SHR. The maximum increases in WKY and SHR amounted 26 +/- 3 and 16 +/- 3 mmHg, respectively, and did not differ significantly from each other. In WKY increase of MAP was associated with significant bradycardia. Administration of AVP in this strain during blockade of NO synthesis resulted in significantly smaller increase of blood pressure (13 +/- 5 mmHg) than under control conditions (p < 0.001), and in nonsignificant changes of HR. In SHR AVP caused a progressive significant decrease of blood pressure associated with transient tachycardia. The results indicate that blockade of NO synthesis does not enhance but reduces increase of blood pressure in WKY and transforms the pressor action of this peptide into the hypotensive effect in SHR. This phenomenon is discussed in relevance to the possible unfavorable effects of AVP on coronary and/or cerebral circulation during blockade of NO formation.


[Interleukin-38 expression and clinical significance in serum of patients with chronic obstructive pulmonary disease].
Objective: To investigate the serum level of interleukin-38 (IL-38) and its clinical significance in patients with chronic obstructive pulmonary disease (COPD). Methods: Totally 72 patients with acute exacerbation of COPD (AECOPD group) and 65 patients with stable COPD (S-COPD group) were recruited from Tianjin Chest Hospital from June 2016 to August 2017. In the same period 40 elderly healthy subjects were selected as control group (C group). The general data and laboratory examination results of these subjects were recorded. Serum IL-38 was measured by double antibody enzyme-linked immunosorbent assays (ELISA). The inter-group differences of above parameters were analyzed. Pearson correlation or Spearman rank correlation analysis was used to analyze the correlation between IL-38 and each variable, and multivariate stepwise regression analysis was used to determine the influencing factors of serum IL-38 in COPD patients. Results: The serum level of IL-38 was higher in AECOPD group than in S-COPD group[(57.88±13.72) vs (51.75±14.06) ng/L, P<0.05], and was higher in either of the two COPD groups than in C group[(46.37±13.18) ng/L](both P<0.05). Correlation analysis of single factor showed that serum IL-38 levels were positively correlated with body mass index (r=0.190, P<0.05), and negatively correlated with C reactive protein (CRP), fibrinogen (FIB), forced expiratory volume in one second as a percentage of estimated value (FEV1%pred) and the number of acute exacerbations in the past 1 year (r=-0.344, -0.176, -0.195, -0.229, all P<0.05). The CRP level and the number of acute exacerbations in the past 1 year were independent factors affecting the serum level of IL-38 (β=-0.204, -0.183, both P<0.05) in patients with COPD. Conclusion: IL-38 is compensatory increased in serum of patients with COPD and may be used as one of the serological markers for evaluation of COPD.


Diurnal time courses in psychomotor performance and waking EEG frequencies.
The present study examined the similarities between the diurnal time courses in the waking EEG activity and the psychomotor performance. The aim was to verify if some ongoing changes in the excitability of the cortical nerve cells across the daytime could facilitate the sensorimotor processing. EEG recordings and performance results for the Four Choice Reaction Time Test (FCRTT) were obtained every two hours, from morning to late evening period, in 8 young normal subjects (21.3 +/- 0.5 years). ANOVAs were used to verify the presence of diurnal variations in the two measures. Nonparametric correlations were obtained to test the similarity between the changes across the day in the two measures. Three EEG frequency bands (delta, sigma, and beta1) and the reaction time measures varied across the daytime. The changes in the sigma (12.00-13.75 Hz) and the beta1 (14.00-19.75 Hz) bands were similar to the diurnal variations in the reaction time measures. It is suggested that the changes in the sigma and the beta1 bands may facilitate the processing of the sensorimotor treatment.


Are there other persistent organic pollutants? A challenge for environmental chemists.
The past 5 years have seen some major successes in terms of global measurement and regulation of persistent, bioaccumulative, and toxic (PB&T) chemicals and persistent organic pollutants (POPs). The Stockholm Convention, a global agreement on POPs, came into force in 2004. There has been a major expansion of measurements and risk assessments of new chemical contaminants in the global environment, particularly brominated diphenyl ethers and perfluorinated alkyl acids. However, the list of chemicals measured represents only a small fraction of the approximately 30,000 chemicals widely used in commerce (>1 t/y). The vast majority of existing and new chemical substances in commerce are not monitored in environmental media. Assessment and screening of thousands of existing chemicals in commerce in the United States, Europe, and Canada have yielded lists of potentially persistent and bioaccumulative chemicals. Here we review recent screening and categorization studies of chemicals in commerce and address the question of whether there is now sufficient information to permit a broader array of chemicals to be determined in environmental matrices. For example, Environment Canada's recent categorization of the Domestic (existing) Substances list, using a wide array of quantitative structure activity relationships for PB&T characteristics, has identified about 5.5% of 11,317 substances as meeting P & B criteria. Using data from the Environment Canada categorization, we have listed, for discussion purposes, 30 chemicals with high predicted bioconcentration and low rate of biodegradation and 28 with long range atmospheric transport potential based on predicted atmospheric oxidation half-lives >2 days and log air-water partition coefficients > or =5 and < or =1. These chemicals are a diverse group including halogenated organics, cyclic siloxanes, and substituted aromatics. Some of these chemicals and their transformation products may be candidates for future environmental monitoring. However, to improve these predictions data on emissions from end use are needed to refine environmental fate predictions, and analytical methods may need to be developed.


[Evaluation and diagnosis for castration resistant prostate cancer: CRPC].
When considering the diagnosis of castration resistant prostate cancer (CRPC), one of the possible approaches consists of performing examination and diagnosis to determine the presence of CRPC. The definition of CRPC is simple-disease progression despite a serum testosterone value below 50 ng/dL after androgen deprivation therapy (ADT). It is similar to an earlier definition--"an initial relapse" occurring after primary ADT. Therefore, it is important to determine the histopathological type of CRPC to establish a course of treatment thereafter. Regarding the "examinations" and "diagnosis" for the staging of CRPC, it is likely that the circulating tumor cell assay and quantitative imaging examinations will be needed, instead of bone scintigraphy, in the future.


Efficient synthesis of a new structural phenanthro[9,10,3',4']indolizidine starting from pyrrole.
A new structural phenanthroindolizidine, 2,3,6,7-tetramethoxyphenanthro[9,10,3',4']indolizidine, has been synthesized efficiently from pyrrole. An important feature of this synthesis is that intramolecular oxidative coupling and rearrangement of 6,7-bis(3,4-dimethoxyphenyl)-8-methoxy-1,2,3-trihydroindolizin-5-one by using VOF3 and TFA have been achieved in one pot.


Ion channels in cancer-induced bone pain: from molecular mechanisms to clinical applications.
Cancer-induced bone pain (CIBP) caused by bone metastasis is one of the most prevalent diseases, and current treatments rely primarily on opioids, which have significant side effects. However, recent developments in pharmaceutical science have identified several new mechanisms for CIBP, including the targeted modification of certain ion channels and receptors. Ion channels are transmembrane proteins, which are situated on biological cell membranes, which facilitate passive transport of inorganic ions across membranes. They are involved in various physiological processes, including transmission of pain signals in the nervous system. In recent years, there has been an increasing interest in the role of ion channels in chronic pain, including CIBP. Therefore, in this review, we summarize the current literature on ion channels, related receptors, and drugs and explore the mechanism of CIBP. Targeting ion channels and regulating their activity might be key to treating pain associated with bone cancer and offer new treatment avenues.


Polypills for the secondary prevention of cardiovascular disease: effective in improving adherence but are they safe?
International guidelines recommend blood pressure-lowering therapy, statins and aspirin for people who have had a cardiovascular event but use of these medications is low, particularly for lower income countries. Clinical trials have demonstrated that combining these medications into a single pill or capsule (a 'polypill') improves adherence, systolic blood pressure and low density lipoprotein cholesterol compared with usual care in secondary prevention. Uptake of polypill-based care has been underwhelming, possibly due to safety concerns. Overall, results from the clinical trials of polypill use among people who have had a cardiovascular event show no immediate safety concerns. Increased use and adherence to medications will always be associated with side effects however use within a combination medication has not been shown to be any less safe than individual component medications. Research investigating the relative consequences of nonadherence to a polypill compared with individual components would be useful.


Errors in aerial survey count data: Identifying pitfalls and solutions.
Accurate estimates of animal abundance are essential for guiding effective management, and poor survey data can produce misleading inferences. Aerial surveys are an efficient survey platform, capable of collecting wildlife data across large spatial extents in short timeframes. However, these surveys can yield unreliable data if not carefully executed. Despite a long history of aerial survey use in ecological research, problems common to aerial surveys have not yet been adequately resolved. Through an extensive review of the aerial survey literature over the last 50 years, we evaluated how common problems encountered in the data (including nondetection, counting error, and species misidentification) can manifest, the potential difficulties conferred, and the history of how these challenges have been addressed. Additionally, we used a double-observer case study focused on waterbird data collected via aerial surveys and an online group (flock) counting quiz to explore the potential extent of each challenge and possible resolutions. We found that nearly three quarters of the aerial survey methodology literature focused on accounting for nondetection errors, while issues of counting error and misidentification were less commonly addressed. Through our case study, we demonstrated how these challenges can prove problematic by detailing the extent and magnitude of potential errors. Using our online quiz, we showed that aerial observers typically undercount group size and that the magnitude of counting errors increases with group size. Our results illustrate how each issue can act to bias inferences, highlighting the importance of considering individual methods for mitigating potential problems separately during survey design and analysis. We synthesized the information gained from our analyses to evaluate strategies for overcoming the challenges of using aerial survey data to estimate wildlife abundance, such as digital data collection methods, pooling species records by family, and ordinal modeling using binned data. Recognizing conditions that can lead to data collection errors and having reasonable solutions for addressing errors can allow researchers to allocate resources effectively to mitigate the most significant challenges for obtaining reliable aerial survey data.


Involvement of both caspase-8 and Noxa-activated pathways in endoplasmic reticulum stress-induced apoptosis in triple-negative breast tumor cells.
Recent evidences indicate that triple-negative breast cancer (TNBC) cells with a mesenchymal phenotype show a basal activation of the unfolded protein response (UPR) that increases their sensitivity to endoplasmic reticulum (ER) stress although the underlying cell death mechanism remains largely unexplored. Here we show that both caspase-8-dependent and -independent apoptotic mechanisms are activated in TNBC cells undergoing sustained ER stress. Activation of the extrinsic apoptotic pathway by ER stress involves ATF4-dependent upregulation of tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5). In addition, accumulation of BH3-only protein Noxa at the mitochondria further contributes to apoptosis following ER stress in TNBC cells. Accordingly, simultaneous abrogation of both extrinsic and intrinsic apoptotic pathways is required to inhibit ER stress-induced apoptosis in these cells. Importantly, persistent FLICE-inhibitory protein (FLIP) expression plays an adaptive role to prevent early activation of the extrinsic pathway of apoptosis upon ER stress. Overall, our data show that ER stress induces cell death through a pleiotropic mechanism in TNBC cells and suggest that targeting FLIP expression may be an effective approach to sensitize these tumor cells to ER stress-inducing agents.


Differential proteomics of dehydration and rehydration in bryophytes: evidence towards a common desiccation tolerance mechanism.
All bryophytes evolved desiccation tolerance (DT) mechanisms during the invasion of terrestrial habitats by early land plants. Are these DT mechanisms still present in bryophytes that colonize aquatic habitats? The aquatic bryophyte Fontinalis antipyretica Hedw. was subjected to two drying regimes and alterations in protein profiles and sucrose accumulation during dehydration and rehydration were investigated. Results show that during fast dehydration, there is very little variation in protein profiles, and upon rehydration proteins are leaked. On the other hand, slow dehydration induces changes in both dehydration and rehydration protein profiles, being similar to the protein profiles displayed by the terrestrial bryophytes Physcomitrella patens (Hedw.) Bruch and Schimp. and, to what is comparable with Syntrichia ruralis (Hedw.) F. Weber and D. Mohr. During dehydration there was a reduction in proteins associated with photosynthesis and the cytoskeleton, and an associated accumulation of proteins involved in sugar metabolism and plant defence mechanisms. Upon rehydration, protein accumulation patterns return to control values for both photosynthesis and cytoskeleton whereas proteins associated with sugar metabolism and defence proteins remain high. The current results suggest that bryophytes from different ecological adaptations may share common DT mechanisms.


Production of class A biosolids with anoxic low dose alkaline treatment and odor management.
The feasibility of full-scale anoxic disinfection of dewatered and digested sludge from Winnipeg, Manitoba with low lime doses and lagoon fly ash was investigated to determine if a class A product could be produced. Lime doses of 50 g, 100 g, and 200 g per kg of biosolids (dry) were used along with fly ash doses of 500 g, 1,000 g, and 1,500 g per kg of biosolids (dry). The mixed product was buried in eight-10 cubic metre trenches at the West End Water Pollution Control Center in Winnipeg. The trenches were backfilled with dirt and trapped to simulate anoxic conditions. Sampling cages were packed with the mixed product and pathogens non-indigenous to Winnipeg's biosolids. The cages were buried amongst the mixed biosolids in the trench. The non-indigenous pathogens spiked in the laboratory were the helminth Ascaris suum and the enteric virus reovirus. Samples were removed at days 12, 40, 69, 291, and 356 and were tested for the presence of fecal Coliform, Clostridium perfringens spores, Ascaris suum eggs, and reovirus. The pH, total solids, and free ammonia content of the mixed product were also determined for each sample. Odor was quantified for samples at both 291 and 356 days. Fecal Coliform bacteria and reovirus were completely inactivated for doses as low as 100 g lime per kg biosolids (dry) and 50 g lime + 500 g fly ash per kg biosolids (dry). Spores of the bacteria C. perfringens experienced a 4-log reduction when treated with 100 g lime per kg biosolids and a 5-log reduction when treated with doses as low as 50 g lime + 500 g fly ash per kg biosolids (dry) after 69 days. Ascaris eggs were completely inactivated in 5 gram packets for all treatments involving 100 g lime per kg biosolids (dry) after 69 days. Class A pathogen requirements were met for all treatments involving a lime dose of at least 100 g per kg biosolids. The odor potential from the produced biosolids is also assessed.


Sandwich-Like Fibers/Sponge Composite Combining Chemotherapy and Hemostasis for Efficient Postoperative Prevention of Tumor Recurrence and Metastasis.
Intraoperative bleeding is an essential factor leading to the earliest recurrence and tumor metastasis frequently seen after resection of solid tumors. Local drug delivery implants show the unique advantages on postoperative cancer therapy. Herein, a sandwich-like cisplatin-loaded fibers/sponge composite (CFSC) combining chemotherapy and hemostasis is constructed. The obtained implantable CFSC is able to simultaneously stop bleeding and absorb disseminated tumor cells after tumor resection. More importantly, sustained released cisplatin can kill local residual tumor cells as well as those concentrated in the CFSC, which significantly inhibits local tumor recurrence and distant tumor metastasis on the subcutaneous postoperative recurrence model and metastasis models. This dual functional implant strategy with low toxicity to healthy organs may inspire new aspects for efficient postoperative cancer therapy.


Increased capsid oligomerization is deleterious to dengue virus particle production.
The capsid protein (C) of dengue virus is required for viral infectivity as it packages viral RNA genome into infectious particles. C exists as a homodimer that forms via hydrophobic interactions between the α2 and α4 helices of monomers. To identify C region(s) important for virus particle production, a complementation system was employed in which single-round infectious particles are generated by trans-encapsidation of a viral C-deleted genome by recombinant C expressed in mosquito cells. Mutants harbouring a complete α3 deletion, or a dual Ile65-/Trp69-to-Ala substitution in the α3 helix, exhibited reduced production of infectious virus. Unexpectedly, higher proportions of oligomeric C were detected in cells expressing both mutated forms as compared with the wild-type counterpart, indicating that the α3 helix, through its internal hydrophobic residues, may down-modulate oligomerization of C during particle formation. Compared with wild-type C, the double Ile65-/Trp69 to Ala mutations appeared to hamper viral infectivity but not C and genomic RNA incorporation into the pseudo-infectious virus particles, suggesting that increased C oligomerization may impair DENV replication at the cell entry step.


Electric signal synchronization as a behavioural strategy to generate social attention in small groups of mormyrid weakly electric fish and a mobile fish robot.
African weakly electric fish communicate at night by constantly emitting and perceiving brief electrical signals (electric organ discharges, EOD) at variable inter-discharge intervals (IDI). While the waveform of single EODs contains information about the sender's identity, the variable IDI patterns convey information about its current motivational and behavioural state. Pairs of fish can synchronize their EODs to each other via echo responses, and we have previously formulated a 'social attention hypothesis' stating that fish use echo responses to address specific individuals and establish brief dyadic communication frameworks within a group. Here, we employed a mobile fish robot to investigate the behaviour of small groups of up to four Mormyrus rume and characterized the social situations during which synchronizations occurred. An EOD-emitting robot reliably evoked social following behaviour, which was strongest in smaller groups and declined with increasing group size. We did not find significant differences in motor behaviour of M. rume with either an interactive playback (echo response) or a random control playback by the robot. Still, the robot reliably elicited mutual synchronizations with other fish. Synchronizations mostly occurred during relatively close social interactions, usually when the fish that initiated synchronization approached either the robot or another fish from a distance. The results support our social attention hypothesis and suggest that electric signal synchronization might facilitate the exchange of social information during a wide range of social behaviours from aggressive territorial displays to shoaling and even cooperative hunting in some mormyrids.


A novel model of acute murine hindlimb ischemia.
The McGivney hemorrhoidal ligator (MHL), a band designed to cause tissue necrosis, is the preferred experimental tool to create hindlimb ischemia-reperfusion (I/R) injury in rodents. This report defines and compares the ex vivo band tension exerted by MHL and orthodontic rubber bands (ORBs) along with select in vivo characteristics of I/R. As to method, ex vivo band tension was measured over relevant diameters using a tensiometer. In vivo assessment of murine limb perfusion during ischemia with ORB and MHL was compared using laser Doppler imaging and measurement of wet weight-to-dry weight ratio. Neuromuscular scoring and histological extent of muscle fiber injury after I/R with MHL and ORB were also compared. A dose-response curve, between the duration of ORB-induced I/R with both mitochondrial activity (methyl-thiazol-tetrazolium) or tail perfusion [laser Doppler imaging (LDI)], was generated. As a results, ex vivo measurements showed that ORB exerted significantly less force than the MHL. Despite less tension in ORB, in vivo testing of the ORB confirmed complete ischemia by both LDI and wet weight-to-dry weight ratio. After I/R, caused by ORB, there was significantly less neuromuscular dysfunction. Histological assessment confirmed similar degrees of muscle fiber injury after I/R with either the MHL or ORB. Increasing durations of ischemia created by the ORB followed by reperfusion significantly decreased mitochondrial activity and tail perfusion after 24 h of ischemia. In conclusions, ORB produced similar levels of tissue ischemia in murine models of limb I/R with fewer levels of nonspecific injury. ORB may be the preferred model for selected studies of limb I/R.


The role of nurse prescribers in memory services and their continuing professional development: A review of the literature.
Nurse prescribers (NPs) in memory services have a potentially important role in alleviating the burden of dementia on health care, but they require continuing professional development (CPD) specific to their scope of practice. To inform development of CPD workshops for mental health NPs working in memory services, a review of the literature was undertaken regarding role and CPD issues of this professional group. Healthcare databases were searched using defined search terms alongside lateral searches. Study characteristics were extracted systematically, with results grouped thematically in the style of a narrative review. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, adapted for current methods (see Supporting Information File S1). Nine articles specifically addressing nurse prescribing in memory services were found. Studies from broader areas were drawn upon. Considerable variation was found for how the role of memory service NPs might be defined, due in part to variation in characteristics of memory services. NPs, other clinical staff and patients have provided positive feedback to the introduction of the role in memory services and elsewhere. However, concerns around prescribing cautiousness of NPs were apparent. Little clinical or economic outcome data were found to compare opinions and experiences to, with none for NPs in memory services. Literature addressing CPD issues for NPs in memory services was nonexistent. Studies from surrounding areas suggest a problem with availability of CPD opportunities for nurse prescribers. This review highlights the paucity of literature for this area of inquiry, particularly for clinical, economic and other patient outcome data. Variation in the little existing evidence suggests development of CPD opportunities should spend time understanding issues at the local level. The gap in the literature in this area may impact policy decisions in the UK and elsewhere.


'Rejection or infection' predictive value of T-cell subject ratio, before and after heart transplantation.
Peripheral T-cell subsets were monitored in ten heart and two heart-lung recipients pre- and up to one year post-operatively. Prior to transplantation four patients had T-helper/T-cytotoxic suppressor ratios (TH/TS-C) above the range for normal healthy controls and all required treatment for rejection episodes, as compared with three of eight patients whose pre-transplantation ratios were within the normal range. No patient with high TH/TS-C ratios developed cytomegalovirus infection as compared with all of the eight patients with normal ratios. Post-transplantation cytomegalovirus infection was the major cause of alterations in TH/TS-C ratios. T-cell subset inversion always preceded the diagnostic rise in cytomegalovirus antibody titre in both primary and secondary cytomegalovirus infections. Inversion was also noted with Pneumocystis carinii infection. Reversal of the TH/TS-C ratio was due to a major increase in the absolute numbers of TS-C cells and was usually followed by a rise in the number of cells expressing a natural killer cell phenotypic marker (Leu-7). All patients with primary cytomegalovirus and two of four cases with secondary cytomegalovirus retained inversion throughout follow-up and showed significantly increased numbers of TS-C and Leu-7 bearing cells. However, the absolute numbers of TH fell by 200 days after transplantation in all patients irrespective of their TH/TS-C ratio. Although TH/TS-C ratio inversion was a predictor of cytomegalovirus infection, no association was found between changes in T-cell subsets after transplantation and rejection episodes.


[Primary sclerosing cholangitis and autoimmune cochlear deafness: a new syndrome?].
Association of autoimmune cochlear hearing loss with primary sclerosing cholangitis is reported in two patients. Endocochlear sensorineural hearing loss was associated with the presence of anti-cochlear antibodies in the serum directed against the walls of vessels in the stria vascularis. The hearing loss appeared at the same time or shortly after the diagnosis of cholangitis. This association, which has never been described, may reinforce the theory of the role of immunologic factors in the pathogenesis of primary sclerosing cholangitis, possibly linked to or initiated by vasculitis.


Dirofilariasis in Iowa coyotes.
(Dirofilaria immitis) were found in eight of 220 (3.6%) coyotes (Canis latrans) collected from fur buyers in Adams, Carroll, Cass, and Warren counties in southwestern Iowa. Infections ranged from one to 23 worms per coyote.


[Determination of streptomycin in honey determined by hydrophilic interaction chromatography combined with tandem mass spectrometry].
To establish a method for the determination of streptomycin in honey by determined hydrophilic interaction chromatography combined with tandem mass spectrometry (HILIC-MS/MS). A hilic column was used, and the mobile phase was consisted of acetonitrile (5 mmol/L ammonium acetate and 0.1% formic acid, 60:40). Samples were extracted by the cation-exchange SPE cartridge. The extraction samples were then identified and quantitated by HILIC-ESI-MS/MS. Linear calibration curves were obtained at the concentration ranges from 10. 5 microg/kg to 105 microg/kg (the correlation coefficients were above 0.99). The limit of detection was 1.05 microg/kg. The average recoveries for streptomycin spiked in honey ranged from 71.3 to 82.5% and their relative standard were between 3.4% and 8.2%. The method for determination of streptomycin in honey could be simple, sensitive and accurate.


Gastric secretory response to graded doses of pentagastrin alone or in combination with carbacholine in unoperated duodenal ulcer patients.
Dose-response studies of pentagastrin-stimulated secretion were performed in 6 unoperated duodenal ulcer patients. On different days pentagastrin was given in doses of 0.15, 1.5, and 15 mug/kg/hr, either alone or in combination with carbacholine, 2 mug/kg/hr. There were no significant differences between mean acid or pepsin outputs or mean volumes of gastric juice after infusion of pentagastrin alone or pentagastrin plus carbacholine at any dose step of pentagastrin. The dose of pentagastrin required to elicit half maximal acid output (Km) and the calculated maximal acid output (Vmax) were the same for pentagastrin alone and pentgastrin plus carbacholine. Thus, carbacholine did not increase the sensitivity of the parietal cells to pentagastrin in the unoperated duodenal ulcer patients.


Prediction of axillary lymph node metastases in a screened breast cancer population. South-East Sweden Breast Cancer Group.
To define a subgroup of patients, in whom axillary dissection could be omitted, we analysed the frequency of pathologically confirmed lymph node metastases depending on tumour size, hormonal receptors, DNA ploidy, S-phase fraction (SPF), and clinical nodal status among 1,145 patients with stage I-II breast cancer from an area with ongoing screening. Clinical nodal status and tumour size were strongly correlated to pathological nodal status. Also SPF > 10% was strongly correlated to node positivity in univariate analysis. In multivariate analysis there was still a significant correlation among cases with tumour size < or = 20 mm. In conclusion, patients with clinically negative nodal status, and tumour size < or = 20 mm and < or = 10 mm had pathologically positive nodes in 25% and 15% of cases respectively. The addition of SPF did not lower these figures significantly since small tumours with high SPF are few.


[BIOLOGICAL ACTIVITY OF ANTIMICROBIAL PEPTIDES OF ENTEROCOCCUS FAECIUM].
Isolate bacteriocins from Enterococcus faecium metabolites and characterize their effect on cells of Gram positive (Listeria monocytogenes) and Gram negative (Escherichia coli) bacteria. Methods of solid-phase extraction, ion-exchange and reversed phase chromatography were applied for isolation of bacteriocins from cultural medium of bacteria MALDI time-of-flight mass-spectrometry was used for characterization of the obtained preparations. The mechanism of biological effect of peptides was evaluated using DNA-tropic dyes (SYTO 9 and PI) with subsequent registration of fluorescence spectra: Atomic-force microscopy (AFM) was used for characterization of morpho-functional reaction of target cells. Peptide fractions with mass of 1.0 - 3.0 kDa were isolated from enterococci metabolites, that inhibit the growth of indicator microorganisms. E. faecium strain exoproducts were shown to increase membrane permeability during interaction with L. monocytogenes, that results in subsequent detectable disturbance of normal cell morphology of listeria. Alterations of E. coli surface during the effect of purified peptide fraction was detected using AFM. The studies carried out have revealed the effect of bacteriocins of enterococci on microorganisms with various types of cell wall composition and have confirmed the importance of bacterial barrier structure permeability disturbance in the mechanism of antimicrobial effect of enterocins.


Achieving ultrahigh triboelectric charge density for efficient energy harvesting.
With its light weight, low cost and high efficiency even at low operation frequency, the triboelectric nanogenerator is considered a potential solution for self-powered sensor networks and large-scale renewable blue energy. As an energy harvester, its output power density and efficiency are dictated by the triboelectric charge density. Here we report a method for increasing the triboelectric charge density by coupling surface polarization from triboelectrification and hysteretic dielectric polarization from ferroelectric material in vacuum (P ~ 10-6 torr). Without the constraint of air breakdown, a triboelectric charge density of 1003 µC m-2, which is close to the limit of dielectric breakdown, is attained. Our findings establish an optimization methodology for triboelectric nanogenerators and enable their more promising usage in applications ranging from powering electronic devices to harvesting large-scale blue energy.Triboelectric nanogenerators (TENGs) harvest ambient mechanical energy and convert it into electrical energy. Here, the authors couple surface polarization from contact electrification with dielectric polarization from a ferroelectric material in vacuum to dramatically enhance the TENG output power.


Carbon-bridged Oligo(phenylenevinylene)s as Light-harvesting Antenna for Porphyrins.
The efficacy of carbon-bridged oligo(phenylenevinylenes)s (COPVs) as light-harvesting antenna for porphyrins is demonstrated using a series of 5,15-di-COPVn-substituted free-base and zinc porphyrins, COPVn-MP-COPVn (n=1-3, M=H2 , Zn). These molecules were synthesized by Suzuki-Miyaura cross-coupling reactions of COPVn-Bpin and Br-H2 P-Br. The absorption spectra of these compounds in solution show a significant expansion of the Soret band region together with a bathochromic shift of the Q band, suggesting a significant interaction between these chromophores in the ground state. The photoluminescence quantum yield of the porphyrin-COPV conjugates is enhanced up to four times relative to the parent porphyrins. Theoretical calculations also indicated interactions between these chromophores in the HOMO, which suggests that the light-harvesting ability stems from the expansion of the π-electron-conjugation system.


Specificity of the digoxin radioimmunoassay with respect to dihydrodigoxin.
An investigation was conducted to determine the specificity of the digoxin antibody provided in a commercially available radioimmunoassay kit with respect to dihydrodigoxin. Over the concentration range of 0.5 to 8.0 ng./ml. dihydrodigoxin displaced the 125I digoxin derivative from the antibody to a degree that could be significant at clinically observed serum and urine digoxin concentrations.


Assessment of haemodynamic changes and acid-base equilibrium during hypovolaemia and after infusion of plasma substitutes in dogs.
The following haemodynamic values were determined in anaesthetized mongrel dogs: heart rate, systolic blood pressure in the ascending aorta, left ventricular pressure at the peak dp/dt, left ventricular end-diastolic pressure, time interval from Q in ECG to the onset of the systolic wave of dp/dt, time interval from Q in ECG to peak dp/dt, maximum rate of left ventricular pressure rise, femoral arterial flow, and certain indices of left ventricular contractility. It was concluded from the results of these experiments that infusion of a modified gelatin solution Fluigel prevented haemodynamic and metabolic changes produced by experimental hypovolaemia more effectively than infusion of Plasmagel.